TWI238066B - Percutaneous absorption promoting agents and cosmetic compositions containing the same - Google Patents

Abstract

This invention relates to percutaneous absorption promoting agents (a) comprising oils with a solubility parameter delta in a range of 15.7 < delta <= 17.2 as their effective contents, and cosmetic compositions comprising such content (a) and materials (b) having whitening, antiphlogistic and wetting effects. This percutaneous absorption promoting agent is able to promote the percutaneous absorptivity of the effective contents remarkably when they are used on skin externally, and has little stimulation on skin, thus has excellent safety.

Description

1238066 Printed by the Consumer Standards Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs A7 _______ B7_ V. Description of the Invention (1) Technical Field The present invention relates to a percutaneous absorption of effective ingredients that can promote external use of the skin, and has low skin irritation and is safe. Transdermal absorption enhancer with excellent properties, and cosmetics using the same. BACKGROUND ART Heretofore, in external preparations for skin such as cosmetics, various substances have been used as components that exert a moisturizing effect, a whitening effect, and the like through percutaneous absorption. However, the stratum corneum, the outermost layer of the skin, was originally a tissue with a physiological function to prevent the invasion of foreign bodies from outside the body. Therefore, it is not possible to obtain sufficient transdermal absorbability by combining the above-mentioned substances with external agents, and to exhibit the same. The role of the ingredients. In addition, even substances that exhibit excellent effects through absorption through the skin may not exhibit their original effects because of the low percutaneous absorption capacity of the stratum corneum. In order to improve the percutaneous absorption of various substances in recent years, the industry has used percutaneous absorption of dimethylarylene, dimethylformamide, dimethylacetamide, methyldecylarylene, etc. Accelerator. However, these percutaneous absorption enhancers do not provide satisfactory percutaneous absorption promotion effects, and because the skin is highly irritating, erythema may be generated on the skin, so its effects, safety, and feeling of use are not required. Satisfied. Therefore, the object of the present invention is to provide a transdermal absorption enhancer with excellent percutaneous absorption promotion effect, low skin irritation, and high safety, and granules using the transdermal absorption enhancer. . The summary of the invention has the above facts. After intensive research, the inventors finally found that it has a special -4- paper size applicable to the Zhongguanjia Standard (CNS) M specification (2lQx 297). (Please read the note on the back first Matters re-page)

丨 Order line Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs 1238066

、 Explanation of the invention (疋 An oil agent with solubility parameter has excellent skin-enhancing effect of external ingredients and low skin irritation. In addition, it has been found that if this oil agent has a moisturizing, whitening or anti-inflammatory effect, The combination of the substances can achieve a cosmetic material with excellent skin roughening effect, whitening effect, and anti-inflammatory effect, so the present invention is completed. Specifically, the present invention provides a solubility parameter d in the range of i 5 7 &lt; d S 17.2 The oil agent (a_i) is an effective ingredient of a transdermal absorption enhancer. The invention also provides an oil agent (heart 1) and 17.5 with a solubility parameter d in the range of 15 7 &lt; d $ 17: &lt; The oil agent (a_ 2) in the range of $ d $ 21〇 is a percutaneous absorption enhancer of an active ingredient. In addition, the present invention provides a granulated granule, which is characterized by: containing: ⑷ selected from a solubility parameter j in u 7 &lt; d $ 21 〇 range of oil ^ 1) one or more than one, and (b) a substance having a whitening effect, anti-inflammatory effect or moisturizing effect. Furthermore, the present invention further provides an ingredient ⑷ (called one or two or more selected from oils having a solubility parameter d in the range of 15.7 &lt; d S 17.2, and (, -2) selected from the solubility parameters ... " ... oil agent t within the range of the heart. One or two or more of the above-mentioned granules combined. The best form for carrying out the invention The oil agent (η) used as an active ingredient in the present invention is a solubility parameter: 15 … Within the range of 17.2. Here, the resolution parameter refers to the scale of the object! ';, which can be obtained by calculating the one-third / person element; the valley resolution parameter using the following formula 又. Also, in the formula, the right side T Shijian &lt;

Krevelen's Mohr's gravitational constant is calculated by formulas (Η) ~ (iv). -5 Paper Size Shicai Guanjia County (CNS) (210X297 ^)-~

1238066 Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs A7 B7 V. Description of the invention (5) Isotridecyl isononanoate is used as the ingredient (a_2). Diisoglyceryl isostearate and myristate monoglyceride should be used. In this case, other oils may be used in combination. When 'combined component (a-1) and component (a_2) are used, the weight ratio is (a -1) / (a-2) = 10/1 ~ 1/2, especially preferably 10 / Within the range of 1 to 2/1. By using the component (a) [the component (a-1) alone or the combination of the component (aq) and the component (b -1)] of the present invention to promote transdermal absorption, as long as it is used in 通 # Skin external preparations can be absorbed by the skin and exert their effects. There are no special restrictions. For example, moisturizers, whitening agents, anti-inflammatory agents, external absorption agents, amino acids, plant extracts, deoxidizers, sulfur Oxidants, blood promoters, sterols, etc. Among them, the moisturizer (b-1) may be any user in general cosmetics, and it is subject to special restrictions. For example, sugars, polyhydric alcohols, amidine compounds, neural amines, etc. may be used. Specifically, examples of the sugars and polyhydric alcohols include ethylene glycol, glycerol, glucose, maltose, maltitol, sucrose, lactose, Z sugar alcohol, sorbitol, maltotriose, and threitol. , Pentaerythritol, amylolytic sugar reducing alcohol, ethylene glycol, butanediol, diglycerol, triglycerol, tetraglycerol, 1,3-butanediol, propylene glycol, dipropylene glycol, polyethylene glycol, 1% propylene glycol, and the like. As another example, as the amidine compound, a melting point of 0 to 5 (rc, preferably 10 to 40 amidine compound. Outside this range, it is difficult to mix stably in the composition. Also, in the present invention The melting point is based on 1 (2) -8-This paper is the standard for financial and family care (CNS) A4 regulations (please read the precautions on the back before ^ f this page) | installation · ^^ 4 1238066 5. Description of the invention (6 is determined by extrapolating the melting point starting temperature. As examples of this amidine compound, examples of the ammonium isostearate isostearate, isomerizate, isomerate, etc., or The following general formulae (1) to (3): R1

0H

0H (1) (where 'R1 and R2 may be the same or different, representing that the number of carbons is lightenable: te group'; R represents a linear or branched chain sintered group having a carbon number of 6 or Single bond, R4 represents a hydrogen atom, a straight or branched fluorenyloxy group of 2, or 12 carbon atoms, or 2,3_dihydroxypropoxyl. R4 is a hydrogen atom when R3 is a single bond. R1 · 0Η (2) ( (Please read the notes on the back before this page)

Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs, 1T, R2A0R3a ^ 4a (where R1 and R2 have the same definitions as above, and R3a represents a straight or branched chain alkyl group with 3 to 6 carbons; Represents a linear or branched alkoxy group with a carbon number of 丨 ~ ^) R1

9- (3) The size of the paper is applicable to the Chinese National Standard (CNS) A4 (210x 297 male thin) 1238066 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention (7) (where 'R, The definitions of R and R are the same as above, R4b represents a chlorine atom, a straight or branched chain alkoxy group having 1 to 12 carbon atoms, or 2,3-epoxypropyloxy group; when R3 is a single bond, R4b is a hydrogen atom ) Shown amidine derivatives. Among them, in the amine derivative (1), R1 and R2 may be the same or different, and represent linear or branched saturated or unsaturated hydrolyzable hydrocarbyl groups having 1 to 40 carbons. Examples of R1 and R2 include methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, and ten. Three, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty one, twenty two, twenty nine, thirty, isostearyl , Isoheptadecyl, 2-ethylhexyl, 1-ethylheptyl, 8-heptadecyl, 8-heptadecenyl, 8,11-heptadecyl (dienyl), 2-heptyl undecyl , 9-octadecenyl, 1-hydroxynonyl, b-hydroxypentadecyl, 2-hydroxypentadecyl, 15 · hydroxypentadecyl, 11-hydroxyheptadecyl, and u_hydroxy_8_heptadecene Base and so on. As R, it is preferably a straight-chain or branched alkyl or fluorenyl group having 8 to 26 carbons. Examples thereof are: octyl, decyl, dodecyl, tridecyl, isostearyl , 2-ethylhexyl, 2-heptylundecyl, 9-nonadecenyl, and the like. As R1, a particularly good straight-chain or branched-chain alkyl group having 12 to 22 carbon atoms is exemplified by dodecyl, tetradecyl, hexadecyl, octadecyl, 222, and methyl And branched stearyl. As R2, S is a straight-chain or branched alkyl or alkenyl group having 9 to 25 carbons, and examples thereof are nonyl, undecyl, dodecyl, pentadecyl, heptayl, and twentieth Mono-, non-decyl, iso-heptadecyl, ethylheptyl, 8-heptadecyl, 8-heptadecenyl, 8, n-heptadecyl (dienyl), hydroxy nonyl, 丨 hydroxy ___ -10- This paper size applies to Chinese National Standard (CNS) A4 specification ((Please read the note on the back first ^ 5 then Bengon), 11 1238066

15-base 2-¾-base 15-base, 15-base-based 15-base, 11-base-based 15-base and 1 1-hydroxy-8-heptadecenyl, etc. . As r2, a particularly preferred hydrocarbon group is a carbon number of 11 to 21 &lt; a straight or branched chain alkyl group, and examples thereof are undecyl, tridecyl, pentadecyl, heptyl, twenty-one and methyl Heterogeneous branched chain and other seven bases and so on. R represents carbon number! Straight or branched alkylene or single bond of ~ 6; as the alkylene group, examples include: alkylene, ethylene, propylene, butyl, hexyl, 1-methyl Ethyl, dimethylmethyl, 2-methylphenyl, 1,1-dimethylethyl, dimethylethyl, methylbutyl, 2-ethylphenyl, and the like. As R3, a straight-chain alkylene group having a carbon number of 1 to 6 is preferred. Among them, a methyl group, an ethyl group and a propyl group are particularly preferred. R4 represents a hydrogen atom, and the number of carbons is a straight-chain or branched-chain alkoxy group or a 2,3-dienylpropoxy group. As the alkoxy group, examples thereof are a methoxy group, an ethoxy group, and a propoxy group. , Butoxy, hexyloxy, octyloxy, decyloxy, ^ methylethoxy, 2-ethylhexyloxy, and the like. As R4, a hydrogen atom, an alkoxy group having 1 to 8 carbon atoms, and 2,3-dihydroxypropoxy group are preferable, and among them, a hydrogen atom, a methoxy group, an ethoxy group, a propoxy group, Butoxy, ^ methylethoxy, 2-ethylhexyloxy and 2,3-dihydroxypropoxy. As the amine derivative (1), compounds having general formulae R1, R2, and 3 and R4 which are each a group within the above-mentioned particularly preferable range are particularly preferable. In the amidine derivative (2), R1 and R2 are preferably the same groups having the same meanings as described above. In addition, as R3a, the alkylene group exemplified in R3 of the amidine derivative (1) does not include methylene and ethylene. As R3a, it is preferably a straight-chain alkylene group having 3 to 6 carbon atoms, and particularly preferred is a propylene group. As an example of the alkoxy group of ruler 43, it can be exemplified with amine-11-this paper size applies the Chinese National Standard (CNS) A4 specification (210X 297 mm) (please read the precautions on the back first) Order line 1238066 A7 ___B7 V. Description of the invention (9) The same base as R4 of the derivative (1) is preferred. In the amide derivative (3), r1, r2 &amp; r3 have the same meanings as described above, R represents a hydrogen atom, and a straight or branched bond of W2 is alkoxy or 2,3-ethoxy. Propylpropoxy. Specific examples of r1, r2 &amp; r3 are the same groups as those of amidine and amidine (1), and preferably the same base. As the counter carbon number 1 to 12, the straight or branched chain alkoxy group may be the same group as IR4 in the amidine derivative (1), preferably a hydrogen atom and the same alkoxy group as R4 And 2,3-ethoxypropoxy. Among these amidine derivatives (1) to (3), particularly preferred are those represented by the general formula (丨). The amidamine derivative (1) can be produced, for example, by the following production or production method 2. (Please read the notes on the back before

, = 'Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economy of the People's Republic of China -12- -------- This paper size applies to the Chinese National Standard (CNS) A4 specification (210X 297 mm) 1238066 A7 B7 V. Description of the Invention (10) (7) '0, lc 丨 Kco—Force ^ (8 F) 哞 Thin One R] (Please read the precautions on the back before this page)

Central Consumers Bureau of the Ministry of Economic Affairs

This paper size applies to Chinese National Standard (CNS) A4 specification (210X297 mm) 1238066 A7 B7 V. Description of the invention (11 Ka Yingxue (2 F) (1 7) 哞 Thin 1 20 (12) R1: R Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs

-14- The paper scale is applicable to the Chinese National Standard (CNS) A4 specification (210X 297 mm) (Please read the precautions on the back before this page) 1238066 A7 B7 V. Description of the invention (12) (where R1, R2 and R3 have the same meaning as above, R4f represents a chlorine atom or a linear or branched alkoxy group having 1 to 12 carbon atoms. However, when R3 is a single bond, R4f is a hydrogen atom. R6, R8, R1Q and Rn represents a linear or branched saturated or unsaturated hydrocarbon group having a carbon number of i to s, preferably a straight or branched chain alkyl group having a carbon number of 1 to 5, particularly preferably a methyl group. R9 is a hydrogen atom , Alkali metal atom or COR8 group, R7 and R12 represent _ prime atom, methyl continuous base, methylbenzene continuous base, etc. As R, from the point of view of easy availability, etc .: A gas atom and a bromine atom are particularly preferably a chlorine atom. As rU, from the viewpoint of easy availability and the like, 'methanesulfonium sulfonium group and tosylsulfonium sulfonium group are preferred). (Please read the notes on the back before this page)

Printed by the Consumer Cooperatives of the Central Commission of the Ministry of Economic Affairs-15- This paper size is applicable to the Chinese National Standard (CNS) M specification (2 丨 〇 &gt; &lt; 297 Gong 1238066 A7 B7 V. Description of the invention (13) R Factory (7) H2NIRcorg Corpse (8C) (Please read the precautions on the back before this page) Printed by the Staff Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs

(ΫΈΒ102G)

R2S2RG ^ 8

、 1T -16- This paper size applies to Chinese National Standard (CNS) A4 specification (210X 297 mm) 1238066 A7 V. Description of the invention (14) Must be thin. (17) R] o Γ? Ο ~ 3g 1 V \ o / (XA \ o (1 6 G) ^ / 0 \ &gt; KN0 / v (0 Chicken R5 R -R) o / ^ Ya (15) 蔼, R3RJ3ft (3G) 0 (Please read the back Note for re-ip? This I) Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 1 Q rox ^ o OG)

