CN101495078B

CN101495078B - Combination pressure therapy

Info

Publication number: CN101495078B
Application number: CN200780010115.7A
Authority: CN
Inventors: 卡尔·E·林顿; 艾伦·鲁斯科夫斯基; 托马斯·杰克逊·蒂德韦尔
Original assignee: CVAC Systems Inc
Current assignee: CVAC Systems Inc
Priority date: 2006-02-08
Filing date: 2007-02-08
Publication date: 2013-02-13
Anticipated expiration: 2027-02-08
Also published as: CN101495078A

Abstract

Methods for administering pressure changes to a user for the treatment and prevention of diseases and conditions are disclosed herein. Methods of administering Cyclic Variations in Altitude Conditioning Sessions (CVAC Session(s)) for the treatment of hypertension, blood production, stem cell therapy, spinal cord injury, intervertebral disc therapy, inflammation, wound healing, ischemia, diabetes and associated complications, Alzheimer's disease, and cancer are disclosed herein.

Description

Combination pressure therapy

The intersection application case

The application's case is advocated the rights and interests of following provisional application case: No. the 60/771st, 848, the U.S. Provisional Application case of application on February 8th, 2006; No. the 60/772nd, 647, the U.S. Provisional Application case of application on February 10th, 2006; No. the 60/773rd, 460, the U.S. Provisional Application case of application on February 15th, 2006; No. the 60/773rd, 585, the U.S. Provisional Application case of application on February 15th, 2006; No. the 60/774th, 441, the U.S. Provisional Application case of application on February 16th, 2006; No. the 60/775th, 917, the U.S. Provisional Application case of application on February 22nd, 2006; No. the 60/775th, 521, the U.S. Provisional Application case of application on February 21st, 2006; No. the 60/743rd, 470, the U.S. Provisional Application case of application on March 13rd, 2006; No. the 60/745th, 721, the U.S. Provisional Application case of application on April 26th, 2006; No. the 60/745th, 723, the U.S. Provisional Application case of application on April 26th, 2006; No. the 60/824th, 890, the U.S. Provisional Application case of JIUYUE in 2006 application on the 7th; No. the 60/822nd, 375, the U.S. Provisional Application case of application on August 14th, 2006; No. the 60/826th, 061, the U.S. Provisional Application case of JIUYUE in 2006 application on the 18th; With No. the 60/826th, 068, the U.S. Provisional Application case of JIUYUE in 2006 application on the 18th, described application case is to be incorporated herein by reference.

Technical field

The present invention relates to that the air pressure therapy is used for the treatment of and the disease preventing regulate to benefit from hypoxia and the purposes of the patient's condition.

Background technology

Hypertension (Hypertension is commonly referred to hypertension (high blood pressure)) is to cause the root of multiple health problem and usually occur prior to more significant health problem (such as coronary heart disease, heart attack and apoplexy).When the blood in the large artery trunks is too high, think generation hypertension.Only in the U.S., 50,000,000 people that just have an appointment are affected by hypertension and are more general in elderly population.It is unknown that the etiology of most of hypertension case still belongs to, but because hypertension can heredity and to cross over ethnic group different with the racial line performance, therefore think that the hereditism plays a role.Environment also plays very important effect for hypertension, and body weight and body constitution also are like this.Comprise diet and have the known multi-medicament that can increase the side effect of blood pressure with hypertension generation and the relevant other factors that makes progress.

Cause that hypertensive other not too common reason comprises the disease of kidney or endocrine gland, and can not cause death because it has specific symptoms in some cases, therefore be referred to as " reticent killer (the silent killer) ".Compare with having normotensive people, untreated hyperpietic is more likely because of cardiovascular complication death or disabilities such as apoplexy, heart attack, heart failure, arrhythmia and renal failure.Hypertensive current treatment comprises change (diet, exercise, non-smoking etc.) and the pharmacotherapy of life style.The current main species that is used for the treatment of hypertensive medicine comprises adrenergic neuron antagonist (it is peripheral action), alpha-2-adrenergic agonist components (it is central action), alpha-1 adrenergic blocker, α and Beta receptor blockers, angiotensin-ii receptor blockers, Angiotensin-Converting (ACE) inhibitor, Beta-3 adrenergic blocker, calcium channel blocker, thiazine (Thiazide) and relevant diuretic, and vasodilation (it works by directly lax vascular smooth muscle).Yet, must often monitor and regulate these known treatment schemes, and most of therapeutic scheme all is lifelong.

In every year, donating blood all provides the blood source to save millions of people's life by the patient to the extra blood of needs.During damage, operation, childbirth and hematologic disease, can lose blood, and medical facilities rely on the blood supply of contributing that medical services are provided.Keep blood supply to need blood donor's stable supply, and the increase of the demand that is caused by accident and other problem (blood supply is contaminated, blood bank's facility deficiency etc.) so that global blood supply go short of.Use autoblood to have some advantages that are better than common donated blood.Described advantage comprises the Risk Reduction that blood group coupling is guaranteed, catches because of contaminated blood and anaphylactoid risk does not occur.When needing, the blood donor's blood with known volume in body is donated blood the medical service organ that allows donating blood is transported in blood donor's body immediately.Yet the restriction of using for donating blood in body is donated blood is identical with common donated blood, and because of hemoglobin concentration cause for the restriction of donating blood for etc. pending capital operation (comprising open heart operations) the child donate blood from body unfavorable especially.[the people such as Sang Suoni V (SonzogniV), before child's the erythropoietin therapy of experience open heart operations and the art from body donate blood (Erythropoietin therapy and preoperative autologous blood donation in children undergoingopen heart surgery), Britain's anesthesia magazine (Brit.J.Anaesth.), 87 (3): 429-34 (2001)] except the crowd donate blood ratio low, consider the restriction for donate blood volume and frequency, blood bank need often seek to improve the quality of its blood supply and quantity and need not higher cost, need not use can draw back blood donor's medicine or other reagent with fear or other parameter is introduced mode in system of blood bank.

The nineties is early stage, and research worker and the public begin to pay close attention to stem cell and it is used for the treatment of the potential use of disease.Because of directly related with hemopoietic and be applicable to the genetic modification initial interest autoimmune disease of multipotency precursor and the treatment of cancer, but after this expanded to nearly all field of human diseases for the discriminating of the cell with the potential that is divided into any cell type that exists in the organism and ability.Except the bone marrow repairing and treating for cancer (such as leukemia) and autoimmune disease, also just considering stem cell therapy is used for the treatment of, comprise and repair the organ-tissue that damages after the disease.These stem cell therapies that propose relate to former generation stem cell and/or modified stem cell throw with organism in the particular organization position.Noticeable application comprises diabetes, hepatopathy, spinal cord regeneration, bore regenerating, eye regeneration and myocardial repair.[for example referring to La Yagepaer L (Rajgobal, L), the catholicon of stem cell therapy-all diseases? (Stem CellTherapy-A Panacea for all Ills?), postgraduate's medical journal (J.Postgrad.Med.), 51:161-163 (2005)].

In general, stem cell therapy is subjected to the restriction of autologous stem cells supply.Initial trial mainly utilizes the bone marrow aspiration technology to gather autologous stem cells (from someone self stem cell) and allosome stem cell (from the stem cell in other source except someone self).Recently, preferably collect patient's stem cell by the method that is called mobilization.Mobilization be utilize with high dosage throw and cytotoxic drug and/or somatomedin realize.Stem cell is implanted has low success rate, and no matter institute throws and cell volume how, all can't successfully be implanted by many stem cell of mobilizing generation, thereby make the convalescent period prolongation and the cost relevant with described program obviously increased.[tall assorted SS. (Joshi, SS.), Miller K. (Miller, K.), Jackson J.D. (Jackson, J.D.), Wa Kenjin P. (Warkentin, P.) and Kai Sijie A. (Kessinger, A.), come to gather with the blood stem cell after erythropoietin+G-CSF mobilization in comfortable cancer patient's body the monocytic immunological characteristic (Immunological propertiesofmononuclear cells from blood stem cell harvestsfollowing mobilization with erythropoietin+G-CSF incancer patients) of thing, cell therapy (Cytotherapy), 2 (1): 15-24 (2002)].

People's spinal column (spine) comprise a plurality of by the soft tissue intervertebral disc separate by articulated bone element (vertebra).Intervertebral disc is flexible joint, and it makes relative to each other bending of vertebra, elongation and rotation, therefore helps stability and the mobility of spine in axial bone.Intervertebral disc comprises the central inner portion of soft, the amorphous mucoid material of matter (vertebral pulp), is the annular ring encirclement by the thickness that is called fibrous ring, fibrous material layer around the described vertebral pulp.Delimitd a boundary line by the endplate that is positioned at adjacent vertebrae lower end and upper end in the top and bottom of vertebral pulp and fibrous ring integral body (that is, head and afterbody).The periphery of these soleplates (it is to be made of the hyaline cartilage thin layer) directly links to each other with the flaggy of fibrous ring inside.The flaggy of fibrous ring outside directly links to each other with skeleton at the external margin place of adjacent vertebrae.

For promoting fluid motion to intervertebral disc, the vertebral plate on each intervertebral disc either side is via the nutrition that is positioned at capillary bed on the cartilage endplate and keeps most intervertebral disc.Capillary bed receives the blood flow from the tremulous pulse of supply vertebra.Neovascularization is associated with impaired intervertebral disc, and also show vascularization [Martin MD (Martin MD) via capillary bed from the healthy disc that corpse separates, James Boxell CM (Boxell CM) and Malong DG (Malone DG), the pathophysiology of Lumbar Intervertebral Disc Degeneration: literature review (Pathophysiology of Lumbar Disc Degeneration:AReview of the Literature), neurosurgery focus (Neruosurg.Focus), 13 (2): El, 2002].Other research confirms, and the obstruction that is caused by various pathology and the capillary bed size and the density reduction that cause can cause nutrient and the fluid loses its in the intervertebral disc and cause subsequently the intervertebral disc degeneration disease.[the nanogram LM (Benneker LM) of class, black Buddhist nun PF (Heini PF), Ali Buddhist nun M (Alini M), Anderson SE (Anderson SE) and her rattan K (Ito K), young logist encouraged the first prize in 2004: endplate bone marrow contact channels blocks and intervertebral disc degeneration (2004 YoungInvestigator Award Winner:vertebral endplate marrow contact channel occlusions andintervertebral disc degeneration), spine magazine (Spine), 30 (2): 167-73 (2005); This JP of ell (Urban JP), Smith S (Smith S), Fairbanks JC (Fairbank JC), the threpsology of intervertebral disc (Nutrition of the intervetebral disc), spine magazine (Spine), 29 (23): 2700-9 (2004)].

Intervertebral disc degeneration disease (DDD) entail dangers to normal fluid power function.DDD relates to the reduction of the 26S Proteasome Structure and Function of one or more intervertebral disc, and usually with old and feeble relevant with spinal trauma.Although the etiology of DDD not yet is completely understood, a visible integral body that unanimously is changed to Dan Baiduotang proteoglycan PG content in vertebral pulp and the fibrous ring reduces from the intervertebral disc of regression.The loss of Dan Baiduotang proteoglycan PG content causes the concomitant loss of intervertebral disc water content.The minimizing of intervertebral disc structure aquation dies down fibrous ring, causes intervertebral disc to be subject to the impact of (such as outstanding) of intervertebral wound.The outstanding nucleus material that usually causes squeezing out is touched spinal cord or nerve, thereby causes pain, weak and cause in some cases permanent disability.Spinal cord injury is characterised in that spinal nervous tissue is impaired.Described damage may be by impact injury, the relevant autoimmune patient's condition or cancer (being tumor etc.) is caused and/or be the result of the operation relevant with some operative procedure.Decide on damage location, the miopragia of related Neurons can cause the reduction of muscle response or function, and comparatively serious infringement can cause partially or completely paralysing.Near the spinal cord top (cervical region) damage usually can cause paralysis and generally include by the caused breathing of diaphragm afunction weakening.The damage that is positioned at central spinal cord (chest) and lower end (waist) can cause multiple infringement, and this tends to corresponding with the body part of damage location and lower end nearside.

Identical with spinal injury, local inflammation and swelling are normally caused by local damage, wound or infection, and similar events as also can cause systemic inflammatory.The feature of inflammation is the part forfeiture of the hyperemia, swelling, temperature, pain and the affected area domain-functionalities that increase usually.Destruction or the malfunction of inflammatory reaction regulation and control also can cause chronic disease, such as arthritis, inflammatory bowel, asthma, anaphylaxis and many other inflammation patient's condition.

Wound healing represents the health problem that another is important, and no matter cause how, its inevitable bioprocess with a complexity.Generally speaking, between the reaction period, clean wound by permeation cell and fluid at related inflammation.Be proliferation period after this initial inflammatory phase, wherein different cell types provide wound healing or fill the necessary factor and organizational environment by suitable cell (such as fibroblast, cell and multiple other cell).When epithelial cell is filled in the wound gradually, other event also occurs, shrink such as angiogenesis and wound.Decide on the order of severity of wound and the efficient of inflammatory phase, this one-phase tends to continue approximately 7-10 days.Length, immunodeficiency and the environment such as pressure and other environmental factors can affect wound healing such as the age.Long-term wound exposure can make the probability increase of infections, unfavorable inflammation impact and cicatrization and possible chronic trauma.Usually, wound healing process can be finished with reinventing the phase along with the period of maturation.Collagen protein is changed, and reinvent and crosslinked, thereby increase the intensity of new tissue of growing, and with unnecessary blood vessel, cell with organize lentamente and remove from wound site.Because health trends towards healing the stage at last, so the sustainable nearly several years of this final stage.

The tissue that lacks blood and oxygen can cause ischemic necrosis or infarction, usually causes permanent histologic lesion.Myocardial ischemia is commonly referred to " angina pectoris ", " heart disease " or " heart attack ", and cerebral ischemia is commonly referred to " apoplexy ".Myocardial ischemia and cerebral ischemia are to be reduced and caused by blood and oxygen flow, and it causes to a certain degree cerebral lesion, heart tissue infringement or the two subsequently usually.It may be to be caused by obstruction of artery, angiorrhexis, developmental disorder, blood viscosity or the change of other quality or health wound that blood flow and Oxygenation reduce.Before the real heart onste, myocardial ischemia can the angina pectoris mode present.Angina pectoris is that the moderate that experienced by the chest that cardiovascular and tissue local ischemia cause is to severe pain.It stops up the indication of aggravation for heart arter, and usually occurs before in ischemia event (such as heart attack).In addition, myocardial ischemia also can cause being called the PD of congestive heart failure.Congestive heart failure is a kind of patient's condition that heart no longer effectively is pumped into the blood of enough volumes health.Described having a weak heart normally caused by the myocardial ischemia of oppressing or damage heart tissue.Once or made once heart tissue weak or cause heart attack that scar tissue in the heart produces after, also congestive heart failure can appear.No matter ischemic mechanism how, the complication of congestive heart failure is all relevant with myocardial ischemia or caused by myocardial ischemia.

Type 2 diabetes mellitus (namely, diabetes (diabetes mellitus), non-insulin-dependent diabetes mellitus, the outbreak type diabetes of growing up) usually be considered to a kind of by hyperglycemia cause disease, medical research has turned to the abnormal plasma glucose content of understanding as the symptom of the potential disease relevant with the lipid metabolism imbalance.Therefore, high fatty acid content can cause multiple fat toxicity, such as insulin resistance, pancreatic beta cell apoptosis be called the disease of " metabolic syndrome ".Similarly, metabolic syndrome can relate to glucose transport imbalance, and this will cause the cell resistance of insulin and be subjected to that the content of fatty acid increase affects in the blood.[Shu Erman G. (Schulman, G.), the cell mechanism of insulin resistance (Cellular Mechanisms of InsulinResistance), Journal of Clinical Investigation (J.Clin.Invest.), 106 (2): 171-76 (2000).] usually by blood insulin content increase, the blood sugar content of response oral glucose tolerance test (OGTT) increases, or the response insulin is thrown and phosphorylated protein kinase b (AKT) content detect insulin resistance.Insulin resistance is caused by the Reduced susceptibility of Insulin receptor INSR Signal Transduction system in the cell and/or the β loss cell in the pancreas.Also evidence suggests, insulin resistance can have potential inflammatory components and characterize.In the past, regard type 2 diabetes mellitus as a kind of relatively different disease entity, but recent understanding discloses, normally more widely a kind of performance of potential disease of type 2 diabetes mellitus (hyperglycemia or the metabolism of blood glucose relevant with it are unusual), and it comprises metabolic syndrome as indicated above.This syndrome is sometimes referred to as the X syndrome, and is a succession of risk of cardiovascular diseases factor, and except glucose intolerance, described factor also comprises hyperinsulinemia, dyslipidemia, hypertension, intra abdominal obesity, hypercoagulability and microalbuminuria.Diabetic symptom can cause multiple complications.Described complication comprises the metabolic syndrome that above describes in detail, and visual disorder, neuropathy, nephropathy and angiopathy (such as heart disease, apoplexy and extremity ulcer/amputation).The problem relevant with diabetes is weak and normally fatal, so the treatment of diabetes is very important for these serious complication of prevention.

The symptom of the A Zihai Mo's disease of usually noticing at first is the loss of memory, and it is by seeming the forgetful more deep recent memory forfeiture that proceeds to simple and usually fluctuation, be relevant familiar and well-known ability or purpose or personnel's the loss of memory subsequently.Aphasia, disorientation and inhibition are removed and usually are attended by the loss of memory.The A Zihai Mo's disease also can comprise previous people's without certain behavior history behavior change, such as violent conflict or excessively blunt.In the latter half, if do not involve the death that is caused by certain external cause (for example heart attack or pneumonia), to see the degeneration of muscular tissue and mobility so, thus cause being unable to leave the bed (bedfastness), can't take care of oneself and incontinence.

