TWI378799B - - Google Patents

Description

1378799 IX. Description of the invention: Long-term storage and stability [Technical field 1 of the invention] The present invention relates to a skin external application which is superior to the skin and has a high skin and whitening effect. [Prior Art] Usually, as a cosmetic The skin of the blended skin is used in various applications, and various kinds of pores and dispersions are used.

In order to ensure the long-term stability of the cosmetic in the normally stored warm surfactant to achieve the solubilization of the insoluble components, and the 'in the water or oil' is more affected by the temperature, the active agent must be managed. The amount of the preparation is set so much that it is not irritating to the skin. In addition, in the external preparation for skin which is usually formulated as a cosmetic, p-hydroxybenzoic acid or the like is generally used to prevent spoilage and deterioration caused by microorganisms. A preservative such as phenoxyethanol, but its irritation to the skin itself has long been regarded as a problem. In particular, in the near future, the skin is subjected to various external and internal stresses, such as dryness or ultraviolet rays, and the pollen that causes allergic symptoms, such as the psychological impact of social life, etc. The skin may become sensitive even if it is slightly stimulated. Therefore, the industry is seeking to pay more attention to irritating skin external preparations. Rhododendrol and its derivatives are known to prevent and improve the pigmentation of skin such as spots and freckles (refer to patent document 137274.doc « , ' · · -U ) 'but about the rhododendron and its streets The situation in which organisms are used for anti-corrosion prevention is not known. In addition, Du Qu and its sputum in the water towel rotation (four), formulated with a preparation of rhododendrol and its derivatives, especially in the almost no viscous lotion 2, in order to improve the stability of the preparation More polyoxyethylene bake-added nonionic surfactants, which are used as solubilizers, must be managed. Combinations of lower alcohols are a cause of increased skin irritation. [Patent Document 1] Japanese Patent No. 3340928 (Patent Document 2) 曰 Patent No. 334 〇 935 [Patent Document 3] 曰 Patent No. 34554〇6 (Invention) The present invention provides The external preparation for skin, which comprises: (4) one or more selected from the group consisting of azadirachtin represented by the following formula (1) and a derivative thereof, and (b) selected from the group consisting of a sugar fatty acid vinegar and a polyglycerin fatty acid. Vinegar makes it a species or two species • above, and (c) a polyol. [Chemical 1]

(In the formula, R is a hydrogen atom, a fluorenyl group having 2 to 2 carbon atoms, or a sugar residue of a monosaccharide or a disaccharide). [Embodiment] The present invention provides a skin external preparation which stably mixes sterol and its derivative 137274.doc * 6 - 1378799 into a skin external preparation, and reduces a surfactant which is considered to be a cause of skin irritation or The amount of the preservative added, and thus the irritancy, was actively studied by the inventors of the present invention and the like, and it was found that by using the sterol fatty acid ester and/or the sucrose fatty acid ester and/or When the polyglycerin fatty acid g is used in combination with a polyol, it is possible to obtain an external preparation for skin which is excellent in stability of the preparation, has low skin irritation, and is excellent in antiseptic and antifungal effects. According to the present invention, a skin external preparation capable of stably blending dodecyl alcohol and a derivative thereof can be provided. The towel of the present invention can suppress the use of a polyoxyethylene-added nonionic surfactant having a skin irritation problem and thus can reduce skin irritation. Furthermore, since the antifungal and antifungal effects of the rhododendrol and its derivatives are excellent, the use of the preservative such as the para-hydroxybenzoic acid ester or the phenoxyethanol can be suppressed, and the preservative can also be reduced. The skin irritation caused by the skin is provided to provide an external preparation for skin which is also excellent in safety. Hereinafter, the configuration of the present invention will be described in detail. In the external preparation for skin of the present invention, ascorbic acid represented by the following formula (1) or a derivative thereof is formulated as the component (a). [Chemical 2]