R- ·

OH0 / &lt; λ \ 0- SI QHSCORCO) N factory \ ^ / \ Λ \ os ^ / \ / \ (1 4 G) PD.S% R / (13) / 0, OH (OSRCO) '(/ A 、 OSRco This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 1238066 Five A7 B7 、 Invention description (15) (where R1, R2, R6 ~ R12 have the same definition as above, R3s represents carbon The number is 1 to 6 of linear or branched elongation groups. The reaction conditions for each step of Production Method 1 and Production Method 2 are as follows. Step 1) Glycidyl ether (7) and amine (8F) or (8G), solvent-free or lower alcohols such as water, methanol, ethanol, isopropanol, etc., ether solvents such as tetrahydrofuran, diamine, benzene, ethylene glycol dimethyl ether, hexane, benzene, toluene, In the case of a hydrocarbon solvent such as toluene, or an arbitrary mixed solvent of these solvents, etc., it can be reacted at ▲ / m ~ 150C to produce an amine alcohol derivative or. Step 2) Make fatty acid ester (9), fatty acid lower alkyl esters such as fatty acid methyl ester, fatty acid ethyl ester, etc., and amine alcohol derivative (4F) or (4G) in potassium hydroxide, sodium hydroxide, etc. Alkaline earth metal hydroxides such as alkali hydroxides, calcium hydroxide, alkali metal carbonates such as potassium carbonate, alkali earth metal carbonates such as calcium carbonate, sodium methoxide, sodium ethoxide, and potassium tert-butoxide In the presence of alkali catalysts such as alkali metal alcoholates, etc., under normal pressure ~ 0.001 mmHgt reduced pressure, at room temperature ~ 15 (rc order it to react, can produce amidine derivatives (2F) or (2 G). At this time, the amount of alkaline catalyst used should be 0.01 to 0.02 equivalents relative to the amine alcohol derivative (4ρ) or (4G). Also, the alcohol produced by the reaction is divided by one side. Outside the system, the reaction can be accelerated, which is satisfactory. Step 3) ^ Make the fatty acid gas (10) and the amine derivative (2F) or (2G) or the amine alcohol derivative (4F) or (4G) 18-Paper in a solvent-free, solvent-free, gas-imitated, two-gas, two-gas, and two-gas-fired hydrocarbon-based dissolved coal, 'tetrahydrofuran, dioxane, ethylene glycol dimethyl ether, etc. Standards apply to China National Standard Umbrella (CNS) A4 (please read the precautions on the back first and then this page)-Yibu printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 1238066 A7 B7 V. Description of the invention (16 ether series, mixed media, Alkane, benzene, toluene, di-Pu Shi Hong Li-Jia Piao Temple heart hydrocarbon series solvent, or any mixed solvent of this temple-like medium, the presence of a base such as ammonium amine, etc. Ethylamine and other third-order protons are reacted in the presence or absence of 'coamine-cool derivatives ⑽) or ⑴G) at a temperature of ~ 100 ° C, and step 4) Oxygen 2 is oxidized and hydroxide Test of metal hydroxides such as sodium, hydrogen emulsified Maisi reading soil metal hydroxides, potassium carbonate, etc. ^ butyl oxide, etc. Tests of metal alcohols, etc .: Test strips; Sexual hydrolysis can also be manufactured. Step 5) The Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs prints an order of 1 to 20 equivalents of the epoxide (12) ', which should be surface gas alcohol, under the cover solvent, or water or tetrahydro squeaking, dinox, Ether solvents such as ethylene glycol dimethyl bonds, such as hydrocarbon solvents such as hexane, benzene, toluene, xylene, etc., or any mixed solvent of these solvents, etc., are in the range of ～~ 0 equivalents of potassium hydroxide, Testing of metal hydroxides such as sodium hydroxide, testing of hydroxides, soil metal nitrogen oxides, alkali metal carbonates such as potassium carbonate, calcium carbonate and other alkaline earth metal carbonates, and ammonium derivatives (2f) * (2g) can be reacted at room temperature to 150 ° F to produce amine derivatives (3F) or (3G). At this time, in terms of yield, it is preferable to use tetrabutylammonium bromide, tetrabutylammonium gas, cetyltrimethylammonium gas, cetyltrimethylammonium bromide, stearyltrimethylammonium gas, and di (tetraoxyethylene) Base) Quaternary ammonium salts such as stearyl methyl ammonium gas, or beet tests such as lauryl dimethyl carboxy ammonium beet test and the like in the presence of phase-shifting catalysts. Step 6) 19- This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 1238066 A7 B7 V. Description of the invention (17) The amidine derivative (3F) or (3G), Under alkaline conditions, such as metal hydroxides such as sodium hydroxide, earth metal hydroxides such as hydroxide, alkali metal carbonates such as potassium carbonate, alkaline earth metal carbonates such as calcium carbonate, or Acidity of inorganic acids such as sulfuric acid and hydrochloric acid, Lewis acid such as boron trifluoride and tin tetrachloride, carboxylic acids such as acetic acid, tetradecanoic acid, and hexadecanoic acid, and acid acids such as p-toluenesulfonic acid Under the conditions, or under the condition of alkali-acid mixed core, hydration at room temperature ~ 300 ° C, can produce amidine derivatives (1F) or (1 G) 〇Step 7) amidine derivatives (1F) or ( 1G), by making the carboxylic acid derivative (13), preferably a lower fatty acid such as acetic acid, a lower fatty acid alkali metal salt such as sodium acetate, an anhydrous lower fatty acid such as anhydrous acetic acid, etc., alone or in combination with amidine Derivatives (3F) or (3G) in the presence or absence of basic catalysts such as tertiary amines such as triethylamine After the reaction, it is converted into an ester-amidine derivative (14F) or (14G). Step 8) The § motif is used to test metal hydroxides such as hydrogen emulsified potassium, steel hydroxide, and calcium hydroxide. Alkaline earth metal hydroxides, alkali metal carbonates such as potassium carbonate, alkali earth metal carbonates such as calcium carbonate, alkali metal alcoholates such as sodium methoxide, sodium ethoxide, and third butoxide, etc. It can also be produced under conditions such as selective hydrolysis. Step 9) Let the carbonyl compound (15), preferably an aliphatic ketone such as acetone, methyl ethyl ketone, etc., and the amidine derivative (1F) or (1G) or the amidine derivative (3F) or (3G) in sulfuric acid, Inorganic acids such as hydrochloric acid and phosphoric acid, carboxylic acids such as acetic acid, boron trifluoride, 4-20- This paper size applies to China National Standard (CNS) A4 specifications (21〇X 297 mm) -----.- -^-I ^ II (Please read the precautions on the back before printing this 5 Printed by the Central Consumers Bureau of the Ministry of Economic Affairs Consumer Cooperatives 1238066

1238066 A7 B7 V. Description of the invention (20)

0H, 0CH3 C15H31 C13H27 〇H C16H33

OH CH3 (CH2) mCH (CH2) nCH2, I ch3

.OH, 0CH3 C13H27- (Please read the precautions on the back first, then this page)-Equipment · (m and n represent m + n = 10 ~ 16, m = 4 ~ 10, n = 4 ~ 10, and = 7, n = 7 is the number of distributions of vertices.), 11 CH3 (CH2) mCH (CH2) nCH2, ch3

OH OCHc CH3 (CH2) mCH (CH2) r I CH3. 12 ^ 25 \ CH3 (CH2) mCH (CH2) I CHs

Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs

OH

OH (m and n have the same definitions as above.) (M and η have the same definitions as above. 0Η

Cl6H33 \ n / ^ 〇 \ A ^ C cis-9-C! 7H33 '-23- This paper size is applicable to China National Standard (CNS) A4 specification (210 X 297 mm) 1238066, invention description (21), gas k An example of the fermented amine derivative (1) obtained by method 2 is c16H33.

OH, 0, person. OH is as follows, (l · C16H33

OH 0, 1 JH, OH R2 / \ 〇 oh (R2 = Ci7H35 + Ci5H3i + Ci3H27) CH3 (CH2) mCH (CH2) nCH2

OH (Please read the precautions on the back page)

1T CH3 C13H27 〇 / ΊΓοη Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (m and n stand for m + n = 10 to 16, m = 4 to 10, n = 4 to 10, and have m = 7 And n = 7 is the number of distributions of vertices.) Also, as a sulfonamide compound, an N_ substituted sulfonamide compound having a total carbon number of 30 or more is particularly preferable. The 'amidamine compound' is preferably one in which it is bound to water in an amount of 1% by weight or more, and particularly 5% by weight or more. Here, combined with the content of water, you can first add water to the sample at room temperature to determine the maximum addition that can maintain a uniform phase. -24- This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) ) 1238066 V. Description of the invention (22) A7 B7

The amount is taken as the combined water amount, and then the relative weight of the blue is expressed as a percentage, and then obtained by the following formula. <'Total weight of water in ancient water (g) i Total of material 〇0—Contained water content (weight 〇 / 〇) Among the humectants of the two components (A), as neural amines, it can be The examples are given in addition to the conventional compounds represented by the following general formula (4), and also neuroceramide-like structural substances shown. &gt; 0, II total

-C-NH I CH — CH ·; nr I ^ R6-CH-0H

—0H (Please read the precautions on the back before this page) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economics [where R5 and R6 can be the same or different, representing a straight bond or branched chain with a carbon number of 8 '. Or unsaturated hydrocarbon group] In the general formula (4), the hydrocarbon group represented by R5 and R6 is a straight or branched chain hydrocarbon group having 8 to 26 carbon atoms, which may be saturated or unsaturated, and an example is: octyl Base, nonyl, decyl, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty Base, twelve base, twenty three base, twenty four base, twenty five base, twenty base, nonenyl, decenyl, alkenyl, dodecenyl, tridecenyl, tetradecenyl Base, pentadecenyl, hexadecenyl, heptenyl, octadecenyl, undecenyl, eicosenyl, behenyl, behenyl, behenyl, Tetracosenyl, pentadecenyl, hexacosenyl, nonadienyl, decadienyl, undecylenyl, dodecyl (difluorenyl), tridecyl (diene) Base, tetradecyl (diene) base, ten (Diene) -based, hexadecadiyl-based, ten-25-This paper size applies to China National Standard (CNS) A4 (210X297 mm) Order-printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 1238066 A7 _ B7 _ --- ~ ------------------ ------ 5. Description of the invention (23) Hepta (diene), eighteen (two) Alkenyl), nineteen (dienyl), icos (difluorenyl), twenty-one (dienyl), twenty-two (dienyl), twenty-three (diene) yl, twenty-four (Difluorenyl), twenty-five (difluorenyl), twenty-sevenT (difluorenyl), 2-hexyldecyl, 2-octylundecyl, decyltetradecyl, isostearyl, etc. . These fluorenyl groups may be substituted by more than one substituent. As R5, a linear alkyl group having 15 to 23 carbons, particularly fifteen, seventeen, and twenty-two groups; as R6, a linear saturated or unsaturated 15 to 23 linear carbons The alkynyl or alkenyl group is particularly preferably a pentadecyl group, a heptyl group, and a heptyl group. Among the neuraminamines represented by the general formula (4), particularly preferred compounds are those in which R5 and R6 in the formula (4) are each a combination of the above-mentioned preferred ranges. R7—〇-ch9 I One

CH-O ^ CCH ^ .- CCHY ^ b-H (5)

0 CH2— (CH2) c-0 one (CHZ% —H

[Wherein 'R7 represents a linear or branched saturated or unsaturated hydrocarbon group having a carbon number of 10 to 26' R represents a straight or branched chain saturated or unsaturated hydrocarbon group having a carbon number of 9 to 25 'Y1 and Z1 represent hydrogen Atom or hydroxyl group, a represents the number of 0 or 1, ^ represents the integer of 0 ~ 4, b and d represent the integer of 0 ~ 3] These neuraminamines are similar structural substances, which can be obtained according to conventional methods [eg p〇Ush Journal of Chemistry (p.j.Chem.), 1059 (1978); same magazine il, 1283 (1978); Japanese Patent Publication No. 54_117421, Japanese Patent No. '1443〇8, Japanese Patent No. 54-147937, No. 62_228〇48, No. 63_216852] ______ -26- This paper size standard for household towels (CNS) 7¾ (2ι〇χ297) (Please read the precautions on the back and then this page)-installation, -Mouth line 1238066 Α7 Β7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Production description (24) Manufacturing. The number of carbons shown by 'R7 in the general formula (5) is saturated or straight-chain or branched. Or unsaturated nicotine, examples of which are straight bonds where the number of carbons in R5 and R6 above is 10 to 26, and the number of carbons shown in reverse is 9 to 25. Examples of branched saturated or unsaturated nicotyl groups are those in which the number of carbons in rule 5 and trans 6 is 10 to 26. R7 is a linear saturated alkyl group having 12 to 18 carbons. Particularly preferred is Tetradecyl, hexadecyl, and octadecyl; R8 is a linear saturated alkyl group having 9 to 18 carbons, particularly preferably nonyl, pentadecyl, and heptyl. The general formula (5) Among the neuraminamine-like structural substances, a particularly good compound is a compound of the general formula (5) in which r7 and R8 are each a combination of the above-mentioned preferred ranges. Also as a whitening agent (b-2), as long as it has a Substances for whitening can be used in skin external preparations without special restrictions. For example, L-ascorbic acid and its derivatives, hydroquinone derivatives, osmic acid and its derivatives, placental extracts, Whitening-derived plant extracts, spiro ether compounds, etc. Specifically, there are no restrictions on ascorbic acid and its derivatives, and examples thereof include ^ ascorbic acid phosphate, a monovalent metal salt of L-ascorbic acid phosphate Ester sodium salt, L-ascorbyl phosphate potassium salt, divalent metal salt ^ Ascorbyl phosphate magnesium salt, L-ascorbyl phosphate calcium salt, L-ascorbyl phosphate aluminum salt of trivalent metal salt; Sodium salt of monovalent metal salt of L-ascorbyl sulfate, L-ascorbyl sulfate potassium salt 、 Ascorbyl sulfate magnesium salt of divalent metal salt, L_ascorbic acid sulfate calcium salt, L-ascorbic acid sulfate aluminum salt of trivalent metal salt, L_ascorbic acid monovalent metal salt ^ ascorbic acid sodium salt, L- Potassium ascorbate and divalent metal salt ^ Anti-acid _____- 27- This paper size applies to China National Standard (CNS) A4 (21〇χ 297 mm) (Please read the precautions on the back before

、 \ 5 口 线 1238066 25 Printed by A7 B7 of the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (salt, j-ascorbate, L-ascorbate, trivalent metal salt, etc .. Derived as hydrogen gm And specific restrictions, which can be exemplified by ammonia condensate and sugar condensate, alkyl hydrogen condensate and sugar condensate produced by hydrogen radical introduction-carbon number, etc. Ursolic acid and its derivatives are not particularly limited. For example, examples include: osmic acid, acetic acid monobutyl vinegar, osmic acid-octyl vinegar, osmic acid-palmit vinegar, Acid-stearic acid vinegar, acetic acid-cinnamon vinegar, acetic acid-benzoic acid vinegar, bismuth dibutyl molybdenum, dipalmitate gallate, distearyl gallate, dioleate, etc. Ethyl acetate, etc., and 'as placental extract' can be used as a water-soluble placental extract-a cosmetic raw material sold by the user, for example, a placenta of a mammal such as a cow or a human being can be used Wash, 峪 ', after removing blood, breaking and freezing, extract the water-soluble components, and then The material obtained by removing impurities. As a plant extract having a whitening effect, examples thereof are: chrysanthemum, tea, clove, licorice, tincture, tang tong, korean tincture, yeyao, mountain mask 'maimendong, Extraction of Ginger, Mochi, Mulberry, Magnolia, Yinchen Song, Axian = Huang Cen, San Hui, Hollyhocks' Shimogao, Qitian Qi, Suna, Hong Fu Zi Zhuo, Rosemary, Coriander, etc. Among them, the chrysanthemum extract can be taken from the flower of chrysanthemum [Cham〇miUa MC〇mp〇sitae)] with a hydrophilic organic solvent such as methanol, ethanol, propanol, propylene glycol, i 3 butanediol or the like. The mixed media is extracted in the form of an extract, and the extract can also be obtained in the form of a dry powder by drying the extract. In addition, ramie oil, peach kernel oil, flowing stone trowel, soybean oil, myristate, isoproteol, lower fatty acid triglyceride, intermediate fatty acid trigan-28- This paper standard is applicable to Chinese National Standard (CNS) Α4 Specifications (

