JPH0242805B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention provides N-amino acids or mixtures thereof.
The present invention relates to a novel cosmetic composition containing at least one acylated product as an active ingredient. It is known to acylate amino acids or mixtures thereof with fatty acids containing more than 5 carbon atoms in the molecular chain. However, although these known acylated products are fat-soluble, they are generally insoluble in water and common solvents. The inventors have now discovered that acylation of α-amino acids or mixtures thereof with butyric acid yields acylated products that are fat-soluble and also soluble in water and many polar and non-polar solvents. . In particular, acylation of amino acids or mixtures thereof with butyric acid yields products soluble in alcohols, ketones, ethyl acetate, benzene, chloroform, diethyl ether, and the like. Of course, solubility in fat, water and various solvents will vary depending on the type of amino acid. These acylates are also soluble in a mixture of polar and non-polar solvents such as methanol and chloroform, but are insoluble in petroleum ether, hexane,
Further, some of the above acylated products are insoluble in isopropyl ether. Compared to lipoamino acids obtained by acylating amino acids or mixtures thereof with fatty acids containing more than 5 carbon atoms in the molecule, acylation with butyric acid results in a shorter molecular chain of the acyl group. , compounds with a greater acidifying capacity (this is the acidity of the free carboxyl group) are obtained. This N-acylated product exhibits good permeability through the skin, and also exhibits useful effects as an active ingredient in cosmetics. Therefore, according to the present invention, a method for protecting skin, hair and nails, which contains as an active ingredient at least one N-acylated α-amino acid obtained by acylating an α-amino acid with butyric acid. A cosmetic composition is provided. In the present invention, salts of the above acylated products with inorganic, organic or biological bases or metals can be used as well. According to the invention, the α-amino acids can be replaced by mixtures of amino acids obtained by any suitable method, for example by complete hydrolysis of proteins. Any product obtained by acylating an amino acid or a mixture of amino acids with butyric acid is an N-acylated derivative; however, in amino acids with other basic functional groups, these functional groups are also partially oxidized by butyric acid. Alternatively, it can be completely acylated. Regarding the salts of the N-acylates of these amino acids or mixtures thereof, the salts may be prepared using any suitable inorganic or organic base such as triethanolamine, diethylamine and morpholine or various known salts such as lysine, arginine or nithine. can be obtained by the action of basic amino acids, or biological bases such as choline and guanidine. The corresponding salts are obtained simply by reacting the previously obtained N-acylated product with the selected base. Regarding the production of metal salts of the N-acylates of the present invention, such metal salts can be easily produced by reacting the N-acylates with the hydroxide or carbonate of the selected metal under heating; Preferred metals are those known as oligo-elements. When producing the N-acylated product of α-amino acid with butyric acid used in the present invention, it is preferable to use butyric anhydride, which generates free butyric acid and completely reacts with the amino acid; ~twenty five%
Although it is preferred to use excess, if the amino acids being treated have other functional groups that can be acylated, these should be considered when determining the appropriate proportion of butyric anhydride to use. It will be necessary to take into account all of the functional groups. An example of the production of an N-acylated product of α-amino acid with butyric acid used in the present invention will be shown below. Production Example 1 Production of butyrylglycine A stirrer was attached and heated in a water bath.
30 g (0.4 mol) of glycine was poured into a 500 ml reaction vessel, and 40 ml of 30% sodium hydroxide solution was slowly added with stirring. When the reaction mixture became clear, 65 g of butyric anhydride were slowly added, maintaining the pH at 10-10.5 (temperature 40-45 DEG C.) until the end of the addition.
