TW200932205A - External skin preparation for pimpled skin - Google Patents

Abstract

Disclosed is an external skin preparation for a pimpled skin, which has an excellent prophylactic or ameliorating effect on acne, can prevent or ameliorate the pigmentation on an acne scar, has no irritation to the skin, and is highly safe. Specifically disclosed is an external skin preparation for a pimpled skin, which is characterized by comprising at least one member selected from a rhododendrol represented by general formula (1) and a derivative thereof. (In general formula (1), R represents a hydrogen atom, an acyl group having 2 to 20 carbon atoms, or a sugar residue of a monosaccharide or a disaccharide.)

Description

200932205 IX. OBJECTS OF THE INVENTION: The present invention relates to a acne-prone skin which is excellent in prevention and improvement of pigmentation of acne lesions in addition to the prevention and improvement of acne A skin external preparation 'and an anti-acne acnes (p. acnes) composition. [Prior Art] The symptoms of acne (usual acne) can be roughly classified into: 丨) non-inflammatory rash, ie, acne, 2) inflammatory hysteresis such as red sclerotherapy, 3) scarring, and 4) post-inflammatory pigmentation. At the time of treatment, 1} topical topical therapy, 2) systemic internal therapy, 3) physical therapy, or combination of these treatments are performed according to the symptoms. Among them, topical topical therapy is regarded as a symptom other than scar An effective treatment method has been developed to prepare various external active ingredients (Non-Patent Document 1). The pathogenesis of acne can be roughly divided into two stages. In the first stage, a facial gun was formed, and the first stage caused inflammation. Due to excess sebum secretion and keratinization of the pores, the pores are blocked and sebum is accumulated in the hair follicles, thereby forming a blister. Since the blister is a living environment suitable for the skin-prone bacteria Propionibacterium acnes (hereinafter referred to as ρ. acnes), the number of the bacteria in the blister increases, and the extracellular inflammation-inducing substance is generated, so that red is caused. Inflammatory papules such as papules (Non-Patent Document 2). As a measure for prevention and improvement of acne, there are known methods for washing sebum to prevent sebum (triglyceride) or horny hypertrophy, to use anti-serum leakage agent such as vitamin B6, and to use resorcinol. Or water 137291.doc 200932205 Salicylic acid and the like for early exfoliation of unwanted keratin, and antibacterial substances having high bactericidal effect such as isopropylmethyl benzene which are inhibited by p-mail (10) are prevented from being deteriorated, and anti-inflammatory agents are used. (Non-Patent Document 3). 'For the pigmentation after inflammation, the topical topical treatment using vitamins (ascorbic acid) derivatives (Non-patent literature), further reported by the inhibition of the activity of the lysinase with antibacterial or anti-seat A combination of a sore agent to pre-treat or improve the acne scar blackening (Patent Document 2). $#面' includes P. acnes, which is a resident of the skin, except for acne or leather. The cause of the heart is that there is also a hindrance to the invasion of pathogenic bacteria. Therefore, anti-acne preparations using antibacterial substances with strong bactericidal activity may also inhibit the growth of resident bacteria which are beneficial to the skin. Therefore, it is proposed to maintain In particular, it can be used as a cosmetic material such as Staphylococcus epidermidis (hereinafter referred to as s (10) and the like (Patent Document 3) in the skin surface layer, such as decomposition of lipids or alkali neutralization (Patent Document 3). The anti-bacterial and bactericidal activity of plant extracts, sebum inhibition, absorption activity, lipase inhibitory activity, testis have been reported for the prevention and improvement of acne Ketone 5 α-reductase inhibitory activity, and technique for inhibiting the activity of androgen receptor (see Patent Documents 4 to 8). Previously, rhododendrol and its derivatives, Acer nikoense extract containing dobutyl alcohol It is known that it is possible to prevent and change the pigment deposition of skin such as spots and freckles (see Patent Documents 9 to u), but it is not known about the specific antibacterial effect of dulobenol or the like. [Patent Document 1] Japanese Patent Laid-Open No. 2002-145802, No. 137,291, doc, 200932, 205, PCT Patent No. 2, 883, 368, PCT Patent No. 2, 883, 368, PCT Patent Application No. Japanese Patent Laid-Open Publication No. JP-A-2004-161623 (Patent Document No. JP-A-2004-161623) [Patent Document 7] Japanese Patent Laid-Open No. Hei. No. 2006-241059 [Patent Document 9] Japanese Patent No. 3340928 Specification No. [Patent Document 10] Japanese Patent No. 3340935 (Patent Document 11) Patent Patent No. 345 No. 5406 [Non-Patent Document 1] FRAGRANCE JOURNAL, 2007, Vol. 35, No. 5, p. 12-17 [Non-Patent Document 2] COSMETIC STAGE, 2007, Vol. 1, No. 5, p. 23- [Non-Patent Document 3] FRAGRANCE JOURNAL, 2003, Vol. 31, No. 3, p. 23 to 28 [Invention] The present invention provides a skin external preparation for acne skin and an anti-P. acnes composition, which are characterized It is characterized in that it contains at least one selected from the group consisting of rhododendrol represented by the following formula (1) and a derivative thereof. [Chemical 1]

