Skin composition

Abstract

To provide a method for promoting skin wound healing and a composition for use in promoting skin wound healing; to provide a method or composition useful for preventing or improving ulcers and pressure ulcers; to provide a method for suppressing skin aging and a composition for use in suppressing skin aging; to provide a composition useful for preventing or improving skin damage caused by anticancer drugs; and further, to provide a method for enhancing the regenerative capacity of epidermal stem cells and a composition for enhancing the regenerative capacity of epidermal stem cells. [Solution] By using a composition characterized by containing as an active ingredient a substance selected from the group consisting of a substance that induces or maintains the expression of COL17A1 in cells, a substance that suppresses the degradation of COL17A1 in cells, a substance that promotes the competitive amplification ability of epidermal stem cells, a substance that suppresses genomic stress or oxidative stress in cells, and a substance that suppresses DNA damage in cells, it is possible to promote skin wound healing, protect from anticancer drugs, suppress skin aging, and enhance the regenerative capacity of epidermal stem cells.

Claims

1. A composition for use in promoting the healing of skin wounds, or in preventing or improving skin ulcers or pressure ulcers, characterized in that it contains as an active ingredient a substance selected from the group consisting of a substance that induces or maintains the expression of COL17A1 in cells, a substance that inhibits the degradation of COL17A1 in cells, a substance that maintains the self-renewal ability of epidermal stem cells, a substance that suppresses genomic stress or oxidative stress in cells, and a substance that suppresses DNA damage in cells.

2. A composition for use in suppressing skin aging, characterized in that it contains as an active ingredient a substance selected from the group consisting of a substance that induces or maintains the expression of COL17A1 in cells, a substance that suppresses the degradation of COL17A1 in cells, a substance that maintains the self-renewal ability of epidermal stem cells, a substance that suppresses genomic stress or oxidative stress in cells, and a substance that suppresses DNA damage in cells.

3. A composition for enhancing the regenerative capacity of epidermal stem cells, characterized in that it contains as an active ingredient a substance selected from the group consisting of a substance that induces or maintains the expression of COL17A1 in cells, a substance that inhibits the degradation of COL17A1 in cells, a substance that maintains the self-renewal ability of epidermal stem cells, a substance that suppresses genomic stress or oxidative stress in cells, and a substance that suppresses DNA damage in cells.

4. A composition for use in preventing or improving skin damage caused by anticancer drugs, characterized in that it contains as an active ingredient a substance selected from the group consisting of a substance that induces or maintains the expression of COL17A1 in cells, a substance that inhibits the degradation of COL17A1 in cells, a substance that maintains the self-renewal ability of epidermal stem cells, a substance that inhibits genomic stress or oxidative stress in cells, and a substance that inhibits DNA damage in cells.

5. A composition for anti-wrinkle use, characterized in that it contains as an active ingredient a substance selected from the group consisting of a substance that induces or maintains the expression of COL17A1 in cells, a substance that inhibits the degradation of COL17A1 in cells, a substance that maintains the self-renewal ability of epidermal stem cells, a substance that suppresses genomic stress or oxidative stress in cells, and a substance that suppresses DNA damage in cells.

6. The composition according to claim 5, wherein the anti-wrinkle effect is due to at least one selected from the group consisting of improvement of skin elasticity, improvement of stratum corneum function, improvement of skin moisturizing ability, and improvement of skin barrier function.

7. A composition for use in anti-blemish treatment, characterized in that it contains as an active ingredient a substance selected from the group consisting of a substance that induces or maintains the expression of COL17A1 in cells, a substance that inhibits the degradation of COL17A1 in cells, a substance that maintains the self-renewal ability of epidermal stem cells, a substance that suppresses genomic stress or oxidative stress in cells, and a substance that suppresses DNA damage in cells.

8. A composition for use in improving rough skin, characterized in that it contains as an active ingredient a substance selected from the group consisting of a substance that induces or maintains the expression of COL17A1 in cells, a substance that inhibits the degradation of COL17A1 in cells, a substance that maintains the self-renewal ability of epidermal stem cells, a substance that suppresses genomic stress or oxidative stress in cells, and a substance that suppresses DNA damage in cells.