(In the formula, R is a hydrogen atom, a fluorenyl group having 2 to 2 carbon atoms, or a sugar residue of a monosaccharide or a disaccharide). 137274.doc [Si 1378799 In the above formula (1), rhododendrol [4_(p-hydroxyphenylbutanol) wherein r is a hydrogen atom is a well-known compound, and is known in maple (Acer nik0ence Maxim.) and the like. The compound may be synthesized by a conventionally known method, or a commercially available product may be used. Alternatively, it may be purified from the extract of maple. The rhododendrol and the rhododendrol used in the present invention are derived. The optical isomer may be present, and the (+) body or the (I) body may be used alone, or a mixture of the (+) body and the (I) body may be used (indicated as (±), Japanese Patent Laid-Open No. Hei. No. Hei. No. Hei. In the rhododendrol derivative represented by the formula (1), the fluorenated rhododendron having a fluorenyl group having a carbon number of 2 to 20 is not particularly limited as long as it is a usual user. The thiolated rhododendrol can be used. It is easily obtained by thiolation of rhododendol by a previously known method. Here, examples of the fluorenyl group include an ethyl group, a propyl group, a butyl group, a pentyl group, a hexyl group, and a fluorenyl group. Etc., in terms of stability and ease of synthesis, In addition, as the fluorenyl ruthenium alcohol used in the present invention, (+), (a), and (phantom) which are brewed with rhododendrol and acetamidine, etc. In the rhododendhol derivative represented by the formula (1), the sugar residue in the rhododendron glycoside having a sugar residue is a monosaccharide or a disaccharide which is reduced, and specific examples thereof include glucose. Monosaccharides such as galactose, xylose, mannose, and glucosamine, such as maltose, cellobiose, and gentiobiose. The sugar in the present invention has α-bond and β-bond. The isomers, which may be used singly or in combination, may be used. The azaleaf glycoside of the present invention may be a method known from the synthesis method of arbutin for the public 137274.doc 1378799 (USP No. 3201385) For example, by using trifluoro(tetra) or phase chloride as a catalyst in an organic solvent such as toluene, the rhododendron/acetate may be condensed, and then the ethyl sulfonyl group may be liberated in the presence of a base. The azadiitol sugar of the present invention is easily obtained in the form of white powder crystals Further, it can be obtained by reducing raspberry ketone glucoside. Further, it can be obtained by isolation from a natural product. Further, an optical isomer exists in the glycoside of the present invention, and (+) body can be used alone. (_) The mixture of the optical isomers (±) may also be used. As the specific glycoside used in the present invention, rhodamine-D-glucoside (α and β-form), rhodamine· ε>-galactoside (〇1 and !3 bodies), rhodamine-D-xylosides (α and β bodies), rhodamine _D_maltoside glucosides, and (+) bodies (±) Body: Among the components (a), the rhododendrol and its derivatives are particularly good in terms of antiseptic and mildew-proof effects and skin irritation. In the case where the content of the component (a) used in the present invention is in the case where R is a hydrogen atom in the general formula (1), it is preferably 0·1 to 1 based on the total amount of the external preparation for skin. 3 mass%, more preferably 0.2 to 3 mass%, particularly preferably 0.5 to 3 mass. . Further, in the case where r is a thiolated retinol having a carbon number of 2 to 20, based on the total amount of the external preparation for skin, it is preferably 〇·1 to 5 mass%, more preferably 0.5. ～5% by mass, particularly preferably 1 to 5% by mass. Further, in the case where R is a sterol glycoside of a sugar residue, it is preferably 0.1 to 5% by mass, more preferably 5% to 5% by mass, based on the total amount of the external preparation for skin. It is 1 to 5 mass%. If the content is within these ranges, the antiseptic and antifungal effects can be effectively exerted, and a wide degree of freedom in the formulation of the external preparation for skin can be obtained. In the external preparation for skin of the present invention, the non-ionic surfactant selected from the sucrose fatty acid ester and the polyglycerin fatty acid ester as the component (b) and the component (c) are blended together with the component (a). Polyol. Examples of the sucrose fatty acid ester include a sucrose mono-fatty acid ester, a sucrose di-fatty acid ester, and a sucrose tri-fatty acid ester. In the present invention, it is preferred to use a mixed sucrose fatty acid ester having the following ester distribution: Based on the total amount of sucrose fatty acid ester, the sucrose mono-fatty acid ester is 60 to 90% by mass. The curtain sugar bismuth fatty acid vinegar is 5 to 40% by mass. The fatty acid ester of the sucrose fatty acid ester is a saturated or unsaturated fatty acid having a carbon number of 12 to 18, which can be used as a blending ratio, such as lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, etc. The sucrose mono-fatty acid ester is preferably sucrose monolaurate or succinate monostearic acid. The average degree of polymerization of glycerin in the polyglycerin fatty acid ester used in the present invention is preferably from 2 to 16. The degree of esterification may, for example, be a monoester, a diacetate or a triester. In the present invention, the average degree of polymerization of glycerin is preferably from 2 to 10, and is a single vinegar. The fatty acid in the polyglycerin fatty acid ester used in the present invention is preferably a fatty acid having a carbon number of 10 to 18. Particularly preferably, lauric acid, myristic acid, citric acid, stearic acid, isostearic acid, oleic acid, linoleic acid or camellic acid can be exemplified. The polyglycerin fatty acid vinegar used in the present invention is commercially available in various forms, and as a particularly preferable polyglycerin fatty acid ester, it can be exemplified: ten glycerin monolauric acid vinegar, ten glycerin monooleic acid vinegar, ten glycerin monostearate vinegar Wait. I37274.doc 1Λ -1U - [S] 1378799 The specific nonionic surfactant (b) used in the present invention preferably has a HLB value (hydrophilic-lipophilic balance value) of 10 or more. Especially good is 11~18. If the HLB is in this range, the component (c) is easily formulated into the emulsified formulation, and particularly good results can be obtained in the stability of the component (a) in the formulation. Further, when two or more kinds of nonionic surfactants are used in combination, if the mixed HLB value is within the above range, the HLB value of a part of the nonionic surfactant may be 1 Torr or less. Here, the mixed HLB value is calculated by multiplying the HLB values of the respective non-ionic surfactants by the respective ratios and summing the obtained values. The HLB value of each nonionic surfactant can be calculated according to J. T. Davies and B. Κ Rideal, Interfacial Phenomea, Academic Press, New York 1963, pp. 371-383. The polyol (c) used in the present invention may, for example, be glycerin, diglycerin, 1,3-butylene glycol, polyethylene glycol, dipropylene glycol, propylene glycol, hexamethylene, isoprene glycol or erythropolis. Alcohol, xylitol, maltitol, trehalol, sorbitol, and the like. Among them, glycerin, hydrazine, 3-butanediol, and propylene glycol are particularly preferred. In the present invention, the component (b) and the component (c) act together to solubilize the (&) component, and when the external preparation for the skin is made into an emulsion, it functions as both an emulsifier and a preparation. The stability is related. The content of the component (b) of the present invention, i.e., the specific nonionic surfactant, is preferably from 1 to 5 by mass based on the total amount of the external preparation for skin. /. More preferably, it is 0'05 to 3 mass%. In the content range β, the basic functions of the surfactant 137274.doc I S1 1378799 are good solubilization, emulsifying, and dispersing, and the use of the skin external preparation is also excellent. Further, it is also less likely to cause irritation caused by the surfactant. Further, the content of the component (C), that is, the polyol, is preferably from 0.1 to 30% by mass, more preferably from 〇 to 20% by mass based on the total amount of the external preparation for skin. Within the above-mentioned range, the basic functions of the surfactant are solubilization, emulsification, and dispersion, and the use of the external preparation for skin is also excellent. The rhododendrol or its derivative used in the present invention has an excellent antibacterial effect itself, even if it is not formulated to prevent the primary and secondary pollution of the preparation, the paraben and/or phenoxyethanol. In the case, it is also possible to prevent spoilage and deterioration of the preparation caused by microorganisms. Therefore, it is preferred that the external preparation for skin of the present invention contains substantially no p-hydroxybenzoate and/or phenoxyethanol. The skin external preparation of the present invention may further contain a substance called "Firethorn" in Chinese. "Firethorn" is the genus R〇saceae pyracantha

