External skin treatment composition

Description

TECHNICAL FIELD
The present invention relates to an external skin treatment composition in which the stability of vitamin A is extremely improved.
BACKGROUND ART
It has been well known that vitamin A is effective for prevention or treatment of keratodermatitis and, prevention of and recovery from dermal aging.
Vitamin A, however, is structurally very unstable and can readily cause isomerization, decomposition, polymerization, etc., with light, air, heat, metal ion, etc. Thus, it has been difficult to stably formulate vitamin A into an external skin treatment composition.
SUMMARY OF THE INVENTION
Accordingly, the present invention relates to an external skin treatment composition in which the stability of vitamin A is extremely improved by formulating a stabilizer for improving the stability of vitamin A.
In accordance with the present invention, there is provided an external skin treatment composition comprising (I) vitamin A and (II) at least one stabilizer selected from the group consisting of (1) chelating agents and polysaccharides, (2) oils having an iodine value of 70 or more, (3) polyethylene glycol and/or polypropylene glycol, (4) hydroxy carboxylates, (5) neutral amino acids, (6) (i) at least one oil-soluble antioxidant selected from the group consisting of butyl hydroxytoluene, butyl hydroxyanisole, .alpha.,.beta.,.gamma.,.delta.-tocopherol, nordihydrogualaretin, propyl gallate, fatty acid esters of vitamin C and sorbic acid, (ii) at least one ethylenediaminetetraacetate and (iii) at least one benzophenone compound, (7) (i) at least one oil-soluble antioxidant selected from the group consisting of butyl hydroxytoluene, butyl hydroxyanisole, .alpha.,.beta.,.gamma.,.delta.-tocopherols, nordihydrogualaretin, propyl gallate and fatty acid esters of vitamin C, (ii) at least one compound selected from the group consisting of ascorbic acid, ascorbic acid salt, isoascorbic acid, isoascorbic acid salt, sorbic acid and sorbic acid salt and (iii) at least one benzophenone compound, (8) inclusion compounds of cyclodextrins including antioxidants and/or ultraviolet absorbers, (9) at least one kind of butanediol and/or at least one oil-soluble antioxidant, (10) at least one water-soluble benzophenone compound, (11) at least one compound selected from the group consisting of basic amino acids and the salts thereof, (12) at least one compound selected from the group consisting of acidic amino acids and the salts thereof, (13) at least one polar oil selected from the group consisting of pentaerythritol fatty acid esters and trimethylolpropane fatty acid esters, and (14) at least one water-swellable clay mineral.
BEST MODE FOR CARRYING OUT THE INVENTION
In consideration of the above circumstances, the present inventors have conducted extensive study and research efforts. As a result, it has been found that the stability of vitamin A is extremely improved by formulating the specified stabilizer therein. Thus the present invention has been achieved.
The present invention will be described in detail below.
As vitamin A used in the present invention, vitamin A (also called retinol), all-trans type vitamin A or 13-cis type vitamin A is desirable. A mixture thereof can also be used.
The amount of vitamin A to be formulated into the external skin treatment composition according to the present invention is not particularly limited. However, if the effect on the skin as a function of vitamin A is taking into consideration, the amount is 0.0001% by weight or more, based upon the total weight of the composition. If further effects of vitamin A are required, 0.001% by weight or more of the same is preferably used. The upper limit of the formulation amount is preferably 1% by weight in view of the properties as an external skin treatment composition.
According to the first embodiment of the present invention, as a stabilizer, the combination of a chelating agent and a polysaccharide is used.
As a chelating agent used in the present invention, mention may be made of inorganic alkali salts of ethylenediaminetetraacetate such as sodium salts and potassium salts thereof, organic alkali salts of ethylenediaminetetraacetate such as ethanolamines salts thereof (mono, di, tri and tetra salts), citric acid and inorganic alkali salts of citric acid such as sodium and potassium salts thereof, organic alkali salts of citric acid such as ethanolamine salts and basic amino acid salts thereof (mono, di, tri salts); metaphosphoric acid salts, polyphosphoric acid salts, tartaric acid salts.
The amount of a chelating agent to be formulated in accordance with the present invention is 0.001% by weight or more and the upper limit of the formulation amount cannot be particularly limited. However, when an extremely large amount of the agent is formulated, although the effects of the present invention are not impaired, crystals of the agent are possibly deposited or undesirable phenomena may occur, so that qualities as external skin treatment compositions cannot be maintained. The formulation amount is preferably 1% by weight or less.
As polysaccharides used in the present invention, mention may be made of cellulose, quinsseed, chondroitin sulfate, starch, galactan, dermatan sulfate, glycogen, gum arabic, heparan sulfate, hyaluronic acid, gum traganth, keratan sulfate, chondroitin, gum xanthane, mucoitin sulfate, guargum, dextran, keratosulfate, locust bean gum, succinoglucan, charonin, and the salts thereof.
The amount of polysaccharides to be formulated into the external skin treatment composition of the present invention is not particularly limited in view of the effects of the present invention. However, it is preferably 0.00001 to 5.0% by weight.
In the second embodiment of the present invention, as oils having an iodine value of 70 or more to be formulated as a stabilizer, typically, mention may be made of plant oils belonging to the drying oil group such as linseed oil, tung oil, soybean oil, sunflower oil, walnut oil, eno oil, evening primrose oil, cherrykernel oil and grape seed; plant oils belonging to the nondrying oil such as sesame oil, rape seed oil, cotton seed oil, rice bran oil and wheat embryo bud oil; avocado oil; olive oil; camellia oil; macadamia nut oil; fish oils such as sardine oil, mackerel oil, herring oil, cod-liver oil, oyster oil.
In these oils, iodine values are, for example, 168-190 in linseed oil, 114-138 in soybean oil, 122-150 in sunflower oil, 94-107 in rape seed oil, 90-121 in cotton seed oil, 75-90 in olive oil, 73-87 in camellia oil, 136-195 in sardine oil, 99-119 in herring oil.
Further, among free fatty acids and higher alcohols derived from these fats and oils, those having an iodine value of 70 or more include, for example, oleic acid, palmitic acid, linoleic acid, linolenic acid, eleostearic acid, .gamma.-linolenic acid, arachidonic acid, eicosapentaene acid, oleyl alcohol.
One or more kinds of these oils are formulated into the composition. The formulation amount thereof for the purpose of exhibiting the effects of the present invention is preferably 0.01% by weight or more. Further, even if an excess amount of the same is formulated, the effects of the present invention are not impaired. However, if an extremely large amount of the same is formulated, qualities as external skin treatment compositions sometimes can be impaired. Thus caution should be taken not to impair the qualities. The formulation amount is particularly preferably 0.1 to 60% by weight.
According to the third embodiment of the present invention, as a stabilizer, one or two or more kinds of compounds selected from polyethylene glycol (PEG) and/or polypropylene glycol (PPG) are formulated.
As PEG, PPG to be formulated in accordance with the present invention, PEG200, PEG300, PEG400, PEG1500, PEG4000, PEG6000, PEG20000 as well as PPG400, PPG750, PPG1200, PPG2000, PPG3000 have been typically known.
One or more kinds of these compounds are formulated into the composition. The formulation amount thereof for the purpose of exhibiting the effects of the present invention is preferably 0.1% by weight or more. Further, even if an excess amount of the same is formulated, the effects of the present invention are not impaired. However, if an extremely large amount of the same is formulated, qualities as external skin treatment compositions sometimes can be impaired. Thus caution should be taken not to impair the qualities of the composition. The formulation amount is particularly preferably 1 to 80% by weight.
In the fourth embodiment of the present invention, as hydroxycarbonates included in the external skin treatment composition as a stabilizer, mention may be made of inorganic alkali salts such as sodium salts and potassium salts of citric acid, lactic acid, malic acid and tartaric acid, organic alkali salts such as ethanolamine salts and basic amino acid salts of citric acid, lactic acid, malic acid and tartaric acid (mono, di and tri salts are typically known).
One or two or more kinds thereof are included in the present composition. The formulation amount thereof for the purpose of exhibiting the effects of the present invention is preferably 0.001% by weight or more. Further, even if an excess amount of the same is formulated, the effects of the present invention are not impaired. However, if an extremely large amount of the same is formulated, qualities as external skin treatment compositions sometimes can be impaired. Thus caution should be taken not to impair the qualities of the composition. The formulation amount is particularly preferably 0.01 to 1% by weight.
In the fifth embodiment of the present invention, as neutral amino acids included in the external skin treatment composition as a stabilizer, mention may be made of glycine, alanine, seline, phenylalanine, proline and hydroxyproline.
One or two or more kinds thereof are included in the present composition. The formulation amount thereof for the purpose of exhibiting the effects of the present invention is preferably 0.001% by weight or more. Further, even if an excess amount of the same is formulated, the effects of the present invention are not impaired. However, if an extremely large amount of the same is formulated, the formulation amount exceeds individual solubility to possibly cause the precipitation of the crystals so that qualities as external skin treatment compositions sometimes can be impaired. Thus caution should be taken not to impair the qualities of the composition. The formulation amount is particularly preferably 0.01 to 10% by weight.
In the sixth embodiment of the present invention, as oil-soluble antioxidants included in the external skin treatment composition as a stabilizer, mention may be made of butyl hydroxytoluene (BHT), butyl hydroxyanisole (BHA), .alpha.,.beta.,.gamma.,.delta.-tocopherols, nordihydrogualaretin, propyl gallate, a fatty acid ester of vitamin C and sorbic acid.
An amount thereof to be formulated in accordance with the present invention is prefearbly 0.001% by weight or more, more preferably 0.01% by weight or more. In order to maintain the effects of the invention for a long time, the formulation amount is preferably 0.03% by weight. The upper limit of the formulation amount depends on the form of the external skin treatment composition and the formulation amount can be optionally selected. Thus, although the upper limit cannot be set, in view of the property of the external skin treatment composition, it is preferably 10% by weight or less.
As ethylenediaminetetraacetate used in the present invention, mention may be made of inorganic alkali salts such as sodium salts and potassium salts and organic alkali salts such as ethanolamines salts (mono, di, tri, tetra salts).
The formulation amount thereof is 0.001% by weight or more. The upper limit of the formulation amount cannot be particularly set. However, if an extremely large amount of the same is formulated, the effects of the present invention are not impaired, but crystals can be precipitated to impair the qualities of the external skin treatment composition. Thus the formulation amount is preferably 0.005 to 1% by weight.
As the benzophenone compound used in the present invention, mention may be made of 2,4-dihydroxybenzophenone (hereinafter referred to as benzophenone-1), 2,2',4,4,-tetrahydroxybenzophenone (hereinafter referred to as benzophenone-2), 2-hydroxy-4-methoxybenzophenone (hereinafter referred to as benzophenone-3), 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (hereinafter referred to as benzophenone-4), sodium 2-hydroxy-4-methoxybenzophenone-5-sulfonate (hereinafter referred to as benzophenone-5), 2,2'-dihydroxy-4,4'-dimethoxybenzophenone (hereinafre referred to as benzophenone-6), 2-hydroxy-5-chlorobenzophenone (hereinafter referred to as benzophenone-7), 2,2'-dihydroxy-4-methoxybenzophenone (hereinafter referred to as benzophenone-8), disodium 2,2 -dihydroxy-4,4'-dimethoxybenzophenone-5,5'-sulfonate (hereinafter referred to as benzophenone-9), 2-hydroxy-4-methoxy-4'-methylbenzophenone (hereinafter referred to as benzophenone-10) and 2-hydroxy-4-octyloxybenzophenone (hereinafter referred to as benzophenone-12).
The formulation amount thereof to the external skin treatment composition of the present invention is 0.001% by weight or more. The upper limit of the formulation amount cannot be particularly set. However, if an extremely large amount of the same is formulated, the effects of the present invention are not impaired, but crystals can be precipitated to impair the qualities of the external skin treatment composition. Thus the formulation amount is preferably 0.01 to 10% by weight.
In the seventh embodiment of the present invention, as a stabilizer, are formulated
(A) at least one oil-soluble antioxidant selected from a group consisting of butyl hydroxytoluene (BHT), butyl hydroxyanisole (BHA), .alpha.,.beta.,.gamma.,.delta.-tocopherols, nordihydrogualaretin, propyl gallate and a fatty acid ester of vitamin C,
(B) at least one compound selected from the group consisting of ascorbic acid, ascorbic acid salts, isoascorbic acid, isoascorbic acid salts, sorbic acid and sorbic acid salts, and
(C) at least one benzophenone compound.
As oil-soluble antioxidants according to the present invention, mention may be made of BHT, BHA, .alpha.,.beta.,.gamma.,.delta.-tocopherols, nordihydrogualaretin, propyl gallate and a fatty acid ester of vitamin C.
An amount thereof to be formulated in accordance with the present invention is prefearbly 0.001% by weight or more, more preferably 0.01% by weight or more. In order to maintain the effects of the invention for a long time, the formulation amount is preferably 0.03% by weight. The upper limit of the formulation depends on the forms of the external skin treatment composition and the formulation can be optionally made. Thus, although the upper limit cannot be set, in view of the property of the external skin treatment composition, it is preferably 10% by weight.
As ascorbic acid (another name: vitamin C), isoascorbic acid (another name: erythorbic acid), sorbic acid and salts thereof, mention may be made of inorganic alkali salts such as sodium salts and potassium salts thereof as well as organic alkali salts such as ethanolamines salts and basic amino acids thereof. Particularly, ascorbic acid, sodium ascorbate, isoascorbic acid (another name: erythorbic acid), sodium isoascorbate (another name: sodium erythorbate), sorbic acid, sodium sorbate and potassium sorbate are preferably used.
In a system where each acid and a basic substance are co-utilized, a salt also can be formed.
An amount thereof to be formulated in accordance with the present invention is prefearbly 0.001% by weight or more. The upper limit of the formulation amount cannot particularly be set. However, if an extremely large amount of the same is formulated, the effects of the present invention are not impaired, but crystals can be precipitated to impair the qualities of the external skin treatment composition. Thus the formulation amount is preferably 10% by weight or less.
As the benzophenone compound used in the present invention, mention may be made of 2,4-dihydroxybenzophenone (hereinafter referred to as benzophenone-1), 2,2',4,4'-tetrahydroxybenzophenone (hereinafter referred to as benzophenone-2), 2-hydroxy-4-methoxybenzophenone (hereinafter referred to as benzophenone-3), 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (hereinafter referred to as benzophenone-4), sodium 2-hydroxy-4-methoxybenzophenone-5-sulfonate (hereinafter referred to as benzophenone-5), 2,2'-dihydroxy-4,4'-dimethoxybenzophenone (hereinafter referred to as benzophenone-6), 2-hydroxy-5-chlorobenzophenone (hereinafter referred to as benzophenone-7), 2,2'-dihydroxy-4-methoxybenzophenone (hereinafter referred to as benzophenone-8), disodium 2,2'-dihydroxy-4,4'-dimethoxybenzophenone-5,5'-sulfonate (hereinafter referred to as benzophenone-9), 2-hydroxy-4-methoxy-4'-methylbenzophenone (hereinafter referred to as benzophenone-10) and 2-hydroxy-4-octyloxybenzophenone (hereinafter referred to as benzophenone-12).
The formulation amount thereof to the external skin treatment composition of the present invention is 0.001% by weight or more. The upper limit of the formulation amount cannot be particularly set. However, if an extremely large amount of the same is formulated, the effects of the present invention are not impaired, but crystals can be precipitated to impair the qualities of the external skin treatment composition. Thus the formulation amount is preferably 10% by weight.