I!-. 1 .--- „-I ^ --- (Please read the precautions on the back before this page) 1238066

V. Description of the invention (%) The purpose of the oil, steaming oil to the sun, hexanoic acid neobutanediol g organic solvent or its missed solvent. In this hair: in-one or two Λ of mother chrysanthemum extract. In this chrysanthemum extract, it generally contains, Mingguang: oxycoumarin, chrysanthemum, chrysanthemum, celery, oxalazine, spiroether, and so on. The extraction method 'is exemplified as follows. The first step is to dry the mother chrysanthemum flower, add squalane finely, and then stir the lower bagan, ", and then squeeze and separate it to obtain the extract. After extracting it to temperature: 50 ℃, immerse, &Amp; This extraction appears to be filtered to form a chrysanthemum extraction extraction compound: As a spirulina compound ', for example, it can be used in combination with the following compounds: Dandelion sterol, feather (please read the precautions on the back first, then this page)

(6),-= 'mouth [where the wavy line represents that the bonding state can be Z or ε] The Spiro ether compound (6) is printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs. It is reported that Cosmos chamomile gerbera (Biomedical Miscellaneous, 64 volumes, 384 ~ 388 pages, ΐ &quot; 2 years), daisy lettuce (Agric. Biol · Chem · 48 volumes, 1367 ~ 1369 pages, 1984), = Several species of Asteraceae, such as Asteraceae, Artemisia, Leucanthemum, etc., can be isolated by ordinary methods after the components obtained by solvent extraction and steam distillation are isolated. This spiro ether compound ⑷ can inhibit the production of pigments in melanocytes, reduce or eliminate pigments caused by external stimuli such as ultraviolet rays; -29- This paper size applies Chinese National Standard (CNS) A4 (210X297) Centimeter) 1238066 A7 B7

V. Description of the invention (28), it is advisable to mix 0% by weight, especially 0.005% to 5% by weight in the overall composition, and if 0.0001 to 5% by weight is blended, the use feeling is more satisfactory. Also, 'when using plant extracts, based on the starting point of whitening effect and stability', it should be converted into dry solids in the entire composition, and 0.00001 ~ 5 heavy scratches should be blended ', especially 0.005 ~ 3% by weight. If it is formulated with 0.001 to 2 weights of 0 / 〇, sufficient whitening effect, moisturizing effect, and prevention of rough skin can be obtained. The effect is improved, and the use feeling and stability are also good and satisfactory. It has an anti-inflammatory effect The substance (b-3) may be used in combination of one kind or two or more kinds. In the overall composition, it is preferable to mix 0.001 to 5% by weight, especially 0.001 to 2% by weight. If 0.001 to 1% by weight is blended. In addition, in addition to the above-mentioned ingredients, the cosmetic of the present invention may be appropriately blended with oils, organic acids, alkalis, Surfactants, External absorbents, powders, pigments, dyes, preservatives, rust inhibitors, antioxidants, chelating agents, tackifiers, perfumes, water and other commonly used ingredients in pharmaceuticals, substances other than pharmaceuticals, and makeup. Specific In terms of oil content, examples include fluid paraffin, squalane, higher fatty acids, and higher alcohols; as organic acids, examples include citric acid, lactic acid, and the like; as bases, examples include Examples are caustic soda, triethylamine, etc. Among the surfactants, as hydrophilic surfactants, non-ionic surfactants can be exemplified by polyethylene oxide castor oil, polyethylene oxide Hardened castor oil, lauric acid polyoxyethylene hardened castor oil, Iso-31-This paper size is applicable to China National Standard (CNS) A4 specification (21〇 × 297 mm) I. Home-(Please read the back first (Items on this page), 1T 1238066 Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention (29) Hard moon acid acid polyethylene oxide hardened castor oil, polyethylene oxide hardened castor oil tar t Stearic acid di Polyethylene oxide sesame oil or hardened linseed oil derivatives, polyethylene oxide sorbitol monolaurate, polyethylene oxide sorbitol-standard palmitate, polyethylene oxide sorbitan monostearic acid Esters, polyoxyethylene sorbitan monoisostearate, polyoxyethylene sorbitan tetraoleate, and other polyoxyethylene sorbitan fatty acid esters, polyoxyethylene glyceryl monostearate, Fatty acid esters of polyethylene oxide glycol, such as polyethylene oxide glyceryl monoisostearyl ester, polyethylene oxide glyceryl triisostearyl ester, polyethylene oxide lauryl ether, polyethylene oxide hexyl decyl ether, polyethylene oxide Polyhexadecyl ether, polyoxyethylene stearyl ether, polyoxyethylene octadecyl ether, polyethylene oxide camellia ether, polyoxyethylene nonylphenyl ether, polyoxyethylene polyoxypropylene decyl tetradecyl ether, and other polyethylene oxides Polyalkylene oxide fatty acid ethers such as alkyl ethers, polyoxyethylene monooleic ethers, etc. Additive surfactants; other examples include polyglyceryl alkyl ethers, polyglycerol fatty acid esters, and sucrose fatty acids Ester and so on. / Also as an anionic surfactant, examples of which are: poly (ethylene oxide) 聚 polyoxyethylene alkyl sulfate-based surfactants such as lauryl ether triethanolamine, sodium lauryl sarcosinate, and lauryl urethane N-fluorenyl amino acid salt type surfactants such as sodium methalamic acid, sodium polyoxyethylene lauryl ether phosphate, sodium polyoxyethylene cetyl ether phosphate, diethylene oxide alkyl ether phosphate, trimer Polyoxyethylene alkyl ether phosphate surfactants such as ethylene oxide alkyl ether phosphate, dimer ethylene oxide nonylphenyl ether phosphate, sodium polyoxyethylene lauryl ether phosphate, sodium dimer ethylene oxide lauryl ether phosphate and many more. As amphoteric surfactants, the examples are alkyl betaine, alkane-32- This paper size applies Chinese National Standard (CNS) A4 specification (21〇X 297 mm)

1238066 A7 B7 V. Description of the invention (30) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs, betaine, alkyl betaine, etc .; as cationic surfactants, examples include dilong chain alkyl Quaternary ammonium salt, mono-long-chain alkyl quaternary ammonium salt, di-long-chain alkyl polyoxyethylene quaternary ammonium salt, bis (hydroxyalkyl) quaternary ammonium salt, quaternary ammonium salt with ammonium amine / ester chain Wait. Among them, a polyethylene oxide addition-molding nonionic surfactant is preferable, and an ethylene oxide calcined mole number of 20 to 60 is particularly preferable. As the ultraviolet absorber, exemplified are: benzophenone, tert-butyl-4-methoxy-diphenylhydrazone, dimethoxyglyceryl ethylhexanoate, ethylhexyl-4- Methoxycinnamic acid, para-amino benzoate, phenyl salicylate, and the like. The cosmetic material of the present invention can be produced according to a general method, and can be formed into any of liquid, water-in-oil or water-in-oil emulsion, gel, paste, and solid forms. Especially suitable for skin granules such as lotions, lotions, creams, beauty liquids, etc. The transdermal absorption enhancer of the present invention can remarkably promote the transdermal absorption of an effective ingredient blended in a skin external preparation, and has low skin irritation and excellent safety. That is to say, the granules of the present invention have low irritation to the skin and good feel for use, and the effective ingredients of the substance I have a moisturizing, whitening or anti-inflammatory effect. The transdermal absorption is improved, and it can be obtained at a low amount. Excellent skin roughening effect, whitening effect or anti-inflammatory effect. /, Examples Hereinafter, the present invention is illustrated by examples, but the present invention is not limited by these examples. Also, in the manufacturing examples 丨 ~ 丨 〇, the amine derivatives (in accordance with the above L—— ______- 33- This paper size is suitable for National Standards (CNS) A4 specifications (210x1 ^^ 7 1 In ·: it-=% 11-I iy li ·:---I (Please read the precautions on the back before this page) Thread 1238066

2. Description of the invention (S1, manufactured by the manufacturing method. The compounds used in the following examples are: The combination state of z in the corrugated portion of the general formula (6) is z, and the spiro ether compound B indicates that it is E. It is represented by the spiro ether compound e. Production Example 1 First, 2 liters of 3-methoxypropylamine 743 (834 moles) were fed into a 2 liter five: flask equipped with a dropping funnel, a nitrogen introduction tube, and a distillation device. Ethanol 15 liters, and then heated and stirred at 8 ° C under a nitrogen atmosphere, and 165.9 g (0.56 mol) of hexadecyl glycidyl ether was added dropwise thereto. After the dropwise addition was completed, the temperature was further increased at 80 C. It was stirred for 12 hours, and then ethanol and excess 3-methoxypropylamine were distilled off under reduced pressure. Finally, the residue was purified by a silica gel column to obtain 196.5 g of an amine alcohol derivative (4a). The rate is 91%, relative to hexadecyl hydroglyceryl ether.) (Step 1)., (Please read the precautions on the back before this page) ΟίδΗββ '

The physical properties of the amine alcohol derivative (4a) obtained by OH and vtf printed by J (4 a) N &lt; I (C'H2) 3 — OCH3 H, which are printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs, are shown below. Melting point of white solid: 53 ° C IR (Pneat, cm 3; 3340, 2930, 2855, 1470, 1310, 1120, 1065, 955, 900, 720 ° ^ -NM ^ CDCls 0.88 (t, J = 6.3Hz, 3H) , 1.25 ~ 1.45 (m, 26H), 1.45 ~ 1.85 (m, 6H), 2.57 ~ 2.76 (m, 4H), 3.32 (s, 3H), 3.38 ~ 3.48 (m, 6H), 3.77 ~ 3.89 -34- This paper size applies to China National Standard (CNS) A4 (210X 297 mm) '~ 1238066 A7 B7 V. Description of the invention (32 (ηι, αΗ) 〇r,; Η Equipped with stirring device, drip funnel, Into a 1-liter five-necked flask with a nitrogen introduction tube and a distillation device, distill the molten compound (4 a) obtained in the above (step base 1) 61.3 g (158.1 mmol) and a 28% solution of sodium methoxide in 1.53. G (7.91 mmol), and stirred at 60 ° C for 30 minutes under a nitrogen atmosphere. Secondly, under the same conditions, 38.3 g (15 8.1 mmol) of methyl tetradecanoate was added dropwise over 1 hour under the same conditions. Ear). After the dropwise addition was completed, the mixture was stirred at 60 ° C for 5 hours under reduced pressure (80-10 Torr) to terminate the reaction. After the reaction was cooled, it was purified by a silica gel column to obtain Amine derivatives (2a) 88.7 (Yield 94%) (step 2). (Please read the precautions on the back before this page)

OCHc (2 a), 11 Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs The physical properties of the amidine derivative (2a) obtained are shown below. Melting point of white solid: 48X: IR (^ neat? CHI ^ 3440, 2930, 2860, 1650, 1625, 1470, 1225, 1210, 1110, 950, 720. iH-NMK ^ CDCh, d): 0.88 (br t , J = 6.3Hz, 6H), 1.15 ~ 1.95 (m, 53H), 2.36 (t, J = 7.5Hz, 2H), 3.29 ~ 3.55 (m, 10H), 3.33 (m, 3H), 3.85 ~ 3.95 ( m, 1H). In a 1-liter five-neck flask equipped with a stirring device, a nitrogen introduction tube, and a distillation device, feed 94.5 g (158.0 mmol-35-35-) of the compound (2a) obtained in the above (step 2). CNS) A4 specification (210X297 mm) 1238066 A7 B7 V. Description of the invention (33) ears), 1.53 g of tetrabutylammonium bromide (4.74 mmol), 32.2 g of epichlorohydrin (347.6 mol), sodium hydroxide 12.6 g (315.0 mmol) and 66 liters of toluene were stirred under nitrogen at 45 ° C for 10 hours. Then, the obtained reaction mixture was washed three times with water at 70 ° C, and toluene and excess epichlorohydrin were heated under reduced pressure, and the residue was purified on a silica gel column to obtain a pyramine derivative (3a ) 94.9 g (92% yield) (step 5).

The physical properties of the obtained amidine derivative (3 a) are shown below.

Melting point of white solid: 38 ~ 39 ° C yneat, cni!); 2930, 2855, 1650, 1470, 1425, 1380, 12105 1120, 905, 840, 720 ^ -NMRCCDCls ^): 0.88 (br t, J = 6.0Hz, 6H), 1.10 ~ 1.45 (m, 46H), 1.45 ~ 1.90 (m, 6H), 2.2) ~ 2.48 (m, 2H), 2.50 ~ 2.68 (m, 1H), 2.70 ~ 2.85 ( m, 1H), 3.02 to 3.20 (m, 1H), 3.20 to 4.00 (m, 13H), 3.32 (s, 3H). In a 100 ml autoclave equipped with a stirring device, feed 71.3 g (109.0 mmol) of the compound (3 a) obtained above (step 5), 78 g (654.1 mmol) of water U, and hydroxide. 0.087 g of sodium (2.18 mmol) and 087 g of tetradecanoic acid (4.36 mmol); stirred in a closed system at 160 ° C. for 6 hours. In the reaction mix-36- This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) 'f Please read the precautions on the back before loading. · The consumer cooperation of the Central Standards Bureau of the Ministry of Economic Affairs, printed 1238066 Μ Β7 V. Description of the invention (34) After cooling, 'washed twice with 2% saline at 80X, and purified by a dream gel column' to obtain the target amine derivative (la) 68 3 g ( Yield (step 6)

0H

0H (la) Printed by the Consumers' Cooperative of the Central Bureau of Standards of the Ministry of Economy The physical properties of the amidine derivative (1 a) obtained are shown below. Colorless and transparent liquid JROneahCnT1); 3445, 2930, 2860, 1630, 1470, 1420, 1380 1305, 1210, 1120, 720 〇1H-NMR (CDC13 ^ δ) · 〇.88 (br t, J = 6.7Hz, 6Η) , 1.15 to 1.44 (m, 46Η), 1.44 to 1.95 (mι, 8Η), 2.25 to 2.45 (m, 2Η), 3.20 to 3.90 (m, 16Η), 3.33 (s, 3Η). In a 500-ml four-neck flask equipped with a stirring device, a nitrogen introduction tube, and a distillation device, 31.0 g (47.4 mmol) of the compound (3a) obtained in the above (step 5) and 11.9 g (663.7 mmol) of water were fed. ), 13.6 g (165.9 mmol) of sodium acetate and 104.9 g (1746.8 mmol) of acetic acid, stirred at 7 (TC for 19 hours under a nitrogen atmosphere. Then, excess acetic acid was distilled off under reduced pressure, A mixture containing ester · amidine derivatives (14a-1), (14a-2), and (14a_3) was obtained (step 7). C16H33

0H (Please read the precautions on the back before this page)-Binding · Order C13H27

On ^^ A ^ OCOCH; (CH2) 3-och3 (1 4 a-1 -37- This paper size applies to the Chinese National Standard (CNS) A4 specification (210X297 mm) 1238066 A7 B7 V. Description of the invention (35)

Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs. After removing the mixture containing these ester-amidamine derivatives from the flask, add 59.3 g of a 48% aqueous sodium hydroxide solution (711 2 mol), 18 g of water and 200 ml of butanol, and stirred at 80 ° C for 3 hours. After ordering ', the butanol was heated under reduced pressure, and the residue was diluted in 25OmL of toluene, and then washed twice with water at 70 ° C. Next, toluene was distilled under reduced pressure, and the residue was purified by a silica gel column to obtain the target amidine derivative (la) | 22.3 g (yield 70%) (step 8). Xin ^

