WO2010041417A1 - Préparation externe pour la peau - Google Patents

Préparation externe pour la peau Download PDF

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Publication number
WO2010041417A1
WO2010041417A1 PCT/JP2009/005170 JP2009005170W WO2010041417A1 WO 2010041417 A1 WO2010041417 A1 WO 2010041417A1 JP 2009005170 W JP2009005170 W JP 2009005170W WO 2010041417 A1 WO2010041417 A1 WO 2010041417A1
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WIPO (PCT)
Prior art keywords
rhododendrol
skin
carbon atoms
acyl group
note
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PCT/JP2009/005170
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English (en)
Japanese (ja)
Inventor
晃司 佐藤
稔 佐々木
毅 池本
華子 杉本
Original Assignee
花王株式会社
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Priority to JP2010532804A priority Critical patent/JPWO2010041417A1/ja
Priority to CN2009801377144A priority patent/CN102164489A/zh
Publication of WO2010041417A1 publication Critical patent/WO2010041417A1/fr

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    • 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
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/37—Esters of carboxylic acids
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/02—Halogenated hydrocarbons
    • A61K31/025—Halogenated hydrocarbons carbocyclic
    • A61K31/03—Halogenated hydrocarbons carbocyclic aromatic
    • 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
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34—Alcohols
    • A61K8/347—Phenols
    • 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
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/10—Anti-acne agents
    • 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
    • A61Q15/00—Anti-perspirants or body deodorants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/005—Antimicrobial preparations

Definitions

  • the present invention relates to an external preparation for skin.
  • Blots and freckles are those in which the balance between production and excretion of melanin is lost and melanin is excessively accumulated in epidermal cells. These causes are various, such as inflammation, hormonal balance, genetic factors, etc., but are promoted by the influence of ultraviolet rays.
  • a whitening agent relieves increased pigmentation.
  • kojic acid, arbutin, hydroquinone monobenzyl ether, hydrogen peroxide, etc. are known to be applied to whitening cosmetics to prevent skin darkening, spots and freckles, and to maintain the original white skin. It has been.
  • Vitamin C and its derivatives are known as whitening agents that suppress inflammation caused by ultraviolet rays. However, these were not satisfactory in terms of the degree of whitening effect and the stability in the preparation.
  • parabens such as methylparaben, ethylparaben, propylparaben, and butylparaben have been frequently used as an antiseptic disinfectant in cosmetics, quasi drugs, and pharmaceuticals.
  • cosmetics appealing for low irritation and sensitive skin have been put on the market, and reductions in the amount of parabens used, alternative methods, etc. are desired.
  • Various methods such as blending plant extracts and blending alkanediols such as 1,2-pentanediol and 1,2-hexanediol have been proposed (Patent Documents 1 to 5).
  • Patent Documents 1 to 5 it has been a problem that the amount of these components to be used is limited from the viewpoint of the texture and stability of the preparation when blended in cosmetics and the like, and the taste such as odor.
  • the pathological conditions of acne are broadly divided into 1) comedones that are non-inflammatory skin rashes, 2) inflammatory papules such as red papules, 3) scars, and 4) post-inflammation pigmentation.
  • the treatment is performed by one or a combination of the following three treatment methods: 1) topical external therapy, 2) systemic internal use therapy, and 3) physical therapy.
  • topical external therapy is considered to be an effective treatment method for symptoms other than scarring, and external preparations containing various active ingredients have been developed so far (Non-patent Document 1).
  • the pathogenesis of acne is divided into two major stages. The first stage is comedone formation and the second stage is inflammation.
  • the comedones are formed when the pores are blocked and sebum is stored in the hair follicles due to excessive sebum secretion and increased keratinization of the pores. Since comedones are a habitat suitable for the anaerobic bacterium Propionibacterium acnes, which is a skin-resident bacterium, in the comedones, the number of bacteria increases and extracellular inflammation-inducing substances are produced. Therefore, inflammatory papules such as red papules are induced (Non-patent Document 2).
