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WO2012008767A2 - Dérivés rétinoïdes et composition cosmétique les comprenant - Google Patents

Dérivés rétinoïdes et composition cosmétique les comprenant Download PDF

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Publication number
WO2012008767A2
WO2012008767A2 PCT/KR2011/005174 KR2011005174W WO2012008767A2 WO 2012008767 A2 WO2012008767 A2 WO 2012008767A2 KR 2011005174 W KR2011005174 W KR 2011005174W WO 2012008767 A2 WO2012008767 A2 WO 2012008767A2
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WO
WIPO (PCT)
Prior art keywords
present
cosmetic composition
mdrpda
skin
compound
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/KR2011/005174
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English (en)
Other versions
WO2012008767A3 (fr
Inventor
Bong Youl Chung
Jin Hun Cho
Sung Sik Bang
Byoung Young Jeon
Ick Je Woo
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
PARAON Inc
Coway Co Ltd
Original Assignee
PARAON Inc
Woongjin Coway Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
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Publication of WO2012008767A2 publication Critical patent/WO2012008767A2/fr
Publication of WO2012008767A3 publication Critical patent/WO2012008767A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • 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
    • 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
    • A61K8/67—Vitamins
    • A61K8/671—Vitamin A; Derivatives thereof, e.g. ester of vitamin A acid, ester of retinol, retinol, retinal
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C403/00—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone
    • C07C403/24—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by six-membered non-aromatic rings, e.g. beta-carotene
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated

Definitions

  • the present invention relates to retinoid derivatives and a cosmetic composition comprising the same. More particularly, the present invention relates to retinoid derivatives having an excellent collagen synthesis increasing effect, being non-irritating, being non-toxic, having good stability, being easily absorbed to the skin and being long-wearing, and a cosmetic composition comprising the same.
  • Retinoids are derivatives of vitamin A, and include retinol, retinal, retinoic acid, retinyl esters such as retinyl acetate, retinyl propionate, retinyl linoleate and retinyl palmitate, etc.
  • the retinoids are very unstable to light, heat, oxygen, water, etc., they need to be stabilized for practical use. Also, the retinoids have the problems of in vivo stability and cytotoxicity as a side effect due to retinoic acid receptor (RAR). Therefore, many researchers have been studied to develop retinoid derivatives having good stability, being non-toxic, and being non-irritating, as well as having the anti-photoaging effect.
  • RAR retinoic acid receptor
  • US Patent No. 4,677,120 which is incorporated in its entirety here by reference, discloses 2-(all-trans-retinoyloxy)-4-methoxyacetophenone, which is relatively low irritating and has the effects of inhibiting skin cancer and photoaging.
  • N-(4-hydroxyphenyl) retinamide and retinyl ⁇ -glucuronide are known to have the anti-aging effect, but have not solved the problem of the toxicity [ see : FASEB J., 10, 1014-1024, 1996, which is incorporated in its entirety here by reference].
  • WO 03/037385 which is incorporated in its entirety here by reference, discloses retinoid derivatives wherein fat-soluble retinoids are esterified or cyclized with polyethylene glycol to improve water-solubility.
  • the retinoid derivatives are easy to process and formulate, and well suited for administration by inhalation to allow administration of smaller doses of the retinoid derivatives to achieve therapeutically useful levels in treating chronic obstructive pulmonary diseases such as emphysema, thereby increasing their bioavailability and reducing their systemic toxicity.
  • the retinoid derivatives have the problem that polyethylene glycol (PEG) backbone and retinoic acid are rapidly decomposed by an enzyme in the blood.
  • the present inventors have researched to overcome the above problems of the known retinoid derivatives, and found that the retinoid derivatives according to the present invention have an excellent collagen synthesis increasing effect, is non-irritating, is non-toxic, have good chemical stability, is easily absorbed to the skin, and is long-wearing.
  • An object of the present invention is, therefore, to provide a retinoid derivative of the following formula (I), which can be used as an ingredient of functional cosmetics.
  • Another object of the present invention is to provide a cosmetic composition comprising the retinoid derivative of the following formula (I).
  • the present invention relates to a retinoid derivative of the following formula (I), which can be used as an ingredient of functional cosmetics.
  • X is NH, O, or S, particularly NH or O;
  • R 1 and R 2 are identical or different, and hydrogen or C 1 -C 6 alkyl, particularly different, and hydrogen or methyl.
  • the retinoid derivative according to one embodiment of the present invention is particularly a compound of the above formula (I) wherein X is NH, R 1 is methyl, and R 2 is hydrogen, that is, 2-methyl-1,5-diretinylpentanediamide (MDRPDA).
  • MDRPDA 2-methyl-1,5-diretinylpentanediamide
  • C 1 -C 6 alkyl as used herein means a straight or branched hydrocarbon having 1 to 6 carbon atoms, which includes methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, etc. but is not limited thereto.
  • the retinoid derivative according to the present invention can be prepared as follows.
  • the retinoid derivative according to the present invention can be prepared by reacting a compound of the following formula (II) wherein Y is hydroxy with a compound of the following formula (III) in a solvent in the presence of a coupling agent and an organic amine catalyst (hereinafter "Process I").
  • the retinoid derivative according to the present invention can be prepared by reacting a compound of the following formula (II) wherein Y is halogen with a compound of the following formula (III) in a solvent in the presence of an organic amine (hereinafter "Process II").
  • Y is hydroxy or halogen
  • X is NH, O, or S
  • R 1 and R 2 are identical or different, and hydrogen or C 1 -C 6 alkyl.
  • the coupling agent can include N,N,N',N'-tetramethyl-(benzotriazol-1-yl)-uronium tetrafluoroborate (TBTU), N-(3-dimethylaminopropyl)-N'-ethyl-carbodiimide (EDC), N,N'-diisopropylcarbodiimide (DIC), or N,N‘-dicyclohexylcarbodiimide (DCC), but is not limited thereto.
  • the organic amine catalyst to accelerate the coupling reaction can include diisopropylethylamine (DIPEA) and 4-dimethylaminopyridine (DMAP), but is not limited thereto.
  • the solvent can include anhydrous organic solvents such as dichloromethane, benzene, toluene, tetrahydrofuran and diethyl ether, but is not limited thereto.
  • the coupling reaction can be carried out under nitrogen atmosphere with blocking out light and moisture at cooled or warmed temperature.
  • the organic amine functions as a base, which can include pyridine and triethylamine, but is not limited thereto.
  • the organic amine can be used in an amount of 1.0 to 2.0 equivalents based on the compound of the above formula (III).
  • the solvent can include anhydrous organic solvents such as dichloromethane, benzene, toluene, tetrahydrofuran and diethyl ether, but is not limited thereto.
  • the coupling reaction can be carried out under nitrogen atmosphere with blocking out light and moisture at cooled or warmed temperature.
  • the compound of the above formula (II) wherein Y is halogen which is used as a starting material in the above Process II, can be prepared by reacting retinoic acid with a halogenating agent such as phosphorous trichloride, thionyl chloride and oxalyl chloride.