The cyclodextrin (CD) used in the present invention is cyclic oligosaccharides such as CD having the structure of .alpha., .beta. or .gamma. due to the difference in glucose number (.alpha.-CD, .beta.-CD, .gamma.-CD); those to which a lower alkyl group is introduced, i.e., methyl CD (M-CD), ethyl CD (E-CD); hydroxyalkylated compounds, i.e., hydroxymethyl CD (HM-CD), hydroxyethyl CD (HE-CD), hydroxypropyl CD (HP-CD), hydroxybutyl CD (HB-CD).
Among these, .alpha.-CD and .gamma.-CD have good solubility in water, but if they are produced according to a starch decomposition method, the yield of the product is low and therefore, this method is insufficient in view of the cost. .beta.-CD is advantageous from the viewpoint of cost, but the solubility thereof is somewhat insufficient. In each case, if individual properties are well known and a compound is utilized on the basis of these well-known properties, the effects of the present invention can be sufficiently obtained.
In view of the frequent utilization thereof for external skin treatment compositions, due to their good solubility and low cost, methylated CD and hydroxylakylated CD are preferable, particularly, methyl-.beta.-CD, hydroxyalkyl-.beta.-CD are the most preferable.
The formulation amount of each CD to the external skin treatment composition of the present invention is 0.01% by weight or more. The upper limit of the formulation amount cannot be particularly limited by the effects of the present invention. However, if an extremely large amount of the same is formulated, the effects of the present invention are not impaired, but crystals can be precipitated to impair the qualities of the external skin treatment composition. Thus, the formulation amount of .alpha.-CD and .gamma.-CD is preferably 10% by weight or less. While, regarding .beta.-CD, 1% by weight or less and regarding lower alkylated CD, hydroxyalkylated CD, the amount is 30% by weight or less.
As oil-soluble antioxidants formulated into the external skin treatment composition according to the present invention, mention may be made of nordihydrogualaretin, BHT, BHA, .alpha.,.beta.,.gamma.,.delta.-tocopherols, propyl gallate, a fatty acid ester of vitamin C and sorbic acid. Among these, BHT, BHA, .alpha.,.beta.,.gamma.,.delta.-tocopherols are preferably used.
The formulation amount thereof used in the present invention is preferably 0.001% by weight or more, more preferably 0.01%.by weight or more. In order to maintain the effects of the invention for a long time, the formulation amount is preferably 0.03% by weight. The upper limit of the formulation depends on the form of the external skin treatment composition and the formulation can be optionally made. Thus, although the upper limit cannot be set, in view of the property of the external skin treatment composition, the antioxidant is preferably formulated in the amount of 1% by weight.
Examples of the ultraviolet absorber used in the present invention include benzophenone compounds represented by 2-hydroxy-4-methoxybenzophenone; cinnamic acid compounds represented by octylmethoxycinnamate, mono/di(methoxycinnamyl)-mono/dioctylglyceride; salicylic compounds represented by octylsalicylate; benzoic acid compounds represented by paraaminooctylbenzoate; dibenzoylmethane compounds represented by 4-t-butyl-4' methoxybenzoylmethane. Benzophenone compounds, cinnamic acid compounds and dibenzoylmethane compounds are preferably used.
The formulation amount thereof used in the present invention is preferably 0.001% by weight or more, more preferably 0.01% by weight or more. In order to maintain the effects of the invention for a long time, the formulation amount is preferably 0.03% by weight. The upper limit of the formulation depends on the form of the external skin treatment composition and the formulation can be optionally made. Thus, although the upper limit cannot be set, in view of the property of the external skin treatment composition, it is preferably 1% by weight.
A method for making antioxidants and ultraviolet absorbers to be included in the above-described CDs generally comprises the step of adding an antioxidant and an ultraviolet absorber to an aqueous solution of CDs (the concentration is 20 to 60% by weight) in an amount of 0.01 to 0.2 part on the basis of the amount of CD, then stirring the resulting mixture (50 to 3000 rpm) at a temperature of 20 to 60.degree. C., whereby the inclusion compound can be obtained. It takes about 2 to 12 hours to obtain the same. The inclusion compound thus obtained is in a solubilized or emulsified state in an aqueous solution and can be used as it is as an external skin treatment composition. Alternatively, this solution can be lyophilized or spray-dried to form a powder.
Further, it is also possible to separately formulate CDs, an antioxidant and an ultraviolet absorber into an external skin treatment composition and to effect the inclusion of these compounds together therein.
In the ninth embodiment of the present invention, as butanediols to be formulated as a stabilizer, mention may be made of 1,2-butanediol, 1,3-butanediol, 1,4-butanediol.
One or more kinds thereof are included in accordance with the present invention. The formulation amount thereof for the purpose of exhibiting the effects of the present invention is preferably 0.01% by weight or more. Further, even if an excess amount of the same is formulated, the effects of the present invention are not impaired. However, if an extremely large amount of the same is formulated, qualities as external skin treatment compositions sometimes can be impaired. Thus the caution should be taken not to impair the qualities of the composition. The formulation amount is particularly preferably 0.1 to 40% by weight.
Examples of oil-soluble antioxidants to be formulated in accordance with the present invention include butyl hydroxytoluene (hereinafter, abbreviated as BHT), butyl hydroxyanisole (hereinafter, abbreviated as BHA), .alpha.,.beta.,.gamma.,.delta.-tocopherols, nordihydrogualaretin, propyl gallate and a fatty acid ester of vitamin C.
The formulation amount thereof is preferably 0.001% by weight or more, more preferably 0.005% by weight or more. In order to maintain the effects of the invention for a long time, the formulation amount is preferably 0.01% by weight or more. Although the upper limit of the formulation amount cannot be particularly set in view of the effects of the present invention, if an extremely large amount of the same is formulated, crystals can be precipitated so that the qualities as the external skin treatment composition sometimes can be impaired. Thus, caution should be taken so as not to impair the qualities of the composition. A preferable formulation amount is 10% by weight.
In the tenth embodiment of the present invention, as the water-soluble benzophenone compound used as a stabilizer, mention may be made of 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (hereinafter referred to as benzophenone-4) and the salt thereof, sodium 2-hydroxy-4-methoxybenzophenone-5-sulfonate (hereinafter referred to as benzophenone-5) and disodium 2,2'-dihydroxy-4,4'-dimethoxybenzophenone-5,5'-disulfonate (hereinafter referred to as benzophenone-9).
The formulation amount thereof to the external skin treatment composition of the present invention is preferably 0.001% by weight or more, particularly preferably 0.01% by weight or more. The upper limit of the formulation amount cannot be particularly set. However, if an extremely large amount of the same is formulated, the effects of the present invention are not impaired, but crystals can be precipitated to impair the qualities of the external skin treatment composition. Thus the formulation amount is preferably 5% by weight or less.
In the eleventh embodiment of the present invention, as a basic amino acid and the salt thereof to be formulated as a stabilizer, mention may be made of arginine, lysine, hydroxylysine, ornithine, and the hydrochloride, acetate, aspartate, pyrrolidone carboxylate thereof.
In addition to these, a basic amino acid and other acidic substances are co-utilized in the external skin treatment composition and a salt can be formed in situ.
One or more kinds of these compounds are formulated into the composition. The formulation amount thereof for the purpose of exhibiting the effects of the present invention is required to be 0.001% by weight or more. Further, even if an excess amount of the same is formulated, the effects of the present invention are not impaired. However, if an extremely large amount of the same is formulated, qualities as external skin treatment compositions sometimes can be impaired, for example, by precipitation of crystals. Thus, caution should be taken not to impair the qualities of the composition. The formulation amount is preferably 0.01 to 5% by weight.
The pH of the system is preferably 6 or more, more preferably 7 or more.
In the twelfth embodiment of the present invention, as an acidic amino acid and the salt thereof to be formulated as a stabilizer, mention may be made of acidic amino acids such as aspartic acid and glutamic acid, and inorganic alkali (sodium and potassium) salts thereof as well as organic alkali (ethanolamine and basic amino acids) salts thereof. Further, pyrrolidone carboxylic acid and the salt thereof also can be applied.
One or two or more kinds thereof are included in the present composition. The formulation amount thereof for the purpose of exhibiting the effects of the present invention is preferably 0.001% by weight or more, more preferably 0.01% by weight or more. Further, even if an excess amount of the same is formulated, the effects of the present invention are not impaired. However, if an extremely large amount of the same is formulated, the formulation amount exceeds individual solubility to possibly cause the precipitation of crystals so that qualities as external skin treatment compositions sometimes can be impaired. Thus, caution should be taken not to impair the qualities of the composition. The formulation amount is preferably 10% by weight or less.
In the thirteenth embodiment of the present invention, a polar oil used as a stabilizer is selected from a group consisting of pentaerythritol fatty acid ester preferably having 6 to 12 carbon atoms and trimethylolpropane fatty acid ester preferably having 6 to 12 carbon atoms. Examples thereof include pentaerythritol-tetra(2-ethylhexanoate), pentaerythritoltetracaprate, trimethylolpropane-tri(2-ethylhexanoate) and trimethylolpropane-tricaprate.
The amount thereof to be formulated in accordance with the present invention cannot be particularly limited because of the wide variety of utilization forms. However, if an extremely small amount of an oil is used, it cannot solubilize vitamin A or an oil-soluble antioxidant so that the effects of the present invention cannot be exhibited. Accordingly, an oil is desirably used in an amount over the total amount of vitamin A and an oil-soluble antioxidant to be formulated in the external skin treatment composition. The oil is preferably used in an amount of 0.002% by weight or more, more preferably 0.1% by weight or more. The upper limit of the formulation amount of the oil cannot be particularly set because of the wide variety of utilization forms. However, the upper limit can be determined by subtracting the sum of an oil-soluble antioxidant and vitamin A from the total amount of the external skin treatment composition.
Examples of oil-soluble antioxidants to be formulated into the external skin treatment composition in accordance with the present invention include BHT, BHA, .alpha.,.beta.,.gamma.,.delta.-tocopherols, nordihydrogualaretin, propyl gallate, a fatty acid ester of vitamin C and sorbic acid.
The formulation amount thereof used in the present invention is preferably 0.001% by weight or more, more preferably 0.01% by weight or more. In order to maintain the effects of the invention for a long time, the formulation amount is preferably 0.03% by weight.
The upper limit of the formulation depends on the forms of the external skin treatment composition and the formulation can be optionally determined. Thus, although the upper limit cannot be set, in view of the property of the external skin treatment composition, it is preferably 10% by weight.
In the fourteenth embodiment of the present invention, as a water-swellable clay mineral to be formulated as a stabilizer, mention may be made of, generally, a kind of colloidal water-containing aluminumsilicate. Specifical examples thereof include natural or synthetic smectite such as montmorillonite, bidelite, nontrolite, saponite, hectolite. As the commercially available products, mention may be made of Kunipia, Smectone (both are available from Kunimine Kogyo K.K.), Vegum (available from Vanderbilt K.K.), Laponite (available from Lapolt K.K.), Fluorotetrasilicon modified mica (available from Topee Kogyo K.K.). Further, synthetic mica known as sodium silicic mica and sodium or lithium teniolite also can be used.
The formulation amount thereof in the external skin treatment composition of the present invention is 0.01% by weight or more, preferably 0.1% or more. The upper limit of the formulation amount cannot be particularly set in view of the effects of the present invention. However, if an extremely large amount of the same is formulated, gelatin may be produced thus deteriorating the qualities of the external skin treatment composition. Thus, caution should be taken not to deteriorate the qualities of the composition. The formulation amount is preferably 50% by weight or less.
Examples of an antioxidant to be formulated in accordance with the present invention include butyl hydroxytoluene (hereinafter abbreviated as BHT), butyl hydroxyanisole (hereinafter abbreviated as BHA), nordihydrogualaretin, .alpha.,.beta.,.gamma.,.delta.-tocopherols, propyl gallate, vitamin C (ascorbic acid), erythorbic acid (isoascorbic acid), erythorbate, vitamin C fatty acid ester, sorbic acid and sorbic acid salt.
The formulation amount thereof used in the present invention is preferably 0.001% by weight or more, more preferably 0.01% by weight or more. In order to maintain the effects of the invention for a long time, the formulation amount is preferably 0.03% by weight.
The upper limit of the formulation amount depends on the forms of the external skin treatment composition and the formulation can be optionally determined. Thus, although the upper limit cannot be set, in view of the property of the external skin treatment composition, it is preferably 10% by weight.
Examples of the ultraviolet absorber used in the present invention include benzophenone compounds represented by 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid and 2,2'-dihydroxy-4,4'-dimethoxybenzophenone; cinnamic acid compounds represented by octylmethoxycinnamate, mono/di(methoxycinnamyl)-mono/dioctylglyceride; salicylic compounds represented by octylsalicylate; benzoic compounds represented by paraaminooctylbenzoate; benzoylmethane compounds represented by 4-t-butyl-4'-methoxybenzoylmethane.
One or more kinds thereof are formulated in the present composition. The formulation amount thereof for the purpose of exhibiting the effects of the present invention is preferably 0.001% by weight or more. Further, even if an excess amount of the same is formulated, the effects of the present invention are not impaired. However, if an extremely large amount of the same is formulated, qualities as external skin treatment compositions can sometimes be impaired. Thus, caution should be taken not to impair the qualities of the composition. The formulation amount is preferably 10% by weight or less.
As a chelating agent used in the present invention, mention may be made of inorganic alkali salts such as sodium salts and potassium salts of ethylenediaminetetraacetate, organic alkali salts such as ethanol amines salts of ethylenediaminetetraacetate (mono, di, tri and tetra salts), citric acid and inorganic alkali salts such as sodium and potassium salts of citric acid, organic alkali salts such as ethanol amine salts and basic amino acid salts of citric acid (mono, di, tri and tetra salts). Further, metaphosphoric acid salts or polyphosphoric acid salts can be used.
One or two or more kinds thereof are included in the present composition. The formulation amount thereof for the purpose of exhibiting the effects of the present invention is required to be 0.001% by weight or more. Further, even if an excess amount of the same is formulated, the effects of the present invention are not impaired. However, if an extremely large amount of the same is formulated, crystals can be precipitated so that the qualities as external skin treatment compositions can sometimes be impaired. Thus, caution should be taken not to impair the qualities of the composition. The formulation amount is preferably 1% by weight or less.
In addition to the above-described essential components, the external skin treatment composition according to the present invention can optionally contain a conventional base material of the external skin treatment composition usually used in cosmetics and quasi-drugs and other conventional components such as humectant, surfactant, preservative, water, alcohol, thickener, oil, drug, perfume, colorant, and ultraviolet absorber in an amount which does not deteriorate the effects of the present invention. The composition can be converted to liquid, gel, paste, cream, powder and solid form.

EXAMPLE
The present invention will be further described in more detail, by, but by no means limited to, the following Examples.
Production method and temperature test method of Examples 1-1, 1-2 and Comparative Examples 1-1, 1-2
Each oil component is completely dissolved at 60.degree. C., and then has added thereto a solution of POE(10) oleyl ether, edetic acid salt, ethanol and dipropylene glycol dissolved in purified water, followed by cooling the resulting solution to 40.degree. C. Thereafter, vitamin A is completely dissolved therein, and the solution is sealed in a brown glass sample tube. The tube is further wrapped with aluminum foil to completely cut light and is stored in a constant temperature bath at 40.degree. C.