In addition, existence and the closely related [violent R.A. (Whitmer in gloomy island of dementia in old age of middle age (40 to 44 years old) central vessel risk factor (diabetes, hypertension, hypercholesterolemia and smoking) have been found, the people such as R.A.), middle age cardiovascular risk factors and risk of dementia in old age (Midlife cardiovascular risk factors and risk of dementia inlatelife), neurological (Neurology), 64:277-281 (2005)].Some researchs are pointed out, can delay the outbreak of A Zihai Mo's disease and reduce its ultimate risk such as non-steroidal anti-inflammatory drugs (NSAID) such as ibuprofen (ibuprofen) and aspirin (aspirin).According to the cohort study, in time several years, continue every day and use a small amount of NSAID (such as ibuprofen (

,

)) progress of the A Zihai Mo's disease that as if will slow down.NSAID can affect the outbreak of disease, but after progression of disease arrived early stage or ripe (full-blown) A Zihai Mo's disease, it was little for the described disease use for the treatment of.In addition, vitamin combination (such as vitamin E and vitamin C) may be passed in time and sharply be reduced the risk of A Zihai Mo's disease, but only have when dosage be every day the 400i.u. vitamin E add 500mg or more just useful during Multivitamin C every day.Small amount (such as the amount seen in the Multivitamin sheet) seems obviously not too effective.[praise enlightening P.P. (Zandi, the people such as P.P), the Risk Reduction of the A Zihai Mo's disease of the user of additional antioxidant vitamins: Ka Shi county research (Reduced risk ofAlzheimer disease in users of antioxidant vitamin supplements:the Cache County Study), neurological archives (Arch.Neurol.), 61:82-88 (2004).]

Cancerous cell, growth and tumor also show and are faced with the challenge that utilizes chemotherapeutic agent and medicament, X-ray therapy and other method effectively to treat.For instance, along with the increase of tumor size, its increase because of blood, nutrient and oxygen demand in the high growth district in outside reduces or cuts off to the blood supply of inside tumor core.This causes tumor center's anoxia and selects lower oxygen concentration resistance Growth of Cells in the core.These for want of blood supplies of core cell, lack nutrient and the oxygen lack that causes thus and radiation and chemotherapeutant are had stronger resistance.The shortage of described blood and oxygen prevents that chemotherapeutant and other chemical compound (antibody, proteotherapy etc.) from entering the tumor core and reacting to bring into play its therapeutical effect with oxygen.Similarly, owing to lacking the reactive oxygen that can be used for peroxide and free radical formation in the anoxia tumor core, the ionizing radiation therapy is usually also invalid.Therefore, when to patient's throwing of suffering from tumor and chemotherapy and/or radiation, but the cell of kill tumor outside, but can't kill the cell of internal core.Even when utilizing usually effectively treatment, tumor still can continue to grow vigorously and shift, and this just needs the other therapies course for the treatment of and usually chemotherapy, radiation, other chemical compound therapy or its combination of higher dosage.

The therapy that needs the treatment of the above-mentioned indication of improvement.Also need with traditional method simultaneously or act on the other therapies for the treatment of above-mentioned indication.Need valuably the therapy that works with operative treatment one.Also need the therapy without the potential negative side-effects of medicine and somatomedin scheme.Perhaps, need to reduce by changing medicine and somatomedin scheme the negative side-effects of described scheme, can work with medicine and somatomedin scheme one valuably, or can synergistic therapy when being used in combination with medicine and somatomedin scheme.Also need the therapy that can be valuably works with non-pharmaceutical admixtures one.

Summary of the invention

Comprise one group of target altitude mixture control cyclical fluctuation course for the treatment of (Cyclic Variations in Altitude Conditioning Session, CVACSession, CVAC course for the treatment of), and described target is multiple atmospheric pressure.CVAC comprises starting point and terminal point the course for the treatment of, and the target of carrying out between Origin And Destination more than.These targets are to carry out with transformable precise order transmission and with various modes, and described pattern includes, but is not limited to circulation, repeats and/or linear change.When such as performance objective that this paper expects, performed target comprises the pressure in the CVAC device also as described herein is become another force value from a force value.Starting point and the terminal point of any CVAC in the course for the treatment of all is preferably the ambient pressure that transmits the place.Any CVAC in the course for the treatment of intrinsic target all be that changeover portion by appointment connects or is bonded together.For instance, the pressure target that utilize to connect or be bonded together can make these changeover portion pressure risings or pressure decreased or described the two combination.When needs are regulated other target of time, temperature or humidity and condition, also will described other target with the pressure target while, successively or interval At All Other Times to move.

Because CVAC comprises different atmospheric pressure and comprises in certain embodiments other target component the course for the treatment of, so it is better than previous static low-voltage therapy.For instance, other target component can comprise different time sections.Compare with previous low pressure therapy, can (but nonessential) in obviously shorter time range, throw with CVAC the course for the treatment of, the benefit relevant with the low pressure therapy is provided simultaneously, and it is reported other relevant benefit of blood vessel pneumatic action (vaso-pneumatic effect) of at least part of and described course for the treatment of user being brought into play.In addition, CVAC also can provide the beneficial effect of low pressure therapy the course for the treatment of, also avoids simultaneously the usually illeffects relevant with previous low pressure therapy.

Have now found that, can throw with CVAC course for the treatment of with treatment hypertension, blood generation, stem cell therapy, spinal cord injury, intervertebral disc therapy, inflammation, wound healing, ischemia, diabetes and related complication, A Zihai Mo's disease and cancer.

The invention provides the purposes of a kind of altitude mixture control cyclical fluctuation (CVAC) device, described device comprises through adjusting with the pressure vessel unit around user, described CVAC device comprises in time range and makes the fast-changing member of pressure, described pressure comprises pressure starting point, pressure terminal point and the atmospheric pressure target between described pressure starting point and described pressure terminal point more than, and described device is to be used for the treatment of to be selected from following disease or the patient's condition: hypertension, blood generate (erythropoiesis), ischemia, diabetes or diabetes related conditions.According to the present invention, blood is generated as stem cell and generates.

The present invention also provides the purposes of a kind of altitude mixture control cyclical fluctuation (CVAC) device, described device comprises through adjusting to center on user, thereby provide the pressure vessel unit of at least one CVAC course for the treatment of of variable low pressure target, the target that described CVAC has starting point, terminal point and carries out between described starting point and described terminal point more than one course for the treatment of, described purposes comprises following steps: use at least one CVAC course for the treatment of; Measure the CVAC effect of the course for the treatment of via parameter change; And by the user adjusting parameter course for the treatment of, described device is to be used for the treatment of to be selected from following disease or the patient's condition: hypertension, blood generate (erythropoiesis), ischemia, diabetes or diabetes related conditions.According to the present invention, described target is to carry out with transformable precise order transmission and with various modes, and described pattern includes, but is not limited to circulation, repeats and/or linear change.According to one embodiment of present invention, CVAC be the course for the treatment of with the single course for the treatment of or one group the course for the treatment of form use.Preferably, use CVAC approximately 10 minutes course for the treatment of, approximately 20 minutes, approximately 30 minutes, approximately 40 minutes, approximately 60 minutes, between between 10 and 20 minutes, between between 20 and 30 minutes, between between 30 and 60 minutes or between 60 and 120 minutes.According to another embodiment of the present invention, CVAC be the course for the treatment of with the single course for the treatment of or one group the course for the treatment of form use.According to another embodiment of the present invention, can use the course for the treatment of or continuously the frequency of the course for the treatment of for continuing for 8 weeks 3 times weekly, continued for 8 weeks 4 times weekly, continuing weekly 8 weeks or 6 lasting 8 weeks weekly for 5 times.In addition, CVAC further comprises temperature or humidity target and preferably the course for the treatment of, described temperature or humidity target can with pressure target simultaneously, before or after pressure target, implement.

The invention provides a kind of method that produces (erythropoiesis) or promote the stem cell therapy of user to treat hypertension, increase blood and/or hemocyte with pressure change that user is thrown.In one aspect of the present invention, throw with at least one CVAC course for the treatment of with treatment hypertension.In one embodiment of the invention, throw with at least one CVAC course for the treatment of to improve hypertensive impact.In another embodiment, throw with at least one CVAC course for the treatment of with prophylaxis of hypertension.In the present invention on the other hand, throw with at least one CVAC course for the treatment of to stimulate erythropoiesis.In the present invention on the other hand, throw with CVAC course for the treatment of to improve stem cell therapy.In one embodiment of the invention, throw with at least one CVAC course for the treatment of to improve stem cell mobilization.Another embodiment of the present invention is implanted to improve stem cell for throwing with at least one CVAC the course for the treatment of.Another embodiment of the present invention is for throwing with at least one CVAC course for the treatment of to improve the recovery behind the stem cell therapy.In above-mentioned each side and embodiment, can throw the course for the treatment of with a plurality of CVAC.In above-mentioned each side and embodiment, with at least one CVAC course for the treatment of and other and/or standard treatment and method at the appointed time in the interval or with random appearance combination throw with.The effect of described dispensing is prevention, treats or improves hypertension; Improve erythropoiesis; Implant and/or the stem cell transplantation recovery with improvement stem cell mobilization, stem cell.

The present invention also provides a kind of user is thrown and the method for pressure change with treatment spinal cord injury, treatment intervertebral disc, treatment inflammation and swelling and treatment wound.Treatment comprises that method that application discloses is to be used for prevention, prophylactic treatment, present situation treatment, to improve and to recover as used herein.Using the method that discloses helps to recover from Acute spinal cord injury and related surgical.In addition, use the method that discloses and to strengthen complete neuron path, and improve related Neurons and muscle function and control and intervertebral disc aquation and health.Similarly, can improve the shortening of inflammation and wound healing by using the method that discloses.

One aspect of the present invention is for throwing with one or more CVAC course for the treatment of with treatment spinal cord injury.In one embodiment of the invention, before spinal cord injury occurs, expection operation on spinal cord or anticipate in the time of to affect by any way any operation of spinal cord, throw the course for the treatment of with at least one CVAC.At the appointed time throw the course for the treatment of with CVAC in the interval or with random appearance.In other embodiments, after spinal cord injury, throw with CVAC the course for the treatment of.The effect of described dispensing be to alleviate spinal cord injury symptom, reduce the lasting infringement to neuron and myeloid tissue, and/or reduce the adverse effect of spinal cord injury.

Another aspect of the present invention is and throw with one or more CVAC courses for the treatment of so that the intervertebral disc aquation.In one embodiment of the invention, before the intervertebral disc wound occurs, expection operation on spinal cord or anticipate in the time of to affect by any way any operation of spinal cord or intervertebral disc, throw the course for the treatment of with at least one CVAC.At the appointed time throw the course for the treatment of with CVAC in the interval or with random appearance.In other embodiments, behind intervertebral disc wound, operation or relevant spinal operation, throw with CVAC the course for the treatment of.The effect of described dispensing is to regulate the intervertebral disc aquation, reduces the lasting infringement to intervertebral disc and myeloid tissue, and/or reduces the adverse effect of intervertebral disc wound.

Another aspect of the present invention is and throw with CVAC course for the treatment of with treatment inflammation or swelling or its combination.In one embodiment of the invention, be inflamed or swelling before or throw when pre-stage operation or the two course for the treatment of with at least one CVAC.At the appointed time throw the course for the treatment of with CVAC in the interval or with random appearance.In other embodiments, after by damage, wound, infection and/or immune system destruction or the caused inflammation of functional disorder or swelling, throw the course for the treatment of with CVAC.The effect of described dispensing be to reduce inflammation symptom, alleviate swelling, reduce the lasting infringement to inflammation or swelling tissue, or the adverse effect of minimizing inflammation or swelling, and its combination.

Another aspect of the present invention is and throw with CVAC course for the treatment of with the treatment wound.In one embodiment of the invention, throw with at least one CVAC course for the treatment of to improve or to reduce the actual healing time of wound.At the appointed time throw the course for the treatment of with CVAC in the interval or with random appearance.The effect of described dispensing is to reduce the healing time of wound and improves wound healing.

Other embodiments of the invention comprise the healing time that shortens wound, the fluid that increases involved area or the drainage of toxin or its combination, and/or regulate the related gene element of inflammation and immunoreation and the expression of the molecule that obtains thus.

Another aspect of the present invention is and throw with one or more CVAC course for the treatment of with the treatment ischemic disease.In one embodiment of the invention, before ischemic disease outbreak, throw the course for the treatment of with at least one CVAC, and at the appointed time throw in the interval and CVAC course for the treatment of.In other embodiments, after the ischemia event and/or before the operation relevant with ischemic disease, throw with CVAC the course for the treatment of.The effect of described dispensing is to alleviate ischemic conditions, reduces the ischemia infringement of tissue and/or the adverse effect of minimizing ischemia event.

One embodiment of the present of invention are for throwing with CVAC course for the treatment of to treat cerebral ischemia and relevant local ischemic event.Other embodiments of the invention are included in the cerebral ischemia event before and throw after the local ischemic event with CVAC the course for the treatment of, to treat, to prevent or improve the impact of cerebral ischemia.Other embodiment is included in before the operation relevant with cerebral ischemia and throws afterwards with CVAC course for the treatment of with prevention with improve the adverse effect that is caused by described operation.

Another embodiment of the present invention is for throwing with CVAC course for the treatment of to treat ischemic heart desease and relevant local ischemic event.Other embodiments of the invention are included in before the heart ischemia event and throw afterwards with CVAC the course for the treatment of, to treat, to prevent or improve the impact of ischemic heart desease.

Another embodiment of the present invention for throw with CVAC course for the treatment of with treatment, prevent and/or improve congestive heart failure.Other embodiment is included in before the operation relevant with ischemic heart desease and throws afterwards with CVAC course for the treatment of with prevention and/or improve the adverse effect that is caused by described operation.

The present invention provides on the other hand a kind of user is thrown with CVAC course for the treatment of to treat diabetes and/or relevant or by the method for its complication that causes with it.One embodiment of the present of invention are for throwing with CVAC course for the treatment of with the treatment diabetes.In another embodiment of the present invention, throw with at least one CVAC and treat diabetes with promotion the course for the treatment of.Another aspect of the present invention is and throw with at least one CVAC course for the treatment of to reduce the dependence about the traditional remedies of diabetes (for example medicine, such as insulin).Another aspect of the present invention is and throw with CVAC course for the treatment of with the treatment diabetic complication.Another aspect of the present invention is and throw with CVAC course for the treatment of with the treatment metabolic syndrome.

Another aspect of the present invention is and throw with CVAC course for the treatment of with treatment A Zihai Mo's disease.In one embodiment of the invention, throw and at least one CVAC course for the treatment of of the progress with prevention or the A Zihai Mo's disease that slows down.In another embodiment, throw with at least one CVAC course for the treatment of with prevention A Zihai Mo's disease.At the appointed time throw the course for the treatment of with CVAC in the interval or with random appearance.The effect of described dispensing is to alleviate fluid communication and/or the drainage of amyloid beta deposition thing and/or nerve degeneration and improvement involved area.

Another aspect of the present invention is and throw with CVAC course for the treatment of with treatment cancer, tumor or its combination.In one embodiment of the invention, throw before the treatment cancer and/or during the combination of expection cancer operation or its course for the treatment of with at least one CVAC.Another embodiment is included in and throws during the treatment cancer course for the treatment of with at least one CVAC.At the appointed time throw the course for the treatment of with a plurality of CVAC in the interval or with the random time interval.In other embodiments, behind treatment cancer and/or tumor, throw with CVAC the course for the treatment of.The effect of described dispensing is the slow down growth of cancer, the size of minimizing cancerous tissue, the adverse effect that prophylaxis of cancer shifted or reduced known chemical therapy, radiation therapy, other known cancer therapy and/or its combination.

In other embodiment (comprise above-described embodiment and aspect), the target of CVAC course for the treatment of includes, but is not limited to pressure, temperature, time, humidity parameter or its any combination.Can according to individual need customize target and the course for the treatment of parameter.In another embodiment of the present invention (comprise above-described embodiment and aspect), with the CVAC course for the treatment of and pharmaceutical admixtures combination throw with to be used for above-mentioned indication.Other embodiment (comprising above-described embodiment and aspect) comprise with the CVAC course for the treatment of and other therapies and non-drug therapy combination throw with to be used for above-mentioned indication.

Description of drawings

Figure 1A is described in the chart overview of the various pressure of using in time during exemplary CVAC course for the treatment of.Y-axis represents atmospheric pressure level and X-axis express time.The pressure (change such as the value on the Y-axis is indicated) that changes is applied to various time spans (change such as the value on the X-axis is indicated).Be 20 minutes length the exemplary CVAC course for the treatment of described in Figure 1A.

Figure 1B is described in the different chart overviews of the various pressure of using in time during another exemplary CVAC course for the treatment of.Y-axis represents atmospheric pressure level and X-axis express time again.Again, different pressures (change such as the value on the Y-axis is indicated) is applied to various time spans (change such as the value on the X-axis is indicated).This exemplary CVAC course for the treatment of also is 20 minutes length.

The specific embodiment

Pressure vessel unit (PVU) is that a kind of user environment on every side that promotes accurately and promptly changes the system of pressure.PVU can provide the atmospheric pressure that reduces and increase.The example of the correlation technique of unique PVU and the described PVU internal pressure of control is described in open case the 2005/0056279th A1 number of the United States Patent (USP) and it is incorporated herein by reference.Multiple PVU can use with Combination of Methods disclosed herein, includes, but is not limited to the PVU described in No. the 2005/0056279th, the open case of United States Patent (USP) and the PCT PCT/US04/21987 number, such as the low voltage unit of variation or fixation pressure and temperature.The those skilled in the art is with known other pressure unit or chamber and can use it in the method that discloses.

