JP2000264811A - Inhibitor of maillard reaction - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject inhibitor capable of expecting prevention of aging of skin by inhibiting the production of a proteinic modified substance caused by the Maillard reaction in the skin, stable in a formulation and useful for medicines, cosmetics, etc., by including a cultured product of a lactic acid bacterium. SOLUTION: This inhibitor is obtained by including a cultured product of a lactic acid bacterium obtained by culturing the lactic acid bacterium, e.g. Streptococcus thermophilus using a culture medium containing a nitrogen source or a carbon source usually used for culturing the lactic acid bacterium such as skimmilk, peptone or gluocose and further an additive such as vitamins, e.g. nicotinic acid or nicotinamide, a yeast extract or a buffer solution added thereto and, as necessary, removing solid substances by centrifugation, filtration, etc. When formulating the inhibitor in a skin preparation for external use, the inhibitor is preferably formulated in an amount of 0.01-20% based on the total amount of the skin preparation for external use.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a Maillard reaction inhibitor which is expected to prevent aging of the skin by suppressing the production of proteinaceous denatured substances caused by the Maillard reaction in the skin, and which is stable in preparations.

[0002]

2. Description of the Related Art In an environment where proteins and carbohydrates coexist, as in living organisms, proteins may be denatured by the Maillard reaction. Among the proteins present in the skin, collagen, in particular, has a slow metabolic rate and is susceptible to denaturation by the Maillard reaction, which is known to cause aging cross-linking of collagen. It is considered that this aging cross-linking of collagen further delays collagen metabolism and causes a vicious cycle, thereby causing aging of the skin itself, such as wrinkles, lack of tension, and lumps. (Daisaburo Fujimoto: Modern Science, December, p. 36, 1990). It has also been recently discussed that the accumulation of reaction products due to the Maillard reaction is related to dullness of the skin. In this sense, it can be said that suppressing the production of proteinaceous denatured substances caused by the Maillard reaction is effective for preventing skin aging. Although urea, guanidine, proanthocyanidin and the like have already been proposed as inhibitors of the Maillard reaction, they have problems in stability and have not been practically satisfactory. It is not known that a bacterial culture suppresses the Maillard reaction.

[0003]

SUMMARY OF THE INVENTION In view of the above circumstances, the present inventors have enthusiastically pursued a search aiming at preventing the aging of the skin by suppressing the production of proteinaceous denatured substances caused by the Maillard reaction in the skin. As a result of the study, they found that a lactic acid bacterium culture had an inhibitory activity on the Maillard reaction, which led to the completion of the present invention. The purpose of the present invention was to provide a Maillard reaction inhibitor that was stable in the formulation. To be.

[0004]

The above object is achieved by a Maillard reaction inhibitor characterized by containing a culture of lactic acid bacteria.

[0005]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, embodiments of the present invention will be described in detail.

A lactic acid bacterium culture, which is an active ingredient of the Maillard reaction inhibitor of the present invention, is, for example, Streptococcus thermoph
ilus, Lactobacillus bulugaricus, Lactococcus lacti
Add lactic acid bacteria such as s, Bifidobacterium bifidum etc. to skim milk, peptone, glucose etc., nitrogen sources and carbon sources usually used for culturing lactic acid bacteria, or vitamins such as nicotinic acid or nicotinamide, yeast extract, and additives such as buffer. It can be obtained by culturing using a cultured medium, and if necessary, one from which solids have been removed by centrifugation, filtration or the like, or one that has been sterilized by heating or the like can also be used. In addition, after adding a polyhydric alcohol as a preservative to the culture, it can be used as a preservative.

The form of use of the Maillard reaction inhibitor of the present invention includes an external preparation for skin, such as ointment, cream,
Lotions, emulsions, gels, and the like can be used, and can be applied to pharmaceuticals, quasi-drugs, cosmetics, and the like. The base of the external preparation may be a known external base and is not particularly limited.

[0008] The amount of the Maillard reaction inhibitor of the present invention to be added to the external preparation for skin is 0% based on the total amount of the composition, taking into account the concentration of the Maillard reaction that sufficiently suppresses the Maillard reaction and the concentration at which the color and odor of the culture are hardly produced. It is preferably set to 0.01% to 20%.