Production Example 2 J First, in a 10-liter five-necked flask equipped with a dropping funnel, a nitrogen introduction tube, and a distillation apparatus, 4680 g (3-2.5 mol) of 3-methoxypropylamine and ethanol were fed. |. 900 grams, then heated and stirred at 80 ° C under a nitrogen atmosphere, and hexadecyl glycidyl ether 1.045 g (3.55 mol) was dripped into it for 3 hours, dripping | after the end 'Down again at 80 C; drop for 1 hour, and then heat the ethanol and excess methyl j oxypropylamine under reduced pressure, and finally crush the residue with a chromatography column i

I

I

-38-I The paper size is in accordance with the Chinese National Standard (CNS) A4 specification (2 丨 0X297 mm) 1238066 A7 B7 V. Description of the invention (36) Purification to obtain the product with amine alcohol derivative (4a) as the main component (Step 0. To the product obtained in the above (Step i) using the compound (2 a) in a 10-liter five-necked flask as the king component, add 9 82 g (0175 mmol) of potassium hydroxide in Under nitrogen inhalation, under reduced pressure (60 ～ 10〇〇ΓΓ) at 80. (: Feed the generated water, and shake it for 3 hours. Next, mix it under the same conditions. On one side, 8823 g (3.64 mol) of methyl tetradecanoate was added dropwise over 3 hours. At this time, the methanol produced was distilled off. After the dropwise addition was completed, nitrogen was blown under 'under reduced pressure ( 60 ~ 10 Torr) The remaining methanol is left at 60 ~ 45 ° C and stirred for 丨 0 hours, so that the reaction is completed, and a product containing the amidine derivative (2 a) as the main component is obtained (step 2 ). Add tetrabutylammonium bromide to the product obtained in the above (step 2) with the compound (2a) in the 10-liter five-necked flask as the main component. 33 9 g (0,105 mol), 712.5 g (7.70 mol) of epichlorohydrin and 21,000 g of toluene, under a nitrogen blow at 45 ° C under reduced pressure (150 to 50 Torr) While stirring, 1750.0 g (21.0 mol) of 48% hydroxide steel falling liquid was dripped in for 2 hours. After the dripping was completed, it was stirred for 10 hours under the same conditions to complete the reaction. The reaction was completed. After the mixture was washed 4 times with water at 70 ° C, toluene and excess epichlorohydrin were heated and distilled off under reduced pressure to obtain a product containing the amidine derivative (3 a) as the main component (step 5). The Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs printed 378.2 g (21.0 mole) of water in the product obtained in the above (step 5) with the compound (3a) in the 10-liter five-necked flask as the main component. , 48% sodium hydroxide aqueous solution 5.83 g (0.070 mol) and tetradecanoic acid 32.0 g (0.14 mol) 'under a nitrogen atmosphere, stirred at 100 ° C for 2.5 days. Then, the reaction mixture was stirred at 80 C After washing 3 times with 2% saline, add it under reduced pressure -39- This paper size applies Chinese National Standard (CNS) A4 specifications (2 10X 297 mm) 1238066 A7 B7 V. Description of the invention (37) Thermal dehydration to obtain 2261.5 g of the product containing the target compound (la) as the main component (step 6). This product contains 70% of the compound (1 a) In addition, it contains intermediates, reaction by-products, and the like represented by the following formula.

Cl6H33 \, ΟΗ cieH33 \

'OH I \ (CH2) 3 — 0CH3 k, (ch9) 3 — 〇ch3 H Ci3H27 ^ a c13H2? C〇2H C 13H27C02N’a

OH

OH (Please read the precautions on the back before this page) |

, 1T

OH C16H33〇

C13H27 eight 〇

Ox ^ A ^^ OCOC 13H27 〇CH3

Printed by the Staff Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs

0Λ-Η (n is an integer from 2 to 10) C16H33〇 C13H27

OH V〇C16H33

° CH3i 〇3〇 Cl3H27 -40- This paper size is applicable to China National Standard (CNS) A4 size (210X 297 mm) 1238066 A7 B7 V. Description of the invention (38

C16H330

OH 0H C13H27

OCirH 16Π33 (Please read the precautions on the back first, then this page) —install · too och3 C13H97

OH

Line 1T Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs

Production Example 3 Except that the tetradecanoate methyl ester in Step 2 of Production Example 1 was replaced by hexadecanoate phosphonium hexadecanoate, the same reaction as in Steps 1 and 2 of Production Example 1 was performed to obtain an amidine derivative (2b) (steps 1 and 2). (2 b) The size of this paper applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 1238066 A7 B7 V. Description of the invention (39) &gt; The physical properties of the amidine derivative (2 b) obtained as follows As shown. White solid

Melting point: 5 5 ° C IR (yneat, cm 3430, 2930, 2855, 1620, 1470 1205 1110 950, 720 ° 1H-NMR (CDC13 ^): 0.88 (br t, J = 6.4Hz, 6H), 1 26 to 1.89 (m, 57H), 2.36 (t, J = 7.6 Hz, 2H), 3.29 to 3.52 (m, 10H), 3.33 (s, 3H), 3.88 to 3.95 (m, 1H). After that, except Substituting the compound (2 &amp;) in Step 5 of Production Example 1 with the compound (2b) obtained in the above (Step 2), the same reaction as in Step 5 of Production 1 was performed to obtain a pyramine derivative (3b) (Step 5) (Please read the precautions on the back before this page)

1. The physical properties of the amidine derivative (3b) obtained by the 1T Consumer Standards Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs are shown below.

Melting point of white solid · 44 ~ 45 ° C IR (, eat, cm · 1); 2930, 2860, 1650, 1470, 1425, 1380, 1210, 1120, 910, 845, 755, 720 ° 1H-NMR (CDC13 ^ ά): 〇.88 (br t, J = 6.7Hz, 6Η), 1.15 ~ 1.45 (m, 50Η), 1.45 ~ 1.73〇, 4Η), 1.73 ~ 1.90 (m, 2Η), 2.25 ~ 2.48 (m, 2Η), 2.50 ~ 2.68 (m, __- 42 -___ This paper size applies to China National Standard (CNS) A4 specification (210X: 297 mm) 1238066 at B7 V. Description of the invention (40 iH) , 2.70 to 2.85 (m, 1H), 3.00 to 3.18 (m, 1H), 3 18 to 400 (m, 13H), 3.32 (s, 3H). Then, except for step 6 in Manufacturing Example 1, Compound (3 "was replaced with compound (3b) obtained in the above (Step 5), and tetradecanoic acid was replaced with hexadecanoic acid. The same reaction as in Step 6 of Production Example 1 was performed to obtain The target amine derivative (lb) (step 6). C16H33

(CH2) 3-0CH3 C15H31

0H (lb) (Please read the precautions on the back before this page) Printed by the Consumers Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs The physical properties of the amidine derivative (lb) obtained are shown below. White solid ^ Melting point: 3 3 ° C IR (^ neat, cm!); 3445, 2930, 2860, 1650, 1630, 1470, 1420, 1380, 1305, 1210, 1120, 1080 〇 ^ -NMRCCDCls ^): 0.88 ( br t, J = 6.4Hz, 6Η), 1.15 ~ 1.45 (m, 50Η), 1.45 ~ 1.95 (m, 7H), 2.25 ~ 2.55 (m, 3H), 3.20 ~ 3.92 (m, 16H), 3.33 (s , 3H). In a 500-ml four-necked flask equipped with a mixing device and a nitrogen introduction tube, 34.1 g (500 mmol) of the compound (3b) obtained in the above (step 5) and 25.5 g (250.0) of anhydrous acetic acid were fed. Mmol) and 25.3 g (250.0 mmol) of triethylamine, and stirred at 100 ° C. for 10 hours under a nitrogen atmosphere. Then, the reaction mixture was heated and concentrated under reduced pressure, and the obtained residue was subjected to a silica gel chromatography column-43- This paper is in accordance with China National Standard (CNS) A4 specification (21〇 × 297 mm), ιτ 1238066 A7 B7 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs. 5. Description of the invention (41) Purified and obtained 34.9 g (85% yield) of ester-amidamine derivative (14b) (step 7). The physical properties of the ester-fluorenamine derivative (14b) obtained by adding OCOCHs (14b) Cl5H3 to pyrene-_ are shown below. Brown transparent liquid ^ -NMRCCDCls ^) 0.88 (br t, j = 6.4Hz, 6H), 1.26 ~ 1.83 (m, 56H), 2.03 ~ 2.20 (m, 6H), 2.33 (t, J = 7.1Hz, 2H ), 3.12 to 4.35 (m, 15H), 3.32 (s, 3H), 5.04 to 5.43 (m, 1H) 〇 In a 200 ml four-necked flask equipped with a delivery device and a nitrogen introduction tube, feed the above ( Step 7) The obtained compound (14b) is 33.9 g (43.2 mmol), 0.42 g (2 · 16 mmol) of 28% methanol solution of sodium methoxide, and 200 ml of methanol in a nitrogen atmosphere. Stir at warm for 3.5 hours. Then, the reaction mixture was concentrated under reduced pressure while heating the reaction mixture, and the obtained residue was purified by a silica gel column to obtain 16.0 g (yield 53%) of the desired amidine derivative (lb) (step 8). Followed by "into a 3 liter four-neck flask equipped with a stirring device and a nitrogen introduction tube, feed 45.2 g (72.0 mmol) of the compound (2b) obtained in the above (step 2), 2.86 g of sodium hydride (119.2 Millimoles) and 800 ml of toluene were stirred under nitrogen at 55C for 30 minutes. Then, 34.8 g (121.5 mmol) of 1,2, isopropylidene dioxo-3-toluenesulfonylpropane was added thereto, and the mixture was stirred at -44-

(Please read the precautions on the back before this page). Binding and binding This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm) 1238066 Α7 Β7 V. Description of the invention (42) Mix for 8 hours. Thereafter, the reaction mixture was added with 20-liters of 2-propanol under ice-cooling, and the unreacted sodium hydride was made inert, and then concentrated under reduced pressure under heating. The obtained residue was purified by a silica gel column to obtain 51.0 g (yield 96%) of H-dimethycenane-fluorenamine derivative (16b) (step 11).

ch3〇 ^ C CH3 C16H33 (16b) N: C15H31, (ch2) 3-och3 (please read the precautions on the back and then the page) — the one obtained 1,3-dioxane-fluorenamine derivative ( The physical properties of 16b) are shown below. Colorless transparent liquid 1H-.NMR (CDC13): 0.88 (br t, J = 6.4Hz, 6H), 1.20 ~ 1.90 (m, 62H), 2.36 (t, J == 7 〇Hz 2H), 3.30 ~ 4.25 (m, 19). In a 2-liter four-neck flask equipped with a stirring device and a nitrogen introduction tube, feed the compound (16b) 51 obtained in the above (step 11) 51. 0 g (68 9 mmol), 0.50 g (2.63 mmol) of toluenesulfonic acid monohydrate, and 50 ml of methanol were stirred at room temperature under a nitrogen atmosphere for 12 hours. Then, the reaction mixture was added in It was concentrated under reduced pressure, and the obtained residue was purified by a silica gel chromatography column to obtain 41.0 g (yield 85%) of the amidine derivative (lb) (step 10). ^ Production Example 4 Except the steps of Production Example 1 The methyl tetradecanoate in 2 was replaced by dodecane_ -45- This paper is suitable for towel standard (CNS) A4 size (210X297 mm) ----------- -11 Central Printed by Standards Bureau Consumer Cooperatives 1238066 A7 B7 V. Description of the Invention (43) Except for methyl acid ester, the same reactions as those in steps j and 2 of Production Example i were carried out to obtain the amidine derivative (2c) (steps 1 and 2).

(CH2) 3 — 〇ch3 (2 c)

The physical properties of the obtained amidine derivative (2 c) are shown below. Colorless transparent liquid (OneaoCitT1); 3435, 2930, 2855, 1620, 1470, 720 〇H-NMR (CDC13 ^ ά): 0.88 (br t? J = 6.4Hz, 6H), 1.20 ^ l.9〇 (m49H) , 2.36 (t, J = 7.6 Hz, 2H), 3.25 to 3.52 (m, 10H), 333 (s3H) 3.88 to 3.95 (m, 1H). '' After that, except that the compound (2a) in Step 5 of Production Example 1 was replaced by the compound (2e) obtained in (Step 2), the same reaction as in Step 5 of Preparation 1 was performed to obtain 醯Amine derivatives (3e) (step 5), J 1220 111〇, (please read the precautions on the back before this page), 11 Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs

(3c) The physical properties of the obtained amine derivative (3c) are light yellow liquid as shown below. 46- This paper size is applicable to Chinese National Standard (CNS) A4 specification (210X297 mm) 1238066 A7 B7 Central Bureau of Standards, Ministry of Economic Affairs Printed by Employee Consumer Cooperatives. 5. Description of Invention (44) IR (yneat, cm * 1); 2940, 2875, 1750? 1650, 1470, 1380, 1210, 1120, 910, 845. iH-NMRCCDCh, d): 0.88 (br t, J = 6.4Hz, 6H), 1.15 ~ 1.45 (m, 42H), 1.45 ~ 1.75 (m, 4H), 1.75 ~ 1.90 (m, 2H), 2.25 ~ 2.50 (m, 2H), 2.50 to 2.68 (m, 1H), 2.70 to 2.85 (m, 1H), 3.00 to 3.18 (m, 1H), 3.18 to 4.00 (m, 13H), 3.32 (s, 3H). Then, except that the compound (3 a) in Step 7 of Production Example 1 was replaced with the compound (3 c) obtained in (Step 5) above, the other reactions were performed as in Steps 7 and 8 of Production Example 1. The target amine derivative (ic) is obtained (steps 7 and 8). The physical properties of the amidine derivative (lc) obtained from 0H C 16½J (1 c) l ^ (CH2) 3 ~ 〇CH3 are shown below. Colorless and transparent liquid IROr ^ cnT1); 3430, 2930, 2860, 1650, 1630, 1470, 1380, 1260, 1210, 1115, 1080, 795, 720. ^ -NMRCCDCls · 0.88 (br t, J = 6.7 Hz, 6H), 1.15 to 1.45 (m, 42H), 1.45 to 1.97 (m, 8H), 2.25 to 2.45 (m, 2H), 3.15 to 3.92 (m, 16H), 3.33 (s, 3H). Manufacturing Example 5 Except replacing the tetradecanoic acid methyl ester in Step 2 of Manufacturing Example 1 with Kao Corporation _—_ -47- This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) (please first Read the notes on the back, and then on this page) — Packing. Taiji Line 1238066 A7 B7 V. Description of the Invention (45) The weight of your Lunaco P-70 (weight of tetradecanoic acid, hexadecanoic acid, and octadecanoic acid) Ratio 3.70.27), except for the methyl ester of Lunacu p_70 produced by reaction with methanol under heating and reflux in the presence of a catalyst, the other steps are the same as those in steps 1 and 2 of Production Example 1 The reaction yields a fluorenamine derivative (2d) (steps i and 2). C16H33

(CH2) 3-〇CH3 (2d) (a = c13c27, c15h31, c17h35 mixture) The physical properties of the desired amine derivative (2 d) are shown below. Melting point of white solid: 50 ° C IR (^ neat, cm!); 3430, 2930, 2860, 1620? 1470, 1205, 1110, 950, 720 ° After 'except the compound (2b) in Step 11 of Manufacturing Example 3 ) Instead, it is reacted with the compound (2d) obtained in the above (Step 2), and the resulting 1,3-dioxane-fluorenamine derivative (16d) is subjected to the next step without purification. Except for the reaction, other reactions were carried out in the same manner as in Steps 11 and 10 of Production Example 3 to obtain the desired amidine derivative (Id) (Steps 11 and 10). (Please read the notes on the back before this page)

1T, printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs

0H L \ CH2) 3-〇CH3 (Id) (A = mixture of CnC27, Ci5H31, C17H35) -48- This paper size applies to China National Standard (CNS) A4 (210X 297 mm) 1238066 Central Standard of the Ministry of Economic Affairs Printed by the Consumer Cooperative of the Bureau A7 B7 V. Description of the invention (milk) The physical properties of the amidine derivative (1 d) obtained are shown below. White solid

Melting point: 3 2 ° C 2930, 2860, 1650, 1630, 1470, 1380, 1210, 1120, 1080, 720 〇 Manufacturing Example 6 Except replacing the hexadecyl glycidyl ether in Step 1 of Manufacturing Example 1 with ten Except for the octyl glyceryl ether, the same reaction as in Step 1 of Production Example 1 was performed to obtain an amine alcohol derivative (4e) (Step 1).

