WO2013077641A1 - Agent d'amélioration de la réparation de la peau contenant des facteurs de croissance - Google Patents

Agent d'amélioration de la réparation de la peau contenant des facteurs de croissance Download PDF

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WO2013077641A1
WO2013077641A1 PCT/KR2012/009919 KR2012009919W WO2013077641A1 WO 2013077641 A1 WO2013077641 A1 WO 2013077641A1 KR 2012009919 W KR2012009919 W KR 2012009919W WO 2013077641 A1 WO2013077641 A1 WO 2013077641A1
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Prior art keywords
growth factor
skin
skin regeneration
ppm
regeneration
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PCT/KR2012/009919
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English (en)
Korean (ko)
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김정환
이창근
백수정
김혁
정연수
전상훈
신홍주
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(주)아모레퍼시픽
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18—Growth factors; Growth regulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/30—Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations

Definitions

  • the present invention relates to a skin regeneration accelerator comprising a growth factor
  • the skin acts as a shield to protect the body from the outside. If such a wound occurs on the skin, the healing is achieved by the natural healing action of the living body.
  • the wound healing process is divided into four stages: inflammatory, re-epithelial, proliferative and mature stages.
  • inflammatory re-epithelial
  • proliferative mature stages.
  • immune cells migrated from blood vessels appear at the wound site, which usually progress briefly in the absence of significant infection.
  • granular tissues including fibroblasts, inflammatory cells, and extracellular matrix components, such as immaturity collagen, fibronectin, or hyaluronic acid, are placed on the wound site. Is formed. The rapid filling and organization of these granular tissues is a key to wound healing.
  • the exfoliated wound surface is then covered by a layer of keratinocytes, creating a new epidermis and reconstructing the epidermal layer. This means that in the process of wound healing, promoting the regeneration of fibroblasts or keratinocytes can quickly heal skin wounds and minimize scarring.
  • Patent Document 1 Korean Patent Publication No. 10-2010-0098298 (Published September 9, 2010)
  • the present invention seeks to provide agents that promote skin regeneration and specifically promote skin wound and burn healing.
  • the present invention is to provide a cosmetic composition and a pharmaceutical composition having an excellent skin regeneration promoting effect, including the skin regeneration accelerator as described above.
  • EGF epidermal growth factor
  • PDGF-AA platelet-derived growth factor-AA
  • IGF-1 insulin-like growth factor-1
  • Another aspect of the present invention provides a cosmetic composition and a pharmaceutical composition comprising the skin regeneration accelerator.
  • the preparations according to the invention comprise epithelial growth factor, platelet derived growth factor-AA and insulin-like growth factor-1, and optionally further comprise one or more growth factors of transforming growth factor- ⁇ and fibroblast growth factor. As a result, it has an excellent skin regeneration effect, further promotes skin wound and burn healing, and minimizes scarring.
  • 1 is a graph showing the effect of growth factors or combinations thereof on human keratinocyte regeneration.
  • FIG. 2 is a graph showing the effect of growth factors or combinations thereof on human fibroblast regeneration.
  • Figure 3 is a diagram showing the observation of the extent to which the growth factors or combinations of artificial skin regeneration.
  • skin refers to a tissue covering the body surface of an animal, and is a broad concept including not only tissues covering the body surface such as the face or body, but also the scalp and hair.
  • One aspect of the present invention is epidermal growth factor (EGF), platelet-derived growth factor-AA (PDGF-AA) and insulin-like growth factor-1 (IGF-1, Insulin It provides a skin regeneration accelerator comprising -like growth factor-1).
  • Another aspect of the present invention provides a skin regeneration promoter further comprising one or more growth factors of transforming growth factor beta (TGF- ⁇ ) and fibroblast growth factor (FGF).
  • TGF- ⁇ transforming growth factor beta
  • FGF fibroblast growth factor
  • the growth factors promote growth and regeneration of keratinocytes and fibroblasts.
