JP5873319B2 - Maillard reaction inhibitor - Google Patents

Description

The present invention relates to a Maillard reaction inhibitor containing mucopolysaccharide or a salt thereof as an active ingredient, and more specifically, is particularly useful for the prevention and treatment of dysfunction expressed by the progress of Maillard reaction, The present invention relates to a Maillard reaction inhibitor that can be used for a wide range of uses such as pharmaceuticals, quasi drugs, cosmetics, and foods and drinks.

In 1912, L. C. The saccharification reaction, which was discovered by Maillard and produces a brown pigment by the non-enzymatic condensation reaction of an amino acid and a reducing sugar, is called the Maillard reaction. The Maillard reaction can be roughly divided into an early stage involving reversible addition and transfer reactions and a late stage involving irreversible oxidation, elimination, hydrolysis, transfer, condensation, and the like. In the first stage, the amino group of amino acids and the carbonyl group of reducing sugars such as glucose react with each other non-enzymatically to form a Schiff base, and then through the intermediate enanol, the Amadori transfer reaction Amadori compound is produced by such as. In the later stage, Amadori compounds and compounds such as α-dicarbonyl compounds and Schiff bases produced from the Amadori compounds are further subjected to a decomposition reaction, a lipid peroxidation reaction, a transfer reaction and a condensation reaction to produce a terminal glycation product (AGEs: Advanced). Glycation End Products).

AGEs is a general term for products that have undergone a wide variety of reaction pathways, and is not a compound that exhibits a certain structure. AGEs have been elucidated to date, including substances generated in vitro, and are generally yellow-brown to brown, having fluorescence of about Ex: 370 nm and Em: 440 nm, and cross-linking between proteins. It is known that it has physicochemical properties that form selenium and biological properties that are recognized by vascular endothelial cells and macrophages.

The increase in AGEs in in vivo proteins is a phenomenon that is also observed by aging of healthy individuals, but it is known that the degree of increase is high in patients with diabetes, Alzheimer's disease, arteriosclerosis and the like. AGEs cause disordered physical and physiological changes (degeneration) by creating disordered crosslinks within and between protein molecules, so AGEs are a direct cause of these diseases and complications associated with these diseases It is being revealed. It has also been clarified that when collagen and elastin, which are skin constituent proteins, are saccharified, these elastic fibers are cross-linked to cause skin aging such as hardening, wrinkles and dullness of the skin.

Maillard reaction inhibitors that inhibit the production of AGEs are likely to be therapeutic or preventive agents for these diseases and symptoms. Therefore, aminoguanidine, a Maillard reaction inhibitor, has already been used as a preventive agent for diabetic complications (non- Patent Document 1) and ALT-711 are used for clinical trials as a therapeutic agent for aging diseases (Non-Patent Document 2). In addition, as a Maillard reaction inhibitor used in the pharmaceutical field, a thiazoline derivative (Non-patent Document 3), a hydatoin derivative or a salt thereof (Patent Document 4), a pyrazole derivative or an aminopyrazole derivative (Patent Documents 5 and 6) These compounds are known, but these have strong effects but have problems such as side effects and have not yet been put into practical use as pharmaceuticals. In addition, plant extracts such as akebi, aloe, apricot, hippopotamus, cypress, trash, sanchinin ginseng, taukogi, narukoyuri, chickweed, hamadisha, bukkyou, yuzu are also known as Maillard reaction inhibitors (Patent Document 6). These are prone to alteration by heat and light, and also have problems such as causing allergies because they are derived from plants. Furthermore, most of the currently available Maillard reaction inhibitors are expensive and difficult to use in large quantities for one product. Therefore, particularly in product forms such as cosmetic compositions and foods that are applied or taken daily, there has been a demand for Maillard reaction inhibitors that are high in safety and storage stability and inexpensive.

Am J Nephrol. 2004, 24, 32-40 J Card Fail. 2005, 11 (3), 191-195 Diabetes, 1997, 46 (5), 895-889 JP-A-6-135968 JP-A-6-298737 JP-A-6-298738 JP 2002-241293 A

As typical substances of mucopolysaccharide, hyaluronic acid, chondroitin sulfate, chondroitin, ketalan sulfate, heparin, heparin sulfate, dermatan sulfate and the like are known.
Mucopolysaccharides are generally known to have an effect of water retention of animals and human bodies, and are widely used as pharmaceuticals, cosmetics, and health foods, but are not known about the Maillard reaction inhibitory effect.