TABLE 1-1______________________________________Cosmetic oil formulation and vitamin Aquantitative determination results (% by weight) Comp. Example Example Example 1-1 1-2 1-1______________________________________Vitamin A 0.01 0.02 0.01Disodium edetate 0.001 0.005 --Hyaluronic acid 0.001 0.001 --Purified water 0.1 0.2 --Glycerol tri 2-ethylhexanoate balance balance balancetriglycerideIsopropyl myristate 10 35 10Squalane 15 15 15Dipropylene glycol 15 15 15Ethanol 8 8 8POE(10) oleyl ether 2 2 2Vitamin A quantitative determination valueImmediately after preparation (%) 100 100 100After two weeks at 40.degree. C. (%) 93 98 56______________________________________
In Examples 1-1 and 1-2, the stability of vitamin A is improved as compared with Comparative Example 1-1. This is the effect according to the present invention.
Quantitative determination method of vitamin A
According to the absorbance determination method at 325 nm using ethanol as a solvent, the quantitative determination was effected.
In the calculation, at the maximum absorption 325 nm, E (1%, 1 cm)=1835 was used.
TABLE 1-2______________________________________Emulsion formulation and vitamin A quantitativedetermination results (% by weight) Exam- Exam- Comp. Comp. ple ple Ex. Ex. 1-3 1-4 1-3 1-3______________________________________Vitamin A 0.03 0.001 0.03 0.001Disodium edetate 0.01 -- -- --Trisodium citrate 0.02 0.02 -- --Cetylisoocatnoate 10 7 10 7Glycerol 2-ethylhexanoate 2 4 2 4Squalane 2 2 2 2Cetyl alcohol 2 2 2 2Vaseline 1 1 1Glyceryl monostearate 1.5 1.5 1.5 1.5POE(60) hardened castor oil 1.3 1.3 1.3 1.3Carboxyvinyl polymer 0.2 0.3 0.2 0.3Gum xanthane 0.05 0.1 -- --Caustic potash 0.06 0.08 0.06 0.08Glycerol 10 10 10 10Propylene glycol 3 3 3 3Ethyl paraben 0.2 0.2 0.2 0.2Purified water To total amount 100Vitamin A quantitative determination valueImmediately after preparation (%) 100 100 100 100After one month at 40.degree. C. (%) 95 97 31 38______________________________________
In Examples 1-3 and 1-4, the stability of vitamin A is improved as compared with Comparative Example. This is the effect according to the present invention.
TABLE 1-3______________________________________Cosmetic lotion and vitamin A quantitativedetermination results (% by weight) Exam- Exam- Exam- Comp. ple ple ple Ex. 1-5 1-6 1-7 1-4______________________________________Disodium edetate 0.5 -- 0.05 --Tetrapotassium edetate -- 0.3 0.05 --Sodium hyaluronate 0.1 0.05 -- --Soium chondroitin sulfate -- -- 0.2 --Ethanol 5.0 5.0 5.0 5.0Methyl paraben 0.1 0.1 0.1 0.1Vitamin A 0.0001 0.0001 0.0001 0.0001Octadodecanol 0.001 0.001 0.001 0.001POE(60) hardened castor oil 0.4 0.4 0.4 0.4Lactic acid 0.01 0.01 0.01 0.01Sodium lactate 0.1 0.1 0.1 0.1Glycerol 2.0 2.0 2.0 2.0Purified water To total amount 100Vitamin A quantitative determination valueImmediately after preparation (%) 100 100 100 100After two weeks at 40.degree. C. (%) 95 93 91 49______________________________________
In Examples 1-5, 1-6, and 1-7, the stability of vitamin A is improved as compared with Comparative Example. This is the effect according to the present invention.
______________________________________Example 1-8: Cosmetic lotion (% by weight)______________________________________Oleyl alcohol 0.005Vitamin A 0.0001POE(50) oleyl ether 0.7Trisodium edetate 1Lactic acid 0.01Sodium lactate 0.09Soium chondroitin sulfate 0.1Ethanol 8Glycerol 2Methyl paraben 0.2Purified water To total amount 100______________________________________
______________________________________Example 1-9: Cream (% by weight)______________________________________Squalane 15Glycerol tri 2-ethylhexanoate 8Isopropylmyristate 7Vitamin A 0.3Vaseline 2Butyl paraben 0.1Propyl paraben 0.1Glycerol monooleate 3Diglyceroldiisostearate 2PEG400 dioleate 1Glycerol 10Cellulose powder 1Dipropylene glycol 5Disodium edetate 0.01Triethanolamine 0.02Purified water To total amount 100______________________________________
______________________________________Example 1-10: Oilessence (% by weight)______________________________________Glycerol tri 2-ethylhexanoate 50Octyldodecanol 20Squalane 10Vitamin A 1Dibutylphthalate 9Ethyl alcohol 9.989Cellulose powder 0.01Sodium edetate 0.001______________________________________
______________________________________Example 1-11: Oil gel (% by weight)______________________________________Glycerol tri 2-ethylhexanoate 60POE(20) octyldodecylether 16Vitamin A 0.1Glycerol 16Sodium hyaluronate 0.01Disodium edetate 0.05Purified water To total amount 100______________________________________
______________________________________Example 1-12: Cream (% by weight)______________________________________Cetostearyl alcohol 3.5Squalane 30.0Beeswax 3.0Reduced lanolin 5.0Ethyl paraben 0.3POE(50) oleyl alcohol ether 2.0Glycerol monostearate 2.0Diethanol amine edetate 0.01Perfume 0.03Vitamin A 0.0001Dermatan sulfate 0.1Glycerol 15.0Purified water balance______________________________________
______________________________________Example 1-13: Pack (% by weight)______________________________________Gum xanthane 1.0Polyvinyl alcohol 10.0Propylene glycol 7.0Ethanol 10.0Vitamin A 0.01Monosodium edetate 0.1Methyl paraben 0.05POE(60) hydrogenated castor oil 0.2Perfume 0.05Purified water balance______________________________________
______________________________________Example 1-14: Compact face powder (% by weight)______________________________________Vitamin A 0.0005Talc 85.4Stearic acid 2.5Squalane 3.5Sorbitansesquioleate 1.8Triethanolamine 1.2Quinsseed 0.001Salt of edetic acid 0.001Pigment q.s.Perfume q.s.______________________________________
______________________________________Example 1-15: Lipstick (% by weight)______________________________________Vitamin A 0.00001Microcrystalline wax 3.0Bees wax 3.0Ceresin wax 5.0Liquid paraffin 19.0Squalane 20.0Carnauba wax 3.0Candellira wax 3.0Gum arabic 0.01Monosodium salt of edetic acid 0.01Color controlling colorant 7.0Dibutylhydroxytoluene 0.05Perfume q.s.Lanolin balance______________________________________
______________________________________Example 1-16: Emulsion (% by weight)______________________________________Vitamin A 1.0Hyaluronic acid 0.1Tetraethanol amine edetate 1.0Ethanol 2.0Glycerol 10.0Propylene glycol 3.0Carboxyvinyl polymer 0.3KOH 0.1Methyl paraben 0.1Cetanol 2.5Vaseline 2.0Squalane 10.0Isopropyl myristate 5.0Glycerylmonostearate 2.0POE(25) Cetyl ether 2.0Purified water balance______________________________________
______________________________________Example 1-17: Emulsion (% by weight)______________________________________Vitamin A 0.3Chondroitin sulfate 0.01Trisodium citrate 0.1Ethanol 5.0Glycerol 5.0Propylene glycol 5.0Carboxyvinyl polymer 0.2KOH 0.06Methyl paraben 0.2POE(60) Hydrogenated castor oil 1.0Squalane 3.0Isopropyl myristate 3.0Purified water balance______________________________________
The external skin treatment compositions of Examples 1-8 to 1-17 were excellent in the stability of vitamin A in daily use.
As described hereinabove, in the external skin treatment composition of the present invention, by formulating one or more chelating agents and polysaccharides such as hyaluronic acid and chondroitin sulfate, the stability of vitamin A can be extremely improved
Example 2-1 to 2-3 and Comparative Example 2-1 to 2-2
TABLE 2-1______________________________________Vitamin A stability determinationresults in various oils (% by weight) Comp. Comp.Example Example Example Example Example2-1 2-2 2-3 2-1 2-2______________________________________Olive oil 99 -- -- -- --(IV = 75)Cotton seed -- 99 -- -- --oil(IV = 95)Evening -- -- 50 -- --primroseOil(IV = 190)Squalane -- -- 49 49 99(IV = 1)Palm oil -- -- -- 50 --(IV = 12)Vitamin A 1 1 1 1 1Quantitative determination value of vitamin AImmediately 100 100 100 100 100afterpreparation(%)After ten 93 98 97 58 39days at50.degree. C. (%)______________________________________
In Examples 2-1, 2-2 and 2-3, the stability of vitamin A is improved as compared with Comparative Example. This is the effect according to the present invention.
Quantitative determination method of vitamin A
According to the absorbance determination method at 325 nm using ethanol as a solvent, the quantitative determination was effected.
In the calculation, at the maximum absorption 325 nm, E (1%, 1 cm)=1835 was used.
______________________________________Example 2-4: Cream (% by weight)______________________________________Cetanol 3Glycerylmonostearate 2POE(25) Cetyl ether 1Stearic acid 3Vaseline 3Olive oil (IV = 80) 3Cotton seed oil (IV = 100) 1Squalane 5Vitamin A 0.1BHT 0.05Perfume q.s.Propylene glycol 3Potassium hydroxide 0.2Purified water To total amount 100______________________________________
The oil phase portion (A) and the aqueous phase portion (B) are thermally melted at 70.degree. C., then A is added to B, the resulting mixture is emulsified, and subsequently subjected to a cooling treatment to form a cream.
______________________________________Example 2-5: Lipstick (% by weight)______________________________________Solid paraffin 8Carnauba wax 4Candellira wax 4Microcrystalline wax 6Hydrogenated lanolin 15Castor oil (IV = 85) 46.7Oyster oil (IV = 160) 5Evening primrose oil (IV = 190) 3Vitamin A 1BHT 0.3Mixed colorant (red type) 7Perfume q.s.______________________________________
Each of the above-described starting materials is thermally melted at 80.degree. C., and thereafter, the molten product is poured into a given container to obtain a lipstick.
______________________________________Example 2-6: Cosmetic lotion (% by weight)______________________________________Vitamin A 0.0001Oleyl alcohol (IV = 80) 0.01.alpha.-tocopherol 0.005POE(20) Octyldodecanol 0.8Ethanol 8Propylene glycol 3Glycerol 1Methyl paraben 0.15Lactic acid 0.01Sodium lactate 0.09Purified water To total amount 100______________________________________
______________________________________Example 2-7: Eye wrinkle oil (% by weight)______________________________________Macadamia nut oil (IV = 75) 40Glycerol tri .gamma.-linolenate (IV = 198) 1Glycerol tri 2-ethylhexanoate 25Sunflower oil (IV = 130) 20Squalane 10PEG600 dioleate 2.8.delta.-tocopherol 1Vitamin A 0.2______________________________________
______________________________________Example 2-8: Night cream (% by weight)______________________________________Olive oil (IV = 80) 8Evening primrose oil (IV = 185) 2Squalane 20PEG400 diisostearate 1Diglycerol dioleate 1Butyl paraben 0.15Glycerol monoleate 2Vitamin A 0.25Glycerol 10Magnesium sulfate 0.2Purified water To total amount 100______________________________________
The external skin treatment compositions of Examples 2-4 to 2-8 were excellent in the stability of vitamin A in daily use.
As described hereinabove, in the external skin treatment composition of the present invention, by formulating an oil having an iodine value of 70 or more, the stability of vitamin A can be extremely improved.
Example 3-1 to 3-3 and Comparative Example 3-1 to 3-2
TABLE 3-1______________________________________Vitamin A stability determinationresults in various bases (% by weight) Exam- Exam- Exam- Comp. Comp. ple ple ple Example Example 3-1 3-2 3-3 3-1 3-2______________________________________PEG400 99.9 -- -- -- --PEG1500 -- 99.9 -- -- --PPG1200 -- -- 50 -- --Propylene glycol -- -- 49.9 29.9 --Squalane -- -- -- 70 99.9Vitamin A 0.1 0.1 0.1 0.1 0.1Quantitative determination result of vitamin AImmediately after 100 100 100 100 100preparation (%)After five days 92 93 90 58 39at 50.degree. C. (%)______________________________________
In Examples 3-1, 3-2 and 3-3, the stability of vitamin A is improved as compared with the Comparative Example. This is the effect according to the present invention.
Quantitative determination method of vitamin A
According to the absorbance determination method at 325 nm using ethanol as a solvent, the quantitative determination was effected.
In the calculation, at the maximum absorption 325 nm, E (1%, 1 cm)=1835 was used.
______________________________________Example 3-4: Cream (% by weight)______________________________________A. Cetanol 3 Glyceryl monostearate 2 POE(25) Cetyl ether 1 Stearic acid 3 Vaseline 3 Isopropyl myristate 5 Squalane 5 Vitamin A 0.1 BHT 0.05 Perfume q.s. PEG1500 3 Glycerol 9 Potassium hydroxide 0.2 Purified water To total amount 100______________________________________
The oil phase portion (A) and the aqueous phase portion (B) are thermally melted at 70.degree. C., then A is added to B, the resulting mixture is emulsified, and subsequently subjected to a cooling treatment to form a cream.
______________________________________Example 3-5: Lipstick (% by weight)______________________________________Solid paraffin 8Carnauba wax 2Candellira wax 4Microcrystalline wax 6Hydrogenated lanolin 15Isopropyl myristate To total amount 100Glyceryl diisostearate 30PPG3000 15Vitamin A 1BHT 0.3Mixed colorant (red type) 7Perfume q.s.______________________________________
Each of the above-described starting materials is thermally melted at 80.degree. C., and thereafter, the molten product is poured into a given container to obtain a lipstick.
______________________________________Example 3-6: Cosmetic lotion (% by weight)______________________________________Vitamin A 0.0001Oleyl alcohol 0.001.alpha.-tocopherol 0.005POE(20) Octyldodecanol 0.8Ethanol 8PEG300 3PEG1500 1Methyl paraben 0.15Lactic acid 0.03Sodium lactate 0.07Purified water To total amount 100______________________________________
______________________________________Example 3-7: Eye wrinkle oil (% by weight)______________________________________Olive oil 40Glycerol tri 2-ethylhexanoate 26Squalane 30PPG4000 2PEG20000 0.9.delta.-tocopherol 1Vitamin A 0.1______________________________________
______________________________________Example 3-8: Beauty paste (% by weight)______________________________________PEG300 30PEG1500 40PEG4000 10Vitamin A 0.3Isopropyl myristate 5POE(25) Cetyl ether 2Stearic acid 5Purified water To total amount 100______________________________________
______________________________________Example 3-9: Night cream (% by weight)______________________________________Squalane 15Isopropyl myristate 5Silicon dioxide 3Vaseline 6Glyceryl monoisostearate 2POE(7) Hydrogenated castor oil 1.5Propyl paraben 0.2Vitamin A 0.4PEG6000 3PEG400 3Glycerol 17Purified water To total amount 100______________________________________
The external skin treatment compositions of Examples 3-4 to 3-9 were excellent in the stability of vitamin A in daily use.