  • formulations comprising the same may promote skin regeneration, further promoting skin wound and burn healing, and reducing scars.
  • growth factor refers to a polypeptide that promotes the division, growth and differentiation of multiple cells, and refers to epidermal growth factor (EGF), platelet derived growth factor-AA (PDGF-AA), insulin-like growth factor- 1 (IGF-1), transforming growth factor- ⁇ (TGF- ⁇ ) or fibroblast growth factor (FGF), but is not limited thereto.
  • EGF epidermal growth factor
  • PDGF-AA platelet derived growth factor-AA
  • IGF-1 insulin-like growth factor- 1
  • TGF- ⁇ transforming growth factor- ⁇
  • FGF fibroblast growth factor
  • Epidermal growth factor is a growth factor that promotes growth, differentiation and division of epithelial cells by secreting not only from the skin but also from mucous membranes such as the oral cavity and gastrointestinal tract. It is known to prevent tissue damage from the factor.
  • Platelet derived growth factor-AA is a growth factor that has an important effect on mesenchymal stem cell division during development. In addition to the developmental process, the adult is known to promote the growth, division and migration of mesenchymal-derived cells, and in particular, to promote fibroblast division in the skin.
  • Insulin-like growth factor-1 is basically a growth factor that acts similar to insulin in the body. Examples include skeletal muscle cells, bone cells, chondrocytes, liver cells, kidney cells, nerve cells, skin cells, and hematopoietic cells. It is known to promote the growth of all kinds of cells in the body. In addition, since the growth factor plays an important role in growth, growth deficiency may appear when the growth factor is deficient in infancy, and it is known to play a role in regulating energy assimilation after growth.
  • Transforming growth factor- ⁇ is a growth factor that plays a role in maintaining cell homeostasis by controlling cell division and differentiation.
  • induction of apoptosis (apoptosis) in a number of cells, epithelial cells and cancer cells act as a factor that inhibits division. It is known that the skin may have a whitening effect by inhibiting tyrosinase.
  • Fibroblast growth factor promotes the growth and division of epithelial cells, and is superior to vascular endothelial growth factor (VEGF).
  • VEGF vascular endothelial growth factor
  • this growth factor is known to be involved as an important growth factor in the wound healing process by making new blood vessels in the wound site, proliferating fibroblasts to create granulation tissue.
  • Skin regeneration promoter comprising epidermal growth factor, platelet-derived growth factor-AA, and insulin-like growth factor-1 according to one aspect of the present invention
  • each growth factor 1-5: 1-5: 1-5, specifically 1-3 may be included in the weight ratio of 1 to 3: 1 to 3, more specifically 1 to 2: 1 to 2: 1-2.
  • a skin regeneration promoter comprising epidermal growth factor, platelet derived growth factor-AA, insulin-like growth factor-1, transforming growth factor- ⁇ and fibroblast growth factor may be selected from each growth factor.
  • -5: 1-5: 1-5: 1-5: 1-5: 1-5: 1-5, specifically 1-3: 1-3: 1-3, 1-3: 1-3, more specifically 1-2: 1- 2: 1 to 2: 1 to 2: may be included in the weight ratio of 1-2.
  • Skin regeneration accelerator according to one aspect of the present invention is 1 ⁇ 10 -6 to 1 ⁇ 10 4 % by weight, specifically 1 ⁇ 10 -4 to 1 ⁇ 10 3 % by weight, more specifically based on the total weight of the skin regeneration accelerator 1 ⁇ 10 ⁇ 2 to 1 ⁇ 10 2 weight percent of growth factors or combinations thereof.
  • When included in the above range is not only suitable for showing the intended effect of the present invention, it can satisfy both the stability and safety of the accelerator, it may be appropriate to include in the above range in terms of cost-effectiveness.
  • One aspect of the present invention provides a cosmetic composition comprising a skin regeneration accelerator comprising the growth factor.
  • the cosmetic composition may have a skin regeneration effect, and in particular, may heal skin wounds and burns and reduce scars.
  • Cosmetic compositions according to the invention may be provided in all formulations suitable for topical application.
  • it may be provided in the form of a solution, an emulsion obtained by dispersing an oil phase in an aqueous phase, an emulsion obtained by dispersing an aqueous phase in an oil phase, a suspension, a solid, a gel, a powder, a paste, a foam, or an aerosol composition.
  • Compositions of such formulations may be prepared according to conventional methods in the art.