The reaction mixture was heated at 70° C. for 0.5 h and then cooled. To obtain butyrylglycine from its sodium salt, hydrochloric acid was slowly added with stirring until the pH reached 2. The oily supernatant layer thus formed was separated and distilled under reduced pressure (on an oil bath) to remove water and hydrochloric acid. After cooling, petroleum ether was added to precipitate butyrylglycine and remove butyric acid; this treatment was repeated twice. Thus, 51 g (88% yield) of product was obtained,
The analytical value is the theoretical value (molecular weight 145; C ₆ H ₁₁ NO ₃ )
Acid index: measured value, 382 (theoretical value: 386). Production Example 2 Production of butyrylphenylalanine The same method as Production Example 1 was carried out using 33 g (0.2 mol) of phenylalanine and 36 g of butyric anhydride. 42 g (90% yield) of product was obtained, the analysis of which was in complete agreement with the theoretical value (molecular weight 235; C ₁₃ H ₁₇ NO ₃ ): acid index; observed value, 235 (theoretical value: 238). . Production Example 3 Production of butyrylthreonine The same method as in Production Example 1 was carried out using 36 g (0.3 mol) of threonine and 51 g of butyric anhydride. 57 g (99% yield) _of product were obtained, the analysis of which was in complete agreement with the theoretical value (molecular weight _{189; C8H15NO4 )} : acid index; found value, 293 (theoretical value: 296). . Production Example 4 Production of butyryl aspartic acid The same method as Production Example 1 was carried out using 53 g (0.4 mol) of aspartic acid and 64 g of butyric anhydride; however, after the water and hydrochloric acid removal step, the remaining It was necessary to remove the butyric acid by distillation under reduced pressure at 130-140°C (on an oil bath). The anhydrous residue was treated with an equal weight of distilled water and then with carbon black.
75 g (94% yield) _of product were obtained, the analysis of which was in perfect agreement with the theoretical value (molecular weight ₂₀₃ ; _C8H13NO5 ): acid index; found, 382 (theoretical value 386). Production Example 5 Production of butyrylvaline The same method as Production Example 1 was carried out using 58 g (0.5 mol) of valine and 85 g of butyric anhydride. Butyrylvaline is only slightly soluble in cold water, so
Butyric acid was removed by washing with ice water. 85 g (92% yield) of product were obtained, the analysis of which was in perfect agreement with the theoretical value (molecular weight ₁₈₇ ; _C9H17NO3 ): acid index; found, 294 (theoretical _value 297). Production Example 6 Production of Butyryl Leucine A method similar to Production Example 1 was carried out using 65 g (0.5 mol) of leucine and 85 g of butyric anhydride; since butyryl leucine is only slightly soluble in cold water, Removal was performed in the same manner as in Production Example 5. 89 _g (92% yield) of product were obtained, the analysis of which was in perfect agreement with the theoretical value (molecular weight ₂₀₁ ; _C10H19NO3 ): acid index; found, 277 (theoretical value 280). Production Example 7 Production of dibutyryl risine Using 60 g of a 50% solution of lysine (0.2 mol) and 64 g of butyric anhydride for the dibutyryl derivative,
The same method as in Production Example 1 was carried out. 51 g (yield 85%) of product were obtained, the analysis of which was in perfect agreement with the theoretical value (molecular weight ₂₈₆ ; _{C14H26N2O2 )} : acid index; observed value, 193 (theoretical _value : 195). Production Example 8 Production of butyrylproline The same method as Production Example 1 was carried out using 23 g (0.2 mol) of proline and 40 g of butyric anhydride. 34 g (92% yield) _of product was obtained, the analysis of which was in complete agreement with the theoretical value (molecular weight ₁₈₅ ; _C9H15NO3 ): acid index; found value, 304 (theoretical value: 302). . Preparation Example 9 Preparation of mono- and dibutyryl hydroxyproline 52 g (0.4 mol) of hydroxyproline and 75 g
The same method as in Production Example 1 was carried out using butyric anhydride. 75 g (yield: 87%) of product was obtained, and analysis showed that the product was a mixture of mono-substituted (35%) and di-substituted (65%) products. Theoretical values for these compounds are as follows: Monosubstituted: molecular weight 201; C ₉ H ₁₅ NO ₄ ; acid index
279, di-substituted type; molecular weight 271; C ₁₃ H ₂₁ NO ₄ ; acid index 207; actual value for acid index was 230. Production Example 10 Production of dibutyrylhydroxylysine The same method as in Production Example 1 was carried out using 32 g (0.2 mol) of hydroxylysine and 40 g of butyric anhydride. 53 g (yield 88%) of product was obtained, the analysis of which was _in complete agreement with the theoretical value (molecular weight _{302 ; C14H26N2O5} ): acid index; observed value, 187 (theoretical value: 184). Production Example 11 Production of butyrylmethionine The same method as in Production Example 1 was carried out using 45 g (0.3 mol) of methionine and 50 g of butyric anhydride. 61 g (92% yield) of product were obtained, the analysis of which was in perfect agreement with the theoretical value (molecular weight ₂₁₉ ; _C9H17NO3S ): acid index; found, 257 ( _theoretical : 255). ). Production Example 12 Production of dibutyrylcystine The same method as Production Example 1 was carried out using 48 g (0.2 mol) of cystine and 64 g of butyric anhydride. 73 g (91% yield) of product was obtained, the analytical value of which was in perfect agreement with the theoretical value (molecular weight 380; C ₁₄ H ₂₄ N ₂ O ₆ S ₂ ): acid index; observed value, 305 (theoretical). value:
294). Production Example 13 Production of butyrylcysteine The same method as Production Example 1 was carried out using 48 g (0.4 mol) of cysteine and 64 g of butyric anhydride. 71 g (97% yield) of product were obtained, the analysis of which was in perfect agreement with the theoretical value (molecular weight ₁₉₁ ; _C7H13NO3S ): acid index; found, 307 ( _theoretical : 297). ).
