CN102869789A - Genetic signatures and gene chips associated with administration of electrically conducted radio frequency current to skin and methods and treatments relating thereto - Google Patents

Genetic signatures and gene chips associated with administration of electrically conducted radio frequency current to skin and methods and treatments relating thereto Download PDF

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Publication number
CN102869789A
CN102869789A CN2011800197739A CN201180019773A CN102869789A CN 102869789 A CN102869789 A CN 102869789A CN 2011800197739 A CN2011800197739 A CN 2011800197739A CN 201180019773 A CN201180019773 A CN 201180019773A CN 102869789 A CN102869789 A CN 102869789A
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skin
gene
processing
treatment
collagen
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CN102869789B (en
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D·J·韦斯格伯
N·E·阿农齐阿塔
T·J·莫勒
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Syneron Medical Ltd
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Procter and Gamble Ltd
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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6813—Hybridisation assays
    • C12Q1/6834—Enzymatic or biochemical coupling of nucleic acids to a solid phase
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N13/00—Treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6813—Hybridisation assays
    • C12Q1/6834—Enzymatic or biochemical coupling of nucleic acids to a solid phase
    • C12Q1/6837—Enzymatic or biochemical coupling of nucleic acids to a solid phase using probe arrays or probe chips
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers

Abstract

A gene panel comprising genes regulated in mammalian skin in response to generation of a radio frequency current in a tissue volume of the mammalian skin sufficient to heat the tissue volume to a treatment temperature, wherein at least one gene is selected from Table 1 or Table 2 and at least one gene is selected from Table 3. Further there is a method for providing a benefit to mammalian skin, the benefit comprising inducing collagen formation and/or dermal remodeling in a dermal layer of the mammalian skin in the absence of a skin-damaging inflammatory cytokine response, the method comprising generating a radio frequency current in a tissue volume of the mammalian skin for a treatment cycle sufficient to heat the tissue volume to a treatment temperature while avoiding an upregulation in expression of genes listed in Table 3.

Description

The gene label that is associated to using of skin with the radio-frequency current of conductivity and gene chip and associated method and processing
Invention field
The present invention relates to makeup skin treatment scheme, described scheme comprise use conductivity radio-frequency current by skin to provide beneficial effect to skin, and relate to the assessment based on genomics to described beneficial effect and processing, with monitoring, screen and optimize described skin treatment scheme.
Background of invention
Processing skin to avoid or to alleviate the effect of aging of the aging and external environmental correclation of skin inherence, is the industry of a multi-million dollar, and what lay the first stone for this industry is aspect the exploitation of new technology and the checking even the investment of huger fund.Electromagnetism (EM) energy is by to the application of skin surface and namely known before the application to skin many decades, and with multiple multi-form and be implemented by multiple delivery apparatus.In general, can be divided into separability and process non-separability based on the skin processing method of EM, although the two all utilizes the hot release effects of EM energy apply.
There are various products to make to improve skin for human consumers and delay and/or prevent typical aging sign.This type of sign comprises for example microgroove, wrinkle, hyperpigmentation, sallow, sagging, black eye, swollen eye, inhomogeneous skin color, the pore of increase, the epidermic cell metabolism of minimizing and unusual furfur or exfoliation.Yet for some human consumer, various obtainable product and the raising on technique in skin care still can not produce the result of expectation, and some human consumer feels to seek help from more invasive therapy.
Separability process such as separability laser have been proved to be for reinventing or removing of skin is effective on the surface on the general form, for example scar and removing in the process of tatooing, and to be proved to be for processing and improving aging outward appearance with skin light injury be effective.Although the separability process is effective in mouth week and all zones of socket of the eye of fragility aspect the beauty treatment of skin of face for the outward appearance of improving microgroove and wrinkle, its main shortcoming comprises long rehabilitation and restored cycle, and this is so that the human consumer bears the beauty treatment outward appearance that is badly damaged undesirable in over a long time.In addition, irregular these the potential side effects of the infection that may cause, cicatrization and pigementation are thought it is being unacceptable aspect the beauty treatment by the human consumer usually, when especially relating to skin of face.
Therefore, recent research-and-development activity has focused on to the human consumer more cheap, more convenient and safer non-separability skin anti-aging and the processing of rejuvenating is provided.Relate to that to apply heat energy to skin be well known in this area with the beauty treatment scheme of the skin appearance that promote to improve.There have been nearly ten years in the electromagnetic energy delivery technique of the hand-held device form of using at home for the human consumer on market.The improvement of above-mentioned technology and improvement to the thermoinducible beneficial effect maximization of darker target skin histology, make simultaneously to target tissue with to the damage that does not conform with expectation of peripheral and surface structure and all are minimised as the center.It is believed that optionally thermal treatment causes new collagen to form, and optionally thermal damage causes, particularly, dermal matrix is reinvented.Yet at present available technology is known causes debatable damage, and that this type of passive side effect that continues that does not conform with expectation comprises is overheated, burn, erythema and anochromasia.
In the past, the effect of these devices and composition is only determined by externalist methodology.That is, if exist visible to improve at the extexine of skin, the energy delivery apparatus must work so.But, almost do not have the method for Best Times, temperature and the composition of determining these energy delivery apparatus.In addition, widely acceptedly be, the many visible that occur at skin surface change, and are the results of the variation that occurs in the corium of the skin under the surface and the epidermal area.Not knowing that a kind of device is cutaneous layer below how, is be difficult to know for sure performance how to control and maximize this device.
The selective photothermolysis of skin histology is the cosmetic treatments form of widespread use, particularly in the processing of using that comprises one-wavelength laser energy and wide spectrum intense pulsed light (IPL) energy.In these technology, luminous energy is applied directly to the surface of skin, and infiltration depends on the transmission of passing epidermis and the absorption in the corium.Dark skin and supracutaneous dark color spots can hinder transmission and hinder the effect of processing by absorbing energy, and can cause the overheated of pigment regions, overheated cause blistering, burn and other beauty treatments on the effect do not expected.
As the replacement scheme based on the pyrolysis of EM, the radio frequency of conductivity (RF) electric current is also studied as the beauty treatment skin processing mode.RF electric current and pulse radiation frequency (pRF) are known in the use of field of medicaments, but the RF electric current still is relative novelty as the skin return of spring technology of the non-separability of sending for human consumer oneself.In the application of skin, the transmission of bipolar RF electric current is undertaken by two electrodes that directly apply to skin at the RF electric current.Therefore, electric current directly flows through skin corium, conducts to electrode from electrode, and this makes its application that is different from the EM energy, and the EM energy focuses on by epidermis, and the restriction of those factors of the wavelength depth of penetration that is affected.
The RF electric current use the significant skin treatment advantage that as if application that is better than the EM energy is provided in theory.For example, be different from electromagnetic energy, the RF energy of conductivity be do not rely on chromophoric, this avoided with skin pigment and non-pigmented between relevant complication and the efficacy problems of absorption difference, and the problem in the processing of the dark skin with more endergonic melanocyte and light skin that can reflecting light that causes.In two kinds of situations, result's consistence all is impaired, and the thermal control that comprises in the chromophoric skin still is problematic.
Yet, the RF electric current with energy level that the thermal treatment effect can be provided to using of skin be subject to the investigator can not parameters optimization to realize desired beneficial effect and don't to have the skin injury that does not conform with expectation.The RF electric current is sent by the skin tissue under the skin surface, and is limited to the accessible surface of skin by the effect monitoring that temperature or humidity sensor carry out.The RF current impedance is the function that tissue forms and comprise the various skin organizational attribution of collagen density and integrity degree, water of hydration equality.Although the distance between the electrode and to being conditioned on the control theory such as the parameter of pulse length and frequency, so that effect optimization and avoid safety problem, but do not have certain equipment or other modes to monitor the benefit of the variation of organization factors, this type of adjusting almost is impossible.Based in the sending of EM energy, the skin on surface reaches the highest treatment temp usually, so that can avoid the hypodermic unexpected damage of his-and-hers watches at the temperature monitoring on surface.Yet with regard to the RF electric current, in fact epidermis undertissue reaches the higher treatment temp of skin of specific surface, so that damage may occur in darker tissue and not have from the teeth outwards measurable performance.Therefore, under the medical worker's that process screws up discipline the supervision and outside the clinical setting of the superior instrument of use, generally avoided based on device and the scheme for human consumer individual use of sending of RF electric current separately, because in the situation that does not have monitoring mechanism under the suitable epidermis, still there is safety issue at effective processing horizontal.It in fact is unknown providing the RF electric current as unique processing form and for the hand-held energy delivery apparatus that the house human consumer uses.A kind of so device (STOP that claims TM, Ultragen Ltd) and be positioned in Europe the individual for the human consumer, but the processing tolerance level of this device is set so lowly for fear of the damage that does not conform with expectation, so that the objective evidence of the clinical efficacy under the control condition does not still exist.
Therefore, the effect of RF in skin treatment is limited in fact as the additional or preparatory function that combines with other hot dispose procedures.For example, in 2002, Bitter and Mulholland(" Report of a new technique for enhanced non-invasive skin rejuvenation using a dual mode pulsed light and radio frequency energy sources:selective radiothermolysis, " J.Cosmet Dermatol 2002; 1:142-145) proposed processing scheme based on the combination of RF electric current and IPL, and reported the result who processes based on 100 bit test experimenters' face, although above-mentioned author does not disclose concrete Treatment Design parameter.In this research, RF is reported to have increased the effect that IPL processes.Side effect comprises the report of the pigmentation effect that does not conform with expectation in the beauty treatment, and has controlled human consumer's pain perception by the cooling on surface.
