JP6235779B2 - Folic acid-containing composition and method for stabilizing folic acid - Google Patents

Description

The present invention relates to a folic acid-containing composition that is stable to light and the like, and a method for stabilizing folic acid, and is particularly useful as an external preparation for skin or a cosmetic.

Folic acid is also called vitamin M, vitamin B9, and pteroylglutamic acid, and is an essential nutrient for living bodies involved in the synthesis of amino acids, proteins, erythrocytes and nucleic acids. Since folic acid is not synthesized de novo in the human body, it must be taken with food. In recent years, attention has been particularly focused on the effect of folic acid, although the probability of a newborn with a neural tube abnormality being born increases due to folic acid deficiency during pregnancy of the mother, but this can be prevented by administration of folic acid (Non-patent Document 1). . In addition, it has been reported that folic acid has a protective action against cancer, particularly epithelial cancer (Non-patent Document 2), and the importance of folic acid is being recognized again. For this reason, the Ministry of Health, Labor and Welfare recommends taking folic acid at 240 μg / day for general adults and 440 μg / day for pregnant women. Folic acid is abundant in vegetables and fruits such as spinach, but its content is low compared to the daily requirement, and it is difficult to get all the necessary folic acid from the diet. Many. Therefore, dietary supplements containing folic acid have been developed, and supplements are widely used especially for pregnant women.

On the other hand, it has been reported that folic acid has an effect of repairing damaged DNA in the skin, and is particularly effective for preventing and repairing DNA damage caused by ultraviolet rays. (Patent Document 1). In addition, 7,8-dihydrofolic acid, which is a reduced folic acid, specifically inhibits the binding of SCF to the c-kit receptor on the melanocyte surface, causing browning of the skin and generation of spots and freckles associated with excessive production of melanin. It has been reported to have a preventive or ameliorating effect (Patent Document 2).

As described above, it has been reported that folic acid is useful for the prevention and treatment of various diseases and phenomena, and maintenance of health. In recent years, the necessity and importance of folic acid ingestion and topical use has been increasing. Is an unstable compound, and it is very difficult to ensure the stability of a composition containing folic acid, particularly an aqueous composition.
Folic acid can exist stably in a limited region from weakly acidic to neutral region. In addition, since folic acid is easily decomposed by light and heat (Non-patent Document 3), the content of folic acid in the composition decreases with time, resulting in discoloration and precipitation unless properly stored in a cool and dark place. . Therefore, preserved when folic acid-containing beverages, drops, cosmetics, etc., especially containers with low light shielding properties such as PET bottles are applied, or when the composition is displayed over the counter and exposed to strong light as a product. There was a big problem with stability.

In order to overcome this, conventionally, a method has been reported in which folic acid is used in combination with trehalose or erythritol to facilitate dissolution in water and to improve thermal stability. However, the blending amount of folic acid is extremely small (about 0.00007%), and it is not a sufficient amount for exhibiting the usefulness of folic acid. In addition, since saccharides are blended as a stabilizer, sweetness is produced when used as a food and drink, and satisfactory in terms of poor usability (stickiness) when used as a skin external preparation. It did not go (Patent Document 3).

In addition, there has also been reported a technique (Patent Document 4) that maintains thermal stability by combining folic acid and a large amount of a large amount of amino acids in a specific pH region so that the various amino acids complement each other. However, since the amount of amino acid blended as a stabilizer is very large (about 10%), it is likely to generate a strange odor due to heat and light, and when it is used as a food or drink, it has a unique flavor and taste. When used as an external preparation for skin, it was not a preferable method in terms of poor usability (feeling sticky).

In addition, as a method for enhancing the photostability of folic acid, a method of blending catechins or polyphenols has been reported. However, it is satisfactory in that it produces a specific flavor and taste when used as a food and drink, and has problems in terms of safety such as sensitization of catechins and polyphenols when used as a skin external preparation. It was not a thing (patent documents 5, 6).
In other words, these methods for stabilizing folic acid, although the purpose of stabilizing folic acid is achieved, are seriously harmful to the stabilizer from the viewpoint of functionality (flavor, taste, feel, etc.) and safety. . Accordingly, there has been a demand for a stabilization method that achieves the objective of stabilizing folic acid and has a small effect on the sensory (flavor, taste, feel, etc.) and safety.

JP 2002-212077 A JP 2008-31094 A JP 2002-97141 A Japanese Patent Laid-Open No. 11-158061 JP 2006-296379 A JP 2006-315985 A Pediat. Gastroenterol. Nutr. 1995 vol. 20 4-16 Nutr. Cancer 1994 vol. 22: 101- J Biol Chem. 1949 vol. 180 (1): 389-398.

The present invention provides a method for suppressing deterioration of folic acid without impairing sensory (flavor, taste, touch, etc.) and safety. Moreover, the composition which improved stability of folic acid is provided.

As a result of intensive studies to solve the above problems, the present inventor has found that the stability to light of a composition in which folic acid is dissolved can be improved by adding a specific amino acid. Moreover, it discovered that stability was further improved by using specific water-soluble polymer together with these, and came to complete this invention.
That is, the present invention is as follows.
(1) the following components (A) and (B);
(A) Folic acid (B) A folic acid-containing composition comprising at least one selected from lysine, arginine, tryptophan, hydroxyproline, and salts thereof.
(2) The folic acid-containing composition according to (1), further comprising at least one component selected from component (C) phosphoric acid, citric acid, succinic acid, lactic acid and salts thereof.
(3) The folic acid-containing composition according to (1) or (2), wherein the blending mass ratio of (A) and (B) is 5: 1 to 1: 5.
(4) The folic acid-containing composition according to any one of (1) to (3), further comprising a component (D) carboxyvinyl polymer and / or an alkyl-modified carboxyvinyl polymer.
(5) The folic acid-containing composition according to any one of (1) to (4), wherein the composition is an external preparation for skin or a cosmetic.
(6) A method for stabilizing folic acid, comprising blending at least one selected from lysine, arginine, tryptophan, hydroxyproline, and salts thereof.
(7) The method for stabilizing folic acid according to (6), further comprising at least one component selected from component (C) phosphoric acid, citric acid, succinic acid, lactic acid and salts thereof.
(8) The method for stabilizing folic acid according to (6) or (7), wherein the blending mass ratio of (A) and (B) is from 5: 1 to 1: 5.

In the present invention, folic acid is stabilized by blending a specific amino acid as a stabilizer. The present invention prevents folic acid from being deteriorated by light and does not cause changes in appearance or odor over time. In addition, it feels good as an external preparation for skin and has high safety. Furthermore, folic acid is further stabilized by blending a specific water-soluble polymer.

Hereinafter, embodiments of the present invention will be described. In the present specification, “to” means a range including numerical values before and after.