  • Such acne prevention and improvement measures include sebum (triglyceride) and facial cleansing to prevent keratin thickening that cause pore closure, the use of antiseborrheic agents such as vitamin B6, and the early use of unnecessary keratin due to resorcin and salicylic acid.
  • Exfoliation, P.I. Prevention of deterioration by an antibacterial substance having a high bactericidal effect such as isopropylmethylphenol that inhibits the growth of acnes, and the use of anti-inflammatory agents are known (Non-patent Document 3).
  • Non-Patent Document 1 topical topical therapy with vitamin C (ascorbic acid) derivatives has attracted attention (Non-Patent Document 1), and further, a tyrosinase activity inhibitor and an antibacterial or anti-acne agent are combined.
  • a tyrosinase activity inhibitor and an antibacterial or anti-acne agent are combined.
  • odor which is a unique odor among human body odors, is caused by glycoproteins and lipids secreted by the apocrine sweat glands in the axilla, which are decomposed by enzymes produced by skin bacteria, resulting in the removal of volatile and off-flavor fatty acids. It is caused by production (Non-patent Document 4).
  • a causative bacterium that generates a particularly strong and unpleasant odor there is Corynebacterium xerosis, and since it is a lipophilic bacterium, it is detected in the buttocks where there are many sebaceous glands and sweat glands.
  • Antibacterial agents effective against bacteria belonging to the genus Corynebacterium compositions for odors, sucrose esters of fatty acids that have been used conventionally as preservatives and preservatives for foods and cosmetics (Patent Document 8), disinfection and sterilization Ingredients such as triclosan and isopropylmethylphenol (patent document 9), edible flower extract of licorice (patent document 10), alkanediol and lysozyme (patent document 11) for enhancing antibacterial activity have been proposed. In order to prevent the bad smell, two functions of antiperspirant and sterilization are necessary.
  • an aluminum salt such as hydroxyaluminum chloride (aluminum chloride hydrate) has been used as an astringent as an example of antiperspirant.
  • a substance having a wide bactericidal activity such as benzalkonium chloride has been used as an antibacterial agent (Non-patent Document 3).
  • benzalkonium chloride has been used as an antibacterial agent (Non-patent Document 3).
  • no deodorant active agent having a sufficient effect has been found yet.
  • Non-patent Document 12 rhododendrol and some of its derivatives have an excellent whitening action, and exhibit antibacterial effects against specific bacteria, so that application to an external preparation for skin has been proposed.
  • Patent Document 12 phenylbutanoids containing rhododendrol have been reported to exhibit antibacterial activity against several types of bacteria.
  • the present invention is a novel rhododendrol derivative with improved solubility in low-polarity solvents and easy application to various cosmetic preparations, and whitening effect, antiseptic antibacterial effect, acne prevention / improvement effect containing this It is another object of the present invention to provide an external preparation for skin having excellent deodorizing effects.
  • the present invention was completed by confirming that the growth inhibitory effect against acnes, the effect of preventing and improving acne scars, and the bactericidal effect against Corynebacterium Xerosis, which is a causative bacterium that generates an unpleasant odor, can be sufficiently exhibited.
  • this invention provides the skin external preparation containing the rhododendrol derivative represented by following General formula (1).
  • R 1 represents an acyl group having 2 to 20 carbon atoms
  • R 2 represents a hydrogen atom or an acyl group having 2 to 20 carbon atoms.
  • the present invention also provides a rhododendrol derivative represented by the following general formula (1b).
  • R 1b and R 2b each represents an acyl group having 3 to 20 carbon atoms.
  • the present invention also provides a whitening agent, antiseptic fungicide, anti-acne agent and deodorant containing a rhododendrol derivative represented by the following general formula (1a) as an active ingredient.
  • R 1a represents an acyl group having 2 to 4 carbon atoms.
  • the present invention provides use of the rhododendrol derivative represented by the above general formula (1a) for producing a whitening agent, antiseptic / antibacterial agent, anti-acne agent or deodorant.