  • the cosmetic composition according to the present invention may include other ingredients in addition to the above-mentioned substances within the range not impairing the main effect, preferably giving a synergistic effect to the main effect.
  • the cosmetic composition according to the present invention may further include a moisturizer, an emulsifier, a surfactant, a ultraviolet absorber, a preservative, a bactericide, an antioxidant, a pH adjuster, organic and inorganic pigments, flavors, coolants, or limiting agents. have.
  • the blending amount of the above components can be easily selected by those skilled in the art within the range that does not impair the object and effect of the present invention, the blending amount may be 0.01 to 5% by weight, specifically 0.01 to 3% by weight based on the total weight of the composition have.
  • One aspect of the invention provides a pharmaceutical composition comprising a skin regeneration accelerator comprising the growth factor.
  • the pharmaceutical composition may have a skin regeneration effect, and specifically may have a skin wound and burn healing and amelioration effect and a scar reduction effect.
  • composition according to one aspect of the present invention may be administered orally, rectally, topically, transdermally, intravenously, intramuscularly, intraperitoneally, subcutaneously, and the like.
  • Formulations for oral administration may be tablets, pills, soft and hard capsules, granules, powders, fine granules, solutions, emulsions or pellets, but are not limited thereto. It is not. These formulations may contain, in addition to the active ingredient, diluents (e.g. lactose, dextrose, sucrose, mannitol, sorbitol, cellulose or glycine), glidants (e.g. silica, talc, stearic acid or polyethylene glycol), or binders (e.g. magnesium aluminum Silicates, starch pastes, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose or polyvinylpyrrolidine). It may optionally contain pharmaceutical additives such as disintegrants, absorbents, colorants, flavors, or sweeteners.
  • the tablets can be prepared by conventional mixing, granulating or coating methods.
  • Formulations for parenteral administration may be, but are not limited to, injections, drops, lotions, ointments, gels, creams, suspensions, emulsions, suppositories, patches or sprays.
  • the active ingredient of the pharmaceutical composition according to one aspect of the present invention will vary depending on the age, sex, weight, pathology and severity of the subject to be administered, the route of administration or the judgment of the prescriber. Dosage determination based on these factors is within the level of one skilled in the art and its daily dosage may be, for example, from 0.1 mg / kg / day to 100 mg / kg / day, more specifically from 5 mg / kg / day to 50 mg / kg. May be, but is not limited to.
  • One aspect of the present invention provides a food composition comprising the skin regeneration accelerator.
  • the food composition has a skin regenerating effect and specifically can heal skin wounds and burns and reduce scars.
  • the formulation of the food composition is not particularly limited, but may be, for example, formulated into a liquid such as tablets, granules, powders, drinks, caramels, gels, bars, and the like.
  • the food composition of each formulation may be suitably selected by a person skilled in the art according to the formulation or purpose of use in addition to the active ingredient, and may be synergistic when applied simultaneously with other raw materials.
  • the daily dosage of the active ingredient is within the level of those skilled in the art, the daily dosage of which is for example from 0.1 mg / kg / day to 5000 mg / kg / day, more specifically from 50 mg / kg / day to 500 mg / kg / day, but is not limited thereto, and may vary depending on various factors such as age, health condition, and complications of the subject to be administered.
  • HaCaT cells human-derived keratinocyte cell lines, were treated with 10% fetal bovine serum (JRH Bioscience, Tokyo, Japan), 100 mg / ml penicillin and 100 mg / ml streptomycin (both GIBCO , DMEM medium (Invitrogen, Carlsbad, Calif.) was added at 37 °C, 5% CO 2 conditions. Incubate the cells in a 12-well plate at 3.5 X 10 5 per well, wait overnight for the cells to adhere to the wall, wash the cells once with PBS and scrape the cells with a 200 ⁇ l pipette tip. I made a vertical scratch in the middle.
  • Wound Fill Rate (%) ⁇ (0 Hour Scratch Area-24 Hour Scratch Area) / 0 Hour Scratch Area ⁇ X 100