One of the fruits of the fruit is called "Chiyangzi", which is known to have the effects of strengthening the spleen and treating indigestion. X, which has a guanylase activity inhibitory effect and a melanin production inhibitory effect, has been proposed as a whitening cosmetic formulated with an extract thereof (Japanese Patent Laid-Open No. Hei 5, 5587 公报). The fruit of the "Firethorn" is the active ingredient of the Chinese medicine called "Chiyangzi" (hereinafter referred to as "Firethorn Extract"), which is a mixture of lower alcohol such as water, methanol, ethanol or propanol or a mixture thereof. And extracted. The extract may be directly formulated in the external preparation for skin, and it is preferably used by powdering it by cold, east drying method or spray drying method. Alternatively, use 137274.doc •12· 1378799 • Liquid-liquid distribution, adsorption chromatography, etc. to purify the extract, and prepare the liquid. The Pyracantha extract obtained in this manner can also be used as a reducing agent for suppressing browning of a preparation caused by high temperature or light in terms of its characteristics. = - based on the total amount of the external preparation for skin, the content of the component (d) in the external preparation for skin of the present invention, that is, the above-mentioned pyracantha extract, is calculated by the solid matter of the extract, preferably 0.001 to 5 The mass% is more preferably 0.005 to 2% by mass. If it is within these ranges, the browning of the preparation can be more effectively inhibited. Further, when the external preparation for skin of the present invention contains a polyoxyethylene-added nonionic surfactant, there is a function of hindering the component (b) depending on the blending balance, and a stable blending of the rhododendrol or its derivative is In the case of a large influence, the content of the component (b) is 5% by mass or less, preferably 20% by mass or less, and particularly preferably, the polyoxygen is substantially not contained. Ethylene addition molding nonionic surfactant. Further, in addition to the above-mentioned essential components, the skin external preparation of the present invention may be appropriately formulated with other ingredients such as oils, such as oils, quasi-drugs, cosmetics, etc., as needed within the scope of the effects of the present invention. Agent, interface active biocide, tackifier, metal ion chelating agent, pH adjuster, water, alcohol, chemical reagent, ultraviolet absorber, ultraviolet scattering agent, pigment, fragrance, etc. Further, it can be made into any dosage form such as an ointment, a lotion, an emulsion, a cream, and a mask. [Examples] 137274.doc 1378799 Next, the present invention will be described in more detail by way of examples, but the invention is not limited to the examples. Furthermore, the blending amount is mass 0/〇. In the examples, the stability of the formulation was carried out by evaluation of the appearance of turbidity and precipitation, the evaluation of discoloration under accelerated conditions, and the evaluation of discoloration under exposure to sunlight. Further, the skin irritation was carried out by evaluation of the skin irritation of a group of female functional inspectors, and the antiseptic and antifungal properties were carried out by evaluation using standard bacteria. Hereinafter, specific test methods for each evaluation will be described. • Stability evaluation (1) After the evaluation sample was stored at 45 ° C for 2 months, its appearance (with or without turbidity and precipitation) was visually evaluated according to the following criteria. (Evaluation criteria) x : There is a large amount of precipitate or turbidity △: There is precipitation or turbidity 〇: There is a little precipitation or turbidity ◎: No precipitation, turbidity • Stability evaluation (2) The valence sample is stored under 601! After months The degree of discoloration was evaluated by visual comparison according to the following criteria. (Evaluation criteria) X: Severe discoloration △: Discoloration 〇: slight discoloration ◎: no discoloration • Stability evaluation (3) 137274.doc 1378799 After the evaluation sample was exposed to sunlight for one week, it was evaluated according to the following US standard visual comparison. Degree of discoloration (Evaluation Criteria) X : Severe discoloration Δ : Discoloration 〇: Slight discoloration® : No discoloration • Skin irritation evaluation by 20 female functional inspectors who believe that skin is sensitive (2 to 50 years old to 50 Many years) to evaluate. The female functional inspector was used twice a day for three consecutive days, and the test sample was used. On the last day, the feeling of skin irritation was evaluated based on the following criteria. One evaluation sample was evaluated once, and after 2 days of rest, the evaluation of the next evaluation sample was carried out in the same manner. (Evaluation Criteria) Score 3: Sensation of stimulation Score 2: Slightly felt stimulation Score 1: Almost no stimulation was found Score 0 ·· No stimulation was felt at all. The number of occurrences is taken as a result and shown in Table 4. From this, it was confirmed that the external preparation for skin of the present invention is also excellent in terms of low irritation. • Antiseptic and mildew resistance evaluation using fungi designated as standard bacteria [Aspergi丨lus niger ATCC 16404 'Blackface mildew ATCC 16404), yeast (Candida albicans 137274.doc -15- 1378799 ATCC 10231, Candida albicans ATcc 1023 1)] and bacteria (Escherichia coli ATCC 8739, E. coli ATCC 8739) strain, relative to each 1 g. Flat 4 shells. The mouth reaches the 1X10 colony forming unit (c〇l〇ny f〇rrning unit, hereinafter referred to as cfu), inoculates the mold cells or the yeast cultured 48 hours ago, or reaches lxl〇6 efu relative to the evaluation sample per 1 g. The bacteria cultured 24 hours before the inoculation were placed at room temperature. The number of viable microorganisms in the samples was evaluated by sputum measurement from the first day to the 28th day after the inoculation, and was evaluated in three levels according to the following criteria. Further, the lowest evaluation among molds, yeasts, and bacteria was evaluated as a comprehensive evaluation of antiseptic and mildew resistance. (Evaluation criteria) —------ 〇: The inoculated mold was reduced to less than lxl02cfu/g for 28 days. The inoculated yeast was reduced to less than ixi 〇 2 cfu/g for 28 days. The inoculated bacteria were reduced to less than lxl 〇 2 cfu/g for 14 days. ---------- △: The inoculated mold was reduced to 1Χ1〇2~ixl04 efu/g in 28 days. The inoculated yeast was reduced to 1χ1〇2~ixl04 cfu/g in 28 days. The inoculated bacteria were reduced to ΙχΙΟ2~ixi〇5 efu/g for 14 days. X: Inoculated mold was not reduced to 1χ1〇4 Cfu/g or less. The inoculated yeast was not reduced to lxl〇4 Cfu/g or less. The inoculated bacteria were not reduced to lxl〇5 Cfu/g or less for 14 days. Example 1 ～24, Comparative Examples 1 to 6 (makeup water) Various evaluation tests for preparing lotion were carried out by the usual method in accordance with the formulations shown in Tables 1 to 3 above. The results are also shown together. -16- 137274.doc [S] 1378799 [I Ϊ I37274.doc 一一一一一一一Γ0 ΙΌ Γ0 ΙΌ ΙΌ ΙΌ 〇〇〇〇¥#葚<3 ◎〇〇〇◎〇〇ΙΌ ΙΌ ΙΌ 〇◎〇Ο