It is being useful in the beauty treatment skin that the application of the luminous energy of orientation is combined is processed that RF also is suggested, and is studied.In general, according to this processing scheme design, RF is attached to luminous energy and is used, and is employed according to some parameters of luminous energy.For example, at the people such as Hammes (" Electro-optical synergy(ELOS TM) for nonablative skin rejuvenation:a preliminary prospective study; " Journal of European Academy of Dermatology.and Venereology 2006,20,1070-1075), the author focuses on the pulse-repetition of coordinating between RF electric current and the luminous energy, and propose between these form of energy, to exist synergy, this can allow lower, the use of the luminous energy of less invasive level, and the scheme of the relevant side effect of the independent application of proposition and RF by above-mentioned merging has been lowered or avoided.In addition, adopt the scheme of these devices to comprise in response to the overheated so that method of skin Physical temperature-lowering or prevent overheated method.
In another example, U.S. Patent Application Publication 2008/0033516 A1 of Altshuler discloses " temperature controlled photo bio excites " of skin histology, and it relates to heated skin to the target degree of depth with the combination in electromagnetic radiation target area of irradiation territory.Altshuler mentions the prior art of the skin processing method that stimulates based on low-level illumination, Low level laser, monochrome and quasi-monochromatic light, they are considered to improve the production of production, cell proliferation and the protein of ATP usually, and by inducing low grade inflammation to reply to have triggered growth to reply, but also mentioned inconsistent result's report and to the shortage of the clinical confirmation of effect.The application of Altshuler imagination heat energy can strengthen light stimulus and reply.Altshuler has instructed the high heat of the skin of certain volume can be increased to by the temperature that can make described volume preferred any known source between 37 ° and 45 ℃ and has realized, and particular instantiation the heating carried out of the EM radiation of use by warm air, AC or DC electric current, conductivity thermal source, ultrasonic wave or microwave radiation or any suitable wavelength in the 380-2700nm scope.Yet, in all embodiments of Altshuler, be to rely on the EM energy to realize desired treatment effect.Altshuler has instructed heat that the cooperative reinforcing of the desired effect of light stimulus is provided, but also proposed in the situation that there is not EM, heat can cause not conforming with the biostimulation of expectation, for example slow down production and the modification of the zymetology process of related those to the regeneration that is included in skin histology and in repairing of the reparation, heat shock protein (it has set up the tolerance to the application of subsequently heat) of radiation-induced dna damage, and usually oppositely instructed heat in the situation that do not exist illumination as the skin treatment mode.Altshuler does not have to propose how to overcome and the defective that can not assess or the subcutaneous skin of monitoring form is relevant.
In addition, for the device of present existence, human consumer's compliance always is a problem.The human consumer only has the limited amount time every day for their beauty treatment scheme.Although the manufacturers of device wants to recommend the human consumer to use the long time of these devices to obtain maximum beneficial effect to guarantee them, the human consumer is unlikely to be deferred to.Therefore, in the usefulness of suggestion extension fixture with admit that only having limited amount free time at them one day of human consumer exists a kind of balance between the using appts.
When design apparatus, composition and scheme, human consumer's experience also is important.For example, audiogram is the method for generally using and huge medical beneficial effect is provided.But the gel that uses in the audiogram process is dense thick and be difficult to remove, and has caused human consumer's discomfort.In addition, the skin of a lot of energy delivery apparatus heating surface is too fast or too hot, has caused the consumer experience that makes us unhappy.
Therefore, need to substantially improve skin so that avoid need to more invasive therapy and avoid the method for associated risk always.And existence is to the demand of the better method of the effect of mensuration energy delivery apparatus, and these methods can be used to set up the experience that the human consumer can accept more, realize simultaneously the result of the skin appearance of desired improvement.
Also there is the demand to the scheme of safety and effective non-separability skin treatment and return of spring device, methods for the treatment of and suitable human consumer individual use in this area.Particularly, exist by promoting the synthetic and corium of collagen to reinvent the subcutaneous skin of processing list and don't can causing demand to the damage mode that does not conform with expectation of handled target tissue or tissue on every side.The effect that has the processing that assessment and monitoring are carried out based on the human consumer of RF electric current in this area, to optimize the demand for the method for the application of the RF electric current that desired beneficial effect is provided, and have the demand based on the methods for the treatment of of RF electric current to optimizing, described methods for the treatment of avoided with based on the relevant problem of the methods for the treatment of of EM and do not rely on and process the Physical temperature-lowering that combines.
Summary of the invention
Correspondingly, the new development of the biotechnology by utilizing genomics and proteomics (they are so that the accurate and multiple feedback of replying that cell is handled physical and chemical factor becomes possibility), inventor research and having determined about the RF electric current of the conductivity genetic fingerprint to the effect of skin histology, and developed creative gene chip and utilize these gene chips to provide safely and effectively based on the processing scheme of RF electric current and process the method for screening procedure.The inventor unexpectedly finds to provide the beneficial effect synthetic relevant with collagen to the optimization based on the processing of RF electric current, and provide the beneficial effect of some wound inducement, it has stimulated corium to reinvent, and has avoided simultaneously the inflammatory cytokine of more debatable wound inducement to reply.Also unexpectedly find, according to the processing scheme based on the RF electric current of the present invention not the energy that replenishes of needs send, do not comprise specifically using of electromagnetism (EM) energy outside the radio frequency wavelength part of EM radiation wide spectrum, and do not need Physical temperature-lowering.Therefore, beneficial effect of the present invention has obtained providing not existing with the EM energy in the situation of the relevant problem of using of skin.
One embodiment of the invention relate to the gene panel, described gene panel comprises in response to the generation of the radio-frequency current in the tissue volume of mammal skin the gene that quilt is regulated and control in described mammal skin, and described radio-frequency current enough is heated to treatment temp with described tissue volume.The gene of described panel is selected from table 1 and/or table 2, and precondition is that at least a gene is selected from table 3.The aspect comprises microarray and based on its gene label.
Another wide in range embodiment relates to the method that beneficial effect is provided to mammal skin, described beneficial effect comprises, in the situation that the inflammatory cytokine that does not have injured skin is replied, in the skin corium of mammal skin, induce formation and/or the corium of collagen to reinvent, described method is included in the tissue volume of the inherent described mammal skin for the treatment of cycle and produces radio-frequency current, described radio-frequency current enough is heated to treatment temp with described tissue volume, avoids simultaneously the rise of the expression of listed gene in the table 3.
According to another embodiment, provide the method for the processing effect of assessment energy delivery apparatus.Described energy delivery apparatus is designed to provide beneficial effect by heated skin to described skin in appearance, and can be evaluated by a kind of method, and described method comprises: process described skin by using described energy delivery apparatus; Extract mRNA the sample of the skin after described processing; And produce express spectra for gene panel as described in the present invention.According to another embodiment, the effect aspect also can replying for the inflammatory cytokine that injured skin is not provided provide collagen and/or corium to reinvent beneficial effect to mammal skin and screen or assess the skin of face processing scheme.Described method comprises: according to processing scheme process facial skin; Extract mRNA the sample of the skin of face after described processing; Produce gene expression profile for gene panel as described in the present invention; Described gene expression profile and reference spectrum are compared; And when described express spectra reflects the rise of the gene that is selected from table 1 and/or table 2 and be selected from the in fact shortage of regulation and control of gene of table 3, determine that described facial processing scheme is effective.Of the present invention aspect some, beautifying active substance and/or composition also can be by similarly just according to being the invention provides beneficial effect or just screened with the synergy for the treatment of process of the present invention or assess.
Summary of drawings
Although this specification sheets by particularly point out and clearly claimed letter of authorization requirement of the present invention draw a conclusion, should believe by following explanation and can understand better the present invention by reference to the accompanying drawings, wherein:
Fig. 1 is the schematic diagram of naturally occurring injuring and repairing circulation in the human skin;
Fig. 2 A, 2B show the characteristic of human collagen;
Fig. 3 is the schematic diagram of the biological model of RF electric current efficacy;
Fig. 4 A, 4B are that 24 hourly average multiples of compiling gene change;
Fig. 5 A, 5B are that 24 hourly average multiples of typical gene change;
Fig. 6 A, 6B are that 1 monthly average multiple of compiling gene changes;
Fig. 7 A, 7B are that 1 monthly average multiple of typical gene changes;
Fig. 8 A, 8B are two width of cloth figure of RF simple heat transfer;
Fig. 9 is the schematic diagram of RF simple heat transfer;
The schematic diagram in the crow's feet zone of Figure 10 human consumer's around eyes;
Figure 11 is the regional A of human consumer's skin;
Figure 12 is the regional B of human consumer's skin;
Figure 13 is the regional C of human consumer's skin;
Figure 14 is the regional D of human consumer's skin;
Figure 15 is the regional E of human consumer's skin; And
Figure 16 is the regional F of human consumer's skin.
Detailed Description Of The Invention
Except as otherwise noted, the Science and Technology term that uses relatively with invention as herein described should have those of ordinary skill in the art the implication usually understood.In addition, unless context has requirement in addition, singular references should comprise plural number, and plural term should comprise odd number.In general, the technology of cell and tissue culture as herein described, molecular biology and protein and widow or polynucleotide chemistry and hybridization and with the name that these use relatively, be well known in the art and general those of use.For example, used for the purifying of genetic material (nucleic acid) and the synthetic standard technique of preparation, chemical analysis and oligonucleotide.Enzyme reaction and purification technique are according to specification sheets or the ordinary method in this area or as described herein the carrying out of manufacturer.Technology described herein and program be generally according to ordinary method known in the art, and implement as described in the reference various routines and more concrete of quoting in this specification sheets and discussing.Laboratory as herein described rules and technology and the name of using relatively are well known in the art and general those of use.