Hyaluronic acid is widely used as a health food and supplement in addition to being used as a skin moisturizer as a moisturizer and as a joint injection as a joint function improving agent. Also, autoimmune disease symptom mitigating action (Patent Document 8), skin improving action (Patent Document 9), liver disease treatment effect (Patent Document 10), stress protein expression enhancing action, cell damage inhibiting action, cell death inhibiting action (special Physiological actions such as Kaihei Patent Document 11) and IL-12 expression regulating action (Patent Document 12) are also known, but Maillard reaction inhibitory action is not known.

JP 2008-266171 A Japanese Patent Laid-Open No. 2002-356432 JP 2001-354572 A JP-A-9-227386 Japanese Patent No. 4234439

Chondroitin sulfate is taken as a health food with the expectation of effects such as “helping bone formation” and “preventing arteriosclerosis and hypertension”, and is also added to a topical skin preparation as a moisturizing agent. In addition, there are known osteoarthritis mitigating effects by internal use (Patent Document 13), postoperative intraocular pressure lowering effects of Cataract (Patent Document 14), etc., but Maillard reaction inhibitory effects are not known.

Curr Med Res Opin. 2008, 24 (11), 3029-3035 Ann Ophthalmol. 1989, 21 (3), 85-88

Heparin is known to have a blood coagulation inhibitory action and is widely used as an anticoagulant for the treatment of thromboembolism, artificial dialysis, anticoagulation in extracorporeal circulation, etc., but it is known about the Maillard reaction inhibitory action. It is not done.

As described above, mucopolysaccharide is a substance that has been widely used in foods and the like, and is also a highly safe substance that can be obtained at low cost. As described above, mucopolysaccharides having a wide variety of functionalities and being highly safe and easily available can be said to be one of the very useful components in constituting a cosmetic composition or food.

An object of the present invention is to solve the problems in the prior art and achieve the following objects. That is, the present invention is suitable as a drug for treating and preventing various diseases and symptoms caused by Maillard reaction, specifically, diabetes, Alzheimer's disease, arteriosclerosis, skin aging, etc. An object is to provide a Maillard reaction inhibitor that is highly stable and inexpensive.

As a result of intensive studies in view of the above situation, the present inventors have found that mucopolysaccharide is excellent in the effect of suppressing the Maillard reaction. Furthermore, as a result of comparing the Maillard reaction inhibitory action of various molecular weights and modified hyaluronic acid, it was confirmed that hyaluronic acid having a molecular weight of 5 to 110,000 shows a particularly high Maillard reaction inhibitory action. Furthermore, it was confirmed that these were excellent in safety and storage stability, and the present invention was completed.
That is, the present invention provides (1) a Maillard reaction inhibitor containing mucopolysaccharide, or a hydrolyzate thereof, or a derivative thereof, or a salt thereof as an active ingredient. (2) hyaluronic acid or chondroitin sulfate, a decomposition product thereof, or Maillard reaction inhibitor containing derivative or salt thereof as active ingredient (3) Maillard reaction inhibitor containing hyaluronic acid having a weight average molecular weight of 50,000 to 110,000 or a salt thereof as active ingredient Is.

According to the present invention, a novel Maillard reaction inhibitor can be provided. The Maillard reaction inhibitor of the present invention is a polysaccharide derived from a living body, and has high storage stability and safety, and is inexpensive. Therefore, it can be used in various fields, and can be suitably used particularly in the fields of cosmetics, pharmaceuticals, quasi drugs, foods (including beverages), and the like.

Comparison of Maillard reaction inhibition effect in water-soluble polymers Comparison of Maillard reaction inhibitory effect of mucopolysaccharide Comparison of Maillard reaction inhibitory effect of sodium hyaluronate

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

The Maillard reaction targeted by the present invention means the Maillard reaction in a broad sense among those defined in the field, and amino acids of peptides, amino acids, peptides, proteins, ketones, aldehydes, and reducing sugars react in multiple stages. All the steps until generation of AGEs are included. Also included is a reaction (caramelization reaction) in which sugars are heated to react with each other to turn brown and become a reducing polymer compound. Moreover, the Maillard reaction inhibitor of this invention should just exhibit the inhibitory (suppression) effect with respect to all the processes, if it exhibits the inhibitory (suppression) effect with respect to at least 1 process of a Maillard reaction. There is no.