  • EGF TGF- ⁇ PDGF-AA bFGF IGF-1 Sum Control 0 0 0 0 0 0.06 ppm EGF 0.06 ppm 0 0 0 0.06 ppm TGF- ⁇ 0 0.06 ppm 0 0 0 0.06 ppm PDGF-AA 0 0 0.06 ppm 0 0 0.06 ppm bFGF 0 0 0 0.06 ppm 0 0.06 ppm IGF-1 0 0 0 0 0.06 ppm 0.06 ppm EGF + TGF- ⁇ 0.03ppm 0.03ppm 0 0 0 0.06 ppm EGF + PDGF-AA 0.03ppm 0 0.03ppm 0 0.06 ppm EGF + FGF 0.03ppm 0 0 0.03ppm 0 0.06 ppm EGF + IGF-1 0.03ppm 0 0 0 0.03ppm 0.06 ppm TGF- ⁇ + PDGF
  • each growth factor and combination of growth factors promotes the regeneration of keratinocytes.
  • a combination of epithelial growth factor and platelet derived growth factor-AA a combination of epithelial growth factor and platelet derived growth factor-AA, a combination of epithelial growth factor, transforming growth factor- ⁇ and platelet derived growth factor-AA.
  • Combination of epithelial cell growth factor, platelet-derived growth factor-AA and insulin-like growth factor-1, and combination of transforming growth factor- ⁇ , platelet-derived growth factor-AA and insulin-like growth factor-1 It showed a cell regeneration promoting effect. It can be seen that growth factors or combinations thereof may promote cell regeneration to promote skin regeneration and further promote skin wound and burn healing.
  • each growth factor and combination of growth factors promotes the regeneration of fibroblasts.
  • a combination of platelet-derived growth factor-AA and fibroblast growth factor, epithelial cell growth factor, a combination of platelet-derived growth factor-AA and fibroblast growth factor, epithelial cell growth factor, platelet-derived growth factor-AA and insulin-like growth The combination of factor-1 and the combination of epithelial growth factor, platelet derived growth factor-AA and fibroblast growth factor showed a particularly good fibroblast regeneration promoting effect. It can be seen that growth factors or combinations thereof may promote cell regeneration to promote skin regeneration and further promote skin wound and burn healing.
  • Infrared skin is irradiated with a CO 2 laser to create a thermal wound, which is a combination of epidermal growth factor (EGF), platelet-derived growth factor-AA (PDGF-AA), and insulin-like growth factor-1 (IGF-1).
  • EGF epidermal growth factor
  • PDGF-AA platelet-derived growth factor-AA
  • IGF-1 insulin-like growth factor-1
  • the EpiDermFT Full Thickness Skin Model (MatTek) was grown in growth media for artificial skin for 4 days, and CO 2 laser (eCO2, Lutronic) was applied to the artificial skin for tip type 120, 40mJ.
  • the wound was made by treatment with an energy of 8 mm in size and a density of 150 spots / cm 2 .
  • a growth factor composition consisting of a combination of epidermal growth factor (EGF), platelet derived growth factor-AA (PDGF-AA), and insulin-like growth factor-1 (IGF-1) having a total skin concentration of 3 ppm or less. (GF Mix.) And DMEM / F12 media containing 4 ppm epidermal growth factor (EGF) and DMEM / F12 media (control) without growth factor, respectively.
  • epithelial growth factor EGF
  • platelet-derived growth factor-AA PDGF-AA
  • artificial base cells treated with a growth factor composition (GF Mix.)
  • GF Mix Composed of a combination of insulin-like growth factor-1 (IGF-1) at a concentration of 3 ppm or less in total, as well as the basement membrane (dermis / epidermal border) and dermis.
  • IGF-1 insulin-like growth factor-1
  • GF Mix Consisting of a combination of epidermal growth factor (EGF), platelet derived growth factor-AA (PDGF-AA) and insulin-like growth factor-1 (IGF-1), which is an embodiment of the present invention.
  • EGF epidermal growth factor
  • PDGF-AA platelet derived growth factor-AA
  • IGF-1 insulin-like growth factor-1
  • Ointments are prepared according to conventional methods with the compositions described in the table below.
  • a cream is prepared according to a conventional method with the composition described in the table below.
  • Epithelial growth factor Epithelial growth factor, insulin-like growth factor-1, platelet-derived growth factor-AA and fibroblast growth factor 8.0 Polyethylene Glycol Monostearate 2.0 Glycerin Monostearate 5.0 Cetyl alcohol 4.0 Squalene 3.0 Tri2-ethylhexaneglyceryl 6.0 Sphingolipid 1.0 1,3-butylene glycol 7.0 Purified water Remaining amount
  • Epithelial Cell Growth Factor Epithelial Cell Growth Factor, Platelet-derived Growth Factor-AA and Insulin-like Growth Factor-1 ... 100 g
  • the above ingredients are mixed according to a conventional method for preparing a health beverage, then stirred and heated at 85 ° C. for about 1 hour, and then the resulting solution is filtered and sterilized.