OH RO

(1) 137291.doc 200932205 (wherein R is a hydrogen atom, a fluorenyl group having 2 to 20 carbon atoms, or a sugar residue of a single enzyme or a second type). Further, the present invention provides a use of at least one or more selected from the group consisting of the above-mentioned crow alcohol and a derivative thereof for producing a skin external preparation for acne skin and an anti-caries acnes composition. Further, the present invention provides a acne treatment method and a treatment for p acnes infection, characterized in that at least one selected from the group consisting of the above-mentioned rhododendrol and a derivative thereof is applied to the skin. [Embodiment] The present invention provides an external preparation for acne skin, which is excellent in prevention and improvement of acne, and which can prevent and improve pigmentation of acne scars and is excellent in safety. The inventors of the present invention conducted research on the skin external preparation for acne skin and the anti-P. acnes agent for the above purpose, and as a result, it was completely unexpectedly found that: sterol or its derivative is less irritating to the skin, and is caused by acne. The bacterium 〇p. acnes has an excellent inhibitory effect on proliferation, and has a weaker effect on S. epidermidis, which is originally beneficial to the skin, and is compared with ascorbic acid or arbutin, compared with the previous anti-acne component. The prevention and improvement of acne scars is more effective.纟Invention of skin external preparations for the prevention and improvement of acne as a skin problem, and the prevention and improvement of pigmentation on acne lesions are excellent, and T #过刀Ψρ system is beneficial to maintain normal skin barrier function The skin is often colonized by bacteria. Further, the irritation to the skin is suppressed, and the safety as a skin external preparation is also sufficient. 137291.doc 200932205 Hereinafter, the configuration of the present invention will be described in detail. The compound of the above formula (1) used in the present invention, wherein R is a gas atom, is a well-known compound, and is also known in maple _ nikoence Maxim. This compound is contained in the like. Decocohol can be synthesized by a previously known method, and a commercially available product can also be used. Further, it can also be purified from the extract of maple. ❹

The optical isomers present in the Du Fu and the rhododendamine derivatives used in the present invention may be used alone (1), and the mixture of the optical isomers may also be used [represented as (1)' Japanese Patent Special Opening In the crow alcohol derivative represented by the formula (1) used in the present invention, the mercaptohydroduric acid having a carbon number of 2 to 20 is not particularly limited as long as it is a usual user. The Si-based compound can be easily obtained by thiolation of the rhododendrol by a previously known method. Here, examples of the fluorenyl group include an ethyl hydrazide group, a propyl aryl group, a butyl fluorenyl group, a amyl fluorenyl group, a hexyl fluorenyl group, and a hexamethylene laurel group. In terms of stability and ease of synthesis, it is preferred. It is a linear saturated sulfhydryl group. Further, examples of the fluorenated rhododendron used in the present invention include (+), (i), and (±) bodies such as hexamethylene sterol and acetamidine. In the rhododendhol derivative represented by the formula (I), the sugar residue in the rhododendron glycoside in which R is a sugar residue is a reducing monosaccharide or disaccharide bait body: glucose a monosaccharide such as galactose, xylose, mannose or N-acetylglucosamine, a cool class such as maltose, cellobiose, gentian disaccharide, etc. The presence of α-bond or β-bond in the glycoside of the present invention The heterogeneous 137291.doc 200932205 can be used alone or in combination. The azathioprine of the present invention can be used as a well-known method using the synthetic method of bearberry (USP No. 32〇1385). For example, it is possible to condense a ruthenium alcohol with an acetylated sugar by using a tri-degenerate butterfly or a helium-filled gas or the like as a catalyst in an organic solvent such as a stupid compound, and then detach the acetamidine group in the presence of a base. Thereby, the azadirachtin glycoside of the present invention can be easily obtained in the form of a white powder crystal. Further, it can be obtained by reducing the raspberry glucoside, and further, it can be obtained by separating from a natural product. In the glycoside of the invention, © 纟 optical isomerism The body ' can be used alone (+) or (i), and a mixture of these optical isomers (±) can also be used. As the specific glycoside used in the present invention, dantrol _ D-glucoside ( α and/or β body), rhodamine _D_galactoside (and/or mouth), rhodamine _D-xyloside (7) and/or β body), azadirachtin _D•maltoside (α and / Or (1) body, (1) body, (1) body, etc. 5 In the mysterious crow alcohol and its derivatives, 'the anti-P. acnes effect is strong, the anti-ρ • acnes effect is different from the antibacterial effect on the skin resident bacteria. . The content of the rhododendrol or a derivative thereof used in the present invention is preferably in the case where the R of the formula (1) is a hydrogen atom, and is based on the total amount of the external preparation for skin or the composition. It is 〇1 to 5 mass%, more preferably 〇3 to 5 mass%, and particularly preferably 0.4 to 3 mass%. Further, in the case where R is a fluorenated rhododendyl group having a carbon number of 2 to 20, the total amount of the external preparation for skin is preferably from 1 to 7 mass%, more preferably 0.3. ~6 quality. /〇, particularly preferably 0.5 to 5% by mass. Further, in the case where r is a sugar residue, the alkaloid glycoside 13729I.doc 200932205, based on the total amount of the external preparation for skin, preferably 〇丨7 mass% 'better is 〇.3~6 Quality ❹ /. Especially good is 〇5~5 mass%. In this range, not only is the antibacterial effect of p. acnes particularly excellent, but it can also minimize the effects on other beneficial skin-contained bacteria. Degree of freedom. In the present invention, in addition to the above-mentioned active ingredient, a plant extract which promotes epidermal cell cerebral ceramide sigma and/or an inflammatory inhibitory effect is formulated in an external preparation for acne skin, thereby further improving the acne pretreatment. Beta prevention, improvement, and prevention and improvement of acne scars. As the substance for promoting epidermal cell ceramide synthesis in the present invention, nicotinamide, carnitine, yeast extract or a culture containing the same may be mentioned. In the present invention, these substances are used alone or in combination of two or more kinds as needed, and are blended with the above-mentioned sterols in an external preparation for skin for acne skin. The nicotine amide used in the present invention is a well-known substance which can be extracted from natural matter (rice bran, etc.) or can be synthesized by a well-known method. The content of the final guanamine in the present invention is preferably from (7)% by mass, particularly preferably 〇% by weight based on the total amount of the medicinal agent or composition. The meat used in the present invention is a tetramethylamino-based butylbutyric acid, which is a well-known substance. Carnitine in this application refers to L-carnitine, DL-meat, and the hydrochloride of such meats, and derivatives of such substances. In the above-mentioned carnitines, it is preferred to use the hydrochloride of carnitine, i.e., gasification. In particular, the hydrochloride salt of carnitine, that is, L-carnitine chloride can be used. - the base and the hydrochloride of the carnitine, and the derivatives of the substances in the skin cosmetic preparations of 137291.doc 200932205, have been disclosed (Japanese Patent Laid-Open No. 51_ 148042) It is known that carnitine can enhance the barrier strength of the epidermis (Japanese Patent Laid-Open (1) 302143). However, it has not been reported that the pre-treatment, the improvement, and the prevention and improvement of the acne scar are improved by the combination of at least one of pedestal and/or a derivative thereof. The content of the carnitine in the present invention is preferably from 0.05 to 5% by mass based on the total amount of the external preparation for skin or the composition, and particularly preferably 〇丨~詈. Stem As the yeast extract or the culture of the bacterium which is used in the present invention, the yeast extract disclosed in Japanese Laid-Open Patent Publication No. Hei 08-217658, or the culture of the bacterium containing the same, or the like. For the yeast extract, commercially available reagents, industrial yeast extracts, and the like can be exemplified, and specific examples thereof include yeast extracts for reagents (manufactured by Difc® & Division), and Cytodyne as a yeast extract for industrial raw materials. (Manufactured by BR〇〇KS INDUSTRIES), Cyt〇CatalyZer (manufactured by Bi〇_DELL), plant〇s〇l _ (manufactured by Arch Personal Care Pr〇ducts L p), T〇msKiN (manufactured by Silab), etc. . In addition, the culture of the bacterium containing the yeast extract used in the present invention may, for example, be a lactic acid bacteria culture cultured in a medium containing a yeast extract or a bacterial culture of a mushroom. Examples of the lactic acid bacteria include Strept〇c〇ccus thermophilus, Lactobacillus bulgaricus, and Streptococcus Iactis, and also as the Grignard strain. For example, Lentinus edodes, Pleurotus ostreatus, Flammuiina velutipes, I37291.doc 200932205