The external preparations for promoting percutaneous absorption of the present invention include, in addition to the above, coloring pigments such as tar dyes and iron oxide, preservatives such as paraben and phenoxyethanol, dimethylpolysiloxane, methylphenylpolysiloxane, and cyclic silicone. Silicon oil such as paraffin, hydrocarbons such as petrolatum, olive squalane, rice squalane, rice germ oil,
Vegetable oils such as jojoba oil, castor oil, safflower oil, olive oil, macadamia nut oil, sunflower oil, waxes such as beeswax, mocro, carnauba wax, octyl dodecyl myristate, cetyl palmitate, isostearyl isostearate, and esters such as isopropyl myristate oil,
Lower alcohols such as ethanol, cetanol, behenyl alcohol, stearyl alcohol, higher alcohols such as long-chain branched aliphatic alcohols, cholesterol, phytosterols, branched fatty acid cholesterol esters,
Sterols and derivatives such as macadamia nut fatty acid phytosteryl ester, processing oils such as hardened oil, stearic acid, myristic acid, isostearic acid, oleic acid,
Higher fatty acids such as iso-type long-chain fatty acids and anteiso-type long-chain fatty acids, terpenes such as limonene and hydrogenated bisabolol, glyceryl tricapryl / caprate, glyceryl 2-ethylhexanoate, glyceryl triiso-type long-chain fatty acid and glyceryl tripalmitate Anionic surfactants such as triglyceride, sodium cetyl sulfate, N-stearoyl-L-glutamate, polyoxyethylene alkyl ether, polyoxyethylene fatty acid ester, polyoxyethylene polyhydric alcohol fatty acid ester, polyoxyethylene cured castor Nonionic surfactants such as oil, polyhydric alcohol fatty acid ester, polyglycerin fatty acid ester, modified silicone, sucrose ester,
Cationic surfactants such as tetraalkylammonium salts, amphoteric surfactants such as betaine type, sulfobetaine type and sulfoamino acid type, natural surfactants such as lecithin, lysophosphatidylcholine, ceramide, cerebroside, and titanium oxide , Zinc oxide, etc., antioxidants such as dibutylhydroxytoluene, inorganic salts such as sodium chloride, magnesium chloride, sodium sulfate, potassium nitrate, sodium sulfate, sodium metasilicate, calcium chloride, sodium citrate, potassium acetate, succinic acid Organic acids such as sodium, sodium aspartate, sodium lactate, dichloroacetic acid, mevalonic acid, glycyrrhizic acid and salts thereof, ethanolamine hydrochloride, ammonium nitrate, arginine hydrochloride, diisopropylamine salt, urea, decarboxyca Organic amines such as nosin and salts thereof, chelating agents such as edetic acid, xanthan gum, carboxyvinyl polymer, carrageenan, pectin, alkyl-modified carboxyvinyl polymer, thickeners such as agar, potassium hydroxide, diisopropanolamine, triethanol Neutralizing agents such as amines, hyaluronic acid, collagen, biopolymers such as chondroitin sulfate, N-acetylglucosamine and its oligomers, yeast, culture products such as mushrooms, chamomile, aloe, peach, carrot, horsetail,
Plant extracts such as mulberry, peach leaf, sage, loquat leaf, cucumber, vegetation, hibiscus, turmeric, rosemary, pecan nut, licorice, fire spike, camellia seed, tea seed, etc., placenta extract, hydroxymethoxybenzophenone UV absorbers such as sulfonates, polyhydric alcohols such as dipropylene glycol, 1,3-butylene glycol, glycerin, propylene glycol, sorbitol, malbitol, diglycerin, raffinose, serine, threonine, γ-aminobutyric acid, β- Hydroxy-γ
-Amino acids such as aminobutyric acid, N-methyl-L-serine,
Amino acid derivatives such as sarcosine, vitamins such as ascorbic acid, niacin, biotin, and tocopherol, and vitamin derivatives such as ascorbic acid sulfate, ascorbic acid phosphate, and tocopherol nicotinate, but are not limited thereto. Absent.

[0010]

The present invention will be described below in more detail with reference to Examples, Test Examples and Formulation Examples. Hereinafter, each method of the Maillard reaction inhibition test and the formulation stability test using the Maillard reaction inhibitor of the present invention will be described.