  • the present invention provides a whitening method, antiseptic sterilization method, acne treatment method or deodorization method characterized by applying a rhododendrol derivative represented by the above general formula (1a).
  • the rhododendrol derivative of the present invention has high solubility in a low-polarity solvent, can be easily applied to various cosmetic preparations, and also has a whitening effect, antiseptic antibacterial effect, acne prevention / improvement effect, and deodorant effect.
  • An excellent skin external preparation can be provided.
  • the rhododendrol derivative used in the present invention is a compound represented by the general formula (1).
  • R 1 is an acyl group having 2 to 20 carbon atoms
  • R 2 is a hydrogen atom.
  • R 1 and R 2 may be both acyl groups having the same carbon number, or may be acyl groups having different carbon numbers.
  • the acyl groups of R 1 and R 2 may be saturated or unsaturated, and may have a functional group such as an amino group. Of these, a saturated alkanoyl group is more preferred.
  • an alkanoyl group having 2 to 18 carbon atoms is preferable, an alkanoyl group having 2 to 8 carbon atoms is more preferable, and in the case of an acetyl group, propionyl group, butyroyl group, or isobutyroyl group having 2 to 4 carbon atoms, It is particularly preferable because it can be easily applied to a preparation.
  • the compound represented by the following general formula (1b) is a novel compound.
  • R 1b and R 2b each represents an acyl group having 3 to 20 carbon atoms.
  • R 1 is an acyl group having 2 to 8 carbon atoms (particularly having 2 to 4 carbon atoms) from the viewpoint of applicability to whitening agents, antiseptics, anti-acne agents, deodorants, and the like.
  • a compound in which R 2 is a hydrogen atom or an acyl group having 2 to 8 carbon atoms (particularly a hydrogen atom or an acyl group having 2 to 4 carbon atoms) is preferable, and is particularly represented by the following general formula (1a). Are preferred.
  • R 1a represents an acyl group having 2 to 4 carbon atoms.
  • the production method of the rhododendrol derivative used in the present invention is obtained by separating and purifying from a rhododendrol obtained by a known synthesis method or an extract of a plant containing rhododendrol such as muslinoki or birch. And can be produced using known acylation reactions. For example, there is a method of reacting rhododendrol and acid chloride or acid anhydride in a pyridine solvent. It can also be obtained by acylating a plant extract such as a medulinary tree by an appropriate method and then separating and purifying the target rhododendrol derivative.
  • the rhododendrol derivative obtained by the above method has optical isomers, but the (+) isomer, the ( ⁇ ) isomer alone, or a mixture thereof can also be used.
  • the rhododendrol derivative represented by the general formula (1) has excellent whitening action, antiseptic sterilization action, acne prevention improvement action, deodorization action and solubility in a low-polarity solvent as shown in Examples below. Since it is excellent, it is useful as a whitening agent, whitening cosmetic, anti-acne agent, acne skin external preparation, antiseptic disinfectant, deodorant, and deodorant skin external preparation.
  • the rhododendrol derivative used in the present invention may be any one of the rhododendrol derivatives represented by the above general formula (1), or a mixture of two or more thereof. It may be used as
  • the content of the rhododendrol derivative of the present invention cannot be defined unconditionally depending on the purpose of blending and what is to be blended, but is usually 0.00001% by mass to 10.0% by mass based on the total amount of the external preparation for skin, The amount is preferably 0.001% by mass to 5.0% by mass, more preferably 0.01% by mass to 3.0% by mass.
  • the skin external preparation of the present invention includes hydroquinone, arbutin, ellagic acid, vitamin C and derivatives thereof (for example, ascorbic acid glucoside, ascorbic acid phosphate ester) which are already known whitening agents.
  • hydroquinone arbutin, ellagic acid, vitamin C and derivatives thereof (for example, ascorbic acid glucoside, ascorbic acid phosphate ester) which are already known whitening agents.
  • biphenyl derivatives eg, dehydrodicreol, 2,2′-dihydroxy-5,5′-dipropylbiphenyl, etc.