9. The composition according to any one of claims 1 to 8, wherein the substance that induces or maintains the expression of COL17A1 in cells further maintains the self-renewal ability of epidermal stem cells.

10. The composition according to any one of claims 1 to 9, wherein the substance that induces or maintains the expression of COL17A1 in cells is selected from the group consisting of NADPH oxidase inhibitors, COX inhibitors, iNOS inhibitors, ROCK inhibitors, and estrogen-like substances.

11. The composition according to claim 10, wherein the NADPH oxidase inhibitor is selected from the group consisting of apocynin, ebselen, diphenyleneiodonium (DPI), GKT137831, AEBSF, GK-136901, ML171, Coenzyme Q10 (CoQ10), VAS2870, and VAS3947.

12. The composition according to claim 10, wherein the COX inhibitor is selected from the group consisting of celecoxib, delacoxib, tolfenamiic acid, difluic acid, FR122047, LM-1685, SC-791, BTB02472, nimeslide, SPB04674, curcumin, diclofenac, 4'-hydroxydiclofenac, DuP-697, ebselene, ETYA, fluviprofen, ibuprofen, indomethacin, meloxicam, NPPB, NS-398, pterostilbene, resveratrol, SC-560, SKF-86002, TXA (tranexamic acid), TXC (cetyl hydrochloride tranexamate), astaxanthin, and sulindac sulfide.

13. The composition according to claim 10, wherein the iNOS inhibitor is selected from the group consisting of 1400W, L-NIL, aminoguanidine, BYK190123, S-ethylisothiourea, S-methylisothiourea, S-aminoethylisothiourea, 2-iminopiperidine, butylamine, ONO-1714 ((1S,5S,6R,7R)-7-chloro-3-imino-5-methyl-2-azabicyclo[4.1.0]heptane hydrochloride), AMT hydrochloride (2-amino-5,6-dihydro-6-methyl-4H-1,3-thiadin hydrochloride), AR-C102222, L-NG-nitroarginine, L-NG-monomethylarginine, L-nitroarginine methyl ester, L-NIO, dexamethasone, estrogen, astaxanthin, and apigenin.

14. The composition according to claim 10, wherein the ROCK inhibitor is selected from the group consisting of Y-27632, ripasudil (K-115), thiazovivin, fasudil (HA-1077), GSK429286A, RKI-1447, GSK269962, netalusudil (AR-13324), Y-39983, ZINC00881524, KD025, hydroxyfasudil (HA-1100), GSK180736A, and AT13148.

15. The composition according to claim 10, wherein the estrogen-like substance is selected from the group consisting of estrogen, ethinylestradiol, biochanin A, soybean extract, isoflavone, iris extract, and Pueraria mirifica root extract.

16. The composition according to any one of claims 1 to 9, wherein a substance that induces or maintains the expression of COL17A1 in cells is selected from the group consisting of apocynin, ebselen, celecoxib, apigenin, Y-27632, lipasudil, 1400W, ethinylestradiol, biochanin A, necrostatin 1, Rhodiola rosea extract, Mulberry extract, Gymnema sylvestris extract, Tea extract, Loquat leaf extract, Milk thistle extract, Black turmeric extract, Plantago major seed extract, Coffee seed extract, Prunus yedoensis leaf extract, Melia azadirachta leaf extract, Mandarin orange peel extract, Lavandula angustifolia flower extract, Sophora flavescens root extract, Rice bran extract, Rosa canina fruit extract, Hamemaris radiata leaf extract, Eucalyptus globulus leaf extract, Hawthorn extract, and Carrot extract.

17. The composition according to any one of claims 1 to 9, wherein the substance that inhibits the degradation of COL17A1 in cells is selected from the group consisting of neutrophil elastase (ELANE) inhibitors and matrix metalloproteinase (MMP) inhibitors.

18. The composition according to claim 17, wherein the ELANE inhibitor is selected from the group consisting of siberestat sodium hydrate (Monosodium N-{2-[4-(2,2-dimethylpropanoyloxy)-phenylsulfonylamino]benzoyl}aminoacetate tetrahydrate), ONO-6818 (2-(5-Amino-6-oxo-2-phenylhydropyrimidinyl)-N-[2-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1-(methylethyl)-2-oxoethyl]acetamide), α1 antitrypsin (α1-AT), depelestat, Neilwan (sodium trifluoride isopropyloxopropylaminocarbonylpyrrolidinecarbonylmethylpropylaminocarbonylbenzoylaminoacetate), perilla leaf ferment, parsley ferment, bell pepper ferment, antibody against ELANE, siRNA against the gene encoding ELANE, and antisense oligonucleotide against the gene encoding ELANE.