Cl8H37 \ 〇, Y ^ OH? X (CH2) 3 ~ 0CH3, Η. · 'The physical properties of the obtained amine derivative (4e) are shown below.

White solid melting point: 57 ~ 5 8 ° C IR〇neat, cnn1); 3340, 2930, 2855, 1470, 1120, 960, 900, 840, 720 ^ -NMRCCDCls, d): 〇.88 (t? J = 6.3Hz? 3H)? 1.25 ^ 1.45 (m, 30H)? 1.45 ^ 1.85 (m? 6H) 5 2.55 ~ 2.75 (m, 4H), 3.32 (s, 3H), 3.35 ~ 3.50 (m, 6H), 3.77 to 3.89 (m, 1H). After that, except for replacing the compound (4a) in step 2 of manufacturing example 1 with the compound (4e) obtained in the above (step 1), other systems were implemented and manufactured __ _-49- This paper standard applies to China Standard (CNS) A4 specification (210X297 mm) (Please read the precautions on the back before this page)

T 1238066 A7 B7 V. Description of the invention (47 1 Same step 2 reaction to obtain the amidine derivative (2c) (step 2) C 18½ (2 e)) ^ (CH2) 3-0CH3 C13H27 / \ 〇 The physical properties of the amidine derivative (2C) are shown below. White solid Melting point: 49 ° C IR (^ neat, cm'1); 3440, 2930, 2860, 1650, 1625, 1470, 1225, 1210, 1110, 950, 720. 1H-NMR (CDC13 ^ d): 0.88 (br t, J = 6.3Hz, 6H), 1.15 ~ 1.95 (m, 57H), 2.36 (ΐ, J = 7.5Hz, 2H), 3.30 ~ 3.55 (m, 10H), 3.33 Fen, 3H), 3.85 ~ 3.95 (m, 1H). Then, except that the compound (2 a) in Step 5 of Production Example 1 was replaced with the compound (2 e) obtained in (Step 2) above, the other reactions were performed as in Step 5 of Production Example 1 to obtain the purpose. Hydrazine derivative (3e) (step 5). (Please read the notes on the back before this page)

, 1T Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economy C 1 and 7

j ^ (ch2) 3-och3 ^ The physical properties of the amidine derivative (3e) obtained are shown below. Colorless transparent liquid vn © at, cm »2930, 2860, 1650, 1425? 1380? 1260 1210 -50- This paper size applies to China National Standard (CNS) A4 (210X297 mm) 1238066 Employees' Cooperatives, Central Standards Bureau, Ministry of Economic Affairs Printing A7 B7 V. Description of the invention (48) 1120, 910, 720 ^ -NMRCCDCls ^): 0.88 (br t, J = 6.0Hz, 6H), 1.10 ~ 1.45 (m, 50H), 1.45 ~ 1.90 (m , 6H), 2.25 to 2.50 (m, 2H), 2.50 to 2.68 (m, 1H), 2.70 to 2.85 (η, 1Η), 3.01 to 3.20 (m, 1Η), 3.20 to 4.00. , 13Η), 3.32 (s, 3Η). Then, except that the compound (3a) in Step 7 of Production Example 1 was replaced with the compound (3e) obtained in (Step 5) above, the same reactions as those in Steps 7 and 8 of Production Example 1 were performed to obtain The target amidine derivative (le) (steps 7 and 8).

0H C. 13H37. (1 e)

The physical properties of nC JL XCH2) 3--0CH3 C-13H27 '' and the obtained amidine derivative (1 e) are shown below. White solid Melting point · 2 3 ° C IR (P neat, cm)); 3425, 2930, 2860, 1650, 1630, 1470, 1380, 1220, 1210, 720. ^ -NMRiCDCls ^): 0.88 (br t, J = 6.7Hz, 6H), 1.17 to 1.45 (m, 49H), 1.45 to 1.92 (m, 8H), 2.22 to 2.45 (m, 2H ), 3.20 ~ 3.90 (m, 17H), 3.33 (s, 3H). Manufacturing Example 7 Except replacing the compound (4 a) in Step 2 of Manufacturing Example 1 with -51 of Manufacturing Example 6-This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) (Please read first (Notes on the back page)

,-! 1238066 A7 B7

The compound (4e) obtained in step 1 was replaced with twelve carboxylic acid methyl ester, except for methyl methyl ester, and the same procedure as in step 2 of Production Example 1 was performed. Wherever amidine derivatives were obtained (2 f) (steps 1 and 2).

The physical properties of the obtained amidine derivative (2 f) are shown below. Melting point of white solid: 54 ~ 55 ° C IR ^ neaucnT1); 3430, 2930, 2855, 1620, 1470, 1220, 1205 1110, 950, 885, 720 ° 1H-NMR (CDC13 ^ ά): 0.88 (br t , J = 6.4Hz, 6H), 1.25 ~ 1.95 (m, 61H), 2.36 (t, J = 7.6Hz, 2H), 3.29 ~ 3.52 (m, 10H), 3.33 (s, 3H), 3.88 ~ 3.95 ( m, 1H). Thereafter, except that the compound (2a) in Step 5 of Production Example 1 was replaced by the above-mentioned compound (2 f), the same reaction as in Step 5 of Production Example 1 was performed to obtain a pyramine derivative (3 f). (Step 5). (Please read the precautions on the reverse side before ^! ^ This page) — Install · Book, 11th line · Printed by the Employees' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs

The physical properties of the obtained amidine derivative (; 3 f) are shown below. -52- This paper size applies to Chinese National Standard (CNS) A4 (210X 297 mm) 1238066 A7 B7 V. Description of the invention (50) White solid

'Married' point: 4 5 ~ 47 C cm-1); 2930, 2860, 1650, 1470, 1425, 1380, 1210, 1120, 910, 845, 755, 720 ^ -NMRCCDCls ^ d): 0.88 ( br t, J = 6.7Hz, 6H), 1.15 to 1.45 (m, 54H), 1.45 to 1.73 (m, 4H), 1.73 to 1.90 (m, 2H), 2.25 to 2.48 (m, 2H), 2.50 to 2.68 (m, 1H), 2.70 to 2.85 (m, 1H), 3.00 to 3.18 (m, 1H), 3.18 to 4.00 (π, 13H), 3.32 (s, 3H). Thereafter, except that the compound (3a) in Step 7 of Production Example 1 was replaced with the compound (3f) obtained in the above (Step 5), the same reactions as those in Steps 7 and 8 of Production Example 1 were performed. The desired amidine derivative (if) is obtained (steps 7 and 8). (Please read the notes on the back before this page)

, 1T

The physical properties of the amidine derivative (1 f) obtained by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs are shown below. White solid Melting point: 3 5Ό IR〇neat, cm · 1); 3445, 2930, 2860, 1650, 1630, 1470, 1420, 1380, 1305, 1210, 1120, 1080. iH-Nl ^ CDCh, β): 〇.88 (br t, J = 6.4Hz, 6Η), 1.15 ~ 1.45 (m, 54Η), 1.45 ~ 1.95 (m, -53-) This paper is applicable to China National Standard (CNS) Α4 Specification (210X297 mm) Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 1238066 Α7 _______B7 V. Description of the Invention (51) 7Η (, 2.25 ~ 2.55 (m, 3H), 3.20 ~ 3.95 (m, 16H), 3.33 (s, 3H). Production Example 8 Except that the hexadecyl glycidyl ether in Step 1 of Production Example 1 was replaced by tetradecyl glycidyl ether, Step 1 of Production Example 1 was implemented By the same reaction, an amine alcohol derivative (4 g) was obtained (step 1).

The physical properties of the obtained amine alcohol derivative (4 g) of CuH29 \ 〇, ^ OH N &lt; Ug) ((CH'2) 3-OCH3) are shown below. White solid

Melting point: 47 ° C IR (^ neat, cm'1); 3340, 2930, 2855, 1470, ΠΙΟ, 1120? 1065, 995, 900, 720. 1H-NMR (CI) C13 ^ δ): 0.88 (t, J = 6.3Hz 3H), 1.25 to 1.45 (m, 26H), 1.45 to 1.85 (m, 6H), 2.57 to 2.75 (m, 4H) , 3.32 (s, 3H), 3.38 to 3.48 (m, 6H), 3.75 to 3.88 (η, 1Η) 〇, except that the compound (4 &amp;) in Step 2 of Production Example 1 was replaced by The compound (4g) obtained in the above (step 1) 'was replaced with methyl cetanoate except methyl hexadecanoate, and the same reaction as in step 2 of Production Example 1 was performed to obtain amidine. Derivative (2g) (step 2).

Cl4H.29 \ '〇 / Yad (2g) 1 &gt; αΗ2) 3-〇〇.Η3 C15H31 -54- This paper size applies to China National Standard (CNS) A4 (210X 297 mm) (Please read the back (Notes on this page)

1T 1238066 A7 B7 V. Description of the invention (52) The physical properties of the amidine derivative (2 g) obtained from the household tablet are shown below. White solid melting point: 47X: IR (pneat, cm) '3440, 2930, 2855, 16205 1470 1205 1110 950, 720 c ^ -NMRCCDCls ^ δ): 0.88 (br t, J = 6.4Hz, 6H), 1.26 ~ 1.89 (m, 52H), 2.36 (t, J = 7.6 Hz, 2H), 3.29 to 3.52 (m, 11H), 3.33 (s, 3H), 3.88 to 3.95 (m, 1H). Then, except that the compound (2 a) in Step 5 of Production Example 1 was replaced with the compound (2g) obtained in the above (Step 2), the same reaction as in Step 5 of Production Example 1 was performed to obtain 醯Amine derivative (3 g) (step 5). (Please read the notes on the back before ^^ this page) |

The physical properties of the donkey amine derivative (3 g) obtained by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs are shown below. Colorless transparent liquid neat, cm]); 2930, 2860, 1650, 1470, 1425, 1380, 1210, 1120, 910, 845, 755, 720 〇h-NMRCCDCU, d): 0.88 (br t, J = 6.7Hz, 6H), 1.15 to 1.45 (m, 46H), 1.45 to 1.73 (m, 4H), 1.73 to 1.90 (m, 2H), 2.25 to 2.50 (m, 2H), 2.50 to 2.68 (m , 1H), 2.70 ~ 2.85 (m, 1H), 3.00 ~ 3.18 (m, 1H), 3.18 ~ 4.00 (m, -55-) This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 1238066 Economy Printed by the Consumer Standards Cooperative of the Ministry of Standards of the People's Republic of China A7 B7 5. Invention Description (53) 13H), 3.32 (s, 3Π) 〇 Then, except that the compound (38) in Step 7 of Manufacturing Example 1 was replaced by the above (Step 5) Except for the obtained compound (3g), the same reactions as those in steps 7 and 8 of Production Example 1 were performed to obtain the desired amidine derivative (lg) (steps 7 and 8).

0H J. (Lg) L (CH2) 3—OCH3

The physical properties of the amidine derivative (1 g) obtained by C15H3I are shown below.

White solid melting point: 27 ° C IR (Pneat, cm 4; 3445, 2930, 2860, 1650, 1630, 1470, 1420, 1380, 1305, 1210, 1120, 1080, 720 〇1H-NMR (CDC13 ^ ά): 〇 .88 (br t, J = 6.4Hz, 6H), 1.15 to 1.45 (m, 45H), 1.45 to 1.93 (m, 7H), 2.20 to 2.60 (m, 3H), 3.20 to 3.90 (m, 17H), 3.33 (s, 3H). Production Example 9 Except the replacement of 3-methoxypropylamine in Step 2 of Production Example 1 with 2-methoxyethylamine, other examples of implementation and production The same reaction as in step 1 of 1 to obtain the amine alcohol derivative (4h) (step 1). (Please read the precautions on the back before ipf this page), -5 mouth

1238066 A7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs _____B7 V. Description of the invention (54) The physical properties of the amine alcohol derivative (4 h) obtained by Lu Jin are shown below. Melting point of white solid · 54 ~ 55 ° C IR (Pneat, cm); 3430, 2920, 2855, 1470, 1120, 1065, 900, 720 ^ -NMRCCDCls ^ d): 0.88 (t, J = 6.3Hz, 3H ), 1.25 to 1.70 (m, 30H), 2.57 to 2.76 (m, 4H), 3.32 (s, 3H), 3.38 to 3.46 (m, 6H), 3.77 to 3.89 (m, 1H). After that, except that the compound (4a) in Step 2 of Production Example 1 was replaced with the compound (4h) obtained in the above (Step 1), and tetradecyl methyl ester was replaced with methyl cetanoate Otherwise, the same reaction as in Step 2 of Production Example 1 was performed to obtain a fluorenamine derivative (2h) (Step 2). The physical properties of the amidine derivative (2h) obtained from Cl6H33 \ ^ J (2h) pXCH2) 2-0CH3CisHsi ^ O are shown below. Melting point of white solid: 51 ~ 52 ° C IROneat, cm-1); 3420, 2920, 2855, 1620, 1470, 1110, 720 0 1H-NMR (CDC13 ^): 0.87 (t, J = 6.4Hz, 6H), 1.15 to 1.70 (m, 55H), 2.25 to 2.50 (m, 2H), 3.20 to 4.00 (m, 11H), 3.34 (s, 3H). ____- 57-_ This paper size applies to China National Standard (CNS) A4 (21 OX 297 mm) (Please read the precautions on the back before this page) |

， 1T-age — 1238066 Printed A7 ______ B7 by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (W) and then 'except that the compound (2 a) in step 5 of manufacturing example 1 is replaced by the above (step 2 ) Except for the obtained compound (2h), the same reaction as in step 5 of Production Example 1 was performed to obtain a fluorenamine derivative (3h) (step 5).

The physical properties of the obtained amidine derivative (3h) are shown below. Colorless and transparent liquid IR〇neat, cm · 1); 2930, 2855, 1650, 1470, 1420, 1380, 131Q, 1250, 1190, 1120, 910, 850, 720. ^ -NMRCCDCls ^^): 0.88 (br t, J = 6.4Hz, 6Η), 1.13 ~ 1.45〇, 50Η), 1.45 ~ 1.70 (m, 4H), 2.30 ~ 2.50 (m, 2H), 2.50 to 2.70 (m, 1H), 2.70 to 2.85 (m, 1H), 3.00 to 3.20 (m, 1H), 3.20 to 4.00 (m, 13H), 3.32 (s, 3H). Then, except that the compound (3 a) in Step 6 of Production Example 1 was replaced by the compound (3 h) obtained in the above (Step 5), the same reaction as in Step 6 of Production Example 1 was performed to obtain the purpose. Amidamine derivative (lh) (step 6).

0H. (1 h) L XCH2) 2--〇CH3 C15H31 -58- This paper size applies Chinese National Standard (CNS) A4 specification (21 〇χ297 mm) (Please read the precautions on the back before this page) — Equipment · Taiding 1238066 A7 B7 V. Description of the invention (56) The physical properties of the amidine derivative (1 h) obtained are shown below.

