WO2002067873A2 - Procede de reduction par suppression de l'elasticite de la peau - Google Patents
Procede de reduction par suppression de l'elasticite de la peau Download PDFInfo
- Publication number
- WO2002067873A2 WO2002067873A2 PCT/JP2002/001757 JP0201757W WO02067873A2 WO 2002067873 A2 WO2002067873 A2 WO 2002067873A2 JP 0201757 W JP0201757 W JP 0201757W WO 02067873 A2 WO02067873 A2 WO 02067873A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- skin
- phase
- decrease
- active ingredient
- matrix
- Prior art date
Links
Classifications
-
- 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
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
- A61K8/9783—Angiosperms [Magnoliophyta]
- A61K8/9789—Magnoliopsida [dicotyledons]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/0212—Face masks
-
- 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
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
- A61K8/4926—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having six membered rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/30—Oestrogens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q1/00—Make-up preparations; Body powders; Preparations for removing make-up
- A61Q1/02—Preparations containing skin colorants, e.g. pigments
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/74—Biological properties of particular ingredients
- A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
- A61K2800/782—Enzyme inhibitors; Enzyme antagonists
Definitions
- the present invention relates to an agent for suppressing skin aging, which suppresses female hormones associated with ovarian insufficiency, in particular, skin aging associated with the reduction of female hormones due to menopause, particularly sagging. More particularly, the present invention relates to an agent for inhibiting skin aging associated with a decrease in female hormones associated with ovarian dysfunction, which comprises, as an active ingredient, a substance having an excellent inhibitory effect on the activity of matrix meta-oral protease. . Background art
- the present inventors have proposed changes in skin aging after menopause, With the aim of elucidating the mechanism involved in this, we used ostomyctomy mice, which have been academically recognized, as a menopausal model, and studied the mechanism of the occurrence of skin aging, such as sagging. As a result, the cause of the sagging that occurs after menopause is due to the decrease in female hormones in the skin after menopause, and more specifically, the matrix meta-oral proteases in the skin, and more specifically, the matrix meta-oral proteases. It was found that the expression of gelatinase belonging to the group was increased (see Fig. 1).
- Matrix meta-oral proteases are zinc-containing proteolytic enzymes that hydrolyze extracellular matrix components such as collagen (Biochemistry Vol. 71 (12) pl 387) _______________________0114 (199 9)), which is known to be the cause of changes associated with skin aging, ie, wrinkles, dullness, disappearance of texture, etc. See No. 122 publication). However, the increased expression was attributed mainly to UV irradiation (Gary J. Fischer et al. Nature, 379 (25), 335 (1996); Gary J. Fischer et al. The New England). Journal of Medicine, 337 (20), 1419 (1997)), and the relationship between decreased female honolemon and increased expression of matrix metaoral proteases has not been elucidated.
- the inventor of the present application has found that an increase in the amount of this enzyme accompanying a decrease in female hormones after menopause causes an increase in the degradation of extracellular matrices constituting skin cells and an increase in “sag”.
- topical application of a substance that inhibits matrix meta-oral protease was applied topically to a menopausal model mouse, it was found that the “slack” that increases due to a decrease in female hormones was significantly suppressed (see Fig. 2).
- a matrix metallobate oralase inhibitor is effective in preventing and improving skin aging phenomena such as “sag”, which increases with a decrease in female hormones, such as after menopause, and completes the present invention. Reached. Disclosure of the invention
- the present invention relates to a skin aging inhibitor which contains a matrix meta-oral protease inhibitor as an active ingredient and suppresses skin aging associated with a decrease in female hormones associated with ovarian dysfunction.
- the decrease in female hormones associated with ovarian dysfunction is due to menopause.
- the skin aging is characterized by sagging skin.
- the matrix meta-oral protease is a protease belonging to the group of gelatinases.
- the present invention further relates to a method for inhibiting skin aging, comprising applying the skin aging inhibitor to the skin.
- the active ingredient of the skin aging inhibitor is not particularly limited as long as it is a substance that inhibits matrix meta-oral protease.