The mucopolysaccharide of the present invention is a collective term for polysaccharides including amino sugars, and is not particularly limited, but a typical example is glycosaminoglucan. Glycosaminoglucan is composed of repeating disaccharides, and one of the disaccharides is composed of either D-glucosamine or D-galactosamine. Examples of glycosaminoglucan include hyaluronic acid, chondroitin sulfate, chondroitin, ketalan sulfate, heparin, heparin sulfate and dermatan sulfate. The mucopolysaccharide of the present invention may have a carboxyl group structure in addition to the sulfate ester. Further, the mucopolysaccharide of the present invention can be used without particular limitation as long as it is usually used in the field of pharmaceuticals, quasi drugs, cosmetics or foods and drinks, Two or more kinds may be used in any combination.

The method and origin for obtaining the mucopolysaccharide of the present invention are not particularly limited, but examples include fish such as sea bream and sea bream, other aquatic animals such as whales and sea cucumbers, and land animals such as cows, pigs, chickens and horses. Bone, cartilage, skin, scale, etc. (hereinafter referred to as mucopolysaccharide-containing tissue) can be obtained in a state containing a large amount of protein or the like by alkali treatment, enzyme treatment or the like. Further, in order to remove the protein and the like from the mucopolysaccharide containing the protein and obtain a highly pure mucopolysaccharide, a treatment such as ultrafiltration may be performed. Also, mucopolysaccharides can be obtained by synthesis, semi-synthesis, fermentation, or the like.

The degradation product of the present invention is a product obtained by reducing the molecular weight of mucopolysaccharide. Examples of the decomposition method include decomposition by heating, chemical hydrolysis by acid or base, hydrolysis by various enzymes, and the like. it can.

The derivatives of the present invention are those in which various substituents are introduced into mucopolysaccharides, but those in which substituents are introduced into at least one carboxy group or hydroxy group of mucopolysaccharides or those in which salts are formed. preferable. For example, an ester of mucopolysaccharide in which an acetyl group or a benzyl group is introduced as a substituent, or a cross-linked product in which a formyl group is introduced.

The salt of the present invention is an alkali metal salt such as sodium or potassium, an alkaline earth metal salt such as magnesium or calcium, an alkanolamine salt such as ammonium salt or monoethanolamine, or a mixture thereof. . Alkali metal salts such as sodium salts are preferred.

The hyaluronic acid of the present invention is a high-molecular polysaccharide formed by alternately bonding the 3-position of β-D-N-acetylglucosamine and the 4-position of β-D-glucuronic acid. Although the production method and origin of hyaluronic acid are not particularly limited, for example, the hyaluronic acid can be obtained by extraction from animal tissues such as chicken crowns or microbial fermentation.

The weight average molecular weight of the hyaluronic acid of the present invention is not particularly limited, and may be one obtained by decomposing hyaluronic acid to lower the molecular weight, preferably 5000 to 300,000, particularly preferably 50,000 to 110,000. The weight average molecular weight of hyaluronic acid used in the present invention is determined from the weight average molecular weight and retention time of the standard product using hyaluronic acid with a known weight average molecular weight as a standard product, subjecting the sample and standard product to high performance liquid chromatography. A standard curve can be obtained, and the weight average molecular weight corresponding to the retention time of the sample solution can be obtained. The weight average molecular weight of the standard product was determined by measuring the intrinsic viscosity according to the thirteenth revised Japanese Pharmacopoeia: General Test Method, Item 36 Viscosity Measurement Method, and using the formula of Laurent et al. (Biochim. Biophys. Acta, 42, 476 ( 1960) The hyaluronic acid of the present invention is not particularly limited and may be appropriately selected depending on the intended purpose, for example, hyaluronic acid FCH-201S (weight average molecular weight 1.8 million to 2,200,000), Examples thereof include FCH-121S (weight average molecular weight 1 million to 1.4 million), FCH-SU-S (weight average molecular weight 50,000 to 110,000) (manufactured by Food Chemifa), BIO-SODIUM HYALURONATE (manufactured by Bioland).

The hyaluronic acid derivative of the present invention is one in which a substituent is introduced into at least one carboxy group or hydroxy group of hyaluronic acid, or a salt is formed. As the substituent, an ester such as an acetyl group or a benzyl group, or a group capable of forming a crosslink such as a formyl group is preferable. For example, a substance in which one or more carboxyl groups in hyaluronic acid are esterified (for example, benzyl esterified hyaluronic acid (trade name Hyaff (registered trademark), Fidia Advanced Biopolymers)), hyaluronic acid crosslinked with formaldehyde, Examples thereof include a polymerized substance (for example, trade name Synvisc (registered trademark), Biomatrix)), acetylated hyaluronic acid in which one or more hydroxy groups in hyaluronic acid are acetylated, and the like. Of these, acetylated hyaluronic acid is particularly preferred.

The sodium chondroitin sulfate of the present invention is a sodium salt in which sulfuric acid is bound to a sugar chain in which two sugars of β-DN-acetylgalactosamine and β-D-glucuronic acid are repeated.

Furthermore, the Maillard reaction inhibitor of the present invention is applied to lotion, emulsion, cream, ointment, lotion, oil, pack, facial cleanser, skin cleanser, shampoo, rinse, hair treatment, hair cream, pomade, hair spray, hair styling. , Perm, hair dye, hair dye, hair restorer, foundation, white powder, white, lipstick, blusher, eye shadow, eyeliner, mascara, eyebrow, beauty nail, perfume, bath preparation, toothpaste, in mouth A cosmetic composition can be constituted by using it for a refreshing agent / an gargle, a liquid odor / anti-odor preventing agent, sanitary goods, sanitary cotton, wet tissue, and the like. In addition, nutritional supplements in the form of capsules, liquids, granules, tablets, processed fishery products such as kamaboko and chikuwa, livestock products such as sausages and ham, Western confectionery, Japanese confectionery, raw noodles, Chinese noodles, boiled Noodles such as noodles, buckwheat, sauces, soy sauce, sauce, sugar, honey, powdered candy, syrups such as syrups, spices such as curry powder, mustard powder, pepper powder, jam, marmalade, chocolate spread, pickles, soy sauce , Sprinkles, processed vegetables and fruits such as canned and bottled vegetables and fruits, dairy products such as cheese, butter and yogurt, processed products of cereals, fermented food, miso soup, soup, fruit juice, vegetable juice, whey The use for general foods and beverages such as beverages, soft drinks, and alcoholic beverages is also possible as in the case of the cosmetic composition. The content of each of the above-mentioned components in the product varies slightly depending on the type, quality, and expected action of the Maillard reaction inhibitor and cosmetic composition or food, but is not particularly limited. Then, it is 0.00001 to 1% by mass (hereinafter simply referred to as “%”), and more preferably 0.0001 to 0.05%. If it exists in this range, this active ingredient can be mix | blended stably and a high effect can be exhibited.

In addition, the above-mentioned preparations are components that are usually used in preparations such as cosmetics, quasi-drugs, and external medicines as long as they do not impair the effects of the present invention, that is, water (purified water, hot springs). Water, deep water, etc.), alcohol, oil agent, surfactant, metal soap, gelling agent, powder, alcohols, water-soluble polymer, film-forming agent, resin, UV protection agent, inclusion compound, antibacterial agent, Perfume, deodorant, salt, pH adjuster, refresher, animal / microbe-derived extract, plant extract, blood circulation promoter, astringent, antiseborrheic agent, whitening agent, anti-inflammatory agent, active oxygen scavenger, Cell activators, humectants, chelating agents, keratolytic agents, enzymes, hormones, vitamins and the like can be added.

  Hereinafter, the present invention will be described in more detail with reference to Examples such as test examples, skin external preparations and cosmetic formulation examples, but the present invention is not limited thereto.

About various mucopolysaccharides, the Maillard reaction inhibitory effect was measured and evaluated by the following method.
(Examples 1 and 2 and Comparative Examples 1 to 7)
(Sample preparation)
Samples are mucopolysaccharides such as sodium hyaluronate (Food Chemifa Co., Ltd.) and chondroitin sulfate Na (manufactured by Maruha Co., Ltd.), and comparative examples other than mucopolysaccharides such as sclerotium gum, locust bean gum, xanthan gum, and polysaccharides. Common water-soluble polymers such as carbomer, sodium alginate, hydroxyethyl cellulose, and hydroxypropyl cellulose were used. Na hyaluronic acid having a weight average molecular weight of 1,800,000 to 2,200,000 was used, and each sample was dissolved in purified water so that the final concentration of the dry solid was 0.03%.