Tuber magnatum (Turk's truffle), Tuber melanosporum (black truffle), etc. Specific examples of the culture containing the yeast extract include whey CPA (registered trademark) manufactured by ICHIMARU PHARCOS Co., Ltd., Fermentage Pear B or Achromaxyl manufactured by Arysta LifeScience Co., Ltd., and the like. It is preferred that the content of the yeast extract or the culture containing the same in the present invention is 'in the case of the yeast extract' (in dry solids) based on the total amount of the external preparation for skin or the composition. 0·001 to 5 mass 〇/〇, particularly preferably 0.005 to 0.5% by mass. Further, in the case of the culture containing the yeast extract, (in terms of dry solid content), based on the total amount of the external preparation for skin or the composition, it is preferably 0.005 to 2% by mass, particularly preferably 0.01 to 10% by mass. If the content is within the above-mentioned preferred range, the prevention and improvement of acne and the prevention and improvement of acne scars are particularly excellent, and a good preparation can be obtained in terms of color and odor. Examples of the plant extract having an inflammation suppressing effect in the present invention include: Gardenia Florida, paeonia Albifl〇ra root, Lonicera japonica flower, and Zizyphus jujuba fruit. Citrus unshiu peel, Citrus aurantium amara peel, Phell〇dendr〇n amurense bark, Betula alba bark, MeHssa 〇fficinaiis leaf, Artemisia princeps Leaf) The resulting extract. In the present invention, in terms of improving the prevention and improvement of acne and the prevention and improvement of acne scars, it is more preferable to formulate at least one selected from the group consisting of the plant extracts 137291.doc 14 200932205. . The blending amount of the plant extract having an inflammation inhibiting effect in the present invention is a dry solid fraction based on the total amount of the external preparation for skin or the composition; preferably, it is 0,01 to 20% by mass, more preferably It is 〇〇5~1〇% by mass, especially preferably 0.1~5 mass ❶/. . If the content is in the above-mentioned preferred range, the improvement of the acne and the improvement of the acne scar and the effect of improving the effect are particularly exemplified. In the towel of the present invention, the anti-sebum (four) related substance is known to be selected from the selected materials. The components of the group consisting of heart alcohol and sterol Z and its derivatives, which are based on salt bismuth (tetra) alcohol, can also improve the treatment of acne. Specific examples of the vitamin B6 related substance f include hydrochloric acid, octanoic acid, arsenic alcohol, galantimonic acid, glycyrrhizic acid, pyridinium dilaurate, and pyridoxine tripalmitate. , pyridinium phosphate, pyridoxine, and the like. In addition to the above ingredients, the above-mentioned ingredients are formulated with well-known plant extracts, phytochemicals, and medicinal ingredients. As plant extracts, there are listed kernels. Saxifrage, tea fruit, sapling, :/:, honeysuckle, peach juice, wheat germ, ...", moon peach leaf, apricot fruit kum fruit, and,,, *, 17 degree ancient eucalyptus leaves, West Indian cherry Seeds, Chinese cabbage, rose hips, candied dates, black tea, the yam, λ poor ^ Malong umbrella, sea bream, : two people 山, arnica, ginkgo, chamomile, sophora, mulberry, seven, brown algae, thyme The extract, also cuts a little pear oil, grape Xuan oil 0 乍 is an acid yeast, can be cited as lotus _ as a drug Zasuke 4 seeds, soy milk yeast, etc., can be cited as: ethyl glucose bud , sodium hyaluronic acid, Gan I37291.doc 200932205 oxalic acid-dehydrogenation age, L_alanine, L_proline, [_serine, N-methyl-L-serine, mevalonic acid Ester (mevai〇n〇丨act〇ne), flavin gland, nucleus dinuclear (tetra) di-nano, fertility expectant acetic acid δ, fertility secret test vinegar, _ Carrot streptozotocin, cerebral Amides 2, 3 brain Amides like. ❹