10Ό IL •一 •一 Γ0 Γ0 ΙΌ ΙΌ ΓΟ Ο © Ο χ 〇 〇〇 〇〇 ΙΌ ΙΌ ΙΌ 〇 〇〇 ζ ΓΟ ΓΟ 〇〇〇 ΙΌ ΙΌ ΙΌ 〇〇 ◎ 〇〇 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3

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Example: g 1 1 Ο Ο 剩余 Remaining amount 〇 ◎ 〇〇 cn ΓΊ ., S 1 1 VO 2 inch remaining amount 〇 ◎ 〇〇 (Ν CN νη 1 Climb 00 1 1 m »n cn o Remaining amount 〇 ◎ 〇〇m « 1 1 | » cn 1 1 m un cn Remaining amount 〇 〇〇 1 1 1 ' S 1 1 mm <N oo Remaining amount 〇 ◎ 〇〇 〇〇 \ . 1 1 ,.^ 1 1 c〇 (N CN Remaining amount 〇 ◎ 〇 〇 00 • 1 1 ^―( 1 . g 1 1 r〇to (N | 0.005 I Remaining amount 〇 ◎ 〇〇 。.,, mii 1 ( m ^ (N c5 remaining amount ◎ 〇〇〇m • 1 1 〇I 1 〇1 1 m (N d> remaining amount: ◎〇〇〇»n ^ ,, 0.05 :0.05 1 1 m in (N 1 remaining amount: ◎ X <] inch ^ ,, 0.05 0.05 1 1 ro ^ CN o 0.1 0.1 Remaining amount 〇 ◎ ◎ 〇 m » - η ^ , _ 0.05 0.05 1 1 m < N Remaining amount ◎ ◎ 〇 Ν (Ν ^ ,. T-4 c; ' o 1 1 mm cs Remaining amount ◎ 〇〇讳 1 截 w 敏 敏 S S 9 S S S S S 铿 π π π π π π π π l l l J J J J J J J J J J J J J J J运松Αίατ ιίσι ax; a^ a^ 鹊溲 tears Φ1 i〇/*-sd ω 0/ Έ Q invites ω, S畤璲鮏灭墩^苏^ -β Loading fee t0 ό ¢5^ ^ —”1 i Pyracantha extract &- key B·鮏i-4 »0 Ground ¥ 澈®ί (Ν '―· ^ C: ^ 5 ^ ^ Ξ Η- i〇^ ^ ,:, s food l photo <β3 <i〇涠137274.doc -18· 1378799 [Table 3]

Comparative Example 1 2 3 4 5 6 Toluene Alcohol 1.5 1.5 1.5 1.5 1.5 - Ethyl sterol • - - - - - Rhododendrol-D-glucoside - - - - - Sucrose fatty acid ester (Note 1) - - - - 0.05 0.05 Polyglycerol fatty acid ester (Note 2) - - - - - - Polyglycerol fatty acid ester (Note 3) - - - - 0.05 0.05 Polyoxyethylene hardened castor oil (60ΕΌ.) 0.1 1 - 0.5 - - Polyoxygen Ethylene sorbitan monolaurate (20E.O.) - 0.5 0.5 1,3-butanediol 3 3 3 3 - 3 dipropylene glycol 5 5 5 5 - 5 glycerol 2 2 2 2 - 2 Pyracantha extract 0.1 0.1 0.1 0.1 0.1 0.1 methyl p-hydroxybenzoate. • - _ _ phenoxyethanol - - - - - Purified water residual halo remaining amount remaining amount remaining amount remaining amount remaining amount turbid · precipitation (45 ° C, 2 Month) XXXX Δ ◎ Discoloration (60 ° C, month) 〇〇〇〇 ◎ 〇 Discoloration (exposed for 1 week under simmering light) ◎ ◎ Antibacterial and mildew resistance ~ Δ △ 〇〇 Δ X