White solid Melting point: 31 ~ 32 ° C Han 0neat, cm-1); 3450, 2930, 2860, 1630, 1470, 1380, 1300, 1190, 1160, 720. 1H-NMR (CDC13 ^): 0.88 (t, J = 6.4 Hz, 6H), 1.15 to 1.75 (m, 54H), 2.20 to 2.45 (m, 3H), 3.20 to 3.90 (m, 17H) , 3.33 (s, 3H). After that, except that the compound (2b) in Step 11 of Production Example 3 was replaced by the compound (2h) obtained in the above (Step 2), the same reaction as in Step 11 of Production Example 3 was performed to obtain 1 , 3-Dioxane-fluorenamine derivative (16h) (step 11). ch3 V ^ ch3

Cl6Hs3 \ / 、 '〇 / 丫 (1 6 h)

Wch2) 2-〇ch3

CibHsi / ^ O Printed by the Consumer Standards Cooperative of the Central Bureau of Standards of the Ministry of Economics The physical properties of the 1,3 · dioxane-fluorenamine derivative (16h) obtained are shown below. Colorless transparent liquid ^ -NM ^ CDCh ^ δ): 0.88 (t, J = 6.4Hz, 6Η), 1.15 ~ 1.70 (m, 54Η), 1.34 (s, 3Η), 1.40 (s, 3H), 2.36 (t, J = 7.0 Hz, 2H), 3.25 to 4.30, 19H). -59- This paper size applies the Chinese National Standard (CNS) A4 specification (210X 297 mm) 1238066 Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7. 5. Description of the invention (57) Except for the manufacturing example 3 The compound (16b) in step 10 is replaced with the compound (16h) obtained in the above (step 11), and the same reaction as that in step 11 in Production Example 3 is performed to obtain the target amidine derivative. 0h ) (Step 10). Production Example 10 Except for replacing 3-methoxypropylamine in Step 1 of Production Example 1 with ethylamine, the same reaction as in Step 1 of Production Example 1 was performed to obtain an amine alcohol derivative (4i) ( step 1).

The physical properties of the obtained amine alcohol derivative (4i) are shown below.

Melting point of white solid: 60 ~ 61 ° C IROneat, cm 3: 3400, 2930, 2855, 1470, 1310, 111〇, 955 720-^ -NMRCCDCls ^ ά): 〇.88 (t, J = 6.4Hz, 3Η) , L.ll (t, J = 7.2Hz, 3 ，), 1.15 ~ 1.70〇, 3〇H), 2.55 ~ 2.80 (m, 4H), 3.35 ~ 3.53 (m, 4H) 3.79 ~ 3 93 (m , 1H). After that, except that the compound (4a) in Step 2 of Production Example 1 was replaced with the compound (4i) obtained in the above (Step 1), and the methyl tetradecanoate was replaced with methyl hexadecanoate Other than that, the implementation is the same as step 2 of manufacturing. _ _60_ This paper size is applicable to the Chinese National Standard (CNS) M specification (BOX29? Male thin) (Please read the precautions on the back before this page}. 1238066 A7 B7 V. Description of the invention (58) Reaction to obtain the amidine derivative (2i) (step 2)

(2 i) The physical properties of the obtained amidine derivative (2i) are shown below. White solid Melting point: 5 6 ° C IR (^ neat, cm'1); 3410, 2930, 2860, 1625, 1470, 1380, 1305, 1245, 1210, 1110, 950, 855, 720. ^ -NMRCCDCls ^). 0.88 (t, J = 6.4 Hz, 6H), 1.15 to 1.75 (m, 57H), 2.34 (t, J = 7.6 Hz, 2H), 3.30 to 3.55 (m, 9H), 3.85 ~ 4.00 (m, 1H) 〇f 乂, and then except the compound (2a) in Step 5 of Production Example 1 replaced by the compound (2i) obtained in the above (Step 2), other implementation and production examples The same reaction as in step 5 of 1 yields the amidine derivative (3i) (step 5). (Please read the notes on the back before

, 11 Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs C16H33

The physical properties of the amidine derivative (3i) obtained by C15H31 (3 i) are shown below. Colorless and transparent liquid IR (Pneat, 011 ^)., 2930, 2855, 1650, 1470, 1425, 1380, 1210 · -61-This paper size applies to China National Standard (CNS) A4 (210X 297 mm) Ministry of Economic Affairs Printed by the Consumer Standards Cooperative of the Central Bureau of Standards 1238066 A7 _____ B7 V. Description of the Invention (59) 1120, 905, 840, 720 ° 1H-NMR (CDC13 ^ d): 0.88 (br t, J = 6.4Hz, 6H) , 1.10 ~ 1.75 (m, 57H), 2.25 ~ 2.50 (m, 2H), 2.50 ~ 2.70 (m, 1H), 2.70 ~ 2.85 (m, 1H), 3.00 ~ 4.00 (ιη, 12Η ) 〇, except that the compound (3a) in Step 6 of Production Example 1 is replaced by the compound (3 丨) obtained in (Step 5) above, the same reaction as in Step 6 of Production Example 1 is performed, The desired amidine derivative (li) is obtained (step 6).

0H C ΐ6Η33 J (1 i) * j &ch; ch2-ch3

The physical properties of the obtained amidine derivative (li) are shown below.

White solid Melting point: 35 ~ 36 ° C IR〇neat, cm]); 3445, 2930, 2860, 1630, 1470, 1420, 1380, 1305, 1210, 1120, 720. 1H-NMR (CDC13 ^ δ) 0.88 (br t, J = 6.4Hz, 6Η), 1.13 ~ 1.75 (m, 57Η), 2.31 (t, J = 7.5Hz, 2H), 3.20 ~ 3.90 (m, 16H). Examples 1 to 10 The cosmetics having the composition shown in Table 1 were produced by a general method, and the skin permeability and skin rough chain improving effects of the amine compounds used as moisturizers and agents were evaluated. 62- This paper size is in accordance with Chinese National Standard (CNS) A4 specification (210X 297mm) (Please read the precautions on the back before this page) li clothes · order 1238066 Α7 Β7 V. Description of the invention (60) The results are shown in in FIG. 1. (Evaluation method) (1) Skin permeability A quantitative measurement of one of the cosmetic materials was applied to the skin surface of Fa, Luo + Meng Bu on the Yucatan peninsula mini pig, and placed in a constant temperature room (temperature: 3rc, humidity: saturation) in. After a certain period of time has elapsed, after removing the non-permeated components remaining on the skin surface, the permeated components are drawn out and collected to determine the percutaneous absorption of the amine compound. Transdermal absorption is expressed in terms of unit area (&quot; g / cm2). (2) Skin roughening improvement effect A 200- to 50-year-old female i 0 who had rough skin on the cheeks in winter was used as a test subject, and different skin external agents were applied to the left and right frequencies for 2 weeks. On the next day after the end of the application for 2 weeks, the appearance of rough skin was observed with the naked eye, and the measurement was performed based on the following criteria. Scores are expressed as average 値. 〇: No rough skin 1: Slight rough skin 2: Slight rough skin 3: Slightly rough skin 4: Severe rough skin (please read the precautions on the back first, then this page) — Packing, 11 threads Economy, Deng Central Bureau of Standards, Consumer Co-operation, Printing --____ -63- This paper size is applicable to CNS Standard A4 (2⑴χ 297 mm) 1238066 A7 ------——__ B7 V. Invention Explanation (62) From the results in Table 1, it can be known that the granules with percutaneous absorption enhancer of the present invention are all those with high skin penetration of amine test derivatives and excellent skin roughness improvement effects. In addition, its skin irritation is low. The application feeling also belongs to: Good 0 Example 1 1 to 2 0 The cosmetic material having the composition shown in Table 2 was manufactured by a general method, and evaluated in the same manner as in Example 1. Improves skin permeability and rough skin. Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs -65- This paper size applies to the Chinese National Standard (CNS) A4 (210X 297 mm)

Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 1238066 • Description of the invention (64) From the result of =, it can be seen that the granulated material of the present invention, which is formulated with a percutaneous absorption enhancer, has a high permeation amount of the hydrazine derivative, And have excellent skin rough round improvement effect. x, its skin irritation is low, and the use feeling is also good. Examples 21 to 2 2 Cosmetics having the composition shown in Table 3 were produced by a general method, and their skin permeability and skin roughness improvement effects were evaluated in the same manner as in Example 1. Table 3 Ingredients (% by weight) Example 21 22 Polyoxyethylene octyldodecyl ether (2eo) 2 2 Sorbitol 5 Diglyceryl isononanoic acid isotridecyl ester (β: 16.56) 1 5 1 1 Isostearic acid-myristic acid diglyceride (β: 18 · 43) 1 丄 1 Succinic acid 0.5 0.5 Water and other Gutton gum 0.5 0.5 Skin roughness improvement effect 1.1 +0.3 1.3 +0.4 Ingredients are all moisturizers Those with high skin penetration and excellent skin roughness improvement. In addition, the skin irritation is low, and the use feeling is also good. Example 2 3 to 3 2 Cosmetics having the compositions shown in Tables 4 and 5 were produced by a general method, and were evaluated in the same manner as in Examples 1 to 10, and the skin permeability of the spiro ether compound as a whitening agent was evaluated. The results are shown in Tables 4 and 5. -67- This paper size applies to China National Standard (CNS) A4 (210X297 mm)

1238066 A7 B7 V. Explanation of the invention (67 is shown in Table 4, Table 5 Correspondence β η, and the present invention is formulated with a granule 1 containing a percutaneous absorption enhancer. The compound has high skin permeability and has excellent properties. Whitening. It has high safety and good use feeling. Example 3 3 ~ 3 4 The composition of π in Table 7 is <whitening granules, manufactured according to a general method. These whitening cosmetics are the same as the examples. The method of 1 to 10 was used to test the permeability of the spiro ether compound to the skin. In addition, the whitening effect was tested by the following method. The results are shown in Table 7 of TF (the whitening effect test for pigment spots caused by UV-B). Twenty healthy male subjects irradiated the ultraviolet rays in the UV-B area with a minimum of twice the amount of erythema in the inner part of the upper wrist, and irradiated them twice a day for j times! Total! Monthly test samples are continuously applied to the test site to investigate its whitening effect. The evaluation was performed using a color difference meter (minolta &amp; Co., CR_300), and L * was calculated from the obtained Munsel 値値, use aal * 値 for its recovery. Also, AAL * 値 is The definitions are as follows: L * 値 of the coated area and the uncoated area of the sample before the sample starts to be coated are respectively set to Lq, L0, and L * 値 of each location after continuous coating for 1 month, respectively Let it be, L !, and AAL * is represented by the following formula: Δ AL * = (Li-L〇)-(Li'-L〇 ·) The evaluation result is an average of the evaluation scores of 20 test subjects. The relationship between the evaluation scores and the judgment criteria is shown in Table 6. -70- This paper size applies to China National Standard (CNS) A4 specification (210X297 mm) (Please read the precautions on the back before

Ordered by the Consumer Standards Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs 1238066 V. Description of Invention (68) A7 B7 Table 6 Evaluation Criteria Judging Criteria 5 1.0 ^ AAL * 4 0.5 ^ AAL * &lt; 1.0 3 0.2 ^ AAL * &lt; 0.5 2 0 ^ AAL * &lt; 0.2 1 △ △ L * &lt; 0 (please read the precautions on the back before printing this page) li Printed by the Staff Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs -71-This paper size applies to Chinese national standards (CNS) A4 specifications (210X 297 mm) 1238066 A7 B7 V. Description of the invention (70) Examples 35 to 37 The cosmetic materials with the composition shown in Table 8 were manufactured by a general method, and were the same as those in Examples 3 3 to 3 4 Way to evaluate the whitening effect. The results are shown in Table 8. Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 73- This paper size is applicable to the Chinese National Standard (CNS) A4 (210X297 mm) 1238066 A7 ________B7___ V. Description of the Invention (72) Examples 38 to 40 The composition shown in Table 9 The cosmetic is manufactured according to a general method, and its anti-inflammatory effect is evaluated. The results are shown in Table 9. (Evaluation method) To the inside of the upper wrist of 20 healthy male subjects, a Toshiba FS-20SE lamp 'was used to irradiate ultraviolet rays in the UV-B area with a minimum of 2 times the amount of erythema (2MED). Immediately afterwards, various cosmetics of 15 ju 1 were applied, and the degree of redness (a * 値) and skin temperature after 24 hours were measured. The degree of reddening was measured using a color difference meter (CR-300 manufactured by Minolta Corporation), and a * 値 was calculated from the obtained Munsell 赛. The degree of a * after UV-B irradiation for 24 hours is higher than that before UV-B irradiation, which is defined as Δ #. The skin temperature was measured using a radiation thermometer (manufactured by Tasco Japan, thi_50).

Determination. J results are expressed as mean 値. (Please read the notes on the back before ^^ this page)-Yikou Ding Printed by the Consumers Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 75 This paper size applies to the Chinese National Standard (CNS) A4 specification (21 OX 297 mm) 1238066 A7 B7 V. Description of the Invention (74) Example 4 1 to 4 5 A whitening cosmetic having the following composition was produced by a general method. Example 4 printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs (Emulsion) (ingredients) (% by weight) (1) Palmitic acid 1.0 (2) Stearic acid 1.0 (3) Hexadecanol 1.0 (4) One ( Hexadecyl) osmic acid steel salt 2.0 (5)-sorbitan stearate 0.5 (6) glycerol 10.0 (7) ethanol 5.0 (8) spiro ether compound Z 0.5 (9) isononanoic acid isotridecyl ether (D = 16.56) 3.0 (10)-Isostearic acid monomyristic acid diglyceride = 18.43) 1.0 (11) Lactic acid 2.0 (12) Blood protein 3.0 (13) Pure water The rest of Example 42 (emulsion) (ingredients) ) (% By weight) (1) 1,3-butanediol 3.0 (2) Glycerin 5.0 (3) Sodium hyaluronate 0.2 (4) Polypropionic acid (Carbopol, manufactured by Goodrich) 0.2 (5) Hydroxide Potassium 0.06 -77- This paper size is in accordance with Chinese National Standard (CNS) A4 (210X 297 mm) (Please read the precautions on the back before this page) li clothes • • 4 1238066 Α7 Β7 V. Description of the invention ( 75) 1.0 0.2 0.2 0.01 5.0 1.0 1.5 2.0 1.0 5.0 (16) bovine placenta extract (compared with EUFA LUKE CP-20, manufactured by Ichimaru FALUX) 1.0 (6) polyethylene oxide hardened castor oil (40E. Ο. ") (7) —Istearylglyceryl ether (8) —Sorbital stearate (9) Spiroether compounds (10) Isotridecyl isononanoate (d = 16.56) (11) Monoisostearic acid Monomyristic acid diglycerol vinegar (β = 18.43) (12) Succinic acid (13) Urea (14) ε-pentylhexanoic acid (15) Matricaria (mature chrysanthemum liquid, manufactured by Ichimaru Fluxus) ( (Please read the precautions on the back first, then this page) 1.1 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (17) Pure water remaining * 1: Ethylene oxide addition mole number Example 43 (Cream ) (Ingredients) (% by weight) (1) 2.0 stearic acid (2) —Isotridecyl nonanoate = 16.56) 7.0 (3) —Istearic acid monomyristic acid diglyceride (β = 18.43) 4.0 (4) Cholesterol 3.0 (5) Cetyl alcohol 2.0 (6) 2-hexadecyl phosphate arginine 2.0 (7) Polyoxyethylene hardened castor oil (40E.O · ") 0.5 (8) α--iso Stearyl Glyceryl Ether 0.2 (9) Spiroether Compounds 0.01 0.01 -78- The size of this paper applies to Chinese National Standard (CNS) A4 (210 X 297 mm), 1T 1238066 A7 B7 V. Description of the invention (76) Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs (10) Ether compound E (11) Succinic acid (12) Phenolic acid (13) Glycerin (14) Sodium hyaluronate (15) Polyacrylic acid (Kaporbo, manufactured by Goodrich) (16) Sodium hydroxide C17) Pure water * 1 ·· Molybdenum Ethylene Glycol Example 44 (Cream-like primer) (Composition) (1) Titanium oxide (2) Sericite (3) Iron oxide (red, yellow, black) (4) Yamanashi Glycolic anhydride fatty acid ester (Leodolu MO-6, manufactured by Kao Corporation) (5) Isotriyl isononanoic acid g (d = 16.56) (6) —Istearic acid myristic acid diglyceride (D = 18.43) (7) Dimethyl polysiloxane (KF96A6cs, manufactured by Shin-Etsu Chemical Co., Ltd.) (8) Spiro ether compound Z (9) Glycerin (10) Pure water Example 45 (foundation) (ingredient) (1) ) Titanium oxide 〇〇〇 1. 〇 0 0 05 15 The rest (heaviness ° / °) 6.〇8.〇1.2 5.〇12.0 3.0 30.0 0.01 2.0 The rest (wt%) 10.0