- N-hydroxy-12 (R) [( 4-Methoxyphenyl) sulfonyl] (3-picolyl) monomethylbutanamide (referred to as active ingredient A) or a salt thereof, for example, the hydrochloride is preferred.
- the structure of the hydrochloride of active ingredient A is shown by the following formula:
- compositions that inhibit matrix meta-oral proteases other than the hydroxamic acid derivative include doxycycline having a tetracitalin skeleton, and those that have excellent gelatinase inhibitory activity in natural products.
- Cumin and plant extracts containing the same e.g., konkon extract
- plant extracts that have been shown to inhibit matrix meta-oral protease include mangosteen (Garcinia mangostana L.) and Daun Duduk power S. Can be
- Mangosteen (Garcinia mangostana L.) is a plant belonging to the family uutt if erae (Hypericaceae;) and the genus Garcinia. An evergreen fruit tree cultivated in the tropics. The skin contains tannins and a yellow pigment (mangosteen). Dry bark also becomes a black dye.
- mangosteen G. mangostana
- peel or bark it is particularly preferred to use the peel or bark, but other sites can be used.
- each of the above-mentioned plants can be obtained by a conventional method.
- each of the above-mentioned plants can be obtained by immersing or heating under reflux with an extraction solvent, followed by filtration and concentration.
- Any extraction solvent can be used as long as it is a solvent generally used for extraction.
- water, methanol, ethanol, propylene glycol, 1,3-butylene glycol, glycerin Alcohols, hydrous alcohols, organic solvents such as black form, dichloronorethane, carbon tetrachloride, acetate, ethyl acetate, hexane, etc. can be used alone or in combination. .
- the extract obtained by extraction with the above solvents is used as it is, or the concentrated extract is adsorbed by an adsorption method, for example, by removing impurities using ion exchange resin, or by a column of a porous polymer (for example, Amperlite XAD-2) After the reaction, elution with methanol or ethanol and concentration can also be used.
- a partitioning method for example, an extract extracted with water-Z-ethyl acetate is also used.
- Matrix meta-oral protease includes, for example, skin matrices. MMP1 that degrades type I and III collagens, which are the main components of the mix; MMP2 that belongs to the group of gelatinases that degrade basement membrane components such as type IV collagen and laminin, and the dermal matrix component elastin. Gelatinase A), MMP9 (gelatinase B); proteoglycin type IV collagen, MMP3, MMP10 belonging to the stramalysin group which degrades laminin and the like.
- the agent for inhibiting skin aging according to the present invention is effective for preventing and improving skin aging due to a decrease in female hormones associated with ovarian dysfunction, particularly sagging skin.
- Ovarian insufficiency associated with decreased female hormones includes various ovarian insufficiencies associated with reduced ovarian function, which produces female hormones, such as menopause and ovarian deficiency.
- the female hormones include estrogen (estrogens), for example, estradiol, estrin, estriol, and luteinizing hormone (progesterone).
- skin aging associated with a decrease in female hormones associated with ovarian dysfunction refers to changes in the skin caused by an increase in matrix meta-oral protease in the skin, such as skin elasticity It refers to a decrease in sex, specifically, for example, skin wrinkles, disappearance of texture, sagging, etc., particularly sagging.
- the degree of “sag” in the present invention can be determined mainly by measuring the elasticity of the skin, and can be determined by a method well known to those skilled in the art. For example, this elasticity can be determined by measuring the rate of return of the skin stretched at a given pressure as the recovery rate (%). In this case, it can be determined that the higher the recovery rate is, the higher the elastic force is and the less "slack" is.
- the measurement of such a recovery rate can be carried out using, for example, a skin viscoelasticity measuring device, Cutometer (manufactured by COURAGE KHAZAKSA).
- FIG. 1 is a graph showing the relationship between ovarian dysfunction and the amount of matrix metaoral protease.
- FIG. 2 is a graph showing the effect of the matrix meta-oral protease inhibitor of the present invention on sagging skin.