  • a halogenating agent such as phosphorous trichloride, thionyl chloride and oxalyl chloride.
  • the compound of the above formula (I), which is prepared as above can be purified using common purification methods such as recrystallization and column chromatography.
  • the retinoid derivative of the above formula (I) according to the present invention can be used for skin care and skin disorders, for example for treating skin cancer, acne, skin wrinkles, freckles, etc.
  • the retinoid derivative according to the present invention is characterized by being non-irritating, being easily absorbed to the skin, stimulating collagen synthesis, and inhibiting the decomposition of elastin to have a skin regeneration effect, and having high selectivity to the retinoic acid receptor.
  • the present invention further relates to a cosmetic composition, particularly an anti-aging cosmetic composition, comprising the retinoid derivative of the above formula (I).
  • the cosmetic composition of the present invention can contain 0.01 to 20.0 wt%, particularly 0.1 to 10.0 wt% of the retinoid derivative of the above formula (I) as an active ingredient.
  • the particular amount of the active ingredient can be determined depending on the purpose of use.
  • the cosmetic composition of the present invention can include cosmetic ingredients usually used in the art, for example, common adjuvants such as anti-oxidant, stabilizer, solubilizer, vitamin, colorant and perfumery, and carriers, in addition to the retinoid derivative according to the present invention.
  • cosmetic ingredients usually used in the art for example, common adjuvants such as anti-oxidant, stabilizer, solubilizer, vitamin, colorant and perfumery, and carriers, in addition to the retinoid derivative according to the present invention.
  • the cosmetic composition of the present invention can be formulated as any form usually used in the art, for example, solution, suspension, emulsion, paste, gel, cream, powder, spray, etc.
  • the examples of the carriers include animal oil, vegetable oil, wax, paraffin, starch, tragacanth, cellulose derivative, polyethylene glycol, silicon, bentonite, silica, talc, zinc oxide, etc.
  • the examples of the carriers include lactose, talc, silica, aluminum hydroxide, calcium silicate, polyamide powder, etc.
  • the cosmetic composition can further include propellant such as chlorofluorohydrocarbon, propane/butane and dimethyl ether.
  • the examples of the carriers include solvent, solubilizer and emulsifier such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylglycol oil, glycerol fatty acid ester, polyethylene glycol, sorbitan fatty acid ester, etc.
  • the examples of the carriers include liquid diluent such as water, ethanol and propylene glycol, suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystalline cellulose, aluminum methahydroxide, bentonite, agar, tragacanth, etc.
  • the cosmetic composition of the present invention can be applied to cosmetics such as skin, lotion, cream, essence, pack, foundation, coloring cosmetics, sun block cream, two-way cake, face powder, compact, makeup base, skin cover, eye shadow, lip stick, lip gloss, lip fix and eyebrow pencil.
  • cosmetics such as skin, lotion, cream, essence, pack, foundation, coloring cosmetics, sun block cream, two-way cake, face powder, compact, makeup base, skin cover, eye shadow, lip stick, lip gloss, lip fix and eyebrow pencil.
  • the retinoid derivatives according to the present invention have an excellent collagen synthesis increasing effect, is non-irritating, is non-toxic, have good chemical stability, is easily absorbed to the skin, and is long-wearing to show superior skin regeneration and anti-aging effects.
  • the retinoid derivative according to the present invention can be effectively used as an active ingredient of cosmetics or medicine.
  • Fig. 1 is a graph illustrating the collagen synthesis effects of the compound (MDRPDA) according to the present invention, and retinyl palmitate, retinoic acid, ethyl retinoate and PEG-retinamide as comparative compounds.
  • Figs. 2 to 6 are graphs illustrating the cytotoxicities of retinyl palmitate, retinoic acid, ethyl retinoate and PEG-retinamide as comparative compounds, and the compound (MDRPDA) according to the present invention, repectively.
  • Fig. 7 is a graph illustrating the hydrolysis rates of the compound (MDRPDA) according to the present invention, and retinyl palmitate, ethyl retinoate and PEG-retinamide as comparative compounds.
  • Example 1 Preparation of 2-methyl-1,5-diretinylpentanediamide (MDRPDA) (compound of formula (I) wherein X is NH, R 1 is methyl, and R 2 is hydrogen)
  • Example 2 Preparation of 3-methyl-1,5-diretinylpentanediester (MDRPDE) (compound of formula (I) wherein X is O, R 1 is hydrogen, and R 2 is methyl)
  • retinoic acid 25.0 g (0.083 mol) was dissolved in 200 ml of anhydrous toluene, and 4.92 g (0.042 mol) of 3-methyl-1,5-pentanediol, 20.6 g (0.100 mol) of dicyclohexylcarbodiimide (DCC) and 11.2 g (0.092 mol) of 4-dimethylaminopyridine (DMAP) were added threreto, followed by stirring at room temperature with blocking out light and moisture under nitrogen atmosphere for 15 hours.
  • DCC dicyclohexylcarbodiimide
  • DMAP 4-dimethylaminopyridine
  • the collagen synthesis effect test was performed to confirm the anti-aging effect of the compound (MDRPDA) obtained in Example 1 according to the present invention.
  • comparative compounds were used retinyl palmitate, retinoic acid, ethyl retinoate, and PEG-retinamide, which are being used as an ingredient of anti-aging medicine and cosmetics.