For the purpose of explaining and illustrate many aspects of the present invention, a large amount of details are listed in hereinafter.Yet those skilled in the relevant art will be understood that do not have these detail embodiment of the present invention also can be implemented.In other examples, for the present invention being described effectively and avoiding the purpose of fuzzy creative aspect, show more in general manner and known structure and device be discussed.Should be pointed out that many different and substituting structure, device, software and the technology that exist their embodiment of invention disclosed and illustration to be suitable for.Multiple embodiments and these full breadth of inventing self are not limited to specifically described embodiment.
During all scopes that value is provided, be to be understood that, each value between two parties, until 1/10th (unless context has clear in addition) of the unit of lower limit, between between the upper and lower bound of this scope and value any other statement in the scope in this statement or between two parties, include within the scope of the invention.The constraint that any concrete removing property limits in the scope of being stated, the upper and lower bound of the scope that these are less can be included in the described less scope independently, and also is included within the scope of the invention.When all scopes of stating comprise in its limit one or whole two, got rid of one of these limits that are included or whole two scopes and also be included within the present invention.Except as otherwise noted, represent whole numerals of the amount of employed reactant, reaction conditions etc. in this specification sheets and the claim, all should be understood to be in the modification that all is subjected to term " about " in all situations.
Should understand, unless otherwise indicated, the step of any method of enumerating in claims that this paper adds can any order be carried out.For example, in enumerated steps (a) and (b) and (c) claim to a method book, step (c) can step (a) and (b) before or between carry out.In addition, although be enumerated as different steps, independent step can be between the cycle overlapping carrying out or overlapping carrying out fully partly.
This paper " adjusting keratinous tissue conditions " refers to improve skin and/or preventative regulation of skin situation, and comprises and for example protect described tissue to exempt from ultraviolet radiation, and the regulation of skin aging sign.This paper " improves mammiferous skin " and refers to cause visually and/or appreciable positive variation in the sense of touch at the look and feel of described tissue.The situation that can be conditioned and/or improve includes but not limited to one or more following situations: reduce the appearance of wrinkle and coarse dark line, microgroove, crackle, lump and thick pore; The thickening of skin (for example, epidermis and/or corium and/or the subcutaneous layer of structure skin, and refer to/stratum corneum (if applicable) of toenail and hair shaft to be to alleviate skin, hair or refer to/the toenail atrophy); Increase the spiral structure (also being called as relations with network) at corium-epidermis edge; Prevent from causing skin or hair loss of elasticity owing to forfeiture, damage and/or the inactivation of for example skin function elastin, cause such as elastosis, sagging, forfeiture skin or these situations of hair deformation-recovery function; Reduce liparitosis; Change skin, hair or refer to/toenail painted, for example black eye, rash spot (such as the red spotty staining that causes owing to for example acne erythematosa), sallow, the variable color, drying, embrittlement and the hair graying that cause owing to telangiectasis or spider shape blood vessel.
" signs of skin aging " used herein include but not limited to, perceptible performance in the outward appearance vision that causes owing to skin aging and the sense of touch, and any macroscopic view or microphenomenon.These signs are produced by following effect, and described effect includes but not limited to the development of texture discontinuity, such as wrinkle and coarse dark line, microgroove, skin striped, crackle, lump, thick pore, unevenness or anchor; Furfur; Dry; The forfeiture skin elasticity; Variable color (comprising black eye); The rash spot; Shoal; The cutaneous pigmentation zone is such as senile plaque and freckle; Keratinization; Abnormal differentiation; Parakeratosis of skin; Elastosis; Decomposition of collagen, and stratum corneum, corium, epidermis, vascular system (such as telangiectasis or spider shape blood vessel) and especially change near other histology in those lower-hierarchies (such as fat and/or muscle) of skin.
As used herein, " hyperpigmentation " refers to that wherein pigmentation is greater than the Pigmented skin area of skin adjacent domain (such as eyespot, senile plaque etc.).
In this article, " personal care composition " refers to be suitable for being applied topically to the composition on the mammal skin.Personal care composition as herein described can comprise one or more skin care actives.As used herein, " skin care actives " or " active substance " refers to for example by beneficial effect being provided or improving the compound that described skin helps regulation of skin and other mammiferous skin.
As used herein, " energy delivery apparatus " refers to for any device to mammal skin and/or hair delivery of energy.In this article, " delivery of energy " is to instigate skin surface and/or layer to be exposed to the energy of being launched by the energy delivery apparatus, and wherein its is penetrable to required skin layer, comprises hair shaft and/or hair follicle.
As used herein, " constant level " refers to that energy or energy output that device is sent remain on the constant in fact level between device start time and device down time.
As used herein, " pulse " refers between device start time and device down time.Energy output is characterized in that higher output period (pulse) and alternately generation of low output period with predictable variation.The beginning of pulse can be for unexpected or progressive." predictable " refers to that the timed interval between pulse peak intensity, pulse shape, pulse duration and the pulse is in fact identical.Can change pulse duration and the time between pulse.
As used herein, " hand-held " is that finger device has the comfortable weight of holding of general grownup of being fit to and size.
Human skin can be divided into two main structural sheets: the corium of epidermis and below the epidermis.Epidermis has conduct to the stratum corneum of the biological containment of environment.At the stratum basale of epidermis, exist and be called as melanocytic chromatogenous cell, they are main determining factors of skin color.
Following corium provides skin main structural support.It mainly is comprised of the extracellular protein that is called as collagen.Collagen is produced by inoblast, and synthetic by three polypeptide chains as triple helices, and these three polypeptide chains link to each other by heat-labile and heat-staple chemical bond.When the tissue that comprises collagen was heated, the physical property of these albumen substrates changed in the characteristic temperature.Along with the collagen contraction of collagen stroma and the structural transformation of reinventing occur in heating.
In skin, produce the repairing activity of some amounts, with the generation that promotes that collagen continues.In weathering process, the speed that damage occurs can raise faster than repairing activity, and perhaps damage can continue to occur with constant substantially speed, but repairing activity slows down.The result is the minimizing of collagen and the impaired outward appearance that occurs as old and feeble sign in both cases, comprises outward appearance such as microgroove, wrinkle and the Hyperpigmented spot of surface imperfection.Normal repairing activity circulation and along be shown in Fig. 1 and 3 impact that outward appearance produces time lapse.
In Fig. 1, box indicating causes the regular element of collagen production.Owing to many reasons, the increase of collagen in skin, with and the speed of repairing and replacing help skin to look fuller, more healthy and more attractive.The propagation that continues and corium are reinvented natively and are occured, but regrettably, and these processes slow down along with our ageing.When skin sustains damage, for example, in inflammation or after being subject to such as the infringement from the radiation of the sun, also can produce collagen.Circle among Fig. 1 has represented more collagenogenic mechanism and how can follow the trail of its generation.MMP and cytokine activity only are to help to follow the trail of the reparation of collagen and two measurable amounts of replenishment cycles.
Fig. 3 is the schematic diagram of the dual-use function biological model of Elure effect 20.Skin 21 has been divided into three layers, stratum corneum 30, epidermis 32 and corium 34.Reinventing with the newly production of collagen of collagen betides in the skin corium.Normal infringement 22 to skin 21 occurs constantly, comprises that normal aging, UV infringement, pH change, chemistry is encroached on and other.Normal infringement 22 causes impaired collagen 24.Similarly, normal low-level inflammation 26 causes cytokine, HSP and HSF active.At last, low-level heat energy repeatedly causes the MMP activity 36 that raises, and the result is the production of collagen fragment.The increase of heat is so that cause the formation of collagen and the rise 38 of the cytoactive of reparation.Mechanism 36 and 38 all causes the formation of healthy collagen 28 and reinvents.
Although collagen has paramount 50 ℃ melting temperature (Tm) through measurement, the interpolation of repairing the heat that circulation can be by lower level is changed and strengthens.The crosslinked thermo-cracking of intramolecular hydrogen bond produces by the balance between cracking event and the relaxation events (the again formation of hydrogen bond).The generation of this process does not need external force.Therefore, the molecule internal stress produces by the thermo-cracking of intramolecular hydrogen bond.The contraction structure of the tertiary structure of crosslinked molecule has produced initial intermolecular contraction vector.RF model heating curve is shown among Fig. 8.
Dermis mainly is comprised of collagen 1.Collagen is expressed by inoblast with the precollagenous form of the protein of strand.Precollagen is truncated to collagen 1 when expressing, and is folded into the triple helices structure that is called as " tropocollagen ".RF model heating curve is shown among Fig. 8 A, Fig. 8 B and Fig. 9.
Dermis mainly forms Fig. 2 A and Fig. 2 B by collagen 1,50.Collagen is expressed by inoblast with the form of the protein precollagen 52 of strand.Precollagen 52 is truncated to collagen 150 when expressing, and is folded into the triple helices structure 54 that is called as " tropocollagen ".This process graphical is in Fig. 2 A and 2B.
The crosslinked of collagen can be intramolecular (covalent linkage or hydrogen bond) or intermolecular (covalent linkage or ionic linkage).Cause collagen to comprise heat energy infringement, machinery infringement, pH to impact, the hydrated state of collagenase and MMP speed according to the reason of age sex change and can " pull on " or the generality of the natural balance of the collagen microfibril of " untiing " is destroyed, described destruction causes them easily to be digested by MMP.Although these have represented multiple infringement type, all be that speed is subjected to temperature controlled.In addition, the normal collagen replacement cycle can be regulated and control in＜37 ℃-43 ℃ temperature range.
The cracking that also can send out key collagenogenic in lower temperature, but be with lower speed.Be associated with relaxation phenomenon in a lot of situations of low-level thermo-cracking, in relaxation phenomenon, key forms in the situation of the net change that does not have molecular length again.
