CN100430105C - Method and device for preventing infection in tissue bag around implantation aapliance - Google Patents

Abstract

The present invention relates to an improved implantable inlet hole device which comprises a casing which can be implanted in a subcutaneous tissue bag. The present invention is characterized in that metallic silver, inorganic silver compounds, organic acid salt of silver or other antimicrobial substances, such as taurolidine, exist on an outer surface which is in contact with or is close to the tissue bag in the inlet hole device.

Description

Overcome the device of implanting the infection in the utensil tissue bag on every side

Technical field

The present invention briefly relates to medical implant apparatus and using method thereof.More specifically, the present invention relates to prevent or suppress near the subcutaneous implantation utensil patient inner infect or with use the relevant infection of described utensil, also relate to prevention or alleviate the partial inner device that infects." suppress infection " and change to be meant prophylactic treatment of avoiding infection and the therapeutic treatment of eliminating already present infection at this used term.More specifically, the present invention relates to prevent or the hemodialysis that suppresses to implant enters near the aperture apparatus (hemodialysis port) infection.

Background technology

Utensil subcutaneous and that percutaneous is implanted can be used for various purposes, as is used for drug diffusion and hemodialysis access.Cardiac pacemaker has been common.All these are implanted utensil all the danger that infection takes place.

Focus of the present invention provides the hemodialysis access system, to enter the vascular system of people or animal patient, carries out the blood exchange of high flow rate between vascular system and external treatment device.Developed and variously entered aperture apparatus and be described in numerous prior art documents through improved.

These devices typically use conduit and the subcutaneous implantation that is connected with blood vessel or other body cavitys or cavity enter aperture apparatus.This enters aperture apparatus and has the perforate that is used to hold the Guan Ruzhen that percutaneous enters.Typically entering aperture apparatus is disclosed in the following United States Patent (USP): 5,180,365,5,226,879,5,263,930 and 5,281,199.

Enter aperture apparatus and have more obvious improvement, and have the basic design feature of many routines than percutaneous catheter.Enter aperture apparatus itself and make,,, and comprise the housing that forms reservoir as polysulfones as titanium, pottery and various plastic material by various materials.Seal with barrier films highdensity, self sealss on the surface of this reservoir, and this barrier film is normally made by silicone rubber.Typically, be implantation catheter with what enter that the aperture apparatus housing is connected, the blood vessel or other positions that need to spread medicine in this conduit and the patient's body are communicated with.Implant that this device is normally following to carry out: under local anesthesia, form little subcutaneous pocket in patient's the appropriate area.The conduit of implanting enters desirable diffusion position by passage.When the nursing staff wishes to enter aperture apparatus diffusion or remove some material by this, insert hypodermic needle, this hypodermic needle is thrust in the skin by diffusing into aperture apparatus.

Recently, developed modifying device, and be described in the 5th, 954, No. 691 United States Patent (USP)s and in the 09/083rd, No. 078 U.S. Patent application of application on May 21st, 1998, the content of these documents is incorporated herein by reference at this at these problems.These inventions relate to the hemodialysis access system, to enter the vascular system of people or animal patient, carry out the blood exchange with the volume flow rate above 250ml/ minute between vascular system and external treatment device.

Yet, in this subcutaneous improvement structure that enters aperture apparatus, still there is defective, postponed the practical application in medical treatment.Particularly, can infect at any time in capsule around implanting device or the bag.Owing to reason described herein, these infection are difficult to treatment, and often need remove this and enter aperture apparatus or other implanting device.

Well-known is, to that is to say that this surface is hard and non-porous if the artificial utensil that skin is implanted down or the outer surface of device are non-permeabilitys for tissue growth, then common harder tissue capsule or " bag " relatively that form around it.The formation of bag typically takes place in several weeks behind the described utensil of implantation in subcutaneous tissue.Around the implantation utensil, closely form the thick capsule of about 1mm.These capsules are white or peach normally, and be quite sliding for the contact of inside.The outside of this capsule sticks on patient's the normal subcutaneous tissue, and its substrate does not under normal circumstances have blood vessel or vascularization low-down.If implant metal, plastics or elastomer that utensil comprises non-porous, described capsule can not adhere to or stick on this artificial material usually.Described bag largely but and not exclusively sealing implant utensil, itself and living tissue are on every side separated.

It is also known that what the infection that enters aperture apparatus of subcutaneous implantation was the most frequent is because acupuncture causes by the skin bacterium that skin enters.Antibacterial in the space between the outer surface of access to plant and the relative tissue surface then is attached on the outer surface that enters aperture apparatus, and growth film forming or lamellated bacterium colony, forms so-called biomembrane (biofilm).

Though only be confined to during beginning in the bag that forms around the device, these bacterium colonies can not cause disease or show as infection in the long time.Yet the antibacterial in the biomembrane bacterium colony might come off and stride across a bag film, forms thus and infects.These infection become local tissue infection, and its symptom is local swelling, suppuration, local pyrexia and pain etc., but also can cause systemic blood to infect.These infection of mentioning afterwards are very serious, and if do not treat, cause disease and final dead through regular meeting.