Further, in the external preparation for skin or the composition of the present invention, in addition to the above-mentioned components, the effect of the present invention can be prevented without undue adjustment of other components, such as an oil agent, which are usually formulated in a usual drug, a quasi drug, a cosmetic or the like as needed. , humectants, surfactants, tackifiers, anti-corrosion metal ion chelating agents, enthalpy regulators, 7 phenols, chemical reagents, UV absorbers, extraneous scattering agents, pigments, fragrances, etc. [Examples] Hereinafter, the features of the present invention will be described in detail based on examples and comparative examples, but the present invention is not limited by the examples. Further, the % of the blending amount in the examples is mass 〇/0. Example 1 (Evaluation of Antibacterial Property) The characteristics of the antibacterial property of the Durantol of the present invention were evaluated in accordance with the following antibacterial test. (Test: Wanfa) The antibacterial property was evaluated by measuring the minimum growth inhibitory concentration (mIC' mg/mL) according to the fat-filled plate dilution method of the Japanese Society of Chemotherapy. That is, the evaluation sample is added so as to be [5000, 1000 (), 15 = (10) Kg / mL], or [62.5, 125, 25 〇, 5 〇〇, (10) ζυυυ, 4 〇〇〇 pg / mL] The medium was prepared, and the proliferation of various microorganisms dried in the table was evaluated using the medium. About the medium, I: 137291.doc • 16 - 200932205 acnes using brain heart extracts in the soil fat medium, using clot alfalfa agar medium for c. albicans (Candida albicans, Candida albicans), and soy protein protein for other microorganisms On agar medium, P. acnes was cultured under anaerobic conditions for 72 hours at 37 ° C. C· albicans was cultured at 25 ° C for 72 hours under aerobic conditions, and other microorganisms were cultured at 30 ° C under aerobic conditions. After 48 hours, the proliferative properties of the microorganisms were confirmed. The results are shown in Table 2. [Table 1] Chinese name name strain number S. epidermidis Staphylococcus epidermidis IAM 1296 S. epidermidis Propionibacterium acnes RIMD 1640001 P. acnes Corynebacterium xerosis ATCC 373 C. xerosis Escherichia coli IAM 1239 E. coli Pseudomonas aeruginosa IAM 1007 P. aeruginosa Bacillus subtilis IAM 1069 B. subtilis Staphylococcus aureus IAM 12082 S. aureus Candida albicans IFO 0579 C. albicans [Table 2] Minimum growth inhibition of test bacteria Concentration (MIC, pg/ml) resveratrol isophthalic acid isopropyl methyl phenol vitamin C glycoside β arbutin S. epidermidis 10000 4000 125 15000<15000< P. acnes 2000 2000 250 15000<15000< C. xerosis 4000 2000 125 15000<15000< E. coli 4000 4000 250 15000<15000< P. aeruginosa 10000 2000 1000 15000<15_< B. subtilis 10000 4000 125 15000<15000< S. aureus 4000 4000 125 15000<15000< C. albicans 5000 100 00 250 15000<15000< As can be seen from Table 2 above, the antibacterial activity of the rhododendol of the present invention against p. acnes, E. coli, S. aureus and the like having the highest pathogenicity is the same as that of resorcinol. 17- 200932205 Strong 'other side' has a weaker antibacterial effect on the skin s epidermidis. Example 2 to 5 'Comparative Examples 1 to 5 (External Agent for Skin for Acne Skin) The external preparation for skin for acne skin (lotion) was prepared according to the formulation shown in Table 3 below and evaluated according to the following evaluation method. Its anti-acne effect and skin irritation were evaluated. [Table 3] -_ P Dosage (°/〇) Example Comparative Example 2 3 4 5 1 2 3 4 5 Dobutanol 0.8 0.1 3 5 Benzene II 08 Isopropylmethylphenol 01 Vitamin C glycoside ns Cold Arbutin 0.8 13-丁二-蜉5 5 5 5 5 5 5 0.5 0.5 Polyoxyethylene (60) hardened castor oil 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 Ethanol 5 5 5 5 5 5 5 5 5 Purified water remaining Remaining amount remaining amount remaining amount remaining amount remaining 鼋 remaining scene remaining 詈 remaining scene & good 4 1 4 5 0 5 0 0 0 acne slightly improved 4 4 5 5 3 3 2 1 1 improved no change 2 5 1 0 4 1 5 6 6 Slightly worsened 0 0 0 0 3 1 3 2 3 Anti-spasm deterioration 0 0 0 0 0 0 0 1 0 Improved effect 3 2 4 5 0 0 2 1 0 Slightly improved 4 3 4 4 3 0 3 4 0 No change in symptoms 3 4 2 1 3 6 4 3 5 Slight deterioration 0 1 0 0 2 3 1 2 2 Deterioration 0 0 0 0 2 1 0 0 3 Skin irritation 2 1 2 2 7 10 5 3 2 ❹