- the skin metal aging inhibitor containing a matrix metallobate oralase inhibitor used in the present invention exhibits a skin aging inhibitory effect associated with a decrease in female hormones associated with ovarian dysfunction, for example, a menopausal skin aging inhibitory effect, It has been found for the first time by the present inventors. Further, it has been found that the skin aging inhibitor containing the matrix meta-oral protease inhibitor of the present invention is particularly effective in preventing and improving sagging of menopausal skin.
- the amount of the matrix metallobate-oralase inhibitor in the skin aging inhibitor of the present invention is preferably 0.0001 to 20.0% by weight, as a dry matter, of the total amount of the skin aging inhibitor. 0 0 0 1 to:. is the L 0 0 weight 0/0.. If the amount is less than 0.001% by weight, the effects of the present invention cannot be sufficiently exerted, and if it exceeds 20.0% by weight, it is not preferable because formulation becomes difficult. Further, even if the content is 10.0% by weight or more, the effect is not so much improved.
- the matrix meta-oral protease inhibitor-containing skin aging inhibitor of the present invention includes components usually used in external preparations for skin such as cosmetics and pharmaceuticals, for example, whitening agents, humectants, An antioxidant, an oil component, an ultraviolet absorber, a surfactant, a thickener, an alcohol, a powder component, a coloring agent, an aqueous component, water, various skin nutritional agents, and the like can be appropriately compounded as necessary.
- sequestering agents such as sodium edetate, sodium edetate, sodium citrate, sodium polyphosphate, sodium metalate, and gluconic acid, caffeine, tannin, Verapamil, tranexamic acid and its derivatives, licorice extract, glabridin, hot water extract of kalin fruit, various crude drugs, drugs such as tocopherol acetate, daricyl ritinic acid and its derivatives or salts thereof, vitamin C, Other whitening agents such as magnesium phosphonolevic acid phosphate, ascorbic acid darcoside, argyptin, kojic acid, sugars such as glucose, fructose, mannose, sucrose, trehalose, retinoic acid, retinol, retinol acetate, Vitamin A, such as retinol panolemitinate, etc. may also be added as appropriate. Can.
- drugs such as tocopherol acetate, daricyl ritinic acid and its derivatives or salts thereof, vitamin C
- the matrix meta-oral protease inhibitor-containing skin aging inhibitor of the present invention may be any of those conventionally used for skin external preparations, such as ointments, creams, emulsions, lotions, packs, baths, and the like.
- the dosage form is not particularly limited.
- the present invention will be described in more detail by way of examples.
- the present invention is not limited by this.
- the compounding amount is% by weight.
- mice Female hair mice were subjected to bilateral oophorectomy, which was used as a climacteric (ovarian dysfunction) animal model. A mouse that had not undergone such ovariectomy was regarded as a normal animal. Two months after the ovariectomy, the skin was excised from the back of the female hairless mouse, the subcutaneous tissue was removed, and the epidermis and dermis were separated using a water bath at 60 ° C. The dermis was extracted with 0.05 M Tris-HCl buffer, centrifuged (800 g, manufactured by Hitachi, Ltd.), and the amount of gelatinase in the centrifuged supernatant was analyzed by gelatin zymography. .
- the numerical value of the amount of the ratinase was determined by analyzing the intensity of the pan obtained by gelatin zymography using F10ur-Smu1tii Mager (BIORAD). The amount of gelatinase in the skin of normal animals was also measured according to the same protocol.
- mice Five-week-old female hairless mice were subjected to bilateral ovariectomy, which was used as a menopause model. 1% inhibitor in 80% ethanol, 15% 1,3-butylene glycol and 5% dynamite glycerin
- the rate of return of the skin section was measured as the recovery rate, and the average value and standard deviation value of each group were determined. The larger the value, the more elastic and the less “sag”.