As described hereinabove, in the external skin treatment composition of the present invention, by formulating polyethylene glycol and/or propylene glycol, the stability of vitamin A can be extremely improved.
Examples 4-1 to 4-3 and Comparative Example 4-1
TABLE 4-1______________________________________Vitamin A stability determinationresults in emulsion (% by weight) Comp. Example Example Example Example 4-1 4-2 4-3 4-1______________________________________Purified water To toal amount 100Glycerol 10 10 10 10Carboxyvinyl polymer 0.2 0.2 0.2 0.2Caustic potash 0.03 0.03 0.06 0.06Ethyl alcohol 5 5 5 5Methyl paraben 0.1 0.1 0.1 0.1Cetyl alcohol 2 2 2 2Vaseline 3 3 3 3Squalane 5 5 5 5Isopropyl myristate 4 4 4 4Glyceryl monostearate 1.5 1.5 1.5 1.5POE(60) Hydrogenated 2 2 2 2castor oilTrisodium citrate 0.08 -- 0.04 --Sodium lactate -- 0.09 0.05 --Vitamin A 0.3 0.3 0.3 0.3Quantitative determination value of vitamin AImmediately after 100 100 100 100preparation (%)After two weeks at 98 93 95 7540.degree. C. (%)______________________________________
In Examples 4-1, 4-2 and 4-3, the stability of vitamin A is improved as compared with the Comparative Example. This is the effect according to the present invention.
Quantitative determination method of vitamin A
According to the absorbance determination method at 325 nm using ethanol as a slovent, the quantitative determination was effected.
In the calculation, at the maximum abosrption 325 nm, E (1%, 1 cm)=1835 was used.
______________________________________Example 4-4: Cream (% by weight)______________________________________A. Cetanol 3 Glycerylmonostearate 2 POE(25) Cetyl ether 1 Stearic acid 3 Vaseline 3 Olive Oil 3 Isopropyl palmitate 1 Squalane 5 Vitamin A 0.1 BHT 0.05 Perfume q.s.B. Propylene glycol 3 Potassium hydroxide 0.2 Trisodium citrate 1 Purified water To total amount 100______________________________________
The oil phase portion (A) and the aqueous phase portion (B) are thermally melted at 70.degree. C., then A is added to B, the resulting mixture is emulsified, and subsequently subjected to a cooling treatment to form a cream.
______________________________________Example 4-5: Beauty essence (% by weight)______________________________________Carboxyvinyl polymer 0.4Glycerol 5Propylene glycol 5Sodium lactate 0.05Triethanolamine 3.8POE(60) Hydrogenated castor oil 0.5Vitamin A 0.1Squalane 1.alpha.-tocopherol 0.05Methyl paraben 0.2Ethyl alcohol 6Purified water To total amount 100______________________________________
______________________________________Example 4-6: Cosmetic lotion (% by weight)______________________________________Glycerol 2Ethanol 7POE(50) Oleyl ether 0.5Oleyl alcohol 0.002Vitamin A 0.0001Trisodium citrate 0.1Methyl paraben 0.1Purified water To total amount 100______________________________________
______________________________________Example 4-7: Oil gel (% by weight)______________________________________Vitamin A 1Glycerol tri 2-ethylhexanoate 40Olive oil 10BHT 0.1BHA 0.05POE(20) Octyldodecyl ether 16Glycerol 15Disodium citrate 0.1Purified water To total amount 100______________________________________
______________________________________Example 4-8: Night Cream (% by weight)______________________________________Squalane 15Glycerol tri 2-ethylhexanoate 5Vaseline 5Butyl paraben 0.2Diglycerol diisostearate 2PEG400 Diisostearate 0.5Vitamin A 0.1Glycerol 10Trisodium citrate 0.3Sodium lactate 0.1Lactic acid 0.1Purified water To total amount 100______________________________________
The external skin treatment compositions of Examples 4-4 to 4-8 were excellent in the stability of vitamin A in daily use.
As described hereinabove, in the external skin treatment composition of the present invention, by formulating hydroxycarboxylate, the stability of vitamin A can be extremely improved.
Examples 5-1 to 5-3 and Comparative Example 5-1
TABLE 5-1______________________________________Vitamin A stability determinationresults in emulsion (% by weight) Comp. Example Example Example Example 5-1 5-2 5-3 5-1______________________________________Purified water To total amount 100Glycerol 10 10 10 10Carboxyvinyl polymer 0.2 0.2 0.2 0.2Caustic potash 0.06 0.06 0.06 0.06Ethyl alcohol 5 5 5 5Methyl paraben 0.1 0.1 0.1 0.1Cetyl alcohol 2 2 2 2Butyl alcohol 1 1 1 1Vaseline 3 3 3 3Squalane 5 5 5 5Isopropyl myristate 4 4 4 4Glyceryl monostearate 1.5 1.5 1.5 1.5POE(60) Hydrogenated 2 2 2 2castor oilBHT 0.03 0.03 0.03 0.03Glycine 1 -- -- --Hydroxy proline 1 0.5 0.01 --Vitamin A 0.3 0.3 0.3 0.3Quantitative determination result of vitamin AImmediately after 100 100 100 100preparation (%)After two weeks at 98 96 88 5540.degree. C. (%)______________________________________
In Examples 5-1, 5-2 and 5-3, the stability of vitamin A is improved as compared with the Comparative Example. This is the effect according to the present invention.
Quantitative determination method of vitamin A
According to the absorbance determination method at 325 nm using ethanol as a solvent, the quantitative determination was effected.
In the calculation, at the maximum absorption 325 nm, E (1%, 1 cm)=1835 was used.
______________________________________Example 5-4: Cream (% by weight)______________________________________A. Cetanol 3 Glyceryl monostearate 2 POE(25) Cetyl ether 1 Stearic acid 3 Vaseline 3 Olive oil 3 Isopropyl myristate 1 Squalane 5 Vitamin A 0.1 BHT 0.5 Perfume q.s.B. Propylene glycol 3 Potassium hydroxide 0.2 Alanine 5 Hydroxy proline 5 Purified water To total amount 100______________________________________
The oil phase portion (A) and the aqueous phase portion (B) are thermally melted at 70.degree. C., then A is added to B, the resulting mixture is emulsified, and subsequently subjected to a cooling treatment to form a cream.
______________________________________Example 5-5: Beauty essence (% by weight)______________________________________Carboxyvinyl polymer 0.4Glycerol 5Propylene glycol 5Alanine 1Triethanolamine 3.4POE(60) Hydrogenated castor oil 0.5Vitamin A 0.1Squalane 1.alpha.-tocopherol 1Methyl paraben 0.2Ethyl alcohol 6Purified water To total amount 100______________________________________
______________________________________Example 5-6: Cosmetic lotion (% by weight)______________________________________Glycerol 2Ethanol 7POE(50) Oleyl ether 0.5Oleyl alcohol 0.002Vitamin A 0.0001Serine 0.3Leucine 0.1Lactic acid 0.02Sodium lactate 0.07Methyl paraben 0.1Purified water To total amount 100______________________________________
______________________________________Example 5-7: Oil gel (% by weight)______________________________________Vitamin A 1Glycerol tri 2-ethylhexanoate 40Olive oil 10BHT 0.2BHA 0.05POE(20) Octyldodecyl ether 16Glycerol 15Glycine 0.1Purified water To total amount 100______________________________________
______________________________________Example 5-8: Night cream (% by weight)______________________________________Liquid paraffin 15Glycerol tri 2-ethylhexanoate 7Vaseline 6Solid paraffin 2Diglycerol dioleate 1.5Triglycerol diisosearate 1.5Vitamin A 0.1Propyl paraben 0.2Propylene glycol 4Glycerol 15Glycine 1Hydroxyproline 1Purified water To total amount 100______________________________________
The external skin treatment compositions of Examples 5-4 to 5-8 were excellent in the stability of vitamin A in daily use.
As described hereinabove, in the external skin treatment composition of the present invention, by formulating, a neutral amino acid, the stability of vitamin A can be extremely improved.
Example 6-1 to 6-2 and Comparative Example 6-1 to 6-2
TABLE 6-1______________________________________Cosmetic oil formulation and vitamin A.quantitative determination results (% by weight) Comp. Comp. Example Example Example Example 6-1 6-2 6-1 6-2______________________________________Vitamin A 0.01 0.2 0.01 0.2BHT 0.005 0.03 0.005 0.03d1-.alpha.-tocopherol -- 0.01 -- 0.01Benzophenone-3 0.05 0.1 -- --Octylmethoxycinnamate -- -- 0.05 0.1Disodium edetate 0.001 0.005 -- 0.005Purified water 0.1 0.2 -- 0.2Glycerol tri 2- 45 20 45 20ethylhexanoateIsopropyl myristate 10 35 10 35Squalane 24.834 24.455 24.935 24.455Dipropylene glycol 10 10 10 10Ethanol 8 8 8 8POE(10) Oleyl ether 2 2 2 2Vitamin A quantitative determination valueImmediately after 100 100 100 100preparation (%)After two months at 93 98 68 8240.degree. C. (%)______________________________________
In Examples 6-1 and 6-2, the stability of vitamin A is improved as compared with Comparative Example. This is the effect according to the present invention.
Production method and temperature test method of Examples 6-1, 6-2 and Comparative Examples 6-1, 6-2
BHT, tocopherol, benzophenone and octylmethoxycinnamate are each completely dissolved in oil at 60.degree. C., then to the resulting solution is added a solution of edetate, ethyl alcohol and dipropylene glycol dissolved in purified water, followed by cooling the resulting solution to 40.degree. C. Thereafter, vitamin A is completely dissolved therein, and the solution is sealed in a brown glass sample tube. The tube is further wrapped with aluminum foil to completely cut light and is stored in a constant temperature bath at 40.degree. C.
Quantitative determination method of vitamin A
According to the absorbance determination method at 325 nm using ethanol as a solvent, the quantitative determination was effected.
In the calculation, at the maximum absorption 325 nm, E (1%, 1 cm)=1835 was used.
Production method and temperature test method of Examples 6-3. 6-4 and Comparative Examples 6-3, 6-4
BHT, tocopherol and benzophenone-2 are each completely dissolved in oil and a surfactant at 70.degree. C., and thereafter, immediately before emulsification, vitamin A is completely dissolved therein to form an oil phase.
Glycerol, propylene glycol, carboxyvinyl polymer, caustic potash, trisodium edetate and benzophenone-5 are completely dissolved in purified water. The oil phase is added to the resulting aqueous phase heated to 70.degree. C., then the mixture obtained is emulsified by a homomixer type emulsifier. Then the resulting product is subjected to a cooling treatment by a heat exchanger to 30.degree. C. to form an emulsion.
The emulsion is filled in a glass bottle having a metal coat applied thereto, tightly sealed and is stored in a constant temperature bath at 40.degree. C.
TABLE 6-2______________________________________Emulsion formulation and vitamin Aquantitative determination results (% by weight) Comp. Comp. Example Example Example Example 6-3 6-4 6-3 6-4______________________________________Vitamin A 0.3 0.01 0.3 0.01BHT 0.05 0.01 0.05 0.01di-.alpha.-tocopherol 0.01 0.02 0.01 0.02Trisodium edetate 0.02 0.02 0.02 --Benzophenone-2 0.1 0.05 -- 0.02Benzophenone-5 -- 0.05 -- --Cetylisooctanoate 10 7 10 7Isopropyl myristate 2 4 2 4Squalane 2 2 2 2Cetyl alcohol 2 2 2 2Vaseline 1 1 1 1Glyceryl monostearate 1.5 1.5 1.5 1.5POE(60) hydrogenated 1.3 1.3 1.3 1.3castor oilCarboxyvinyl polymer 0.2 0.3 0.2 0.3Caustic potash 0.06 0.08 0.06 0.08Glycerol 10 10 10 10Propylene glycol 3 3 3 3Ethyl paraben 0.2 0.2 0.2 0.2Purified water To total amount 100Vitamin A quantitative determination valueImmediately after 100 100 100 100preparation (%)After one month at 97 99 29 2240.degree. C. (%)______________________________________
In Examples 6-3 and 6-4, the stability of vitamin A is improved as compared with the Comparative Example. This is the effect according to the present invention.
Quantitative determination method of vitamin A
According to the absorbance determination method at 325 nm using ethanol, the quantitative determination was effected. A sample was prepared by removing vitamin A from Examples and Comparative Examples (control) and the absorption at 325 nm was measured, which was used for correcting an absorbance as the absorbance of a base material.
(absorbance of a sample of Example and Comparative Example at 325 nm)-(an absorbance of a countrol)=the absorbance of vitamin A
In the calculation, at the maximum absorption 325 nm, E (1%, 1 cm)=1835 was used.
______________________________________Example 6-5: Cosmetic lotion (% by weight)______________________________________Oleyl alcohol 0.002Benzophenone-12 0.001.alpha.-tocopherol 0.001Vitamin A 0.0001POE(50) Oleyl ether 0.7Lactic Acid 0.1Sodium lactate 0.9Ethanol 8Glycerol 2Methyl paraben 0.2Trisodium edetate 0.01Purified water To total amount 100______________________________________
______________________________________Example 6-6: Oil essence (% by weight)______________________________________Glycerol tri 2-ethylhexanoate 30Octyldodecanol 20Squalane 12BHT 1.alpha.-tocopherol 9Vitamin A 8Dipropylene glycol 12.899Ethyl alcohol 5Benzophenone 0.1Disodium edetate 0.001______________________________________
______________________________________Example 6-7: Cream (% by weight)______________________________________Squalane 15Glycerol tri 2-ethylhexanoate 8isopropyl myristate 7BHT 0.05BHA 0.01.alpha.-tocopherol 0.01Vitamin A 0.3Vaseline 2Butyl paraben 0.1Propyl paraben 0.1Glycerol monooleate 3Diglyceroldiisostearate 2PEG400 dioleate 1Glycerol 10Dipropylene glycol 5Disodium edetate 0.01Benzophenone-6 0.1Benzophenone-4 0.03Triethanolamine 0.04Purified water To total amount 100______________________________________
______________________________________Example 6-8: Oil essence (% by weight)______________________________________Isopropyl myristate 10Octyldodecanol 20Squalane 30BHT 1.alpha.-tocopherol 9Vitamin A 1Dibutyl phthalate 9Ethyl alcohol 9.999Benzophenone-12 7Benzophenone-6 3Sodium edetate 0.001______________________________________
______________________________________Example 6-9: Oil gel (% by weight)______________________________________Glycerol tri 2-ethylhexanoate 60POE(20) octyldodecyl ether 16Vitamin A 0.1Benzophenone-12 0.1Glycerol 16Benzophenone-5 0.05Trisodium edetate 0.02BHA 0.01BHT 0.01Purified water To total amount 100______________________________________
The external skin treatment compositions of Examples 6-5 to 6-9 were excellent in the stability of vitamin A in daily use.
As described hereinabove, in the external skin treatment composition of the present invention, by formulating
(A) one or two or more of oil-soluble antioxidant selected from the group consisting of a butyl hydroxytoluene, butyl hydroxyanisole, .alpha.,.beta.,.gamma.,.delta.-tocopherol, nordihydrogualaretin, propyl gallate, a fatty acid ester of vitamin C and sorbic acid,
(B) one or two or more of ethylenediaminetetraacetate and
(C) one or two or more of benzophenone compound, the stability of vitamin A can be extremely improved.