(Evaluation method) • The effect of acne improvement is set to 1 group of males (female 5, female 13729 丨.doc -18- 200932205 5) of the 18- to 30-year-old adult with acne. The samples were evaluated for evaluation. After washing the face with the same cleansing soap twice a day in the morning and evening, each evaluation sample was used in the f-type (bHnd). By visual inspection and photo shooting, compare the acne status before and after the use of the face to "improvement", "slight improvement", "no change", "slightly worse" and "deterioration". Changes are judged. • The acne scar improvement effect allows the evaluator of the above-mentioned “acne improvement effect” to continue to use the sample, and by visual inspection and photo shooting, the acne of the face after 4 weeks from the start of use|improvement”, the state of the five grades on the scar and After 1 week, the status was compared and evaluated by "slight improvement", "no change", "slightly worse", and "deterioration". • Skin irritation Let users beta temper each sample to the skin, and record the number of people who feel irritating during use as a result. (Evaluation results)

As a result of the s-validation shown in Table 3, it was found that the skin external preparations of the present invention of Examples 2 to 5 were superior in the acne-improving effect and the acne scar-improving effect as compared with the skin external preparations of any of the other comparative examples. Further, regarding the skin irritation, the subject who felt the irritation was very less than the comparative example. Examples 6 to 11 (External preparation for skin for acne skin) The anti-acne effect and skin irritation of the external preparation for skin for acne skin (make lotion) were prepared in the same manner as the above test according to the formulation shown in Table 4 below. Sexual evaluation. As is apparent from the evaluation results shown in Table 4, the anti-acne skin external preparation of the present invention has an excellent effect. 137291.doc • 19· 200932205 [Table 4] Formulation amount (°/〇) Example 6 7 8 9 10 11 Rhodamine 0.8 0.8 0.8 0.8 0.8 0.8 Nicotinamide 0.5 Gasified L-carnitine Cytocatalyzer (Note 1) Cytodyne (Note 2) 0.5 0.5 0.5 Yeast Liquid ZB (Note 3) Fermentage Pear B (Note 4) 0.5 0.5 1,3-butanediol 5 5 5 5 0.5 0.5 Polyoxyethylene (60) hardened castor oil 0.05 0.05 0.05 0.05 0.05 Ethanol 5 5 5 5 5 5 Purified water Remaining amount Remaining amount Remaining amount Remaining amount Remaining amount Residual amount improvement 6 4 5 6 4 7 Slight improvement 3 6 3 2 5 1 Improvement in treatment No change 1 0 2 2 1 2 Slight deterioration 0 0 0 0 0 0 Deterioration 0 0 0 0 0 0 Improvement 3 5 2 3 3 2 Slight improvement 6 4 5 4 5 6 No change in cancer treatment 1 1 3 2 2 2 Slight deterioration 0 0 0 1 0 0 Deterioration 0 0 0 0 0 0 Skin irritation 0 2 1 2 2 2 Q (Note l) Manufactured by BIO-DEL (Note 2) Manufactured by BROOKS INDUSTRIES (Note 3) Manufactured by ICHIMARU PHARCOS (Note 4) Manufacturing Example of ICHIMARU PHARCOS 1 2 to 26, Comparative Examples 6 to 7 (external preparation for skin for acne skin) according to Table 5 and Table 6 below. In the formulation shown, an external preparation for acne skin (emulsified composition) was prepared in the following manner. That is, the (A) component and the (B) component are uniformly dissolved at 75 ° C, respectively, and then 137291.doc -20-200932205 is added to the component (A) with stirring, and the component (B) is added and emulsified and dispersed, and then While maintaining this state, the mixture was cooled to 50 ° C while stirring, and the component (C) was blended, and the temperature was cooled to 30 ° C to prepare a skin external preparation for acne skin. [table 5]

_ (described in Table 6) [Table 6] Reference Example 12 Example 13 Example 14 Example 15 Example 16 Example 17 Example 18 Example 19 Example 20 Example 21 Example 22 Example 23 Example 24 Example 25 Example 26 Azathiol or its derivative, rhododendrol, rhodamine-D-glucoside, ruthenium, anthraquinone, azalea, alkaloid, rhododendron, galactosyl, rhodamine, rhodamine, rhodamine, rhodamine, rhodamine, rhodamine, rhodamine, rhododendron Alcohol-D-glucoside, ruthenium, ruthenium, ruthenium, anthraquinone, rhodamine-D-galactoside 1.5 1 0.7 0.1 0.5 1.5 2 2.5 0.8 1 1.5 Plant extract (Note) Radix Astragali extract, peony extract, honeysuckle extract Jujube extract, tangerine peel extract, bitter orange peel extract, cork extract, white birch extract, bee leaf extract, worm leaf extract 0.1 0.1 0.] 0.1 0.10.1 0.1 0.10.1 0.1

