JP6117607B2 - Maillard reaction product concentration reducing agent - Google Patents

Description

  The present invention relates to a Maillard reaction product concentration reducing agent and a Maillard reaction inhibitor.

  Maintaining the body in a young and healthy state is a hope for many people, and there are many cosmetics and foods that promote health and beauty maintenance.

  Deterioration of the function of a living body progresses due to various factors, and it is known that one of the causes is a Maillard reaction in which a protein and a sugar are non-enzymatically bound in a living body. The initial product of this Maillard reaction is a protein-sugar conjugate called an Amadori compound, and advanced glycation end products (AGEs) are formed by further polymerization of the Amadori compound.

  Protein glycation by this Maillard reaction leads to arteriosclerosis and diabetic complications in the body, reduces elasticity such as collagen and elastin in the skin, and causes coloration that causes skin dullness. Furthermore, since the Maillard reaction can occur due to exposure to ultraviolet rays or stress, it is considered that suppressing the Maillard reaction is very important for maintaining health and beauty regardless of age.

  For this reason, the search of the material which suppresses Maillard reaction is calculated | required, and aminoguanidine is known as a Maillard reaction inhibitor by the present. However, this has the disadvantage of having a safety problem.

  In addition, Maillard reaction-suppressing external preparations containing flavans as active ingredients (Patent Document 1), Maillard reaction inhibitors containing hydrolyzable tannin and its degradation products as active ingredients (Patent Document 2), rutin, quercetin and the like as active ingredients There are known methods for suppressing the production of terminal glycation products of Maillard reaction (Patent Document 3), etc., all of which have problems in effectiveness and usability, and all are sufficiently satisfactory It's not something to go about.

  On the other hand, development of the technique which decomposes | disassembles the Maillard reaction product produced | generated by the Maillard reaction is also calculated | required. In other words, as described above, the Maillard reaction product reduces the elasticity of skin collagen, elastin, and the like. Therefore, it is possible to return the skin to its original state by decomposing and removing the product. It is to become.

  However, the present condition is that the compound which has a strong decomposition activity with respect to a Maillard reaction product has not been found until now.

JP 7-324025 A JP 9-40519 A JP 2009-96731 A JP2002-179581

  Therefore, the present invention finds a substance that acts on the Maillard reaction product to reduce its concentration and a substance that can effectively suppress the Maillard reaction, and uses this to maintain skin flexibility, improve dullness, etc. It is an object of the present invention to provide a Maillard reaction product concentration-reducing agent and a Maillard reaction inhibitor useful for the above.

  The present inventors have extensively searched for the Maillard reaction possessed by a highly safe natural substance or an action on its product, and an extract of herbal medicine called Mitsuchoka acts on the Maillard reaction product, The present invention has been completed by finding that it has a decomposing activity for reducing the concentration and has an effect of effectively suppressing the Maillard reaction.

  That is, the present invention is a Maillard reaction product concentration reducing agent containing an extract of water clove as an active ingredient.

  Moreover, this invention is a Maillard reaction inhibitor which uses the extract of water clove incense as an active ingredient.

  Still further, the present invention is an extract of water clove incense with 1,3-butylene glycol or a solvent containing the same.

  The extract of water scent used in the present invention is a substance having both a Maillard reaction product concentration lowering effect and a Maillard reaction inhibitory effect, and is highly safe.

  Therefore, a skin external preparation or the like containing this is extremely effective for improving or treating symptoms caused by or related to the Maillard reaction.

  In this specification, the Maillard reaction product concentration-reducing agent is a preparation that acts on a series of compounds from terminal glycation products already produced on the skin and the like to end glycation products such as Amadori compounds, and reduces or decomposes the concentration. Means. In addition, the Maillard reaction product concentration reducing agent of the present invention is particularly characterized in that the target Maillard reaction product is pentosidine. Pentosidine is a major terminal glycation product found in many tissues containing collagen such as skin and dura mater membranes, and it has been suggested to be involved in inflammatory diseases. Is considered to be very important for maintaining skin flexibility and preventing inflammatory diseases.

  In this specification, the Maillard reaction inhibitor means a preparation that suppresses the Maillard reaction in the skin or the like. In addition, the Maillard reaction inhibitor of the present invention is particularly characterized by having a pentosidine production inhibitory action.

Mizuchoka used as an active ingredient in the Maillard reaction product concentration-reducing agent or Maillard reaction inhibitor of the present invention is a herbal medicine in the family Acabana, and its scientific name is Ludwigia octovalvis .

  About this thing, it is known that the ethanol extract has an antioxidant action and an active oxygen removal action, and it is described in patent document 4 that it is effective in the aging of a biological body.

  However, it has not been known at all that this water clove extract has a Maillard reaction product concentration lowering action or a Maillard reaction suppressing action.

  In addition, although the details of the mechanism of the above-described action by the water clove extract have not been elucidated, there are compositions that do not show the concentration-reducing action of the already produced Maillard reaction product even though they have the Maillard reaction suppression action. From this, it is considered that the water scent extract extracts two effects by different mechanisms. In addition, the present inventor has found a compound that does not show Maillard reaction product concentration lowering action even though it has active oxygen removal action, and Maillard reaction product concentration lowering action and active oxygen removal action are not correlated. it is conceivable that.

  The extract of scented scent used in the present invention (hereinafter referred to as “scented scented extract”) is a part of the plant body such as whole grass, flower, leaf, branch rhizome, root bark, seed, etc., as it is or dried. It is obtained by chopping, pulverizing, etc. and then extracting with an appropriate solvent. Of these, it is particularly preferable to use stems.