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Abstract

La présente invention concerne un agent d'amélioration de la réparation de la peau contenant un EGF (facteur de croissance épidermique), un PDGF-AA (facteur de croissance dérivé des plaquettes AA) et un IGF-1 (facteur de croissance 1 analogue à l'insuline).
PCT/KR2012/009919 2011-11-22 2012-11-22 Agent d'amélioration de la réparation de la peau contenant des facteurs de croissance WO2013077641A1 (fr)

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KR10-2011-0122388 2011-11-22
KR20110122388 2011-11-22

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EP2943564A4 (fr) * 2013-01-09 2016-10-26 Int Stem Cell Corp Petites molécules favorisant la régénération de la peau
KR102218427B1 (ko) * 2017-09-20 2021-02-22 차의과학대학교 산학협력단 단백질 약물을 포함하는 코아세르베이트 조성물 및 이를 포함하는 창상 치료제
KR101973960B1 (ko) * 2017-09-29 2019-04-30 티앤에이치바이오(주) 글루타티온이 함유된 캡슐형 표피 성장 인자의 조성물 및 이로 제조되는 글루타티온이 함유된 캡슐형 표피 성장 인자
KR102179476B1 (ko) * 2018-10-10 2020-11-17 의료법인 성광의료재단 줄기세포 배양액을 이용한 3차원 인공피부의 제조방법
KR102047808B1 (ko) 2019-05-10 2019-11-22 (주)이노진 특유의 성장인자들의 조합을 유효성분으로 함유하는 피부재생 또는 주름개선용 조성물

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JPH06316530A (ja) * 1992-03-17 1994-11-15 Pharmed Dr Liedtke Gmbh 局所用インスリン含有製剤
KR20010071577A (ko) * 1998-06-22 2001-07-28 데이비드 디마레스트 혈소판이 풍부한 개선된 상처 치유제
KR20030043313A (ko) * 2001-11-27 2003-06-02 한스바이오메드 주식회사 사람 각질세포 및 성장인자가 함유된 피브린 접착제를주재로 한 피부재생촉진제 및 그의 제조방법
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