19. The composition according to claim 17, wherein the MMP inhibitor is selected from the group consisting of Marimast, Batimastat, PD166793, Ro32-3555, WAY170523, UK370106, TIMP1, TIMP2, TIMP3, and TIMP4.

20. The composition according to any one of claims 1 to 9, wherein the genomic stress is DNA damage stress caused by ultraviolet light, radiation, or anticancer drugs, or replication stress associated with cell division.

21. The composition according to claim 2, wherein skin aging is at least one selected from the group consisting of (a) to (f) below. (a) Thinning, weakening, atrophy, or loss of firmness of the epidermis, dermis, and / or adipose tissue (b) Impaired epidermal barrier function or dry skin (c) Reduction or immaturity of hemidesmosomes in the basement membrane (d) Loss of fibroblasts in the upper dermis, or fine wrinkles or crepe wrinkles due to dry skin. (e) Wrinkle formation due to a decrease in collagen in the dermis (f) age spots, lentigines, or depigmented spots

22. The composition according to claim 2, for use in suppressing wrinkles.

23. A pharmaceutical composition, according to any one of claims 1 to 22.

24. A composition according to any one of claims 1 to 23, comprising a pharmaceutically acceptable excipient.

25. A composition according to any one of claims 1 to 24, which is a coating agent.

26. A cosmetic composition according to any one of claims 1 to 22.

27. The cosmetic composition according to claim 26, comprising an active ingredient in an amount of 0.01 to 15% by weight.

28. A cosmetic composition according to claim 26 or 27, which is a composition for use in skincare.

29. A cosmetic composition according to any one of claims 26 to 28, further comprising at least one of a skin anti-aging agent, a skin tone adjuster, an anti-inflammatory agent, and a sunscreen.

30. A method for screening substances that are effective in promoting the healing of skin wounds or preventing or improving skin ulcers, inhibiting skin aging, controlling cell competition, improving the regenerative capacity of epidermal stem cells, preventing or improving skin damage caused by anticancer drugs, anti-wrinkle, and / or improving rough skin, i) A step of bringing cells and a test substance into contact in vitro. ii) A step of measuring the expression of COL17A1 in cells, and iii) A step to determine whether the test substance increases the expression of COL17A1. Methods that include...

31. A method for evaluating skin aging using the expression of COL17A1 in cells as an indicator.

32. A kit for use in a method of evaluating skin aging, comprising an antibody against COL17A1, or a probe for the gene encoding COL17A1, or a primer for amplifying said gene.

33. A method for evaluating epidermal stem cells using COL17A1 expression in cells as an indicator.

34. A kit for use in evaluating epidermal stem cells, comprising an antibody against COL17A1, or a probe for the gene encoding COL17A1, or a primer for amplifying said gene.

35. A method for selecting epidermal stem cells using COL17A1 expression in cells as an indicator.

36. A kit for use in a method for selecting epidermal stem cells, comprising an antibody against COL17A1, or a probe for the gene encoding COL17A1, or a primer for amplifying said gene.

37. A method for amplifying epidermal stem cells and / or epidermal cells, comprising the step of measuring the expression level of COL17A1 using an antibody against COL17A1, or a probe for the gene encoding COL17A1, or a primer for amplifying the gene, and selecting epidermal stem cells with high expression levels of COL17A1.

38. A kit for use in a method of amplifying epidermal stem cells and / or epidermal cells, comprising an antibody against COL17A1, or a probe for the gene encoding COL17A1, or a primer for amplifying said gene.

39. A functional food or beauty supplement characterized by containing as an active ingredient a substance selected from the group consisting of substances that induce or maintain the expression of COL17A1 in cells, substances that suppress the degradation of COL17A1 in cells, substances that maintain the self-renewal ability of epidermal stem cells, substances that suppress genomic stress or oxidative stress in cells, and substances that suppress DNA damage in cells.