It is the biophysics phenomenon that occurs at cell and molecular level that corium is reinvented.The molecular contraction of collagen or partially denaturing relate to the effect of energy source, and its heat-labile key by the cracking triple helices is so that the longitudinal axis of molecule is unstable.Therefore, produced the stress of the inter-molecular linkage of breaking matrix.This is in fact the extracellular process, and the contraction of cell needs one period lag-phase for migration of fibroblast cells and the zone of breeding to damaged.Callus is replied and is related generally to initial inflammatory process, and it comprises white cell or the leukocytic infiltration of processing cell debris.Following by inoblast in the propagation of injury site and/or the increase of renewal, finally is can be for the increase of the collagen of deposition.Inoblast is divided into contractile myofibroblast, and the latter is the source of cell retract soft tissue.After the cellular contraction, collagen is deposited in the soft tissue structure of tension as static supported matrix.With regard to purpose attractive in appearance, the deposition of the scar matrix at this initial stage and reinventing subsequently provide and have changed the denseness of soft tissue and the approach of geometrical shape.
Heat application causes the cascade reaction of injuring and repairing, with the improvement of final realization skin surface outward appearance, is as known in the art, yet at present available technology is associated with known shortcoming.For example, the laser delivery apparatus uses the light of specific wavelength, the light transdermal of described specific wavelength, is combined with specific chromophoric group and removes multiple pigment and pigment by the process that is called as the selective light heat effect from skin.Laser apparatus is large-scale, expensive capital equipment, only processes particular problem or color in the skin, is easy to occur laser burn, stays scar, can causes superpigmentation and/or very few and may cause user and patient that ocular injury occurs.Strong wide band light is according to the light of system generation multi-wavelength, and equally by the variable color of selective photothermolysis improved effect skin, percutaneous heating non-specifically improves texture.Above-mentioned system is same relatively large and expensive, and the improvement of texture and wrinkle is very little, and has equally the problem of skin burn, hypopigmentation or too much and scar.Generally speaking, the application of electromagnetic energy realizes by epidermis, and penetration degree is subject to the pigmentation factor on surface and the composition of skin corium.
Radio-frequency technique also is known in the skin treatment field.RF utilization electric current heats corium, and stimulates collagen and the production that makes the solid elastin fiber of compacting of skin.Yet, because can not the optimization process parameter, have shortcoming in essence in the current Status of development in this field.The RF electric current be applied in the generation thermal gradient opposite with other heat energy delivery technique in the skin.The application of RF electric current is by placing the electrode at a distance of some distances on the skin to carry out.Electric current conducts between electrode, by corium, so that the temperature of corium raises quickly than the temperature of skin surface.Because most of skin parameters measuring apparatuss are designed the measurement for skin surface, the superheated of corium may just be recognized after generation.
Therefore, avoided in the art do not exist be designed for the hot-quenching of the inner heating of control go out, the processing of passing through the RF electric current in Physical temperature-lowering or the other technologies situation.
Yet, utilizing the new development of the biotechnology of genomics and proteomics, the inventor has developed for the method for assessment RF electric current in the effect of using of corium.Particularly, the inventor has screened one group and is accredited as and relates to dermal collagen matrix, corium inflammation and reinvent and the potential gene of epidermal differentiation.When standing specific RF current processing parameter, condition and scheme, gene label and gene chip component based on resulting gene expression profile have been determined in the regulation and control of the difference of above-mentioned potential gene by analysis and verifying.
The energy that is delivered to skin and/or skin layer can be the form of RF energy, comprises for example rf wave and microwave.Exemplary RF energy device be disclosed in following United States Patent (USP) open in: 6,889,090; 6,702,808; 6,662,054; 5,569,242; 5,755,753; 6,241,753; 6,430,446; 6,350,276; 5,919,219; 5,660,836; 6,413,255; 6,228,078; 5,366,443; With 6,766,202.
The application of RF by corium and the processing scheme that comprises the application of RF electric current can be designed the effect processed for optimizing desired RF for the first time.When the analysis and verifying gene expression data, unexpectedly find, potential gene data energy collecting enough is reduced to three subsets, in the optimization process scheme with lower what do not exist the damage of more debatable inflammatory cytokine to reply, provide during the corium of the stress-inducing of the increase of dermal collagen and desired poisonous substance excitement reinvents, above-mentioned three subsets have unique effect.With regard to known to the inventor, this has represented genomics and has been applied to for the first time using in the processing of RF current technique.Above-mentioned express spectra shows, controlled causes coercing of positive poisonous substance excitement with optimized application, the coercing of described positive poisonous substance excitement causes and keeps desired corium and reinvent, avoided simultaneously the traditional damage that is associated with the biological effect that does not conform with expectation.The invention provides novel gene chip, gene label, screening method and based on the optimizable scheme of these discoveries.
Comprise gene (FBN1, FBLN1, TNXB, the FN1 relevant with the integrity of dermal matrix as the studied gene of potential gene, LOXL2, COL3A1, COL1A1, ELN and LOXL1), reinvent relevant gene (TIMP2 with the corium inflammation causes, IL1A, TIMP1, TNF, MMP1, MMP9, MMP3, SOD2 and IL1B) with gene (KRT2, the KRT6A relevant with the barrier function of epidermis, CLDN1, LOR, FLG, IVL, DRT10, AQP3 and KRT14).Derive from subset to the analysis of the expression data of these genes such as table 1(corium mark), table 2(matrix reinvents mark, namely, positive poisonous substance excitement coerce the releaser) and the table 3(inflammatory cytokine mark of replying, that is, repair the damage outside replying) in listed.
Gene expression profile provides about the information to the cell response of one group of situation.Gene comprises for the instruction of making messenger RNA(mRNA) (mRNA).Yet at any given time point, each cell is only made mRNA from the part of its gene that carries.If a gene is used to produce mRNA, then being referred to as is " opening ", is " closing " otherwise just be referred to as.Term " regulation and control " refers to cause the transcriptional state of the contrast state that is different from gene.For example, " rise " can only comprise and opening, perhaps can refer to improve transcription rate to being higher than the baseline rate that derives from contrast or reference conditions.
In expression pattern analysis, the relative quantity of the mRNA that expresses in two or more experiment conditions is measured.The mRNA level that changes hints the variation to the demand of the protein of being encoded by this mRNA.For example, corresponding to the rising of substrate level in cellular environment of enzyme, observe the transcribing of rising of enzyme catalyst or cofactor.
In general, gene expression profile is included in those genes of showing significant difference under the experiment condition of change.This is the subset of some data set (it can comprise whole genome) normally.For one type cell, the expression pattern of its combination is one group of gene of the specific characteristic of specified criteria, has consisted of the gene label of this condition.Gene label can be used to, and for example, selection can be benefited from the patient of particular procedure, and perhaps design is used so that the maximized processing scheme of desired feature.
The gene expression profile of potential gene data collection can be measured with microarray.The exemplary commercially available acquisition of cDNA microarray, and can be available from such as Agilent Technologies, Affymetrix Inc.(Santa Clara, Calif.), Nanogen(San Diego, Calif.) and Protogene Laboratories(Palo Alto, Calif.) company.The specific hybrid technical description that can be used to equally to produce the express spectra that adopts in the method for the present invention discloses 5,143 in United States Patent (USP), 854; 5,288,644; 5,324,633; 5,432,049; 5,470,710; 5,492,806; 5,503,980; 5,510,270; 5,525,464; 5,547,839; 5,580,732; 5,661,028; In 5,800,992; Above-mentionedly openly be incorporated herein by reference; And WO 95/21265; WO 96/31622; WO 97/10365; WO 97/27317; EP 373 203; In EP 785 280.Generally speaking, in these methods, it expresses the array that the detected decisive gene of phenotype has comprised " probe " nucleic acid of a probe for each, contacts with listed as mentioned target nucleic acid.Contact is carried out under hybridization conditions such as stringent hybridization condition, then removes unconjugated nucleic acid.The pattern of the nucleic acid of resulting hybridization provides the information about the expression of every kind of detected gene, wherein said expressing information be about gene whether be expressed and, normally, which kind of horizontal expression (to work as expression data with, be express spectra, in the time of can being both qualitative and quantitative) aspect.Alternatively, described express spectra can be measured by quantitative PCR or for other quantivative approachs that detect mRNA.
One embodiment of the invention provide the gene panel, described gene panel comprises in response to the generation of the radio-frequency current in the tissue volume of mammal skin the gene that quilt is regulated and control in described mammal skin, and described radio-frequency current enough is heated to treatment temp with described tissue volume.At least a gene is selected from table 1 or table 2, and at least a gene is selected from table 3.In specific embodiment, at least a gene is selected from each of these three tables.All gene panels according to the present invention are all expected and are comprised at least a gene that is selected from table 3, do not show do not have " bad " damage to reply because these genetic expressions change.Probe can be designed to for the every kind of gene that forms gene chip of the present invention, to make up very specific microarray, for design, screening, adaptation or the monitoring processing scheme for desired effect, or for the described processing scheme of checking in accepting the experimenter who processes.Imagined microarray, described microarray comprises one group of fixing nucleic acid probe, described fixing nucleic acid probe can with form according to the gene recombination of gene panel of the present invention and detect this gene.