CVAC comprises one group of target the course for the treatment of, and described target is a plurality of atmospheric pressure, and CVAC comprises starting point and terminal point and the target of carrying out more than the course for the treatment of between Origin And Destination.These targets are to carry out with transformable precise order transmission and with various modes, and described pattern includes, but is not limited to circulation, repeats and/or linear change.When such as performance objective that this paper expects, performed target comprises the pressure in the CVAC device also as described herein is become another force value from a force value.Method as herein described is better than previous described static low-voltage therapy in many aspects, and it can comprise the Applicative time scope of minimizing and unique atmospheric pressure change and combination.In addition, CVAC course for the treatment of also can via with use the described course for the treatment of relevant blood vessel aerodynamic characteristic beneficial effect be provided.Can throw with novel and unique CVAC course for the treatment of with treatment hypertension, blood generation, stem cell therapy, spinal cord injury, intervertebral disc therapy, inflammation, wound healing, ischemic disease, diabetes and related complication, A Zihai Mo's disease and cancer.Throw the course for the treatment of with CVAC with variable frequency, last preferably at least 10 minutes and more preferably at least 20 minutes.Other the dispensing period can include, but is not limited to approximately 10 minutes, approximately 20 minutes, approximately 30 minutes, approximately 40 minutes, approximately 60 minutes, between between 10 and 20 minutes, between between 20 and 30 minutes, between between 30 and 60 minutes and between 60 and 120 minutes.The course for the treatment of or continuously the frequency of the course for the treatment of can include, but is not limited to every day, per month or medically indication or official hour.Can change the frequency of the course for the treatment of and persistent period being fit to medical condition to be treated, and can preferably utilize the preparation course for the treatment of (Set-UpSession) as described herein with the single course for the treatment of or one group the course for the treatment of form throw the course for the treatment of with CVAC.For instance, can throwing and the course for the treatment of or continuously the frequency of the course for the treatment of continued for 8 weeks 4 times weekly, continue weekly 8 weeks or 6 lasting 8 weeks weekly for 5 times for continuing for 8 weeks 3 times weekly.Can be easy to set up other frequency for each indivedual user.Similarly, also can change or regulate target in the described course for the treatment of to be fit to individuality and medical condition to be treated.In case user or operator on duty determine and can't well stand the described course for the treatment of, then can preferably start urgent interruption and user is reduced safely and break away from the described course for the treatment of.Can customize for individuality the arrangement of target, and can again under any those skilled in the art (such as the treatment doctor's) help, differentiate.In addition, can be as described throw and change with regular interval and order or with random time interval and order.The change of quantity, frequency and the persistent period of target and the course for the treatment of can be used for utilizing all Therapeutic Method of CVAC as herein described.

The method of altitude mixture control cyclical fluctuation (CVAC) program:

Method of the present invention contains one group and has the pressure target of specifying changeover portion.Can comprise other target, such as temperature or humidity, and can with pressure target simultaneously, before or after pressure target, implement these targets.Can be for individuality to be treated and patient's condition customization target array.Some terms relevant with this method will define to understand such as employed method in the context of the invention better hereinafter.

The CVAC program:Each user is reacted to the change of the air pressure, temperature and the oxygen content that occur in the altitude mixture control cyclical fluctuation process in the mode of uniqueness.This needs a kind of method for customizing that efficient and effective program is delivered to each user.Described program is by forming one group of course for the treatment of, in certain embodiments can with the described course for the treatment of with continuous wheel or circulation form throw with.This means that user can have such course for the treatment of, that is, it begins and repeats predetermined number of times and proceed to subsequently the predetermined treatment duration that the next one will repeat predetermined number of times.Program can contain one group of one or more course for the treatment of, and it preferably has the timetable of repetition separately.Preferably with the order transmission of the described course for the treatment of to be scheduled to, described order itself just repeats as same ring, therefore within a certain period of time user is thrown and gone through a course for the treatment of predetermined number of times.Subsequently, throwing is gone through predetermined number of times with next predetermined treatment duration to user.Preferably repeat this process, until to user throw with the predetermined treatment duration group in last.After finishing essential repetition, from the predetermined treatment duration group first of preferred described process itself begins repetition.The course for the treatment of or the group repeat count course for the treatment of time can be become the follow-up course for the treatment of or course for the treatment of group subsequently, but also flow process only can be thrown with once, begin successively next course for the treatment of subsequently.Can contain the target identical with the last course for the treatment of the follow-up course for the treatment of, or it can implement new required target array.The combination of the target in the course for the treatment of and each course for the treatment of is that the evaluation according to required physiology result and user customizes.In addition, in certain embodiments, user also can be regulated the CVAC parameter of the course for the treatment of in described unit, thereby real-time user feedback and change is provided.Use such as the parameter about CVAC course for the treatment of, regulate and comprise any positive and negative change that the parameter of CVAC course for the treatment of has been done.Described parameter as described herein.This comprises altitude mixture control cyclical fluctuation (CVAC) program.

CVAC course for the treatment of: CVAC comprises one group of target the course for the treatment of, and described target is pressure, is preferably the pressure that the mankind or mammal user can tolerate.CVAC comprises starting point, terminal point and the target of carrying out more than the course for the treatment of between Origin And Destination.These targets are preferably with transformable precise order transmission, and with the various modes execution, described pattern includes, but is not limited to circulation, repeats or linear change or its any combination.Starting point and the terminal point of any CVAC in the course for the treatment of all is preferably the ambient pressure that transmits the place.Any CVAC in the course for the treatment of intrinsic target all be by specifying changeover portion to connect or being bonded together.These changeover portions are the increase (decline) of pressure or the reduction (rising) of pressure, or the combination of the two.The character of any changeover portion all can characterize by " Δ P/T " (pressure over time) function.Changeover portion can be linear or produces waveform.Preferred all changeover portions all produce waveform.The most desirable waveform is sinusoidal wave (Sine), trapezoidal wave and square wave.When needs are regulated other target of time, temperature or humidity and its combination and condition, also will described other target with the pressure target while, successively or interval At All Other Times to move.Although the time of each course for the treatment of can according to throw with CVAC course for the treatment of required result change, the whole set of target and changeover portion is preferably transmitted with 20 minutes CVAC the course for the treatment of.For instance, can be through throwing the course for the treatment of with CVAC such as 5,10,15,16,17,18,19,20,25,30 minutes or longer minute increment.In a preferred embodiment, can customize each CVAC length of the course for the treatment of for each user.

Prepare the course for the treatment of: prepare also can be regarded as the course for the treatment of program.It is so that the single course for the treatment of that the maneuver that has more invasive that faces in the follow-up course for the treatment of that new user will experience for it or changeover portion are prepared through design.Prepare to illustrate the course for the treatment of institute's has age and physique and the patient's condition, and adopt and ear structure is more adapted to and make every grade of more comfortable motion minimal gradient of pressure balance in the ear structure.The purpose of preparing the course for the treatment of is to make new user for getting ready based on the program of its residing group customization.The function of preparing the course for the treatment of is to make the user can be desirably or without adapt to the multiple pressure change of specifying in the course for the treatment of uncomfortablely.Preparing course for the treatment of changeover portion can be linear or produces waveform.Preferred all changeover portions all are linear.This can increase by the gradient yardstick of formulating pressure target (from minimum increment to larger increment) and slowly the changeover portion increase until have no to realize the maximum changeover portion of pressure target maximum difference and realize uncomfortablely.Preferably prepare the structure of the course for the treatment of as follows: all identical with any course for the treatment of, starting point and terminal point are preferably ambient pressure.Realize being equivalent to target greater than environment 1000ft via steady linear transitions.Via slowly realizing being equivalent to the second target less than first object 500ft to moderate transition.Repeat these two steps until user to (in certain embodiments) CVAC management personnel or via airborne interface (on-board interface) reply " continuations " or " by " answer.When user indicates it to prepare to continue, initial target (1000ft) is increased 500ft, thereby make it become 1500ft.It is identical that the second target (than the little 500ft of first object) kept in the whole course for the treatment of, until reach the stage of withdrawing from (exit stage).When user indicates it to prepare to increase its gradient, just make target increase 500ft.At this moment, it is identical that changeover portion keeps, but can utilize the selection that increases the gradient (the short period factor) in the changeover portion.In case of necessity, user preferably has the selection of the low gradient of recovery.Can exist and make this select suitable icon or pad on the present airborne interface screen.The preferred preparation continues to be no more than 20 minutes the course for the treatment of.Prepare usually maximum 20 minutes of operation and when last changeover portion of beginning, execution the drops to ambient atmosphere pressure at last course for the treatment of.Preparing the course for the treatment of is new user program, until (namely continue target and changeover portion to high gradient) can be finished and prepared the course for the treatment of to user fully without interrupting or urgent the interruption.When throwing with CVAC course for the treatment of for therapeutic treatment, customizable preparation course for the treatment of is to be fit to the demand of its medical condition.Can determine the suitable preparation course for the treatment of according to the medical and technical staff's that qualification is arranged of user (such as the treatment doctor) guidance or the medical and technical staff that qualification is arranged (such as the treatment doctor) by the consulting user.

Interrupt: need to stop at user during any stage of the course for the treatment of of one period short period of the course for the treatment of, user can be carried out and stops by activating other appropriate device on icon or airborne interface touch screen or the control pad.This preferably makes the described course for the treatment of in interrupt phase maintenance one period predetermined time section, and such as 1 minute, will automatically continue the described course for the treatment of of this moment.Preferably can be interrupted the course for the treatment of 3 times, segmentation decline after this will occur and will need user to leave pressure vessel.The user archives will be marked, and user are got back to prepare the course for the treatment of, until it can be finished the course for the treatment of satisfactorily.The each use when interrupting can show warning or prompting on the screen, and it will inform the consequence that user has used how many times to interrupt and further use.During any course for the treatment of (no matter being to prepare the course for the treatment of or the course for the treatment of of other type), if user ear or nasal sinuses discomfort occur or no matter wishes to stop the course for the treatment of for any reason, also can use segmentation to descend.In certain embodiments, segmentation descend can every one-level the slowly sine wave decline changeover portion of 1000ft and the again rising of 500ft characterize.Decline can have higher or lower changeover portion, but ratio is generally approximately 1.5:1.In any moment between the segmentation decrement phase, user all can interrupt descending and keeping specified level or recover previous level until feel comfortable.If it is too violent that segmentation descends, user also can be selected to raise again so.As indicated above, all can carry out any again rising in each stage.User can be indicated " continuation " and will be recovered progress when descending.Continue this classification, until reach ambient pressure, this moment, top cover was opened, so that user can leave pressure vessel.

The urgent interruption: in a preferred embodiment, the present invention includes urgent interrupt function.When user is wished to finish immediately the course for the treatment of and speeded away pressure vessel, can activate urgent interrupt function." the urgent interruption " icon that touches on airborne interface, touch pad or the screen activates this selection.Can activate time prompt, confirm instruction and inquire user whether definite its wanted urgent interruption.User indicates it to assert instruction by pressing " continuation " or "Yes".Program is urgent interrupts and realizes that linear the deceleration descends until ambient pressure, and this moment, top cover was opened and user leaves.The archives of user are marked.When user is accepted its course for the treatment of next time, need the inquiry user whether to cause urgent interruption by discomfort.If so, user is got back to and prepared the program course for the treatment of.If not, inquire so whether user recovers its conventional predetermined treatment duration.Its conventional predetermined treatment duration of recovery is provided or returns the selection of preparing the course for the treatment of to the client.

Program and target criteria comprise major criterion medically:

The user that preferably will have similar build and a similar characteristics according to the answer of questionnaire is classified as one group.The information that obtains from questionnaire will guide the customization CVAC program that makes up each individuality.When throw with the CVAC program with treatment hypertension, improve that blood generates or when being used for stem cell therapy, also can determine with the health status of user suitable pressure and other parameter (such as persistent period, temperature or humidity) of target.Can throw and the target course for the treatment of that customizes according to medical condition and required therapy.Acceptable suitable target component can obtain by doctor or other the suitable medical personnel that seek advice from user before the course for the treatment of in the design target course for the treatment of and throwing and CVAC.Yet the contraindication of known CVAC is similar with the contraindication of commercial flight, allows thus multiple application.

The particular instance diagram of CVAC course for the treatment of is illustrated among Figure 1A and the 1B.Two graphic in, the parameter of described program is showed with the line chart form with axle, described axle is corresponding to time (x axle) and pressure variation (y axle).

Hypoxia is regulated:

The initial understanding of relevant Effect of hypoxia concentrates on via EPO and produces the Oxygenation that the increase that increases the erythrocyte generation that mediates increases blood in the affiliated field.Can make erythrocyte produce increase although believe the increase that EPO produces, its effect is not limited only to this behavior.EPO produces and multiple other behavior by the regulation and control of the molecule (such as HIF) of hypoxia inducible, comprises metabolism, angiogenesis and antiotasis, stimulates these behaviors can both the hypoxia infringement that protective tissue is avoided secondary be played a role.This protects preventability, occurs after ischemia or traumatic event; and [storehouse is K.U. (Eckardt K.U.) hereby to promote the generation of stem cell mobilization and erythrocyte; the storehouse is A. (Kurtz hereby; A.); the regulation and control (Regulation of erythropoietin production) that erythropoietin produces; Europe Journal of Clinical Investigation (Eur.J.Clin.Invest.), 35 ([Dan 3): 13-19, (2005)].About having concentrated on, the trial that increases donate blood volume and frequency throws and the erythropoietin aspect.Known erythropoietin can induce erythrocyte to produce, thereby increases the erythrocyte volume in the patient body.[the people such as Leo Kirch KA (Kirsh KA), erythropoietin as volume regulation and control hormone: summary (Erythropoietin asa volume-regulating hormone:an integrated view.), nephrology journal (Semin.Nephrol.), 25 (6): 388-91 (2005)].Nearest studies show that, behind throwing and erythropoietin child's erythrocyte volume is significantly increased.This increase allows the child that studies can donate blood from body before carrying out open heart operations.The increase of erythrocyte volume especially can prevent usually reducing with the erythrocyte volume of donating blood relevant of child.Keep stable red blood cell count(RBC) and allow each children operation of expection to have enough blood volume to carry out from body to donate blood (even within 20 day time, repeating to donate blood), and keep enough blood and count to allow subsequently operation.[the people such as Sang Suoni V (Sonzogni V), before child's the art of erythropoietin therapy and experience open heart operations from body donate blood (Erythropoietin therapyand preoperative autologous blood donation in children undergoing open heart surgery), Britain's anesthesia magazine (Brit.J.Anaesth.), 87 (3): 429-34 (2001)].Other research shows that also erythropoietin is for increasing erythrocyte volume, donating blood volume and the effect of the ability of repeatedly donating blood.[the people such as Gourde(G) promise LT (Goodnough LT), the experience invasive is from body bloodletting and acceptance and the art proerythrocyte production (Preoperative red cell production in patients undergoing aggressive autologousblood phlebotomy with and without erythropoietin therapy) of not accepting the patient of erythropoietin therapy, blood transfusion magazine (Transfusion), 32 (5): 441-5 (1992); Than people such as this horse DH (Biesma DH), the effect (The efficacy of subcutaneous recombinanthuman erythropoietin in the correction of phlebotomy-induced anemia in autologous blooddonors) of the anemia that subcutaneous recombinant human erythropoietin brings out for the bloodletting of proofreading and correct from the body blood donor, blood transfusion magazine (Transfusion), 33 (10): 825-9 (1993)].

Except throw with EPO, it is known that therapy provides some beneficial effects for increasing erythrocyte generation, blood oxygenation and packed cell volume such as carrying out that oxygen is peeled off etc. under static air pressure and quiet hour piece.[the people such as Hai Nike K (Heinicke K), long term exposure causes blood in human body in Lactoferrin mass penalty in intermittence low-oxygen, the blood plasma volume reduces and erythropoietin plasma content rising (Long-term exposure to intermittent hypoxia results in increasedhemoglobin mass, reduced plasma volume, and elevated erythropoietin plasma levels inman), Europe applied physiology magazine (Eur.J.Appl.Physiol.), 88 (6): 535-43 (2003)].Can cause histologic lesion and even death although the oxygen of health or particular organization is peeled off, peel off when reaching special time period when the controlled oxygen that applies under given conditions health or particular organization or its combination, it may be for useful.Can by reduce in the atmosphere oxygen content or by reducing atmospheric pressure (low pressure condition) thus reducing the oxygen availability provides static hypoxia adjusting for effectively breathing.

About improve throwing that trial that stem cell mobilization, implantation and transplanting recover afterwards concentrated on erythropoietin with.Known erythropoietin (EPO) can induce erythrocyte to produce, thereby increases the erythrocyte volume in the patient body.[the people such as Leo Kirch KA (Kirsh KA), erythropoietin as volume regulation and control hormone: comprehensive visual angle (Erythropoietin as a volume-regulating hormone:anintegrated view.), nephrology journal (Semin.Nephrol.), 25 (6): 388-91 (2005)].Typical mobilization scheme utilizes cytokine granulocyte colony-stimulating factor (G-CSF).Yet also known interpolation EPO can strengthen hemopoietic progenitor cell (stem cell) and immune effector cell, thereby improves collection and increase cell percentage ratio for successfully implanting during mobilizing.[tall assorted SS. (Joshi, SS.), Miller K. (Miller, K.), Jackson J.D. (Jackson, J.D.), Wa Kenjin P. (Warkentin, P.) and Kai Sijie A. (Kessinger, A.), come to gather with the blood stem cell after erythropoietin+G-CSF mobilization in comfortable cancer patient's body the monocytic immunological characteristic (Immunological properties of mononuclear cells fromblood stem cell harvests following mobilization with erythropoietin+G-CSF in cancerpatients) of thing, cell therapy (Cytotherapy), 2 (1): 15-24 (2002)].The final mobilization factor is cytokine VEGF (VEGF).Except stimulating angiogenesis, also VEGF is associated with the increase of bone Marrow Stem Cell Mobilization, transplant front another factor of mobilizing thereby provide to improve.