Production method and temperature test method of Examples 7-1, 7-2 and Comparative Examples 7-1, 7-2
BHT, tocopherol, benzophenone and octylmethoxycinnamate are each completely dissolved in oil at 60.degree. C., then to the resulting solution, is added a solution of sorbic acid and dipropylene glycol dissolved in ethyl alcohol, followed by cooling the resulting solution to 40.degree. C. Thereafter, vitamin A is completely dissolved therein, and the solution is sealed in a brown glass sample tube. The tube is further wrapped with aluminum foil to completely cut light and is stored in a constant temperature bath at 40.degree. C.
TABLE 7-1______________________________________Cosmetic oil formulation and vitamin Aquantitative determination results (% by weight) Comp. Comp. Example Example Example Example 7-1 7-2 7-1 7-2______________________________________Vitamin A 0.01 0.2 0.01 0.2BHT 0.005 0.03 0.005 0.03d1-.alpha.-tocopherol -- 0.01 -- 0.01Benzophenone-3 0.05 0.1 -- --Octylmethoxycinnamate -- -- 0.05 0.1Sorbic acid 0.001 0.005 -- 0.005Glycerol tri 2- 45 20 45 20ethylhexanoateIsopropyl myristate 10 35 10 35Squalane To total amount 100Dipropylene glycol 10 10 10 10Ethanol 8 8 8 8POE(10) Oleyl ether 2 2 2 2Vitamin A quantitative determination valueImmediately after 100 100 100 100preparation (%)After two months at 95 96 71 6940.degree. C. (%)______________________________________
Quantitative determination method of vitamin A
Japanese Pharmacopoepia (11th revision) In accordance with the second method of vitamin A quantitative determinaiton method, the quantitative determinaiton was effected by an absorbance determination method using isopropanol. In examples 7-1 and 7-2, the stability of vitamin A is improved as compared with the Comparative Example. This is the effect according to the present invention.
Production method and temperature test method of Examples 7-3, 7-4 and Comparative Examples 7-3, 7-4
BHT, tocopherol and benzophenone-2 are each completely dissolved in oil and a surfactant at 70.degree. C., thereafter, immediately before emulsification, vitamin A is completely dissolved therein to form an oil phase.
Glycerol, propylene glycol, carboxyvinyl polymer, caustic potash, ascorbic acid and benzophenone-5 are completely dissolved in purified water. The oil phase is added to the resulting aqueous phase heated to 70.degree. C., then the mixture obtained is emulsified by a homomixer type emulsifier. Then the resulting product is subjected to a cooling treatment by a heat exchanger to 30.degree. C. to form an emulsion.
The emulsion is filled in a glass bottle having a metal coat applied thereto, tightly sealed and is stored in a constant temperature bath at 40.degree. C.
TABLE 7-2______________________________________Emulsion formulation and vitamin Aquantitative determination results (% by weight) Comp. Comp. Example Example Example Example 7-3 7-4 7-3 7-4______________________________________Vitamin A 0.3 0.01 0.3 0.01BHT 0.05 0.01 0.05 0.01d1-.alpha.-tocopherol 0.01 0.02 0.01 0.02Ascorbic acid 0.05 0.05 0.05 --Benzophenone-2 0.1 0.05 -- 0.05Benzophenone-5 -- 0.05 -- --Cetyl isooctanoate 10 7 10 7Squalane 5 5 5 5Cetyl alcohol 2 2 2 2Vaseline 1 1 1 1Glyceryl- 1.5 1.5 1.5 1.5monostearatePOE(60) 1.3 1.3 1.3 1.3hydrogenatedcastor oilCarboxyvinyl 0.2 0.3 0.2 0.3polymerCaustic potash 0.06 0.08 0.06 0.08Glycerol 10 10 10 10Propylene glycol 3 3 3 3Ethyl paraben 0.2 0.2 0.2 0.2Purified water To total amount 100Vitamin A quantitative determination valueImmediately after 100 100 100 100preparation (%)After two weeks 96 98 47 41at 40.degree. C. (%)______________________________________
In Examples 7-3 and 7-4, the stability of vitamin A is improved as compared with the Comparative Example. This is the effect according to the present invention.
Quantitative determination method of vitamin A
According to the absorbance determination method at 325 nm using ethanol, the quantitative determination was effected. A sample was prepared by removing vitamin A from Examples and Comparative Examples (control) and the absorption at 325 nm was measured, which was used for correcting an absorbance as the absorbance of a base material.
(absorbance of a sample of Example and Comparative Example at 325 nm)-(absorbance of a control)=the absorbance of vitamin A
In the calculation, at the maximum absorption 325 nm, E (1%, 1 cm)=1835 was used.
______________________________________Example 7-5: Cosmetic lotion (% by weight)______________________________________Oleyl alcohol 0.002Benzophenone 0.001.alpha.-tocopherol 0.001Vitamin A 0.0001POE(50) Oleyl ether 0.7Lactic acid 0.1Sodium lactate 0.9Ethanol 8Glycerol 2Methyl paraben 0.2Sodium erythorbate 0.5(Sodium isoascorbate)Purified water To total amount 100______________________________________
______________________________________Example 7-6: Oil essence (% by weight)______________________________________Glycerol tri 2-ethylhexanoate 10Octyldodecanol 20Squalane 39BHT 1.alpha.-tocopherol 9Vitamin A 1Dipropylene glycol 12.89Ethyl alcohol 5Benzophenone 0.1Sorbic acid 0.01______________________________________
______________________________________Example 7-7: Cream (% by weight)______________________________________Squalane 15Glycerol tri 2-ethylhexanoate 8Isopropyl myristate 7BHT 0.05BHA 0.01.alpha.-tocopherol 0.01Vitamin A 0.3Vaseline 2Butyl paraben 0.1Propyl paraben 0.1Glycerol monooleate 3Diglyceroldiisostearate 2PEG400 dioleate 1Glycerol 10Dipropyl glycol 5Sodium ascorbate 0.01Benzophenone-8 0.1Benzophenone-4 0.03Triethanolamine 0.04Purified water To total amount 100______________________________________
______________________________________Example 7-8: Beauty essence (% by weight)______________________________________Glycerol 30Propylene glycol 10Olive oil 2BHT 0.1.alpha.-tocopherol 0.1Vitamin A 0.1Ethyl alcohol 4Ascorbic acid 10Potassium sorbate 0.1Gumxanthane 0.8POE(60) hydrogenated caster oil 0.6Purified water To total amount 100______________________________________
______________________________________Example 7-9: Oil gel (% by weight)______________________________________Glycerol tri 2-ethylhexanoate 60POE(20) octyldodecyl ether 16Vitamin A 0.1Benzophenone-12 0.1Glycerol 16Erysorbic acid (Isoascorbic acid) 0.05Benzophenone-5 0.05BHA 0.01BHT 0.01Purified water To total amount 100______________________________________
The external skin treatment compositions of Examples 7-5 to 7-9 were excellent in the stability of vitamin A in daily use.
In the external skin treatment composition of the present invention, by formulating
(A) at least one oil-soluble antioxidant selected from the group consisting of a butyl hydroxytoluene, butyl hydroxyanisole, .alpha.,.beta.,.gamma.,.delta.-tocopoherol, nordihydrogualaretin, propyl gallate and a fatty acid ester of vitamin C,
(B) at least one compound selected from the group consisting of ascorbic acid, ascorbic acid salt, isoascorbic acid, isoascorbic acid salt, sorbic acid and sorbic acid salt, and
(C) at least one benzophenone compound, the stability of vitamin A can be extremely improved.
Examples 8-1 to 8-2 and Comparative Examples 8-1 to 8-2
TABLE 8-1______________________________________Vitamin A stability determinationresults in emulsion (% by weight) Comp. Comp. Example Example Example Example 8-1 8-2 8-1 8-2______________________________________Purified water To total amount 100Glycerol 10 10 10 10Carboxyvinyl polymer 0.2 0.2 0.2 0.2Caustic potash 0.06 0.06 0.06 0.06Ethyl alcohol 5 5 5 5Methyl paraben 0.1 0.1 0.1 0.1Cetyl alcohol 2 2 2 2Vaseline 3 3 3 3Squalane 5 5 5 5Isopropyl myristate 4 4 4 4Glycerylmonostearate 1.5 1.5 1.5 1.5POE(60) hydrogenated 2 2 2 2castor oilHP-.beta.-CD 5 5 -- --BHT 0.05 -- 0.05 --Octylmethoxycinnamate -- 0.05 -- 0.05Vitamin A 0.3 0.3 0.3 0.3Vitamin A quantitative determination valueImmediately after 100 100 100 100preparation (%)After two weeks 98 93 65 55at 40.degree. C. (%)______________________________________
As compared with Examples 8-1, 8-2, and the Comparative Examples, the stability of vitamin A is improved. This is the effect according to the present invention.
Quantitative determination method of vitamin A
According to the absorbance determination method at 325 nm using ethanol, the quantitative determination was effected. A sample was prepared by removing vitamin A from Example 8-2 and Comparative Example 8-2 (control) and the absorption at 325 nm was measured, which was used for correcting an absorbance as the absorbance of a base material.
(Absorbance of a sample of Example and Comparative Example at 325 nm)-(Absorbance of a control)=Absorbance of vitamin A
In the calculation, at the maximum absorption 325 nm, E (1%, 1 cm)=1835 was used.
TABLE 8-2______________________________________Emulsion formulation and vitamin Aquantitative determination results (% by weight) Comp. Comp. Example Example Example Example 8-3 8-4 8-3 8-4______________________________________.beta.-M-CD 1 1 -- --.alpha.-CD 3 1 -- --.gamma.-CD 2 1 -- --BHT 0.05 0.01 0.05 0.01d1-.alpha.-tocopherol 0.01 0.02 0.01 0.02Vitamin A 0.3 0.01 0.3 0.01Cetyl isooctanoate 10 7 10 7Squalane 5 2 5 2Cetyl alcohol 2 2 2 2Vaseline 1 1 1 1Glyceryl- 1.5 1.5 1.5 1.5monostearatePOE(60) 1.3 1.3 1.3 1.3hydrogenatedcastor oilCarboxyvinyl 0.2 0.2 0.2 0.2polymerCaustic potash 0.06 0.06 0.06 0.06Glycerol 10 10 10 10Propylene glycol 3 3 3 3Methyl paraben 0.2 0.2 0.2 0.2Purified water To total amount 100Vitamin A quantitative determination valueImmediately after 100 100 100 100preparation (%)After one month 97 94 60 59at 40.degree. C. (%)______________________________________
In Examples 8-3 and 8-4, the stability of vitamin A is improved as compared with the Comparative Example. This is the effect according to the present invention.
Quantitative determination method of vitamin A
In accordance with the second method of vitamin A quantitative determination method, Japanese Pharmacopoeia (11th revision), the quantitative determination was effected by an absorbance determination method using isopropanol.
______________________________________Example 8-5: Cosmetic lotion (% by weight)______________________________________Oleyl alcohol 0.002.beta.-CD 0.01BHA 0.001Vitamin A 0.0001POE(50) Oleyl ether 0.7Lactic acid 0.01Sodium lactate 0.09Ethanol 5Glycerol 1Methyl paraben 0.2Purified water To total amount 100______________________________________
______________________________________Example 8-6: Beauty essence (% by weight)______________________________________HP-.beta.-CD 30BHT 1Vitamin A 1Isopropyl myristate 10POE(60) hydrogenated caster oil 1POE(20) sorbitan laurate 1Carboxyvinyl polymer 0.3Triethanolamine 2.3Ethanol 3Methyl paraben 0.1Purified water To total amount 100______________________________________
______________________________________Example 8-7: Cream (% by weight)______________________________________HE-.beta.-CD 3BHT 0.012-hydroxy-4-methoxybenzophenone 0.02Vitamin A 0.3Glycerol tri-2-ethylhexanoate 10Vaseline 2Squalane 18Butyl paraben 0.1Propyl paraben 0.1Glycerol monooleate 3Diglyceroldiisostearate 2PEG400 dioleate 1Glycerol 10Dipropylele glycol 5Purified water To total amount 100______________________________________
______________________________________Example 8-8: Cosmetic lotion (% by weight)______________________________________Vitamin A 0.001BHT inclusion-.beta.-HPCD 5(BHT:.beta.-HPCD = 1:100)Glycerol 2Citric acid 0.03Trisodium citrate 0.07Ethanol 5Methyl paraben 0.1Purified water To total amount 100______________________________________
______________________________________Example 8-9: Beauty powder (% by weight)______________________________________Vitamin A 0.3.alpha.-tocopherolinclusion-.alpha.-CD 10(.alpha.-tocopherol:.alpha.-CD = 1:150)Ultraviolet absorber inclusion-.beta.-HPCD* 30(Ultraviolet absorber:.beta.-HPCD = 1:150)D-mannitol To total amount 100______________________________________ *: Ultraviolet absorber: Octylmethoxycinnamate
The external skin treatment compositions of Examples 8-5 to 8-9 were excellent in the stability of vitamin A in daily use.
As described hereinabove, in the external skin treatment composition of the present invention, by formulating cyclodextrin including an antioxidant and/or an ultraviolet absorber, the stability of vitamin A can be extremely improved.
Examples 9-1 to 9-2 and Comparative Examples 9-1 to 9-2
TABLE 9-1______________________________________Vitamin A stability determinationresults in emulsion (% by weight) Comp. Comp. Example Example Example Example 9-1 9-2 9-1 9-2______________________________________Purified water To total amount 100Glycerol 10 10 10 10Carboxyvinyl polymer 0.2 0.2 0.2 0.2Caustic potash 0.06 0.06 0.06 0.06Ethyl alcohol 5 5 5 5Methyl paraben 0.1 0.1 0.1 0.1Cetyl alcohol 2 2 2 2Vaseline 3 3 3 3Squalane 5 5 5 5Isopropyl myristate 4 4 4 4Butylhydroxytoluene 0.05 0.05 0.05 0.05Glyceryl monostearate 1.5 1.5 1.5 1.5POE(60) hydrogenated 2 2 2 2castor oil1,3-butanediol 0.01 5 -- --Propylene glycol -- -- 5 --Dipropylene glycol -- -- -- 5Vitamin A 0.3 0.3 0.3 0.3Vitamin A quantitative determination valueImmediately after 100 100 100 100preparation (%)After one month 93 92 65 69at 40.degree. C. (%)______________________________________
In Examples 9-1 and 9-2, the stability of vitamin A is improved as compared with the Comparative Example. This is the effect according to the present invention.
Quantitative determination method of vitamin A
In accordance with the second method of vitamin A quantitative determination method, Japanese Pharmacopoeia (11th revision), the quantitative determination was effected by an absorbance determination method using isopropanol.
______________________________________Example 9-3: Cream (% by weight)______________________________________A. Cetanol 3 Glycerylmonostearate 2 POE(25) Cetyl ether 1 Stearic acid 3 Vaseline 3 Olive oil 3 Isopropyl myristate 1 Squalane 5 Vitamin A 0.1 BHT 0.05 Perfume q.s.B. 1,2-butanediol 3 1,3-butanediol 3 1,4-butanediol 3 Potassium hydroxide 0.2 Purified water To total amount 100______________________________________
The oil phase portion (A) and the aqueous phase portion (B) are thermally melted at 70.degree. C., then A is added to B, the resulting mixture is emulsified, and subsequently subjected to a cooling treatment to form a cream.