One of inventor of the present invention, doctor Sodemann has checked the operative site at 79 years old patient's obduction place, and the hemodialysis that this patient has been equipped with implantation entered aperture apparatus about 6 months.Show that without any incident or symptom active the infection arranged.But find that behind obduction the outer surface of implanting device is formed with bacterial clump.Can draw to draw a conclusion: antibacterial does not also breed the outer periphery tissue of capsule, and therefore also forms infection.

Infection near subcutaneous implanting device is normally usually treated by general administration antibiosis after the human body symptom occurring.These treatments are not often had an effect, and must remove the device of implantation, make the patient stand other wound, and make the patient can not obtain the usefulness of this device when remove infecting and replacing the device of being removed with another device.In addition, needing also be expensive to patient's administration antibiotic often, and the patient who suffers from repeated infection also forms usually antibiotic is produced chemical sproof bacterial strain.

Doctor Sodemann is to a kind of new aperture apparatus that enters that is used for the blood samples of patients dialysis--- Carried out clinical research, wherein used patented conduit Lip river gram (lock) solution, with infection in the conduit that prevents to insert and obstruction.In 14 middle of the month of this research, in all patients, use patented bactericidal properties Lip river gram (locking) solution, just when the dialysis stage finishes, only in conduit, pour into Locke's solution, and when the next stage begins, it is discarded.65 patients (each patient's the implantation time is several thoughtful 2 years) enroll oneself for is arranged in this research, and total accumulation implantation time is about 60 years.This studies show that, is using When entering aperture apparatus and patented conduit Locke's solution, the total infection rate in per 1000 days hemodialysis is about 0.9 infection incident.Its details is, is per 1000 days about 0.1 incidents for blood infection, is per 1000 days about 0.8 incidents for pocket infections.It is very favorable that these result of infection are compared with results reported in the existing document, and the latter is per 1000 days about 2-10 incident.

But inventor of the present invention is by obtaining in the above-mentioned discussion to draw a conclusion: the risk of pocket infections is still a problem.In the process that each enters, the patient has the contacted risk of its tissue and antibacterial or fungus, and the process that enters needs weekly to carry out for patient's the remaining years 3 times, unless this patient has accepted successful transplanting.In hemodialysis clinical, various skin infections have been full of.Studies show that the patient of 25-30% and the medical personnel in the hemodialysis clinic are carriers of encountered pathogenic bacteria.Implanting device surface observation in capsule forms bacterium colony to antibacterial, and inventor of the present invention is obtained to draw a conclusion: the tissue capsule barrier layer makes the lip-deep antibacterial of implanting device can not be subjected to the immune effect of patient.Therefore, the method that still needs the implanting device infection on every side in the resisted organize bag.

In the first of doctor's Sodemann clinical research, the most of patients that participates in research has all produced pocket infections.There are 7 among these patients and treat, just use the antibiotic that the antibacterial that causes infecting and identified is had a specific effect to carry out the administration of general for a long time with normal method.This Therapeutic Method can not be eliminated infection sometimes, and the device of implanting must be performed the operation and removed.Removing immediately is the method for recommending, because be difficult to be infected by treatment on the device of existing biomembrane bacterium colony, and residual infection might cause death on long terms in the health.These infection are a kind of crag-fast situation for the patient, and on the one hand, it must lose the probability of kidney replacement therapy, and on the other hand, must earn a bare living again.Consequently, the patient must adopt other alternative method, and this patient its entry site of limit usually.

Because to being discontented with of this situation, doctor Sodemann begins to treat the patient who suffers from pocket infections with new method.These patients are according to normal method general administration antibiotic, but also treat with the local antibiotic slow releasing agent at infection site extraly.Doctor Sodemann is the specific antibiotic of direct injection 1ml in the capsule space around the implanting device.In 12 tissue infections, the clinical indication of local infection disappears fast.These pocket infections are eliminated, and not recurrence.Therefore, by direct local instillation antibiotic in the inner space of capsule, eradicated with the reluctant tissue infection of whole body antibiotic therapy.

Next think, even can before pocket infections takes place, prevent it.Yet, must determine in capsule itself, whether can store germicidal solution, and the active component that takes place whether can be reduced in subcutaneous injection and intramuscular injection the time is transferred in the circulation normally.Therefore, doctor Sodemann has begun safety experiment, to check the antibacterial that whether can store high dose in capsule.Also test, be transported to the path in the blood flow and the transport velocity of these medicines by complete tissue capsule to determine whether to exist medicine.He injects the gentamycin (every ml saline 160mg) of normal dose in the capsule that is implanted with the patient who enters aperture apparatus.Measured the gentamicin concentration in the blood samples of patients during after administration 0,1,4,12,24,48 and 72 hour.

Measurement result shows that blood absorption is slow, reaches the blood dosage of very low (non-pharmacological), keeps steady statue in several days time.This means that described capsule enters for the medicine fast Absorption plays barrier action in the blood.This steady statue continues the long time.Therefore, the scattering nature of the capsule of having an effect with the permeability barrier has determined absorption rate.This also hints, is stored in medicine not degraded during 3 days measurement of capsule inside.