(Measurement of Maillard reaction inhibition effect)
Poly-L-lysine hydride (PLL) and glucose are dissolved in PBS (−) at 7.2 mg / ml and 180 mg / ml, respectively, and then mixed at 1: 1 (volume ratio). The sample solution was added to and mixed with this mixed solution at a ratio of 100: 1 (volume ratio), half was left at 5 ° C., and the other half was left at 60 ° C. Only purified water was added to the control. After 2 to 3 days, the fluorescence intensity (Ex 360 nm, Em 450 nm) of the reaction solution was measured. The Maillard reaction proceeds at 60 ° C, and the Maillard reaction does not proceed at 5 ° C. Therefore, the amount of AGEs generated by the Maillard reaction in each sample is a value obtained by subtracting the fluorescence intensity of the reaction solution left at 5 ° C. from the fluorescence intensity of the reaction solution left at 60 ° C. In this test, the reaction solution to which only purified water was added was used as a control, and the Maillard reaction inhibition rate (%) of each sample was calculated by the following formula.

From the results shown in FIG. 1, polysaccharides other than mucopolysaccharides and general water-soluble polymers have no Maillard reaction inhibitory effect, whereas mucopolysaccharides, such as sodium hyaluronate and chondroitin sulfate Na, have Maillard reaction inhibitory effect. I understand that.

(Examples 3 to 6)
It was verified that mucopolysaccharides other than sodium hyaluronate and chondroitin sulfate Na also have a Maillard reaction inhibitory effect. Samples include sodium hyaluronate (Food Chemifa, molecular weight 1.8 to 2,200,000), squid oviform-derived mucopolysaccharide (manufactured by Koken), shark cartilage-derived mucopolysaccharide (ATRIUM BIOTECHNOLOGIES), chondroitin sulfate Na (Maruha Used). Sample preparation and measurement of the Maillard reaction inhibition effect were performed as described above. The results are shown in FIG.

From the results of FIG. 2, it was found that mucopolysaccharides other than hyaluronic acid Na and chondroitin sulfate Na also have a Maillard reaction inhibitory effect. Furthermore, it can be understood that among mucopolysaccharides, hyaluronic acid Na and chondroitin sulfate Na have a superior Maillard reaction inhibitory effect.

(Examples 7 to 11)
Next, it was verified whether there was a difference in the Maillard reaction inhibitory effect depending on the molecular weight of Na hyaluronate and the presence or absence of substituents. Samples have a weight average molecular weight of 1.8 to 2,200,000, 1,000,000 to 1,400,000, 5 to 110,000, hyaluronic acid Na (Food Chemifa), acetylated hyaluronic acid Na (molecular weight around 100,000, Shiseido), hydrolysis Hyaluronic acid Na (molecular weight of 10,000 or less, manufactured by Kewpie) was used. Sample preparation and measurement of the Maillard reaction inhibition effect were performed in the same manner as described above. The results are shown in FIG.

From the results shown in FIG. 3, it was found that Na hyaluronate has a Maillard reaction inhibitory effect regardless of the molecular weight, and hydrolyzed Na and acetylated hyaluronate Na also has a Maillard reaction inhibitory effect. Furthermore, among these, it was confirmed that sodium hyaluronate having a molecular weight of 50,000 to 100,000 is most excellent in the Maillard reaction inhibition effect.

Example 12: Ointment (component)
(%)
1. Stearic acid 18
2. Cetanol 4
3. Triethanolamine
2
4). Glycerin 5
5). Dipotassium glycyrrhizinate (Note 1) 0.5
6). Hyaluronic acid Na (molecular weight 50,000 to 110,000) 0.03
7). Dl-α-Tocopherol acetate (Note 2)
0.2
8). Methyl paraoxybenzoate
0.1
9. purified water
Remaining amount (Note 1) Wako Pure Chemical Industries, Ltd. (Note 2) Eisai

(Production method)
A. A portion of components 3, 4 and 9 are heat mixed and maintained at 75 ° C.
B. Ingredients 1, 2, 7, and 8 are heat mixed and maintained at 75 ° C.
C. B was gradually added to A, components 5 and 6 dissolved in the remainder of component 9 were added while cooling, and the mixture was stirred to obtain an ointment.

Example 13: Lotion agent (ingredient) (%)
1. Glycerin 5
2.1,3-Butylene glycol 6.5
3. Polyoxyethylene monolaurate (20E.O.) sorbitan 1.2
4). Ethyl alcohol 8
5). Methyl paraoxybenzoate 0.2
6). Chondroitin sulfate Na 0.03
7). Purified water remaining

(Production method)
A. Components 3 to 5 are mixed and dissolved.
B. Components 1, 2, 6, and 7 are mixed and dissolved.
C. A and B were mixed and homogenized to obtain a lotion preparation.