______________________________________Example 9-4: Beauty essence (% by weight)______________________________________Carboxyvinyl polymer 0.31,3-butanediol 251,4-butanediol 15Glycerol 30Triethanolamine 3.5POE(60) hydrogenated castor oil 0.5Vitamin A 0.1Squalane 1.alpha.-tocopherol 0.01Methyl paraben 0.2Ethyl alcohol 6Purified water To total amount 100______________________________________
______________________________________Example 9-5: Cosmetic lotion (% by weight)______________________________________1,3-butanediol 5Ethanol 7POE(50) Oleyl ether 0.5Oleyl alcohol 0.002Vitamin A 0.0001BHT 0.001Citric acid 0.03Trisodium citrate 0.07Methyl paraben 0.1Disodium edetate 0.03Purified water To total amount 100______________________________________
______________________________________Example 9-6: Oil essence (% by weight)______________________________________Vitamin A 1Glycerol tri 2-ethylhexanoate 69Olive oil 10BHT 1.alpha.-tocopherol 91,3-butanediol 5Squalane 5______________________________________
______________________________________Example 9-7: Night cream (% by weight)______________________________________Vaseline 4Squalane 15Liquid paraffin 5Cetyl octanoate 5Glycerylmonooleate 4POE(5) hydrogenated castor oil 1Butyl paraben 0.2Vitamin A 0.21,4-butanediol 21,3-butanediol 8Glycerol 12Trisodium edetate 0.03Purified water To total amount 100______________________________________
The external skin treatment compositions of Examples 9-3 to 9-7 were excellent in the stability of vitamin A in daily use. As described hereinabove, in the external skin treatment composition of the present invention, by formulating butanediol and an oil-soluble antioxidant, stability of vitamin A can be extremely improved.
Examples 10-1, 10-2 and Comparative Examples 10-1, 10-2
Tocopherol, octylmethoxycinnamate, oleyl alcohol, methyl paraben, POE(20) octyldodecyl ether are completely dissolved in ethanol at 40.degree. C., thereafter, vitamin A is completely dissolved therein, and the solution is quickly cooled to form an alcohol portion. The resulting alcohol portion is added to an aqueous portion wherein other components are dissolved in purified water, and sealed in a brown glass sample tube. The tube is further wrapped with aluminum foil to completely cut light and is stored in a constant temperature bath at 40.degree. C.
TABLE 10-1______________________________________Vitamin A stability determinationresults in lotion (% by weight) Comp. Comp. Example Example Example Example 10-1 10-2 10-1 10-2______________________________________Vitamin A 0.001 0.001 0.001 0.001Oleyl alcohol 0.005 0.005 0.005 0.005Octylmethoxycinnamate -- -- 0.001 --Benzophenone-5 0.001 0.1 -- --Benzophenone-3 -- -- -- 0.01POE(20) Octyldodecyl 0.8 0.8 0.8 0.8etherEthanol 18 18 18 18Glycerol 3 3 3 3Methyl paraben 0.1 0.1 0.1 0.1Citric acid 0.03 0.03 0.03 0.03Trisodium citrate 0.07 0.07 0.07 0.07Trisodium edetate 0.02 0.02 0.02 0.02Purified water To total amount 100Vitamin A quantitative determination valueImmediately after 100 100 100 100preparation (%)After one month 92 95 49 52at 40.degree. C. (%)______________________________________
Quantitative determination method of vitamin A
In accordance with the second method of vitamin A quantitative determination method, Japanese Pharmacopoeia (11th revision), the quantitative determination was effected by an absorbance determination method using isopropanol.
In Examples 10-1 and 10-2, the stability of vitamin A is improved as compared with the Comparative Example. This is the effect produced by the addition of a water-soluble benzophenone compound according to the present invention.
Examples 10-3 to 10-4 and Comparative Examples 10-3 to 10-4
TABLE 10-2______________________________________Emulsion formulation and vitamin Aquantitative determination results (% by weight) Comp. Comp. Example Example Example Example 10-3 10-4 10-3 10-3______________________________________Vitamin A 0.3 0.01 0.3 0.01BHT 0.05 0.01 0.05 0.01d1-.alpha.-tocopherol 0.01 0.02 0.01 0.02Benzophenone-5 0.1 0.05 -- --Benzophenone-9 -- 0.05 -- --Octylmethoxy- -- -- 0.1 --cinnamateMethoxybenzoyl- -- -- -- 0.1methane*Cetyl 10 7 10 7isooctanoateSqualane 5 5 5 5Cetyl alcohol 2 2 2 2Vaseline 1 1 1 1Glyceryl 1.5 1.5 1.5 1.5monostearatePOE(60) 1.3 1.3 1.3 1.3hydrogenatedcastor oilCarboxyvinyl 0.2 0.3 0.2 0.3polymerCaustic potash 0.06 0.08 0.06 0.08Glycerol 10 10 10 10Propylene glycol 3 3 3 3Ethyl paraben 0.2 0.2 0.2 0.2Purified water To total amount 100Vitamin A quantitative determination valueImmediately after 100 100 100 100preparation (%)After one month 97 99 29 22at 40.degree. C. (%)______________________________________ *4-(1,1-dimethylethyl)-4methoxybenzoylmethane
Each oil component containing BHT, and tocopherol, and a surfactant are completely dissolved at 70.degree. C., thereafter, immediately before emulsification, vitamin A is completely dissolved therein to form an oil phase.
Glycerol, propylene glycol, carboxyvinyl polymer, caustic potash, benzophenone-9 and benzophenone-5 are completely dissolved in purified water. The oil phase is added to the resulting aqueous phase heated to 70.degree. C., then the mixture obtained is emulsified by a homomixer type emulsifier. Then, the resulting product is subjected to a cooling treatment by a heat exchanger to 30.degree. C. to form an emulsion.
The emulsion is filled in a glass bottle having a metal coat applied thereto, which is tightly sealed and is stored in a constant temperature bath at 40.degree. C.
In Examples 10-3 to 10-4, as compared with the Comparative Example, the stability of vitamin A is improved. This is the effect according to the present invention.
Quantitative determination method of vitamin A
According to the absorbance determination method at 325 nm using ethanol, the quantitative determination was effected. A sample was prepared by removing vitamin A from Example and Comparative Example (control) and the absorption at 325 nm was measured, which was used for correcting an absorbance as the absorbance of a base material.
(Absorbance of a sample of Example and Comparative Example at 325 nm)-(Absorbance of a control)=Absorbance of vitamin A
In the calculation, at the maximum absorption 325 nm, E (1%, 1 cm)=1835 was used.
______________________________________Example 10-5: Cosmetic lotion (% by weight)______________________________________Oleyl alcohol 0.002Vitamin A 0.0001POE(50) Oleyl ether 0.7Lactic acid 0.01Trisodium citrate 0.09Ethanol 8Glycerol 2Methyl paraben 0.2Benzophenone-12 2.5Benzophenone-5 2.5Purified water To total amount 100______________________________________
______________________________________Example 10-6: Oil essence (% by weight)______________________________________Glycerol tri 2-ethylhexanoate 34Isopropyl myristate 35Dibutyl phthalate 10Vitamin A 1Diglyceroldiisostearate 5Dipropylene glycol 14.997Benzophenone-4 0.001Trisodium citrate 0.002______________________________________
______________________________________Example 10-7: Cream (% by weight)______________________________________Squalane 15Glycerol tri 2-ethylhexanoate 8Isopropyl myristate 7.alpha.-tocopherol 0.05Vitamin A 0.3Vaseline 2Butyl paraben 0.1Propyl paraben 0.1Glycerol monooleate 3Diglyceroldiisostearate 2PEG400 dioleate 1Glycerol 10Dipropylene glycol 5Disodium edetate 0.01Benzophenone-4 0.03Triethanolamine 0.04Purified water To total amount 100______________________________________
______________________________________Example 10-8: Oil gel (% by weight)______________________________________Glycerol tri 2-ethylhexanoate 60POE(20) octyldodecyl ether 16Vitamin A 0.1Glycerol 16Benzophenone-5 0.05Purified water To total amount 100______________________________________
The external skin treatment compositions of Examples 10-5 to 10-8 were excellent in the stability of vitamin A in daily use. As described hereinabove, in the external skin treatment composition of the present invention, by formulating a water-soluble benzophenone compound, stability of vitamin A can be extremely improved.
Examples 11-1 to 11-3 and Comparative Example 11-1
TABLE 11-1______________________________________Vitamin A stability determinationresults in emulsion (% by weight) Comp. Example Example Example Example 11-1 11-2 11-3 11-1______________________________________Purified water To total amount 100Glycerol 10 10 10 10Carboxyvinyl polymer 0.2 0.2 0.2 0.2Arginine 0.21 0.28 0.42 0.06Caustic potash -- -- -- 0.06Ethyl alcohol 5 5 5 5Methyl paraben 0.1 0.1 0.1 0.1Cetyl alcohol 2 2 2 2Vaseline 3 3 3 3Squalane 5 5 5 5Isopropyl myristate 4 4 4 4Glycerylmonostearate 1.5 1.5 1.5 1.5POE(60) hydrogenated 2 2 2 2castor oilButylhydroxytoluene 0.05 0.05 0.05 0.05Vitamin A 0.3 0.3 0.3 0.3pH (25.degree. C.) 5.7 6.6 7.4 5.8Vitamin quantitative determination valueImmediately after 100 100 100 100preparation (%)After one month 90 92 95 71at 40.degree. C. (%)______________________________________
In Examples 11-1, 11-2, and 11-3, the stability of vitamin A is improved as compared with the Comparative Example. This is the effect according to the present invention.
Quantitative determination method of vitamin A
In accordance with the second method of vitamin A quantitative determination method, Japanese Pharmacopoeia (11th revision), the quantitative determination was effected by an absorbance determination method using isopropanol.
______________________________________Example 11-4: Cream (% by weight)______________________________________A. Cetanol 3 Glycerylmonostearate 2 POE(25) Cetyl ether 2 Stearic acid 3 Vaseline 2 Olive oil 3 Isopropyl myristate 3 Squalane 5 Vitamin A 0.1 BHT 0.05 Perfume q.s.B. Propylene glycol 3 Potassium hydroxide 0.27 Arginine 0.001 Purified water To total amount 100______________________________________
The oil phase portion (A) and the aqueous phase portion (B) are thermally melted at 70.degree. C., then A is added to B, the resulting mixture is emulsified, and subsequently subjected to a cooling treatment to form a cream. (pH=7.3)
______________________________________Example 11-5: Beauty essence (% by weight)______________________________________Carboxyvinyl polymer 0.4Glycerol 5Propyl glycol 5Lysine 0.5Arginine 4.8POE(60) hydrogenated castor oil 0.5Vitamin A 0.1Squalane 1.alpha.-tocopherol 0.05Methyl paraben 0.2Ethyl alcohol 6Purified water To total amount 100 pH = 6.7______________________________________
______________________________________Example 11-6: Cosmetic lotion (% by weight)______________________________________Glycerol 2Ethanol 7POE(50) Oleyl ether 0.5Oleyl alcohol 0.002Vitamin A 0.0001Lactic acid 0.03Arginine 0.1Ornithine hydrochloride 1Methyl paraben 0.1Purified water To total amount 100 pH = 6.2______________________________________
______________________________________Example 11-7: Oil gel (% by weight)______________________________________Vitamin A 0.5Glycerol tri 2-ethylhexanoate 40Olive oil 10BHT 0.1BHA 0.05PHE(20) octyldodecyl ether 16Glycerol 15Lysine hydrochloride 0.1Purified water To total amount 100 pH = 5.5______________________________________
______________________________________Example 11-8: Night cream (% by weight)______________________________________Solid paraffin 1Microcrystalline wax 2Beeswax 1Squalane 15Glycerol tri 2-ethylhexanoate 10Diglycerol diisostearate 3PEG400 diisostearate 1Propyl paraben 0.2Vitamin A 0.3Glycerol 10Propylene glycol 4Arginine 0.2Pyrrolidone carboxylic acid 0.2Purified water To total amount 100______________________________________
The external skin treatment compositions of Examples 11-4 to 11-8 were excellent in the stability of vitamin A in daily use.
In the external skin treatment composition of the present invention, by formulating a basic amino acid and/or the salt thereof, stability of vitamin A can be extremely improved.
Examples 12-1 to 12-3 and Comparative Example 12-1
TABLE 12-1______________________________________Vitamin A stability determinationresults in emulsion (% by weight) Comp. Example Example Example Example 12-1 12-2 12-3 12-1______________________________________Purified water To total amount 100Glycerol 10 10 10 10Carboxyvinyl polymer 0.2 0.2 0.2 0.2Caustic potash 0.06 0.06 0.06 0.06Ethyl alcohol 5 5 5 5Methyl paraben 0.1 0.1 0.1 0.1Cetyl alcohol 2 2 2 2Butyl alcohol 1 1 1 1Vaseline 3 3 3 3Squalane 5 5 5 5Isopropyl myristate 4 4 4 4Glycerylmonostearate 1.5 1.5 1.5 1.5POE(60) hydrogenated 2 2 2 2castor oilBHT 0.03 0.03 0.03 0.03Trisodium edetate 0.02 0.02 0.02 0.02Arginine aspartate 0.03 0.03 -- --Monosodium glutamate -- 0.5 0.01 --Vitamin A 0.3 0.3 0.3 0.3Vitamin A quantitative determination valueImmediately after 100 100 100 100preparation (%)After two months 90 96 90 69at 40.degree. C. (%)______________________________________
In Examples 12-1, 12-2 and 12-3, the stability of vitamin A is improved as compared with the Comparative Example. This is the effect according to the present invention.
Quantitative determination method of vitamin A
In accordance with the second method of vitamin A quantitative determination method, Japanese Pharmacopoeia (11th revision), the quantitative determination was effected by an absorbance determination method using isopropanol.
______________________________________Example 12-4: Cream (% by weight)______________________________________A. Cetanol 3 Glycerylmonostearate 2 POE(25) Cetyl ether 1 Stearic acid 3 Vaseline 3 Olive oil 3 Isopropyl myristate 1 Squalane 5 Vitamin A 0.1 BHT 0.05 Perfume q.s.B. Propylene glycol 3 Potassium hydroxide 0.2 Monosodium glutamate 5 Purified water To total amount 100______________________________________
The oil phase portion (A) and the aqueous phase portion (B) are thermally melted at 70.degree. C., then A is added to B, the resulting mixture is emulsified, and subsequently subjected to a cooling treatment to form a cream.