Find based on these, designed the method that is used to prevent tissue infection.Instiling in conduit according to normal method has Patent right conduit Locke's solution (CLS), and according to following method the CLS of additional quantity is flowed in the space between natural tissues capsule and the implanting device.

Inject the conduit Locke's solution in the syringe, the volume of this solution is catheter interior volume+0.5ml.After filling conduit, pin is partly withdrawn, so that needle point remains on the porch of implanting device access road.At this some place, remaining 0.5ml in the syringe is injected in the space of implanting device porch, it is flowed in the tissue capsule.

This method is applied on 20 patients clinically, and the time has many months.Cumulative experimental period is about 5000 days.In the patient of this method of use, do not infect.Experiment in the past shows 5 infection of should having an appointment.Therefore, the dispensing antibiotic substance makes us wishing very much in the bag around implanting device.

Some does not have toxic metal to have oligodynamic effect to the patient when small concentration, and this also is known.The 4th, 054, No. 139 U.S. Patent Publications with the percutaneous catheter of oligodynamic medicine coating, described medicine for example is argent or its chemical compound, it is used in combination separately or with other heavy metals such as gold, is used to reduce the infection relevant with these devices.Oligodynamic medicine is coated in the inside and outside of disclosed conduit usually.In another embodiment, the 4th, 923, No. 450 U.S. Patent Publications Pseudomonas aeruginosa, Staphylococcus aureus, Escherichiacoli and fungus are had the medical pipe of percutaneous of antibacterial action, it is to realize by zeolite powder anhydrous or that contain water of crystallization, one of metal that comprises in the wherein said zeolite substitutes with Ag, Cu or Zn, and zeolite is applied to described pipe and rests on the intravital at least a portion of patient or kneading becomes this part.In another embodiment, the 5th, 295, No. 979 U.S. Patent Publications a kind of catheter, it has the tube chamber that drains with oligodynamic metal coat, but also scribbles more valuable metal, be used to produce the coupling of ion penetration electrochemistry, order about the antibacterial ion and enter in the solution.Move to bladder with the outer surface of inhibition microorganism along conduit also according to similar method coating the outside of this conduit.

The plastic coating that comprises the infection material is used in other inventions, produces barrier of infection with the key point place of thrusting skin at conduit.For example, the 5th, 567, No. 495 U.S. Patent Publications have the dish or the ring of anti-infection activity, wherein be dipping anti-infection activity agent and/or form anti-infection activity in their surface at their entry site place.This invention is at least partially based on following discovery: some combination of antibacterial and solvent has changed the surface characteristic of polymer medical treatment device, helps the reservation of antibacterial thus.It is also based on following discovery: add the polymer insert of anti-infection activity in the entry site of medical treatment device, improved anti-infection activity significantly.Similarly, the 5th, 620, No. 424 U.S. Patent Publications a kind of attachable device, be used for being connected with conduit, and dipping or contain antiseptic solution, gel or powder, make this device can place near the outside catheter insertion site, distribute antiseptic solution at the position of inserting conduit thus, be used to prevent to insert position microorganism on every side and cause infecting.

The 5th, 685, No. 961 U.S. Patent Publications be coated with the conduit of multiple layer metal and other medical treatment devices.In some embodiments, the original material layer that applies after special preparation process is a silver.In another embodiment, follow-up metal level covers initiation layer fully, and is silver.Succeeding layer is deposited on the layer of front, and can reduce the generation of micropore or crackle, and is not easy to the genetic horizon separation.Succeeding layer is preferably by different each other metal of each layer.In specific embodiment, the metal of exposure is oligodynamic silver and more valuable platinum, and the silver layer of exposure prevents that thus silver layer from partly beginning corrosion by discontinuous silver layer on the part platinum layer.Manufacture method comprises by the sputtering sedimentation pantostrat in the cylindric magnetron part of vertically arranging, in each part of described magnetron, sequentially applies a coating on the coating that applies in the former part again.

The 5th, 688, No. 516 U.S. Patent Publications compositions and use the said composition flushing and the method for coating medical treatment device.Described compositions comprises the selection combination of chelating agen, anticoagulant or antithrombotic agent and non-glycopeptide antibacterial such as tetracycline antibiotics.This patent also discloses the method for using said composition coating medical treatment device and suppressing catheter infections.The concrete compositions of described material is included in the minocycline in the acceptable diluent or other non-glycopeptide antibacterial and EDTA, EGTA, DTPA, TTH, heparin and/or trematodiasis element on the materia medica.Use sulfadiazine silver coating has also been described as antibacterial.

The 5th, 718, No. 694 U.S. Patent Publications suppress antibacterial, fungus and other the method for similar microorganism adhering on biomaterial surface, wherein biomaterial such as conduit and auxiliary device carry out pretreatment with simple carbohydrate such as monosaccharide or disaccharide.Catheter in blood vessel through so handling can reduce adhering to of S.epidermidis, S.aureus, Candidas and other biologies relevant with hospital infection significantly.