  • 3340935 Melanin inhibitors such as raspberry ketone, hexanoyl raspberry ketone, octanoyl raspberry ketone, rhododendrol, 4- (3-hydroxybutyl) phenyl acetate, fire thorn extract, geoscorea compositor extract, Iwashiro Extract, chamomile extract, adenosine 5'-monophosphate and a salt thereof, linoleic acid derivatives, tranexamic acid and tranexamic acid salts, can be used in combination whitening agent suitable such tranexamic acid derivative.
  • chelating agents such as alcohols, phenoxyethanol, dipropylene glycol, butylene glycol, alkanediol, sodium edetacetate, etc.
  • the bactericidal effect can be improved. Particularly in combination with phenoxyethanol, it is more preferable in terms of antiseptic sterilization effect.
  • the external preparation for skin of the present invention includes moisturizers such as hyaluronic acid, polyhydric alcohols, sugar alcohols, tar pigments, colored pigments such as iron oxide, preservatives such as parabens, fatty acid soap, sodium cetyl sulfate
  • Non-ionic surfactants such as polyoxyethylene alkyl ether, polyoxyethylene fatty acid ester, polyoxyethylene polyhydric alcohol fatty acid ester, polyoxyethylene hydrogenated castor oil, polyhydric alcohol fatty acid ester, polyglycerin fatty acid ester Ionic surfactants, cationic surfactants such as tetraalkylammonium salts, betaine type, sulfobetaine type, sulfoamino acid type, amphoteric surfactants such as sodium N-stearoyl-L-glutamate, lecithin, lyso Natural surface activity such as phosphatidylcholine Natural polymers such as gelatin, casein, starch
  • Semi-synthetic polymers polyvinyl alcohol, polyvinyl methyl ether and copolymer, synthetic polymers such as polyvinylpyrrolidone, sodium polyacrylate, carboxyvinyl polymer, polyethylene oxide polymer, thickeners such as xanthene gum, pigments such as titanium oxide Antioxidants such as dibutylhydroxytoluene can be appropriately blended within a range not impairing the object of the present invention.
  • the form of the external preparation for skin of the present invention is not particularly limited because the rhododendrol derivative is dissolved in a low-polarity solvent, but forms such as an ointment, cream, lotion, sunscreen, cosmetic liquid, emulsion, pack, bath preparation, etc. It can be.
  • the obtained purified product (3.0 g) was placed in a 200 mL eggplant-shaped flask, 80 vol% aqueous methanol solution (120 mL) was added, and the mixture was stirred. Further, ammonium acetate (7.5 g) was added and reacted at 40 ° C. for 48 hours, followed by post-treatment according to a conventional method to obtain a crude product.
  • the obtained crude product was subjected to silica gel column chromatography (silica gel 60N: 100-210 ⁇ m; manufactured by Kanto Chemical Co., Inc.) and purified with ethyl acetate / n-hexane (1/4) as a mobile phase to obtain the target rhododene.
  • a drole derivative (1.1 g) was obtained as a colorless oil.
  • the results of 13 C-NMR are shown below.
  • the obtained crude product was subjected to silica gel column chromatography (silica gel 60N: 100-210 ⁇ m; manufactured by Kanto Chemical Co., Inc.) and purified with ethyl acetate / n-hexane (1/5) as a mobile phase to obtain the desired rhododene.
  • a drole derivative (3.3 g) was obtained as a colorless and transparent oily substance.
  • the results of 13 C-NMR are shown below.
  • the obtained crude product was subjected to silica gel column chromatography (silica gel 60N: 100-210 ⁇ m; manufactured by Kanto Chemical Co., Inc.) and purified using n-hexane as a mobile phase to obtain the target rhododendrol derivative (11.3 g). Obtained as a colorless and transparent oil.
  • silica gel column chromatography silica gel 60N: 100-210 ⁇ m; manufactured by Kanto Chemical Co., Inc.