Method of Test for Maillard Reaction Inhibition BSA and glucose were dissolved in 50 mM phosphate buffer (pH 7.4) to a concentration of 800 μg / ml and 200 mM, respectively, and a Maillard reaction inhibitor was added.
Incubate at 0 ° C. for 30 hours. Trichloroacetic acid was added to precipitate the protein, and the supernatant was removed.
To dissolve and measure the fluorescence intensity (ex 360n
m, em 460 nm). The amount of the Maillard reaction product is measured, and is defined as V. On the other hand, the same reaction was carried out without adding the Maillard reaction inhibitor, the amount of the generated Maillard reaction product was measured, and this was used as VM to calculate the inhibition rate by the following formula. 100− (V ÷ VM) × 100 = inhibition rate (%)

Method of Test for Stability of Formulation The Maillard reaction inhibitor of the present invention and one of each of urea were used.
% Aqueous solution and 10% aqueous solution, and
It was left for 0 hour to check for discoloration and odor.

Example 1 (Lactic acid bacteria culture) Skim milk 10 g, glucose 1 g, nicotinic acid 0.1 g
Purified water was added to 1 g to make up to 100 ml.
For 10 minutes to prepare a medium (Skim milk was Di
fco, glucose and nicotinic acid were from Kanto Chemical Co.). This was pre-cultured in the same medium at 37 ° C. for 24 hours.
Lactobacillus bulgaricus (ATCC 11842) was inoculated at 1%. After culturing at 37 ° C. for 24 hours, the cells were removed by centrifugation, and the culture supernatant was treated at 80 ° C. for 30 minutes to obtain a lactic acid bacteria culture. 40 g of the lactic acid bacteria culture and 10 g of 1,3-butylene glycol were mixed. After that, the mixture was starched to obtain a Maillard reaction inhibitor of the present invention (Example 1). Using the Maillard reaction inhibitor thus selected as a sample, the above Maillard reaction inhibition test and formulation stability test were performed. Table 1 shows the results. As is clear from Table 1, the Maillard reaction inhibitor of the present invention (Example 1) exhibited a Maillard reaction inhibitory effect. In the preparation stability test, unusual odor was observed in the 1% and 10% aqueous solutions of urea, but no odor was observed in the 1% and 10% aqueous solutions of the Maillard reaction inhibitor of Example 1. It was found that the Maillard reaction inhibitor of Example 1 was stable.

[0014]

Hereinafter, application examples of the Maillard reaction inhibitor of the present invention will be described. Formulation Examples 1 to 3 (Skin Cream) The Maillard reaction inhibitor of Example 1 was blended with the composition shown in Table 2, and skin creams were prepared by the following preparation method (Application Examples 4 to 6). (1) Composition

[0016]

(2) Preparation Method The components (A) and (B) were each heated and dissolved at 80 ° C., mixed, cooled with stirring, and cooled to 30 ° C. to prepare a skin cream.

Formulation Examples 4 to 6 (Lotion) The Maillard reaction inhibitor of Example 1 was blended with the composition shown in Table 3, and lotions were prepared by the following preparation method (Application Examples 4 to 6). (1) Composition

[0019]

(2) Preparation method Each component was mixed and dissolved, and stirred to prepare a lotion.

Formulation Examples 7 to 9 (Gel) The Maillard reaction inhibitor of Example 1 was blended with the composition shown in Table 4, and a gel was prepared by the following preparation method (Formulation Example 7).
9). (1) Composition

[0022] * 1: Toshiba Silicone Tospar * 2: Kibun Foot Chemicals Bioceramito

(2) Preparation method The components (A) and (B) were each heated and dissolved at 60 ° C, then mixed, cooled with stirring, and cooled to 30 ° C to prepare a gel. Formulation Examples 10 to 12 (Lipophilic Cream) The Maillard reaction inhibitor of Example 1 was blended with the composition shown in Table 5, and lipophilic cream was prepared by the following preparation method (Application Examples 10 to 12). (1) Composition

[0024] Note 3: ABIL EM90 manufactured by Koort Schmidt Co., Ltd. Note 4: Silicon BY22-008 manufactured by Toray Tow Corning Co., Ltd. Note 5: YOFCO CLE-NH manufactured by Nippon Seika Co., Ltd.

(2) Preparation Method The components (A) and (B) were each dissolved by heating to 60 ° C., mixed, cooled with stirring, and cooled to 30 ° C. to prepare a lipophilic cream.

Formulation Examples 13 to 15 (Sunscreen) The Maillard reaction inhibitor of Example 1 was blended with the composition shown in Table 6, and sunscreens were prepared by the following preparation method (Formulation Examples 13 to 15). (1) Composition

[0027]

(2) Preparation Method The components (A) and (B) were each heated and dissolved at 80 ° C., mixed, cooled with stirring, and cooled to 30 ° C. to prepare a sunscreen.