Generally, these inventions relate to prevention and use infection among the patient of percutaneous catheter and other devices, the permanent but not transdermal temporarily of these devices.In addition, the cavity that relates to these conduits of these inventions carries out disinfection.What lack in the prior art is infection in the closing bag around the method for prevention infection, particularly implanting device, does not have the permanent patient's of penetrating skin this moment.

At least one patent disclosure, people's such as Brugger WO 99/34852 (on July 15th, 1999) has described in the space around the implanting device and has spread antibiotic substance, infects to eliminate before becoming systemic infection.People such as Brugger disclose implant enter aperture apparatus and other devices, these devices are to come disinfectant by inject antibacterial in the zone of device or in the tissue bag around this device.In the first embodiment, antibacterial is to inject by the perforate in the described device, and the interior zone with the described device of flushing before injecting tissue bag outwards washes by the anatomic passages that leads to device then.In another embodiment, the antibacterial direct injection is to the outside target site of device.That implanting device can comprise is special, harder target area usually, to hold the tip of the pin that is used to inject antibacterial.This method needs multiple injection usually.

Therefore, the purpose of this invention is to provide the apparatus and method that implanting device is carried out disinfection or carries out infection mitigation, this device does not have nonvolatil fluid to be connected with the outside of patient skin.Further purpose of the present invention provides the outside of implanting device and common tissue bags that form around these devices carry out disinfection or the device of infection mitigation.A further object of the present invention provides the system that is used for non-antibiotic class antibiotic substance, and described antibiotic substance does not cause the generation of endurance strain.Another purpose of the present invention provides a system that is used for bag protection, and this system and the cavity that is used to protect implant are avoided the cooperative system effect infecting and block.

Summary of the invention

According to the present invention, provide in one embodiment to enter aperture apparatus and other implantable devices, as pacemaker and artificial joint, these devices have the outer surface that comprises antibiotic substance, can reduce near the bacterial infection aperture apparatus of entering of implantation thus.More specifically, this embodiment relates to through the improved implantable aperture apparatus that enters, it comprises the housing that is implanted in the subcutaneous tissue bag, wherein improvements are, in entering aperture apparatus, contact with the tissue of described bag or near the surface it on have the acylate of argent, inorganic silver chemical compound or silver.

In another embodiment, the present invention includes and surround bag shape independent container implanting device, between described device and subcutaneous pocket basically.This bag shaped device has antibacterial properties, slides on the described device before implanting, to cover the major part on implanting device surface.

The 3rd embodiment comprises uses reservoir to hold antiseptic solution or serosity, and this solution or serosity comprise the granule of the low antibiotic substance of dissolubility.In one embodiment, this material can be taurolidine and related substances.In another embodiment, can use silver metal or insoluble relatively silver salt.One of this embodiment becomes example and is to use the implantable pump that can periodically fill again.

In the 4th embodiment, be particularly related to hemodialysis, wherein change and recall the step that connects pin, make described pin at first only partly be withdrawn into preposition, thus can the bag around described device in the conduit Locke's solution of instillation scheduled volume.Particularly preferred in the above-described embodiment taurolidine or its approaching chemical correlative or their mixture of being to use, this is because known these medicines can not form bacterial drug resistance.

The accompanying drawing summary

Fig. 1 is implanted in the part cross sectional representation that the hemodialysis under the skin surface enters aperture apparatus;

Fig. 2 is the part cross sectional representation that enters aperture apparatus;

Fig. 3 is the varying cross-section sketch map that the hemodialysis of implantation enters aperture apparatus;

Fig. 3 a is the close-up cross-sectional view that is embedded in the metallic silver particles in the matrix material;

Fig. 4 is the different views of the implanting device of the same type shown in above figure;

Fig. 5 is another embodiment, and wherein the bag shaped device of being made by permeable material surrounds the device of being implanted;

Fig. 6 a is another embodiment of the invention, and wherein the aperture apparatus that enters of subcutaneous implantation is organized the capsule encirclement;

Fig. 6 b is the close-up cross-sectional view that comprises one of the space of anti-biotic material; And

Fig. 6 c is the embodiment that the permeability bag shaped device surrounds implanting device.

The specific embodiment

The invention provides through improved subcutaneous implanting device, it comprises the device of the infection that is used to suppress its vicinity." suppress infection " at this used term and be meant prophylactic treatment of avoiding infection and the therapeutic treatment of eliminating established infection.Method and apparatus of the present invention is particularly suitable for that the blood vessel of implanting or other are entered aperture apparatus and carries out disinfection, and described device is owing to enter very big infection risk by pin, the repetition percutaneous that enters conduit, stylet etc.But improvements of the present invention also can be used in combination with various other subcutaneous implanting device, as pacemaker, conduit, artificial joint, implantable diffusion pump etc.According to disclosure of the present invention,, then in different accompanying drawings, use identical numbering if indication zone or part are identical basically in each figure.