- matrix meta-oral protease inhibitors are superior because they suppress the decrease in skin elasticity due to a decrease in female hormones, and reduce the "sag" after menopause. Suppress menopausal skin aging This indicates that it is a very useful formulation to add a matrix meta-oral protease inhibitor to an external preparation as an active ingredient of a menopausal skin aging inhibitor. ing. Experiment 3. Preparation of plant extract and MMP s activity inhibitory effect test
- each plant was immersed in methanol at room temperature for one week to obtain an extract. This extract was concentrated to obtain each plant extract (methanol extract).
- the plant extract was dissolved in dimethyl sulfoxide (DMS O) to a concentration of 2% by mass to obtain a plant extract-containing solution.
- DMS O dimethyl sulfoxide
- the plant extract-containing solution was diluted with assay buffer (0. 4 MN a C l, 1 p H 7. 0. 1 M Application Benefits vinegar 4 containing 0 mM C a C 1 2) The concentration was adjusted as shown in Table 2, and this was used as a sample solution, and the following experiment was performed.
- MM P-9 activity inhibition rate The activity inhibition rate was measured using MMP-9 as an enzyme belonging to the gelatinase group. The measurement was performed as follows.
- menopausal model ovariectomized mouse, non-irradiated with ultraviolet light
- the plant extract-containing sample solution was applied at 100 ⁇ 1, 5 times / week for 12 weeks. As a result, it was clarified that the sample solution containing the plant extract improved skin elasticity of the menopausal model.
- soap powder and borax to the ion-exchange water, heat and dissolve. Keep (aqueous phase). Mix the other ingredients, heat and melt, and keep at 70 ° C (oil phase). The oil phase is gradually added to the aqueous phase while stirring to carry out the reaction. After the completion of the reaction, homogenize the mixture with a homomixer and cool to 30 ° C while stirring well.
- phase A Dissolve the carboxybutyl polymer in a small amount of ion-exchanged water (phase A).
- phase A ion-exchanged water
- oil phase to water phase pre-emulsify, add phase A, homogenize homogeneously with homomixer, milk After cooling, cool to 30 ° C while stirring well.
- Carbopol 9400 is uniformly dissolved in ion-exchanged water, while the hydrochloride of active ingredient ⁇ and polyoxyethylene (50 mol) oleyl alcohol ether are dissolved and added to the aqueous phase. Then, after adding other components, neutralize with caustic soda and L-arginine to thicken.
- phase A and phase C Dissolve phase A and phase C uniformly, and add phase A to phase C for solubilization. Then, after adding phase B, filling is performed.
- phase A Dissolve phase A, phase B, and phase C uniformly, and add phase B to phase A for solubilization. Next, this is added to the C phase and then filled.
- Stearic acid 5.0 Stearyl alcohol 4.0 Isopropyl myristate 18.0 Glycerin monostearate 3.0 Propylene glycol 10.0 Mangosteen (bark) 1.0 Caustic acid 0.2 Sodium bisulfite 0. 0 Preservatives
- phase A Dissolve the carboxyvinyl polymer in a small amount of ion-exchanged water (phase A).
- phase A Add polyethylene dalicol 1500 and triethanolamine to the remaining ion-exchanged water, dissolve by heating, and maintain at 70 ° C (aqueous phase). Mix with other ingredients, heat and maintain at 70 ° C (oil phase).
- oil phase to water phase, pre-emulsify, add phase A, homogenize homogeneously with homomixer, cool to 30 ° C while stirring well after emulsification.
- phase A Dissolve phase A, phase B, and phase C uniformly, and add phase B to phase A for solubilization. Next, this is added to the C phase and then filled.
- the skin metal aging inhibitor containing a matrix metallobite thease inhibitor of the present invention exerts a skin aging inhibitory effect on skin aging due to a decrease in female hormones associated with ovarian dysfunction such as menopause, and ⁇ sags '' after menopause. It works effectively for prevention and improvement.