The folic acid of the component (A) of the present invention includes folic acid (pteroyl monoglutamic acid), tetrahydrofolic acid, dihydrofolic acid, substituted tetrahydrofolic acid substituted at the 5-position and / or the 10-position, and polymerized liglutamyl folic acid (2 to 8). Having a glutamic acid residue). Specific examples include folic acid (protail monoglutamic acid), 7,8-dihydrofolic acid, 5,6,7,8-tetrahydrofolic acid, 5-methyltetrahydrofolic acid, 5,10-methylenetetrahydrofolic acid, 5,10-me Tenenyltetrahydrofolic acid, 5,10-formiminotetrahydrofolic acid, 5-formyltetrahydrofolic acid (leucovorin), 5-formyliminotetrahydrofolic acid, 10-formyltetrahydrofolic acid, polymerized polyglutamylfolic acid (from 2 to 8 glutamic acid residues ), Ester forms thereof, salts thereof, and mixtures thereof. Examples of the polymerized polyglutamyl folic acid include dihydrotayl, triglutamyl, tetraglutamyl, pentaglutamyl and hexaglutamyl derivatives of tetrahydrofolic acid such as 5-formimino- (6S) -tetrahydrofolic acid. Also, unless otherwise limited, the term “folic acid” encompasses both enantiomers (αS) and (αR), and for tetrahydrofolic acid, its diastereomers ((6S, αS), (6S, αR) , (6R, αS) and (6R, αR)).
As for protail monoglutamic acid, a synthetic product corresponding to “folic acid” listed in the Japanese Pharmacopoeia or food additive standards can be obtained from BASF Takeda Vitamin Co., Ltd., DSM Japan Co., Ltd. and the like. In the case of food origin, teas such as green tea, oolong tea, black tea, beans such as soybeans and broad beans, mustard greens, spinach, mizukake greens, nabara greens, green asparagus, spring chrysanthemum, sweet potatoes, broccoli, tinning What was extracted from fruits, such as vegetables, such as vegetables, strawberries, papayas, oranges, mandarin oranges according to a usual method, can be used. Extraction of folic acid from these plants is achieved by extracting with hot water or hot water in the case of tea leaves, and in the case of beans, vegetables and fruits, removing the insoluble fraction from the juice and collecting the extract. Is done.
As the component (A) of the present invention, synthetic proteyl monoglutamic acid is most preferable because of its high stability to light and high utilization in vivo.

The blending amount of (A) of the present invention is preferably 0.00001 to 1% by mass (hereinafter abbreviated as “%”), more preferably 0.0001 to 0.5%, and 0.01 to 0.2%. Is particularly preferred. Within this range, it is possible to stabilize folic acid while more effectively using folic acid.

The amino acid of the component (B) of the present invention is selected from lysine, arginine, tryptophan, hydroxyproline and salts thereof, and it is necessary to add one or more of these. The lysine, arginine, tryptophan, hydroxyproline and salts thereof of the component (B) of the present invention are used as the stabilizer of the component (A), and the production method and the like are not particularly limited.
Examples of amino acid salts include lysine hydrochloride, lysine glutamate, arginine hydrochloride, and arginine glutamate.
In the present invention, it is preferable to use L-lysine, L-lysine hydrochloride, L-arginine, or L-arginine hydrochloride as the component (B) from the viewpoint of little odor change, and L-lysine, L-lysine hydrochloride A salt is particularly preferred.

Although the compounding quantity of (B) of this invention can be suitably determined based on the compounding quantity of (A), 0.001 to 5% is preferable, 0.05 to 1% is more preferable, 0.1 -0.5% is particularly preferred. Within this range, folic acid can be sufficiently stabilized, and more favorable in terms of no odor change and usability (feel).

The blending mass ratio of (A) and (B) of the present invention is preferably 1:10 to 10: 1, more preferably 1: 5 to 5: 1 from the viewpoint of usability (feel) as a skin external preparation, From the viewpoint of odor, 1: 2 to 2: 1 is particularly preferable.

Component (C) used in the present invention is a buffer for adjusting the pH to 6 or more from the viewpoint of solubility of folic acid, and one kind selected from phosphoric acid, citric acid, succinic acid, lactic acid, and salts thereof. It is necessary to blend the above. Preferred examples of these salts include disodium monohydrogen phosphate, sodium dihydrogen phosphate, trisodium phosphate, sodium citrate, sodium succinate, sodium lactate, dipotassium monohydrogen phosphate, potassium dihydrogen phosphate. , Tripotassium phosphate, potassium citrate, potassium succinate, potassium lactate and the like. From the viewpoint of folic acid stabilization, the component (C) of the present invention is preferably a combination of citric acid / citrate, lactic acid / lactate or phosphate / phosphate, and disodium monohydrogen phosphate / phosphorus It is particularly preferable to use sodium dihydrogen acid in combination.

The blending amount of (C) of the present invention is appropriately selected depending on the type of buffering agent used, the type of amino acid used and the blending amount, and is usually 0.001 to 5%, preferably 0.005 to 3 mass. %, More preferably 0.01 to 2% by mass. In particular, the blending amount is preferably such that the pH of the entire composition is preferably 6.0 or more, more preferably 6.5 or more.

The carboxyvinyl polymer of component (D) of the present invention is a copolymer of acrylic acid and corresponds to the “carboxyvinyl polymer” listed in the quasi-drug raw material standard. The alkyl-modified carboxyvinyl polymer of component (D) of the present invention is a copolymer of acrylic acid and an alkyl chain added thereto, and “acrylic acid / alkyl methacrylate copolymer” listed in the quasi-drug raw material standard. Is equivalent to. Examples of these commercially available products include Carbopol 940, 941, 934, 980, 1342, Pemulen TR-1, TR-2 (all manufactured by Goodrich Chemical). By adding the component (D) carboxyvinyl polymer or alkyl-modified carboxyvinyl polymer of the present invention in addition to the components (A) to (C), the stability of folic acid is further improved. This is considered to be due to the interaction between the carboxyl group of the carboxyvinyl polymer or the alkyl-modified carboxyvinyl polymer and folic acid. From the viewpoint of stabilizing folic acid, the component (D) of the present invention is preferably an alkyl-modified carboxyvinyl polymer. The component (D) is more preferably neutralized with a neutralizing agent, and sodium hydroxide and potassium hydroxide are preferably used as the neutralizing agent. The component (B) lysine, arginine or these A salt can also be used as a neutralizing agent.

The blending amount of (D) of the present invention is appropriately selected depending on the blending amount of folic acid, the type and blending amount of amino acids used in combination, and is usually 0.001 to 1%, preferably 0.005 to 0.5. It is 0.01 mass%, More preferably, it is 0.01-0.2 mass%. Within this range, not only the stabilizing effect of folic acid is sufficient, but stickiness does not occur, and a more preferable one in terms of usability (feel) can be obtained.

“Stabilization” in the present invention refers to inhibiting folic acid from being decomposed and degraded, and inhibiting changes in content, appearance, and odor. If it is stabilized against light, it means that even if it is placed under the light of a fluorescent lamp (artificial meteor) at 30 ° C. and 8,000 lux, a stabilizing effect against folic acid can be found even slightly. No change in appearance (turbidity, precipitation, discoloration) or odor when placed under conditions for 3 days, particularly preferably appearance (turbidity, precipitation, discoloration) or It means no change in odor. In addition, if it is stabilized against heat, it means that even if it is stored at 40 ° C. for 1 month or more, a stabilizing effect against folic acid can be found, and at that time, the residual ratio of folic acid is 90% or more, preferably 95%. As mentioned above, it means keeping at 98% or more.