Fig. 1 has shown that the hemodialysis of implanting enters aperture apparatus 1 under skin surface 3.Enter aperture apparatus 1 comprise main body 4 with outer surface 2, have an identification ring (identification ring) 8 enter ring 6, this identification ring 8 can make the operator inserting with when entering aperture apparatus 1 and be connected via skin surface 3 by entering pin 10 that ring 6 will have an occluder 12, locatees the subcutaneous inlet that enters aperture apparatus.Occluder 12 blocking-up tissue fragment when inserting pin 10 via skin 3 enters the tip of pin 10.Conduit 14 is stretched out by the far-end 16 that enters aperture apparatus 1.Conduit 14 extends in patient's body, for example in intravasation or other body lumens or chamber or the solid tissue target site.

Though Fig. 1 has shown the aperture apparatus that enters that can be used for such as in the therapy of hemodialysis, but the medical treatment device among the present invention can be the subcutaneous and/or percutaneous implantation device that is used for various purposes, for example is used for device, cardiac pacemaker and other the microelectronic device and the artificial joint etc. of drug diffusion.The subcutaneous implanting device that the device that these implanting device have the risk, particularly pin that produce to infect or other percutaneous to introduce periodically enters.All formative tissue capsule or bag around the device of all these implantation, and can in the interface zone between the outer surface of the inwall of this capsule and implanting device, form infection.

The most basic embodiment of the present invention is to improve this device itself slightly, makes it be used in inflow antibiotic substance, preferred normally used conduit Locke's solution in the space between capsule and the device.This embodiment relates to antibiotic substance is flowed in the space between described device and the tissue bag, discharges antibiotic substance thus in this space.Preferably, antibiotic substance is a conduit Locke's solution used in this device.This method is preferably as follows carries out: will be used for partly recalling at the pin of device delivery catheters Locke's solution, more conduit Locke's solution is provided then, the amount of providing of this solution surpasses the needed amount of the conduit of filling with device and connection.The structure of this device also comprises extra stream, and stream that this is extra and primary flow path fluid connection make part recall described pin and just can open this extra stream.This extra stream opening enters in the tissue bag, makes excessive conduit Locke's solution can inject this tissue bag.

Alternative embodiment is to inject normal ducts Locke's solution conduit Locke's solution in addition by said apparatus or conspicuous for those skilled in the art other devices in tissue bag.One of these materials are polyhexidine.

Fig. 2 is the part cross sectional representation that enters aperture apparatus 1 shown in Figure 1, its demonstration be the cross-sectional view that is evenly distributed on the wall 17 of tissue bag on the external surface peripheral that enters aperture apparatus of implantation or capsule more or less.Cyst wall 17 and the interface 18 that enters between the outer surface 2 of aperture apparatus 1 are zones that the easiest formation is infected.A main purpose of the present invention is the bacterial growth that suppresses in this interface zone 18.

Be known that some metal and other materials and material have antibacterial properties.One of these metals are silver, and it does not have negative physiological action when low concentration.Silver is dissolved in the physiological solution lentamente, and forms silver ion.According to the present invention, the infection that forms in tissue capsule or bag can suppress by the following method: suitable silver alloy forms and enters aperture apparatus on silver or materia medica, perhaps applies with silver or silver alloy or some silver compound and enters aperture apparatus.But this coating must be enough thick, and must have enough surface areas, to guarantee to reach the service life in several years.

The ag material that contains that can be used among the present invention for example is an argent; Inorganic compound is as silver oxide, Disilver carbonate or silver nitrate; And the salt of silver and organic acid formation, as Itrol. or actol.Preferable alloy silver.

If desired, the subcutaneous aperture apparatus that enters of the present invention can form through machined with solid silver strip or silver alloy film.But under normal conditions, preferably enter aperture apparatus, then by any means known silver coating on the outer surface with non-precious materials such as titanium manufacturing.For example, available sputter, chemical plating or other plating methods well known to those skilled in the art (for example referring to the 5th, 685, No. 961 United States Patent (USP)s) are entering silver coating metal on the outer surface of aperture apparatus.

The 5th, 295, the open test of carrying out with nutrient broth in No. 979 United States Patent (USP)s, this situation is considered to the worst condition.This patent shows that when suppressing microorganism, every milliliter of meat soup needs the silver surface of 25-50 square millimeter.Conventional method of coating can not provide the surface area of this order of magnitude.Therefore, when enforcement is of the present invention, wish very much to make the surface area maximization of silver.For the metal of specified rate, making the maximized a kind of method of surface area is to mix very little silver-colored granule in the surface of implanting device, as the silver-colored granule of micron or sub-micrometer range.Another method that increases the external surface area enter aperture apparatus is a fluting or make this surface roughening on described surface, for example by sandblast or etching method, with the contact area of increase depositing silver.Perhaps, can enter the very thin silver-colored granule of adhesion on the outer surface of aperture apparatus by any suitable means such as coating process, wherein said Dispersion of Particles is in polymeric matrix, and this substrate is then attached on the outer surface that enters aperture apparatus.