As shown in Tables 1 to 3, the stability of the examples of the present invention was good, and turbidity and precipitation were observed with respect to Comparative Examples 1 to 5 which did not contain the component (b) or the component (c) of the present invention. There is a problem with stability. Further, in the examples of the present invention, the antiseptic and antifungal properties are excellent. On the other hand, the comparative example id contains dantrol, but since the stability of the preparation is poor, the antiseptic and anti-staining properties cannot be sufficiently exhibited. Although the embodiment 2 is an example of the present invention, since the content ratio of the component (b), that is, the specific nonionic surfactant to all the nonionic surfactants is low, the stability of the formulation is slightly deteriorated. Example 1 5 is a case where the pyracantha extract is not contained, and the preparation for turbidity precipitation is excellent in stability and antisepsis and mildew resistance, but the color change stability is poor at high temperature or exposure to 137274.doc 19 1378799. It can be seen that Pyracantha extract is helpful for the stability of discoloration. Although the formulation of Example 22 was excellent in stability, it contained a relatively large amount of nonionic surfactant, so that skin irritation was caused in actual use. In the case of Example 24, although the stability of the preparation was excellent, since it contained a relatively large amount of polyol, it was felt to be sticky in terms of touch when actually used. Further, the results of skin irritancy evaluation of the above Examples 丨, 12, 13, and 14 and Comparative Example 4 are shown in Table 4. It can be seen that the examples i and 213 of the present invention have almost no irritation to the skin and are excellent in safety. However, if the commonly used preservative is used, it is produced by using the beryllic acid methyl vinegar or the phenoxyethanol together with the rhododendrol. Skin irritation (Example 14). In Comparative Example 4, a non-ionic surfactant, which is a nonionic surfactant which is usually used, was used instead of the nonionic surfactant specified in the present month, and skin irritation was observed, which was found to be inferior in safety. [Table 4]

Excellent results were obtained in the test '137274.doc m *20-1378799 [Table 5] Example 25 Ethanol 3 1,3-butanediol 2 Dipropylene glycol 5 Sucrose fatty acid ester (Note 4) 0.05 Polyglycerol fatty acid ester (Note 3) 0.05 toluene-D-glucoside (β-body) 3 dipotassium glycyrrhizinate 0.1 Pyracantha extract 0.1 Purified water remaining turbid, precipitate (45 ° C, 2 months) ◎ Discoloration (6 (TC, 1 month) ◎ Discoloration (exposed to sunlight for 1 week) ◎ Anticorrosion and anti-mildew evaluation results ◎ (Note 4) SURFH0PE SE COSME C-1216 (manufactured by Mitsubishi Chemical and Food Co., Ltd., HLB = 16) [Table 6] Example 26 Squalene 10 Stearic acid 5 Cetyl alcohol 2.5 Vaseline 2 Beeswax 1 1,3-butanediol 3 Dipropylene glycol 5 Sucrose fatty acid ester (Note 5) 1.5 Sucrose fatty acid ester (Note 6) 0.5 Hexammonium 3 Pyracantha Extract 0.1 Dipotassium Glycyrrhizinate 0.2 Purified water remaining turbid, precipitated (45 ° C, 2 months) ◎ Discoloration (60 ° C, 1 month) ◎ Discoloration (exposed for 1 week under twilight) ◎ Antiseptic , mildew evaluation results ◎

(Note 5) SURFHOPESECOSMEC-1816 (manufactured by Mitsubishi Chemical Food Co., Ltd., HLB=16) (Note 6) 3111^^〇?£3£(:〇31^(:-1807 (manufactured by Mitsubishi Chemical Food Co., Ltd., 1«3 = 7) 137274.doc •21 · 1378799 Further, according to the following formula, the external preparation for skin is prepared by the usual method, and the above various evaluation tests are performed to confirm that the stability of the preparation, the antiseptic and antifungal properties are excellent, and there is no irritation to the skin. Application example ι (makeup) and ingredients ___

1,3-butanediol 2.0 Dipropylene glycol 6.0 Concentrated glycerol 5.0 Rhodamine 1.5 Dipotassium glycyrrhizinate 0.2 Sucrose fatty acid ester (Note 4) 0.3 Sodium hyaluronate 0.01 Pyracantha extract 0.1 Licorice flavonoids (1 1) 0.01 Raffinose ( 1 2) 0.05 Himalayan raspberry root extract (1 3) 0.05 European elderberry extract (1 4) 0.01 Coptis extract (氺5) 0.01 Myrtle extract (1 6) 0.01 Purified too stripped 137274. Doc • 22- IS1 1 1 : Oil-soluble licorice extract Ρ-Τ (40) (manufactured by Maruzen Pharmaceutical Co., Ltd.) *2 : Oligo GGF (made by Asahi Kasei Industrial Co., Ltd.) *3 : Himalayan raspberry extract BG80 (manufactured by Maruzen Pharmaceutical Co., Ltd.) * 4 : Elderberry extract BG (manufactured by Maruzen Pharmaceutical Co., Ltd.) 1378799 *5: Coptis extract - J (manufactured by Maruzen Pharmaceutical Co., Ltd.) * 6 : Myrtle extract BG80 (manufactured by Maruzen Pharmaceutical Co., Ltd.) Application Example 2 (emulsion) )