______________________________________Example 12-5: Beauty essence (% by weight)______________________________________Carboxyvinyl polymer 0.4Glycerol 5Propylene glycol 5Arginine aspartate 0.001Triethanolamine 3.4POE(60) hydrogenated castor oil 0.5Vitamin A 0.001Squalane 1.alpha.-tocopherol 1Methyl paraben 0.2Ethyl alcohol 6Purified water To total amount 100______________________________________
______________________________________Example 12-6: Cosmetic lotion (% by weight)______________________________________Glycerol 2Ethanol 7POE(50) Oleyl ether 0.5Oleyl alcohol 0.002Vitamin A 0.0001Aspartic acid 0.001Lactic acid 0.02Sodium lactate 0.1Methyl paraben 0.1Purified water To total amount 100______________________________________
______________________________________Example 12-7: Oil gel (% by weight)______________________________________Vitamin A 1Glycerol tri 2-ethylhexanoate 40Oliver oil 19BHT 0.1BHA 0.05POE(20) octyldodecyl ether 16Glycerol 15Sodium glutamate 0.01Purified water To total amount 100______________________________________
______________________________________Example 12-8: Beauty liquid (% by weight)______________________________________Vitamin A 0.3Isopropyl myristate 3POE(60) hydrogenated castor oil 0.6Gum xanthane 0.8Glycerol 30Propylene glycol 5Sodium pyrrolidone carboxylate (50%) 20Ethanol 6Methyl paraben 0.1Purified water To total amount 100______________________________________
______________________________________Example 12-9: Night cream (% by weight)______________________________________Squalane 15Microcrystalline wax 4Isopropyl myristate 5Vaseline 4Octyl dodecanol 2Butyl paraben 0.15Vitamin A 0.2Diglycerol diisostearate 4Glycerol 3Propylene glycol 3Sodium glutamate 1Purified water To total amount 100______________________________________
The external skin treatment compositions of Examples 12-4 to 12-9 were excellent in the stability of vitamin A in daily use.
In the external skin treatment composition of the present invention, by formulating an acidic amino acid and/or the salt thereof, stability of vitamin A can be extremely improved.
Examples 13-1 to 13-3 and Comparative Examples 13-1 to 13-2
TABLE 13-1______________________________________Vitamin A stability determinationresults in oil (% by weight) Ex- Ex- Ex- Comp. Comp. ample ample ample Example Example 13-1 13-2 13-3 13-1 13-2______________________________________Vitamin A 1 1 1 1 1Pentaerythritol 99 49 -- -- --esterTrimethylol- -- 50 99 -- --propane esterSqualane -- -- -- 99 --Cetylisooctanoate -- -- -- -- 99Vitamin A quantitative determination valueImmediately after 99 100 99 100 100preparation (%)After one month 96 94 92 40 51at 40.degree. C. (%)______________________________________ Pentaerythritol ester: pentaerythritotetra(2-ethylhexanoate) ester Trimethylolpropane ester: trimethylolpropanetri(2-ethyl-hexanoate)ester
Quantitative determination method of vitamin A
In accordance with the second method of vitamin A quantitative determination method, Japanese Pharmacopoeia (11th revision), the quantitative determination was effected by an absorbance determination method using isopropanol.
In Examples 13-1, 13-2, and 13-3, the stability of vitamin A is improved as compared with the Comparative Example. This is the effect according to the present invention.
Examples 13-4, 13-5 and Comparative Examples 13-3, 13-4
BHT and tocopherol are each completely dissolved in oil at 60.degree. C., then the resulting solution is cooled to 40.degree. C. Thereafter, vitamin A is completely dissolved therein. The resulting solution is filled in a brown glass sample tube and is stored in a constant temperature bath at 40.degree. C.
TABLE 13-2______________________________________Cosmetic oil formulation and vitamin Astability determination results (% by weight) Comp. Comp. Example Example Example Example 13-4 13-5 13-3 13-4______________________________________Trimethylolpropane 75 10 -- --(2-ethylhexanoate)Pentaerythritol -- 80 -- --(2-ethylhexanoate)Dimethylpolysiloxane -- 9.76 -- 39.76Isopropylmyristate -- -- 15 60Squalane 24.985 -- 84.985 --Vitamin A 0.01 0.2 0.01 0.2BHT 0.005 0.03 0.005 0.03d1-.alpha.-tocopherol -- 0.01 -- 0.01Vitamin A quantitative determination valueImmediately after 100 100 100 100preparation (%)After two months at 96 97 59 7340.degree. C. (%)______________________________________
In Examples 13-4 and 13-5, as compared with the Comparative Example, the stability of vitamin A is improved. This is the effect according to the present invention.
Production method and temperature test method of Examples 13-6, 13-7 and Comparative Examples 13-5, 13-6
BHT, tocopherol and each oil and a surfactant are completely dissolved at 70.degree. C., thereafter, immediately before emulsification, vitamin A is completely dissolved therein to form an oil phase.
Glycerol, propylene glycol, carboxyvinyl polymer and caustic potash are completely dissolved in purified water. The oil phase is added to the resulting aqueous phase heated to 70.degree. C., then the mixture obtained is emulsified by a homomixer type emulsifier. Then the resulting product is subjected to a cooling treatment by a heat exchanger to 30.degree. C. to form an emulsion.
The emulsion is filled in a glass bottle having a metal coat applied thereto, which is tightly sealed and is stored in a constant temperature bath at 40.degree. C.
TABLE 13-3______________________________________Emulsion formulation and vitamin A quantitative determination results(% by weight) Comp. Comp. Example Example Example Example 13-6 13-7 13-5 13-6______________________________________Pentaerythritol 10 4 -- --(2-ethylhexanoate)Trimethylolpropane -- 3 -- --(2-ethylhexanoate)BHT 0.05 0.01 0.05 0.01d1-.alpha.-tocopherol 0.01 0.02 0.01 0.02Vitamin A 0.3 0.01 0.3 0.01Cetylisooctanoate -- -- 10 7Squalane 5 2 5 2Cetyl alcohol 2 2 2 2Vaseline 1 1 1 1Glyceryl monostearate 1.5 1.5 1.5 1.5POE(60)Hydrogenated castor 1.3 1.3 1.3 1.3oilCarboxyvinyl polymer 0.2 0.2 0.2 0.2Caustic Potash 0.06 0.06 0.06 0.06Glycerol 10 10 10 10Propylene glycol 3 3 3 3Ethyl paraben 0.2 0.2 0.2 0.2Purified water To total amount 100Vitamin A quantitative determination valueImmediately after 100 100 100 100preparation (%)After one month at 98 96 32 2540.degree. C. (%)______________________________________
In Examples 13-6 and 13-7, the stability of vitamin A is improved as compared with the Comparative Example. This is the effect according to the present invention.
Quantitative determination method of vitamin A
According to the absorbance determination method at 325 nm using ethanol, the quantitative determination was effected.
In the calculation, at the maximum absorption 325 nm, E (1%, 1 cm)=1835 was used
______________________________________Example 13-8: Cosmetic lotion (% by weight)______________________________________Pentaerythritoltetracaprate 0.002tocopherol 0.001.alpha.-tocopherol 0.0005Vitamin A 0.0001POE(50) Oleylether 0.7Lactic acid 0.1Sodium lactate 0.9Ethanol 5Glycerol 1Methyl paraben 0.2Trisodium edetate 0.01Purified water To total amount 100______________________________________
______________________________________Example 13-9: Oil essence (% by weight)______________________________________Pentaerythritoltetra (2-hexanoate) 60Trimethyrolpropanetricaprate 10Squalane 10BHT 1.alpha.-tocopherol 9Vitamin A 5______________________________________
______________________________________Example 13-10: Cream (% by weight)______________________________________Glycerol tri 2-ethylhexanoate 10Pentaerythritoltetra (2-ethylhexanoate) 15BHT 0.05BHA 0.01.alpha.-tocopherol 0.01Vitamin A 0.3Vaseline 2Squalane 8Butyl paraben 0.1Propyl paraben 0.1Glycerol monooleate 3Diglycerol diisostearate 2PEG400 dioleate 1Glycerol 10Dipropylene glycol 5Purified water To total amount 100______________________________________
______________________________________Example 13-11: Eye wrinkle oil (% by weight)______________________________________Pentaerythritoitetra(2-ethylhexanoate) 40Trimethyrolpropanetricaprate 20Glycerol tri 2-ethylhexanoate 20Squalane 19Acetic acid palmitate 1______________________________________
The external skin treatment compositions of Examples 13-8 to 13-11 were excellent in the stability of vitamin A in daily use.
In the external skin treatment composition of the present invention, by formulating at least one polar oil component selected from the group cosisting of pentaerythritol fatty acid ester and trimethylol propane fatty acid ester, the stability of vitamin A can be improved.
In accordance with the present invention, by formulating at least one polar oil selected from the group consisting of pentaerythritol fatty acid ester and trimethylolpropane fatty acid ester, and at least one oil-soluble antioxidant selected from the group consisting of butyl hydroxytoluene, butyl hydroxyanisole, .alpha.,.beta.,.gamma.,.delta.-tocopherol, nordihydrogualaretin, propyl gallate, a fatty acid ester of vitamin C and sorbic acid, the stability of vitamin A can be further noticeably improved.
Examples 14-1 to 14-2 and Comparative Examples 14-1 to 14-2
TABLE 14-1______________________________________Vitamin A stability determination results in emulsion (% by weight) Comp. Comp. Example Example Example Example 14-1 14-2 14-1 14-2______________________________________Purified water To total amount 100Glycerol 10 10 10 10Ethyl alcohol 5 5 5 5Methyl paraben 0.1 0.1 0.1 0.1Glyceryl monostearate 1.5 1.5 1.5 1.5POE(60) hydrogenated 2 2 2 2castor oilCetyl alcohol 2 2 2 2Isopropyl myristate 4 4 4 4Vaseline 3 3 3 3Squalane 5 5 5 5BHT -- 0.05 -- 0.05Trisodium edetate -- 0.03 -- 0.03Natural 2 2 -- --montmorilloniteVitamin A 0.3 0.3 0.3 0.3Vitamin A quantitative determination valueImmediately after 100 100 100 100preparation (%)After one month at 90 95 53 6840.degree. C. (%)______________________________________ *Natural montmorillonite: Trade name Kunipia G4
Quantitative determination method of vitanin A
In accordance with the second method of vitamin A quantitative determination method, Japanese Pharmacopoeia (11th revision), the quantitative determination was effected by an absorbance determination method using isopropanol.
In Examples 14-1, 14-2, the stability of vitamin A is improved as compared with Comparative Example. This is the effect according to the present invention.
TABLE 14-2______________________________________Emulsion formulation and vitamin A quantitative determination results(% by weight) Comp. Comp. Example Example Example Example 14-3 14-4 14-3 14-4______________________________________Natural saponite 3 3 -- --(Veegum HV)Ascorbic acid 0.1 -- 0.1 --BHT 0.05 0.01 0.05 0.01d1-.alpha.-tocopherol 0.01 0.02 0.01 0.02Vitamin A 0.3 0.01 0.3 0.01Cetylisooctanoate 10 7 10 7Squalane 5 2 5 2Cetyl alcohol 2 2 2 2Vaseline 1 1 1 1Glyceryl monostearate 1.5 1.5 1.5 1.5POE(60) hydrogenated 1.3 1.3 1.3 1.3castor oilGlycerol 10 10 10 10Propylene glycol 3 3 3 3Methyl paraben 0.2 0.2 0.2 0.2Purified water To total amount 100Vitamin A quantitative determination valueImmediately after 100 100 100 100preparation (%)After one month at 95 92 63 5140.degree. C. (%)______________________________________
______________________________________Example 14-5: Cream (% by weight)______________________________________A. Cetanol 3 Glycerylmonostearate 2 POE(25) cetyl ether 1 Stearic acid 3 Vaseline 3 Olive oil 3 Isopropyl palmitate 1 Squalane 5 Vitamin A 0.1 BHT 0.05 Perfume q.s.B. Propylene glycol 3 Potassium hydroxide 0.2 Synthetic saponite 0.1 (Trade name: Smectone SA) Citric acid 0.001 Purified water To total amount 100______________________________________
The oil phase portion (A) and the aqueous phase portion (B) are thermally melted at 70.degree. C., then A is added to B, the resulting mixture is emulsified, and subsequently subjected to a cooling treatment to form a cream.
______________________________________Example 14-6: Beauty gel (% by weight)______________________________________Synthetic hectlite 10(Trade name: Laponite XLG)Glycerol 15Propylene glycol 5Citric acid 0.5Triethanolamine 1.82-hydroxy-4-methoxybenzophenone-5- 1sodium sulfonatePOE(60) hydrogenated castor oil 0.5Vitamin A 0.1Octylmetroxycinnamate 9Methyl paraben 0.2Ethyl alcohol 3Purified water To total amount 100______________________________________
______________________________________Example 14-7: Cosmetic lotion (% by weight)______________________________________Glycerol 2Ethanol 7POE(50) Oleyl ether 0.5Oleyl alcohol 0.002Vitamin A 0.0001Synthetic saponite 0.01(Trade name: Smectone SA)Lactic acid 0.01Sodium lactate 0.09Methyl paraben 0.1Purified water To total amount 100______________________________________
______________________________________Example 14-8: Cream (% by weight)______________________________________Squalane 15Glycerol tri 2-ethylhexanoate 10Olive oil 10Butyl paraben 0.2Diglycerol diisostearate 2Glycerylmonooleate 2Natural saponite 3(Trade name: Veegum HV)Dimethylstearylammoniumchloride 1.0Vitamin A 0.5BHT 0.1Disodium edetate 0.01Ascorbic acid 0.01Sodium isoascorbate 0.012-hydroxy-4-methoxybenzophenone 0.3Glycerol 10Phenoxy ethanol 0.1Purified water To total amount 100______________________________________
______________________________________Example 14-9: Oil gel (% by weight)______________________________________Vitamin A 1Glycerol tri 2-ethylhexanoate 40.alpha.-tocopherol 9Squalane 10Natural montmorillonite 10(Trade name: Kunipia G)Natural saponite 10(Trade name: Veegum HV)BHT 12-ethylhexyl paradimethylbenzoate 10POE(20) hydrogenated castor oil 6Purified water 4______________________________________
______________________________________Example 14-10: Beauty powder (% by weight)______________________________________Synthetic hectlite 50(Trade name: Laponite XLG)D-mannitol 48Isopropyl palmitate 1.9Vitamin A 0.1______________________________________
______________________________________Example 14-11: Beauty essense (% by weight)______________________________________Synthetic hectlite 3(Trade name: Laponite XLG)Synthetic saponite 1(Trade name: Smectone SA)Glycerol 20Propylene glycol 5Citric acid 0.03Trisodium citrate 0.07.alpha.-tocopherol 12-hydroxy-4-methoxybenzophenone-5- 0.5Sodium sulfonate4-t-butyl-4'-methoxydibenzoylmethane 0.1POE(60) hydrogenated castor oil 0.5Vitamin A 0.1Sodium hexametaphosphate 0.02Methyl paraben 0.2Ethyl alcohol 3Purified water To total amount 100______________________________________
The external skin treatment compositions of Examples 14-5 to 14-11 were excellent in the stability of vitamin A in daily use.
In the external skin treatment composition of the present invention, by formulating at least one water-swellable clay mineral, the stability of vitamin A can be improved.
In accordance with the present invention, by formulating at least one water-swellable clay mineral and at least one antioxidant, chelating agent and ultraviolet absorber, the stability of vitamin A can be further noticeably improved.