The folic acid-containing composition of the present invention, particularly a skin external preparation or cosmetic, can further enhance the folic acid stabilization effect by combining storage under light-shielding conditions. Storage under light-shielding conditions means storage of the external preparation for skin or cosmetics in a transparent or opaque container in a light-shielded box, etc., and storage of the external preparation for skin or cosmetics in a light-shielding container This means storage that does not directly expose the skin external preparation or the cosmetic itself. Here, the light shielding condition refers to a state in which about 50% or more, preferably about 70% or more, more preferably about 90% or more of visible light is cut. In particular, since light with a short wavelength has high energy, it is desirable that light having a wavelength of about 340 nm or less be cut by about 80% or more, more preferably about 90% or more.

The “stabilized folic acid-containing composition” of the present invention means a folic acid-containing composition that can exist in a stabilized state, and in form, folic acid for addition to a skin external preparation or the like. And an amino acid-containing composition as a raw material for blending, and a composition such as a skin external preparation obtained by adding these raw materials for blending to a stock solution such as a skin external preparation. The property of the composition is not particularly limited, and may be any property such as liquid, paste, gel, solid, and powder. From the viewpoint of use, the composition can be used for external use, internal use, oral intake, injection or infusion, pharmaceutical composition, quasi-drug composition, infusion; skin external preparation, cosmetic (a quasi-drug). A food additive, a beverage composition, or a food composition (nutrient functional food, food for specified health use, functional food, health food, supplement), and the like. The stabilized folic acid-containing composition of the present invention exhibits a sufficient effect even if the blending amount of the folic acid stabilizer is small, so that the beverage composition or food is one of the important qualities such as taste and feel. A composition, or an external preparation for skin or a cosmetic is preferred. Moreover, since it is not sticky when applied to the skin and has good usability (feel), it is particularly preferable to use it as a skin external preparation or cosmetic.

The beverage composition is not particularly limited as an example of the blending form. For example, tea beverages such as green tea, oolong tea and black tea; juices such as apple juice, grapefruit juice and orange juice; fruit juice blended beverages; vegetable juice blended beverages Coffee drinks; cocoa drinks; milk drinks such as milk; carbonated drinks such as cola and cider; sports drinks; soy milk; mineral water; near water drinks; diet support drinks; Moreover, alcoholic beverages, such as beer, a sparkling wine, wine, and sake, may be sufficient. The food composition is a confectionery, bread, yogurt, jelly, frozen confectionery, candy, gum or the like obtained by blending an appropriate amount of the above composition for blending into raw materials and processing it according to a conventional method. The beverage composition of the present invention is preferably a container-packed beverage composition such as juices; fruit juice-containing beverages; vegetable juice-containing beverages; milk beverages; tea beverages.

The above beverage composition or food composition is various sweeteners, acidulants, inorganic acid salts, inorganic acid salts, organic acids that can be used as food additives, as long as the effects of the present invention are not impaired as required. Nutrition enhancer, antioxidant, flavor, pigment, emulsifier, preservative, seasoning, lipids, proteins, peptides, polysaccharides, dietary fiber, fruit juice extract, vegetable extract, nectar extract, pH You may mix | blend a regulator etc. individually or in combination.

Examples of the external preparation for skin or cosmetics of the present invention are not particularly limited, for example, skin care cosmetics such as milky lotion, cream, lotion, cosmetic liquid, pack, cleaning agent, foundation, eye shadow, mascara, blusher, Makeup cosmetics such as lipsticks, hair nourishing agents, hair tonics, shampoos, rinses and other hair cosmetics, dispersions, ointments, liquids for external use, aerosols, patches, poultices, liniments, etc. Good.

In the external preparation for skin or cosmetics of the present invention, components that are usually used in preparations such as cosmetics, quasi-drugs, external pharmaceuticals, etc., as long as they do not impair the effects of the present invention, if necessary, such as water (For example, alkaline simple hot spring water, deep layer water, purified water, etc.), oil agent, surfactant, metal soap, gelling agent, powder, alcohol, water-soluble polymer, resin, UV protection agent, antibacterial agent , Fragrance, salt, refreshing agent, animal / microbe-derived extract, plant extract, blood circulation promoter, astringent, antioxidant, whitening agent, anti-inflammatory agent, active oxygen scavenger, cell activator, moisturizer, chelate Agents, keratolytic agents, enzymes, hormones, vitamins and the like can be added.

The oil agent may be a natural oil, a synthetic oil, or a solid, semi-solid, liquid, etc., as long as it is used in normal skin external preparations or cosmetics. In addition, any oil agent such as hydrocarbons, waxes, fatty acids, higher alcohols, ester oils, silicone oils, fluorine oils and the like can be used. For example, hydrocarbons such as squalane, squalene, ceresin, paraffin, paraffin wax, liquid paraffin, pristane, polyisobutylene, microcrystalline wax, petroleum jelly; waxes such as beeswax, carnauba wax, candelilla wax, whale wax, beef tallow, cattle Animal oils such as leg fat, beef bone fat, hard beef fat, hard oil, turtle oil, pork fat, horse fat, mink oil, liver oil, egg yolk oil; lanolin, liquid lanolin, reduced lanolin, lanolin alcohol, hard lanolin, lanolin acetate, Lanolin derivatives such as lanolin fatty acid isopropyl, POE lanolin alcohol ether, POE lanolin alcohol acetate, lanolin fatty acid polyethylene glycol, POE hydrogenated lanolin alcohol ether; lauric acid, myristic acid, palmitic acid, stearin Fatty acids such as behenic acid, undecylenic acid, oleic acid, arachidonic acid, docosahexaenoic acid (DHA), isostearic acid, 12-hydroxystearic acid; lauryl alcohol, myristyl alcohol, palmityl alcohol, stearyl alcohol, behenyl alcohol, hexadecyl alcohol Higher alcohols such as oleyl alcohol, isostearyl alcohol, hexyldodecanol, octyldodecanol, cetostearyl alcohol, 2-decyltetradecinol, phytosterol, sitosterol, lanosterol, POE cholesterol ether, monostearyl glycerol ether (batyl alcohol) Can be mentioned.

Surfactants are used for emulsification and solubilization of oils and the like, and anionic, cationic, amphoteric and nonionic active agents can be used. For example, anionic surfactants include fatty acids such as stearic acid and lauric acid and their inorganic and organic salts, alkylbenzene sulfates, alkyl sulfonates, α-olefin sulfonates, dialkyl sulfosuccinates, α-sulfones. Fatty acid salt, acylmethyl taurine salt, N-methyl-N-alkyl taurine salt, polyoxyethylene alkyl ether sulfate, polyoxyethylene alkyl phenyl ether sulfate, alkyl phosphate, polyoxyethylene alkyl ether phosphate, polyoxy Examples thereof include ethylene alkylphenyl ether phosphate, N-acyl amino acid salt, N-acyl-N-alkyl amino acid salt, o-alkyl substituted malate, alkyl sulfosuccinate and the like. Examples of the cationic surfactant include alkylamine salts, polyamines and alkanolamine fatty acid derivatives, alkyl quaternary ammonium salts, and cyclic quaternary ammonium salts. Examples of amphoteric surfactants include amino acid type and betaine type carboxylic acid types, sulfate ester types, sulfonic acid types, and phosphate ester types, and those that are safe for the human body can be used. For example, N, N-dimethyl-N-alkyl-N-carboxylmethylammonium betaine, N, N-dialkylaminoalkylene carboxylic acid, N, N, N-trialkyl-N-sulfoalkylene ammonium betaine, N, N- Examples thereof include dialkyl-N, N-bis (polyoxyethylene sulfate) ammonium betaine and 2-alkyl-1-hydroxyethyl-1-carboxymethylimidazolinium betaine. Nonionic surfactants include glycerin fatty acid ester and its alkylene glycol adduct, polyglycerin fatty acid ester and its alkylene glycol adduct, propylene glycol fatty acid ester and its alkylene glycol adduct, sorbitan fatty acid ester and its alkylene glycol adduct, Fatty acid ester of sorbitol and its alkylene glycol adduct, polyalkylene glycol fatty acid ester, sucrose fatty acid ester, glycerin alkyl ether, polyoxyalkylene alkyl ether, polyoxyethylene alkylphenyl ether, polyoxyethylene hydrogenated castor oil, alkylene glycol of lanolin Examples include adducts.

The metal soap is a metal salt other than an alkali salt such as a fatty acid, and examples thereof include aluminum stearate, magnesium stearate, and zinc laurate.

Gelling agents are used to improve the stability and usability of the system, and the feeling of use. Amino acid derivatives such as N-lauroyl-L-glutamic acid, dextrin fatty acid esters such as dextrin palmitate, sucrose fatty acid esters, Examples include organically modified clay minerals.

The powder is mainly used for various purposes such as coloring in makeup cosmetics, hiding skin, or improving the feeling of use, and if it is used in normal cosmetics, its shape (spherical, needle-like, plate , Etc.), particle diameter (smoke, fine particles, pigment grade, etc.) and particle structure (porous, non-porous, etc.) can be used. For example, as the inorganic powder, barium sulfate, calcium carbonate, talc, mica, synthetic mica, mica, kaolin, sericite, silicic acid, anhydrous silicic acid, magnesium aluminum silicate, ceramic powder, boron nitride and the like can be mentioned, Examples of organic powders include polyester powder, polyethylene powder, polystyrene powder, nylon powder, lauroyl lysine, and colored pigments include inorganic pigments such as iron oxide, carbon black, chromium oxide, bitumen, and ultramarine blue, and tar-based pigments. Examples include pearl pigments and natural pigment lakes. Pearl pigments include titanium oxide-coated mica, titanium oxide-coated mica, bismuth oxychloride, titanium oxide-coated bismuth oxychloride, titanium oxide-coated talc, fish scales. Foil, titanium oxide-coated colored mica, etc. Other tar pigments, natural pigments such as carminic acid. These powders may be combined, or surface treatment may be performed with an oil agent, silicone, or fluorine compound.

Examples of alcohols include lower alcohols such as ethanol and isopropanol, glycerin, diglycerin, ethylene glycol, diethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, 1,3-butylene glycol, and polyethylene glycol.

Examples of water-soluble polymers include gum-based polymers such as gum arabic, tragacanth, galactan, carob gum, guar gum, caraya gum, carrageenan, pectin, agar, algae colloid, trant gum, locust bean gum, galactomannan, xanthan gum, dextran, succino. Microbial polymers such as glucan and pullulan; animal polymers such as casein, albumin and gelatin; starch polymers such as starch, carboxymethyl starch and methylhydroxypropyl starch; methylcellulose, ethylcellulose, methylhydroxypropylcellulose and carboxymethylcellulose , Hydroxymethyl cellulose, hydroxypropyl cellulose, cellulose sodium sulfate, sodium carboxymethyl cellulose, crystalline cellulose Cellulose-based cellulose polymers; Alginic acid-based polymers such as sodium alginate and propylene glycol alginate; Polyvinyl methyl ether, polyoxyethylene-based polymers; Polyoxyethylene polyoxypropylene copolymer-based polymers; Sodium polyacrylate, Examples include acrylic polymers such as polyacrylamide; inorganic water-soluble polymers such as polyethyleneimine, cationic polymers, bentonite, laponite, hectorite, resins, and inclusion compounds. Also included are film forming agents such as polyvinyl alcohol and polyvinyl pyrrolidone.

Examples of the resin include polyvinyl pyrrolidone, vinyl pyrrolidone / vinyl acetate copolymer, and other humectants such as protein, mucopolysaccharide, collagen, elastin, and keratin.

As salts, L-ascorbic acid phosphate sodium salt, L-ascorbic acid phosphate magnesium salt, L-ascorbic acid phosphate calcium salt, L-ascorbic acid phosphate potassium salt, L-ascorbic acid sulfate Sodium salt, L-ascorbic acid sulfate magnesium salt, L-ascorbic acid sulfate potassium salt, L-ascorbic acid sulfate calcium salt, sodium pyrrolidonecarboxylate, sodium edetate, sodium chloride, potassium chloride, calcium chloride, magnesium chloride , Sodium citrate, sodium succinate, sodium carbonate, sodium lactate, calcium lactate, sodium sulfate, potassium sulfate, magnesium sulfate, sodium phosphate, sodium malate, g Chirurichin dipotassium, zinc para-phenolsulfonate and the like, can be selected at least one of these as appropriate. Among these, salts of L-ascorbic acid inorganic acid ester, specifically, L-ascorbic acid phosphate sodium salt, L-ascorbic acid phosphate magnesium salt, L-ascorbic acid phosphate calcium salt, L- Ascorbic acid phosphate potassium salt, L-ascorbic acid sulfate sodium salt, L-ascorbic acid sulfate magnesium salt, L-ascorbic acid sulfate potassium salt and L-ascorbic acid sulfate calcium salt are preferable.

Examples of the refreshing agent include L-menthol and camphor, and examples of the anti-inflammatory agent include allantoin, glycyrrhetinic acid, tranexamic acid, and azulene.

Examples of extracts derived from animals or microorganisms include serum deproteinization, egg components such as spleen and birds, eggshell membrane extract, chicken crown extract, shell extract, shellfish extract, royal jelly, silk protein and their degradation products or their Microorganisms such as derivatives, hemoglobin or its degradation products, lactoferrin or its degradation products, mollusks such as squid, fish meat, birds, shellfish, insects, fish, molluscs and other animal-derived extracts, ganoderma extract The extract of origin, etc. are mentioned. By blending an animal or microorganism-derived extract, a moisturizing effect, cell activation effect, whitening effect, anti-inflammatory effect, active oxygen removal effect, blood circulation promoting effect, and the like can be imparted.