  • the obtained crude product was subjected to silica gel column chromatography (silica gel 60N: 100-210 ⁇ m; manufactured by Kanto Chemical Co., Inc.), and fractionated and purified using n-hexane as a mobile phase.
  • the obtained purified product (5.0 g) was placed in a 200 mL eggplant-shaped flask, and 80 vol% acetonitrile aqueous solution (100 mL) was added and stirred. Further, ammonium acetate (6.0 g) was added and reacted at 50 ° C. for 96 hours, followed by post-treatment according to a conventional method to obtain a crude product.
  • the obtained crude product was subjected to silica gel column chromatography (silica gel 60N: 100-210 ⁇ m; manufactured by Kanto Chemical Co., Inc.) and purified with ethyl acetate / n-hexane (1/4) as a mobile phase to obtain the target rhododene.
  • a drole derivative (1.3 g) was obtained as a colorless and transparent oily substance.
  • the results of 13 C-NMR are shown below.
  • the obtained purified product (1.0 g) was placed in a 200 mL eggplant-shaped flask, dissolved in 100 mL of THF, and 1N NaOH aqueous solution was added dropwise. After confirming the disappearance of the reaction product by TLC, it was worked up according to a conventional method. The crude product was dissolved in 0.1N KOH aqueous solution, stirred at room temperature for 30 minutes, and extracted with ethyl acetate.
  • the ethyl acetate layer was concentrated and then subjected to silica gel column chromatography (silica gel 60N: 100-210 ⁇ m; manufactured by Kanto Chemical Co., Inc.) to purify ethyl acetate / n-hexane (1/9) as a mobile phase to obtain the desired rhododene.
  • a drole derivative (0.5 g) was obtained as white crystals.
  • the results of 13 C-NMR are shown below.
  • Test Example 1 Solubility test
  • rhododendrol derivatives obtained in Production Examples 1 to 4 the following solubility test was performed.
  • comparative controls rhododendrol and 4- (3-hydroxybutyl) phenyl acetate were used as Comparative Examples 1 and 2.
  • the rhododendrol derivative of the present invention has improved solubility in a low-polarity solvent as compared with Comparative Example 1 (Rhodendrol) and Comparative Example 2 (4- (3-hydroxybutyl) phenyl acetate). I understand that. Further, from the comparison between Production Example 2 and Comparative Example 2, when an acyl group is added to rhododendrol, the solubility differs depending on the position of addition, and the product of the present invention has a significantly improved solubility compared to Comparative Example 2.
  • Test example 2 antibacterial activity test against general bacteria and fungi
  • rhododendrol derivative obtained in Production Example 2 the antibacterial activity test shown below was performed.
  • rhododendrol (Comparative Example 1) and phenoxyethanol (Comparative Example 3) were used as comparative objects.
  • Test Method Antibacterial activity was evaluated by measuring the minimum growth inhibitory concentration (MIC, unit: ⁇ g / mL) of various microorganisms shown in Table 2 according to the agar plate dilution method of the Japanese Society of Chemotherapy Standard Method. That is, a medium was prepared by adding evaluation samples (Production Example 2 and Comparative Examples 1 and 3) to a concentration in the range of 625 to 10000 ⁇ g / mL, and the growth properties of various microorganisms shown in Table 2 were determined. Was used to evaluate.
  • the medium and culture conditions are as follows.
  • glucose peptone agar medium is used for 72 hours under an aerobic condition at 25 ° C.
  • soybean casein digest agar medium is used for 30 ° C. aerobic condition. After 48 hours of culturing, their proliferation was confirmed.
  • the rhododendrol derivative of Production Example 2 has an excellent antiseptic sterilization having a very high antibacterial activity because the MIC value is low in all strains as compared with the rhododendrol of Comparative Example 2. It was confirmed to be an agent. Moreover, compared with the phenoxyethanol of the comparative example 3, since it showed the same MIC value, it was shown that it is a useful antiseptic antibacterial agent similarly to the phenoxyethanol known as a general antiseptic antibacterial agent. .