As used herein, " probe " refers to oligonucleotide, polynucleotide or dna molecular, no matter is naturally occurring or synthetic generation, and it can be specifically and the nucleic acid hybridization that has with the sequence of this probe complementation.Probe of the present invention specifically refers to the oligonucleotide that is connected with solid support in the dna microarray substrate.Probe can be strand or double-stranded.Probe comprises 15-25 or more Nucleotide usually, although it can comprise Nucleotide still less.The probe of this paper is selected as complementary from the different chains of specific target nucleic acid sequence, and therefore must be fully complementary, in order to can hybridize specifically with their target chains separately under one group of predetermined condition.Therefore, probe sequence needn't reflect the sequence of the accurate complementation of target.For example, non-complementary nucleotide fragments can be connected to 5' or the 3' end of probe, and the rest part of described probe sequence and the complementation of target chain.Alternatively, non-complementary base or long sequence can be dispersed in the probe, as long as have the complementarity that is enough to anneal specifically accordingly between the sequence of described probe sequence and target nucleic acid.
Another embodiment of the invention comprises the method that beneficial effect is provided to mammal skin.Described beneficial effect comprises, in the situation that the inflammatory cytokine that does not have injured skin is replied, in the skin corium of mammal skin, induce formation and/or the corium of collagen to reinvent, and described method is included in the tissue volume of the inherent described mammal skin for the treatment of cycle and produces radio-frequency current, described radio-frequency current enough is heated to treatment temp with described tissue volume, avoids simultaneously the rise of the expression of listed gene in the table 3.In a treatment cycle, the RF electric current can produce repeatedly.
As used herein, term " is processed " and " processing " etc. generally refers to obtain desired beauty treatment or aesthetic, and described effect confirms by the biological answer-reply of target.As used herein, " processing " contained the processing in the Mammals especially mankind, and comprise: (a) prevent or avoid improving looks on do not conform with the development of the skin of expectation, for example microgroove, wrinkle, Hyperpigmented spot and because aging or environmental correclation old and feeble or on other skin abnormalities that the impact of skin causes, (b) suppress, alleviate or postpones to improve looks on do not conform with the appearance of the skin of expectation; (c) do not conform with the skin of expectation or cause its recovery in the reverse beauty treatment.
In one section toeatment period, can carry out one or more treatment in accordance with the present invention cycles.In order to realize that the desired treatment cycle of replying is can be short as much as possible aspect the time length.In specific embodiment, treatment cycle is approximately one minute or still less, and in other specific embodiments, treatment cycle is greater than approximately one minute.In other specific embodiments, treatment cycle continues between approximately 1 and approximately between 6 minutes, and continues in other embodiments between approximately 2 and approximately between 6 minutes.Treatment in accordance with the present invention comprises one or more treatment cycles period, and is at least one week and comprise at least one treatment cycle in specific embodiment.In other specific embodiments, described toeatment period is between a week and 12 weeks.In a more particular embodiment, described treatment cycle is between 3 weeks and 8 weeks.In certain embodiments, each week in the toeatment period comprises the treatment cycle between and six, although should understand in the art, this can change along with the characteristic of the individuality of accepting to process.
Generally speaking, although being applied in of RF electric current caused in the corium than in the higher temperature of skin surface, the temperature of skin on the surface by most convenient ground and non-invasively measuring.Therefore, in certain embodiments, treatment temp (being defined as the temperature of the tissue volume that the RF electric current flows through herein) has realized less than about 45 ℃ the skin surface temperature on described tissue volume.In a more particular embodiment, described treatment temp has realized approximately 37 ℃ and the about skin surface temperature on described tissue volume between 43 ℃.
Can be by from deriving from the sample extraction mRNA of the tissue volume that the RF electric current flows through according to desired beneficial effect of the present invention; Assess with the express spectra of measuring by the gene panel of at least a gene that is selected from table 1 and/or table 2 and at least a genomic constitution that is selected from table 3.The in fact not variation of genetic expression that express spectra reflects the rise of the gene that is selected from table 1 and/or 2 and is selected from table 3, namely showing provides beneficial effect.
Generally speaking, be reflected in according to the regulation and control of gene of the present invention and express among the multiple delta data.Be known in the art exist many for analyzing based on the experiment of microarray identifying the method at different condition difference expressing gene, and the known set that can affect the gene of evaluation on the selection of method.As if multiple change the result that tool repeatability is provided.Multiple changes the ratio (or difference of the average logarithmic value of contrast and the average logarithmic value for the treatment of group data) of the mean value that can be defined as contrast mean value and treatment group observed value.Therefore, multiple is changed to 1 expression with respect to the not variation of contrast observed value.Positive multiple changes the rising that expression was expressed through for some time, is called rise herein, and negative multiple changes the reduction that expression was expressed through for some time, is called downward modulation herein.The significance that multiple changes can be determined by common statistical method.
According to some aspect of the present invention, beneficial effect can be optimized by adjusting treatment temp and/or other processing parameters, described adjustment is in response to the rise maximization of the gene that is selected from therein table 1 and/or table 2, and constant in fact express spectra is kept in the expression that is selected from simultaneously the gene of table 3.Processing scheme of the present invention can comprise safeguards processing, and wherein beneficial effect is processed to be maintained by one or more maintenances and surpassed described toeatment period, and each is safeguarded to process and comprises at least one maintenance intervals.
The creative skin treatment scheme imagination of the present invention is passed through the RF electric current heat application via handheld RF current delivery device conductivity.According to preferred RF delivery apparatus of the present invention, to place the current forms at a distance of conductivity between the electrode of some distances on the skin to send RF.The delivery apparatus of realizing beneficial effect of the present invention conducts radio-frequency current by tissue volume, and does not have visible light or the electromagnetic radiation in the infrared frequency of electromagnetic spectrum, the monochrome of replenishing that does not have the described tissue volume of sensing or polychromatic source and do not have Physical temperature-lowering.
The ability that provides according to the effect in the beneficial effect of the present invention that is combined in of assessing any energy delivery apparatus or energy delivery technique is provided certain embodiments of the present invention.Therefore, assessment is designed to by heated skin to provide the concrete grammar of processing effect of the energy delivery apparatus of beneficial effect to comprise to described skin: process described skin by using described energy delivery apparatus; Extract mRNA the sample of the skin after described processing; And produce express spectra for gene panel as described in the present invention.As shown in embodiment 3 hereinafter, there is RF current delivery device, it comprises the parameter specification dividing value that can be counted to produce according to express spectra of the present invention.A kind of suitable device is made by Syneron.Be not to be designed to realize that it is the RF delivery apparatus that is used by a kind of hand-held individual that Ultragen Ltd makes that genomics of the present invention is replied the example of the device of purpose, its in Europe with STOP TMThe brand issue.This device also is displayed among Fig. 3 and is used for relatively, and it fails to cause the rise of the gene in table 1 and 2.The specification of this device is designed to be fit to based on the scheme that provides that is applied in the less in fact heat energy on the larger skin area, and can not reach the required level of effect that realizes the positive poisonous substance excitement that realizes by device according to the present invention and scheme.
According to another embodiment of the invention, provide the method for screening skin of face processing scheme.Effect aspect described method is replied for the inflammatory cytokine that injured skin can not be provided provide collagen and/or corium to reinvent from beneficial effect to mammal skin and screening.Described method generally comprises according to processing scheme process facial skin; Extract mRNA the sample of the skin of face after described processing; Produce gene expression profile for gene panel as described in the present invention; Described gene expression profile and reference spectrum are compared; And when described express spectra reflects the rise of the gene that is selected from table 1 and/or table 2 and be selected from the in fact shortage of regulation and control of gene of table 3, determine that described facial processing scheme is effective.In specific embodiment, described skin of face processing scheme is included in uses the generation of radio-frequency current generation device by the pulse radiation frequency electric current of the first tissue volume of described skin of face in the treatment cycle.Described processing scheme can be included in the described treatment cycle, and mobile described radio-frequency current generation device and generation are by the pulse radiation frequency electric current of the second tissue volume of described skin of face.
In screening method, for having selected the zone of skin with the consistence of the especially facial characteristic of target treatment zone.The zone of the beauty treatment aspect fragility of skin of face comprises the zone in socket of the eye week and mouthful week.Therefore, be called as the skin of face around the ear of ear week skin, approach with processing the target zone on the structure, but with regard to the infringement that may be caused by micro-biopsy procedure, be not easy to be seen.Therefore, the present invention need to carry out bioptic aspect, needed sample by to the week of the ear after processing skin examination of living tissue obtain, and with reference to by to before processing or untreated ear week skin examination of living tissue obtain.Generally speaking, before the described processing or untreated ear week with reference to skin comprise after the basically contiguous described processing ear week skin skin.In unusual specific embodiment, the multiple that the express spectra that is selected from the gene of table 1 and/or table 2 shows statistically greater than one times of described reference changes.
Be noted that, although because skin of face has caused maximum cosmetic treatments challenge (because it the most easily shows the aging of aging and environmental correclation and the effect of damage, and its initial thinner and more fragile than other regional skins of health) in illustrative embodiment, emphasized skin of face, but the present invention can also provide beneficial effect to the skin outside the skin of face.In addition, for the human consumer of cosmetic treatments technology, skin of face is the zone with topmost importance attractive in appearance.
In certain embodiments, by using beautifying active substance or composition to skin of face synergistically with the generation of pulse radiation frequency electric current, the beneficial effect that is provided by the application of RF electric current can be extended or be strengthened.Described active substance or composition can have reinforcement or synergistic effect according to gene expression profile of the present invention.The limiting examples of the beautifying active substance that is fit to comprises Vogan-Neu propionic ester and derivative, caffeine, hyaluronic acid and general plant milk extract.
With regard to treatment cycle, toeatment period, treatment temp and delivery apparatus, screening method according to the present invention comprises the parameter identical in fact with the treatment in accordance with the present invention method, and described parameter is adjusted with regard to desired screening dividing value.