Can be for example with the substrate formation coating of albumen substrate or organic plastics form, described organic plastics for example is polyethylene, polypropylene, polrvinyl chloride, politef, polyurethanes or siloxanes.If like this, advantageously make the silver/polymer weight ratio maximization in the coating under the normal condition, so that be exposed to outer argent or the particulate amount maximization of silver compound.Typically, these results can followingly realize: disperse described silver-colored granule in the dilute solution of polymer in suitable solvent, method by routine is entering this mixture of coating on the aperture apparatus then, and described method for example is to brush, spray or dip coating, then evaporating solvent.

Be similar to the preparation of photographic negative in another method that enters the thin argent of coating on the outer surface of aperture apparatus.In these methods, silver halide such as silver chloride or Silver monobromide emulsion that preparation is conventional are coated in the outside that enters aperture apparatus then usually in the dark.The coated aperture apparatus that enters is exposed under the light, carries out the reduction of conventional photographic developer then.Consequently at the argent thin layer of the outside deposition high surface that enters aperture apparatus.

People such as Krall have described the method for the little active substance of coating at least two kinds of plastic components of using in health.In the 5th, 516, No. 480 United States Patent (USP)s of authorizing on May 14th, 1996, Krall and Guggenbichler disclose the method for preparing plastic components, can not produce the bacterium colony of antibacterial and fungus on this plastic components.In the method, plastic components at first forms desirable shape.Be coating swelling agent such as acetone or ammonia on the surface.These parts with swelling surface are immersed in the non-group water solution of little active substance such as silver chloride, make silver chloride preferably be absorbed in the swelling part.Evaporate swelling agent and solvent then, containing layer of formation on the treatment surface of effective little active substance.In another method of inventor's imagination of the present invention, the article that are used for medical purpose are made by treated plastics.These treated plastics are following formation: get the plastic plate of suitable substance, then the thin film of little active substance of deposition such as argent on the surface of this plastic plate.After the deposition, pulverize this plastic plate, and in one embodiment, the powder of fusion gained, and be configured as the desirable shape of medical treatment device.So the parts that form have little useful effect.

Entering aperture apparatus or being used to make external coated little effective coating of the material body that enters aperture apparatus, be conspicuous for those skilled in the art on the basis of foregoing description.

In particularly preferred embodiment of the present invention, the external packets argentiferous that enters aperture apparatus of the 5th, 954, No. 691 United States Patent (USP)s and the type in the 09/083rd, No. 078 U.S. Patent application of application on May 21st, 1998, described.Therefore, the used aperture apparatus that preferably enters is the implantable subcutaneous aperture apparatus that enters when enforcement is of the present invention, needing to be suitable for 250ml/ minute or the more application of high flow rate, and it has low pressure drop in the stream that does not have stagnation point basically.

Fig. 3 is the part cross sectional representation that the implantable hemodialysis of type shown in Figure 1 enters aperture apparatus 1.Entering aperture apparatus 1 is implanted under the skin surface 3.The column part 5 of main body 4 has ring-shaped groove 20, and this groove plays the effect that increases total surface area, and silver ion can diffuse in the main body 4 and the interface shape between the surrounding tissue capsule (not shown) that enters aperture apparatus 1 thus.

A plurality of ring-shaped grooves 20 only are examples that increases the external surface area of the medical treatment device of implanting that enters aperture apparatus 1 or other implantation.Within the scope of the invention, also can use annular knurl, etching or sandblast or other to increase the method for surface area.

Substitute and use groove that forms through machined or the above-mentioned additive method that increases the external surface area of implanting device, inventor of the present invention has imagined by suitable method such as coating process and is entering the thin silver-colored granule of adhesion on the outer surface of aperture apparatus, in the polymeric matrix of wherein said Dispersion of Particles on will being attached to the outer surface that enters aperture apparatus.Fig. 3 a is the feature viewgraph of cross-section that is embedded in the metallic silver particles 22 in the matrix material 24.The polymeric layer 24 that inventor's imagination of the present invention is filled with silver can provide the metallic silver particles 22 of needed high surface area.Inventor of the present invention also thinks, within the scope of the invention, being embedded in granule 22 in the substrate can also be low-solubility organic or inorganic salt or other solid phase antibiotic substance of silver, and this antibiotic substance can be at the outer surface 28 of implanting device and produced antibacterial action in the interface shape 26 between the inwall 30 of capsule 32 on every side.

More specifically, be filled with the host material 24 of the coating of silver or relevant solid phase anti-biotic material for these, can for example be formed by protein material or organic plastics, described organic plastics for example is polyethylene, polypropylene, polrvinyl chloride, politef, polyurethanes or silicone rubber.Advantageously make silver in the coating/polymer weight ratio maximization under the normal condition, so that be exposed to argent or the particulate amount maximization of silver compound on the outer surface of described device.Typically, these results can followingly realize: disperse described silver-colored granule in the dilute solution of polymer in suitable solvent, method by routine is entering this mixture of coating on the aperture apparatus then, and described method for example is to brush, spray or dip coating, then evaporating solvent.