Example 14: Latex (oil-in-water type)
(component)
(%)
1. Polyoxyethylene (20E.O.) sorbitan monostearate
1
2. Polyoxyethylene trioleate (20E.O.) sorbitan
0.5
3. Glyceryl monostearate
1
4). stearic acid
0.5
5). Behenyl alcohol
0.5
6). Squalane 8
7). Carboxyvinyl polymer 0.1
8). Methyl paraoxybenzoate 0.1
9. Sodium hydroxide
0.05
10. Hyaluronic acid Na (molecular weight 1 million to 1.4 million) 0.03
11. Ethyl alcohol 5.0
12 purified water
Remaining amount13. Fragrance 0.05

(Production method)
A: Components 7 to 10 are added to component 12 and mixed uniformly at 70 ° C. B: Components 1 to 6 are mixed uniformly at 70 ° C.
C: B is added to A to emulsify, and cooled to room temperature.
D: Components 11 and 13 were added and mixed uniformly to obtain an emulsion.

Example 15: Liquid foundation (oil-in-water cream)
(Ingredient) (%)
1. Acrylic acid / alkyl methacrylate copolymer (Note 3) 0.5
2. Triethanolamine 1.5
3. Purified water remaining amount 4. Glycerin 5
5). Ethyl paraoxybenzoate 0.1
6.1,3-Butylene glycol 5
7). Hydrogenated soybean phospholipid 0.5
8). Titanium oxide 5
9. Bengala 0.1
10. Yellow iron oxide 1
11. Black iron oxide 0.05
12 stearic acid
0.9
13. Glycerol monostearate 0.3
14 Cetostearyl alcohol
0.4
15. Monooleic acid polyoxyethylene (20E.O.) sorbitan 0.2
16. Polyoxyethylene trioleate (20E.O.) sorbitan 0.2
17. 2-methoxyhexyl paramethoxycinnamate 5
18. Hydrolyzed sodium hyaluronate (molecular weight: 5000 to 10,000) 0.03
19. Perfume 0.02
(Note 3) Pemulen TR-2 (manufactured by NOVEON)

(Production method)
A: Components 6 to 11 are dispersed.
B: Components 12 to 17 are added to A and mixed uniformly at 70 ° C.
C: Components 1 to 5 are mixed uniformly at 70 ° C.
D: B is added to C to emulsify, and cooled to room temperature.
E: Components 18 and 19 were added to D and mixed uniformly to obtain an oil-in-water cream liquid foundation.

The various cosmetics or skin external preparations prepared above are excellent in Maillard reaction inhibitory action, and by applying this to the skin, collagen cross-linking that causes hardening of the skin, formation of wrinkles, loss of elasticity and gloss Moreover, coloring which causes dullness of the skin was suppressed, and an excellent skin aging preventing effect and skin beautifying effect were exhibited. Moreover, there was no side effect and it was excellent in storage stability.

Hereinafter, the compounding example in the case of mix | blending the Maillard reaction inhibitor of this invention with a foodstuff is shown. The present invention is not limited to the following formulation examples.

Example 16: Tablet (component) (%)
1. Lactose 24.0
2. Crystalline cellulose 20.0
3. Corn starch 15.0
4). Hyaluronic acid Na (molecular weight 50,000 to 110,000) 1.0
5). Dextrin remaining amount 6. Glycerin fatty acid ester 5.0
7). Silicon dioxide 1.0

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

Example 17: Soft drink
(Ingredient) (%)
1. Fructose dextrose liquid sugar 30.0
2. emulsifier
0.5
3. Hyaluronic acid Na (molecular weight 50,000 to 110,000) 0.1
4). Fragrance
Appropriate amount
5). Purified water remaining

A. Components 1 to 5 were mixed uniformly, and a soft drink was obtained according to a conventional method.

The tablets and soft drinks prepared above were excellent in Maillard reaction inhibitory action, and showed excellent skin aging prevention effects and skin beautifying effects by internal use. Moreover, there was no side effect and it was excellent in storage stability.

Claims (2)

A suppressant of coloring that causes hyaluronic acid having a weight average molecular weight of 50,000 to 110,000 or a salt thereof to be added to cosmetics as an active ingredient and causing dullness of the skin due to Maillard reaction inhibition. A Maillard reaction inhibitor in skin , containing hyaluronic acid having a weight average molecular weight of 50,000 to 110,000 or a salt thereof as an active ingredient for addition to cosmetics .