Comparative Example 7 Phyllostachys pubescens extract Chili violet extract 0.10.1 137291.doc 21 - 200932205 Eight plant extracts having an inflammatory inhibitory effect, added to the weight of each plant material, 50% by weight of 1,3· Butanediol was allowed to stand at room temperature for 7 days while stirring, and the extract obtained by clarification filtration was obtained. The anti-acne effect and skin irritation of the external use of the skin of the acne skin prepared in the above manner were evaluated in the same manner as the above test. The results are shown in Table 7. [Table 7] 实施 实施 Embodiment 12 Embodiment 13 Embodiment 14 Embodiment 15 Embodiment 16 Embodiment 17 Embodiment 18 Embodiment 19 Embodiment 20 Example 21 Example 22 Example 23 Example 24 Example 25 Example 26 Comparative Example 6 Comparative Example 7 6 4 5 5 4 6 0 0 Slight improvement Γ 5 2 3 2 2 2 1 2 1 3 3 2 2 1 0 1 Acne improvement 1 0 2 1 2 4 2 2 0 0 4 4 3 5 6^ 5 6 Anti-acne effect slightly deteriorated 0 1 0 1 1 0 0 0 0 0 1 2 2 2 0 4 2 Deterioration 0 0 0 0 0 0 0 0 0 0 1 0 Skin irritation 〇1 〇❶ 〇0 ❶ 0 2 0 1 _ Cancer scar improvement slightly improved i change i deteriorated j deteriorated 6 3 1〇〇5 2 2 1 0 6 13〇4 3 2 1 7 11〇4 2 1 4 2〇〇3 1〇5 5 0 〇〇6 4 0 0 2 3 2 2 1 2 2 3 3 3 4 2 2 3 2 5 2 I 0 1 3 2 6 2 〇〇2 3 4 As shown in Table 7, the results of the present invention are not The anti-acne effect was remarkably excellent in the examples as compared with the comparative examples. It is also known that the case where the plant extracts are used in combination (Examples 12 to 21) is used in comparison with the case where only the rhododendrols are blended (Examples 22 to 26). The anti-acne effect is enhanced, especially excellent. Further, according to the following formulation, various anti-acne skin external preparations were prepared by the usual method, and various evaluation tests were carried out, and the results showed excellent anti-acne effects, and no skin irritation was observed. Application example ι (makeup) Raw material ingredients _ blending amount (%)

Dipropylene glycol 12.0 concentrated glycerol 5.0 sucrose fatty acid ester (*1) 0.1 ten glycerol monolaurate vinegar 0.05 rhododendron 1.0 ethyl glucoside 0.02 sodium hyaluronate (*2) 0.05 citric acid 0.01 sodium citrate 0.09 phenoxyethanol 0.1 Prolineamine 0.5 Licorice Extract (*3) 0.1 Yeast Extract (Note 3) 0.1 Lotus Seed Extract (*4) 0.05 Tangerine Extract (* 5 ) 0.05 薏苡 Extract (*6) 0.05 Jujube Extract (*7) 0.05 Lonicera japonica extract (*8) 0.05 Peach extract (*9) 0.05 Hazelnut extract (* 10) 0.05 137291.doc -23- 200932205 Saxifrage extract (1 211) 0.05 Tea fruit extract (212) 0.01 Camellia Extract (213) 0.01 Orchid Extract (2 14) 0.05 Moon Leaf Extract (2 15) 0.05 Purified Water Remaining • 24· 1 *1 : SURFHOPE SE COSME C_1216 (Mitsubishi Chemical Food Co., Ltd. *2 : Hyaluronic acid FCH-SU (manufactured by KIBUN FOOD CHEMICAL CO., LTD.) *3 : Licorice extract BG-J (manufactured by Maruzen Pharmaceutical Co., Ltd.) *4: Lotus fruit (manufactured by TECHNOBLE) *5 : Tangerine extract BG (Maruzen Manufactured by a pharmaceutical company) *6: Coix seed extract BG-S (pill Manufactured by a pharmaceutical company) *7: Jujube extract BG-J (manufactured by Maruzen Pharmaceutical Co., Ltd.) *8 : Pharcolex Lonicera SB (manufactured by ICHIMARU PHARCOS) *9 : Pharcolex Peach B (manufactured by ICHIMARU PHARCOS) *10 : Pharcolex B (manufactured by ICHIMARU PHARCOS) * 11 : Saxifrage extract QCHIMARU manufactured by PHARCOS) *12: Tea fruit extract (manufactured by Maruzen Pharmaceutical Co., Ltd.) 2 13 : Camellia seed extract (made by Maruzen Pharmaceutical Co., Ltd.) *14 : Pharcolex Orchid (manufactured by ICHIMARU PHARCOS) *15: Moon peach extract bg (manufactured by Maruzen Pharmaceutical Co., Ltd.) Application example 2 (makeup) 137291.doc 200932205 Ingredients _ Formulation amount (%)