Be similar to the preparation of photographic negative in another method that enters the thin argent of coating on the outer surface of aperture apparatus.In these methods, silver halide such as silver chloride or Silver monobromide emulsion that preparation is conventional are coated in the outside that enters aperture apparatus then usually in the dark.The coated aperture apparatus that enters is exposed under the light, carries out the reduction of conventional photographic developer then.Consequently at the argent thin layer of the outside deposition high surface that enters aperture apparatus.According to foregoing description, be conspicuous for those skilled in the art at the additive method of the external coated silver coating that enters aperture apparatus.

In particularly preferred embodiment of the present invention, the external packets argentiferous that enters aperture apparatus of the 5th, 954, No. 691 United States Patent (USP)s and the type in the 09/083rd, No. 078 U.S. Patent application of application on May 21st, 1998, described.Therefore, the used aperture apparatus that preferably enters is the implantable subcutaneous aperture apparatus that enters when enforcement is of the present invention, needing to be suitable for 250ml/ minute or the more application of high flow rate, and it has low pressure drop in the stream that does not have stagnation point basically.Fig. 1,2 and 3 modes with the part cross sectional representation have shown the subcutaneous aperture apparatus 1 that enters of these implantation.

The alternate embodiment that enters aperture apparatus in above-mentioned ' 691 patents is that the bag-like container with antibacterial properties surrounds above-mentioned implanting device basically.More specifically, described bag-like container is to make with the material that comprises antibiotic substance basically, and wherein said antibiotic substance is dispersed in this material.

Relate in the related embodiment of bag-like container, described bag-like container is a tubulose, surrounds and enters aperture apparatus, and comprise the solid antimicrobial material in the epidermis of water-based body fluids and water solublity antibiotic substance permeability.That is to say that water-based body fluids can make a spot of antibiotic substance infiltrate in the interface shape between the outer surface of the inner bag-like container with the encirclement implanting device of tissue capsule.The example that is included in these antibiotic substance in the bag-like container is argent, silver compound and the taurolidine that has and have antibacterial properties with solid state.The examples of material of making bag-like container is silicone rubber, polyurethanes etc.

Fig. 4 has shown the common implanting device 1 identical with the implanting device shown in the above-mentioned figure.More specifically, enter aperture apparatus 1 and have as shown in Figure 3 ring-shaped groove 20.But in this embodiment, the bag-like container next to the shin 34 that the outer surface 2 that enters aperture apparatus 1 is made by permeable material such as silicone rubber, polyurethane rubber or porous material such as dialyzer (polysulfones and cellulose membrane) covers, and is filled with the antibiotic substance 36 of solid-state, liquid or pasty state in the groove 20.Antibiotic substance 36 dissolves easily in water in the matrix liquid, and this body fluid can see through the material of bag-like container 34, and radially outward diffuses into thus in the interface shape 38 between the inner surface of the radially outmost surface of bag-like container 34 and tissue capsule 17.Therefore, inventor of the present invention imagines the antiseptic solution that interface zone 38 will keep sufficient intensity, and the main body 4 that suppresses implanting device 1 forms on every side and infects.Should also be noted that among Fig. 4 that bag-like container 34 extends beyond the main body 4 of implanting device 1, but under the concrete condition of present embodiment, do not comprise entering aperture apparatus 1 to its conduit that provides access 14.

Fig. 5 is another embodiment, and the bag-like container 34 of wherein being made and be similar to the bag-like container shown in Fig. 4 by permeable material surrounds implanting device 1.Anti-biotic material 40 is solid-state, liquid state or pasty state, remains in rule or the recessed space 42.Embodiment as shown in Figure 4, antibiotic substance 40 freely interact with water-based body fluids, and in the interface shape that outer surface limited 44 of the inwall that diffuses into tissue capsule 17 thus and the bag-like container 34 that surrounds implanting device 1.Antibiotic substance 40 is included in the recessed space, and it is under bag-like container 34, by this space, in the interface volume 46 that the inner surface 48 that the antibiotic substance in the aqueous solution freely diffuses to tissue capsule 17 and the outer surface 50 of bag-like container 34 are limited.The bag-like container 34 interior antibiotic substance 40 that are included in the outer surface 52 of contiguous implanting device 1 for example are argent, silver compound and the solid matter taurolidine with known antibacterial properties.

Inventor of the present invention considers that also except that cylinder groove 20 and sawtooth space 42, the bag-like container shown in Fig. 4 and 5 can be used in combination with various antibiotic store meanses.For example, through the surface of sandblast or the surface that has been etched into particularly advantageous shape all can be used for keeping and storing the water solublity antibiotic substance of q.s, to keep enough antibacterial substances and concentration in the length of life of implanting device in the interface shape between the outer surface of the inner surface of tissue capsule and bag-like container.