-79- This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm) 1238066 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (77) (2) Sericite 30.0 (3) Talc Others (4) Nanling clay 5.0 (5) Iron oxide red pigment 2.0 (6) Yellow iron oxide 2.5 (7) Black iron oxide 0.1 (8) Polyethylene powder 4.0 (9) Isotridecyl isononanoate (d = 16.56) 1.5 (10)-Isostearic acid monomyristate diglyceride = 18.43) 0.6 (11) Dimethicone 12.0 (12) Spiro ether compound Z 0.01 The whitening makeup obtained in Examples 41 to 45 It is expected that the effective ingredients have good transdermal absorption, excellent whitening effect, high safety, and good use feeling. &gt; -80- This paper size applies the Chinese National Standard (CNS) A4 specification (210 '乂 297mm)' Announcement .. Amendment! 8th of this year's supplement: proposed 12 4 application date 86. 11. 05. Case No. 86116465 Category AW Vox The above columns are filled by this bureau) 1238066 Chinese Manual Correction Page (December 87) A4 C4 Cloud 1 Patent Specification Invention I. Name New Type 1 Chinese Transdermal Absorption Accelerator and its containing agent Cosmetics composition English &quot; PERCUTANOUS ABSORPTION PROMOTING AGENTS AND COSMETIC COMPOSITIONS CONTAINING THE SAME &quot; Name Nationality Inventor and Creator h. Nakasaka 3.Kyoko Kawakami 5.Komoko Yamamoto 1-6. Sekiji Yamazaki 4.Yokoko Sasaki 6. Nakajima Co., Ltd., Residence 1-6 · Sumida, Sumida-ku, Tokyo 2_ 1-3 Kao Co., Ltd. The name (name) is set in the research institute Kao Co., Ltd. Employees' Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs. Nationality Residence, Domicile (Office) Name of Representative Name of the Presentation Japanese Nationality Tokyo Nihonbashi Kababacho 1-Chome 10, Chuo-ku, Tokyo 8 Goto Takuya Line 8 123 80 Secret 86116465 Patent Application Chinese Manual Revised Page (March 91) V. Description of Invention () Α7 Β7 Amendment

Supplement for this month and month 3U 5 = (5d2 + 5p2 + 5h2) 1/2 (Γ 5d: Term based on the dispersion force (Vandvar force) of London (dispersion 〒) 5 p: Term based on the molecular polarity (polarity term ): Hydrogen bond-based term (hydrogen bond term) (ϋ) (iii) (iv) 5d = ZFdi / E Vj 5p = (EFpi2) 1/2 / EVi 5h = (EFhi / ZVi) 1/2 Fdi, Fpi , Fhi: Mohr's gravitational constant Vi: Mohr's volume, 5d, 5p, as described above can be calculated from the Mohr's gravitational constant (Fdi, Fpi, Fhi) of the atomic group using the above formulas (U) to (iv), but in In this specification, Mohr's gravitational constant is the value determined by Van Krevelen, and Mohr's volume (V0 is the volume value of the atomic group determined by Fedor. This solubility parameter 5 is in the range of 15.7 &lt; 5 S 17.2. The oils in the range (^) are specific examples, and examples include: ethyl arachidate, ethyl linolenate, isononyl isononanoate, octyl isopalmitate, isopropyl linoleate, and isonon Caprylic acid vinegar, oleyl linoleate, isotridecyl isononanoate, ethyl linoleate, isopropyl isostearate, isohexadecyl octoate, oleyl octanoate, isostearyl octanoate , Isodecyl third valerate, isodecyl isononanoate , Behenyl vinegar vinegar, octyldodecyl oleate, isostearyl tertiary acid, isostearyl isostearate, isoctadecyl isostearate, isostearic acid Fatty ester, octyldodecanoate, isopropyl oleate, octyldodecyl dimethyl octanoate, hexyldecyl dimethyl octanoate, oleyl myristate, stearyl eicosanate, Ethyl oleate, decyl oleate, isohexadecyl stearate, octyl stearate, octyl stearate-6- This paper size applies to the middle head @ 家 标准 (CNS_) M specifications (Zhuo) · public y 123 Revised Page of Chinese Specification for Patent Application No. 86116465 (March 91) Amendment of Α7 Β7, Supplement of March 3 of this year 91. &amp; | g 5. Description of the Invention (Base Dodecyl Acetate, Isostearyl Palmitate, Isohexadecyl palmitate, octyl palmitate, isostearic acid myristate, isohexadecyl myristate, isotridecyl myristate, octyldodecyl myristate, lauric acid Isostearate, hexyl isostearate, myristyl isostearate, lauryl isostearate, stearyl oleate, cetyl oleate, isobutyl stearate, isobutyl palmitate Ester, brown Isopropyl ester, octyl myristate, isooctyl laurate, butyl isostearate, octanoate nonanoate, isopropyl myristate, isoamyl laurate, isohexanoate laurate, pivalic acid meat Myristyl ester, isobutyl nonanoate, lauryl palmitate, myristyl palmitate, ethyl stearate, ethyl palmitate, butyl myristate, ethyl laurate, methyl myristate, laurel Methyl acid, etc. Among these, isotridecyl isononanoate is preferred. These oil agents (a-1) can be used singly or in combination of two or more. In the present invention, it is preferable to use one or two or more kinds of oil agents (a-1) selected from these solubility parameters 5 in the range of 15 · 7 &lt; 5 $ 17 · 2, and selected from the solubility parameter 5 One or two or more kinds of oil agent (a_2) in the range of 17.5S δ $ 21.0. Here, as the component (a-2), an oil agent having a solubility parameter 5 in the range of 175 &lt;: (5 $ 2 1 · 0, for example, propylene glycol dinonanoate vinegar, diisopropyl sebacate, and the like can be exemplified. Propyl ester, glyceryl tricaprylate, glyceryl tridecanoate, 'monoisobutyric acid adipic acid, neopentyl monodecanoate, propylene glycol didecanoate, dihexyl adipate, triethyl Glycerol ricinoleate, diisopropyl adipate, glyceryl tridecanoate, diglyceryl triisostearate, diethyl sebacate, diglyceryl monostearate , Dibutyl adipate g, etc. Among them, particularly preferred is monoisostearic acid myristic acid diglycerol g. Combination ingredients (a-1) and (a-2) are used as ingredients ( a-1) It is advisable to use. This paper size applies to China National Standard (CNS) A4 (210 X 297 mm)

Hold

Line 1238066 amended 3L this month to add 9L3. Chinese Patent Application No. 86116465 Amendment Sheet (March 91)

27 Amendment: Replacement page of Chinese specification of Patent Application No. 12380 ^ 6116465 (April, 1994) V. Description of the invention (ut has the effect of preventing and improving the pigmentation and pigmentation, and has a whitening effect on the skin (Kei 7- No. 206657, etc.), = ,, as the anti-inflammatory agent (b_3), is a substance having anti-inflammatory effect, as long as it is used in skin external preparations of ^ ^, there are no special restrictions, and the examples are · Glycyrrhizic acid and its salts, Glycyrrhetinic acid and its salts, isopropylaminohexanoic acid VIII, &quot; ^, allantoin, chlorinated lysozyme, guaiamus, 'methyl salicylate, oryzanol, etc.' Among them, Glycyrrhetinic acid, glycyrrhetinic acid stearyl lindensate, and 6-pentylhexanoic acid are preferred. These wounds (b) 'can be quickly absorbed to the skin by mixing with component (a) and applying to the skin. In the skin. If it is a component for the purpose of local action, it can be deeply / redundantly penetrated into the skin to exert excellent effects. If it is for the purpose of systemic action, the ingredient will be transferred to the blood and play the same role. Excellent effect. Therefore, with these ingredients (a) and ingredients (1 The effect of (b) is significantly enhanced by the effect of (b). The proportion of these ingredients (b) in the cosmetic of the present invention varies according to their type and purpose, and cannot be generalized. Generally speaking, relative to (a) 丨 parts by weight, 0.0001 to 10 parts by weight are preferably used, which is better. It is used in an amount of 0.001 to 丨 by weight. In the cosmetic of the present invention, the amount of each constituent component varies depending on the type of the component (b), etc. The component (a) is preferably 0.001 to 40% by weight relative to the total amount of the cosmetic, which is particularly good. It is 0.001 to 30 weight. / q. The humectant (b-1) can be used in combination of one kind or two or more kinds, and 0.0001 to 15% by weight, especially 0.0001 to 10% by weight, more preferably 0.0001 to 5% by weight, should be blended in the entire composition. Feels better. Substance (b-2) with whitening effect, can be used in combination of one or two. -30- This paper size is applicable to China National Standard (CNS) A4 specification (210X297 mm) A7 B7 123 16465 Patent Application Chinese Specification Replacement Page (May 1992) V. Description of the invention (61 Skin roughness improvement effect Ϊ cv Hi Hi cold m 1 0 ^ 2 ^^ ^-· »-· p- crq CD Q- 〇cr Ρ Ingredients (% by weight) Poly Ethylene oxide octyl dodecyl ether (20E.Ο.) Polyoxyethylene hexyldecyl ether (20E.〇.) Triisostearic acid polyethylene oxide hardened castor oil (50E.Q) Polyethylene oxide hardened castor oil ( 5 0Ε.Ο.) Polyoxyethylene sorbitan monostearate (20E.〇.) Sorbitan monostearate amide derivative (1 a) Melting point 2 5 ° C Squalane (5-2 15 · 7) Isotridecyl isononanoate ((5 = 1 6.56) Monoisostearic acid-myristic acid diglyceride (6-2 1 8.4 3) Succinic acid 86% glycerol 1,3-butane Glycol Hydroxide 0.4 ± 0.2 15.2 2 1 1 10 2 0.5 10 5 Other 0.5 Example 0.6 ± 0.3 Η- * 2 1 1 10 2 0.5 10 5 Other 0.5 to 0.7 ± 0.2 13.5 2 1 1 2 10 2 0.5 10 5 remaining 0.5 υο 0.4 ± 0. 2 16.4 2 1 1 10 2 0.5 10 5 remaining 0.5 0.4 ± 0.3 15.5 2 1 1 1 10 2 0.5 10 5 remaining 0.5 LTi 0.7 ± 0.3 12.9 2 1 1 5 2 0.5 10 5 remaining 0.5 0.8 ± 0.1 13.6 2 1 1 5 2 0.5 10 5 remaining 0.5 0.9 ± 0.4 12.4 2 1 1 1 5 2 0.5 10 5 remaining 0.5 〇〇0.6 ± 0.2 14.7 2 1 1 5 2 0.5 10 5 remaining 0.5 0.7 ± 0.3 Η-^ 2 1 1 5 2 0.5 10 5 The remaining 0.5 3.0 ± 0.5 U) 1 1 7 0.5 10 5 The remaining 0.5 H—k Comparative Example | This paper size applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm) -64-123 16465 patent application A7 B7 Chinese manual replacement page (May 1992) 5. Description of the invention (Skin roughness improvement effect CV t 2 j ΓΤ3% &gt;) fr Hi 1 ο p 3 sr crq ^ a &gt; cl o cr p Ingredients (% by weight) Polyoxyethylene octyldodecyl ether (20E.O.) Polyoxyethylene hexyldecyl ether (20E.O.) Triisostearic acid Polyethylene oxide hardened castor oil (50E.〇.) Polyethylene oxide hardened castor Sesame oil (50E.O.) polyethylene oxide sorbitan monostearate (20E.O.) sorbitan monostearate amide derivative (If) melting point 35 ° C squalane ( 5 = 15 .7) Isotridecyl isononanoate (5-2 16.56) Monoisostearic acid-myristic acid diglyceride (5 = 1 8.4 3) Succinic acid 86% glycerol 1,3-butanediol hydrogel 0.3 soil 0.1 19.5 2 1 1 10 2 0.5 10 5 remaining 0.5 Example 0.4 ± 0.2 17.9 2 1 1 10 2 0.5 10 5 remaining 0.5 0.5 ± 0.2 15.8 2 1 1 2 10 2 0.5 10 5 remaining 0.5 0.3 ± 0.1 22.4 2 1 1 10 2 0.5 10 5 remaining 0.5 0.6 ± 0.2 15.5 2 1 1 1 10 2 0.5 10 5 remaining 0.5 0.3 ± 0.2 Η- ^ 00 2 1 1 5 2 0.5 10 5 remaining 0.5 0.6 ± 0.1 15.4 2 1 1 5 2 0.5 10 5 remaining 0.5-0.5 ± 0.2 16.3 2 1 1 1 5 2 0.5 10 5 remaining 0.5 0.4 ± 0.2 18.5! 2 1 1 5 2 0.5 10 5 remaining 0.5 0.7 soil 0.3 丨 14.6! 2 1 1 5 2 0.5 10 5 The remaining 0.5 K) 3.4 ± 0.6 • Private 1 1 7 0.5 10 5 The remaining 0.5 K) Comparative example &gt; 2 This paper size applies to China National Standard (CNS) A4 specification (210 X 297 mm) -66- 123 16465 patent Replacement page of the Chinese manual of the application (May 1992) Α7 Β7 qx Five Ming instructions 65 * 1: Man | 一 6 Jiang ^ ram pick seven 鎿 * 2: 鸰 黑 合 岭 参 Ε / 燕 SMb ^ 参 ζ = 5 / 1 ^ δίί ^ # ^ | # (满 1 | ^ | 命 爸爸 ^ 118 + b ^ | ^ Mount | such ^^^ I ^ l ^ l ^ lww (// g ^ n10

k 1 m n o P b ο d e f g h braid! UCVID berry ΦΙΝ + ΗΝ black (20E.OJ ~~ effective! Ub 6 berry hard &amp; l (20Eb / w W 驷 ^ forgive effect ticks ^ berry 脒 ^ ginseng net (50 «02: braid! UCV6 berry Combined stepping ginseng & (5 0 E. 0 / w effect! UbD respect £-doped S | Sf 丨) ¾ garlic 黪 rest (20EO .; E-side iridium i | Sf 丨 garlic 漭 rest bird black ^ Life father ^ ί ^ 509Λ5 · 7) 丨 _ 涔 lick 粦 丨 冱 .§.Weibu Bu 漭 fen rest ^ = 18.43) 6 _; &amp; ^ 觳 (&gt; ^ 黑 (09Π22.23) β ^ β 86% r3-Tl · ^ *, $ ram wheat (畤 #%) 0.67 P5 10 2 P5 10. ° 1 2 d, 0 · 62 ° 1 10 2 0.5 10 5 牯 瘵 0.5 2 0.600 P1 10 2 P5 10 5 pull P5 25 Ρ72 P1 10 2 P5 10 5 0.5 2 26 ds Ρ75 0.1 10 2 P5 10 5 Private game ° 5 27 ο ΟΝ Ο ο ο Κ) ο Κ) Κ) 00 -68- This paper size applies Chinese National Standard (CNS) ) A4 size (210 X 297 mm) Replacement page of Chinese manual for patent application No. 1238 fox No. 16465 (May 1992) A7 B7 V. Description of invention (66) 2