SH: Actual value, 16.8 (theoretical value: 17.1). The preparation example shown below concerns the preparation of an acylated product with butyric acid of an unseparated amino acid mixture obtained by complete hydrolysis of a natural protein. Since these amino acid mixtures substantially contain the amino acids present in the raw protein in quantitative and qualitative proportions, the above amino acid mixtures are designated by the same name as the raw protein. The first step consists of preparing a protein hydrolyzate from the selected protein. After treating 200 g of protein with concentrated hydrochloric acid according to conventional methods and confirming the absence of peptides by the Biuret test, the solution was neutralized (PH 6.5-7), treated with carbon black and filtered. . The solution thus obtained was titrated with formaldehyde to determine the amine functionality available for acylation and the amount of butyric anhydride to be used. A dry extract was prepared using a sample of the hydrolyzate, weighed, treated with methanol to remove sodium chloride and titrated again with formaldehyde. This preliminary operation allows acylation with appropriate proportions of reactants. Production Example 14 Production of butyryl collagen acid Gelatin was used as the raw protein. The average molecular weight of amino acids in the hydrolyzate was 110. about
200 ml of hydrolyzate containing 50 g of amino acids were treated with 80 g of butyric anhydride according to the method described in Preparation Example 1. The acylated product was separated by distillation in the same manner as in Production Example 4, and 74 g (yield: 92%) was obtained. The analytical values were in good agreement with the theoretical values. Nitrogen content: Actual value, 8.2% (theoretical value: 8%) Acid index: Actual value, 335 (theoretical value: 327) Production Example 15 Production of butyryl keratinic acid Horn was used as the raw protein. The average molecular weight of amino acids in the hydrolyzate was 120.
The amount of acylatable amino functionality was determined for cystine. The production of the acylated product was carried out using 300 ml of hydrolyzate and 80 g of butyric anhydride according to the same method as in Production Example 14; in order to improve the solubility of the acylated products of valine, leucine and isoleucine. 3-5% propylene glycol was added. 87 g (96% yield) of product was obtained, the analytical value of which was in acceptable agreement with the theoretical value. Nitrogen content: Actual value, 8.2% (theoretical value: 7.4
%); this difference is due to the presence of dibasic compounds in the amino acid mixture. Acid index: actual value, 287; theoretical value for butyrylcystine is 294. Production Example 16 Production of butyl casein acid Casein was used as the raw protein. The average molecular weight of amino acids in the hydrolyzate was 120. The acylated product was produced using 300 ml of a hydrolyzate containing about 41 g of amino acid according to the same method as in Production Example 14.