After the transplanting, EPO also can play the effect of the reconstruction that improves patient's hemopoietic system.The combination of EPO+G-CSF can be accelerated successfully to implant after stem cell transplantation.[Id.; Depew gram W. (Dempke, W.) and execute More H.J. (Schmoll, H.J.), the possible New Set of erythropoietin therapy (Possible new indications for erythropoietin therapy), clinical medicine (Med.Klin.), (Munich (Munich)), 96 (8): 467-74 (2001)].The improvement that success is implanted is directly related with the improvement that blood samples of patients is rebuild.Known throwing and EPO are equally also by improving that peripheral red blood cells quantity is rebuild and by reducing the recovery time after required transfusion volume between convalescent period improves stem cell transplantation.Reduce recovery time and also reduce the probability of concurrent opportunistic infection and the rear nursing of other transplanting and will reduce cost and the improvement recovery.[Vyacheslav Ivanov V. (Ivanov, V.), Fa Sheer C (Fuacher, C), silent M. (the Mohty that carries, M.), than Ge Er K. (Bilger, K.), the Lay pari restrains P. (Ladaique, P.), Sheng Ai carries D. (Sainty, D.), A Nulite C (Arnoulet, C), look into and cling to your C (Chabannon, C), tie up adopted N. (Vey, N.), Ka Meiluo J. (Camerlo, J.), Bao Abudela R. (Bouabdallah, R.), this P. (Viens of Wien, P.), the strange D. of horse traction Buddhist nun (Maraninchi, D.), bar Du V.J. (Bardou, V.J.), Ai Sidaileni B. (Esterni, B.) and Bu Laisi D. (Blaise, D.), the early stage hemoglobin of improving after the allogeneic stem cell transplantation of reduction intensity adjustments with recombinant erythropoietin of throwing is recovered (Earlyadministrationofrecombinant erythropoietin improves hemoglobinrecovery after reduced intensityconditioned allogeneic stem cell transplantation), bone marrow transplantation (B one Marrow Transplant), 36 (10): 901-06 (2005); Fan Sitelalun G. (Vanstraelen, G.), visit human relations F. (Baron F.), Pi Aier P. (Frere, P), Ha Faou K. (Hafraoui, K.), special G. (Fillet in the Fil, G.) and Billy gold Y. (Beguin, Y.), the effect of 1 month initial recombinant human erythropoietin therapy behind autologous peripheral blood stem cell transplantation (Efficacy of recombinant human erythropoietin therapy started one month afterautologousperipheral blood stem cell transplantation), hematology (Haematologica), 90 (9): 1269-70 (2005)].

The static hypoxia preconditioning of known appropriateness provides protection to avoid tissue and primary cellular defect via toleration.When environment oxygen content reduced (hypoxia), downstream effect comprises provided the infringement of protection to avoid causing because of subsequently hypoxia.[F. (the Sharp of Sharp; the people such as F.); hypoxia preconditioning provides protection to avoid ischemic brain injury (Hypoxic PreconditioningProtects against Ischemic Brain Injury); neurological magazine: U.S. experimental neurology association magazine (NeuroRx:J.Am.Soc.Exp.Neuro.), the 1st volume: 26-25 (2004)].Understand not yet fully for this toleration, but it is associated with various kinds of cell mechanism and molecule, include, but is not limited to such as erythropoietin (EPO) but, hypoxia inducible factor (HIF), tumor necrosis factor (TNF), glycogen, lactate equimolecular.[F. (the Sharp of Sharp; the people such as F.); hypoxia preconditioning provides protection to avoid ischemic brain injury (Hypoxic Preconditioning Protectsagainst Ischemic Brain Injury); neurological magazine: U.S. experimental neurology association magazine (NeuroRx:J.Am.Soc.Exp.Neuro.), the 1st volume: 26-25 (2004)].In addition, useful static hypoxia adjusting is not to add fully.Throw with the continuous course for the treatment of and can have adverse effect.Cross low oxygen concentration and can cause detrimental effect to tissue and whole health.Similarly, the hypoxia adjusting than long duration also can have detrimental effect except some required beneficial effect is provided.[F. (the Sharp of Sharp; the people such as F.); hypoxia preconditioning provides protection to avoid ischemic brain injury (Hypoxic PreconditioningProtects against Ischemic BrainInjury); neurological magazine: U.S. experimental neurology association magazine (NeuroRx:J.Am.Soc.Exp.Neuro.), the 1st volume: 26-25 (2004)].In addition, previous hypoxia Regulating study utilizes static pressure to reach the time range of overlength.Compare with the above-mentioned static hypoxia adjusting that the those skilled in the art is known, CVAC utilizes the height of application and the multiple change of variable time scope the course for the treatment of.Pressure changes the in time multiple beneficial effect relevant with hypoxia condition of combination results of range (comprising the in time interior quick change that changes of scope), stimulates other beneficial effect and can not cause and utilize static hypoxia to regulate being seen detrimental effect.Similarly, although the persistent period of CVAC course for the treatment of is unrestricted, usually want much shorter than the current long-time piece of regulating for static low-voltage.Therefore, produce the alternative method that useful hypoxia effect will provide novel and be better than current static hypoxia control method as indicated above the course for the treatment of with unique CVAC.

Therapeutic Method

Hypertension, blood generate (erythropoiesis) and stem cell therapy

Preferably with variable frequency throw with for hypertension, blood generates and the CVAC course for the treatment of of stem cell therapy (including, but is not limited to recover after helping stem cell mobilization, stem cell to implant and transplant), lasts at least 10 minutes and more preferably at least 20 minutes.Other the dispensing period can include, but is not limited to approximately 10 minutes, approximately 20 minutes, approximately 30 minutes, approximately 40 minutes, approximately 60 minutes, between between 10 and 20 minutes, between between 20 and 30 minutes, between between 30 and 60 minutes and between 60 and 120 minutes.The course for the treatment of or continuously the frequency of the course for the treatment of can include, but is not limited to every day, per month or medically indication or official hour.Can change the frequency of the course for the treatment of and persistent period being fit to medical condition to be treated, and preferably utilize as indicated above preparation course for the treatment of with the single course for the treatment of or one group the course for the treatment of form throw the course for the treatment of with CVAC.For instance, can throwing and the course for the treatment of or continuously the frequency of the course for the treatment of continued for 8 weeks 4 times weekly, continue weekly 8 weeks or 6 lasting 8 weeks weekly for 5 times for continuing for 8 weeks 3 times weekly.Can be easy to set up other frequency for each indivedual user.Similarly, also can change or regulate target in the described course for the treatment of to be fit to individuality and medical condition to be treated.Can customize for individuality the arrangement of target, and can again under any those skilled in the art (such as the treatment doctor's) help, differentiate.In addition, can be as described throw and change with regular interval and order or with random time interval and order.The change of quantity, frequency and the persistent period of target and the course for the treatment of can be used for utilizing all Therapeutic Method of CVAC as herein described.

In one aspect of the present invention, before the clinical hypertension of development or the relevant hypertension patient's condition, throw and the treatment of the CVAC preventability course for the treatment of and/or help prophylaxis of hypertension.In one embodiment, preventative throwing and CVAC also can prevent or be reduced in the histologic lesion in subsequently the hypertension event course for the treatment of.CVAC increases blood flow the course for the treatment of, stimulate angiogenesis, regulate the blood fat pattern and stimulate the ability adjustable tissue of protectiveness cell effect condition and vascular to prevent from proceeding to the hypertension state.As defined herein, hypertensive treatment comprise throw with at least one CVAC course for the treatment of with prophylaxis of hypertension (that is, before diagnosis), throw with at least one CVAC course for the treatment of with treatment hypertension and throwing and at least one CVAC course for the treatment of to improve hypertension.

In addition, it is reported that CVAC is similar to effect and the blood vessel air driven pump of user health the course for the treatment of, stimulate thus flowing of body inner fluid (including, but is not limited to blood and lymph fluid).The negative pressure that CVAC forces the course for the treatment of and malleation can affect flowing of body inner fluid or motion, thereby improve the transmission of useful nutrient, immune factor, blood and oxygen, also improve the removal of harmful toxins, fluid and damaged cell or tissue simultaneously.The combination of the CVAC beneficial effect course for the treatment of is so that can treat hypertension and related conditions.

In the present invention on the other hand, treat the user of wishing to increase the user of blood growing amount or wishing recovery time required between the extraction of shortening blood or the blood drawing (be commonly referred to and donate blood) with altitude mixture control cyclical fluctuation program.Throw with CVAC to increase the Oxygenation of blood; Increase the erythrocyte number in the user body; Increase the generation of HIF; And/or stimulate other related physiological process that affected by the CVAC treatment, move such as fluid (lymph fluid, blood or other body fluid).Treatment be by throw the course for the treatment of with one or more CVAC with.Can be the described course for the treatment of user appointment or customize by the doctor's input by user.Can before any operation or other therapeutic scheme, throw with CVAC course for the treatment of to increase blood growing amount and blood quality so that more effective and donate blood more continually.

In the present invention on the other hand, treat the user that needs stem cell therapy with altitude mixture control cyclical fluctuation program.As defined herein, stem cell therapy comprises the recovery behind mobilization, implantation and the stem cell therapy.In one embodiment, throw with CVAC with stem cell mobilization in blood.As used herein, mobilization comprises the mobilization of the stem cell in any source (from body, allosome etc.).In another embodiment, throwing is implanted stem cell in the user with promotion with CVAC.In another embodiment, throw with CVAC to promote the recovery behind the stem cell therapy.As used herein, mobilize the method for stem cell to be included in to throw before or after the mobilization program course for the treatment of with at least one CVAC.In addition, mobilize the method for stem cell also to comprise specifying or the course for the treatment of with at least one CVAC is thrown at the random time interval.Similarly, the method for implanting such as promotion disclosed herein also include, but is not limited to before the implant procedure, during or throw afterwards the course for the treatment of with at least one CVAC, and its also can specify or the random time interval throw with.Finally, promote from the method that stem cell therapy recovers also include, but is not limited to before the stem cell program, during or throw afterwards the course for the treatment of with at least one CVAC, and its also can specify or the random time interval throw with.Throw with the CVAC course for the treatment of that is used for stem cell therapy and increase erythrocyte number in the user body with the Oxygenation that increases blood; Increase the generation of HIF; And/or stimulate other related physiological process that affected by the CVAC treatment, move such as fluid (lymph fluid, blood or other body fluid).Treatment be by throw the course for the treatment of with one or more CVAC with.Can be the described course for the treatment of user appointment or customize by the doctor's input by user.Can before any operation or other therapeutic scheme, throw and CVAC course for the treatment of, thereby preferably more be fruitful than standard treatment and more effectively mobilize stem cell; Preferably more effectively implant stem cell than standard treatment; And preferred faster and more effectively promote recovery behind the stem cell therapy than standard treatment.

Although be not limited to particular mechanism of action, believe that the CVAC therapy provides the blood flow of increase, red blood cell count(RBC), angiogenesis and the protectiveness cell effect of increase, the ability that EPO produces, VEGF produces and HIF produces can help treatment, prevent and improve hypertension; Improve erythropoiesis; And regulate the recovery behind mobilization, implantation and the stem cell therapy.In addition, it is reported that CVAC is similar to effect and the blood vessel air driven pump of user health the course for the treatment of, stimulate thus flowing of body inner fluid (including, but is not limited to blood and lymph fluid).The negative pressure that CVAC forces the course for the treatment of and malleation can affect flowing of body inner fluid or motion, thereby improve the transmission of useful nutrient, immune factor, blood and oxygen, also improve the removal of harmful toxins, fluid and damaged cell or tissue simultaneously.The combination of the CVAC beneficial effect course for the treatment of is so that can prevent, treat and/or improve hypertension.Similarly, the beneficial effect of CVAC course for the treatment of causes erythropoietic improvement.At last, CVAC also advantageously affects mobilization and the adjusting of the recovery time behind implantation and the stem cell therapy of stem cell the course for the treatment of.In addition, be not limited to CVAC is used for Bone Marrow Stem Cells Transplantation, and CVAC course for the treatment of can with relate to stem cell mobilization, collection and/or throwing and the similar mode of stem cell therapy of any type throw with.

In estimating the CVAC process of the course for the treatment of, regulate and have multiple meaning.In hypertensive situation, adjusting means the blood pressure that reduces user.In the situation that blood generates, adjusting means any change that causes erythrocyte number, packed cell volume or blood volume to increase.In addition, in any shortening of regulating the time between the blood extraction that means success in the improved situation of erythropoiesis.At last, in the situation that stem cell therapy regulate and mean and increase stem cell mobilization, compare with standard treatment and reduce recovery time, recover with the pain that standard treatment is compared low and/or compare with standard treatment more stable physiologic parameters reaction.

Also can with the CVAC course for the treatment of and medicine and somatomedin scheme or non-drug therapy (include, but is not limited to that medical herbs replenishes, vitamin, alteration in nutrition and it is reported can the assist blood generation, stem cell mobilization, implantation and recovery or hypertensive motion scheme) be used in combination.As indicated above, can throw with a kind of medicine, multi-medicament or non-drug therapy before, throw CVAC course for the treatment of with any combination or arrangement simultaneously or afterwards.The various arrangement that pharmacotherapy, non-drug therapy and CVAC make up the course for the treatment of all is possible, and can differentiate the combination of the type that is suitable for medical condition and specific medication under any those skilled in the art (such as the treatment doctor's) help.

Spinal cord injury, intervertebral disc therapy, inflammation and swelling and wound healing

VEGF (VEGF) is the known hypoxia inducible albumen under a kind of HIF-1 of being in α control.Confirm, VEGF for spinal cord injury after mammiferous spinal neuron have the direct neural protective effect.[the people such as fourth XM (DingXM); in vitro in the hypoxia situation external source VEGF to the neuroprotective (Neuroprotective effect of exogenous vascular endothelial growth factor on rat spinal cordneurons in vitro hypoxia) of rat spinal cord neurons; Chinese Medical Journal (English edition) (Chin.Med.J (Engl)); 118 (19): 1644-50, on October 5th, 2005].Shown that intermittent the throwing with static hypoxia condition can increase diaphragm locomotor activity (phrenic nerves is breathed and other organ dysfunction via diaphragm control), and after spinal cord injury, reached the described effect of performance in time in 8 weeks.[up to FJ (Golder, FJ) and John Cameron Mitchell GS (Mitchell, GS), utilize the respiratory function (Spinal synaptic enhancementwith acute intermittent hypoxia improves respiratoryfunction after chronic cervical spinalcordinjury) after the spinal column synapse of acute intermittence low-oxygen strengthen to improve chronic cerebral spinal cord injury, Journal of Neuroscience (J.Neurosci.), 25 (11): 2925-32, on March 16th, 2005].The improvement of spinal cord lesion can strengthen respiratory movement output, and stimulates the neural plasticity in the impaired spinal cord, but long-term hypoxia can have a negative impact.Therefore, chronic, intermittent static hypoxia condition produces the most useful result.[richness is strangled D. (Fuller, the people such as D.), behind cerebral spinal cord injury, strengthen the synapse path (SynapticPathways to Phrenic Motoneurons Are Enhanced by Chronic Intermittent Hypoxia afterCervical Spinal Cord Injury) of diaphragm motor neuron by the chronic intermittent hypoxia, Journal of Neuroscience (J.Neurosci.), 23 (7): 2993-3000, on April 1st, 2003].Other research be presented at throw after the spinal cord injury and the treatment of static hypoxia interval after, the expression of glycolytic enzyme and VEGF and gained content increase.Described effect can be used for inducing hypoxic tolerance and the vascularity of impaired spinal cord.[the people such as Xiao Wei H (Xiaowei H), but hypoxia inducible factor 1 α and the experimentation (Theexperimental study of hypoxia-inducible factor-lal pha and its target genes in spinal cordinjury) of its target gene in spinal cord injury, spinal cord magazine (Spinal Cord), 44 (1): 35-43, in January, 2006].

Pharmacotherapy, physiotherapy and surgical intervention are mainly contained in current treatment about acute spinal cord injury.Surgical intervention for the damage of health greatly and can cause other medical science complication, especially when health because of patient's serious spinal cord injury and/or general health and patient's condition degree weakness to the utmost or all the more so when being badly damaged.Also can use such as medicines such as corticosteroid and treat acute spinal cord injury, but identical with operation, medicine can because of the negative side-effects of chemical compound itself, treatment time length and unforeseen individuality the reaction of medicine is brought other problem.For instance, for amelioration of inflammation and swelling is thrown and glucocorticoid except the adverse effect of known life-time service, also can make the exitotoxicity phase aggravation of nerve injury, thus limit its for the effect of restriction initial damage with and be used for the probability of extended regimen.Physiotherapy also can be improved some adverse effect of spinal cord injury, but this treatment is mainly for influenced muscle group but not spinal cord itself and improve Neuronal Damage.It should be noted that most of spinal injury also is incomplete, therefore the intact neuron path of spinal cord and reserve part is not cut off in described infringement fully.Recently, thus physiotherapy and most of pharmaceutical admixtures can't solve fully and strengthen the demand that these residual paths are improved neurological functions and control.

Pharmacotherapy, physiotherapy and surgical intervention are mainly contained in current treatment about intervertebral disc degeneration.As indicated above, surgical intervention is very big to the damage of health.Also can use such as medicines such as corticosteroid and treat intervertebral disc degeneration, but identical with operation, medicine can because of the negative side-effects of chemical compound itself, treatment time length and unforeseen individuality the reaction of medicine is brought other problem.For instance, for amelioration of inflammation and swelling is thrown and glucocorticoid except the adverse effect of known life-time service, also can make the exitotoxicity phase aggravation of nerve injury, thus limit its for the effect of restriction initial damage with and be used for the probability of extended regimen.Physiotherapy also can be improved some adverse effect of intervertebral disc degeneration, but this treatment is mainly for influenced muscle group but not spinal cord, improve intervertebral disc infringement and vertebral plate infringement.

The treatment of inflammation and swelling utilizes similarly medicine and is usually directed to and throws and steroid with multiple composite and method.In addition, also with multiple non-steroidal compound usually and steroid anti-inflammatory compound or drug regimen be used for the treatment of inflammation.Identical with inflammation, antiphlogistic treatment, antibiotic and physical protection or intervention (binder, sealant, suture etc.) are mainly contained in current treatment about wound.Such as corticosteroid and other based on the medicines such as antibiotic medicine of steroid can because of the negative side-effects of chemical compound itself, treatment time length and unforeseen individuality the reaction of medicine is brought other problem.For instance, for amelioration of inflammation and swelling throw with glucocorticoid have the known detrimental effect relevant with life-time service, thereby limit its effect and it is used for the effectiveness of extended regimen, and the inflammation-inhibiting reaction is not always favourable to wound healing.

Knownly the other therapies such as peel off such as oxygen and also can provide some beneficial effect.Can cause histologic lesion and even death although the oxygen of health or particular organization is peeled off, confirm, peel off when reaching special time period when the controlled oxygen that applies under given conditions health or particular organization or its combination, it may be for useful.Can by reduce in the atmosphere oxygen content or by reducing atmospheric pressure (low pressure condition) thus reducing the oxygen availability provides the hypoxia adjusting for effectively breathing.Two kinds of methods all can provide useful result, comprise preventing the infringement that caused by inflammation and swelling.Yet all current hypoxia forms of regulating all relate to and apply static pressure and relate to relative prolonged application.