If this (^ lII ^ l life parameter 8, h β command ^ lt ^ l one such as ~~ ^^ Ι ^ Ι »Ι ^ Ι ^ Ι (// © Ί)

k 1 mno P 0 defgh ^ llub 6 berry + ll: + l ^ black (20E.OJ) ~~ braid #ubp special &amp; difficult ^ black (2sb · two) VI »Wear (50« 〇 二 \ Effect 烨 二 cvo &gt; ^^ Step on Elephant Fen (5 0 E b / ONE) braid! UCV6 respect &amp;-淞 鏔 飒 §f 丨 涔 涔 黪 黪 睡 (20EO 二: 淞 杂飒 Sf 丨 涔 Garlic 漭 filled with SiMb 呤 Refinate J 瀹 1509Λ5.7) ρ ^ β 丨 丨 Garlic ㈣ 丨 a㈣ € 粦 卜 粦 &gt; '&amp; gg (09H18.4 3) 2i_ ^ 8i (&gt; ^ Black (09H22.23) β ^ β 86% 4 Net rs-Ths !, Λ * Ρ63 2 0 · 5 10 5 Ρ5 0.1 2 0.7 払 2 0.5 10 5 Private 瘵 5 P1 2 6969 2 55 10 5 55 0.1 2 Ρ59 2 0.5 10 5 lot 瘵 Ρ5 0.1 2 29 30 3 1 32 0.18 Ρ5 10 5 轱 棼 0.5 Ρ1 5 0.15 2 0.5 10 5 private treatment 0.5 ° 1 6 -69- This paper size applies to China National Standard (CNS) A4 specifications (210 X 297 mm) Amendment Sheet for Chinese Manual of Patent Application No. (March 91) A7 B7 Amendment This Month 3 Supplement 9L &amp;! 3 V. Description of the Invention (69) * 1: Tick ^ 钚 Consolidation脒 ^ 焯 * 2: 燕 黑 ^ 命 # £ / 喿 禺 ^ 命 参 2: = 5/1 ~ 詾 命 蓥 kb ο de Jf OQ h Debate ^ 6 Tu 涔 ^ Handling bath (50 «〇 / 一) E-difficult pregnancy Turn (cy Λ5.7) 驷 屮 嵙 驷 + ^ 憩 (0? = 16.56) 丨 驷 涔 vegetable braid 丨 2- 丨 Office 嵙 lacquer 4 lacquerware ^ &quot; 18.43) ILSi + _ + l · Rest ^ = 18.53) β 86% 4 Reckless today (14 #%) 4.95 0 · 59 2 1 001 6 2 0.5 10 5 and lacquer P5 昝 1:33 -PX.98 0 · 62 .2 1 001 6 2 0.5 10 5 lacquer P5 詻 詻 j34 2 · 11 Ρ13 ° 5 10 5 Lacquer P5 001 2 vrcv ^ J: 5 -72-

This paper size applies to China National Standard (CNS) Α4 size (210 X 297 mm) A7 B7

Revised Page of Chinese Specification for Patent Application No. 12 ^ 0 ^ 65 (March 91) Five Ming instructions issued * 1 * 2 * 3 * 4 Concentrated bismuth 鸯 摒 (丨 ^ 爷 命 ^ * 鸯 &gt; &gt; 3 ) Go shopping every _ iridium (丨 & Private # &gt; Drive &gt; &gt; Don't) Retrospective VMCV 噼 Jl ^ &gt; &gt; Evaluation score of whitening effect (average 値) Miscellaneous dagger wear &amp; η · Photo ^ Gong Tΐί Π # 参 泽 尊 a ^ pi ^ ^ \ ^ 〇〇 ^ Thin $ 绺 II ^ Garlic 鲥 4 w ^ 〇m «G 〇II · * ^-5 Ingredients (% By weight) 4.23 2 1 0.9 6 6 2 0.5 10 5 The remaining 0.5 LO examples, 1 4.06 2 1 0.9 6 2 0.5 10 5 the remaining 0.5 LO 〇 4.55 2 1 1.0 6 2 0.5 10 5 the remaining 0.5 LO 2.05 2 1 0.9 | 8 0.5 10 5 The rest 0.5 Comparative example '1.98 2 1 1 8 0.5 10 5 The rest 0.5 -74- This paper size applies to China National Standard (CNS) A4 specifications (210 X 297 public love) 1¾ §6% ^ patent Amendment page of the Chinese manual of the application (March 91) A7 B7 Amendment of this month 3 Add 91U3 Ming l2MEDr ^ kf24lvll ^ 卜 1 ^ bismuth 1 ^ (+ core_) | 33 · 一一 33 · 2 | 33 · 一一33100 | 33.7 | 34 Say * 1 &quot; Full!谇 6 谇 ^ 糸 引 ^ 烊 明 * 2: 棊 Ruin-X.CV Mingshen E / ZΠ5 / 1 Sha Fumingshenfa, five ____ 73 to IUCV6 berry 涔 Cold to do _ wear (5 〇E ό / w £-淞 # 郗 Pregnant 丨 涔 Garlic pain 磔 ε 丨 ^ _ 卩 Welding secretion office 筘 (09Λ5.7) 驷 屮 Smoke handle + W ^ (5H16.56) 丨 驷 涔 Garlic braid S (δ Λ8.43) Choosing β 86% 4 buds 1,3-ΤΗ «Swallow casting (141Φ%) 6 2 P5 10 5 Batch paint 0.5 3 * 009 P1 2 38 6 2 0.5 10 5 Lacquer 0.5 Production 06 P1 2 Special 1 ^ Xuan 39 P1 6 2 0.5 10 5 Pull # 0.5 Ϊ 2 0.5 10 5 Lacquer 0.5 Production 87 0.1 2 ° 5 10 5 牯 0.5 Production 69 ° 1 2 9 6 2 ° 5 10 5 Lacquer 0.5 5 2 1 10 -76-

This paper size applies to China National Standard (CNS) Α4 (210 X 297 mm)

Claims (1)

12 a The oil agent (a ") in the range of $ 17 · 2 is an effective ingredient, wherein Ul) is selected from the group consisting of ethyl arachidonic acid ethyl ester, ethyl linolenic acid, isononyl isononanoate, octyl isopalmitate, and linoleic acid. Isopropyl ester, octyl isononanoate, oleyl linoleate, isotridecyl isononanoate, propyl ethyl linoleate, isohexadecyl octoate, oleyl icosanoate, ethyl linoleate , Isostearyl isostearate, isodecyl second valerate, isodecyl isovalerate, behenyl icosanoate, octyldodecyl oleate, isostearyl tertate Esters, isostearyl isostearate, isoodecyl isostearate, isostearyl eicosanoate, octyldodecanoate, isopropyl oleate, octyl dimethyl octanoate Dodecyl vinegar, dimethyl hexyldecanoate, oleyl myristate, stearyl eicosanate, ethyl oleate, decyl oleate, isohexadecyl stearate, octyl stearate, Octyl dodecyl stearate, isostearyl palmitate, isoodecyl palmitate, octyl palmitate, isostearyl myristate, isooctyl myristate, isodedecyl myristate, My bean Octyldodecyl acid, isostearyl laurate, hexyl isostearate, myristyl isostearate, lauryl isostearate, stearyl oleate, cetyl oleate, stearic acid Isobutyl ester, isobutyl palmitate, octyl myristate, isooctyl laurate, butyl isostearate, octanoate, isoamyl laurate, isohexyl laurate, myristyl pivalate, Isobutyl nonanoate, lauryl palmitate, decyl myristate, ethyl stearate, ethyl palmitate, butyl myristate, ethyl laurate, myristate. The paper standards are applicable to Chinese national standards (CNS ) A4 size (210X297 mm) 1238066 6.Scope of patent application Those who threw bismuth methyl ester and methyl laurate. 2 · Transdermal absorption enhancers, based on oil parameter (a_ i) with solubility parameter 5 in the range of i 5. 7 &lt; $ 1 7.2 芡 and $ 2 i · 0 in i 7 · 5 $ The oil agent (a _ 2) inside is an active ingredient, and the oil agent (&amp; _ 1) and (&amp; _ 2) are combined in a weight I ratio (a-10 / 1 ~ 1/2), where (A-1) is selected from the group consisting of arachidonic acid ethyl ester, ethyl linolenate, isononyl isononanoate, octyl isopalmitate, isopropyl linoleate, octyl isononanoate, and linoleate , Isotridecyl isononanoate, ethyl linoleate, isopropyl isostearate, isohexadecyl octanoate, oleyl eicosanoate, stearyl octoate, isodecyl third valerate, isopropyl Isodecyl nonanoate, behenyl icosanoate, octyldodecyl oleate, isostearyl trivalerate, isostearyl isostearate, isoodecyl isostearate, Isodecyl decanoate, octyldodecanoate, isopropyl oleate, dimethyl octyl undecanoate, dimethyl octanoate decanoate, myristyl oleate, Stearyl decadecanoate, ethyl oleate, decyl oleate, hexadecyl stearate, hard Octyl stearate, octyldodecyl stearate, isostearyl palmitate, isoctadecyl palmitate, octyl palmitate, isostearyl myristate, isoctadecyl myristate, isostearyl myristate Tridecyl ester, octyldodecyl myristate, isostearyl laurate, hexadecyl isostearate, myristyl isostearate, lauryl isostearate, stearyl oleate, oil Hexadecyl acid, isobutyl stearate, isobutyl palmitate, octyl vinegar, isooctyl laurate, butyl isostearate, octanoate-2-This paper size applies to Chinese national standards ( CNS) A4 size (210 X 297 mm) ^ Month, Isoprene 1§, Isolaurate, pivalate, hanonisobutanol, palmitate laurel, L fatty acid ethyl ester, P 4th AL team @ 夭, hard one 'palm bismuth ethyl ester , Butyl myristate, ethyl laurate 9 A methyl dancoate and methyl laurate. 3. A cosmetic composition, characterized in that it contains: () 0.001 to 40% by weight of an oil agent (a)) selected from a solubility parameter in a range of 15 7 $ &quot; • 2 &lt; and I ，, (b) a substance having a whitening effect, an anti-inflammatory effect, or a moisturizing effect with respect to the above (a) oil agent 丨 by weight part 0 and the ancient Mα 里 li part eight. (According to the cosmetic composition of item 3 of the patent application, one or two or more kinds of oil agents selected from the range of solubility parameter 5 within the range of 175 &lt; ^ 21〇 ^ are combined. 5) According to item 4 of the scope of patent application The cosmetic composition, wherein (") and U-2) are combined in a weight ratio of (a_1) / (a_2) = i0 / i ~ i / 2. According to the application of the patent scope α or item 2 A transdermal absorption enhancer, wherein (a-1) is isoxononanoic acid isodistriate. 7. The cosmetic composition according to item 3 of the patent application scope, wherein (a ") is selected from arachidonic acid ethyl ester Esters, ethyl linolenate, isononyl isononanoate, octyl isononanoate, isopropyl linoleate, octyl isononanoate, oleyl linoleate, isotridecyl isononanoate, ethyl linoleate Ester, Pesidine isostearate Φ -3-A8 B8 C8 Ϊ238066 Patent application scope Isopropanol, isohexadecyl octanoate, oleyl octanoate, isostearyl octoate, isodecyl third valerate , Isodecanoyl isononanoate, behenate eicosanate, octyldodecyl oleate, isostearyl tertiary acid, isostearyl isostearate, isostearate Hexyl ester, isostearic acid eicosanoate, octyldodecanoate, isopropyl oleate, octyldodecyl dimethyl octanoate, hexyldecyl dioctanoate, oleyl myristate , Stearyl icosate, ethyl oleate, decyl oleate, isohexadecyl stearate, octyl stearate, octyldodecyl stearate, isostearyl palmitate, palmitic acid Isohexadecyl Ester, Octyl Palmitate, Isostearyl Myristate, Isohexadecyl Myristate, Isotridecyl Myristate, Octyl Dodecyl Myristate, Isostearyl Laurate, Isostearate Hexyl stearate, myristyl isostearate, lauryl isostearate, stearyl oleate, cetyl oleate, isobutyl stearate, isobutyl palmitate, propyl palmitate Esters, octyl myristate, isooctyl laurate, butyl isostearate, octyl nonanoate, isopropyl myristate, isovaleryl laurate, isohexyl laurate, myristyl pivalate , Isobutyl nonanoate, lauric vinegar palmitate, decyl myristate, ethyl stearate, ethyl palmitate, myristic acid's butyrate, ethyl laurate, A unitary purpose myristic acid and lauric acid are methyl. 8. A cosmetic composition according to item 7 of the scope of the patent application, wherein (&amp; 1) is isotridecyl isononanoate. 9. Transdermal absorption enhancer according to item 2 of the scope of patent application, wherein (a _ 2) -4-1238066-C8 ____ __- 丨 丨 6. The scope of patent application is selected from propylene glycol dinonanoate, sebacic Diisopropyl acid, glycerol tricaprylate, glycerol tridecanoate, dioxetane adipate, neopentyl glycol monodecanoate, propylene glycol didecanoate, dihexyl adipate, Ethyl ricinoleate, diisopropyl adipate, glyceryl tridecanoate, diglyceryl triisostearate, diethyl sebacate, diglyceryl monoisostearate g purpose and those who have adipic acid dibutyl vinegar. 10. The transdermal absorption enhancer according to item 9 of the scope of the patent application, wherein (a-2) is monoisostearic acid monomyristyl diglyceride or octyldodecyl lactate. 1L The cosmetic composition according to item 4 of the scope of the patent application, wherein (a-2) is selected from the group consisting of propylene glycol dinonanoate, diisopropyl sebacate, glyceryl tricaprylate, glyceryl tridecanoate, and adipic acid Diisobutyl ester, neopentyl didecanoate, propylene glycol didecanoate, hexadecane, hexadecanoate, triethylgreen ricinoleic acid glyceride, diisopropyl adipate, three Capric acid vinegar, diglyceryl triisostearate, diethyl sebacate, monoglyceryl monomyristate and diglycerol adipic acid. 12. The cosmetic composition according to item 11 of the scope of patent application, wherein (a-2) is monoisostearic acid monomyristyl diglyceride or octyldodecyl lactate. 13. The cosmetic composition according to item 3 of the scope of application for a patent, wherein the substance having a blunting effect in (b) is selected from the group consisting of sugars, polyhydric alcohols, gamine compounds, and ceramides. 14. The cosmetic composition according to item 3 of the scope of the patent application, wherein the substance with whitening effect of (13) is selected from L-ascorbic acid and its derivatives. -5- This paper size applies Chinese National Standard (CNS) A4 specifications (210 X 297 mm) 1238066 as B8 C8 D8 6. Scope of patent application, with fel * oxalic acid L-lysed lysohydroquinone derivative, acetic acid and its derivatives, placental extract white effect Plant extracts and spiro ether compounds. 15. The cosmetic composition according to item 3 of the scope of patent application, J. The substance having an anti-inflammatory effect is selected from glycyrrhizic acid and its salts, and its salts, isopropylaminohexanoic acid and its salts, allantoin, enzymes, guaiac Momo, methyl salicylate and 7-oryzanol. -6- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm)