JP5023311B2 - Composition for improving and / or preventing skin disorders - Google Patents

Description

The present invention comprises thioctic acids and chitin hydrolyzate as active ingredients, and improves the inflammation, hardening or thickening of skin by ultraviolet irradiation (hereinafter sometimes referred to as skin disorders ). The present invention also relates to a composition for prevention and a method of using the active ingredient, and to an oral composition such as a food or drink containing the composition.

With recent changes in the global environment (warming, destruction of the ozone layer, etc.), the amount of ultraviolet rays received by organisms on the earth is currently increasing, although it is generally within an acceptable range. There is growing interest in health effects as well as skin beauty. As an effect on the skin by ultraviolet rays, it induces and promotes aging of skin tissues such as stains, freckles, and black skin, wrinkles, sagging, etc. In particular, there are concerns about the frequent occurrence of skin cancer particularly in the western region.

The following is known about the effect of ultraviolet rays on the skin. Among ultraviolet rays contained in sunlight, long-wavelength ultraviolet rays (400 nm to 320 nm, UV-A) are involved in cellular metabolism of the cells to activate cell functions and cause skin tanning (browning). In addition, it acts on the dermis layer to denature proteins and collagen and elastin to denature the skin, thereby causing skin wrinkles and sagging to promote skin aging. In some cases, phototoxicity or photoallergic reaction is induced, and the melanin pigment produced by UV-B is oxidized to turn brown. Medium wavelength ultraviolet light (320 nm to 280 nm, UV-B) acts on the epidermis layer, but pigment cells generate melanin to protect living tissues. It is considered that the skin is tanned (sunburn) red, causing inflammation, erythema and blisters, and contributing to the formation of spots, freckles and the like. In addition, it is said that a large amount of exposure induces immune decline, skin cancer, and cataract. Short wavelength ultraviolet rays (less than 280 nm, UV-C) have a strong bactericidal action and are most destructive to living organisms, but ultraviolet rays below 290 nm are absorbed by atmospheric ozone, oxygen and nitrogen in the atmosphere, so Does not reach,

In order to prevent, ameliorate, or treat skin damage caused by ultraviolet rays, particularly UV-A and UV-B, conventional skin external preparations include cinnamic acid compounds, aminobenzoic acid derivatives, benzophenone derivatives, salicylic acid compounds, urocanic acid derivatives. UV absorbers such as zinc oxide and titanium oxide have been used. However, for example, some cinnamic acid derivatives exhibit phototoxicity, and aminobenzoic acids may be discolored or denatured into a resinous substance, for example, because of safety, stability, usability, cost, etc. A sufficient effect was not obtained.

In addition, various foods and drinks for preventing, improving, or treating skin damage caused by ultraviolet irradiation have been proposed. That is, a radiation damage inhibitor containing a sweet potato-derived extract as an active ingredient and a food containing the same (Patent Document 1), an ultraviolet-induced active oxygen inhibitor containing an organic zinc compound and a food containing the same (Patent Document 2), Combining papaya and aloe, a skin improving agent for oral consumption consisting of a rhizome of a plant or an extract thereof (Patent Document 3), an antioxidant containing a tocopherol derivative, an ultraviolet light inhibitor containing the same, and a food (Patent Document 4) There are foods and drinks (Patent Document 6) containing 2-O-α-D-glucosyl-L-ascorbic acid as a UV absorber.

These are expected to restore the weakness, deterioration or damage of skin tissue function as part of the body's metabolic mechanism by ingesting a prescribed component substance as an active ingredient. In the digestive system, however, there are problems such as degradation and alteration, poor absorbability, slow transfer to the skin tissue, etc., and there are few things that exhibit sufficient desired effects.

By the way, the following things are known about the thioctic acid mentioned later. Thioctic acid is α-lipoic acid, 1,2-diethylene-3-pentanoic acid, 1,2-diethylene-3-valeric acid, 1,2-dithiolane-6-pentanoic acid or 1,2-dithiacyclopentane. It is also called -3-valeric acid. Pale yellow to yellow crystal or crystalline powder with specific odor, melting point: racemic: 60-61 ° C, R: 46-48 ° C, S: 45-48 ° C, slightly in water Dissolves and dissolves in organic solvents such as ethanol and acetone and dilute alkaline water. Thioctic acid is synthesized in the living body of plants, animals / humans, and microorganisms, and is known as a coenzyme for cell energy production. Oxidation of α-keto acids such as pyruvate and α-ketoglutarate produced from glucose glycolysis It is known to catalyze a decarboxylation reaction (for example, conversion of pyruvic acid to acetyl coenzyme A in a living energy production system).

In recent years, research on the functions of thioctic acid and its reduced dihydrothioctic acid (6,8-dimercapto-octanoic acid) has progressed, and these have attracted attention as having strong antioxidative properties. It reacts easily with reactive oxygen species such as peroxy radicals and singlet oxygen, easily reacting to lose the action of reactive oxygen species, reducing damage to living tissue, and interacting with vitamin C and glutathione It is said that it has the effect of protecting vitamins and regenerating vitamin E (Non-patent Document 1). The pharmacological action of thioctic acid has been reported to be effective for pathological models of oxidative stress such as tissue damage during ischemic reperfusion, diabetes, cataracts, neurodegeneration, radiation damage, inflammatory diseases, etc. ( Non-patent document 2). Regarding the relationship between thioctic acid and skin damage caused by ultraviolet irradiation, α-liposome that can be administered orally to inhibit the production of light-induced keratinocyte cell lysis factor by ultraviolet irradiation and prevent the degradation of collagen fibers such as collagen An acid-containing composition has been proposed (Patent Document 7).

Moreover, the following is well-known about the chitin hydrolyzate mentioned later. That is, the crustacean skin (crustacea) such as shrimp, shark and krill is chitinous, and is basically composed of chitin which is a linear polysaccharide in which N-acetylglucosamine is linked by β-1,4. Yes. Chitin raw material is decalcified with acid, deproteinized with alkali, pretreated appropriately, such as explosion, swelling or colloid, strong acid such as hydrochloric acid, sulfuric acid and / or chitinase, lysozyme, chitobiase, N -When an enzyme such as acetylglucosaminidase or N-acetylhexosaminidase is allowed to act to cause a hydrolysis reaction, a chitin hydrolyzate containing N-acetylchitooligosaccharide and / or N-acetylglucosamine can be produced. .

N-acetylchitooligosaccharide and / or N-acetylglucosamine can be used as a sweetener, a substance that promotes the growth of intestinal bacteria such as bifidobacteria, a food material, and a body feeling imparting agent. Among oligosaccharides, N-acetylchitohexaose has a growth inhibitory action on mouse solid tumor types (Sarcoma-180, MM-46, Meth-A, etc.) (Non-patent Documents 3 and 4) Physiological activities such as that chitooligosaccharides from N-acetylchitotetraose to N-acetylchitoheptaose have the effect of enhancing the neutrophil immune activity have been reported (Non-patent Document 5).

In addition, the technology of coating powders and particles as a core substance and surrounding the surface with a hydrophobic substance such as a polymer substance or lipid has been known, and the coating process stably maintains the taste and aroma of the core substance. It has been proposed to prevent or absorb moisture, improve powder flowability, or prevent leakage of the component when the core substance is a water-soluble component. However, the protective action of the core material by such coating treatment is aimed at maintaining the quality of flavor components, moisture resistance, prevention of leakage of water-soluble components, etc.

JP-A-2005-75750 JP 2004-277308 A JP 2004-67663 A JP 2001-279242 A JP 11-253129 A JP-A-3-139288 JP 2005-132823 A Kagan V.K. E. Et al., “Dihydrolipoic acid-A universal antixidant both in the membrane and in the aqueous phase. Reduction of peroxyl, ascorbyl and ascorbyl. Pharmacol. 44, No. 8, pp. 1637-1649 Indrahi Maitra et al., “Α-lipoic acid preventsbuthineine sulfoximine-induced catalyst formation in newborn rats.” (Netherlands), p. 8, No. 8, M A. Tokoro et al., “Growth-inhibitory effect of hexa-N-acetylchitohexaose and chitohexaose aginest Meth-A solid tumor.” (Japan), Chem. Pharm. Bull. 36, p. 784-p. 790 K. Suzuki et al., “Antitutor effect of hexa-N-acetylchitohexose and chitohexose.” (Netherlands), 1986, Carbohydr, Res. 151, pp. 403-408 S. Suzuki et al., “Chitin in Nature and Technology”. Muzzarelli et al. (USA), 1985, Plenum. New York, pp. 485-492.

In view of the current situation, the present inventors have developed a safe and stable material that can significantly prevent, ameliorate, or treat skin damage caused by ultraviolet irradiation by ingestion, and can be effectively utilized industrially. An object was to provide a composition.

In order to solve the above-mentioned problems, the present inventors have made extensive investigations on materials that effectively prevent and improve skin damage caused by ultraviolet rays, particularly UV-B irradiation. As a result, the thioctic acids and chitin degradation products are surprisingly different. The inventors have found that the present invention has remarkable effects, and that these can be effectively used in the fields of foods and drinks, feeds, cosmetics, pharmaceuticals and the like, and have completed the present invention.

That is, according to the present invention, there is provided a composition for improving and / or preventing skin damage caused by ultraviolet irradiation, comprising thioctic acids and a chitin hydrolyzate as active ingredients.

In the composition, the thioctic acids are one or more selected from the group consisting of thioctic acid, its reduced form, their optical racemate, their salts, esters and amides, and these cyclodextrin inclusion products. Furthermore, it is desirable that the thioctic acid, its reduced form, their optical racemate, their salts, esters and amides, one or more crystals, powder and / or particles. More preferably, the outer surface is coated with lipids.

In the above composition, the chitin hydrolyzate is preferably obtained by hydrolyzing chitin with at least one of an acid and an enzyme, and further, N-acetylchitooligosaccharide and / or What contains N-acetylglucosamine as a main component is more preferable.

The skin disorder for improving and / or preventing the composition is more preferably targeted at those having at least one symptom among skin inflammation, hardening, thickening and rough skin caused by ultraviolet irradiation. .

According to the present invention, there is also provided an oral composition characterized in that it comprises a composition for improving and / or preventing skin damage caused by ultraviolet irradiation, and the oral composition is It is desirable to be a food or drink. Furthermore, a skin cosmetic method using thioctic acids and chitin hydrolyzate is provided to improve and / or prevent human skin damage caused by ultraviolet irradiation, and it is desirable that the method of use is ingestion or oral administration. .

The composition of the present invention has excellent quality stability, and when taken orally, the active ingredient is efficiently absorbed without being digested and decomposed in the body, and inflammation caused by ultraviolet rays, particularly UV-B irradiation. Can be suppressed, skin hardening and thickening can be prevented, and rough skin can be prevented and / or treated. For this reason, the composition of the present invention can be effectively used as it is in the above-mentioned composition or in a form blended with various conventional products in the fields of foods and drinks, feeds, pharmaceuticals and the like. The composition of the present invention can also exhibit the same effects as described above even when applied to the skin, and can be effectively used as an external preparation for skin.

The present invention is described in detail below. In the present invention, ultraviolet rays refer to light rays in the wavelength range including the above-mentioned UV-A and UV-B, and it is particularly preferable to target UV-B. Skin damage caused by ultraviolet irradiation is an abnormality that develops when the function of normal skin tissue is degenerated, deteriorated or reduced, and among them, at least one symptom of skin inflammation, hardening, thickening and rough skin. It is preferable to target those exhibiting the above, and more preferable are those exhibiting skin hardening and / or thickening.

The composition according to the present invention is used for improving and / or preventing skin damage caused by ultraviolet irradiation, and is characterized by containing thioctic acids and a chitin hydrolyzate as active ingredients.

Here, the origin and type of thioctic acids are not particularly limited, and natural product extracts of organs such as livers of cattle and pigs, and chemical synthetic products starting from ethylene and adipic acid esters are known. It may be collected and manufactured by the method described above. In addition, since thioctic acid has an asymmetric carbon, optically enantiomers ((R) -enantiomer and (S) -enantiomer) exist, but any one of these thioctic acids according to the present invention can be used in any proportion. Or a racemic mixture or a racemate. In the implementation of the industrial production level, it is easy to use a commercially available racemic body that is inexpensive and easily available, and it is desirable to use the racemic body because the desired effect of the present invention is more strongly expressed.

As the thioctic acids used in the composition according to the present invention, various derivatives in addition to the above thioctic acid can be used as appropriate, and their reduced forms, optical racemates, salts thereof, esters and amides, and cyclodextrins. It is desirable to be one or more selected from the group consisting of inclusions. Specific examples of the reduced form of thioctic acid include dihydrothioctic acid, dihydrolipoic acid, 6,8-dimercapto-octanoic acid and the like. Similarly, optical racemates include (R), (S) -thioctic acid, ( (R), (S) -dihydrothioctic acid and the like, (R) -thioctic acid, (S) -thioctic acid, (R), (S) -thioctic acid, (R) -dihydrothioctic acid, (S ) -Dihydrothioctic acid, potassium salts such as (R), (S) -dihydrothioctic acid, sodium salts, calcium salts, magnesium salts, etc. Examples of esters include (R) -thioctic acid, (S) -thioctic acid, ( R), (S) -thioctic acid, (R) -dihydrothioctic acid, (S) -dihydrothioctic acid, (R), (S) -dihydrothioctic acid and the like and polyhydric alcohols (ethylene glycol, propylene Partial esters or complete esters or glycerides (monoglycerides, diglycerides, triglycerides) with glycol, butanediol, neopentyl glycol, glycerin, erythritol, polyglycerin or the like, or higher alcohols having 10 to 22 carbon atoms ( Monoesters with decanol, lauryl alcohol, myristyl alcohol, cetanol, stearyl alcohol, isostearyl alcohol, behenyl alcohol, etc.) and amides include (R) -thioctic acid, (S) -thioctic acid, (R), (S) Examples include amides such as -thioctic acid, (R) -dihydrothioctic acid, (S) -dihydrothioctic acid, and (R), (S) -dihydrothioctic acid. The cyclodextrin inclusion product may be an inclusion product of α-, β-, γ- or δ-cyclodextrin and the thioctic acid or a derivative thereof. In addition, this invention is not limited by these illustrations.

In the present invention, one or more crystals selected from the group consisting of the above-mentioned thioctic acid, its reduced form, optical racemate, their salts, esters and amides, and these cyclodextrin inclusion products as thioctic acids. , Powders and / or particles whose outer surface is coated with lipids, and this embodiment further suppresses thermal alteration (decomposition, polymerization, discoloration, etc.), moisture absorption or oxidative modification of thioctic acids. Is desirable.

The lipids that coat the outer surface of the thioctic acid crystals, powder, and / or particles may be acceptable as long as they are acceptable in the industrial field in which the present invention is used, such as general edible oils or industrial fats and oils, Fatty acid glycerides, fatty acids, fatty acid esters, fatty acid amides, higher alcohols, waxes, sterols, glycolipids, phospholipids and the like can be used alone or in combination. Of these, lipids having a melting point of about 30 ° C. or higher are preferable in consideration of coating workability and physical properties of the coating (stability, solidification, fluidity, meltability, solubility, etc.). More preferred forms are lipids having a melting point of about 40 ° C. to about 70 ° C., and still more preferred forms are lipids having a melting point of about 40 ° C. to about 60 ° C. When the melting point is less than about 30 ° C., the coating may not be able to maintain a solid state during use, and may form a lump or impair flowability. On the other hand, when the temperature exceeds about 70 ° C., the thioctic acids themselves may be deteriorated due to the influence of heat treatment and mechanical energy when producing the composition according to the present invention.

Specific examples of such lipids include soybean oil, rapeseed oil, corn oil, sunflower oil, cottonseed oil, wheat germ oil, rice oil, sesame oil, olive oil, safflower oil, palm oil, palm kernel oil, coconut oil, linseed oil , Vegetable oils such as peanut oil, animal fats such as beef tallow, lard, fish oil, processed oils and fats that have been subjected to one or more of such treatments as fractionation, transesterification, decolorization, deodorization, etc., partially or completely Various hydrogenated hydrogenated oils, saturated fatty acids having 2 to 22 carbon atoms (acetic acid, butyric acid, caproic acid, caprylic acid, capric acid, lauric acid, myristic acid, pentadecanoic acid, palmitic acid, stearic acid, 12-hydroxystearic acid , Isostearic acid, arachidic acid, behenic acid, etc.) or unsaturated fatty acids (palmitoleic acid, oleic acid, elaidic acid, linoleic acid, α-linolenic acid) , Γ-linolenic acid, ricinoleic acid, arachidonic acid, icosapentaenoic acid (EPA), erucic acid, docosahexaenoic acid (DHA), etc., salts of these arbitrary fatty acids (sodium salt, potassium salt, calcium salt, magnesium salt, etc.) Partially or completely with esters with monohydric alcohols (methanol, ethanol, propanol, butanol, etc.), polyhydric alcohols (monomers or polymers with ethylene glycol, propylene glycol, butanediol, neopentyl glycol, glycerin, erythritol, etc.) Esters or glycerides (monoglyceride, diglyceride, triglyceride), higher alcohols having 10 to 22 carbon atoms (decanol, lauryl alcohol, myristyl alcohol, cetanol, stearyl alcohol, Sostearyl alcohol, behenyl alcohol, etc.), waxes (carnauba wax, rice wax (rice bran wax), candelilla wax and other plant-derived waxes, beeswax, whale wax, shellac wax and other animal-derived waxes, paraffin wax, microcrystalline wax, etc. Oil-derived wax, wax derived from minerals such as montan wax, ozokerite, polyethylene wax, synthetic waxes such as esters of the above fatty acids and higher alcohols, sterols (animal cholesterol, plant campesterol, stigma) Ergosterols derived from fungi such as sterol and sitosterol, and derivatives thereof, phospholipids (lecithin derived from animals and plants, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinos , Phosphatidylserine, phosphatidic acid, sphingomyelin, etc.), glycolipids (monoglucosyl diglyceride, monogalactosyl diglyceride, diglucosyl monoglyceride, digalactosyl monoglyceride, monoglucosyl diglyceride, digalactosyl diglyceride, sucrose fatty acid ester, etc.) be able to. In addition, this invention is not limited at all by these illustrations.

In the present invention, any one or a mixture of two or more of the above-mentioned various lipids can be used. Suitable types of lipids include the above edible oils or industrial fats, fatty acid glycerides, fatty acid esters and Waxes, more preferably edible fats and oils and fatty acid glycerides, and these and one or more selected from fatty acids, higher alcohols, sterols, glycolipids or phospholipids The combination is a more desirable embodiment from the viewpoint of adjusting the melting point of the coated lipid, reinforcing the coating film, and the like.

A known method can be used to coat the outer surface of the thioctic acid crystals, powder and / or particles with lipids. That is, ball mill, flash blender (powder granule mixer), V-type mixer, high-speed mixer, high-speed paddle mixer, heat-melt mixer, ultrasonic super-humidified liquid-type mixer, tumbler mixer, pressure extruder, etc. The thioctic acid crystals, powder and / or particles and the heated and melted lipids are uniformly mixed, cooled and solidified, and then pulverized. A method of coating by spraying or dripping the lipids which have been formed, and stirring and mixing the thioctic acids of the above-mentioned form and particulate lipids at high speed, and bringing them into contact or colliding with each other, thereby producing crystals, powders and / or thioctic acids. Alternatively, a method in which particulate lipids are uniformly attached to the entire surface of the particle and coated is possible. In the present invention, among these, thioctic acid crystals, powders and / or particles and particulate lipids having a specific melting point or higher are mixed with high-speed stirring, and both are brought into contact with or collided with each other to obtain the thioctic acid of the above form. A method of uniformly coating particulate lipids on the entire surface of acids is desirable.

In the above-described coating treatment, the ratio of thioctic acid crystals, powders and / or particles to lipids, thioctic acid crystals, powder and particle shapes and sizes, lipid types and melting points, coating film thickness and Although it is difficult to define uniformly by a factor of properties such as, generally, crystalline thioctic acid, powders and / or particles 1 mass unit lipids about 0.05 mass parts to about 10 mass parts with respect to, preferably is about 0.1 mass part to about 5 mass parts. Coating and lipids is less than about 0.05 mass part state becomes difficult to express the desired effect not sufficient, less thioctic acid content in the coating and greater than about 10 mass unit Conversely, coated In a scene where a product is used, the blending rate and the like are limited, and the practical value may be impaired.

The above-described coating of thioctic acids with lipids is more preferably an embodiment in which the outer surface is further coated with a hydrophilic substance regardless of whether or not this is applied to an aqueous composition such as a beverage. More desirable. Here, the hydrophilic substance means a substance that further coats the outer surface of the coating with lipids and has a coating film-forming ability having an affinity with an aqueous substance. Specific examples include polysaccharides (xanthan gum, guar gum, Tamarind seed gum, psyllium seed gum), starch and modified starch, yeast cell wall components, glucan, mannan, shellac, sodium alginate, gelatin, carrageenan, pullulan, carboxymethylcellulose, soybean protein, whey protein, zein, etc. Can do. More preferably, it is one or more selected from the group consisting of polysaccharides, starch, yeast cell wall components, shellac, gelatin, soybean protein, zein and mannan, and more preferably yeast cell wall components, shellac and gelatin. is there.

In order to coat such a hydrophilic substance, a method according to the above-described method for coating lipids may be employed. That is, the hydrophilic substance is appropriately dissolved in water, ethanol, or other solvent to form a liquid, and this is attached to the outer surface of thioctic acid previously coated with lipids and dried to coat the hydrophilic substance. A film can be formed. Such a coating becomes a double-coated structure having a hydrophilic substance as the outermost layer, and when this is used for foods, drinks, feeds, cosmetics, pharmaceuticals, etc., the affinity with aqueous raw materials and ingredients increases, It becomes easy to prepare a homogeneous composition with thioctic acids having low solubility.

In the above-described coating of thioctic acids with lipids and the double coating in which the coating is further coated with a hydrophilic substance, these include Garcinia camphor peel, red pepper rhizome, guava leaf and extracts thereof (water And / or one or two selected from the group consisting of an extract with a hydrophilic organic solvent (e.g., a lower monohydric alcohol such as ethanol, acetone, its fraction, a solvent fraction or a purified product), and carnitine. As described above, a thioctic acid-containing coating that can further suppress thermal and / or oxidative denaturation and degradation of thioctic acids by coexistence with red pepper rhizome extract and carnitine, most preferably carnitine, and has excellent stability. The thioctic acids of this embodiment are more desirable in the present invention since a product is obtained.

In the embodiment in which these combined raw materials are contained in the above-mentioned thioctic acid-containing coating, (i) the combined raw material is mixed with a coating in which lipids are coated on thioctic acid crystals, powder and / or particles. ) A lipid is coated on a mixture of the thioctic acid crystals, powders and / or particles and the combination raw material. (Iii) A part of the combination raw material is dispersed in the thioctic acid crystals, powder and / or particles. Or (iv) a solution obtained by coating the lipids on the thioctic acid crystals, powder and / or particles, and a solution, dispersion or emulsification containing the combined raw material and the hydrophilic substance. Any of attaching and drying and coating the liquid is possible, and a combination of these embodiments may be used. In the present invention, the aspects (i) and (iv) have the desired effects of the present invention, the production is simple, and the handling workability of the coating is good, but the aspects (ii) and (iii) are desirable. It is easy to express the effect more powerfully.

In such embodiments, the crystalline thioctic acid, mixing ratio of the powders and / or lipids or lipids on the particle and a hydrophilic based coatings material was coated with the combination raw material, the relative said coating 1 mass part combination material of about 0.01 mass parts to about 10 mass parts, more preferably about 0.1 mass part to about 1 mass part. For less than about 0.01 mass part, no longer allow improvement of the desired effect by mixing together raw materials, thioctic of composition further in said coating in an amount greater than about 10 mass part to use it The acid content decreases, and as a result, the thioctic acid content in various products containing the thioctic acid-containing composition is limited, and the desired effect of thioctic acid itself cannot be expected in the product stage.

In the composition according to the present invention, the chitin hydrolyzate is preferably obtained by hydrolyzing chitin with at least one of an acid and an enzyme, and further, N-acetylchitooligosaccharide and / or What contains N-acetylglucosamine as a main component is more preferable. Here, the N-acetylchitooligosaccharide contains a dimer (N-acetylchitobiose) to a heptamer (N-acetylchitoheptaose) of N-acetylglucosamine which is a structural unit. Desirably, the mixing ratio of N-acetylchitooligosaccharide and N-acetylglucosamine may be arbitrary, but the more N-acetylglucosamine is, the better.

Such chitin hydrolyzate may be obtained by a known production method as described above. For example, shellfish such as shrimp and salmon are treated with dilute hydrochloric acid to remove calcium, and then treated with sodium hydroxide to remove protein to prepare chitin. Concentrated hydrochloric acid is added to this chitin and the mixture is heated at 30-50 ° C. for 3 minutes. Stir appropriately for -6 hours to obtain an aqueous solution containing the hydrolyzate. Thereafter, as appropriate, approximately the same amount of cold water is added to the hydrolyzed solution, and further 20 to 50% sodium hydroxide aqueous solution is added to prevent neutralization heat, neutralization treatment, decolorization treatment with activated carbon, dialysis A powdery chitin hydrolyzate can be produced through a desalting treatment using a membrane, a deacetylation product removing treatment using an ion exchange resin, etc., and purification, followed by a drying treatment. This chitin hydrolyzate contains N-acetylchitooligosaccharide and N-acetylglucosamine, and when the degree of purification is low, it contains D-glucosamine which is a deacetylated product.

Also, dissolve the chitin hydrolyzate in water to make 5-10% chitin hydrolyzate aqueous solution, add hydrolase such as chitinase, chitobiase, lysozyme, etc. and gently stir at 30-50 ° C. for 6-48 hours Then, after the hydrolysis reaction is performed, the enzyme is heated and deactivated, and the purification treatment is appropriately performed to produce a chitin hydrolyzate containing N-acetylglucosamine as a main component. In addition, when chitin is directly treated with chitinase, a chitin hydrolyzate containing N-acetylglucosamine dimer (N-acetylchitobiose) as a main component is obtained.

  The composition according to the present invention comprises the thioctic acids and chitin hydrolyzate described above as essential raw materials, and it is a more desirable aspect to use these in combination. In this case, thioctic acids: chitin hydrolyzate = 80 to 20:20 to 80 (weight ratio) is more preferable, and 70 to 50:30 to 50 is most preferable. The composition according to the present invention is a mode in which thioctic acids and chitin hydrolyzate are contained in the same composition, and different compositions containing each are ingested or taken into the living body almost simultaneously. But you can. Such a composition itself can be used as a variety of products in food and drink, pharmaceuticals, cosmetics, and other industrial fields, or can be used in a form of being used as a part of a blended raw material of the various products. In particular, food and drink applications are suitable. Examples of these are described below, but the present invention is not limited thereby.

Specific examples of food and drink include beverages such as vegetable juice, fruit juice drink, soft drink, tea, soup, jelly, pudding, yogurt, cake premix product, confectionery, sprinkle, miso, soy sauce, sauce, dressing, mayonnaise, Vegetable cream, miso, seasonings such as grilled meat sauce and noodle soup, noodles, udon, soba noodles, spaghetti, ham and sausage, etc. , Powders such as spreads and cheese, solid or liquid dairy products, margarine, bread, cakes, cookies, chocolates, candy, gummi, gums, and other general processed foods, powders, granules, pills , Tablets, soft capsules, hard capsules, pasty or liquid dietary supplements, food for specified health use, machine Sex food, mention may be made of health food products, the concentrated liquid diet and dysphagia for food diet and the like.

In order to produce these foods and drinks, a known raw material and the composition of the present invention may be used, or a part of the known raw material may be replaced with the composition of the present invention and produced by a known method. For example, the composition of the present invention and, if necessary, glucose (dextrose), dextrin, lactose, starch or processed product thereof, excipients such as cellulose powder, vitamins, minerals, fats and oils of animals and plants and seafood, protein ( Animal, plant and yeast-derived proteins, hydrolysates thereof, etc.), carbohydrates, pigments, fragrances, antioxidants, other edible additives, powders containing various nutritional functional ingredients, and edible ingredients such as extracts, mixed into powder , Processed into the shape of granules, pellets, tablets, etc., processed into the general foods of the above examples by conventional methods, or coated with gelatin, sodium alginate, carboxymethylcellulose, etc. to form a capsule Or processed into a beverage (drinks) form and used as a dietary supplement or health food. In particular, tablets, capsules and drinks are desirable.

The ratio of the composition of the present invention to be blended in such food and drink is uniform depending on the form of the food and drink, the content of thioctic acids and chitin hydrolyzate in the composition of the present invention, and the types and ingredients of other blended raw materials. defined and difficult but, the food or drink in thioctic acid content of about 0.01 mass% to about 90 mass% of, as more preferably of about 1 mass% to about 50 mass%, thioctic acids , Lipid coatings and / or double coatings, and further appropriate ingredients selected from Garcinia Cambodian peel, red pepper rhizome, guava leaves, these extracts and carnitine, and other food and beverage production ingredients The prescription is designed in combination, and the desired food or drink may be prepared according to a conventional method. The food products such as thioctic acid content below about 0.01 mass% in order to expect the desired effects of thioctic acids must ingest large amounts of food or beverage, while about 90 mass% It is the maximum thioctic acid content in the food and drink of the present invention. In the case of humans, the food and drink of the present invention can be used in any method, for example, by setting a daily thioctic acid intake standard of about 10 mg to about 1000 mg, preferably about 30 mg to about 500 mg, more preferably about 50 mg to about 200 mg. It can be taken into the body by methods such as oral intake and tube administration.

Next, although an Example is given and this invention is demonstrated in detail, this invention is not limited by this. In each example,%, both parts and ratios are by mass basis.

(Production Example 1)
(1) Thioctic acid lipid coating Crystal powder of thioctic acid (manufactured by Degussa, Germany, trade name: ALIPURE (registered trademark), racemic body) heat-melted rapeseed oil (manufactured by Kawaken Fine Chemical Co., Ltd.) (Melting point: 67 ° C., flake shape) 200 g was added, mixed well and dispersed uniformly, and then cooled and solidified to room temperature. Next, the solidified product was pulverized with a high-speed mixer, and sieved with 100 mesh (Tyler mesh; the same applies hereinafter) to obtain a thioctic acid lipid coating (sample 1) having a particle size of 150 μm or less.

200 g of the thioctic acid and 200 g of powdered rapeseed oil (manufactured by Kawaken Fine Chemicals Co., Ltd., melting point: 60 ° C., average particle diameter of about 20 μm) are coated with a fine particle coating granulator (manufactured by POWREC Co., Ltd., model: MP- 25SFP), and the mixture was flowed and mixed for 30 minutes at a rotation speed of a stirring and mixing fan blade of 1000 rpm, and the two raw materials were brought into contact with each other and collided to obtain a thioctic acid lipid coating (sample 2) having an average particle diameter of about 100 μm.

In the production example of the thioctic acid lipid coating (sample 2), 200 g of thioctic acid was replaced with a mixture of 150 g of thioctic acid and 50 g of guava leaf extract (manufactured by BN Co., Ltd., trade name: guava leaf extract powder-S). In the same manner as above, a thioctic acid lipid coating (sample 3) was obtained.

In the production example of the thioctic acid lipid coating (sample 2), 200 g of thioctic acid was charged into a coating granulator and stirred and flowed, soybean oil: 40 parts, carnauba wax: 40 parts and soy sterol: 20 parts Lipid mixture 100 g, L-carnitine-L-tartrate (Lonza Japan, Inc.) 30 g, and sucrose behenate (Mitsubishi Chemical Foods, Ryoto (registered trademark) sugar ester, HLB: 1 2) A homogeneous liquid material obtained by heating, melting and mixing 20 g at 70 ° C. was ejected from a spray nozzle to coat the surface of thioctic acid to obtain a thioctic acid lipid coating (sample 4).

(Production Example 2)
(2) Double coating of thioctic acid Coating granulation using a part of any of the above thioctic acid lipid coatings (sample 1, sample 3) in the production example of the thioctic acid lipid coating (sample 2) A dispersion (made by Kirin Brewery Co., Ltd., trade name: East Wrap (registered trademark)) containing 8.0% yeast cell wall is charged into an apparatus (provided by the company, model: MP-01SFP), and stirred and flowed. It sprayed and the surface of each thioctic acid lipid coating particle was coat | covered with the hydrophilic material, and the thioctic acid double coating (sample 5, sample 7) was obtained. In addition, the thioctic acid lipid coating (sample 2 and sample 4) was treated in the same manner except that the dispersion containing 8.0% yeast cell wall was replaced with an aqueous ethanol solution containing 20% shellac. Coatings (Sample 6, Sample 8) were obtained.

(Production Example 3)
(3) Chitin hydrolyzate A chitin hydrolyzate was prepared by the following method. That is, a mixture of shrimp and salmon shells was decalcified with dilute hydrochloric acid and deproteinized with sodium hydroxide, and then dried and ground to prepare chitin. Add 4 liters of concentrated hydrochloric acid to 1 kg of the chitin, hydrolyze with stirring at 35-40 ° C., dilute by adding the same volume of water, and neutralize with 20% aqueous sodium hydroxide at the same temperature. did. Next, 250 g of activated carbon was added to the neutralized solution for decolorization, and insoluble matters were filtered off to obtain a colorless transparent filtrate. The filtrate was subjected to a dialysis membrane treatment by a conventional method to obtain a desalted solution, which was then packed into a cation exchange resin (manufactured by Mitsubishi Chemical Corporation, trade name: Diaion (registered trademark) SK1B) and anion exchange. The resin (Mitsubishi Chemical Co., Ltd., trade name: Diaion (registered trademark) SA10A) was passed through a packed column for decolorization and purification, followed by concentration and spray drying to obtain 450 g of a white powder. The composition of this powder was analyzed by high performance liquid chromatography. As a result, N-acetyl-D-glucosamine 28%, N-acetylchitobiose 17%, N-acetylchitotriose 19%, N-acetylchitotetraose 16 %, N-acetylchitopentaose 10%, N-acetylchitohexaose 7%, N-acetylchitoheptaose 2%, and others 1% (N-acetylchitooligosaccharide and N-acetyl-D-glucosamine Mixture of: Sample 9).

Further, 50 g of the above white powder was dissolved in 1 liter of water, 750 units of chitinase (manufactured by Sigma, Serratia marcescens) was added, the enzyme was allowed to act for 48 hours while gently stirring at 40 ° C., and then hot water at 95 ° C. The enzyme was inactivated by heating in a bath for 10 minutes. The insoluble matter is then filtered off, and the filtrate is passed through a column packed with activated carbon / Celite (1/1) to remove decolorized and undegraded N-acetylchitooligosaccharide and purified, followed by concentration and drying to obtain a white powder. 34 g was obtained. This was a pure product of N-acetyl-D-glucosamine as a result of high performance liquid chromatography analysis (N-acetyl-D-glucosamine: sample 10).

(Test example)
The effects of the components of the composition of the present invention on the improvement and prevention of skin damage (stretching, thickening and inflammation) caused by ultraviolet irradiation were examined by the method described below. That is, the test substance which is the composition according to the present invention includes (1) thioctic acid, (2) thioctic acid lipid coating, (3) thioctic acid double coating, (4) N-acetyl-D-glucosamine, (5) a mixture of N-acetylchitooligosaccharide and N-acetyl-D-glucosamine, (6) a mixture of thioctic acid and N-acetyl-D-glucosamine (1: 1), (7) thioctic acid and N- Mixture of acetylchitooligosaccharide and N-acetyl-D-glucosamine mixture (2: 1), (8) Mixture of thioctic acid lipid coating and N-acetylchitooligosaccharide and N-acetyl-D-glucosamine mixture (1: 1) and (9) A mixture (3: 1) of thioctic acid double coating and N-acetyl-D-glucosamine. Here, thioctic acid is manufactured by Degussa, Germany, trade name: ALIPURE (registered trademark), thioctic acid lipid coating is sample 1 to sample 4, thioctic acid double coating is sample 5 to sample 8, N-acetyl- D-glucosamine is sample 10, and a mixture of N-acetylchitooligosaccharide and N-acetyl-D-glucosamine is sample 9.

C57BL / 6J male mice (5 weeks old) (manufactured by Japan SLC Co., Ltd.) were preliminarily raised for 1 week, and each group was divided into 8 groups, divided into a normal group, an ultraviolet irradiation group (control group), and a test substance administration group ( 8 groups for each test group). Feed and water were ad libitum during the test period. The back of the mouse was depilated, and after 2 days, the test substance solution suspended in distilled water for the normal group and the control group, and distilled water for the test substance-administered group was used for 2 days a day using a stomach tube. For 2 weeks, 0.1 mL per 10 g of mouse body weight was forcibly orally administered. The dose of the test substance was 50 mg / kg body weight x 2 times / day for each of thioctic acid, thioctic acid lipid coating and thioctic acid double coating, N-acetyl-D-glucosamine, N-acetylchitooligosaccharide and N The mixture of -acetyl-D-glucosamine was 500 mg / kg body weight each. UV irradiation was performed 4 days after hair removal treatment with a UVB lamp (manufactured by Ieda Trading Co., Ltd., model: T-15M, 15 W type, UV wavelength: 312 nm, UV intensity: 1,000 μW / cm ² ) 50 cm away from the back of the mouse. 5 days after irradiation for 20 minutes a day, and thereafter, irradiation was performed every other day under the same conditions. After 15 days, the elongation (elongation) of the skin on the back of the mouse was measured by a suction method, and the thickness (thickening) of the skin was measured using an ultrasonic measuring device. In addition, as an evaluation index for inflammation, the plasma concentration of MCP-1 (Macrophage Chemotactic protein-1), which is one of cytokines, was measured using an MCP-1 specific ELISA kit (manufactured by Endogen).

The results are shown in Table 1 (skin elongation, measurement unit: mm), Table 2 (skin thickening, measurement unit: μm) and Table 3 (plasma MCP-1 concentration, measurement unit: pg / mL). In each table, NAG represents N-acetyl-D-glucosamine, NCO represents N-acetylchitooligosaccharide, and the numerical values were expressed as relative values when the average value of the normal group was 100.

From Table 1, the skin growth (flexibility, tension, elasticity) in the control group was reduced by ultraviolet (UV-B) irradiation, but thioctic acids (thioctic acid, its lipid coating, double coating) were administered orally. It was clarified that administration improved significantly, and chitin hydrolyzate (N-acetyl-D-glucosamine, a mixture of this and N-acetylchitooligosaccharide) was also slightly effective. In particular, when the thioctic acids and chitin hydrolyzate were combined, the stretch of the skin was restored to the value of the normal group not irradiated with ultraviolet rays, and a remarkable improvement effect was confirmed. In addition, in this test, the preventive effect can be greatly expected in consideration of the administration of the test substance before the ultraviolet irradiation.

From the data in Table 2, it has been clarified that when ultraviolet rays (UV-B) are irradiated, the skin is markedly thickened (control group), but thickening (skin sclerosis) symptoms can be remarkably suppressed by oral administration of thioctic acids. . In addition, even if chitin hydrolyzate such as N-acetyl-D-glucosamine or N-acetylchitooligosaccharide was orally administered alone, the effect of reducing skin thickening was not recognized, but these and thioctic acids were used in combination. Then, a synergistic improvement effect was also recognized. As in the case of the above-described skin stretching, thioctic acids are also promising for the prevention of skin thickening symptoms caused by oral intake.

Furthermore, from Table 3, MCP-1 secretion of a cytokine that enhances skin inflammation caused by ultraviolet irradiation is markedly observed when a chitin hydrolyzate such as N-acetyl-D-glucosamine or N-acetylchitooligosaccharide is orally administered. Declined. From this, the effectiveness (improvement and prevention) of chitin hydrolyzate and its combined use with thioctic acids against the worsening of inflammation can be expected.

(Example 1: Food and drink)
Thioctic acid (manufactured by Degussa, Germany, trade name: ALIPURE (registered trademark), racemic body) 170 parts, beeswax 30 parts and medium chain fatty acid triglyceride (Nisshin Oilio Co., Ltd., trade name: ODO (registered trademark) 50 parts) The mixture was heated and mixed to about 50 ° C. to be homogenized, and then subjected to a capsule filling machine, and a gelatin-coated soft capsule preparation having an internal volume of 300 mg per tablet was prepared by a conventional method. Available as

(Example 2: Food and drink)
In Example 1, a dietary supplement was prepared by replacing 170 parts of thioctic acid with 100 parts of thioctic acid and 70 parts of chitin hydrolyzate (sample 10).

(Example 3: Food and drink)
In Example 1, 170 parts of thioctic acid was replaced with 170 parts of chitin hydrolyzate (sample 10), and the same treatment was performed to produce a nutraceutical product.

(Example 4: Food and drink)
About 75 parts of thioctic acid lipid coating (sample 1), 75 parts of chitin hydrolyzate (sample 9), 20 parts of red pepper extract powder (manufactured by BN Co., Ltd.), 30 parts of beeswax and 50 parts of evening primrose oil After thoroughly mixing at 45 ° C. to obtain a homogeneous state, the mixture was supplied to a capsule filling machine, and a gelatin-coated capsule preparation with an inner volume of 250 mg per grain was prepared by a conventional method. This capsule preparation can be taken orally as a dietary supplement.

(Example 5: Food and drink)
Thioctoate lipid coating (sample 2) 47 parts, grape seed extract (Kikkoman Co., Ltd., “Grabinol”) 20 parts, cystine 25 parts, lotus germ extract powder (Maruzen Pharmaceutical Co., Ltd.) 20 parts, creatine ( Germany, Degussa, "Crea Pure") 25 parts, Riboflavin (DSM Nutrition Japan Co., Ltd.) 7 parts, Maltitol (Towa Kasei Co., Ltd.) 105 parts, Tricalcium phosphate (Yoneyama Chemical Industries ( Co., Ltd.) 105 parts and cellulose 26 parts were charged in a mixer and stirred and mixed for 10 minutes. This mixture was subjected to a direct compression tableting machine to prepare uncoated tablets having a diameter of 7 mm, a height of 4 mm, and a weight of 150 mg / piece, and then a shellac film was formed by the coating machine to produce a tablet-shaped food.

(Example 6: Food and drink)
20 g of the thioctic acid double coating (sample 5) of the present invention and chitin hydrolyzate (sample 9) were added to 1 L of commercially available orange juice and mixed well to produce a homogeneous orange flavored drink. Even if this was stored in the refrigerator for 1 week, the appearance and flavor were neither abnormal nor uncomfortable.

The composition comprising the thioctic acid and the chitin hydrolyzate of the present invention, when taken orally or by tube, causes skin elongation (elongation) and thickening caused by ultraviolet rays, particularly UV-B irradiation ( Curing), inflammation, and other disorders can be improved and / or prevented, so that UV-resistant foods, medicines, cosmetics, feeds, etc. can be used effectively.

Claims (4)

An oral preparation for improving and / or preventing skin inflammation, hardening or thickening caused by ultraviolet irradiation, comprising thioctic acids and a chitin hydrolyzate as active ingredients. Here, the thioctic acids are one or more selected from the group consisting of thioctic acid, its reduced form, optical racemate, their salts, esters and amides, or these (a) cyclodextrin inclusions Or (b) the outer surface of the crystal, powder and / or particle is coated with lipids. The lipids are one or more selected from edible fats and oils, industrial fats and oils, fatty acid glycerides, fatty acid esters and waxes, and have a melting point of about 40 ° C to about 70 ° C. The agent according to claim 1, wherein the chitin hydrolyzate is obtained by subjecting chitin to a hydrolysis treatment using at least one of an acid and an enzyme. The agent according to claim 1 or 2 , wherein the chitin hydrolyzate contains N-acetylchitooligosaccharide and / or N-acetylglucosamine as a main component. Skin cosmetic method for improving and / or preventing inflammation, hardening or thickening of human skin caused by ultraviolet irradiation, characterized by orally ingesting or administering thioctic acids and chitin hydrolyzate ( excluding medical practice). ) Here, the thioctic acids are one or more selected from the group consisting of thioctic acid, its reduced form, optical racemate, their salts, esters and amides, or these (a) cyclodextrin inclusions Or (b) the outer surface of the crystal, powder and / or particle is coated with lipids. The lipids are one or more selected from edible fats and oils, industrial fats and oils, fatty acid glycerides, fatty acid esters and waxes, and have a melting point of about 40 ° C to about 70 ° C.