The plant extract is not particularly limited in terms of plant extraction site, extraction method, and the like, and is extracted from, for example, whole plant plants, roots, stems, stems, bark, shoots, leaves, flowers, fruits, seeds, or the like. These can be appropriately treated, such as dried, shredded, pressed, or fermented, and extracted using various appropriate solvents at a low temperature or from room temperature to warming. As the extraction solvent, for example, water; a lower monohydric alcohol such as methyl alcohol or ethyl alcohol; or a liquid polyhydric alcohol such as glycerin, propylene glycol, or 1,3-butylene glycol can be used. . Moreover, it can also extract using lipophilic solvents, such as hexane, acetone, ethyl acetate, and ether, and what was extracted with oily components, such as squalane, may be used. The obtained extract may be filtered, adsorbed, decolored and purified to form a solution, paste, gel or powder. If necessary, purification treatment such as deodorization and decolorization may be further performed within a range not affecting the effect. Plants include asparagus, Neubara (Ages), raspberry, Clara (Kujin), caquette, gokahi, coffee, rice, saishin, hawthorn, white lilies, peonies, tea, beech, grapes, hops, mokka, yukinoshita, altea, ashitaba , Arnica, Ginseng, Nettle, Yellowfin, Hypericum, Honeysuckle (Ginkgo), Salvia (Sage), Siphon, Birch, Mulberry, Forsythia, Ginkgo, Barley, Assembly, Jujube, Rosemary , Grapefruit, gentian, savonso, shobu, jiou, senkyu, mallow (Husbenitachaoi), hamamelis, dandelion, prune, bodaiju, maronier, quince and the like. By blending a plant extract, a moisturizing effect, a cell activation effect, a whitening effect, an anti-inflammatory effect, an active oxygen removal effect, a blood circulation promoting effect and the like can be imparted. (In parentheses, plant aliases and herbal medicine names are listed.)

The active oxygen scavenger is used for the purpose of suppressing the production of lipid peroxide by ultraviolet rays, and superoxide dismutase, mannitol, quercetin, catechin and its derivatives, thiamines (thiamine hydrochloride, thiamine sulfate), riboflavins ( Riboflavin, riboflavin acetate, etc.), pyridoxines (pyridoxine hydrochloride, pyridoxine dioctanoate, etc.), nicotinic acids (nicotinic acid amide, nicotinic acid benzyl, etc.) vitamin B; dibutylhydroxytoluene, butylhydroxyanisole, etc. . By blending these active oxygen scavengers, dullness can be suppressed and a higher anti-aging effect can be exhibited.

Examples of cell activators include carotenoids (such as carotene, lycopene, astaxanthin), vitamin A and derivatives thereof (retinol such as retinol palmitate and retinol acetate; and retinals such as dehydroretinal and derivatives thereof), vitamin C and its derivatives. Derivatives (L-ascorbic acid alkyl esters such as L-ascorbyl dipalmitate and L-ascorbyl tetraisopalmitate, L-ascorbic acid phosphate, L-ascorbic acid sulfate, etc.), vitamin B and its derivatives (thiamine hydrochloride) Salt, thiamine sulfate, riboflavin, riboflavin acetate, pyridoxine hydrochloride, pyridoxine dioctanoate, flavin adenine dinucleotide, cyanocobalamin, folic acid, nicotinamide and benzyl nicotinate (Tinic acids, choline, etc.), ribonucleic acid and salts thereof, deoxyribonucleic acid and salts thereof, α- and γ-linolenic acid, xanthine and derivatives thereof (caffeine, etc.), amino acids and derivatives thereof (serine, glutamic acid, theanine, hydroxy) Proline, pyrrolidone carboxylic acid, etc.), docosahexaenoic acid and its derivatives, eicosapentaenoic acid and its derivatives, citric acid, lactic acid, malic acid, succinic acid, almond extract, apricot extract, ginkgo biloba extract, yellowfin ) Extract, Barley (Bakuga) extract, Kiwi extract, Cucumber extract, Shiitake extract, Japanese horse chestnut extract, Assembly extract, Soybean extract, Jujube extract, Rhizoma extract, Pepper extract, Tokachinka extract, tomato extract, garlic extract, garlic Extract, Bukuryu extract, Grape seed oil, Beech extract, Beech sprout extract, Peach extract, Eucalyptus extract, Lily extract, Lettuce extract, Lemon extract, Rosemary extract, Malt Root extract, animal-derived extract (mollusk and other mollusc extracts, shell extract, shellfish extract, fish extract, chicken crown extract, royal jelly, silk protein and its degradation products, placenta extract, serum deproteinization extraction Product, lactoferrin or its degradation product), yeast extract, microbial fermentation metabolite (derived from lactic acid bacteria, bifidobacteria, etc.), ganoderma extract and the like. These cell activators can be used alone or in combination of two or more.

Examples of moisturizers include proteins such as collagen, elastin and keratin or derivatives thereof, hydrolysates and salts thereof, mucopolysaccharides and derivatives thereof such as hyaluronic acid and chondroitin sulfate, amino acids such as serine, glycine, theanine and aspartic acid. And derivatives thereof, sorbitol, erythritol, trehalose, inositol, glucose, xylitol, sucrose and derivatives thereof, dextrin and derivatives thereof, saccharides such as honey, D-pantenol and derivatives thereof, glycolipid, ceramide and the like. By blending these moisturizers, it is possible to achieve a higher anti-aging effect and realize a transparent skin.

As the chelating agent, for example, edetic acid, ethane hydroxydiphosphate, pyrophosphate, hexametaphosphate, citric acid, tartaric acid, gluconic acid, and salts thereof can be used.

Antioxidants include mannitol, beta carotene, astaxanthin, rutin and derivatives thereof, quercetin, phospholipid, retinol and derivatives thereof (such as retinol palmitate, retinol acetate), retinal and derivatives thereof, carotenoids such as dehydroretinal and carotene Vitamins A, pyridoxines (pyridoxine hydrochloride, pyridoxine dioctanoate, etc.), nicotinic acids (nicotinic acid amide, benzyl nicotinate, etc.), dibutylhydroxytoluene (BHT), butylhydroxyanisole (BHA), vitamin E and its Derivatives and salts thereof, carrot extract, Melissa extract, Yashajitsu extract and the like. Among these antioxidants, vitamin E and derivatives thereof and salts thereof are particularly preferable.

Examples of whitening agents include vitamin C and derivatives thereof and salts thereof, arbutin, hydroquinone and derivatives thereof, kojic acid, ellagic acid, tranexamic acid and derivatives thereof, placenta extract, licorice extract, yokuinin extract, asparagus extract , Agetsu extract, Kiwi extract, Raspberry extract, Kujin extract, Keiket extract, Gokahi extract, Coffee extract, Rice bran extract, Wheat germ extract, Saisin extract, Hawthorn extract, Shirayuri extract, Peonies extract, soybean extract, tea extract such as green tea, black tea, oolong tea, molasses extract, beechlen extract, beech bud extract, grape extract, hop extract, micaika extract, mokka extract and rakan fruit Examples include extracts, ougon extracts, seaweed extracts, and the like. Among these whitening agents, vitamin C and its derivatives and salts thereof are particularly preferable.

The blood circulation promoter is used for the purpose of promoting melanin excretion by promoting the blood flow of the skin, such as chili pepper tincture and γ-oryzanol. Enzymes include lipase and papain.

Examples of skin astringents include tannic acid, examples of antiseborrheic agents include thianthol, and examples of enzymes include lipase and papain.

Anti-inflammatory agents include glycyrrhizic acid and its derivatives, glycyrrhetinic acid and its derivatives, and the like.

Examples of UV inhibitors include paramethoxycinnamate-2-ethylhexyl, oxybenzone, 4-tert-butyl-4′-methoxydibenzoylmethane, 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxybenzophenone- 5-sulfonic acid, 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid sodium, 2-hydroxy-4-methoxybenzophenone-5-sodium sulfate, 2-phenylbenzimidazole sodium sulfate, titanium oxide, zinc oxide, etc. It is done.

Antibacterial agents are used for the purpose of preventing and improving acne and the like, and include benzoic acid, sodium benzoate, paraoxybenzoic acid ester, parachlormetacresol, benzalkonium chloride, phenoxyethanol, isopropylmethylphenol and the like.

Examples of the enzyme include lipase and papain.

Examples of hormones include melatonin and derivatives thereof, adrenocortical hormones and derivatives thereof, plant hormones (auxin, cytokinin, gibberellin, kinetin, abscisic acid, ethylene, etc.) and derivatives thereof.

Examples of vitamins include vitamin A, vitamin B, vitamin C, vitamin D, vitamin F, vitamin K, vitamin P, vitamin U, carnitine and derivatives thereof, vitamin E and derivatives thereof, and the like.

EXAMPLES Next, although an Example is given and this invention is demonstrated further in detail, this invention is not limited to these.

Test Example 1 Photostability test of folic acid (Examples 1-4, Comparative Examples 1-16)
Aqueous solutions having the compositions shown in Tables 1 and 2 were prepared by the following method. The appearance stability and odor stability of folic acid were evaluated and determined by the following methods and criteria, and the results are shown in Tables 1 and 2 together.

(Adjustment method)
A: Component 1 and any one of components 2 to 20 are mixed and dissolved in component 24 (A is not dissolved but only dispersed at this point).
B: Components 21 and 22 are mixed and dissolved in A.
C: Component 23 was added to B, the pH at 25 ° C. was adjusted to 6.0 or more, and component 1 was dissolved to obtain an aqueous solution of folic acid.

(Evaluation method)
50 g of each prepared aqueous solution was filled in a No. 8 glass standard bottle, and allowed to stand in a chamber at 30 ° C. irradiated with light of 8000 lux by a fluorescent lamp. After 1 day, 3 days, and 14 days after the start of the test, the glass standard bottle was taken out from the chamber, shielded with aluminum foil and stored in the chamber, and the appearance change over time (transparency of the aqueous solution and precipitation of precipitation) The presence or absence of was observed. Moreover, the sample evaluated as x one day after the start of the test was evaluated, and the subsequent evaluation was not performed. Regarding the odor change, the glass standard bottle was taken out from the chamber 14 days after the start of the test, the lid was opened, and 10 expert panel members performed sensory evaluation of the odor based on each aqueous solution immediately after preparation.

(Evaluation method: Appearance stability (turbidity, discoloration, no precipitation))
Specialist panel members evaluated the following criteria.
Transparency does not change, and no discoloration or precipitation is confirmed: ◎
Slightly increases in turbidity, but no discoloration or precipitation is confirmed: ○
Slight discoloration and precipitation are confirmed: △
Discoloration and precipitation are clearly confirmed: ×

(Evaluation method: odor stability (no odor change))
Each expert panel member evaluated each sample according to the following criteria, and further determined from the average score of 10 people as follows.
(Evaluation criteria: Odor)
No change: 4 points Almost no change: 3 points Some change: 2 points Clearly change: 1 point (Criteria: Odor)
◎: 3.5 points or more ○: 3.0 points or more and less than 3.5 points Δ: 2.0 points or more and less than 3.0 points ×: less than 1.5 points

As can be seen from Tables 1 and 2, the aqueous solutions of Examples 1 to 4 had almost no change in appearance and odor until after 14 days, and were excellent in the photostabilization effect of folic acid. On the other hand, in Comparative Examples 2 to 4, although folic acid did not change much until 3 days later, stability could not be maintained until 14 days later, and severe odor or precipitation / discoloration was confirmed. For Comparative Examples 1 and 5 to 16, the photostability of folic acid was not maintained even for one day. Pyrosulfite (Comparative Example 15), known as an antioxidant, and sodium hydroxymethoxybenzophenone sulfonate (Comparative Example 16), known as an ultraviolet absorber, did not have a photostabilizing effect of folic acid.

Test Example 2 Photostability test and usability test of folic acid (Examples 5 to 11)
In order to examine the blending ratio of folic acid and amino acid (typically lysine), an aqueous solution having the composition shown in Table 3 was prepared by the following adjustment method. The appearance stability, odor stability, and usability of folic acid were evaluated and determined by the following methods and criteria, and the results are shown in Table 3.

(Adjustment method)
A: Components 1 and 2 are mixed and dissolved in component 6 (component 1 is not dissolved but only dispersed at this point).
B: Components 3 and 4 are mixed and dissolved in A.
C: Component 5 was added to B, the pH at 25 ° C. was adjusted to 6 or more, and component 1 was dissolved to obtain an aqueous solution.

(Evaluation method: appearance stability, odor stability)
In the same manner as in Test Example 1 described above, appearance stability (turbidity, discoloration, no precipitation) and odor stability (no odor change) were evaluated and judged.

(Evaluation method: Usability (no stickiness))
Ten professional panel members applied each sample immediately after preparation to the inner side of the forearm, evaluated the stickiness during and after application according to the following criteria, and further determined from the average score of 10 people as follows.
(Evaluation criteria)
Feels almost non-sticky: 4 points, feels slightly sticky: 3 points clearly feels sticky: 2 points Feels unpleasant stickiness: 1 point (criteria)
◎: 3.5 points or more ○: 3.0 points or more and less than 3.5 points Δ: 2.0 points or more and less than 3.0 points ×: less than 1.5 points

As shown in Table 2, the photostability of folic acid was maintained in the range of Examples 5 to 11, and stickiness was not a problem in use. Further, it was found that when the blending amount of amino acid with respect to folic acid is 5 times or more, the stability of folic acid is further improved, but stickiness tends to be felt. On the other hand, when the ratio of amino acids was lowered, stickiness was reduced, but the photostability of folic acid tended to decrease.

Test Example 3 Photostability test and usability test of folic acid (Examples 12 to 14, Comparative Example 17)
In order to study a method for further improving the photostability of folic acid, an aqueous solution having the composition shown in Table 4 was prepared by the following adjustment method. The appearance stability, odor stability, and usability of folic acid were evaluated and determined by the following methods and criteria. The results are also shown in Table 4.

(Adjustment method)
A: Components 1 and 2 are mixed and dissolved in component 8 (A is not dissolved but only dispersed at this point).
B: Components 5 and 6 are mixed and dissolved in A.
C: Component 7 is added to B, the pH is adjusted to 6 or more, and component 1 is dissolved.
D: Any one of components 3 and 4 is added to C and mixed.

(Evaluation method)
In the same manner as in Test Example 2 described above, appearance stability (turbidity, discoloration, no precipitation), odor stability (no discoloration), and usability (no stickiness) were evaluated and judged. Note that the evaluation after 1 day and 3 days after the start of the test was omitted.

Table 3 shows the effect of adding a water-soluble polymer. As shown in Example 12, the light stability of folic acid was further improved by using an alkyl-modified carboxyvinyl polymer that is a water-soluble polymer having a carboxyl group. As shown in Comparative Example 17, folic acid was not stable to light when lysine was not added and only the alkyl-modified carboxyvinyl polymer and folic acid were used in combination.

Example 15: Lotion (oil-in-water emulsion composition)
(Ingredient) (mass%)
1. Hydrogenated soybean phospholipid * 1 1.0
2.1,3-butylene glycol 3.0
3. 1,2-pentanediol 1.0
4). Glycerin 5.0
5.2-cetyl ethyl hexanoate 1.0
6). Lauroyl glutamic acid
Di (phytosteryl / octyldodecyl) 0.5
7). Purified water 20.0
8). Folic acid 0.1
9. Arginine 0.2
10. Sodium monohydrogen phosphate 0.05
11. Sodium dihydrogen phosphate 0.05
12 Sodium hydroxide 0.0144
13. Alcohol 5.0
14 Purified water remaining * 1: Basis LS-60HR (Nisshin Oillio Group)

(Manufacturing method)
A: Components 1 to 4 are uniformly mixed at 70 ° C.
B: Components 5 to 6 are uniformly dissolved at 70 ° C.
C: Component 7 is uniformly dissolved at 70 ° C.
D: Add B to A and mix uniformly.
E: C is added to D and emulsified.
F: 8 to 14 was added to E and cooled to obtain a lotion.

The lotion of Example 15 was very excellent in the appearance stability of folic acid, which is an oil-soluble drug that deteriorates due to light, to light, no odor change, no stickiness, and the stability of the preparation.

Example 16: lotion (solubilized transparent type)
(Ingredient) (mass%)
1.1,2-Pentanediol 1.0
2. Purified water 30.0
3. POE (20) POP (6)
Decyl tetradecyl ether 0.3
4). Methyl paraoxybenzoate 0.05
5. Perfume appropriate amount 6. l-Menthol 0.1
7). Ethanol 10.0
8). Folic acid 0.01
9. Hydroxyproline 0.05
10. Citric acid 0.02
11. Sodium dihydrogen phosphate 0.05
12 Sodium hydroxide 0.0134
13. Purified water remaining

(Manufacturing method)
A: Components 3 to 7 are mixed and dissolved.
B: Components 1 and 2 are added to A and mixed and dissolved uniformly.
C: Components 8 to 13 were added to B, and mixed and dissolved uniformly to obtain a skin lotion.

The lotion of Example 16 was very excellent in the stability of the folic acid, which deteriorates due to light, to light, no odor change, no stickiness, and the stability of the preparation.

Example 17: Latex (component) (mass%)
1. Stearyl alcohol 2.0
2. Vaseline 3.0
3. Glyceryl tri-2-ethylhexanoate 5.0
4). Titanium oxide 2.0
5. Mica titanium 2.0
6). Sodium stearate 1.0
7). Carboxyvinyl polymer 0.1
8.1,3-Butylene glycol 10.0
9. Folic acid 0.2
10. Lysine 0.05
11. Lactic acid 0.05
12 Sodium lactate 0.05
13. Sodium hydroxide 0.0134
14 Preservative appropriate amount15. Perfume appropriate amount 16. Purified water remaining

(Manufacturing method)
A. Ingredients 1-5 are heated to 75 ° C. and mixed uniformly.
B. Ingredients 6-8, 16 are heated to 75 ° C. and mixed uniformly.
C. Add A to B and emulsify.
D. C was cooled and ingredients 9-15 were added to obtain an emulsion.

The emulsion of Example 17 was very excellent in light stability of folic acid that deteriorates due to light, no odor change, no stickiness, and stability of the preparation.

Example 18: Eye lotion (component) (mass%)
1. Polyoxyethylene (20) sorbitan monooleate 1.0
2. Sorbitan monooleate 1.0
3. Cetostearyl alcohol 1.0
4). Liquid paraffin 5.0
5. Triglyceryl 2-ethylhexanoate 3.0
6. Cholesteryl 12-hydroxystearate 5.0
7). Natural vitamin E 0.5
8). Isotridecyl isononanoate 5.0
9. Purified water remaining amount 10. Edetate disodium 0.1
11. Methyl paraoxybenzoate 0.3
12 Phenoxyethanol 0.5
13. Glycerin 5.0
14 Dipropylene glycol 10.0
15. Hydroxyproline 0.05
16. Polyvinyl alcohol 0.1
17. Gellan gum 0.1
18. Ethanol 5.0
19. Perfume proper amount20. Folic acid 0.05
21. Tryptophan 0.2
22. Citric acid 0.02
23. Sodium dihydrogen phosphate 0.05
24. Sodium hydroxide 0.0134
25. Purified water 3

(Manufacturing method)
A: Components 1 to 8 are dissolved by heating at 70 ° C.
B: A part of component 9, 10-16, is heated and dissolved at 70 ° C., then added to A and emulsified.
C: Component 17 is swollen with the remainder of component 9 heated to 70 ° C.
D: After cooling B to room temperature, a mixture of C and components 19 to 25 was added to obtain an eye emulsion.

The eye lotion of Example 18 was very excellent in the stability of the folic acid, which deteriorates due to light, to light, no odor change, no stickiness, and the stability of the preparation.

Example 19: Cosmetic liquid (oil-in-water emulsion composition)
(Ingredient) (mass%)
1. Hydrogenated soybean phospholipid * 2 1.0
2. Hydrogenated soybean lysophospholipid * 3 0.5
3.1,3-Butylene glycol 3.0
4). Glycerin 5.0
5. Oleyl oleate 2.0
6). Cetostearyl alcohol 0.3
7). Glyceryl monostearate 0.3
8). Purified water 20.0
9. Folic acid 0.1
10. Hydroxyproline 0.2
11. Sodium monohydrogen phosphate 0.05
12 Sodium dihydrogen phosphate 0.05
13. Sodium hydroxide 0.0144
14 Ethanol 5.0
15. Purified water remaining amount 16. Xanthan gum 0.02
17. Polymethacryloyloxyethylene
Phosphorylcholine * 4 0.1
18. Purified water 10.0
* 2: NIKKOL Resinol S-10E (Nikko Chemicals)
* 3: Egg yolk lysolecithin LPC-1 (manufactured by Kewpie)
* 4: LIPIDURE
HM-600 (manufactured by NOF Corporation)

(Manufacturing method)
A: Components 1 to 4 are uniformly mixed at 70 ° C.
B: Components 5 to 7 are uniformly dissolved at 70 ° C.
C: Component 8 is uniformly dissolved at 70 ° C.
D: Add B to A and mix uniformly.
E: C is added to D and mixed uniformly.
F: Add 9 to 14 to E and mix uniformly.
G: F was cooled, 15 to 18 were added, and mixed uniformly to obtain a cosmetic liquid.