  • Test example 3 antibacterial activity test for acne prevention and improvement
  • rhododendrol derivative obtained in Production Example 2 As comparative objects, rhododendrol (Comparative Example 1) and resorcin (Comparative Example 4) were used.
  • Test Example 2 The test was conducted in the same manner as in Test Example 2. That is, a medium was prepared by adding evaluation samples (Production Example 2 and Comparative Examples 1 and 4) to a concentration in the range of 625 to 10000 ⁇ g / mL, and the growth of Propionibacterium acnes was evaluated using these media. did. A brain heart infusion agar medium was used as the medium, and the cells were cultured under anaerobic conditions at 37 ° C. for 72 hours, and then their growth properties were confirmed.
  • Test example 4 (external preparation for acne skin) According to the formulation shown in Table 5 below, acne skin external preparation (skin lotion) was prepared, and its anti-acne effect was evaluated according to the following evaluation method.
  • Example 1 was superior to Comparative Example 5 in acne improvement effect and acne scar improvement effect.
  • Test Example 5 Example of antibacterial activity test regarding deodorization action
  • rhododendrol derivative obtained in Production Example 2 the antibacterial activity test shown below was performed.
  • rhododendrol Comparative Example 1
  • Test Example 2 The test was conducted in the same manner as in Test Example 2. That is, a medium to which evaluation samples (Production Example 2 and Comparative Example 1) were added so as to have a concentration in the range of 625 to 10000 ⁇ g / mL was prepared, and the growth of Corynebacterium xerosis was evaluated using these media. As the medium and culture conditions, a soy bean / casein / digest agar medium was used and cultured for 30 hours under aerobic conditions at 30 ° C., and their growth was confirmed.
  • the rhododendrol derivative of Production Example 2 is an excellent deodorizing active agent having a very high antibacterial activity because it has a low MIC value as compared with the rhododendrol of Comparative Example 1. Indicated.
  • Test Method B16 melanoma cells were seeded in a 12-well culture plate at a volume of 1 ⁇ 10 4 cells / well in a 10 vol% fetal bovine serum-containing MEM medium, and precultured for 24 hours in a conventional manner. After the pre-culture, the medium was replaced with the test medium to which the sample (Production Example 1 and Comparative Example 1) was added, and cultured for 72 hours.
  • As the test medium a medium obtained by adding theophylline to the above-mentioned pre-culture medium so as to be 2 mmol / L was used.
  • Test Example 7 (Whitening practical test) Using the rhododendrol derivative obtained in Production Examples 1 and 2 above and a skin cream blended with rhododendrol, the following whitening practical test was conducted.
  • Test Method Summer sun light was exposed to the skin of the forearm bent side of 20 subjects for 3 hours (1.5 hours per day for 2 consecutive days). After exposure, skin creams of Example 2 and Example 3 in Table 8 below were applied to the subject's left forearm flexion side skin once a day in the morning and evening for 13 consecutive weeks. The skin cream of Comparative Example 6 in Table 8 below was applied to the subject's right forearm bent side skin under the same conditions. At the end of the final application, the degree of whitening before and after continuous use of the left and right forearm skin was evaluated by a specialist judge. In the evaluation, subjects who were confirmed to have a whitening effect were considered to have “whitening effect” and the number of subjects was shown.
  • each cosmetic was produced according to a conventional method according to the following ingredients.