Need to be for another therapy of spinal cord injury, intervertebral disc treatment, inflammation and wound healing.Also need the described therapy without the potential negative side-effects of pharmaceutical admixtures.Perhaps, need to reduce by changing pharmaceutical admixtures the negative side-effects of pharmaceutical admixtures, can work with pharmaceutical admixtures one valuably, or can synergistic therapy when being used in combination with pharmaceutical admixtures.Need within shorter treatment time, make beneficial effect maximization and can not cause such as low pressure or the hypoxia of the detrimental effect that utilizes the current being seen adjusting of static low-voltage control method and regulate.Also need in whole adjustment process, utilize described low pressure or the hypoxia of multiple and/or different pressures to regulate.The low pressure or the hypoxia that also need also to incorporate the pneumatic consideration of blood vessel into except hypoxia is considered are regulated.Present invention disclosed herein provides described demand and its uniqueness and is better than all previous low pressure regulates forms.In numerous benefits, use the beneficial effect that CVAC course for the treatment of provides low pressure to regulate because of the pressure of uniqueness and ageing with the time range of very big shortening.In addition, CVAC also provides blood vessel pneumatic beneficial effect with identical time range the course for the treatment of.

In one aspect of the present invention, throw and the CVAC course for the treatment of that is used for the treatment of spinal cord injury with variable frequency, last preferably at least 10 minutes and more preferably at least 20 minutes.Other the dispensing period can include, but is not limited to approximately 10 minutes, approximately 20 minutes, approximately 30 minutes, approximately 40 minutes, approximately 60 minutes, between between 10 and 20 minutes, between between 20 and 30 minutes, between between 30 and 60 minutes and between 60 and 120 minutes.The course for the treatment of or continuously the frequency of the course for the treatment of can include, but is not limited to every day, per month or medically indication or official hour.Can change the frequency of the course for the treatment of and persistent period being fit to medical condition to be treated, and can preferably utilize as indicated above preparation course for the treatment of with the single course for the treatment of or one group the course for the treatment of form throw the course for the treatment of with CVAC.For instance, can throwing and the course for the treatment of or continuously the frequency of the course for the treatment of continued for 8 weeks 4 times weekly, continue weekly 8 weeks or 6 lasting 8 weeks weekly for 5 times for continuing for 8 weeks 3 times weekly.Can be easy to set up other frequency for each indivedual user.Similarly, also can change or regulate target in the described course for the treatment of to be fit to individuality and medical condition to be treated.In case user or operator on duty determine and can't well stand the described course for the treatment of, then can start urgent interruption and user is reduced safely and break away from the described course for the treatment of.Can customize target array for individuality, and can again under any those skilled in the art (such as the treatment doctor's) help, differentiate.In addition, can be as described throw and change with regular interval and order or with random time interval and order.The change of quantity, frequency and the persistent period of target and the course for the treatment of can be used for utilizing all Therapeutic Method of CVAC as herein described.

In one embodiment of the invention, come prophylactic treatment expection operation on spinal cord maybe may affect the user of any operation of spinal cord with altitude mixture control cyclical fluctuation program.During the expection operation on spinal cord, throw with CVAC to increase the spinal cord Oxygenation, increase HIF produces and to stimulate other related physiological process (such as fluid motion and minimizing swelling) that affected by the CVAC treatment.Treatment be by throw the course for the treatment of with one or more CVAC with.Can be the described course for the treatment of user appointment or customize by the doctor's input by user.Can before any described operation or treatment, throw with CVAC course for the treatment of to help to reduce or prevent any illeffects.

In the present invention on the other hand, throw with CVAC course for the treatment of with the treatment intervertebral disc.As described herein, the intervertebral disc treatment includes, but is not limited to intervertebral disc aquation and prevention, treatment or improves the intervertebral disc wound.Similarly, the treatment of the intervertebral disc dispensing that comprises preventive dosage and be used for the treatment of and keep.Throw and the CVAC course for the treatment of that is used for the treatment of intervertebral disc with variable frequency, last preferably at least 10 minutes and more preferably at least 20 minutes.Other the dispensing period can include, but is not limited to approximately 10 minutes, approximately 20 minutes, approximately 30 minutes, approximately 40 minutes, approximately 60 minutes, between between 10 and 20 minutes, between between 20 and 30 minutes, between between 30 and 60 minutes and between 60 and 120 minutes.The course for the treatment of or continuously the frequency of the course for the treatment of can include, but is not limited to every day, per month or medically indication or official hour.Can change the frequency of the course for the treatment of and persistent period being fit to medical condition to be treated, and can preferably utilize as indicated above preparation course for the treatment of with the single course for the treatment of or one group the course for the treatment of form throw the course for the treatment of with CVAC.For instance, can throwing and the course for the treatment of or continuously the frequency of the course for the treatment of continued for 8 weeks 4 times weekly, continue weekly 8 weeks or 6 lasting 8 weeks weekly for 5 times for continuing for 8 weeks 3 times weekly.Can be easy to set up other frequency for each indivedual user.Similarly, also can change or regulate target in the described course for the treatment of to be fit to individuality and medical condition to be treated.

In another embodiment of the present invention, come prophylactic treatment expection intervertebral disc operation maybe may affect the user of any operation of spinal cord and/or intervertebral disc with altitude mixture control cyclical fluctuation program.When expecting described operation, throwing and other related physiological process (such as fluid motion and minimizing swelling) that CVAC produces with Oxygenation, the increase HIF that increases endplate and stimulation is affected by the CVAC treatment.Described fluid motion further promotes the aquation of intervertebral disc.Treatment be by throw the course for the treatment of with one or more CVAC with.Can be the described course for the treatment of user appointment or customize by the doctor's input by user.Can before any described operation or treatment, throw with CVAC course for the treatment of to help to reduce or prevent any illeffects.

In the present invention on the other hand, treat the user of any type of inflammation of experience or swelling and its combination (comprising the described patient's condition of expection) with altitude mixture control cyclical fluctuation program.Therefore, the treatment of inflammation comprises no matter cause how, is thrown before inflammation or swelling and after inflammation or the swelling outbreak and at least one CVAC course for the treatment of.In one embodiment, throwing and CVAC other related physiological process (moving and minimizing swelling such as fluid (lymph fluid, blood or other body fluid)) that Oxygenation, increase HIF produce and stimulation is affected by the CVAC treatment with increase inflammation or swelling tissue.Treatment be by throw the course for the treatment of with one or more CVAC with.Can be the described course for the treatment of user appointment or customize by the doctor's input by user.In another embodiment, can before or after any operation or other therapeutic scheme, throw with CVAC course for the treatment of to help minimizing or the prevention any illeffects relevant with swelling with inflammation.

Another aspect of the present invention is and throw with CVAC course for the treatment of for wound healing.In one embodiment of the invention, treat the user with any type wound with the altitude mixture control cyclical fluctuation, described wound includes, but is not limited to such as surface injury, incision, scrape scratch, lacerated wound, burn, ulcer, perforating injury, stab and the wound such as shell wound (such as the wound that is caused by firearms shooting or other weapon).Throwing and other related physiological process (such as fluid (lymph fluid, blood or other body fluid) motion and minimizing swelling) that CVAC produces with Oxygenation, the increase HIF that increases wound tissue and/or stimulation is affected by the CVAC treatment.In addition, use CVAC the course for the treatment of wound tissue to be applied micromechanical forces to stimulate cellular proliferation.Before the purposes that CVAC is used for the treatment of wound healing the course for the treatment of is included in wound, wound causes the purposes of the rear described course for the treatment of, reduce the purposes of the inflammatory phase length of wound healing, reduce the purposes of the proliferation period length of wound healing, and reduce the maturation and the purposes of reinventing phase length of During Wound Healing.

Treatment be by throw the course for the treatment of with one or more CVAC with.Can be the described course for the treatment of user appointment or customize by the doctor's input by user.Can before any operation or other therapeutic scheme, throw with CVAC course for the treatment of to help to reduce or prevent any illeffects.Also the CVAC course for the treatment of and pharmaceutical admixtures or non-drug therapy (such as operation, binder, sealant or topical cream, ointment etc.) and its combination can be used in combination to help or improve wound healing.

Although be not unrestricted, it is reported that CVAC is similar to effect and the blood vessel air driven pump of user health the course for the treatment of, stimulate thus flowing of body inner fluid (including, but is not limited to blood and lymph fluid).The negative pressure that CVAC forces the course for the treatment of and malleation can affect flowing of body inner fluid or motion, thereby improve the transmission of useful nutrient, immune factor, blood and oxygen, also improve the removal of harmful toxins, fluid and damaged cell or tissue simultaneously.In addition, it is reported that CVAC also provides the blood flow of increase, red blood cell count(RBC), angiogenesis and protectiveness cell effect, EPO generation and the HIF of increase to produce the course for the treatment of, therefore can help to recover and repair damaged tissues.The combination of the CVAC beneficial effect course for the treatment of causes inflammation and the treatment of swelling and the improvement of its recovery, and is of value to similarly all above-mentioned each side and embodiment.

Ischemia, diabetes, A Zihai Mo's disease and cancer

The static hypoxia preconditioning of known appropriateness can provide protection to avoid the ischemia infringement via toleration.When environment oxygen content reduced (hypoxia), downstream effect comprises provided protection to avoid hypoxia or the caused infringement of ischemia because of subsequently.[F. (the Sharp of Sharp; the people such as F.); hypoxia preconditioning provides protection to avoid ischemic brain injury (HypoxicPreconditioning Protects against Ischemic Brain Injury); neurological magazine: U.S. experimental neurology association magazine (NeuroRx:J.Am.Soc.Exp.Neuro.), the 1st volume: 26-25 (2004)].Understand not yet fully for this toleration, but it is associated with various kinds of cell mechanism and molecule, include, but is not limited to such as erythropoietin (EPO) but, hypoxia inducible factor (HIF), tumor necrosis factor (TNF), glycogen, lactate equimolecular.[F. (the Sharp of Sharp; the people such as F.); hypoxia preconditioning provides protection to avoid ischemic brain injury (HypoxicPreconditioning Protects against Ischemic Brain Injury); neurological magazine: U.S. experimental neurology association magazine (NeuroRx:J.Am.Soc.Exp.Neuro.), the 1st volume: 26-25 (2004)].Except above-mentioned impact, also confirm hypoxia scalable glucose transporter and improve glucose tolerance and insulin sensitivity.The adjusting of glucose transporter can increase via the exchange of the glucose between cell and the blood ability of the amount of the glucose in the cell regulate and control blood.[Qiu (Chiu, the people such as L.L.), " intermittence low-oxygen of prolongation and training are on the impact (Effect of Prolonged Intermittent Hypoxia and ExerciseTraining on Glucose Tolerance and Muscle GLUT4Protein Expression in Rats) of glucose tolerance and the muscle GLUT4 protein expression of rat ", Biomedical Science magazine (J.Biomedical Sci), (2004), 11:838-846; High wooden H. (Takagi, the people such as H.), " hypoxia raises glucose transport activity (Hypoxia Upregulates Glucose Transport Activity Through an Adenosine-Mediated Increaseof GLUT1Expression in Retinal Capillary Endothelial Cells) by the increase that GLUT1 in the retinal capillary endothelium cell of adenosine mediation expresses ", diabetes magazine (Diabetes), (1998) 47:1480-1488.] in studying separately, find that diabetic hyperglycemia suppresses the activation of HIF-1 α.Weaken the ability that raises the HIF-1 alpha target genes and can cause diabetic complication, such as wound healing and retinopathy.This research is further noted that, throws with known HIF-1 α stimulant to help to overcome the hyperglycemia downward modulation that usually sees in the diabetic conditions.[the card kingfisher receives S.B. (Catrina, the people such as S.B.), " but stability and the function (Hyperglycemia Regulates Hypoxia-Inducible Factor-l α Protein Stability and Function) of hyperglycemia regulation and control hypoxia inducible factor l α albumen ", diabetes magazine (Diabetes), (2004) 53:3226-3232.]

Also it is reported; the CVAC therapy provides the blood flow of increase, glucose transport, angiogenesis and the protectiveness cell effect of increase, the β cell function of increase, the β cell quantity of increase, the ability that EPO produces, VEGF produces and HIF produces can help to recover and repair damaged tissues; and promote the treatment of diabetes and metabolic syndrome, comprise and regulate insulin generation, insulin resistance and glucose tolerance.In addition, it is reported that CVAC is similar to effect and the blood vessel air driven pump of user health the course for the treatment of, stimulate thus flowing of body inner fluid (including, but is not limited to blood and lymph fluid).The negative pressure that CVAC forces the course for the treatment of and malleation can affect flowing of body inner fluid or motion, thereby improve the transmission of insulin, glucose, useful nutrient, immune factor, blood and oxygen, also improve the removal of harmful toxins, fluid and damaged cell or tissue simultaneously.The combination of the beneficial effect of CVAC course for the treatment of causes that insulin produces and the improvement of the regulation and control of glucose tolerance.

In the multinomial retrospective study relevant with the A Zihai Mo's disease, conventional physical exercise as if with the reverse relevant [Charles “Karch” Kiraly M.A. (Kiraly of the development of A Zihai Mo's disease, M.A.) and Charles “Karch” Kiraly S.J. (Kiraly, S.J.), exercise is on the impact of Hippocampus integrity: recent research summary (The effect of exercise on hippocampal integrity:review ofrecent research), International Medical psychiatry magazine (Int.J.Psychiatry Med.), 35 (1): 75-89 (2005)].According to reports, the conventional people who the takes exercise risk of suffering from the A Zihai Mo's disease is half of the people of few motion.This research with in fact promising promotion health of heart and reduce stroke risk and as if the measure that designs also reduces the observation of A Zihai Mo's disease risk conforms to.[Kai Ruier JJ. (Kril, JJ.) and Harry's moral G.M. (Halliday, G.M.), A Zihai Mo's disease: its diagnosis and pathogeny (Alzheimer ' s disease:its diagnosis and pathogenesis), international neurobiology summary (Int.Rev.Neurobiol.), 48:167-217 (2001).]

The traditional remedies of many cancers (comprising tumor) relates to chemotherapy, radiation or the combination of the two, but does not have a kind of method can solve the problem relevant with the hypoxia core of tumor.The example of tumor comprises (but being not limited to described example) mammary neoplasms (breast carcinoma), organ tumor (lung, colon, prostate, liver, kidney, bladder, pancreas etc.), the cerebral tumor, tumor of testis and ovarian tumor.In addition, radiation and chemotherapy all have known adverse side effect, comprise destroying healthy fecund tissue, and described tissue includes, but is not limited to hair follicle, bone marrow and stem cell.The chemical compound that is used for described treatment faces the problem that has reduced or cut off the cancer hypoxia core of the cell of blood supply or tumor that approaches usually.[Loews Burger A. (Rosenberg, A.) and nox S. (Knox, S.), utilize the radiation sensitivity of redox modulating agent: a kind of promising method (Radiation sensitization with redox modulators:A promising approach), international radiation oncology-biology-physics magazine (Int.J.Radiat.Oncol.Biol.Phys.), 64 (2): 343-54 (2006).Yet], known such as hemoglobin replenish, packed cell volume strengthens and oxygen the other therapies such as is peeled off some beneficial effect is provided.In the situation that hemoglobin is replenished and packed cell volume strengthens, in patient experience chemotherapy and/or radiation therapy, it is thrown and chemistry or biological fill-in.[Robinson M.F. (Robinson, the people such as M.F.), by increase tumor Oxygenation and radiosensitivity (the Increased tumoroxygenation and radiation sensitivity in two rat tumors by a hemoglobin-based of two rat tumors based on the oxygen carrier preparation of hemoglobin, oxygen-carrying preparation), artificial cell, blood substitute and biotechnology (Artif.Cells Blood Substit.Immobi.Biotechnol.), 23 (3): 431-8 (1995); Hirst D.G. (Hirst, the people such as D.G.), packed cell volume changes the impact (The effect of alternations in haematocrit on tumoursensitivity to X-rays) on tumor X ray sensitivity, international radiobiology and physics, chemistry and medical science correlational study magazine (In.J.Radiat.Biol.Relat.Stud.Phys.Chem.Med.), 46 (4): 345-54 (1984).] packed cell volume that part causes because of EPO and correlation molecule and/or the rising of hemoglobin also provide via erythrocyte with and the increase of oxygen carrying capability and the increase of the tumor core Oxygenation that produces, but regulating effective treatment that tumor is carried out via static low-voltage still has part not obtain explaining [He Dun (Herndon B.L.) and Larry J.J. (Lally, J.J.), atmospheric pressure is on the impact of tumor growth: the hypobaric hypoxia of Muridae transplantable tumor and growth (Atmospheric pressure effects on tumor growth:hypobaric anoxia and growth of a murine transplantable tumor), National Cancer Institute magazine (J.Natl Cancer Inst), 70 (4): 739-45 (1983)], and as indicated above, excessive static low-voltage is regulated the hypoxia that can cause detrimental effects and make in the tumor to be increased.[the people such as Wo Peier P. (Vaupel P.), is content of hemoglobin on the impact of tumor Oxygenation: more high better? (Impact of Hemoglobin Levels on Tumor Oxygenation:theHigher, the Better?), radiation therapy and oncology (Strahlenther Onkol.), 182 (2): 63-71 (2006).]

Although numerous disease as herein described or the patient's condition are treated in useful medicine and/or operation, but still need to be in the situation that can be used for treating or preventing the therapy of described disease and the patient's condition without the relevant health wound of operation.Also need the therapy without the potential negative side-effects of pharmaceutical admixtures.Perhaps, need to reduce by changing pharmaceutical admixtures the negative side-effects of pharmaceutical admixtures, can work with pharmaceutical admixtures one valuably, or can synergistic therapy when being used in combination with pharmaceutical admixtures.The interior maximized low pressure of beneficial effect or the hypoxia for the treatment of phase of the detrimental effect that can not cause the adjusting of low pressure or hypoxia regulated.Also need in whole adjustment process, utilize described low pressure or the hypoxia of multiple and/or different pressures to regulate.The low pressure or the hypoxia that also need also to incorporate the pneumatic consideration of blood vessel into except hypoxia is considered are regulated.

CVAC will accurately provide described selection.Method as herein described provides the application of regulating for the low pressure of various diseases and the patient's condition that is better than current static low-voltage technology.Compare with current low-voltage technology, CVAC can multiple combination and is used with the time range of rapid reduction.Previous low pressure is regulated the static conditions that focuses in relatively long treatment time.The present invention as herein described and method provide a kind of novel executive mode of relevant low-voltage technology and design with and application prospect.

Throw the course for the treatment of with CVAC with variable frequency, last preferably at least 10 minutes and more preferably at least 20 minutes with treatment heart or Imaging in Patients with Cerebral Ischemia Disease, diabetes and related complication, A Zihai Mo's disease and cancer.Other the dispensing period can include, but is not limited to approximately 10 minutes, approximately 20 minutes, approximately 30 minutes, approximately 40 minutes, approximately 60 minutes, between between 10 and 20 minutes, between between 20 and 30 minutes, between between 30 and 60 minutes and between 60 and 120 minutes.The course for the treatment of or continuously the frequency of the course for the treatment of can include, but is not limited to every day, per month or medically indication or official hour.Can change the frequency of the course for the treatment of and persistent period being fit to medical condition to be treated, and can preferably utilize the preparation course for the treatment of as described herein (Set-Up Session) with the single course for the treatment of or one group the course for the treatment of form throw the course for the treatment of with CVAC.For instance, can throwing and the course for the treatment of or continuously the frequency of the course for the treatment of continued for 8 weeks 4 times weekly, continue weekly 8 weeks or 6 lasting 8 weeks weekly for 5 times for continuing for 8 weeks 3 times weekly.Can be easy to set up other frequency for each indivedual user.Similarly, also can change or regulate target in the described course for the treatment of to be fit to individuality and medical condition to be treated.In case user or operator on duty determine and can't well stand the described course for the treatment of, then can start urgent interruption and user is reduced safely and break away from the described course for the treatment of.Can customize for individuality the arrangement of target, and can again under any those skilled in the art (such as the treatment doctor's) help, differentiate.In addition, can be as described throw and change with regular interval and order or with random time interval and order.The change of quantity, frequency and the persistent period of target and the course for the treatment of can be used for utilizing all Therapeutic Method of CVAC as herein described.

Ischemia

In a first aspect of the present invention, treat multiple ischemia the course for the treatment of with CVAC.As defined herein, ischemic treatment comprises prevention ischemia, treatment ischemia, prophylactic treatment ischemia, improves ischemia and recover from the ischemia event.In one embodiment of the invention, be in user in cerebral ischemia (apoplexy) risk with at least one CVAC prophylactic treatment course for the treatment of.Apoplexy is by the caused acute neurological damage of arbitrary process that relates in cerebrovascular a plurality of pathological process.Described process can comprise angiemphraxis, known blood vessel wall is fragile, cerebral blood flow is not enough and rupture of blood vessel in brain.The pretreated diagnosis of relevant apoplexy can realize by the commonly used any mode of medical courses in general community or by the those skilled in the art.

During the expection apoplexy, throw with CVAC to limit damage or the impact of reduction ischemia on brain.Treatment be by throw the course for the treatment of with one or more CVAC with.Can be the described course for the treatment of user appointment or customize by the doctor's input by user.Another embodiment of the present invention comprises when expection treatment cerebrovascular obstruction or similar condition of illness to be used the CVAC course for the treatment of.Can before described medical science or operative treatment, throw with CVAC course for the treatment of to alleviate the potential brain tissue impairment that may occur.Another embodiment of the present invention comprises the low density lipoprotein, LDL (LDL) that reduces user with CVAC the course for the treatment of.Many heart disease types and arteriolosclerosis can produce cerebral embolism.Open heart operations, artificial valve change, heart bypass is performed the operation and angioplasty all can produce the thromboembolism that causes brain tissue damage.Can before any described operation or treatment, throw with CVAC course for the treatment of to help to reduce or prevent any illeffects.

In another embodiment of the present invention, improve or prevent the infringement of ischemic heart desease with one or more courses for the treatment of.Ischemic heart desease is with relevant by the under-supply caused various diseases of oxygen of heart tissue.Oxygen lack may be, non-atherosis obturation inaccessible by atherosclerosis coronarius, causes such as thromboembolism, coronary vasospasm, hypertension or the relevant life style (such as smoking) that reduces the blood oxygen carrying capability.Life style, mental pressure and some personality type or speciality that cardiopathic other life style of known effect is sitting.

Before acute myocardial ischemia, throw with the CVAC preventability course for the treatment of and treat progression of disease and relevant with myocardial ischemia (such as congestive heart failure) or by its complication that causes.Preventative throwing and CVAC also can prevent or be reduced in the histologic lesion in subsequently the myocardial ischemia event course for the treatment of.CVAC increases the ability adjustable tissue of blood flow, stimulation angiogenesis and stimulation protectiveness cell effect condition the course for the treatment of, therefore has less necrosis infringement in myocardial ischemia event subsequently, thereby so that can recover from described event faster and more completely.

Similarly, can promote by the recovery after the caused infringement of ischemic heart desease and treatment congestive heart failure the course for the treatment of with CVAC.Although be not limited to particular mechanism of action, believe that the CVAC therapy provides the blood flow of increase, red blood cell count(RBC), angiogenesis and the protectiveness cell effect of increase, the ability that EPO produces and HIF produces can help to recover and repair damaged tissues.When preventive dosage, these same functions are also regulated tissue and are prevented ischemic illeffects.In addition, it is reported that CVAC is similar to effect and the blood vessel air driven pump of user health the course for the treatment of, stimulate thus flowing of body inner fluid (including, but is not limited to blood and lymph fluid).The negative pressure that CVAC forces the course for the treatment of and malleation can affect flowing of body inner fluid or motion, thereby improve the transmission of useful nutrient, immune factor, blood and oxygen, also improve the removal of harmful toxins, fluid and damaged cell or tissue simultaneously.The combination of the beneficial effect of CVAC course for the treatment of is so that can prevent, treat heart disease, heart attack or other myocardial ischemia event and improve the recovery of heart disease, heart attack or other myocardial ischemia event.

Ischemic heart desease and cerebral ischemia are asymptomatic when the progression of disease degree arrives late period usually.Usually use preventive measure or the therapy of the factor of controlling risk to solve asymptomatic situation.Typical preventive therapy comprises and loses weight, changes diet, smoking cessation, physical exercise and conditioning and pressure minimizing technology.Doctor or others skilled in the art can differentiate and/or write out a prescription above-mentioned and other preventative therapy.In one embodiment of the invention, one or more CVAC courses for the treatment of and these preventative, non-medicine combined measures are used help further prevention or reduce myocardial ischemia and the caused infringement of cerebral ischemia event by subsequently.Combined therapy can be simultaneously, successively or with after measured will to the useful any At All Other Times interval of user or frequency throw with.

Diabetes

Another aspect of the present invention is the purposes that CVAC is used for the treatment of diabetes the course for the treatment of, the purposes that includes, but is not limited to help insulin or insulin resistance and improve glucose tolerance, the purposes of the complication relevant with diabetes with treatment or improvement.As defined herein, the treatment of diabetes includes, but is not limited to: treatment metabolism syndrome, adjusting insulin produce, regulate insulin resistance, regulate glucose tolerance and regulate glucose transport.In one embodiment of the invention, treat the user that needs the treatment diabetes with altitude mixture control cyclical fluctuation program.Other embodiment comprise throw with CVAC produce, regulate glucose tolerance to regulate insulin, increase blood oxygenation, increase erythrocyte number in the user body, increase angiogenesis and improve glucose and the transhipment of insulin, increase HIF generation, raise other Relevant Physiological Courses (such as fluid (lymph fluid, blood or other body fluid) motion) that glucose transport system and/or stimulation are affected by the CVAC treatment.Treatment be by throw the course for the treatment of with one or more CVAC with.Can be the described course for the treatment of user appointment or customize by the doctor's input by user.Can before any standard sugar is urinated the disease therapy, preferably more be fruitful than standard treatment and more effectively throw the course for the treatment of with CVAC, thereby preferably more effectively reduce the demand of standard treatment and preferably faster than standard treatment and more effectively promote insulin to produce and glucose tolerance than standard treatment.

In addition, be not limited to CVAC is used for type 2 diabetes mellitus, and can throw the course for the treatment of with CVAC with the similar mode of diabetotherapy of any type of the regulation and control that relate to insulin, glucose-tolerant and glucose transport.Similarly, can utilize the CVAC therapy to prevent, treat or improve metabolic syndrome.Other embodiments of the invention comprise that using CVAC treats complication relevant with diabetes and/or that caused by diabetes.Complication such as visual disorder, angiopathy and nephropathy is available CVAC course of therapy all.The mechanism of action of the above-mentioned CVAC of being attributable to all can help treatment and/or improve diabetic complication.Regulating angiogenesis, fluid and blood generation, insulin and glucose-tolerant, branching factor (such as HIF-1 α and the hypoxia inducible gene of being correlated with) and blood vessel pneumatic action can be of value to known complication relevant with diabetes and/or that caused by diabetes and treat potential diabetes.

An embodiment comprises the angiopathy that treatment is relevant with diabetes, such as ulcer of the lower limb and amputation.Throw with CVAC and produce, regulate glucose tolerance to regulate insulin, increase blood oxygenation, increase erythrocyte number in the user body, increase angiogenesis and improve glucose and the transhipment of insulin, increase HIF generation, raise other Relevant Physiological Courses (such as fluid (lymph fluid, blood or other body fluid) motion) that glucose transport system and/or stimulation are affected by the CVAC treatment.Identical with the treatment of diabetes, it is reported these mechanism of action (but being not limited only to these mechanism of action) with improvement or adjusting is relevant with diabetes and/or the healing of any complication of being caused by diabetes (comprise that diabetic ulcer, body fluid (such as blood and lymph fluid) flow, angiogenesis and protectiveness cell effect, hypertension and related heart disease, visual disorder (such as glaucoma and retinopathy) and nephropathy).

Another embodiment of present invention disclosed herein comprises the treatment metabolic syndrome.Throw with CVAC and treat, prevent and/or improve metabolic syndrome with promotion the course for the treatment of.Same as the previously described embodiments, use the CVAC scalable course for the treatment of multiple physiologic parameters relevant with metabolic syndrome, comprise insulin resistance, glucose tolerance and glucose transport.

The A Zihai Mo's disease

In the present invention on the other hand, treat with CVAC and suffer from the A Zihai Mo's disease, have its symptom or manifest the user that increases relevant risk factor (such as diabetes, hypertension, hypercholesterolemia and smoking) with the risk of A Zihai Mo's disease.Throw other Relevant Physiological Courses (such as fluid (lymph fluid, blood, brain liquid, spinal fluid or other body fluid) motion) that affected by the CVAC treatment with the Oxygenation that increases affected tissue (for example brain), the generation that increases HIF and/or stimulation with CVAC.Treatment be by throw the course for the treatment of with one or more CVAC with.Can be the described course for the treatment of user appointment or customize by the doctor's input by user.Can before other therapeutic scheme, throw with CVAC course for the treatment of to help to reduce or prevent any illeffects.

Although be not limited to particular mechanism of action, believe that the CVAC therapy provides the blood flow of increase, red blood cell count(RBC), angiogenesis and the protectiveness cell effect of increase, the ability that EPO produces, VEGF produces and HIF produces can help to recover and repair damaged tissues and also can prevent the outbreak of A Zihai Mo's disease or progress.In addition, the blood vessel air driven pump effect of CVAC stimulates the body inner fluid to flow, and described fluid includes, but is not limited to blood, lymph fluid, brain liquid and spinal fluid.The negative pressure that CVAC forces the course for the treatment of and malleation can affect flowing of body inner fluid or motion, thereby improve the transmission of useful nutrient, immune factor, blood and oxygen, also improve the removal of harmful toxins, fluid and damaged cell or tissue simultaneously.In addition, the combination of the beneficial effect of CVAC course for the treatment of be so that can treat the A Zihai Mo's disease, such as the prevent disease outbreak with postpone progression of disease.

Cancer

In the present invention on the other hand, treat the user of suffering from cancer, tumor and/or its combination the course for the treatment of with CVAC.In one embodiment, throw with CVAC with the Oxygenation that increases cancerous tissue with other Relevant Physiological Courses that the treatment for cancerous tissue, the generation that increases HIF and stimulation are subjected to the CVAC treatment to be affected (moving such as fluid (lymph fluid, blood or other body fluid)) is provided.Treatment be by throw the course for the treatment of with one or more CVAC with.Can be the described course for the treatment of user appointment or customize by the doctor's input by user.Can before other therapeutic scheme, during or throw afterwards with CVAC course for the treatment of with effect and/or the reduction that improves described treatment or any illeffects that prevents described treatment.In another embodiment, throw with CVAC course for the treatment of with the treatment tumor.In another embodiment of the present invention, use CVAC with the throwing that helps user and tolerate better initial or follow-up cancer therapy (such as chemotherapy, radiation therapy and its combination) with.Similarly, use CVAC with help user tolerate better more violent and/or Polychemotherapy course for the treatment of, the radiation course for the treatment of or its combination follow-up throwing and.

Usually to the individual pharmaceutical admixtures that arranges of symptom being arranged to treat its ischemic condition of illness, diabetes, A Zihai Mo's disease or cancer.Also the CVAC course for the treatment of and pharmaceutical admixtures combination can be used for prevention, treat or improve described disease and the patient's condition.Also the CVAC course for the treatment of and pharmaceutical admixtures or non-drug therapy (such as physiotherapy) combination can be used for the treatment of, improve or prevent other above-mentioned infringement or progression of disease.Aspect all are above-mentioned and among the embodiment, can throw with a kind of medicine or multi-medicament before, throw CVAC course for the treatment of with any combination or arrangement simultaneously or afterwards.The various arrangement that medicine and CVAC make up the course for the treatment of all is possible, and the combination that is suitable for the type of medical condition and specific medication can be differentiated under any those skilled in the art (such as the treatment doctor's) help.

Although be not unrestricted, believe that the CVAC therapy provides the blood flow of increase, red blood cell count(RBC), angiogenesis and the protectiveness cell effect of increase, the ability that EPO produces and HIF produces can help to recover and repair damaged tissues.When preventive dosage, these same functions are also regulated the illeffects of tissue and prevention ischemia, diabetes, A Zihai Mo's disease and/or cancer.In addition, it is reported that CVAC is similar to effect and the blood vessel air driven pump of user health the course for the treatment of, stimulate thus flowing of body inner fluid (including, but is not limited to blood and lymph fluid).The negative pressure that CVAC forces the course for the treatment of and malleation can affect flowing of body inner fluid or motion, thereby improve the transmission of useful nutrient, immune factor, blood and oxygen, also improve the removal of harmful toxins, fluid and damaged cell or tissue simultaneously.The combination of the beneficial effect of CVAC course for the treatment of is so that can prevent, improve treatment and improve the recovery of apoplexy or other cerebral ischemia event, diabetes and related complication, A Zihai Mo's disease and cancer.

Therapeutic efficiency

Hypertension, erythropoiesis and stem cell therapy

Hypertension

Can utilize multiple imaging known in the affiliated field and assessment technique to assess the CVAC treatment is used for prevention and treats hypertensive effect.The imaging example comprises the methods such as the traumatic imaging carried out such as the nuclear magnetic resonance (MRI) of involved area (such as blood vessel and/or heart), via catheterization or other non-invasive formation method.Under in the field other known evaluation criterion comprise: angiogenesis, erythropoietin produce in the measurement of analysis of blood pressure, blood and/or blood plasma lipide overview, packed cell volume, blood gas analysis, tissue blood groundwater increment, the tissue, VEGF produces, organize the evaluation of cognitive competence after the scope of postmortem and the ischemia event and/or motor capacity after the adjusting of HIF-1 α and related gene expression, ischemia event.

Only for instance, when blood or blood plasma lipide content when being used for estimating physiology's labelling of CVAC effect, during one or more CVAC course for the treatment of or the afterwards adjusting of blood or blood plasma lipide content will be effective to treat for the CVAC treatment, the indication of improvement or prophylaxis of hypertension.In one embodiment, the CVAC treatment that increases to of HDL cholesterol is effectively indicated.On the contrary, the change of the HDL cholesterol of user (or any physiology's labelling as herein described) shortage may not indicate the CVAC treatment can not obtain positive result.Similarly, when analysis of blood pressure when be used for estimating physiology's labelling of CVAC effect, during one or more CVAC course for the treatment of or afterwards blood pressure is adjusted to effectively indication of CVAC treatment.When tissue blood perfusion when being used for estimating physiology's labelling of CVAC effect, during one or more CVAC course for the treatment of or organize afterwards inner blood volume and/or blood exchange increase to effectively indication of CVAC treatment.Angiogenesis in the affected tissue also can be for physiology's labelling of estimating the CVAC effect.During one or more CVAC course for the treatment of or afterwards in the affected tissue vascular development be adjusted to effectively indication of CVAC treatment.In addition, vegf expression initial or regulate also and effectively indicate for the CVAC treatment in the affected tissue during one or more CVAC course for the treatment of or afterwards.The adjusting of one or more CVAC HIF-1 α after the course for the treatment of is also for being used for estimating physiology's labelling of CVAC therapeutic efficiency.In one embodiment of the invention, effective CVAC treatment is indicated in the increase of HIF-1 alpha expression.Organize the scope of postmortem for being used for estimating another physiology's labelling of CVAC effect.Other standard of the treatment of ischemia infringement or ischemia event and prevention be used for estimated is will be for the those skilled in the art known and can be used for estimating the beneficial effect of CVAC program.