  • Human fibroblasts were cultured in a 24-well plate for 24 hours and treated with 1 and 10 ⁇ M of the samples. After 2 hours, the cultured cells were treated with procollagen type I C-peptide EIA kit reagent and cultured for 24 hours. The amount of collagen generated in the culture solution was measured with ELISA. The collagen synthesis effects were determined based on the measured amounts of collagen, and the results are shown in Fig. 1 [ see : Am. J. Pathology, 2004, 165, 167-174; Analytical Biochemistry, 1979, 96, 220-224.; J. Invest Dermatol, 1991, 96, 473-477, which are incorporated in its entirety here by reference].
  • the MDRPDA had better collagen synthesis increasing effect, as compared with the retinyl palmitate, retinoic acid, ethyl retinoate, and PEG-retinamide. Further, when the concentration of the samples was increased to 10 ⁇ M, the MDRPDA had much better collagen synthesis increasing effect, as compared with the above comparative compounds.
  • Example 1 The allergy test of the compound (MDRPDA) obtained in Example 1 according to the present invention was performed in accordance with a safety test using ethanol as a carrier vehicle [ see : J. Appl. Toxicol., 1990, 10(3), 173 ⁇ 180, which is incorporated in its entirety here by reference].
  • Retinyl palmitate, retinoic acid, ethyl retinoate and PEG-retinamide as comparative compounds, and the MDRPDA were dissolved in acetone/olive oil (4/1, v/v) to prepare 0.3% and 1% solutions, respectively.
  • 30 ⁇ l of each solution was applied to both ears of a mouse (Balb/c) for 3 days, and the auricular lymph node of the mouse was separated.
  • the lymph node was pulverized to single cell state, and a radioactive isotope ( 3 H-thymidine) was added thereto, followed by culturing for 24 hours.
  • the amplification degrees (cpm) of the cells were measured, and the results are shown in Table 1.
  • the MDRPDA showed very low allergy inducing effect, as compared with the retinyl palmitate, retinoic acid, ethyl retinoate, and PEG-retinamide.
  • Example 1 The skin irritability of the compound (MDRPDA) obtained in Example 1 according to the present invention was confirmed by a patch test using guinea pigs [ see : Assoc. Food and Drug officials US., 1959, 46-59; Method of testing primary irritant substances, 1973, 38(187), 1500-1541, which are incorporated in its entirety here by reference].
  • the MDRPDA showed significantly low skin irritability, as compared with the retinyl palmitate, retinoic acid, and ethyl retinoate.
  • Example 1 The primary safety of the compound (MDRPDA) obtained in Example 1 according to the present invention as an ingredient of medicine or cosmetics was confirmed by its cytotoxicity using MTT test culturing Chinese hamster lung fibroblast cell line (V79-4) [ see : Journal of Immunological Methods, 1983, 65, 55 ⁇ 63, which is incorporated in its entirety here by reference].
  • retinyl palmitate, retinoic acid, ethyl retinoate, PEG-retinamide, and the compound (MDRPDA) according to the present invention are shown in Figs. 2 to 6, respectively.
  • the MDRPDA showed no cytotoxicity as the ethyl retinoate as a comparative compound did not.
  • the retinyl palmitate and retinoic acid had cytotoxicity at the concentration of 10 ⁇ M or more, and the PEG-retinamide showed significant cytotoxicity at the concentration of 25 ⁇ M or more.
  • Example 1 To confirm the light stability of the compound (MDRPDA) obtained in Example 1 according to the present invention, 10 mg of the sample was irradiated with UV-A light (wave length: 356 nm) (Spectroline Model CM-10; Fluorescence analysis cabinet; Spectronics Corporation, Westbury, New York, USA) depending on the time, and qualitatively analyzed with 1 H NMR (400 MHz). The results are shown in Table 3.
  • UV-A light wave length: 356 nm
  • Spectroline Model CM-10 Fluorescence analysis cabinet; Spectronics Corporation, Westbury, New York, USA
  • the MDRPDA had better light stability than the retinol, retinyl palmitate, retinoic acid and ethyl retinoate, and showed similar light stability as compared with the PEG-retinamide.
  • Example 1 To confirm the heat stability of the compound (MDRPDA) obtained in Example 1 according to the present invention, the sample was stored in a constant temperature and humidity chamber (humidity: 56%) at room temperature, 0 °C, 37 °C and 50 °C for 1 month, and the phase stability was analyzed with high performance liquid chromatography (HPLC) under the following conditions.
  • HPLC high performance liquid chromatography
  • Eluent gradient elution of Solvent A: 0.1% acetic acid containing water, B: 0.1% acetic acid containing acetonitrile, C: 0.1% acetic acid containing methanol, and D: isopropyl alcohol;
  • the MDRPDA had good heat stability at 37 °C and 50 °C.
  • the percutaneous absorption test of the compound (MDRPDA) obtained in Example 1 according to the present invention was performed using retinol, retinyl palmitate, retinoic acid, ethyl retinoate and PEG-retinamide as comparative compounds, and 1:1 mixture of oil (capryliccapric triglyceride) and ethanol as a medium [ see : J. Invest Dermatol., 1998, 91; 56-61, which is incorporated in its entirety here by reference].
  • the skin (on the back region) of a 7-week-old female nude mouse was severed, and 150 ⁇ l of 50 mM sample solution was applied to 1.7 cm 2 of the skin. After 24 hours, the compound absorbed to the skin and receptor solution, which is 50 mM PBS buffer (pH 7.4) containing 2% Volpo 20 (Oleth-20), were extracted with Franz cell and analyzed with HPLC. The results are shown in Table 5.
  • the MDRPDA showed higher percutaneous absorption rate, as compared with the retinol, retinyl palmitate, retinoic acid, and ethyl retinoate. Also, the MDRPDA showed very similar percutaneous absorption rate, as compared with the PEG-retinamide, which is known to have improved solubility.
  • the half-life (t 1/2 ) of the hydrolysis was 8.7 hours for the ester forms and 32 hours for the MDRPDA (amide form). Meanwhile, the PEG-retinamide (amide form) maintained about 60% even after 48 hours.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Dermatology (AREA)
  • Gerontology & Geriatric Medicine (AREA)
  • Birds (AREA)
  • Epidemiology (AREA)
  • Cosmetics (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