  • Example 4 skin lotion
  • Raw material component amount (% by mass) Ethanol 10.0
  • Monolauric acid POE (20) sorbitan 5.0 Phenoxyethanol 0.1 Fragrance 0.05
  • Compound of Production Example 2 2.0 Glycerin 5.0 Xanthan gum 0.1 Hydroxyethyl cellulose 0.1 Purified water balance
  • Example 5 (skin cream) Raw material component amount (% by mass) Glycerol monostearate 2.0 Beeswax 1.0 Monooleic acid POE (20) sorbitan 6.0 Vaseline 4.0 Liquid paraffin 12.0 Compound of Production Example 1 2.0 N-stearoyl-L-glutamate sodium 1.0 Carrageenan 0.3 Methylparaben 0.1 Purified water balance
  • Examples 6 to 7 (cream) Raw material component amount (% by mass)
  • Example 6 Stearic acid 1.0 1.0 Glycerol monoisostearate 2.0 2.0 Behenyl alcohol 2.0 2.0 White beeswax 1.0 1.0 Isocetyl myristate 1.0 1.0 Sorbitan isostearate 1.0 1.0 Retinyl palmitate 0.1 0.1 Hydrogenated lecithin 0.1 0.1 Ubidecarenone 0.03 0.03 Phytosterol 0.1 0.1 Plant squalane 5.0 5.0 Hydrogenated polydecene 5.0 5.0 Dicapryl carbonate 5.0 5.0 1,3-butylene glycol 5.0 5.0 Concentrated glycerin 5.0 5.0 N-acetylglucosamine 0.1 0.1 Ascorbic acid sulfate disodium salt 0.2 0.2 ⁇ -aminobutyric acid 0.1 0.1 Sodium N-stearoyl glutamate 0.2 0.2 Monoammonium glycyrrhizinate 0.1
  • Example 8 (cream) Raw material component amount (% by mass) Isostearic acid 1.0 Glycerol monoisostearate 2.0 Behenyl alcohol 2.0 Sara honey bee 1.0 Isocetyl myristate 1.0 Sorbitan isostearate 1.0 Retinyl palmitate 0.1 Hydrogenated lecithin 0.1 Ubidecarenone 0.03 Phytosterol 0.1 Plant Squalane 5.0 Dicapryl carbonate 5.0 Methyl paraoxybenzoate 0.2 1,3-butylene glycol 10.0 Concentrated glycerin 5.0 N-acetylglucosamine 0.1 Ascorbic acid sulfate disodium salt 0.2 ⁇ -aminobutyric acid 0.1 Sodium N-stearoyl glutamate 0.2 Monoammonium glycyrrhizinate 0.1 Edelweiss extract (Note 3) 0.2 Yeast extract (Note 4) 0.2 Acrylic acid / alkyl methacrylate copolymer 0.05 Nicotin
  • Examples 12 to 14 (Cosmetic liquid) Raw material component amount (% by mass) Example 12
  • Example 13 Example 14 Co-modified silicone (Note 9) 2.0 2.0 2.0 POE modified silicon dispersion (Note 13)-2.0- Squalane--10.0 Decamethylcyclopentasiloxane 15.0 20.0 10.0 Methyl polysiloxane (100 cs) 5.0 2.0 3.0 Long-chain branched fatty acid cholesteryl (Note 14)--2.0 Silicon elastomer dispersion (Note 15) 5.0 2.0- Compound of Production Example 3 0.01 0.1 0.5 P-Hydroxybenzoic acid methyl ester 0.05 0.05 0.05 Sodium chloride 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 Dipropylene glycol 5.0 5.0 5.0 Concentrated glycerin 5.0 5.0 5.0 Raffinose 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0
  • Example 18 (Emulsion) Raw material component amount (% by mass) Methylphenyl polysiloxane (Note 22) 3.0 Dicapryl carbonate 1.0 Olive oil 1.0 Medfoam oil 0.1 Monolauric acid POE (20) sorbitan 0.5 Nicotinic acid dl- ⁇ -tocopherol 0.01 POE (60) hydrogenated castor oil 2.0 Shea fat (Note 23) 0.01 Ascorbyl tetraisopalmitate 0.1 N-acetylglucosamine 0.02 Yeast extract (Note 4) 3.0 1,3-butylene glycol 3.0 Sorbitol solution 3.0 Polyethylene glycol 1000 1.0 Carboxyvinyl polymer 0.1 Compound of Production Example 5 0.01 Methyl paraoxybenzoate 0.2 White jellyfish polysaccharide (Note 24) 0.05 Sodium edetate 0.02 Potassium hydroxide 0.05 Xanthan gum 0.05 Polyacrylamide (Note 25) 0.01 Purified water balance (Note
  • the rhododendrol derivative of the present invention can be applied to the cosmetic preparations of Examples 4 to 18, and by using these, it has excellent whitening action, antiseptic antibacterial action, acne prevention / amelioration action and deodorization action. Expressed.