According to other embodiments of the present invention, provide the gene label of the difference expression gene that is applicable to identify makeup skin beneficiating effect.Described beneficial effect comprises, in the situation that the inflammatory cytokine that does not have injured skin is replied, induce formation and/or the corium of collagen to reinvent in the skin corium of mammal skin, described gene label comprises at least a gene in each that is selected from table 1, table 2 and table 3.Generally speaking, gene label is the subset of the gene that obtains from the data set of the gene relevant with particular characteristics, proterties or biological function.Gene label can be from all or part of acquisition of gene data collection, and can comprise from least about two kinds of genes or form at the most the information of any amount of gene of the quantity of total data set according to label of the present invention.When the subset of described data set was used, described subset can comprise the gene of rise, the gene of downward modulation, the gene of not regulated and control in fact or their combination.
Method of the present invention comprises to the regional step that applies the first man care composition and randomly apply the second personal care composition of mammal skin.Described the first and second personal care compositions can be various ways, include but not limited to lotion, white cream, slurries, foam, gel, spray, salve, facial mask, club, wetting Agent for Printing Inks, patch, powder and/or cleaning piece.In one embodiment, described first man care composition before the delivery of energy and/or during the coating.In an alternative embodiment, described the second personal care composition is coating after described the first composition of coating and delivery of energy.Randomly, method of the present invention can comprise the step that applies the 3rd personal care composition to skin, and wherein said the 3rd composition comprises amendment.In one embodiment, described the 3rd personal care composition applied before the described first man care composition of coating.Preferably, described the 3rd composition coating before delivery of energy at least 24 hours.In an alternative embodiment, described first man care composition applies twice every day, and energy is sent once every day, and is perhaps weekly, perhaps per month once.In one embodiment, twice of every day is coated to described first man care composition on the skin, and once in a week to the dermal delivery energy.
Described first, second, and third personal care composition can comprise Multiple components, and its limiting examples can be present in The CTFA International Cosmetic Ingredient Dictionary and Handbook, the tenth edition (2004).
Composition of the present invention can comprise 50% to 99.9% dermatology acceptable carrier.Carrier of the present invention is emulsion form.Herein, " emulsion " generally includes and contains water and oil phase.Oil can derived from animal, plant or oil, can be natural or synthetic, and can comprise silicone oil.Emulsion carriers includes but not limited to oil-in-water, water-in-oil, water-in-oil-in-water and water-in-silicone bag fat liquor.In one embodiment, the dermatology acceptable carrier comprises O/w emulsion, perhaps water-covered siloxane.Described emulsion can also comprise wetting agent, for example, and the emulsifying agent of glycerine and non-ionic, cationic and/or negatively charged ion.Suitable emulsifying agent is disclosed in, and for example, authorizes the people's such as Dickert United States Patent (USP) 3,755,560, authorize the people's such as Dixon United States Patent (USP) 4,421,769 and McCutcheon ' s Detergents and Emulsifiers, in the North America version 317-324 page or leaf (1986).
Can in larger number change scope, improve skin with composition of the present invention.The amount that is coated to the personal care composition on the skin can change according to the position of health and the beneficial effect of expectation.Exemplary amount comprises 0.1mg/cm 2To 40mg/cm 2An available amount of application is 0.5mg/cm 2To 10mg/cm 2
In the composition in skin or on being administered to skin surface, can produce simultaneously temperature variation.This temperature variation is the variation except any temperature variation that is produced by delivery of energy self.For example, can be before energy be sent with the skin heating, perhaps before energy is sent, during and/or afterwards skin is cooled off.
Use gene panel and gene label after processing, and widely human consumer's investigation, the zone of scheme set up, so that developed size and the optimized treatment time of optimized treatment zone.Find on the contrary with the instruction of this area, using appts is not best treatment process on big area.When excessive when regional processed, the part of beginning can the human consumer again inswept above it before cooling and replying.If the zone of processing is too little, the human consumer can emit the risk of excess processes and unnecessary damage.In addition, processing itself is high-intensity work for the human consumer, processing is divided into little block so that the easier scheme of fully observing of human consumer.Equally, if the human consumer can be applied to less zone with the personal care composition that uses with device, processes this zone, then remove the personal care composition of any remnants, so described composition will to human consumer's more attractive many.Personal care composition is applied on the face whole, perhaps or even one side of something on the face, can cause processing experience and make us unhappy.This has negative impact for human consumer's compliance then.
See now lower Figure 10, wherein the with dashed lines annulus has marked human consumer 62 crow's feet zone 60, and it occurs in the above and below of eye 64 and the tail of the eye of contiguous every a glance.As everyone knows, along with people's ageing, crow's feet zone 60 is easy to form wrinkle and microgroove, and is easy to suffer environmental injury.Figure 11 has shown regional A 70, and the arrow that wherein shows among the regional A has been showed the exemplary process approach of described device (not shown).Above provided the treatment time.Figure 10 shows regional B 72, and it is positioned at the top of same eyes of the human consumer 62, and overlapping with crow's feet zone 60.Shown exemplary arrow, to show possible processing approach.By by this way localized area A 70 and regional B 73, the length of the non-crow's feet zone twice of crow's feet zone 60 is processed regional A and B.This is an important discovery, because need on the face to be processed the human consumer, most microgroove and wrinkle are positioned at the crow's feet zone.
Figure 13 and 14 shows regional C 74 and the D 76 on human consumer 62 the another eyes 64.Can expect as people, these treatment zones and regional A and B are similar in fact and processed in an identical manner.
A kind of alternative processing scheme is shown in Figure 15 and 16, has wherein shown regional E 80 and F 82 human consumer 62.These " C " type treatment zones are each time through out-of-date crow's feet zone 60 of processing Figure 10 once, but long " C " type treatment zone allows each zone of processed skin to cool off a little before returning the process of carrying out another at device.So, human consumer's comfort level has increased, but 60 in the crow's feet of Figure 10 zone is processed in this treatment cycle.
The second personal care composition optionally uses with aforesaid method.Described the second personal care composition can use between the continuous treatment cycle that uses described first man care composition and hot charging to put.Described the second personal care composition preferably comprises at least a skin care actives that is not present in the described first man care composition.
Following embodiment is provided for some feature and advantage that shows multiple embodiments of the present invention, and should not be understood to limit its scope.
Embodiment
Embodiment 1: Processing scheme
The present embodiment has been set forth the regional processing of ear week to skin of face, and the purpose of processing is to carry out genomics and histological assessment.Therefore, be in the control purpose, whole processing is all carried out by the technician under clinical the setting.Four zones in the process range are processed, process amounting to 16 minutes, each zone 4 minutes, on every Wendesdays inferior carrying out for six weeks.These rules are processed the ear week zone that only is applied to a side according to the face that adopts the design of experimenter's own control/neck subregion research, and it is regional to add that by gel false processing that the equipment of not energising forms is applied to ear week of correspondence of opposite side.Process with Thermal Imaging Camera monitoring, in first minute, reach 40-43 ℃ to guarantee the target skin surface temperature, and in each 4 minutes processing, keep but be no more than.
Treatment site is positioned at center, ear below.About 1.5 inches wide of this site, approximately 4 inches long.If process the regional too dry of skin or overheat, can use extra gel.Experimenter's face and neck are clean, and do not have astringent, perfume etc.Hair is cut short from treatment zone.
Device is processed:
1. the amount (approximately 1.4g gel) of squeezing is administered to treatment site, and coating is evenly avoided friction.If skin overheats, represented such as the experimenter, the gel of the amount of squeezing of adding can be applied in case of necessity the cheek of described treatment zone top during the processing, so that the skin cooling.
2. opening unit and set the timer to 4 minutes.
3. the function head of device is applied on the skin, and adopts to seesaw and move along treatment site with slight touching.The head of operating device is kept connectedness across treatment zone the time.Show with suitable the contact by the lens on the application device of skin, it should continue to dodge ruddiness and indicate contact.
4. the thermal camera image is monitored during processing.In second, the skin in the treatment zone reaches 40-43 ℃ ideal temperature at 30-60.Color mode on the heat picture has represented temperature.Generally speaking, along with the device heating, application device is moved across skin rapidly, to avoid causing discomfort because of the temperature that raises.Along with processing is proceeded, move and slowed down to keep desirable temperature.The experimenter is alerted, and device will make us sensible heat, but can not be burnt.
5. if heat picture shows solid red area, then temperature has surpassed 43 ℃.Control temperature by following manner: improve the processing speed that seesaws; Slightly increase the size for the treatment of zone;
Hocket and seesaw and the 8-shaped motor pattern; Perhaps by making function head contact be deposited on the extra gel for this accidental situation on the cheek, and add more gel.
6. if treatment zone fails to reach desirable temperature, perhaps it has cooled off, and should make seesaws slows down, until the major part of described treatment zone is in target temperature.
Embodiment 2: The examination of living tissue rules
The present embodiment has demonstrated for the relative gentle examination of living tissue rules of collection according to the assessment of some aspect of the present invention and monitoring purpose specimen in use, and supported data disclosed herein.
In 30 adult female experimenters, use RF current delivery device to carry out clinical biopsy studies.Ear week (around the ear) zone at skin of face provides processing.The all skin of ear is known as the suitable substitute of socket of the eye week skin at beauty treatment fields.Process and to use clinically Syneron V8 device (referring to embodiment 3) to carry out, four minutes add Thermogram as the target spectrogram.The experimenter accepts weekly three times and processes, and amounts to and carries out for six weeks.Carry out examination of living tissue, according to the variation of processing, and produced the genome spectrum with the histology of detection of skin.