Raw material content of ethanol 5.0 Rhododendron 2.0 Sucrose fatty acid ester (Note 1) 0.5 Nonylphenyl polyoxyalkylene (* 7) 1.0 Methyl polyoxyalkylene (* 8) 1.0 Tris(2-ethylhexanoic acid ) glyceride 1.0 p-methoxy cinnamic acid 2-ethylhexyl ester 0.1 dipropylene glycol 3.0 concentrated glycerol 2.0 carboxyethylene polymer (氺9) 0.25 potassium hydroxide 0.12 disodium edetate 0.01 Pyracantha extract 0.15 carrot Extract (* 10) 0.1 Pear Extract (* 11) 0.1 Blueberry Leaf Extract (* 12) 0.1 Alkenin Glucosin (* 13) 0.1 Seaweed Extract (* 14) 0.01 Purified Water Residue詈* 7 : Silicon FZ-209 (manufactured by UNICAR, Japan) I37274.doc •23· 1378799 * 8 : KF-96A-200cs (manufactured by Shin-Etsu Chemical Co., Ltd.) * 9 · CARBOPOL 941 (manufactured by Noveon INC.) * 10 :Vegetable Collagen (manufactured by Takahashi Co., Ltd.) * 11 : Fermentage PearExtract (manufactured by ICHIMARUPHARCOS Co., Ltd.) * 12 : CureBerry Extract (manufactured by ICHIMARU PHARCOS Co., Ltd.) *13: Enketocin glucoside (manufactured by Hasegawa Spice Co., Ltd.) * 14 : Marine Purge (ICHIMARU PHARCOS Manufacturing Division) Application Example 3 (Emulsion)

Ingredients __ Formulation amount ethanol 10.0 Hydrogenated soybean phospholipid (* 15) 1.0 Cholesterol 0.5 Polyglycerol fatty decyl ester (Note 7) 0.2 N-Mercapto-L-serinate 〇. 〇1 Polyoxyethylene methyl glucoside ( *16) 2.0 Squalene 2.0

Cyclopentasiloxane 1.0 1,3-butanediol 2.0 Polyglycerol 1.0 Dumactone-D-glucoside 2.0 Propylene methacrylate copolymer (* 17) 0.2 Potassium hydroxide 0.1 Dipotassium glycyrrhizinate 0.1 sodium hyaluronate 0.05 triethanolamine 0.5 137274.doc •24- 1378799 Sanxianjiao oi Pyracantha extract 0.1 White mustard hydrolyzed extract (*1 8) 0.01 Lonicera japonica extract (* 19) 0.01 Soymilk yeast (*20) 0.01 Wheat Germ Extract (* 21) 0.01 Dr. Grass Extract (*22) 0.01 Fragrance 0.03 Purified Water_Remaining (Note 7) Sunsoft Q-12S (Manufactured by Sun Chemical Co., Ltd., HLBM6.1) 氺15 : Lecinol S- 10 (manufactured by Nikko Chemical Co., Ltd.) * 16 : NIKKOL BMG-20 (manufactured by Shuguang Chemical Co., Ltd.) * 17 : PEMULEN TR-l (manufactured by Noveon INC.) * 18 : Sinablanca WH (manufactured by TECHNOBLE) * 19 : Pharcolex honeysuckle SB (manufactured by ICHIMARU PHARCOS) 氺20: Soymilk mash (manufactured by the three provinces) * 21 : Clariskin (manufactured by Silab) *22 : Dr. Pharcolex grass B (N) (manufactured by ICHIMARUPHARCOS) Application Example 4 (emulsion) Ingredients _ formulated amount of squalene 2.0 oleophilic monostearate Oleate 1.5 Stearic acid 1.0 Cetyl alcohol 0.4 137274.doc -25 Polyglycerol fatty acid ester (Note 8) 0.2 Polyglycerol fatty acid ester (Note 9) 2.0 1,3-butanediol 3.0 Rhodamine 1.5 Triethanolamine 0.2 Pyracantha Extract 0.05 Lotus Seed Extract (* 23) 0.05 Indian Bitter Leaf Extract (* 24) 0.05 Sea Herb Extract (*25) 0.05 Lupin Extract (* 26) 0.05 Curry Leaf Extract ( * 27) 0.05 Spice 0.02 Purified water remaining 1378799

(Note 8) RYOTO polyglycerate ER-30D (manufactured by Mitsubishi Chemical Food Co., Ltd., HLB = 10)

(Note 9) RYOTO polyglycerate SWA-10D (manufactured by Mitsubishi Chemical Food Co., Ltd., HLB=15) * 23 : Lotus fruit (manufactured by TECHNOBLE Co., Ltd.) 氺24: Indian Bitter Leaf Extract B (manufactured by ICHIMARUPHARCOS Co., Ltd.) * 25 : Sea Lavender SC (manufactured by SECMA) * 26 : Structurine (manufactured by Silab) 氺27 : Curry leaf extract (manufactured by Mikimoto Co., Ltd.) Application example 5 (0/W type (in-water oil) cream) Raw material composition _ blending 137274.doc -26- 1378799 Squalene 1 〇 〇 异丙 〇 〇 20 20 oleophilic monostearic acid glycerin 1 · 〇 stearic acid 7 · 〇 bee ants 1 〇 sucrose fatty acid ester (Note 5) 2-5 sucrose fatty acid ester (Note 6) 0.5 methyl phenyl polyoxy siloxane (氺7) 0.5