  • the rhododendrol derivative of the present invention can be applied to a wide range of dosage forms, for example, cosmetics such as lotions, emulsions, creams, packs, bathing agents, etc. due to improved solubility.
  • cosmetics such as lotions, emulsions, creams, packs, bathing agents, etc. due to improved solubility.
  • the rhododendrol derivative of the present invention has excellent whitening action, antiseptic antibacterial action, acne prevention / amelioration action and deodorization action, the use of a skin external preparation containing the rhododendrol derivative of the present invention makes it possible to Very useful in terms of beauty.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Dermatology (AREA)
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  • Birds (AREA)
  • Engineering & Computer Science (AREA)
  • Cosmetics (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne une préparation externe pour la peau qui peut être facilement appliquée à diverses préparations cosmétiques car sa solubilité dans les solvants faiblement polaires est améliorée. La préparation externe pour la peau présente également un effet de blanchiment de la peau, un effet antibactérien, un effet de prévention/d'amélioration de l'acné et un effet désodorisant qui sont excellents. La préparation externe pour la peau se caractérise en ce qu'elle contient un dérivé de rhododendrol représenté par la formule générale (I). (Dans la formule, R1 représente un groupe acyle contenant 2-20 atomes de carbone, et R2 représente un atome d'hydrogène ou un groupe acyle contenant 2-20 atomes de carbone.)
PCT/JP2009/005170 2008-10-07 2009-10-06 Préparation externe pour la peau WO2010041417A1 (fr)

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JP2019501221A (ja) * 2015-12-30 2019-01-17 アレクサンドル・ヴィレノヴィチ・アサフォフＡＳＡＦＯＶ， Ａｌｅｘａｎｄｅｒ Ｖｉｌｅｎｏｖｉｃｈ 末梢関節、脊椎関節および／または結合組織の細胞外マトリックス構成要素の処置のための製剤、製造方法および使用

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CN105017194B (zh) * 2015-07-08 2018-05-22 渤海大学 含愈创兰烃薁结构的酪氨酸酶抑制剂及其制备方法与应用

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JPH10182410A (ja) * 1996-12-24 1998-07-07 Kanebo Ltd メラニン生成抑制剤および美白化粧料
JPH10265325A (ja) * 1997-03-26 1998-10-06 Kanebo Ltd メラニン生成抑制剤及び美白化粧料
JP2008007432A (ja) * 2006-06-27 2008-01-17 Kao Corp 皮膚外用剤
JP2008081491A (ja) * 2006-09-01 2008-04-10 Kao Corp 皮膚外用剤

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TW464501B (en) * 1996-12-17 2001-11-21 Kanebo Ltd Melanine formation inhibitor and their beautiful-white cosmetic

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JPH10182410A (ja) * 1996-12-24 1998-07-07 Kanebo Ltd メラニン生成抑制剤および美白化粧料
JPH10265325A (ja) * 1997-03-26 1998-10-06 Kanebo Ltd メラニン生成抑制剤及び美白化粧料
JP2008007432A (ja) * 2006-06-27 2008-01-17 Kao Corp 皮膚外用剤
JP2008081491A (ja) * 2006-09-01 2008-04-10 Kao Corp 皮膚外用剤

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2019501221A (ja) * 2015-12-30 2019-01-17 アレクサンドル・ヴィレノヴィチ・アサフォフＡＳＡＦＯＶ， Ａｌｅｘａｎｄｅｒ Ｖｉｌｅｎｏｖｉｃｈ 末梢関節、脊椎関節および／または結合組織の細胞外マトリックス構成要素の処置のための製剤、製造方法および使用

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CN102164489A (zh) 2011-08-24
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TW201019968A (en) 2010-06-01
JPWO2010041417A1 (ja) 2012-03-01

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