The examination of living tissue flow process:
Obtained the living tissue sample of 4mm from the ear week zone on the left side of neck and right side (this zone be positioned at ear under).Use the aseptic syringe needle of 30 wire gauges, will contain and adrenergicly comprise the fix of 2% Xylocitin to the skin for the treatment of biopsy.In case it is numb that the experimenter represents this zone, that adopts namely that the aseptic technique of standard collects suitable size drills through the living tissue sample, then passes through sewn closed.In case of necessity, 20% aluminum chloride aqueous solution is used to homeostasis.After the examination of living tissue, the normal healing of monitoring suture, and after 7 days, remove suture line.
Sample preparation after the examination of living tissue:
Bioptic tissue is divided into two minutes other sample, one is detected for genetic expression, and another is for Histological assessment.Sample is divided into equal two parts with the lines that are parallel to from the stratum corneum picture to the line of corium.The processing of sample is carried out according to industry standard.
Embodiment 3: MRNA extracts and analyzes
The present embodiment has been set forth and has been supported to comprise gene chip, gene label and instruct RF to send evaluation and the analysis of RNA biomarker of certain embodiments of the present invention of discovery of biological model of the design of scheme.
The both sides of the face/neck under ear as indicated above have obtained the living tissue sample 2 times of 4mm according to embodiment 2, and once after final processing 24 hours, 4 weeks after processing once.
Biopsy samples be transferred to comprise 1.5ml tissue store reagent ( Solution, invitrogen, Life Technologies, Carlsbad, CA) the 2ml centrifuge tube in.Centrifuge tube spends the night 2-8 ℃ of refrigeration.Remove storage reagent, and with sample as in-80 ℃ of refrigerators until process.Before facing processing, from refrigerator, shift out sample, to each pipe add 1.5ml phenol and guanidinium isothiocyanate (
Figure BDA00002275584400232
Reagent, Invitrogen, Life Technologies, Carlsbad, CA) a single phase soln and a 3mM wolfram varbide globule (3mM Tungsten Carbide beads, Qiagen, catalog number (Cat.No.) 69997).The sample that homogenizes immediately in mixed grinding device (Quiagen Inc.), carrying out four times 3 minutes processing in 30/ second, joint overturns after each.With the centrifugal sample of 12,000rpm 10 minutes, to remove impurity.Then, supernatant liquid is transferred to the PhaseLock gel that rotates through in advance and heavily manages (Phase Lock gel heavy tubes, Eppendorf, New York, NY, catalog number (Cat.No.) 0032-005-152) in, add 300 μ L chloroforms (Sigma), concuss is avoided excessive vortex.With the centrifugal sample of 12,000rpm 10 minutes, supernatant liquid is transferred in the new 2ml centrifuge tube afterwards.
Regulate conjugation condition by adding 800 μ L, 70% ethanol, the vortex pipe is with mixing, then of short duration rotation.The 830ml sample is transferred in the RNeasy centrifugal mini column chromatography in the vacuum manifold, and uses vacuum.Remaining sample (approximately 830mil) is transferred on the identical RNeasy post and uses vacuum.By using vacuum on damping fluid RW1 to the RNeasy post that pipettes successively 700 μ l and 500 μ l and after each the cleaning, removed pollutent.
Above-mentioned RNeasy centrifugal column is transferred in the new 2mil collection tube, and with the centrifugal pipe of 14,000rpm 2 minutes, with posts transfer to new 1.5ml collection tube.The remaining ethanol of interior ridge suction from each pillar.The water that does not contain the RNA enzyme of 30 μ l preheatings is directly moved liquid to the RNeasy film, hatches film 5 minutes, then with 14,000rpm centrifugal 2 minutes.Collect elutriant, obtain the RNA of water-soluble instant.
After separating, use can be available from Agilent Technologies, Inc.of Santa Clara, RNA 6000 Nano of CA
Figure BDA00002275584400233
Kit#5065-4476 measures RNA output.By single stage method RT-PCR assessment RNA.With regard to the RT-PCR biomarker analysis, RNA is diluted to the final concentration in 5ng/ hole.
Use RT-PCR test kit (QScript TMOne-Step Fast MGB qRT-PCR test kit can be available from Quanta BioScience, Inc., Gaithersburg, MD) RNA of purifying is converted into cDNA.Then the RNA with 500 nanograms mixes with QScript enzyme/damping fluid premixed liquid, and moves at thermal cycler according to the specification sheets of test kit.Then the resulting cDNA with a μ l mixes with Quanta Perfecta Master Mix, and uniformly distributing is to dull and stereotyped (the Custom RT Profiler of custom arrays for the primer of following gene that comprises in advance checking TMPCR Array can be available from SABiosciences, Corp., Federick, MD): KRT2, KRT6A, CLDN1, LOR, FLG, IVL, KRT10, AQP3, KRT14, FBN1, FBNL1, TNXB, FN1, LOXL2, COL3A1, COL1A1, ELN, LOXL1, TIMP2, IL1A, TIMP1, TNF, MMP1, MMP9, MMP3, SOD2 and IL1B.Then seal above-mentioned array dull and stereotyped, and at thermal cycler (StepOnePlus TMReal-Time PCR System Upgrade, from Applied Biosystems, Inc.Foster City, CA) upper operation.
Data analysis is used by SABiosciences of Frederick, and the data analysis software that MD provides is carried out.
Above listed 27 compiling genes are distinguished shown in as mentioned Fig. 4 A, the 4B and Fig. 6 A, 6B at the expression multiple delta data of the target spot time in 24 hours and 4 weeks.The gene relevant with dermal matrix is grouped into 90 and 91, reinvents relevant gene with the corium inflammation and is grouped into 92 and 93, and the gene relevant with epidermal differentiation is grouped into 94 and 95.The multiple delta data of exemplary gene is shown in Fig. 5 A collagen 1A1,5B elastin and Fig. 7 A collagen 1A1 and 7B elastin.Please note many collagen e1A1 genes and the common regulation and control between the elastin gene.
Dimension disclosed herein and value are not appreciated that and are strictly limited to the exact value of quoting.On the contrary, except as otherwise noted, each such dimension all is intended to both to have represented the value quoted, also the scope that is equal on the function of this value of expression.For example, the dimension that is disclosed as " 40mm " is intended to expression " approximately 40mm ".
Unless clearly get rid of or in other words to some extent restriction, each document of quoting herein comprises any cross reference or Patents or patent application, all incorporates in full this paper into way of reference accordingly.The quoting of any document is not it as disclosed herein or be subjected to the prior art of any invention of claims protection; perhaps its individually or with any combination of any other reference, perhaps with reference to, propose, suggestion or disclose the approval of any this type of invention.In addition, if in this document in any implication of term or definition and the document of incorporating into way of reference any implication of same term or define conflict mutually, will be as the criterion with implication or the definition of giving that term in this document.
Although illustrate and described particular of the present invention, it should be apparent to those skilled in the art that in the situation that do not break away from the spirit and scope of the invention and can make many other change and modification.Therefore, claims are intended to contain all these changes and the modification in the scope of the invention.
The multiple delta data is checked and analyzes, grouping to it is found surprisingly, as the separated (IL1A of gene that shows few adjusting in response to described processing, IL1B and TNF) time, they comprise the inflammatory cytokine response gene, are raised under treatment condition and reinvent relevant gene with the synthetic and renewal of collagen and corium.Correspondingly tabulate in table 1 hereinafter, 2 and 3 according to the gene that the multiple delta data is selected.
In addition, also find surprisingly, processing scheme is kept hardly in the time of rear 1 month in processing and to be weakened the positive influence of genetic expression in the time of 24 months.For keeping the genomics effect to exceeding the above-mentioned time, safeguard and process and to need.
The expection gene expression profile reflects the rise in the translation product middle and lower reaches.Although it may be relatively low that viewed multiple changes, the lasting rise of some protein and Enzyme Production in the long term is considered to give substantial lasting beauty treatment beneficial effect to skin.
Embodiment 4: Personal care composition
Figure BDA00002275584400251
Following is for the exemplary personal care composition of following device of the present invention to use.
Table 1
The corium mark
Figure BDA00002275584400261
Figure BDA00002275584400271
Table 2
Matrix is reinvented mark
Figure BDA00002275584400281
Table 3
The inflammatory cytokine respond flag
Figure BDA00002275584400291
Figure IDA00002275585100031
Figure IDA00002275585100041
Figure IDA00002275585100061
Figure IDA00002275585100071
Figure IDA00002275585100081
Figure IDA00002275585100091
Figure IDA00002275585100121
Figure IDA00002275585100131
Figure IDA00002275585100161
Figure IDA00002275585100171
Figure IDA00002275585100191
Figure IDA00002275585100201
Figure IDA00002275585100211
Figure IDA00002275585100221
Figure IDA00002275585100231
Figure IDA00002275585100251
Figure IDA00002275585100271
Figure IDA00002275585100281
Figure IDA00002275585100291
Figure IDA00002275585100301
Figure IDA00002275585100321
Figure IDA00002275585100331
Figure IDA00002275585100341
Figure IDA00002275585100361
Figure IDA00002275585100391
Figure IDA00002275585100401
Figure IDA00002275585100411
Figure IDA00002275585100421
Figure IDA00002275585100451
Figure IDA00002275585100471
Figure IDA00002275585100481
Figure IDA00002275585100491
Figure IDA00002275585100501
Figure IDA00002275585100521
Figure IDA00002275585100531
Figure IDA00002275585100541

Claims (11)

1. gene panel, comprise in response to the generation of the radio-frequency current in the tissue volume of mammal skin the gene of in described mammal skin, being regulated and control, described radio-frequency current enough is heated to treatment temp with described tissue volume, wherein at least a gene is selected from table 1 or table 2, and at least a gene is selected from table 3.
2. gene panel as claimed in claim 1, wherein at least a gene is selected from table 1, and at least a gene is selected from table 2, and at least a gene is selected from table 3.