Claims

1. An external skin treatment composition comprising (I) vitamin A and (II) at least one stabilizer selected from the group consisting of:
(1) (i) at least one oil-soluble antioxidant selected from the group consisting of butyl hydroxytoluene (BHT), butyl hydroxyanisole (BHA), .alpha.,.beta.,.gamma.,.delta.-tocopherol, nordihydrogualaretin, propyl gallate, fatty acid esters of vitamin C and sorbic acid, (ii) at least one ethylenediaminetetraacetate and (iii) at least one benzophenone compound selected from the group consisting of benzophenone-1, benzophenone-2, benzophenone-3, benzophenone-4, benzophenone-5, benzophenone-6, benzophenone-7, benzophenone-8, benzophenone-9, benzophenone-10 and benzophenone-12;
(2) (i) at least one oil-soluble antioxidant selected from the group consisting of BHT, BHA, .alpha.,.beta.,.gamma.,.delta.-tocopherol, nordihydrogualaretin, propyl gallate and fatty acid esters of vitamin C, (ii) at least one compound selected from the group consisting of ascorbic acid, ascorbic acid salts, isoascorbic acid, isoascorbic acid salts, sorbic acid and sorbic acid salts and (iii) at least one benzophenone compound selected from the group consisting of benzophenone-1, benzophenone-2, benzophenone-3, benzophenone-4, benzophenone-5, benzophenone-6, benzophenone-7, benzophenone-8, benzophenone-9, benzophenone-10 and benzophenone-12;
(3) inclusion compounds of (i) cyclodextrins including (ii) at least one compound selected from the group consisting of nordihydrogualaretin, BHT, BHA, .alpha.,.beta.,.gamma.,.delta.-tocopherols, propyl gallate, a fatty acid ester of vitamin C, sorbic acid, benzophenones-1 to 10 and 12, cinnamic acid compounds, salicylic acid compounds, benzoic acid compounds, and dibenzoylmethane compounds;
(4) (i) 1,3-butanediol and/or (ii) at least one oil-soluble antioxidant selected from the group consisting of nordihydrogualaretin, BHT, BHA, .alpha.,.beta.,.gamma.,.delta.-tocopherols, propyl gallate, a fatty acid ester of vitamin C and sorbic acid; and
(5) at least one water-soluble benzophenone compound, wherein the composition comprises 0.0001% by weight or more of vitamin A, and
(A) 0.001% by weight or more of (1) (i) the oil-soluble antioxidant,
(B) 0.001% by weight or more of (1)(ii) the ethylenediaminetetraacetate,
(C) 0.001% by weight or more of (1) (iii) the benzophenone compound, on the basis of the total weight of the composition.
2. An external skin treatment composition comprising (I) vitamin A and (II) at least one stabilizer selected from the group consisting of:
(1) (i) at least one oil-soluble antioxidant selected from the group consisting of butyl hydroxytoluene (BHT). butyl hydroxyanisole (BHA), .alpha.,.beta.,.gamma.,.delta.-tocopherol, nordihydrogualaretin, propyl gallate, fatty acid esters of vitamin C and sorbic acid, (ii) at least one ethylenediaminetetraacetate and (iii) at least one benzophenone compound selected from the group consisting of benzophenone-1, benzophenone-2, benzophenone-3 benzophenone-4, benzophenone-5, benzophenone-6, benzophenone-7, benzophenone-8, benzophenone-9, benzophenone-10 and benzophenone-12;
(2) (i) at least one oil-soluble antioxidant selected from the group consisting of BHT, BHA .alpha.,.beta.,.gamma.,.delta.-tocopherol, nordihydrogualaretin, propyl gallate and fatty acid esters of vitamin C, (ii) at least one compound selected from the group consisting of ascorbic acid, ascorbic acid salts, isoascorbic acid, isoascorbic acid salts, sorbic acid and sorbic acid salts and (iii) at least one benzophenone compound selected from the group consisting of benzophenone-1, benzophenone-2, benzophenone-3, benzophenone-4, benzophenone-5, benzophenone-6, benzophenone-7, benzophenone-8, benzophenone-9, benzophenone-10 and benzophenone-12;
(3) inclusion compounds of (i) cyclodextrins including (ii) at least one compound selected from the group consisting of nordihydrogualaretin, BHT, BHA, .alpha.,.beta.,.gamma.,.delta.-tocopherols, propyl gallate, a fatty acid ester of vitamin C, sorbic acid, benzophenones-1 to 10 and 12, cinnamic acid compounds, salicylic acid compounds, benzoic acid compounds, and dibenzoylmethane compounds;
(4) (i) 1,3-butanediol and/or (ii) at least one oil-soluble antioxidant selected from the group consisting of nordihydrogualaretin, BHT, BHA, .alpha.,.beta.,.gamma.,.delta.-tocopherols, propyl gallate, a fatty acid ester of vitamin C and sorbic acid; and
(5) at least one water-soluble benzophenone compound, wherein the composition comprises 0.0001% by weight or more of vitamin A, and
(A) 0.001% by weight or more of (2) (i) the oil-soluble antioxidant,
(B) 0.001% by weight or more of (2) (ii) the compound, and
(C) 0.001% by weight or more of (2) (iii) the benzophenone compound, on the basis of the total weight of the composition.
3. An external skin treatment composition comprising (I) vitamin A and (II) at least one stabilizer selected from the group consisting of:
(1) (i) at least one oil-soluble antioxidant selected from the group consisting of butyl hydroxytoluene (BHT) butyl hydroxyanisole (BHA), .alpha.,.beta.,.gamma.,.delta.-tocopherol, nordihydrogualaretin, propyl gallate, fatty acid esters of vitamin C and sorbic acid, (ii) at least one ethylenediaminetetraacetate and (iii) at least one benzophenone compound selected from the group consisting of benzophenone-1, benzophenone-2, benzophenone-3, benzophenone-4, benzophenone-5, benzophenone-6, benzophenone-7, benzophenone-8, benzophenone-9, benzophenone-10 and benzophenone-12;
(2) (i) at least one oil-soluble antioxidant selected from the group consisting of BHT, BHA, .alpha.,.beta.,.gamma.,.delta.-tocopherol, nordihydrogualaretin, propyl gallate and fatty acid esters of vitamin C, (ii) at least one compound selected from the group consisting of ascorbic acid, ascorbic acid salts, isoascorbic acid, isoascorbic acid salts, sorbic acid and sorbic acid salts and (iii) at least one benzophenone compound selected from the group consisting of benzophenone-1, benzophenone-2, benzophenone-3, benzophenone-4, benzophenone-5, benzophenone-6, benzophenone-7, benzophenone-8, benzophenone-9, benzophenone-10 and benzophenone-12;
(3) inclusion compounds of (i) cyclodextrins including (ii) at least one compound selected from the group consisting of nordihydrogualaretin, BHT, BHA, .alpha.,.beta.,.gamma..delta.-tocopherols, propyl gallate, a fatty acid ester of vitamin C, sorbic acid, benzophenones-1 to 10 and 12, cinnamic acid compounds, salicylic acid compounds, benzoic acid compounds, and dibenzoylmethane compounds;
(4) (i) 1,3-butanediol and/or (ii) at least one oil-soluble antioxidant selected from the group consisting of nordihydrogualaretin, BHT, BHA, .alpha.,.beta.,.gamma.,.delta.-tocopherols, propyl gallate, a fatty acid ester of vitamin C and sorbic acid; and
(5) at least one water-soluble benzophenone compound, wherein the composition comprises 0.0001% by weight or more of vitamin A, 0.01% by weight or more of (3) (i) the cyclodextrin including 0.001% by weight or more of (3) (ii) the compound, on the basis of the total weight of the composition.
4. An external skin treatment composition comprising (I) vitamin A and (II) at least one stabilizer selected from the group consisting of:
(1) (i) at least one oil-soluble antioxidant selected from the group consisting of butyl hydroxytoluene (BHT), butyl hydroxyanisole (BHA), .alpha.,.beta.,.gamma.,.delta.-tocopherol, nordihydrogualaretin, propyl gallate, fatty acid esters of vitamin C and sorbic acid, (ii) at least one ethylenediaminetetraacetate and (iii) at least one benzophenone compound selected from the group consisting of benzophenone-1, benzophenone-2, benzophenone-3, benzophenone-4, benzophenone-5, benzophenone-6, benzophenone-7, benzophenone-8, benzophenone-9, benzophenone-10 and benzophenone-12;
(2) (i) at least one oil-soluble antioxidant selected from the group consisting of BHT, BHA, .alpha.,.beta.,.gamma.,.delta.-tocopherol, nordihydrogualaretin, propyl gallate and fatty acid esters of vitamin C, (ii) at least one compound selected from the group consisting of ascorbic acid, ascorbic acid salts, isoascorbic acid, isoascorbic acid salts, sorbic acid and sorbic acid salts and, (iii) at least one benzophenone compound selected from the group consisting of benzophenone-1, benzophenone-2, benzophenone-3, benzophenone-4, benzophenone-5, benzophenone-6, benzophenone-7, benzophenone-8, benzophenone-9, benzophenone-10 and benzophenone-12;
(3) inclusion compounds of (i) cyclodextrins including (ii) at least one compound selected from the group consisting of nordihydrogualaretin, BHT, BHA, .alpha.,.beta.,.gamma.,.delta.-tocopherols, propyl gallate, a fatty acid ester of vitamin C, sorbic acid, benzophenones-1 to 10 and 12, cinnamic acid compounds, salicylic acid compounds, benzoic acid compounds, and dibenzoylmethane compounds:
(4) (i) 1,3-butanediol and/or (ii) at least one oil-soluble antioxidant selected from the group consisting of nordihydrogualaretin, BHT, BHA, .alpha.,.beta.,.gamma.,.delta.-tocopherols, propyl gallate, a fatty acid ester of vitamin C and sorbic acid; and
(5) at least one water-soluble benzophenone compound, wherein the composition comprises 0.0001% by weight or more of vitamin A, 0.01% by weight or more of (4) (i) the 1,3-butanediol and 0.001% by weight or more of (4) (ii) the oil-soluble antioxidant, on the basis of the total weight of the composition.
5. An external skin treatment composition comprising (I) vitamin A and (II) at least one stabilizer selected from the group consisting of:
(1) (i) at least one oil-soluble antioxidant selected from the group consisting of butyl hydroxytoluene (BHT), butyl hydroxyanisole (BHA), .alpha.,.beta.,.gamma.,.delta.-tocopherol, nordihydrogualaretin, propyl gallate, fatty acid esters of vitamin C and sorbic acid, (ii) at least one ethylenediaminetetraacetate and (iii) at least one benzophenone compound selected from the group consisting of benzophenone-1, benzophenone-2, benzophenone-3, benzophenone-4, benzophenone-5, benzophenone-6, benzophenone-7, benzophenone-8, benzophenone-9, benzophenone-10 and benzophenone-12;
(2) (i) at least one oil-soluble antioxidant selected from the group consisting of BHT, BHA, .alpha.,.beta.,.gamma.,.delta.-tocopherol, nordihydrogualaretin, propyl gallate and fatty acid esters of vitamin C, (ii) at least one compound selected from the group consisting of ascorbic acid, ascorbic acid salts, isoascorbic acid, isoascorbic acid salts, sorbic acid and sorbic acid salts and (iii) at least one benzophenone compound selected from the group consisting of benzophenone-1, benzophenone-2, benzophenone-3, benzophenone-4, benzophenone-5, benzophenone-6, benzophenone-7, benzophenone-8, benzophenone-9, benzophenone-10 and benzophenone-12;
(3) inclusion compounds of (i) cyclodextrins including (ii) at least one compound selected from the group consisting of nordihydrogualaretin, BHT, BHA, .alpha.,.beta.,.gamma.,.delta.-tocopherols, propyl gallate, a fatty acid ester of vitamin C, sorbic acid, benzophenones-1 to 10 and 12, cinnamic acid compounds, salicylic acid compounds, benzoic acid compounds, and dibenzoylmethane compounds;
(4) (i) 1,3-butanediol and/or (ii) at least one oil-soluble antioxidant selected from the group consisting of nordihydrogualaretin, BHT, BHA, .alpha.,.beta.,.gamma.,.delta.-tocopherols, propyl gallate, a fatty acid ester of vitamin C and sorbic acid; and
(5) at least one water-soluble benzophenone compound, wherein the composition comprises 0.0001% by weight or more of vitamin A and 0.001% by weight or more of (5) the water-soluble benzophenone compound, on the basis of the total weight of the composition.
6. An external skin treatment composition comprising, all on a basis of a total weight of the composition, (I) 0.0001 % by weight or more of vitamin A and (II) at least one stabilizer comprising 0.001 % by weight or more of at least one benzophenone compound selected from the group consisting of benzophenone-1, benzophenone-2, benzophenone-3, benzophenone4, benzophenone-5, benzophenone-6, benzophenone-7, benzophenone-8, benzophenone-9, benzophenone-10 and benzophenone-12.
7. The composition of claim 6, further comprising at least one of (i) or (ii):
(i) 0.001 % by weight or more of at least one oil-soluble antioxidant selected from the group consisting of butyl hydroxytoluene (BHT), butyl hydroxyanisole (BHA), .alpha.,.beta.,.gamma.,.delta.-tocopherol, nordihydrogualaretin, propyl gallate and fatty acid esters of vitamin C; and
(ii) 0.001 % by weight or more of at least one ethylenediaminetetraacetate.
8. The composition of claim 6, further comprising at least one of (i) or (ii):
(i) 0.001% by weight or more of at least one oil-soluble antioxidant selected from the group consisting of butyl hydroxytoluene (BHT), butyl hydroxyanisole (BHA), .alpha.,.beta.,.gamma.,.delta.-tocopherol, nordihydrogualaretin, propyl gallate and fatty acid esters of vitamin C; and
(ii) 0.001% by weight or more of at least one compound selected from the group consisting of ascorbic acid, ascorbic acid salts, isoascorbic acid, isoascorbic acid salts, sorbic acid and sorbic acid salts.
9. An external skin treatment composition comprising, all on a basis of a total weight of the composition, (I) 0.0001 % by weight or more of vitamin A and (II) at least one stabilizer comprising 0.01% by weight or more of inclusion compounds of (i) cyclodextrins including (ii) 0.001% by weight or more of at least one compound selected from the group consisting of benzophenones-1 to 10 and 12, cinnamic acid compounds, salicylic acid compounds, benzoic acid compounds, and dibenzoylmethane compounds.
10. The composition of claim 9, further comprising at least one of nordihydrogualaretin, BHT, BHA, .alpha.,.beta.,.gamma.,.delta.-tocopherols, propyl gallate, a fatty acid ester of vitamin C and sorbic acid.
11. An external skin treatment composition comprising, all on a basis of a total weight of the composition, (I) 0.0001 % by weight or more of vitamin A and (II) at least one stabilizer comprising 0.001 % by weight or more of at least one water soluble benzophenone compound.

Priority Claims (14)

Number	Date	Country
4-227725	Jul 1992	JPX
4-227727	Jul 1992	JPX
4-227728	Jul 1992	JPX
4-227729	Jul 1992	JPX
4-227730	Jul 1992	JPX
4-227731	Jul 1992	JPX
4-227732	Jul 1992	JPX
4-227733	Jul 1992	JPX
4-227734	Jul 1992	JPX
4-227735	Jul 1992	JPX
4-227736	Jul 1992	JPX
4-227737	Jul 1992	JPX
4-227738	Jul 1992	JPX
4-227739	Jul 1992	JPX

Parent Case Info

This application is a division of application Ser. No. 08/204,286, filed Mar. 10, 1994 now U.S. Pat. No. 5,484,816 which is the national stage of PCT/JP93/00969 filed Jul. 13, 1993.

US Referenced Citations (44)

Number	Name	Date
RE33845	Schreuder	Mar 1992
4011323	Thompson	Mar 1977
4154823	Schutt	May 1979
4247547	Marks	Jan 1981
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Divisions (1)

	Number	Date	Country
Parent	204286	Mar 1994

External skin treatment composition

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Abstract