[0029]

As described above, it is apparent that the present invention provides a Maillard reaction inhibitor which is stable in the preparation.

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[Procedure amendment]

[Submission date] May 7, 1999 (1999.5.7)

[Procedure amendment 1]

[Document name to be amended] Statement

[Correction target item name] 0009

[Correction method] Change

[Correction contents]

The Maillard reaction inhibitor of the present invention includes, in addition to the above, tar pigments, coloring pigments such as iron oxide, preservatives such as paraben and phenoxyethanol, dimethylpolysiloxane, methylphenylpolysiloxane, and cyclic silicon. Silicone oil, paraffin, hydrocarbons such as petrolatum, olive squalane, rice squalane, rice germ oil,
Vegetable oils such as jojoba oil, castor oil, safflower oil, olive oil, macadamia nut oil, sunflower oil, waxes such as beeswax, mocro, carnauba wax, octyl dodecyl myristate, cetyl palmitate, isostearyl isostearate, and esters such as isopropyl myristate oil,
Lower alcohols such as ethanol, cetanol, behenyl alcohol, stearyl alcohol, higher alcohols such as long-chain branched aliphatic alcohols, cholesterol, phytosterols, branched fatty acid cholesterol esters,
Sterols and derivatives such as macadamia nut fatty acid phytosteryl ester, processing oils such as hardened oil, stearic acid, myristic acid, isostearic acid, oleic acid,
Higher fatty acids such as iso-type long-chain fatty acids and anteiso-type long-chain fatty acids, terpenes such as limonene and hydrogenated bisabolol, glyceryl tricapryl / caprate, glyceryl 2-ethylhexanoate, glyceryl triiso-type long-chain fatty acid and glyceryl tripalmitate Anionic surfactants such as triglyceride, sodium cetyl sulfate, N-stearoyl-L-glutamate, polyoxyethylene alkyl ether, polyoxyethylene fatty acid ester, polyoxyethylene polyhydric alcohol fatty acid ester, polyoxyethylene cured castor Nonionic surfactants such as oil, polyhydric alcohol fatty acid ester, polyglycerin fatty acid ester, modified silicone, sucrose ester,
Cationic surfactants such as tetraalkylammonium salts, amphoteric surfactants such as betaine type, sulfobetaine type and sulfoamino acid type, natural surfactants such as lecithin, lysophosphatidylcholine, ceramide and cerebroside, titanium oxide , Zinc oxide, etc., antioxidants such as dibutylhydroxytoluene, inorganic salts such as sodium chloride, magnesium chloride, sodium sulfate, potassium nitrate, sodium sulfate, sodium metasilicate, calcium chloride, sodium citrate, potassium acetate, succinic acid Organic acids such as sodium, sodium aspartate, sodium lactate, dichloroacetic acid, mevalonic acid, glycyrrhizic acid and salts thereof, ethanolamine hydrochloride, ammonium nitrate, arginine hydrochloride, diisopropylamine salt, urea, decarboxyca Organic amines such as nosin and salts thereof, chelating agents such as edetic acid, xanthan gum, carboxyvinyl polymer, carrageenan, pectin, alkyl-modified carboxyvinyl polymer, thickeners such as agar, potassium hydroxide, diisopropanolamine, triethanol Neutralizing agents such as amines, hyaluronic acid, collagen, biopolymers such as chondroitin sulfate, N-acetylglucosamine and its oligomers, yeast, culture products such as mushrooms, chamomile, aloe, peach, carrot, horsetail,
Mulberry, peach leaf, sage, loquat leaf, cucumber, vegetative extract such as eucalyptus, hibiscus, turmeric, rosemary, pecan nut, licorice, fire spike, camellia seed, tea seed, etc., placenta extract, hydroxymethoxybenzophenone UV absorbers such as sulfonates, polyhydric alcohols such as dipropylene glycol, 1,3-butylene glycol, glycerin, propylene glycol, sorbitol, malbitol, diglycerin, raffinose, serine, threonine, γ-aminobutyric acid, β- Hydroxy-γ
-Amino acids such as aminobutyric acid, N-methyl-L-serine,
Amino acid derivatives such as sarcosine, vitamins such as ascorbic acid, niacin, biotin, and tocopherol and vitamin derivatives such as ascorbic acid sulfate, ascorbic acid phosphate, and tocopherol nicotinate include, but are not limited thereto. Absent.

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Claims (1)

[Claims] 1. A Maillard reaction inhibitor comprising a lactic acid bacteria culture.