3. a microarray comprises one group of fixing nucleic acid probe, and described fixing nucleic acid probe can and detect described gene with the gene recombination that forms gene panel as claimed in claim 1 or 2.
4. method of assessing the processing effect of energy delivery apparatus, described energy delivery apparatus is designed to provide beneficial effect by heated skin to described skin, and described method comprises: process described skin by using described energy delivery apparatus; Extract mRNA the sample of the skin after described processing; And for gene panel generation express spectra as claimed in claim 1 or 2.
One kind aspect replying for the inflammatory cytokine that injured skin can not be provided provide collagen and/or corium to reinvent effect from beneficial effect to mammal skin and screen the method for skin of face processing scheme, described method comprises: according to processing scheme process facial skin; Extract mRNA the sample of the skin of face after described processing; Produce gene expression profile for gene panel as claimed in claim 1 or 2; Described gene expression profile and reference spectrum are compared; And when described express spectra reflects the rise of the gene that is selected from table 1 and/or table 2 and be selected from the in fact shortage of regulation and control of gene of table 3, determine that described facial processing scheme is effective.
6. method as claimed in claim 5, wherein said skin of face processing scheme comprise, uses the radio-frequency current generation device to produce pulse radiation frequency electric current by the first tissue volume of described skin of face in treatment cycle.
7. method as claimed in claim 6, wherein said processing scheme also comprise, in described treatment cycle, mobile described radio-frequency current generation device also produces pulse radiation frequency electric current by the second tissue volume of described skin of face.
8. method as claimed in claim 7, wherein said skin of face comprises ear week skin, and described sample passes through the examination of living tissue of all skin of ear after processing is obtained, and described reference is by obtaining examination of living tissue before processing or all skin of untreated ear.
9. before the method as claimed in claim 8, wherein said processing or untreated ear week with reference to skin comprise after the basically contiguous described processing ear week skin skin.
10. the expression that method as claimed in claim 9, the gene that wherein is selected from table 1 show statistically greater than one times of described reference improves.
11. gene label that is applicable to identify the difference expression gene of makeup skin beneficiating effect, described beneficial effect comprises, in the situation that the inflammatory cytokine that does not have injured skin is replied, induce formation and/or the corium of collagen to reinvent in the skin corium of mammal skin, described gene label comprises at least a gene in each that is selected from table 1, table 2 and table 3.
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Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9671410B2 (en) 2011-01-16 2017-06-06 The Procter & Gamble Company Biomarker-based methods for identifying and formulating compositions that improve skin quality and reduce the visible signs of aging in skin
EP2691539B1 (en) 2011-03-31 2018-04-25 The Procter and Gamble Company Methods for identifying and evaluating skin-active agents effective for treating dandruff
EP2831272B8 (en) * 2012-03-30 2018-11-21 The Procter and Gamble Company Method of identifying a skin-lightening agent
MX2014014898A (en) 2012-06-06 2015-03-04 Procter & Gamble Systems and methods for identifying cosmetic agents for hair/scalp care compositions.
US10036741B2 (en) 2012-08-15 2018-07-31 The Procter & Gamble Company Systems, models and methods for identifying and evaluating skin-active agents effective for treating an array of skin disorders
MX2017006149A (en) 2014-11-10 2017-07-27 Procter & Gamble Personal care compositions with two benefit phases.
CN107106429B (en) 2014-11-10 2021-06-29 宝洁公司 Personal care composition with two benefit phases
US10966916B2 (en) 2014-11-10 2021-04-06 The Procter And Gamble Company Personal care compositions
WO2019079405A1 (en) 2017-10-20 2019-04-25 The Procter & Gamble Company Aerosol foam skin cleanser
WO2019079409A1 (en) 2017-10-20 2019-04-25 The Procter & Gamble Company Aerosol foam skin cleanser
WO2020112486A1 (en) 2018-11-29 2020-06-04 The Procter & Gamble Company Methods for screening personal care products

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020128641A1 (en) * 1999-08-30 2002-09-12 Arthrocare Corporation Systems and methods for intradermal collagen stimulation
WO2006080012A1 (en) * 2005-01-28 2006-08-03 Syneron Medical Ltd Device for treating skin

Family Cites Families (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3755560A (en) 1971-06-30 1973-08-28 Dow Chemical Co Nongreasy cosmetic lotions
US4421769A (en) 1981-09-29 1983-12-20 The Procter & Gamble Company Skin conditioning composition
US5525464A (en) 1987-04-01 1996-06-11 Hyseq, Inc. Method of sequencing by hybridization of oligonucleotide probes
US5202231A (en) 1987-04-01 1993-04-13 Drmanac Radoje T Method of sequencing of genomes by hybridization of oligonucleotide probes
GB8810400D0 (en) 1988-05-03 1988-06-08 Southern E Analysing polynucleotide sequences
US5143854A (en) 1989-06-07 1992-09-01 Affymax Technologies N.V. Large scale photolithographic solid phase synthesis of polypeptides and receptor binding screening thereof
US6040138A (en) 1995-09-15 2000-03-21 Affymetrix, Inc. Expression monitoring by hybridization to high density oligonucleotide arrays
US5800992A (en) 1989-06-07 1998-09-01 Fodor; Stephen P.A. Method of detecting nucleic acids
US5547839A (en) 1989-06-07 1996-08-20 Affymax Technologies N.V. Sequencing of surface immobilized polymers utilizing microflourescence detection
EP0430881A3 (en) 1989-11-29 1991-10-23 Ciba-Geigy Ag Photochromic compounds, process for their preparation and their use
US5288644A (en) 1990-04-04 1994-02-22 The Rockefeller University Instrument and method for the sequencing of genome
US5324633A (en) 1991-11-22 1994-06-28 Affymax Technologies N.V. Method and apparatus for measuring binding affinity
US5366443A (en) 1992-01-07 1994-11-22 Thapliyal And Eggers Partners Method and apparatus for advancing catheters through occluded body lumens
ATE173767T1 (en) 1992-04-03 1998-12-15 Perkin Elmer Corp SAMPLES COMPOSITION AND METHODS
US5503980A (en) 1992-11-06 1996-04-02 Trustees Of Boston University Positional sequencing by hybridization
US5858659A (en) 1995-11-29 1999-01-12 Affymetrix, Inc. Polymorphism detection
US5470710A (en) 1993-10-22 1995-11-28 University Of Utah Automated hybridization/imaging device for fluorescent multiplex DNA sequencing
GB9401833D0 (en) 1994-02-01 1994-03-30 Isis Innovation Method for discovering ligands
US5458596A (en) 1994-05-06 1995-10-17 Dorsal Orthopedic Corporation Method and apparatus for controlled contraction of soft tissue
WO1997027317A1 (en) 1996-01-23 1997-07-31 Affymetrix, Inc. Nucleic acid analysis techniques
GB9507238D0 (en) 1995-04-07 1995-05-31 Isis Innovation Detecting dna sequence variations
US5755753A (en) 1995-05-05 1998-05-26 Thermage, Inc. Method for controlled contraction of collagen tissue
US6241753B1 (en) 1995-05-05 2001-06-05 Thermage, Inc. Method for scar collagen formation and contraction
US6430446B1 (en) 1995-05-05 2002-08-06 Thermage, Inc. Apparatus for tissue remodeling
US5660836A (en) 1995-05-05 1997-08-26 Knowlton; Edward W. Method and apparatus for controlled contraction of collagen tissue
US5661028A (en) 1995-09-29 1997-08-26 Lockheed Martin Energy Systems, Inc. Large scale DNA microsequencing device
US6228078B1 (en) 1995-11-22 2001-05-08 Arthrocare Corporation Methods for electrosurgical dermatological treatment
US6350276B1 (en) 1996-01-05 2002-02-26 Thermage, Inc. Tissue remodeling apparatus containing cooling fluid
EP1158919B1 (en) 1999-03-09 2005-06-29 Thermage, Inc. Apparatus for treatment of tissue
US6702808B1 (en) 2000-09-28 2004-03-09 Syneron Medical Ltd. Device and method for treating skin
WO2002032332A1 (en) * 2000-10-18 2002-04-25 Mattoli Engineering Ltd. Method and apparatus for plasma skin resurfacing
US6889090B2 (en) 2001-11-20 2005-05-03 Syneron Medical Ltd. System and method for skin treatment using electrical current
US6662054B2 (en) 2002-03-26 2003-12-09 Syneron Medical Ltd. Method and system for treating skin
KR20050062597A (en) 2002-10-07 2005-06-23 팔로마 메디칼 테크놀로지스, 인코포레이티드 Apparatus for performing photobiostimulation
SI22738A (en) * 2008-04-11 2009-10-31 Iskra Medical, D.O.O. Device for radiofrequency circular deep therapy

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020128641A1 (en) * 1999-08-30 2002-09-12 Arthrocare Corporation Systems and methods for intradermal collagen stimulation
WO2006080012A1 (en) * 2005-01-28 2006-08-03 Syneron Medical Ltd Device for treating skin

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
AFFYMETRIX: "Affymetrix Genechip bhuman Genome U133 plus 2.0 Array", 《GEO》, 7 November 2003 (2003-11-07) *
ZELICKSON ET AL: "Histological and Ultrastructural Evaluation of the Effects of a Radiofrequency-Based Nonablative Dermal Remodeling Device", 《HISTOLOGICAL AND ULTRASTRUCTURAL EVALUATION OF THE EFFECTS OF A RADIOFREQUENCY-BASED NONABLATIVE DERMAL REMODELING DEVICE》, 29 February 2004 (2004-02-29) *
炊亚娟等: "应用EMF2008- I 高频治疗仪治疗面部老年性皮肤皱纹", 《中国美容医学》, vol. 18, no. 6, 30 June 2009 (2009-06-30) *

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