Ethanol 5.0 1,3-butanediol 4.0 concentrated glycerin 2.0 diglycerin 1.0 polyoxyethylene hardened castor oil (60E.O.) 1.0 polyoxyethylene sorbitan monolaurate (20E.0.) 0.3 rhododendron - D-glucoside 2.0 Glycyrrhizic acid diclination 0.1 Potassium dihydrogen phosphate 0.07 Acidic acid monohydrogen sodium 0.03 Dehydroabietyl alcohol 0.01 Hydroxybenzoic acid methyl ester 0.1 Glycine 0.01 L-alanine 0.01 L-proline acid 0.01 L-serine 0.01 N-methyl-L-serine 0.1 L-chlorinated meat test 0.5 Mixed fruit extract (* 16) 0.05 Apricot juice (*17) 0.05 Wheat germ extract (*18) 0.05 Dr Grass extract (* 19) 0.05 Indian bitter leaf extract (*20) 0.05 137291.doc -25- 200932205 ❺ ❷ Betula platyphylla extract (*21) 0.1 peony extract (*22) 0.1 Bitter orange peel extract (* 23) 0.1 Purified secondary ember *16 : Multifruits BSC (manufactured by Arch Personal Care Products) *17: Apricot extract k (manufactured by ESPERIS) 氺1^ : Clariskin (manufactured by Silab) *19 : Dr. Pharcolex (N) (manufactured by ICHIMARU PHARCOS) *20: Indian Bitter Leaf Extract B (ICHIMARU PHARCO) *Manufactured by company S) *21 : Betula extract BG (manufactured by Maruzen Pharmaceutical Co., Ltd.) *22: Peony extract BG-JC (manufactured by Maruzen Pharmaceutical Co., Ltd.) * Ο · Bitter orange peel extract B (manufactured by ICHIMARU PHARCOS Co., Ltd.) Application example 3 (Emulsion) Invited L component blending *ί%) Ethanol 10.0 Polyoxyethylene hardened castor oil (40E.O.) 1.0 Nonylphenyl polyoxyalkylene 1.0 Dipropylene glycol 5.0 Concentrated glycerin 2.0 Hexammonium 1.5 Hyaluronic acid (*2) 0.1 137291.doc -26- 200932205 Carboxyvinyl polymer 0.3 Potassium hydroxide 0.15 Phenoxyethanol 0.1 West Indian cherry seed extract (124) 0.1 Came extract (125) 0.1 Fragrant bee leaf extract (126) 0.1 Artemisia argyi extract (127) 0.1 Mevalonolactone 0.1 Flavin adenine dinucleotide disodium (128) 0.01 Final test guanamine 1.0 Hydrochloride 哆 sterol 0.1 Tris(2-hexyl decanoic acid η 哆 哆 ( (129) 0.1 Ascorbyl sulfate disodium (130) 0.1 Tocopherol acetate (131) 0.1 β carotene (132) 0.001 Purified water remaining ❹

137291.doc •27- 1 24 : NICHIREI West Indian Cherry Seed Extract B30 (manufactured by NICHIREI) *25 : NICHIREI Came Extract B3 0 (manufactured by NICHIREI) *26 : Pharcolex Fragrant Bee B (ICHIMARU PHARCOS) Manufactured *27: Ai Ye extract BG (manufactured by Maruzen Pharmaceutical Co., Ltd.) *28 : FAD (manufactured by Kyowa Co., Ltd.) *29 : NIKKOL VB6-IP (manufactured by Shuko Chemical Co., Ltd.) 200932205 *30 : VC-SS (NIHON SURFACTANT) Manufactured by the company *31 : dl-α-tocopherol acetate (manufactured by EISAI) *32 : β-carotene (manufactured by ROCHE)

Application Example 4 (Emulsion) Condiment Composition Hydrogenated Soybean Lipid 1.0 Cholesterol 0.5 Squalene 2.0 Australian Pecan Oil Fatty Acid Plant Sterol 0.5 Cerebral Amine 2 (*33) 0.5 1,3-Butanediol 3.0 Concentrated Glycerin 3.0 Polyglycerol 1.0 squalene 1.0 toluene 1.0 final test guanamine 1.0 sodium hyaluronate (*34) 0.1 acrylic acid alkyl methacrylate copolymer 0.05 three immortals 0.05 sodium hydroxide 0.02 phenoxyethanol 0.3 licorice extract (*3) 0.1 Yeast Extract (*4) 0.1 Chenpi Extract (*5) 0.05 137291.doc -28- 200932205

薏苡 Extract (*6) 0.05 Jujube Extract (*7) 0.05 Honeysuckle Extract (*8) 0.05 Peach Extract (*9) 0.05 Hazelnut Extract (* 10) 0.05 Saxifrage Extract (*11 0.05 Tea extract (*12) 0.01 Camellia extract (*Π) 0.01 Orchid extract (*14) 0.05 month peach leaf extract (* 15) 0.05 Purified spunlace balance*: 33: ceramide TIC- 001 (manufactured by Takasago Co., Ltd.) *34: Hyaluronic acid FCH (FCH-120) (manufactured by KIBUN FOOD CHEMICAL Co., Ltd.) Application Example 5 (skin cream) Raw material ingredient amount ί%) Recorded decyl alcohol 5.0 oleophilic monostearate Ester 1.0 Polyoxyethylene cetyl ether (2E.O.) 0.1 Sucrose fatty acid ester (*35) 0.5 Plant squalene 1.0 Refined jojoba oil 1.0 Refined Australian walnut oil 0.5 Hydrogenated polyisobutylene 0.5 137291.doc - 29- 200932205 ❹ ceramide 3 (136) 0.1 tocopherol nicotinic acid 0.1 tris(2-hexyl decanoic acid) pyridoxine (129) 0.1 eucalyptus oil (137) 0.1 avocado oil (138) 0.1 grape seed Oil (139) 0.1 Concentrated Glycerin 5.0 Rhodamine 2.5 Gasified L-Carnitine 1.0 Cork Extract (140) 0.1 Phenoxyethanol 0 .2 gas phenylglycol ether 0.1 potassium hydroxide 0.3 spice 0.02 purified water

137291.doc -30- 1 35 : Sugar wax A-10E (manufactured by Sakamoto Daiichi Pharmaceutical Co., Ltd.) *36 : Ceramide IIIA (manufactured by COSMOFARM) *37 : Cropure OL (manufactured by CRODA JAPAN) *38 : CropureAvocado ( Manufactured by CRODAJAPAN) *39: Grape seed oil (manufactured by Shuguang Chemical Co., Ltd.) *40 : Cork extract BG-J (manufactured by Maruzen Pharmaceutical Co., Ltd.) Application example 6 (cosmetic liquid) Raw material composition ____ formulated amount (%) Ethanol 7.0 200932205 1,3-butanediol 5.0 concentrated glycerol 5.0 polyethylene glycol 1000 1.0 defatted acid lecithin 0.3 polyoxyethylene hardened castor oil (40E.O.) 0.5 diisostearic acid polyglycerol 0.5 rhododendrol-D- Glucoside 2.5 Sodium Hyaluronate (*2) 0.3 ® Carrageenan 0.2 Phenoxyethanol 0.2