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Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/469,033 US20040077523A1 (en) | 2001-02-26 | 2002-02-26 | Method for pressuring reduction of elasticity of skin |
EP02700812A EP1396255A1 (en) | 2001-02-26 | 2002-02-26 | Method for suppressing reduction of elasticity of skin |
KR10-2003-7011035A KR20030086270A (ko) | 2001-02-26 | 2002-02-26 | 피부의 탄력성 저하를 억제하는 방법 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2001050839A JP2002255850A (ja) | 2001-02-26 | 2001-02-26 | 皮膚老化抑制剤 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2002067873A2 true WO2002067873A2 (fr) | 2002-09-06 |
Family
ID=18911739
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2002/001757 WO2002067873A2 (fr) | 2001-02-26 | 2002-02-26 | Procede de reduction par suppression de l'elasticite de la peau |
Country Status (5)
Country | Link |
---|---|
US (1) | US20040077523A1 (ja) |
EP (1) | EP1396255A1 (ja) |
JP (1) | JP2002255850A (ja) |
KR (1) | KR20030086270A (ja) |
WO (1) | WO2002067873A2 (ja) |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20030138467A1 (en) | 2001-12-27 | 2003-07-24 | Avon Products, Inc. | Methods for improving the aesthetic appearance of skin |
JP4558363B2 (ja) * | 2003-06-19 | 2010-10-06 | 日本メナード化粧品株式会社 | 香料組成物 |
JP4243202B2 (ja) * | 2004-01-20 | 2009-03-25 | 株式会社ナリス化粧品 | シワ改善用皮膚外用剤 |
US20060115556A1 (en) * | 2004-12-01 | 2006-06-01 | Foulger Sidney W | Nutritional supplement drink containing xanthone extracts |
US20060115555A1 (en) * | 2004-12-01 | 2006-06-01 | Foulger Sidney W | Nutritional supplements containing xanthone extracts |
US7776365B2 (en) * | 2005-03-18 | 2010-08-17 | Sakura Properties, Llc | Article with skin protecting and moisturizing compound |
US7749545B2 (en) * | 2005-03-18 | 2010-07-06 | Sakura Properties, Llc | Fucoidan compositions and methods for dietary and nutritional supplements |
US20060210697A1 (en) * | 2005-03-18 | 2006-09-21 | Mower Thomas E | Infant formula composition |
US20070020358A1 (en) * | 2005-03-18 | 2007-01-25 | Mower Thomas E | Sports drink concentrate |
US20060210496A1 (en) * | 2005-03-18 | 2006-09-21 | Mower Thomas E | Compositions for skin protection from ultraviolet damage |
US20060210515A1 (en) * | 2005-03-18 | 2006-09-21 | Mower Thomas E | Hair growth formula |
US7666448B2 (en) | 2005-03-18 | 2010-02-23 | Sakura Properties, Llc | Skin cleansing article |
US20060210692A1 (en) * | 2005-03-18 | 2006-09-21 | Mower Thomas E | Baby food composition |
US20060210688A1 (en) * | 2005-03-18 | 2006-09-21 | Mower Thomas E | Dehydrated sports drink powder |
JP2006349372A (ja) * | 2005-06-13 | 2006-12-28 | Shiseido Co Ltd | 角層中の酸化タンパク質を指標とする肌の柔軟性・弾力性を評価する方法 |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6398753B2 (en) * | 1998-04-03 | 2002-06-04 | Mcdaniel David H. | Ultrasound enhancement of percutaneous drug absorption |
-
2001
- 2001-02-26 JP JP2001050839A patent/JP2002255850A/ja not_active Withdrawn
-
2002
- 2002-02-26 WO PCT/JP2002/001757 patent/WO2002067873A2/ja not_active Application Discontinuation
- 2002-02-26 US US10/469,033 patent/US20040077523A1/en not_active Abandoned
- 2002-02-26 KR KR10-2003-7011035A patent/KR20030086270A/ko not_active Application Discontinuation
- 2002-02-26 EP EP02700812A patent/EP1396255A1/en not_active Withdrawn
Also Published As
Publication number | Publication date |
---|---|
EP1396255A1 (en) | 2004-03-10 |
US20040077523A1 (en) | 2004-04-22 |
JP2002255850A (ja) | 2002-09-11 |
KR20030086270A (ko) | 2003-11-07 |
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