The cosmetic liquid of Example 19 was very excellent in the stability of the folic acid that deteriorates due to light to light, no odor change, no stickiness, and the stability of the preparation.

Example 20: Water-in-oil cream (component) (mass%)
1. Dipolyhydroxystearic acid PEG30 0.5
2. Glycerin 10.0
3.1,3-Butylene glycol 5.0
4). Decamethylcyclopentasiloxane 15.0
5. Glyceryl tri-2-ethylhexanoate 5.0
6). Polyethylene terephthalate powder 3.0
7). Purified water remaining amount 8. Folic acid 0.1
9. Lysine 0.2
10. Sodium monohydrogen phosphate 0.05
11. Sodium dihydrogen phosphate 0.05
12 Sodium hydroxide 0.0144
13. Edetate disodium 0.1
14 Preservative appropriate amount15. Dimethyl distearyl ammonium hectorite 0.5
16. Ethanol 2.0
17. Perfume

(Manufacturing method)
A: Components 1 to 3 are heated and dissolved at 70 ° C.
B: Components 4 to 6 are heated and dissolved at 70 ° C., and then added to A and mixed.
C: Components 7 to 14 are heated and dissolved at 70 ° C., then added to B and emulsified.
D: After cooling C to room temperature, ingredients 15 to 17 were added to obtain a water-in-oil cream.
The water-in-oil cream of Example 20 was very excellent in the stability of folic acid that deteriorates due to light to light, no odor change, no stickiness, and the stability of the preparation.

Example 21: Liquid foundation (formulation) (mass%)
1. Vaseline 7.0
2. Liquid paraffin 5.0
3. Stearic acid 2.0
4). Cetanol 1.0
5. Sesame oil * 6 0.5
6). Soy phospholipid 0.5
7). Paramethoxycinnamic acid-2-ethylhexyl 3.0
8). Glycerin 5.0
9. Triethanolamine 1.0
10. Carboxymethylcellulose 0.7
11. Folic acid 0.1
12 Lysine 0.2
13. Sodium monohydrogen phosphate 0.05
14 Sodium dihydrogen phosphate 0.05
15. Purified water remaining amount 16. Titanium oxide 8.0
17. Fine particle titanium oxide 2.0
18. Zinc oxide 5.0
19. Mica 5.0
20. Talc 6.0
21. Coloring pigment 6.0
22. Buffalo extract * 7 0.5
23. Perfume appropriate amount * 6: Nisshin Oil Co., Ltd. * 7: Maruzen Pharmaceutical Co., Ltd.

(Manufacturing method)
A. Components 1 to 7 are mixed and dissolved.
B. Ingredients 16-21 are added to A, mixed uniformly and kept at 70 ° C.
C. Ingredients 8-15 are dissolved uniformly and kept at 70 ° C.
D. C is added to B and emulsified uniformly.
E. After cooling D, components 22 to 23 were added to obtain a liquid foundation.

The liquid foundation of Example 21 was very excellent in the stability of folic acid that deteriorates due to light to light, no odor change, no stickiness, and the stability of the preparation.

Example 22: Oil-in-water ointment (formulation) (mass%)
1. Stearic acid 18.0
2. Cetanol 4.0
3. Dl-α-tocopherol acetate 0.2
4). Triethanolamine 2.5
5. Glycerin 5.0
6). Dipotassium glycyrrhizinate 0.5
7). Folic acid 0.2
8). Lysine 0.3
9. Methyl paraoxybenzoate 0.1
10. Purified water remaining

(Manufacturing method)
A. Ingredients 1-3 are heated and mixed and maintained at 75 ° C.
B. Ingredients 4-10 are mixed and kept at 75 ° C.
C. B was gradually added to A to obtain an ointment.

The ointment of Example 22 was very excellent in the stability of the folic acid that deteriorates due to light to light, no odor change, no stickiness, and the stability of the preparation.

Example 23: Tablet (prescription) (mass%)
1. Lactose 24.0
2. Crystalline cellulose 20.0
3. Corn starch 15.0
4). Folic acid 0.2
5. Lysine 0.1
6). Arginine 0.05
7). Hydroxyproline 0.05
8). Tryptophan 0.05
9. Citric acid 0.1
10. Dextrin remaining amount 11. Glycerin fatty acid ester 5.0
12 Silicon dioxide 1.0

(Manufacturing method)
A. Components 1 to 12 were mixed uniformly, and tablets were obtained according to a conventional method.

The tablet of Example 23 was very excellent in the stability to light of folic acid that deteriorates due to light, no odor change, and the stability of the preparation.

Example 24: Soft drink (prescription) (mass%)
1. Fructose dextrose liquid sugar 30.0
2. Emulsifier 0.5
3. Folic acid 0.001
4). Lysine 0.002
5. Sodium citrate 0.01
6). Perfume appropriate amount 7. Purified water remaining amount (production method)

A. Components 1 to 7 were mixed uniformly, and a soft drink was obtained according to a conventional method.

The soft drink of Example 24 was very excellent in the stability of folic acid that deteriorates due to light to light, no odor change, and the stability of the preparation.

  ADVANTAGE OF THE INVENTION According to this invention, the method for suppressing deterioration of a folic acid can be provided, without impairing sensory (flavor, taste, touch, etc.) and safety. Moreover, the composition which improved stability of folic acid can be provided. The composition of the present invention can be suitably used as a skin external preparation or cosmetic.

Claims (7)

The following components (A) and (B);
(A) Folic acid (B) A folic acid-containing composition comprising one or more selected from lysine, arginine, tryptophan, hydroxyproline and salts thereof,
The amount of the component (A) is 0.01 to 0.2%,
The blending amount of the component (B) is 0.05 to 1%,
A folic acid-containing composition, wherein the composition is an external preparation for skin or a cosmetic. Furthermore, 1 or more types chosen from component (C) phosphoric acid, a citric acid, a succinic acid, lactic acid, and these salts are mix | blended, The folic acid containing composition of Claim 1 characterized by the above-mentioned. The folic acid-containing composition according to claim 1 or 2, wherein the blending mass ratio of (A) and (B) is 5: 1 to 1: 5. The folic acid-containing composition according to any one of claims 1 to 3, further comprising a component (D) carboxyvinyl polymer and / or an alkyl-modified carboxyvinyl polymer. The following components (A) and (B);
(A) Folic acid
(B) In a skin external preparation or cosmetic characterized by blending at least one selected from lysine, arginine, tryptophan, hydroxyproline and salts thereof,
The amount of the component (A) is 0.01 to 0.2%,
The method for stabilizing folic acid in a skin external preparation or cosmetic, wherein the amount of component (B) is 0.05 to 1% . Furthermore, 1 or more types chosen from component (C) phosphoric acid, a citric acid, succinic acid, lactic acid, and these salts are mix | blended, The folic acid stabilization method of Claim 5 characterized by the above-mentioned. The method for stabilizing folic acid according to claim 5 or 6, wherein the blending mass ratio of (A) and (B) is 5: 1 to 1: 5.