Fermentage Pear B(Note 4) 0.1 Hydrochloric acid "Petolol 0.05 Chenpi Extract (*5) 0.05 薏苡 Extract (*6) 0.05 Jujube Extract (*7) 0.05 Honeysuckle Extract (*8) 0.05 Peach Extract (*9) 0.05 Hazelnut Extract (*1〇) 0.05 Peony Extract (*22) 0.05 Bitter Orange Extract (*23) 0.05 Soymilk Extract (*41) 0,01 Watercress Extract (*42) 0.01 Rosehip Extract (*43) 0.01 Candied Date Extract (*44) 0.01 137291.doc -31 - 200932205 Black Tea Extract (*45) Oolong Tea Extract (*46) Seaweed Extract (*47)茯苓 Extract (*48) Astragalus Extract (*49) Caffeine (*50) Arnica Extract (*51) Ginkgo Biloba Extract (*52) Chamomile Extract (*53) Sophora flaves Extract ( *54) Mulberry white extract (*55) Horse chestnut extract (*56) Brown algae extract (*57) Thyme extract (*58) Purified water ___ 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 #1余量

*41 *42 *43 *44 *45 Soymilk broth (manufactured by Japan's three provinces) WATERCRESS KB (manufactured by Silab) Rosehip extract BG-R (manufactured by Maruzen Pharmaceutical Co., Ltd.) Candied extract WC (manufactured by Maruzen Pharmaceutical Co., Ltd.) Black tea extract (manufactured by ICHIMARU PHARCOS) *46 : Pharcolex Oolong Tea E (manufactured by ICHIMARU PHARCOS) *47 : Phyco ARL EDTA (manufactured by Codif) *48 : Pharcolex(R) B (manufactured by ICHIMARU PHARCOS) 137291.doc -32 · 200932205 *49 : Pharcolex 蔘B (manufactured by ICHIMARU PHARCOS) *50: catechin (manufactured by White Bird Pharmaceutical Co., Ltd.) *51: Arnica extract BG (manufactured by Maruzen Pharmaceutical Co., Ltd.) *52: Ginkgo biloba extract BG ( Manufactured by Maruzen Pharmaceutical Co., Ltd. *53: Chamomile extract BG-J (manufactured by Maruzen Pharmaceutical Co., Ltd.) *54 : Pharcolex Kushen B (manufactured by ICHIMARU PHARCOS) *55 : Pharcolex Sangbai BG (manufactured by ICHIMARU PHARCOS) ® *56 : Horse chestnut extract BG-J (manufactured by Maruzen Pharmaceutical Co., Ltd.) *57 : Pharcolex brown algae (manufactured by ICHIMARU PHARCOS) *58: Thyme extract BG (manufactured by Maruzen Pharmaceutical Co., Ltd.) [Industry Use of the skin for external use of acne skin of the present invention can be used as a preventive and remedy for acne, and can prevent and improve the pigmentation of acne scars, and has a small skin irritation and excellent safety. drug.

137291.doc -33-

Claims (1)

200932205 X. Patent application garden: 1. A skin external preparation for acne skin, characterized in that it contains at least one selected from the group consisting of rhododendrol and its derivatives represented by the following formula (1) , [Chemical 1] 0 (wherein, the ruler is a hydrogen atom, a fluorenyl group having 2 to 20 carbon atoms, or a sugar residue of a monosaccharide or a disaccharide). 2. The skin external preparation for acne skin according to claim 1, wherein the content of one or more selected from the group consisting of rhododendrol and a derivative thereof is 0.1 to 5 mass 〇/〇. For example, the skin external preparation for acne skin of claim 1 further contains a substance which promotes synthesis of brain-enhancing amine. 4. The skin external preparation for acne skin according to claim 3, wherein the substance which promotes synthesis of ceramide is selected from the group consisting of nicotine amide, carnitine, yeast extract, and culture containing the bacteria containing Q thereof. At least one or more. 5. The skin external preparation for acne tendon according to any one of claims 1 to 4, which further comprises a plant extract having an inflammatory inhibitory effect. 6. The skin external preparation for acne skin according to claim 5, wherein the plant extract having an inflammation suppressing effect is selected from the group consisting of Gardenia Florida, Paeonia Albi Hora root, Lonicera japonica flower, and jujube (Zizyphus jujuba fruit), Citrus unshiu peel, citrus aurantium amara peel, Phellodendron amurense bark, white birch (Betula 137291.doc 200932205 alba bark), fragrant bee leaf (MeHssa 〇fficinaHs ieaf) And at least one or more extracts in the group of Artemisia Pdnceps leaf. And a p. acnes composition comprising at least one selected from the group consisting of a crow alcohol represented by the following formula (1) and a derivative thereof, ] (1) (wherein R is a hydrogen atom, a fluorenyl group having 2 to 20 carbon atoms, or a sugar residue of a monosaccharide or a disaccharide). 8. The p. acnes composition according to claim 7, wherein the content of one or more selected from the group consisting of rhododendrol and a derivative thereof is 〇1 to 5 mass%. 137291.doc 200932205 VII. Designation of representative drawings: (1) The representative representative of the case is: (none) (2) The symbol of the symbol of the representative figure is simple: 8. If there is a chemical formula in this case, please reveal the best indication of the characteristics of the invention. Chemical formula: OH 137291.doc