La présente invention porte sur des dérivés rétinoïdes et sur une composition cosmétique les comprenant. Les dérivés rétinoïdes selon la présente invention ont un excellent effet d'augmentation de la synthèse du collagène, ne sont pas irritants, sont non-toxiques, ont une bonne stabilité chimique, sont facilement absorbés par la peau et permettent un usage prolongé, pour représenter d'excellents effets de régénération de la peau et anti-âge. En conséquence, les dérivés rétinoïdes selon la présente invention peuvent être efficacement utilisés pour préparer une composition cosmétique anti-âge.
PCT/KR2011/005174 2010-07-14 2011-07-14 Dérivés rétinoïdes et composition cosmétique les comprenant Ceased WO2012008767A2 (fr)

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KR1020100067823A KR101194337B1 (ko) 2010-07-14 2010-07-14 레티노이드 유도체 및 그를 포함하는 화장료 조성물
KR10-2010-0067823 2010-07-14

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20210371390A1 (en) * 2014-03-19 2021-12-02 The Regents Of The University Of California Amyloid targeting agents and methods of using the same
CN114200036A (zh) * 2021-11-09 2022-03-18 广东省药品检验所（广东省药品质量研究所、广东省口岸药品检验所） 一种化妆品或其原料中添加物的检测方法
US12478693B2 (en) 2018-05-31 2025-11-25 Amydis, Inc. Compositions and methods for detection of traumatic brain injury

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR102105210B1 (ko) 2012-11-26 2020-04-27 코웨이 주식회사 레티노이드 유도체를 안정화시킨 수중유형 유화 화장료 조성물
KR102400114B1 (ko) * 2015-08-13 2022-05-19 코웨이 주식회사 레티노이드 유도체를 유효성분으로 함유하는 피부 탄력 증진용 조성물

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CH314001A (de) * 1952-12-18 1956-05-31 Hoffmann La Roche Verfahren zur Herstellung von Vitamin-A-Estern
US4677120A (en) * 1985-07-31 1987-06-30 Molecular Design International Topical prodrugs for treatment of acne and skin diseases
DK498487A (da) * 1986-10-06 1988-04-07 Hoffmann La Roche Hidtil ukendte retinoider
US7173062B2 (en) * 2001-01-16 2007-02-06 Enprani Co., Ltd. Method for the improvement of skin wrinkles using retinyl retinoate
KR20090113614A (ko) * 2008-04-28 2009-11-02 엔프라니 주식회사 레티놀 유도체를 함유하는 화장료 조성물
KR101057471B1 (ko) * 2008-08-21 2011-08-17 엔프라니 주식회사 레티노이드로 인한 피부자극 완화용 화장료 조성물

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20210371390A1 (en) * 2014-03-19 2021-12-02 The Regents Of The University Of California Amyloid targeting agents and methods of using the same
US11718596B2 (en) * 2014-03-19 2023-08-08 The Regents Of The University Of California Amyloid targeting agents and methods of using the same
US12478693B2 (en) 2018-05-31 2025-11-25 Amydis, Inc. Compositions and methods for detection of traumatic brain injury
CN114200036A (zh) * 2021-11-09 2022-03-18 广东省药品检验所（广东省药品质量研究所、广东省口岸药品检验所） 一种化妆品或其原料中添加物的检测方法
CN114200036B (zh) * 2021-11-09 2023-11-28 广东省药品检验所（广东省药品质量研究所、广东省口岸药品检验所） 一种化妆品或其原料中添加物的检测方法

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KR101194337B1 (ko) 2012-10-24
KR20120007199A (ko) 2012-01-20
WO2012008767A3 (fr) 2012-04-26

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