1,3-butanediol 1 〇. 〇 鹃 - - D-glucoside 3.0 Alcaligenes B16 polymer 〇 · 〇 5 Pyracantha extract 0.1 carrot juice (* 28) 〇.1 orange juice (氺 29) 0.1 Yam extract (*30) 〇-1

Yeast extract (*31) 〇.1 Coral grass extract (* 32) 〇.1 Hydroxide If 0.5 Fragrance 0.03 Purified __Remaining amount* 28 : Hormo Fruit Carrot N (made by ESPERIS) * 29 : Hormo Fruit Orange N (manufactured by ESPERIS) *30: Yam root extract (manufactured by Mitsui Chemicals, Inc.) *31: Yeast extract ZB (manufactured by ICHIMARU PHARCOS) 137274.doc -27· [S] 1378799

* 32 : Coral Grass (manufactured by TECHNOBLE) Application Example 6 (W/0 type (oil-in-water) cream) Raw material ingredient amount Sorbitol monoisostearate 1.0 Mercapto ring polydecane (* 33 10.0 dimethicone copolyol 2.0 squalene 3.0 sucrose fatty acid ester (Note 10) 0.2 sodium chloride 1.0 magnesium chloride 1.0 dipropylene glycol 7,0 hexamethylene oxalate 2.0 glycyrrhetinic acid stearate 0.1 microparticles titanium oxide (* 34) 2.0 p-methoxycinnamate-2-ethylhexyl ester 0.1 Pyracantha extract 0.05 apricot juice (* 35) 0.01 horse chestnut extract (* 36) 0.01 beta-carotene ( * 37) 0.01 Proper amount of purified water Sword Ember (Note 10) SURFHOPE SE COSME C-1811 (Mitsubishi Chemical Food Co., Ltd., HLB = 11) * 33 : TSF405 (manufactured by GE-TOSHIBA SILICONE) 137274.doc -28-

I SI 1378799 * 34 : Tipaque ΤΤΟ-55 (Α) (manufactured by Ishihara Sangyo Co., Ltd.) *35: Apricot extract K (manufactured by ESPERIS) *36: Horse chestnut extract BG-J (manufactured by Maruzen Pharmaceutical Co., Ltd.) * 37 : Beta carotene (manufactured by ROCHE) Application Example 7 (cosmetic liquid) Raw material ingredients _ blending 詈 ethanol 5.0 defatted acid lecithin 〇 5

Polyglycerol fatty acid ester (Note 3) 0.1 Nonylphenyl polyoxyalkylene (*7) 2.0 1,3-butanediol 3.0 Polyoxyethylene decyl glucoside (*16) 0.5 Polyethylene glycol 1000 1.0 Rhododendron Alcohol 3 · 0 Acrylic acid alkyl acrylate copolymer (Note 1) 〇.1 2-Methyl propylene methoxyethylphosphonium choline 0.5

• Mercaptoacrylic acid copolymer (* 38) Dipotassium glycyrrhizinate 0.2 Nicotine decylamine 1.0 L-carnitine chloride 0.3 N-Mercapto-L-serine 0.1 Potassium hydroxide 〇·〇7 Pyracantha extract 0.1 Rock Cabbage extract 0.01 137274.doc -29- 1378799 Lactic acid bacteria broth (* 39) 0.1 γ-aminobutyric acid (*40) 0.02 Tea fruit extract (*41) 0.01 Camellia extract (*42) 0.01 薏苡 extraction (*43) 0.01 Saxifrag extract (*44) 0.01 Rehmannia extract (*45) 0.01 cypress water (*46) 0.01 bitter orange peel extract (*47) 〇.〇1 甲瓦龙酸Ester (* 48) 0.01 Magnolia bark extract (* 49) 〇.〇1 Purified water remaining amount * 38 : Lipidure PMB (PhlO) (manufactured by Sakamoto Oil Co., Ltd.) * 39 · Whey CPA (manufactured by ICHIMARU PHARCOS) *40:810 0 8 8 8 (manufactured by Kyowa Co., Ltd.) 氺41: Tea fruit extract (manufactured by Maruzen Pharmaceutical Co., Ltd.) *42: Camellia seed extract (manufactured by Maruzen Pharmaceutical Co., Ltd.) 氺43: Coix seed extract BG -S (manufactured by Maruzen Pharmaceutical Co., Ltd.) * 44 : Saxifrage extract (manufactured by ICHIMARU PHARCOS) 氺45: Rehmannia extract BG-J (manufactured by Maruzen Pharmaceutical Co., Ltd.) * 46 : Flat Water B (manufactured by Maruzen Pharmaceutical Co., Ltd.) * 47 : Bitter orange peel extract B (manufactured by ICHIMARU PHARCOS) * 48 : Mevalonolactone (made by Asahi Kasei Co., Ltd.) * 49 : Pharcolex Magnolia B (manufactured by ICHIMARU PHARCOS) ) 137274.doc •30· 1378799 Application Example 8 (Sunscreen) 8.0 1.0 0.1 10.0 3.0 .0 0 0 0 0 0 0.1 0.1 0.01 0.01 Remaining amount 3 Ethanol sorbitan monoisostearate polyglycerol fatty acid (Note 2) p-methoxycinnamic acid-2-ethylhexyl methacrylate polyoxyalkylene 8) microparticles titanium oxide (* 50) microparticulate zinc oxide (* 51) anhydrous oxime acid low viscosity methyl hydrogenated polyfluorene Oxyalkyl perfluoroalkyl dimethyl-trimethyl decyloxy decanoic acid cross-linked polyoxyn oxy powder 1,3-butane diol glycerol hexanol lycopene glycyrrhetinic acid stearyl pyrite extract silk extract Liquid hydrolyzed silk liquid (* 52) Purified water * 50 : ZnO-350 (manufactured by SUMITOMO OSAKA CEMENT) * 5 1 : Tipaque TTO-55 (A) (manufactured by Ishihara Sangyo Co., Ltd.) * 52 : Silkgen G Soluble S (ICHIMARU PHARCOS Made by the company) 137274.doc 31 1378799