In one embodiment, initial use CVAC before, one or more CVAC are after the course for the treatment of and/or finish the blood pressure of the continuous CVAC post analysis course for the treatment of CVAC user of any appointment.Obtain blood pressure at first and/or before each follow-up CVAC therapy course for the treatment of and at throwing and the fixed time point of one or more CVAC after the course for the treatment of in beginning.Include, but is not limited to one or more CVAC instant time point after the course for the treatment of, be enough to make the physiologic index of user or parameter to be returned normally or the time point of CVAC after the course for the treatment of of resting state throwing the appropriate time point that obtains measured value the course for the treatment of after with one or more CVAC, and/or known to the skilled any At All Other Times point of health or medical industries.[crin T.G. (Pickering, the people such as T.G.), " suggestion of people and laboratory animal blood pressure measurement: part 1: people's blood pressure measurement: the explanation (Recommendations for Blood Pressure Measurement in Humans and ExperimentalAnimals:Part1:Blood Pressure Measurement in Humans:A statement for ProfessionalsFrom the Subcommittee of Professional and Public Education of the American HeartAssociate Council on High Blood Pressure Research) of american heart association occupation hypertension research relevant to the professional of public education committee ", (2005), hypertension (Hypertension), 45:142-161; Cruz T.W. (Kurtz, the people such as T.W.), " suggestion of people and laboratory animal blood pressure measurement: part 2: the blood pressure measurement of laboratory animal: the explanation (Recommendations for Blood Pressure Measurement in Humans and ExperimentalAnimals:Part2:Blood Pressure Measurement in Experimental Animals:A statement forProfessionals From the Subcommittee of Professional and Public Education of the AmericanHeart Associate Council on High Blood Pressure Research) of american heart association occupation hypertension research relevant to the professional of public education committee ", (2005), hypertension (Hypertension), 45:299-310.] one or both in systolic pressure and the diastolic pressure passs in time and reduce and/or slowly increase indication owing to throwing and effect that one or more CVAC produce the course for the treatment of.Can monitor and throw with the blood pressure of one or more CVAC after the course for the treatment of to estimate the lasting reduction of throwing with one or more CVAC blood pressure after the course for the treatment of.

In another embodiment, can analyze blood pressure to estimate CVAC course for the treatment of in the effect of prophylaxis of hypertension.Throwing with one or more CVAC before the course for the treatment of and subsequently again at the blood pressure of throwing with one or more CVAC monitoring user after the course for the treatment of.Then, according to research the result is compared to determine to have the clinical normal range of the blood pressure of one or more colonies that develop hypertensive known risk factor with Normal Value.Described risk factor include, but is not limited to hereditary inducement, unhealthy body weight, higher fatty acid and/or diet, smoker, typical case's " high pressure " occupation or the working environment of high sodium and known any other risk factor with identifying of technical staff in healthy and hypertension field.Throw with one or more CVAC after the course for the treatment of user blood pressure with respect to the effectively indication of CVAC treatment for prophylaxis of hypertension of being reduced to of control value.

In related embodiment, also can be by comparing to estimate the hypertension prevention that is undertaken by Monitoring of blood pressure with Blood pressure drop, so the hypertension diagnosis parameter unlikely accepted based on medical science of hypertension.[crin T.G. (Pickering, the people such as T.G.), " suggestion of people and laboratory animal blood pressure measurement: part 1: people's blood pressure measurement: explanation (the Recommendations for Blood PressureMeasurement in Humans and Experimental Animals:Part1:Blood Pressure Measurement inHumans:A statement for Professionals From the Subcommittee of Professional and PublicEducation of the American Heart Associate Council on High Blood Pressure Research) ＂ of american heart association occupation hypertension research relevant to the professional of public education committee; (2005); hypertension (Hypertension), 45:142-161; Cruz T.W. (Kurtz, the people such as T.W.), " the suggestion of people and laboratory animal blood pressure measurement: part 2: the blood pressure measurement of laboratory animal: explanation (the Recommendations for Blood PressureMeasurement in Humans and Experimental Animals:Part2:Blood Pressure Measurement inExperimental Animals:A statement for Professionals From the Subcommittee of Professionaland Public Education of the American Heart Associate Council on High Blood PressureResearch) ＂ of american heart association occupation hypertension research relevant to the professional of public education committee; (2005); hypertension (Hypertension), 45:299-310.] hypertensive diagnosis depends on many factors, comprises that blood pressure is higher than Upper Limit of Normal Value.The blood pressure of user is from offer medicine the course for the treatment of for the indication of the effect of prophylaxis of hypertension to the CVAC that is reduced to away from the measured value of the described upper limit near the measured value of Upper Limit of Normal Value.In addition, the technical staff of hypertension diagnosis, treatment and prevention area (such as the doctor) can help determining of described effect and will understand the alternate manner of throwing with one or more CVAC post-evaluation course for the treatment of hypertension preventions.Embodiment for estimating CVAC and be used for the effect of prophylaxis of hypertension as herein described is not limited to use analysis of blood pressure, and can use it for above-mentioned any physiology's labelling for similar evaluation.

Erythropoiesis

Can utilize multiple imaging known in the affiliated field and assessment technique to assess the CVAC treatment and be used for the effect that erythrocyte produces.Known evaluation criterion comprises in the affiliated field: angiogenesis, erythropoietin generation and blood volume and red blood cell count(RBC) are recovered in the measurement of packed cell volume, blood gas analysis, tissue blood perfusion degree, the tissue.Be used for to estimate other standard that erythrocyte produces will be for the those skilled in the art known and can be used for estimating the beneficial effect of CVAC program.

Only for instance, packed cell volume is adjusted to CVAC for the indication of the effect of erythrocyte generation.On the contrary, the change of the packed cell volume of user (or any physiology's labelling as herein described) shortage may not indicate the CVAC treatment can not obtain positive result.Angiogenesis in the affected tissue also can be for physiology's labelling of estimating the CVAC effect.During one or more CVAC course for the treatment of or afterwards in the user tissue or in the body vascular development be adjusted to effectively indication of CVAC treatment.In addition, only for instance, can estimate angiogenesis by multiple imaging and detection method, known alternate manner during described method comprises in dyestuff, MRI, fluoroscopy, splanchnoscopy and the affiliated field.In addition, vegf expression initial or regulate also and effectively indicate for the CVAC treatment in the affected tissue during one or more CVAC course for the treatment of or afterwards.One or more CVAC adjusting that erythropoietin produces after the course for the treatment of is also for being used for estimating physiology's labelling of CVAC therapeutic efficiency.In one embodiment of the invention, effective CVAC treatment is indicated in the increase of erythropoietin expression.Similarly, when blood gas analysis when be used for estimating physiology's labelling of CVAC effect, during one or more CVAC course for the treatment of or afterwards in the blood solution gas be adjusted to effectively indication of CVAC treatment.The representative gases of monitoring comprises oxygen, carbon dioxide and nitrogen.Yet, but the interior being seen any gas of monitoring of blood is to estimate the CVAC effect.When tissue blood perfusion when being used for estimating physiology's labelling of CVAC effect, during one or more CVAC course for the treatment of or organize afterwards inner blood volume and/or blood exchange and combination thereof increase to effectively indication of CVAC treatment.Be used for to estimate other standard that erythrocyte produces will be for the those skilled in the art known and can be used for estimating the beneficial effect of CVAC program.

Stem cell therapy

Under can utilizing in the field known multiple imaging and assessment technique assess that the CVAC treatment is used for stem cell mobilization, stem cell is implanted and stem cell therapy after the effect of recovery.Known evaluation criterion includes, but is not limited in the affiliated field: the recovery of the measurement of the evaluation of the evaluation of EPO content, VEGF content, the evaluation of cytokine profile, peripheral hematopoietic stem cells counting, peripheral blood immune effector cell counting, packed cell volume, blood gas analysis, tissue blood perfusion degree, the interior angiogenesis of tissue and blood volume and red blood cell count(RBC).Be used for to estimate other standard that erythrocyte produces will be for the those skilled in the art known and can be used for estimating the beneficial effect of CVAC program.

Before mobilizing and/or afterwards in the peripheral blood stem cell counting be adjusted to effectively indication of CVAC treatment.Similarly, mobilize before and/or afterwards the immune effector cell counting be adjusted to effectively indication of CVAC treatment.The indication of the effect that is adjusted to that CVAC is used for stem cell mobilization, stem cell is implanted or recovers from stem cell therapy of packed cell volume.On the contrary, the change of the packed cell volume of user (or any physiology's labelling as herein described) shortage may not indicate the CVAC treatment can not obtain positive result.Angiogenesis in the affected tissue also can be for physiology's labelling of estimating the CVAC effect.During one or more CVAC course for the treatment of or afterwards in the user tissue or in the body vascular development be adjusted to effectively indication of CVAC treatment.In addition, only for instance, can estimate angiogenesis by multiple imaging and detection method, described method comprises known alternate manner in dyestuff, MRI, fluoroscopy, splanchnoscopy and the affiliated field.In addition, vegf expression initial or regulate also and effectively indicate for the CVAC treatment in the affected tissue during one or more CVAC course for the treatment of or afterwards.One or more CVAC adjusting that EPO produces after the course for the treatment of is also for being used for estimating physiology's labelling of CVAC therapeutic efficiency.In one embodiment of the invention, effective CVAC treatment is indicated in the increase of EPO expression.Similarly, when blood gas analysis when be used for estimating physiology's labelling of CVAC effect, during one or more CVAC course for the treatment of or afterwards in the blood solution gas be adjusted to effectively indication of CVAC treatment.The representative gases of monitoring comprises oxygen, carbon dioxide and nitrogen.Yet, but the interior being seen any gas of monitoring of blood is to estimate the CVAC effect.When tissue blood perfusion when being used for estimating physiology's labelling of CVAC effect, during one or more CVAC course for the treatment of or organize afterwards inner blood volume or blood exchange and its combination increase to effectively indication of CVAC treatment.

Also can utilize implantation and recovery after any method that above describes in detail is estimated transplanting.For instance, can be used for estimating the CVAC effect relevant with transplanting rear implantation for the flow cytometry of measuring mean fluorecence index (MFI) or average skein cell volume (MRV).Similarly, can carry out recovery after complete blood count is estimated transplantation therapy.Be used for to estimate stem cell mobilization, stem cell is implanted and stem cell therapy after other standard of recovery will be for the those skilled in the art known and can be used for estimating the beneficial effect of CVAC program.

Spinal cord injury, intervertebral disc therapy, inflammation and wound healing

Can utilize multiple imaging known in the affiliated field and assessment technique to assess the effect that the CVAC treatment is used for spinal cord injury, intervertebral disc therapy, inflammation and wound healing.The methods such as the traumatic imaging that example comprises nuclear magnetic resonance (MRI) such as involved area, carry out via catheterization or other non-invasive formation method.Under in the field known other evaluation criterion based on physiology's labelling comprise: angiogenesis, erythropoietin or VEGF produce, organize postmortem scope and spinal cord injury and treatment to move afterwards and/or the evaluation of cognitive competence in the measurement of packed cell volume, blood gas analysis, tissue blood perfusion degree, the tissue.Known multiple imaging and assessment technique in the field under also can utilizing (the traumatic imaging or other non-invasive formation method that carry out such as the nuclear magnetic resonance (MRI) of involved area, via catheterization) are assessed the effect of CVAC treatment.For instance, the intervertebral disc imaging is differentiated the change that degenerates except the radiography via intervertebral disc structure, also can be differentiated the change of the aquation of described intervertebral disc.

Only for instance, when packed cell volume when be used for estimating physiology's labelling of CVAC effect, during one or more CVAC course for the treatment of or the afterwards CVAC treatment that is adjusted to of packed cell volume be effective to treat, improve or prevent the indication of spinal cord injury.In one embodiment, the CVAC treatment that increases to of packed cell volume is effectively indicated.On the contrary, the change of the packed cell volume of user (or any physiology's labelling as herein described) shortage may not indicate the CVAC treatment can not obtain positive result.Similarly, when blood gas analysis when be used for estimating physiology's labelling of CVAC effect, during one or more CVAC course for the treatment of or afterwards in the blood solution gas be adjusted to effectively indication of CVAC treatment.The representative gases of monitoring comprises oxygen, carbon dioxide and nitrogen.Yet, but the interior being seen any gas of monitoring of blood is to estimate the CVAC effect.When tissue blood perfusion when being used for estimating physiology's labelling of CVAC effect, during one or more CVAC course for the treatment of or organize afterwards inner blood volume and/or blood exchange increase to effectively indication of CVAC treatment.Angiogenesis in the affected tissue also can be for physiology's labelling of estimating the CVAC effect.During one or more CVAC course for the treatment of or afterwards in the affected tissue vascular development be adjusted to effectively indication of CVAC treatment.In addition, vegf expression initial or regulate also and effectively indicate for the CVAC treatment in the affected tissue during one or more CVAC course for the treatment of or afterwards.One or more CVAC adjusting that erythropoietin produces after the course for the treatment of is also for being used for estimating physiology's labelling of CVAC therapeutic efficiency.In one embodiment of the invention, effective CVAC treatment is indicated in the increase of erythropoietin expression.Other physiology's labelling of be used for estimating the CVAC effect course for the treatment of is included in during one or more CVAC course for the treatment of or regulates afterwards cognition and/or motor capacity.In one embodiment, the improvement of motor capacity or increase to effectively indication of CVAC treatment.Similarly, in another embodiment, the CVAC treatment that is improved to of cognitive competence is effectively indicated.

Organize the scope of postmortem for being used for estimating another physiology's labelling of CVAC effect.During one or more CVAC course for the treatment of or organize afterwards the adjusting (comprise by known health repair system, path and cascade reparation or effectively remove affected tissue and prevent downright bad initial or lasting) of postmortem to be the indication of the CVAC effect course for the treatment of.Other physical index of be used for estimating the CVAC effect course for the treatment of is included in during one or more CVAC course for the treatment of or the adjusting of afterwards swelling, temperature or tensity and its combination.The CVAC treatment that is reduced to of in one embodiment, swelling, temperature or tensity or its combination is effectively indicated.Similarly, in another embodiment, the chemotactic factor in the immunity that exists in the affected tissue or inflammation mediated cell, the affected tissue and the adjusting of cytokine profile or other immune cell factor or its combination also are effectively indication of CVAC treatment.For instance, can monitor the cytokine profile of interleukin in affected tissue or the health to measure the effect of CVAC treatment.Be used for estimating other standard of the effect of above-mentioned each side and embodiment will be for the those skilled in the art known and can be used for estimating the beneficial effect of CVAC program.

Ischemia, diabetes, A Zihai Mo's disease and cancer

Ischemia

Can utilize multiple imaging known in the affiliated field and assessment technique to assess the effect that the CVAC treatment is used for myocardial ischemia and cerebral ischemia.The methods such as the traumatic imaging that example comprises nuclear magnetic resonance (MRI) such as involved area, carry out via catheterization or other non-invasive formation method.Under in the field other known evaluation criterion comprise: angiogenesis, erythropoietin produce, organize after the ischemia event evaluation of cognitive competence after the scope of postmortem and the ischemia event and/or motor capacity in the measurement of packed cell volume, blood gas analysis, tissue blood perfusion degree, the tissue.

Only for instance, when packed cell volume when be used for estimating physiology's labelling of CVAC effect, during one or more CVAC course for the treatment of or the afterwards CVAC treatment that is adjusted to of packed cell volume be effective to treat, improve or prevent the indication of ischemia event.In one embodiment, the CVAC treatment that increases to of packed cell volume is effectively indicated.On the contrary, the change of the packed cell volume of user (or any physiology's labelling as herein described) shortage may not indicate the CVAC treatment can not obtain positive result.Similarly, when blood gas analysis when be used for estimating physiology's labelling of CVAC effect, during one or more CVAC course for the treatment of or afterwards in the blood solution gas be adjusted to effectively indication of CVAC treatment.The representative gases of monitoring comprises oxygen, carbon dioxide and nitrogen.Yet, but the interior being seen any gas of monitoring of blood is to estimate the CVAC effect.When tissue blood perfusion when being used for estimating physiology's labelling of CVAC effect, during one or more CVAC course for the treatment of or organize afterwards inner blood volume and/or blood exchange increase to effectively indication of CVAC treatment.Angiogenesis in the affected tissue also can be for physiology's labelling of estimating the CVAC effect.During one or more CVAC course for the treatment of or afterwards in the affected tissue vascular development be adjusted to effectively indication of CVAC treatment.In addition, vegf expression initial or regulate also and effectively indicate for the CVAC treatment in the affected tissue during one or more CVAC course for the treatment of or afterwards.One or more CVAC adjusting that erythropoietin produces after the course for the treatment of is also for being used for estimating physiology's labelling of CVAC therapeutic efficiency.In one embodiment of the invention, effective CVAC treatment is indicated in the increase of erythropoietin expression.Organize the scope of postmortem for being used for estimating another physiology's labelling of CVAC effect.During one or more CVAC course for the treatment of or organize afterwards the adjusting (comprise by known health repair system, path and cascade reparation or effectively remove affected tissue and prevent downright bad initial or lasting) of postmortem to be the indication of the CVAC effect course for the treatment of.Other physiology's labelling of be used for estimating the CVAC effect course for the treatment of is included in during one or more CVAC course for the treatment of or regulates afterwards cognition and/or motor capacity.In one embodiment, the improvement of motor capacity or increase to effectively indication of CVAC treatment.Similarly, in another embodiment, the CVAC treatment that is improved to of cognitive competence is effectively indicated.The evaluation that CVAC is used for the treatment of the effect of congestive heart failure can comprise all above-mentioned technology and standards.In addition, can estimate the effect that CVAC is used for the treatment of, prevents and/or improve congestive heart failure the course for the treatment of by swelling or hydrops in the monitoring bodily tissue.In one embodiment, throw the indication that is reduced to effective treatment with one or more CVAC shank and ankle swelling after the course for the treatment of.Other standard of the treatment of ischemia infringement or ischemia event and prevention be used for estimated is will be for the those skilled in the art known and can be used for estimating the beneficial effect of CVAC program.

Diabetes and related complication

Can utilize multiple imaging known in the affiliated field and assessment technique to assess the effect that the CVAC treatment is used for regulating insulin regulation and control, glucose-tolerant and glucose transport.Known evaluation criterion includes, but is not limited in the affiliated field: the evaluation of the evaluation of insulin content, the evaluation of blood sugar content and the glucose uptake research of being undertaken by the oral glucose load, cytokine profile, blood gas analysis, tissue blood perfusion degree and the interior angiogenesis of tissue.Be used for to estimate other standard for the treatment of diabetes will be for the those skilled in the art known and can be used for estimating the beneficial effect of CVAC program.