40. The functional food or beauty supplement according to claim 39, wherein the substance that induces or maintains the expression of COL17A1 in cells is selected from the group consisting of NADPH oxidase inhibitors, COX inhibitors, iNOS inhibitors, ROCK inhibitors, and estrogen-like substances.

41. A functional food or beauty supplement according to claim 39 or 40, wherein a substance that induces or maintains the expression of COL17A1 in cells is selected from the group consisting of apocynin, ebselen, celecoxib, apigenin, Y-27632, lipasudil, 1400W, astaxanthin, ethinylestradiol, biochanin A, necrostatin 1, Rhodiola rosea extract, Mulberry extract, Gymnema sylvestris extract, Tea extract, Loquat leaf extract, Milk thistle extract, Black turmeric extract, Plantago major seed extract, Coffee seed extract, Prunus yedoensis leaf extract, Melia azadirachta leaf extract, Mandarin orange peel extract, Lavandula angustifolia flower extract, Sophora flavescens root extract, Rice bran extract, Rosa canina fruit extract, Hamemaris radiata leaf extract, Eucalyptus globulus leaf extract, and Hawthorn extract.

42. A functional food or beauty supplement according to any one of claims 39 to 41, intended for oral intake.

43. A functional food or beauty supplement according to any one of claims 39 to 42, in the form of a tablet, powder, semi-solid, jelly, or liquid.

44. A functional food or beauty supplement according to any one of claims 39 to 43, further comprising at least one of a skin anti-aging agent, a vitamin, collagen, and a mineral.

45. A cell composition comprising isolated cells expressing COL17A1.

46. The cell composition according to claim 45, wherein the cells are epidermal keratinocytes or mucosal epithelial keratinocytes.

47. A cell composition according to claim 45 or 46 for use in transplantation.

48. A cell composition according to any one of claims 45 to 47, for use in the treatment of skin diseases or injuries.

49. at least 1 × 10 ３ A cell composition according to any one of claims 45 to 48, comprising a single cell.

50. The cell composition according to any one of claims 45 to 49, wherein at least 50% of the cells express COL17A1.

51. The cell composition according to any one of claims 45 to 50, wherein the cells are stem cell-derived cells.

52. A cell composition according to any one of claims 45 to 51, wherein the cells are frozen.

53. The cell composition according to any one of claims 45 to 52, wherein the cells are contained in a single container.

54. The cell composition according to any one of claims 45 to 53, wherein the cells are cells treated with a substance that induces or maintains the expression of COL17A1 in the cells.

55. The cell composition according to claim 53, wherein a substance that induces or maintains the expression of COL17A1 in cells is selected from the group consisting of NADPH oxidase inhibitors, COX inhibitors, iNOS inhibitors, ROCK inhibitors, and estrogen-like substances.

56. The cell composition according to claim 54 or 55, wherein a substance that induces or maintains the expression of COL17A1 in cells is selected from the group consisting of apocynin, ebselen, celecoxib, apigenin, Y-27632, lipasudil, 1400W, astaxanthin, ethinylestradiol, biochanin A, necrostatin 1, Rhodiola rosea extract, Mulberry extract, Gymnema sylvestris extract, Tea extract, Loquat leaf extract, Milk thistle extract, Black turmeric extract, Plantago major seed extract, Coffee seed extract, Prunus yedoensis leaf extract, Melia azadirachta leaf extract, Mandarin orange peel extract, Lavandula angustifolia flower extract, Sophora flavescens root extract, Rice bran extract, Rosa canina fruit extract, Hamemaris radiata leaf extract, Eucalyptus globulus leaf extract, Hawthorn extract, and Carrot extract.

57. A cell sheet comprising the cell composition according to any one of claims 45 to 56.

58. A composition for use in controlling cell competition, characterized in that it contains as an active ingredient a substance selected from the group consisting of a substance that induces or maintains the expression of COL17A1 in cells, a substance that inhibits the degradation of COL17A1 in cells, a substance that maintains the self-renewal ability of epidermal stem cells, a substance that suppresses genomic stress or oxidative stress in cells, and a substance that suppresses DNA damage in cells.

59. A method for evaluating cell competition in keratinocytes by culturing them in three dimensions.

60. A kit for evaluating cell competition in keratinocytes, including keratinocytes and a 3D culture device.

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