Fig. 6 a has shown another embodiment of the invention.Shown in previous drawings, be to enter aperture apparatus at this implanting device that schematically shows, but basic infection principle is applicable to the medical treatment device of any subcutaneous implantation.In Fig. 6 a, the aperture apparatus 1 that enters of subcutaneous implantation is organized capsule 17 encirclements.Form a plurality of spaces 54 on the outer surface that enters aperture apparatus 1, this each space all comprises antibiotic substance 56.This antibiotic substance 56 preferably has the solid of enough dissolubility in water-based body fluids, to keep the antiseptic solution layer of enough concentration in the interface shape 58 that separates at the outer surface 2 with tissue capsule 17 and implanting device 1.But though antibiotic substance 56 is solid-state in Fig. 6 a, inventor of the present invention thinks also can use suitable antibacterial gel or the ointment that has suitable dissolubility in body fluid.Fig. 6 b is one of them feature viewgraph of cross-section that comprises the space 58 of antibiotic substance 56.Water-based body fluids and antibiotic substance 56 interacts, to keep enough concentration and enough long antiseptic solution in the interface shape 58 that separates at the outer surface 2 with the inwall 59 of tissue capsule 17 and implanting device 1.

Fig. 6 c shows the wherein embodiment of permeability bag-like container 60 encirclement implanting device 1.Be stored in antibiotic substance 56 in the recess 54 and be dissolved in by bag-like container 60 diffusions and migrate to subsequently in the body fluid of outside of this container, antiseptic solution is carried enter in the interface zone that the inner surface by the outer surface 62 of bag-like container 60 and tissue bag 17 limits.

Have antibacterial properties and surrounding basically in another embodiment of bag-like container of implanting device, described bag-like container is to be made by the material that comprises antibiotic substance basically, and this antibiotic substance is dispersed in the described material.In another embodiment, bag-like container is piped, encirclement enters aperture apparatus, and comprises the solid antimicrobial material in the epidermis of water-based body fluids and water solublity antibiotic substance permeability, makes water-based body fluids that a spot of antibiotic substance is infiltrated in the body fluid between tissue capsule and the implanting device.The example of these antibiotic substance is argent, silver compound and the taurolidine that has and have antibacterial properties with solid state.

It will be apparent to one skilled in the art that now and in spirit of the present invention and scope, still other embodiments, improvement and application can be arranged.Scope of the present invention only limits to appending claims, and comprises equivalent according to Patent Law.

Claims (16)

1, a kind of implantable medical treatment device, it has an outer surface, and it is characterized in that being provided with coating on the described outer surface of this implantable device, and described coating comprises antibiotic substance, and on this outer surface, being provided with at least one groove, described antibiotic substance is applied in this groove.

2, medical treatment device as claimed in claim 1, wherein said coating comprises the material that is selected from following group: the acylate of argent, inorganic silver chemical compound, silver.

3, medical treatment device as claimed in claim 1 wherein exists argent, inorganic silver chemical compound or silver-colored acylate on the outer surface of described implantable medical treatment device.

4, medical treatment device as claimed in claim 1, wherein said implantable medical treatment device be used to make fluid and patient body internal communication enter aperture apparatus.

5, medical treatment device as claimed in claim 4, the wherein said aperture apparatus that enters is the hemodialysis access system.

6, medical treatment device as claimed in claim 5, wherein said hemodialysis access system comprises:

(a) skin that strides across the patient provides the device of continuous stream between dialysis position outside the patient and patient's internal blood vessel, this device is included on the direction without any the slight mozzle that changes, its inner surface is level and smooth, on flow area, there is not lofty variation, and qualification is suitable for the stream of hemodialysis flow velocity, and do not hinder, make that flow resistance is low and avoided any stagnation point;

(b) be used for the device that a some place under patient skin blocks described stream; And

(c) be used to remove the device of the circuit portion of passing patient skin.

7, medical treatment device as claimed in claim 6, it also comprises the extra stream with the mutual fluid connection of described stream, makes part recall at least one inlet device the conduit Locke's solution that comprises antibiotic substance is diffused in the described device space on every side.

8, medical treatment device as claimed in claim 1, wherein said antibiotic substance comprises oligodynamic metal.

9, medical treatment device as claimed in claim 8, the outer surface of wherein said medical treatment device was roughened by sandblast or etching method before applying described oligodynamic metal.

10, medical treatment device as claimed in claim 8, wherein said oligodynamic metal is to be applied in by the method for downloading in following group: sputter, chemical plating and conventional plating method.

11, medical treatment device as claimed in claim 8, wherein said oligodynamic metal are silver.

12, medical treatment device as claimed in claim 11, wherein said silver is applied in by the following method: the coating silver halide magenta-sensitive emulsion, this silver halide magenta-sensitive emulsion is exposed under the light, the silver emulsion through exposure is developed.

13, medical treatment device as claimed in claim 1, the wherein said coating that comprises antibiotic substance comprises the combination of oligodynamic metal and polymeric matrix.

14, medical treatment device as claimed in claim 1, the wherein said coating of antibiotic substance that comprises comprises silver-colored acylate or inorganic compound.

15, medical treatment device as claimed in claim 14, the inorganic compound of wherein said silver is salt.

16, medical treatment device as claimed in claim 8, wherein said medical treatment device is made of plastics, and at first make this plastics swelling, this medical treatment device is immersed in the non-group water solution of described little effective metal then, apply described oligodynamic metal thus with the swelling agent.

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