Application Example 9 (mask) Raw material into a male formula, ethanol 10.0 Polyethylene glycol 13.0 1,3-butanediol 1.0 Dipropylene glycol 2.0 Glycerin 2.0 Methyl stupid polyoxo (氺7) 0.2 Myristate octyl 12 Alkyl esters.0.2 Sucrose fatty acid esters (Note 1) 0.05 Squalene 0.2 Rhodamine 2.0 Carboxyvinyl polymer 0.1 Sodium hyaluronate 0.01 Hydroxyethyl cellulose 0.05 Aminomethyl propanol 0.05 Pyracantha extract 0.05 European white willow leaf Extract (氺53) 0.05 Purified water remaining 詈* 53 : ASTRESSYL (manufactured by Silab) Further, the composition of the perfume used in the above application examples is shown in Table 7. [Table 7] Fragrance Formula Ingredients % Ingredient % % terpineol 10.00 vanillin 2.00 pine oil brain ester 2.00 6 base vanillin 0.10 137274.doc • 32- 1378799 Table II Hydrogen jasmonate (Cepionate) 60.00 Musk Mouscone 0.50 Dihydrojasmonic acid methyl ester 250.00 Ethylene glycol ethyl ester 42.00 吲哚0.05 4,6,6,7,8,8-hexamethyl-1,3,4,6,7,8- Hexahydrocyclopentabenzopyran 60.00 2-methyl-3-(3,4-methylenedioxyphenyl)propanal 3.00 cyclopentadecene _ 20.00 hydroxy citronellal 20.00 yellow geranide 1.00 hydroxy Citronellol 10.00 γ·11 Xuan vinegar 0.40 to t-butyl-α-methylhydrocinnamic aldehyde 35.00 γ-decalactone 0.10 4-(4-hydroxy-4-methyl-pentyl)-3- Cyclohexene-1 -formaldehyde 75.00 4·(4-hydroxyphenyl)-2-butylamine 0.50 3-methyl-5-phenylpentanol 20.00 Musk ketone 0.10 Phenylethanol 10.00 Skatole 0.01 α - Violet Ming 10.00 cis-jasmine 0.05 β-iurolan 20.00 phenylethyl acetate 0.10 y-methyl ionone 10.00 civetone 0.20 dihydro-P-ionone 25.00 γ-decalactone 0.05 benzyl salicylate 150-00 α-santalol 0,20 Cis-3-hexenyl salicylate 30.00 β-santalol 0.20 eugenol 0.80 syringyl acetate 0.10 cinnamyl 5.00 α-hexyl cinnamaldehyde 20.00 cinnamaldehyde 0.50 α- 厥 厥 0.0 0.0 0.0 0.0 0.0 0.0 0.0 -- 厥 厥 0.02 0.02 guaiacol 0.50 β-thinenone 0.01 cembyl acetate 5.00 δ- 厥 厥 0.01 0.01 曱 柏 cedar ketone 30.00 rose essence 0.50 6,7-dihydro-1,1,2,3, 3-pentamethyl-4(5H)-indane 2.00 rose oil 4.50 fragrant root acetate 10.00 sandalwood oil 2.00 3-mercapto-5-(2,3,3-trimethyl-3-cyclopentene- 1-yl)-pentan-2-ol 2.00 rock rose essence 0.05 2-ethyl-4-(2,3,3-tridecyl-3-cyclopenten-1-yl)-2-butene Small alcohol 0.80 rock rose essence 0.01 isodecyl cyclohexanol 35.00 lava oil 0.50 geranyl aldehyde 10.00 guaiac oil 0.10 coumarin 2.00 total 1000.00

[Industrial Applicability] According to the present invention, it is possible to provide an external preparation for skin which is less irritating to the skin, has excellent long-term storage stability, and has a high skin and whitening effect. 137274.doc -33- m

Claims (1)

1378799 X. Patent Application Range: Patent Application No. 097150734 (Chinese Patent Application Serial No. 097150734) A skin external preparation characterized by containing ya) selected from the following formula (1) (2) one or more selected from the group consisting of sucrose fatty acid esters and polyglycerol fatty acid esters; and (c) polyhydric alcohols The amount of the component (a) is 〇1 to 3% by mass when R is a hydrogen atom, and 〇·ι 5 mass% when r is an acid group of 2 to 20. 〇, when R is a bile residue, it is 0·1 to 5 mass%, [Chemical 1] 0Η (In the formula, R 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 external preparation for skin according to claim 1, wherein the component (a) is rhodamine. 3. The skin external preparation according to claim 1, wherein the component (b) is one or more selected from the group consisting of sucrose fatty acid esters having a HLB of 1 Å or more and polyglycerol fatty acid esters. 4. The external preparation for skin of any one of claims 1 to 3 which contains (d) the fruit of the Chinese name "Pyracantha fortuneana" of the Rosaceae Pyracantha The skin external preparation according to any one of claims 1 to 3, wherein the content of the component (b) is 〜1 to 8 mass%, and the content of the component (c) is 〇.1~ 30% by mass. The skin external preparation according to any one of claims 1 to 3, which does not substantially contain a paraben and/or a phenoxyethanol. 7. The skin external preparation according to any one of claims 1 to 3, which does not substantially contain a polyoxyethylene addition type nonionic surfactant. 137274-1010622.doc 2-