Only for instance, the CVAC treatment that is adjusted to of insulin content is effectively indicated.On the contrary, the change of the insulin of user (or any physiology's labelling as herein described) shortage may not indicate the CVAC treatment can not obtain positive result.The adjusting of insulin resistance also is effectively indication of CVAC treatment.Similarly, glucose content be adjusted to effectively indication of CVAC treatment, and glucose transport be adjusted to CVAC to the indication of the effect of diabetotherapy.Can come the monitoring glucose transhipment by (but being not limited to) check GLUT protein expression (such as defined any gene in the GLUT family) and/or glut gene expression.Angiogenesis in the affected tissue also can be for physiology's labelling of estimating the CVAC effect.During one or more CVAC course for the treatment of or afterwards in the user tissue or in the body vascular development be adjusted to effectively indication of CVAC treatment.In addition, only for instance, can estimate angiogenesis by multiple imaging and detection method, described method comprises known alternate manner in dyestuff, MRI, fluoroscopy, splanchnoscopy and the affiliated field.In addition, vegf expression initial or regulate also and effectively indicate for the CVAC treatment in the affected tissue during one or more CVAC course for the treatment of or afterwards.One or more CVAC adjusting that EPO produces after the course for the treatment of is also for being used for estimating physiology's labelling of CVAC therapeutic efficiency.In one embodiment of the invention, effective CVAC treatment is indicated in the increase of EPO expression.Similarly, when blood gas analysis when be used for estimating physiology's labelling of CVAC effect, during one or more CVAC course for the treatment of or afterwards in the blood solution gas be adjusted to effectively indication of CVAC treatment.The representative gases of monitoring comprises oxygen, carbon dioxide and nitrogen.Yet, but the interior being seen any gas of monitoring of blood is to estimate the CVAC effect.

In one embodiment, the increase that insulin produces after the CVAC treatment at least one times (as comparing with the measured value obtained before the CVAC treatment) is the indication of CVAC treatment to the positive role of β cell function and insulin generation.In another embodiment, the CVAC treatment that is adjusted to of HbAlc is effectively indicated.HbAlc is visible a kind of known albumen in the blood, and its content will represent blood sugar content.In another embodiment, throw with the oral glucose Road test after positive result (as with the CVAC treatment before throw with the result of oral glucose Road test compare) be that CVAC treats the indication to the positive result of the glucose tolerance of health.The throwing of described test with and measured value will be well-known for the those skilled in the art.

Can estimate the effect that the CVAC treatment is used for regulating, treating and/or improve diabetic complication by multiple technologies known in the affiliated field.For instance, can by throw with one or more CVAC course for the treatment of during or the afterwards degree of ulcer healing or the change of healing estimate the effect that CVAC is used for the diabetic ulcer healing.Similarly, can be by estimate the prevention of ulcer through the intragroup ulcer incidence rate of CVAC treatment with respect to the control population analysis.During one or more CVAC course for the treatment of or the afterwards adjusting of angiogenesis can be that CVAC is used for improving and/or the indication of the effect of the angiopathy for the treatment of diabetics.During one or more CVAC course for the treatment of or the afterwards adjusting of urinary albumin excretion can be the indication of effect that CVAC is used for the treatment of or improves the nephropathy of diabetics.Be used for to estimate other standard of the treatment of diabetic complication will be for the those skilled in the art known and can be used for estimating the CVAC program for the beneficial effect of described indication.

The A Zihai Mo's disease

Can utilize multiple imaging known in the affiliated field and assessment technique to assess the effect that the CVAC treatment is used for the A Zihai Mo's disease.The methods such as the traumatic imaging that example comprises nuclear magnetic resonance (MRI) such as involved area, carry out via catheterization or other non-invasive formation method.Other known evaluation criterion comprises in the affiliated field: angiogenesis, erythropoietin generation, the interior Mottling formation scope of affected tissue in the measurement of packed cell volume, blood gas analysis, tissue blood perfusion degree, the tissue, and the evaluation of other index (such as language and cognitive competence, memory and identification power and body harmony and motion).Be used for to estimate other standard of the treatment of A Zihai Mo's disease will be for the those skilled in the art known and can be used for estimating the beneficial effect of CVAC program.

Only for instance, the scope of amyloid plaques formation is for being used for estimating physiology's labelling of CVAC effect.During one or more CVAC course for the treatment of or the afterwards adjusting that forms of amyloid plaques (comprise by known health repair system, path and cascade reparation or effectively remove affected tissue and prevent the initial or lasting of Mottling formation) is the indication of the CVAC effect course for the treatment of.On the contrary, the change of the amyloid plaques of user formation (or any physiology's labelling as herein described) shortage may not indicate the CVAC treatment can not obtain positive result.Other evaluation criterion of the CVAC effect course for the treatment of be included in during one or more CVAC course for the treatment of or afterwards cognitive competence, memory ability, identification capability, body harmony and motor capacity with and the adjusting of combination.In another embodiment, the chemotactic factor in the immunity that exists in the affected tissue or inflammation mediated cell, the affected tissue and the adjusting of cytokine profile or other immune cell factor or its combination also are effectively indication of CVAC treatment.For instance, can monitor the cytokine profile of interleukin in affected tissue or the health to measure the effect of CVAC treatment.Angiogenesis in the affected tissue also can be for physiology's labelling of estimating the CVAC effect.During one or more CVAC course for the treatment of or afterwards in the affected tissue vascular development be adjusted to effectively indication of CVAC treatment.In addition, only for instance, can estimate angiogenesis by multiple imaging and detection method, described method comprises known alternate manner in dyestuff, x ray, MRI, fluoroscopy, splanchnoscopy and the affiliated field.In addition, vegf expression initial or regulate also and effectively indicate for the CVAC treatment in the affected tissue during one or more CVAC course for the treatment of or afterwards.One or more CVAC adjusting that erythropoietin produces after the course for the treatment of is also for being used for estimating physiology's labelling of CVAC therapeutic efficiency.In one embodiment of the invention, effective CVAC treatment is indicated in the increase of the expression of circulation erythropoietin or amount.In addition, when packed cell volume when be used for estimating physiology's labelling of CVAC effect, during one or more CVAC course for the treatment of or afterwards packed cell volume is adjusted to the indication that the CVAC treatment is effective to treat the A Zihai Mo's disease.In one embodiment, the CVAC treatment that increases to of packed cell volume is effectively indicated.Similarly, when blood gas analysis when be used for estimating physiology's labelling of CVAC effect, during one or more CVAC course for the treatment of or afterwards in the blood solution gas be adjusted to effectively indication of CVAC treatment.The representative gases of monitoring comprises oxygen, carbon dioxide and nitrogen.Yet, but the interior being seen any gas of monitoring of blood is to estimate the CVAC effect.When tissue blood perfusion when being used for estimating physiology's labelling of CVAC effect, during one or more CVAC course for the treatment of or organize afterwards inner blood volume or blood exchange and its combination increase to effectively indication of CVAC treatment.Be used for to estimate other standard of the treatment of A Zihai Mo's disease will be for the those skilled in the art known and can be used for estimating the beneficial effect of CVAC program.

Cancer

Can utilize multiple imaging known in the affiliated field and assessment technique to assess the effect that the CVAC treatment is used for cancer.The methods such as the traumatic imaging that example comprises nuclear magnetic resonance (MRI) such as involved area, carry out via catheterization or other non-invasive formation method.Can be used for estimating other evaluation criterion that CVAC is used for the treatment of the effect of cancer the course for the treatment of comprises: in the measurement of packed cell volume, blood gas analysis, tissue blood perfusion degree, the tissue angiogenesis, erythropoietin produce, the scope of affected tissue inner tissue postmortem, and the evaluation of other physical index (such as the minimizing that reduces and/or shift quantity of tumor or cancerous tissue size).Chemotactic factor in the immunity that exists in the affected tissue or inflammation mediated cell, the affected tissue and the evaluation of cytokine profile or other immune cell factor also can help to assess effect.Be used for to estimate other standard for the treatment of of cancer will be for the those skilled in the art known and can be used for estimating the initial of CVAC program or other beneficial effect.

Only for instance, one or more CVAC adjusting that erythropoietin produces after the course for the treatment of is also for being used for estimating physiology's labelling of CVAC therapeutic efficiency.For example (but not limited to), the increase indication CVAC treatment of erythropoietin expression effectively.On the contrary, the change of the erythropoietin content of user (or any physiology's labelling as herein described) shortage may not indicate the CVAC treatment can not obtain positive result.In another embodiment, the CVAC treatment that increases to of packed cell volume is effectively indicated.When packed cell volume when be used for estimating physiology's labelling of CVAC effect, during one or more CVAC course for the treatment of or afterwards packed cell volume is adjusted to the indication that the CVAC treatment is effective to treat cancer.Organize the scope of postmortem for being used for estimating another physiology's labelling of CVAC effect.During one or more CVAC course for the treatment of or organize afterwards the adjusting (comprise by known health repair system, path and cascade reparation or effectively remove affected tissue) of postmortem to be the indication of the CVAC effect course for the treatment of.Other physical index of be used for estimating the CVAC effect course for the treatment of is included in during one or more CVAC course for the treatment of or the adjusting of afterwards cancerous tissue or tumor size and/or its combination.In one embodiment, the CVAC treatment that is reduced to of cancerous tissue piece and/or tumor mass size is effectively indicated.In another embodiment, the minimizing of shifting in the user body or prevention are the indication of CVAC effect.Similarly, the minimizing via cancerous tissue in the body that utilizes suitable detection antibody, molecule and/or compound test cancerous tissue antigen to understand also can be used for estimating the effect that CVAC is used for treatment of cancer the course for the treatment of.Other embodiment comprises blood gas analysis.When blood gas analysis when be used for estimating physiology's labelling of CVAC effect, during one or more CVAC course for the treatment of or afterwards in the blood solution gas be adjusted to effectively indication of CVAC treatment.The representative gases of monitoring comprises oxygen, carbon dioxide and nitrogen.Yet, but the interior being seen any gas of monitoring of blood is to estimate the CVAC effect.When tissue blood perfusion when being used for estimating physiology's labelling of CVAC effect, during one or more CVAC course for the treatment of or organize afterwards inner blood volume or blood exchange and its combination increase to effectively indication of CVAC treatment.Angiogenesis in the affected tissue also can be for physiology's labelling of estimating the CVAC effect.During one or more CVAC course for the treatment of or afterwards in the affected tissue vascular development be adjusted to effectively indication of CVAC treatment.In addition, vegf expression initial or regulate also and effectively indicate for the CVAC treatment in the affected tissue during one or more CVAC course for the treatment of or afterwards.Similarly, in another embodiment, the immunity that exists in the affected tissue or inflammation mediated cell, also effectively indicate for the CVAC treatment for the adjusting of the antibody of cancerous tissue or tumor antigen, chemotactic factor in the affected tissue and cytokine profile or other immune cell factor or its combination.For instance, can monitor the cytokine profile of interleukin in affected tissue or the health to measure the effect of CVAC treatment.Be used for to estimate other standard for the treatment of of cancer will be for the those skilled in the art known and can be used for estimating the beneficial effect of CVAC program.

Example

Example 1:Be the evaluation CVAC effect of the course for the treatment of, 4 individualities are thrown the course for the treatment of with CVAC, and measure subsequently its red blood cell count(RBC), packed cell volume, and record respectively be worth.The increase of red blood cell count(RBC) will be indicated the CVAC effect course for the treatment of, and similarly, erythropoietic change is indicated in the change of packed cell volume.For described research, one group 4 individual throwings with CVAC are reached 40 minutes the course for the treatment of, continue 8 time-of-weeks 4 times weekly.Within the testing period in 8 weeks, with 5 kinds of different time interval measurement erythrocyte content (RBC).Result of study is as follows:

RBC on average increases: 4.7%.

RBC increases indication CVAC and successfully effectively regulates red blood cell count(RBC) and packed cell volume, and two measured values are all indicated erythropoietic increase.Therefore, within the research phase in described 8 weeks, throw with CVAC and successfully improve erythropoiesis the course for the treatment of.

Example 2:In the research identical with example 1, be to estimate the CVAC effect of the course for the treatment of, 4 are individually thrown with the CVAC course for the treatment of and measure subsequently its packed cell volume, and each value of record.The change of the change indication red blood cell concentration of packed cell volume, and indicate erythropoietic change.For described research, one group 4 individual throwings with CVAC are reached 40 minutes the course for the treatment of, continue 8 time-of-weeks 4 times weekly.Within 8 testing periods in week, with 5 kinds of different time interval measurement packed cell volumes (HCT).Result of study is as follows:

HCT on average increases: 5.3%.

Separately or increase combined HCT with RBC as example 1 described in and increase indication, CVAC successfully effectively regulates the packed cell volume amount course for the treatment of and is another indication of erythropoiesis increase.Therefore, within the research phase in described 8 weeks, throw with CVAC and successfully improve erythropoiesis the course for the treatment of.

Example 3:Be to estimate the CVAC effect of the course for the treatment of, 13 individualities (age is all between 20 years old and 40 years old) are thrown and the CVAC course for the treatment of and the change of measuring its erythropoietin (EPO) content.The frequency of CVAC dispensing is 1 hour every day, continues for 7 weeks in 5 days weekly.Throw with CVAC before and the increase of 3 hours measurement EPO behind throwing and the CVAC, and EPO concentration represented with mIU/ml.Therefore, can represent by following formula the change of EPO: EPO mIU/ml before the EPO mIU/ml-CVAC behind the Δ EPO=CVAC.The research discovery, along with the research phase carries out, colony's EPO content obviously changes.Specifically, the average change value of EPO concentration from CVAC throw and front 2 weeks after 0.2mIU/ml be increased to CVAC throw with 8 weeks after 2.0mIU/ml.The significant change of the EPO content seen in the Research Group shows, throws with CVAC and can effectively regulate the EPO generation course for the treatment of, thereby substituting and effective ways of external source EPO dispensing is provided.

Example 4:2 diabetic individual (1 type and 2 types) are thrown and CVAC course for the treatment of of 20 minutes, continue 9 time-of-weeks 3 times weekly.Each time point during studying is estimated triglyceride (TGC), cholesterol level (HDL and LDL) and HbAlc content.Search time and result are as follows:

No. 1 individuality: type 2 diabetes mellitus, women;

No. 2 individualities: type 1 diabetes, male.

Result from two Different Individual shows that its (LDL+TGC)/HDL ratio obviously reduces, and shows that HDL improvement and LDL and/or TGC reduce.Therefore, in this research, throwing causes that (LDL-TGC)/HDL ratio reduces greater than 9% with CVAC the course for the treatment of, successfully reduces LDL and the TGC content of diabetic individual, and the HDL content of diabetic individual is raise.It can cause (LDL+TGC)/HDL ratio to reduce at least 5% in addition, (LDL+TGC)/the HDL ratio reduces at least 5-10%, or (LDL+TGC)/and the HDL ratio reduces greater than 10%.

Each side of the present invention mentioned above and embodiment only are example and are not to limit by any way.In the situation that do not depart from spirit of the present invention and claims scope, can carry out various changes, modification or change to these embodiment.

Claims

1. the purposes of an altitude mixture control cyclical fluctuation device, described device is selected from the equipment of following disease or the patient's condition for the preparation for the treatment of:

Hypertension;

Blood generates;

Ischemia;

Diabetes; Or

The diabetes related conditions,

Wherein said altitude mixture control cyclical fluctuation device comprises through adjusting with the pressure vessel unit around user, described altitude mixture control cyclical fluctuation device comprises in time range and makes the fast-changing member of pressure, and described pressure comprises pressure starting point, pressure terminal point and the atmospheric pressure target between described pressure starting point and described pressure terminal point more than.

2. purposes according to claim 1, wherein said blood are generated as stem cell and generate.

3. the purposes of an altitude mixture control cyclical fluctuation device, described device is selected from the equipment of following disease or the patient's condition for the preparation for the treatment of:

Hypertension;

Blood generates;

Ischemia;

Diabetes; Or

The diabetes related conditions,

Wherein said altitude mixture control cyclical fluctuation device comprises through adjusting to center on user, thereby provide the pressure vessel unit of at least one altitude mixture control cyclical fluctuation course for the treatment of of variable low pressure target, the target that described altitude mixture control cyclical fluctuation has starting point, terminal point and carries out between described starting point and described terminal point more than one course for the treatment of, described purposes comprises following steps: use at least one altitude mixture control cyclical fluctuation course for the treatment of; Come measuring height to regulate the cyclical fluctuation effect of the course for the treatment of via parameter change; And by the user adjusting parameter course for the treatment of.

4. purposes according to claim 3, the wherein said target of carrying out between described starting point and described terminal point more than are to carry out with transformable precise order transmission and with various modes, and described pattern comprises circulation, repeats and/or linear the change.

5. purposes according to claim 3 is wherein used described altitude mixture control cyclical fluctuation course for the treatment of with variable frequency, lasts at least 10 minutes or at least 20 minutes.

6. purposes according to claim 3 is wherein used described altitude mixture control cyclical fluctuation approximately 10 minutes course for the treatment of, approximately 20 minutes, approximately 30 minutes, approximately 40 minutes, approximately 60 minutes, between between 10 and 20 minutes, between between 20 and 30 minutes, between between 30 and 60 minutes or between 60 and 120 minutes.

7. purposes according to claim 3, wherein said altitude mixture control cyclical fluctuation be the course for the treatment of with the single course for the treatment of or one group the course for the treatment of form use.

8. purposes according to claim 5, wherein can use the course for the treatment of or continuously the frequency of the course for the treatment of for continuing for 8 weeks 3 times weekly, continued for 8 weeks 4 times weekly, continuing weekly 8 weeks or 6 lasting 8 weeks weekly for 5 times.

9. purposes according to claim 3, wherein said altitude mixture control cyclical fluctuation further comprise temperature or humidity target the course for the treatment of.

10. purposes according to claim 9, wherein said temperature or humidity target can with described pressure target simultaneously, before or after described variable low pressure target, implement.