It was carried out using 60 g of butyric anhydride. 63 g (95% yield) of product was obtained, the analytical value of which was in good agreement with the theoretical value. Nitrogen content: actual value, 8.2% (theoretical value: 7.3%). Acid index: Actual value; 260 (theoretical value: 253). The cosmetic composition of the invention consists of 0.1 to 5% by weight of active ingredient (N-acylated α-amino acid with butyric acid) and a suitable carrier; higher contents of the active ingredient are usually used. It probably won't be necessary. Examples of the cosmetic composition of the present invention are shown in the following examples. Example 1 Skin protection cream a Butyryl hydroxyproline (50%) 3 Stearin 5 Polyoxyethylene Cetylic alcohol 5 Isopropyl palmitate 10 Glycerol 10 Preservative and water to make up 100 b Butyryl proline 1 a 99 c Butyryl cystine 1 Carrier for a 99 d Butyryl hydroxyproline (50%) 2 Polyoxyethylene glycol stearate 5 Preservative and water to make a total of 100 e Butyrylglycine 2 Carrier for a 98 f Butyryl cystine Carrier for lylcollagenate 2a 98 g Butyrylcaseinate 1 Butyrylkeratic acid 1a carrier 98 h Aluminum butyrylcollagenate 2a carrier 98 Note: This cream shows activity in antiperspirant. Example 2 Hair protection lotion a Butyrylcysteine 1 Ethanol 15 Water Amount that makes the whole 100 b Butyrylmethionine 1 Water Amount that makes the whole 100 c Butyrylcystine 0.5 Butyrylmethionine 0.5 Propylene glycol 5 Water The whole amount makes 100 NOTE: These lotions may also be administered to animals. Example 3 Nail protection lotion a Butyrylcystine 1 Water Amount b that makes the total 100 Butyrylmethionine 1 Ethanol 15 Water Amount comparison test that makes the whole 100 α- As mentioned above, the N-acylation of amino acids with butyric acid is as follows:
It has a greater acidifying capacity (i.e. acidity potential) and therefore the N-
When acylated products are applied locally to the body, they have the property of lowering the pH of the skin and urine. This property indicates that the N-acylated product used in the present invention improves the skin condition and has good permeability through the skin. This is a useful property when used as an active ingredient. N by butyric acid of α-amino acid used in the present invention
-As mentioned above, acylated products can affect the pH of the skin and urine.
In order to specifically demonstrate that it has the property of lowering the skin temperature and has good permeability through the skin, the following tests were conducted. The subjects, consisting of 24 females and 12 males (age 22-67 years), were divided into 6 groups, each consisting of 4 females and 2 males. For all of these groups, the PH of the skin of the left arm
(PH of our office) was measured. At the same time, urine was collected from each subject. Each group of six subjects was then treated with a different formulation as described below. This treatment was performed by applying the preparation to the skin of the left arm where the PH was measured.

[Table] Urine was then collected from each subject for up to 6 hours; after 6 hours, the PH of the skin of each subject was measured, and the PH of the entire collected urine was also measured. These measured PH values are shown in Table 1 below. The composition of the base emulsion used to prepare the above formulation is as follows: Polyethylene glycol stearate 10 Stearic acid 5 Glycerin 3 Polyoxyethylated cetyl alcohol 2 Water 80 100 parts PH of base emulsion = 6.1 Above During the test, the hydration index of the skin in the area treated with the formulation was also measured before and 6 hours after treatment with the formulation. Skin hydration (water retention) can be used as a measure of skin health. The degree of hydration was determined by measuring the resistance value of the skin, and expressed in the following grade based on the measured value. Grade degree of hydration 11-12 Extremely insufficient hydration 13-16 Slightly insufficient hydration 17-19 Standard hydration state 20 Excessive hydration The measurement results of the hydration index are also shown in Table 1. Ta. From the data shown in Table 1, the N-acylated product of the present invention has a greater ability to lower skin PH than acylated products with shorter chain fatty acids or longer chain fatty acids, and has a greater ability to reduce skin PH. It is recognized that the permeability is high and the property of improving skin hydration is also good.

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Claims (1)

[Scope of Claims] 1. A cosmetic for protecting skin, hair, and nails, which contains as an active ingredient at least one N-acylated product of α-amino acid obtained by acylating α-amino acid with butyric acid. composition. 2. The composition according to claim 1, wherein the active ingredient is an acylated product of a mixture of amino acids obtained by complete hydrolysis of proteins with butyric acid. 3. A composition according to claim 1 or 2, containing about 0.1 to 5% active ingredient.