  The extraction method can be carried out by a commonly used method. As a preferable method, for example, 2 to 50 times the amount of an appropriate extraction solvent is preferably added to scented scented raw powder. 10 to 30 times the amount, and a temperature of 4 ° C. or higher, preferably 4 ° C. to 50 ° C., particularly preferably 10 ° C. to 35 ° C. for a fixed time or stirring. Although the extraction time is not particularly limited, it is preferably performed for 3 days or more, particularly preferably 1 week to 2 weeks, if the extraction temperature is 10 ° C to 35 ° C.

  The extract thus obtained can be filtered or centrifuged as necessary. Moreover, although an extract, a filtrate, etc. can be used as it is, you may give lyophilization | freeze-dry or concentration dryness.

  In this extraction method, the extraction solvent used is, for example, water, an aqueous solvent such as an acidic or basic aqueous solvent, for example, a lower alcohol such as methanol or ethanol, or a mixed solvent thereof with water, ethylene glycol, propylene glycol. Polyhydric alcohols such as 1,3-butylene glycol or mixed solvents thereof with water, ketones such as acetone, esters such as diethyl ether, dioxane, acetonitrile, and ethyl acetate, organics such as xylene, benzene, and chloroform A solvent is mentioned, These can be used individually or as a 2 or more types of liquid mixture.

  Preferred examples of the extract of water scented are extracts from polyhydric alcohols or a solvent containing the same, more preferably extracts from glycols or a solvent containing the same, 1,3-butylene glycol or the like. An extract with a solvent is particularly preferred. Specifically, an extract with a solvent in which a polyhydric alcohol and water are combined is exemplified, and particularly preferable is an extract with a solvent containing the polyhydric alcohol and water in a ratio of 100: 0 to 30:70. Can be mentioned.

  The blending amount of the water scent extract in the above preparation can be appropriately adjusted according to the purpose, but generally 0.0001 to 1% by mass (hereinafter referred to as “%”) as the water scent extract (dry solid content). ), Preferably 0.0005 to 0.1%. In addition, the said compounding quantity is 0.00135 to 13.5% as raw material conversion, Preferably it is 0.00675 to 1.35%.

  In the Maillard reaction product concentration-reducing agent or Maillard reaction inhibitor of the present invention, the above-mentioned extract of water clove may be used as it is, but it is usually a carrier that is pharmaceutically or cosmetically acceptable according to conventional methods. It is preferable to use it as a skin external preparation or the like.

  The above-mentioned external preparation for skin can be blended with known ingredients used in the fields of cosmetics, pharmaceuticals, quasi-drugs and the like as long as the effects of the present invention are not hindered. These known components include, for example, water, alcohols, oil components, surfactants, preservatives, fragrances, pigments, moisturizers, thickeners, antioxidants, chelating agents, pH adjusters, foaming agents, and ultraviolet absorption. -Examples include scattering agents, powders, vitamins, amino acids, antibacterial agents, seaweed extracts, and various drugs.

  Among these, specific examples of the oil component include macadamia nut oil, castor oil, olive oil, cacao oil, coconut oil, palm oil, tree wax, jojoba oil, grape seed oil, avocado oil, and other vegetable oils; mink oil, egg yolk oil Animal fats such as beeswax, whale wax, lanolin, carnauba wax, candelilla wax, etc .; hydrocarbons such as liquid paraffin, squalane, microcrystalline wax, ceresin wax, paraffin wax, petrolatum; capric acid, myristin Natural and synthetic fatty acids such as acid, palmitic acid, stearic acid, behenic acid, lanolin fatty acid, linoleic acid, linolenic acid, lauric acid, myristic acid, oleic acid, isostearic acid; cetanol, stearyl alcohol, hexyl decanol, octyldodecanol, Lauryl alcohol Illustrate natural and synthetic higher alcohols such as capryl alcohol, myristyl alcohol, cetyl alcohol, cholesterol, phytosterol; esters such as isopropyl myristate, isopropyl palmitate, octyldodecyl myristate, octyldodecyl oleate, cholesterol oleate, etc. Can do.

  Specific examples of the surfactant include sorbitan monolaurate, sorbitan monopalmitate, sorbitan sesquioleate, sorbitan trioleate, polyoxyethylene sorbitan monolaurate, polyoxetylene sorbitan monostearate, polyethylene glycol monooleate, Polyethylene glycol alkylate, polyoxyethylene alkyl ether, polyglycol diether, lauroyl diethanol amide, fatty acid isopropanol amide, maltitol hydroxy fatty acid ether, alkylated polysaccharide, alkyl glucoside, sugar ester, lipophilic glycerin monostearate, self-emulsifying Type glycerol monostearate, polyglycerol monostearate, polyglycerol alkylate, sorbitan mono Nonionic interfaces such as rate, polyethylene glycol monostearate, polyoxyethylene sorbitan monooleate, polyoxyethylene cetyl ether, polyoxyethylene sterol, polyoxyethylene lanolin, polyoxyethylenated beeswax, polyoxyethylene hydrogenated castor oil Activating agent: sodium stearate, potassium palmitate, sodium cetyl sulfate, sodium lauryl phosphate, triethanolamine palmitate, sodium polyoxyethylene lauryl phosphate, sodium N-acyl glutamate, sodium palmitate, sodium laurate, lauric acid Sodium, potassium lauryl sulfate, alkyl sulfate triethanolamine ether, funnel oil, linear dodecylbenzene sulfate, polyoxyethylene hard Anionic surfactants such as castor oil maleic acid and acylmethyl tauri, cationic surfactants such as stearyldimethylbenzylammonium chloride, stearyltrimethylammonium chloride, stearyltrimethylammonium chloride, benzalkonium chloride and laurylamine oxide; alkylaminoethyl hydrochloride Examples include amphoteric surfactants such as glycine solution and lecithin.

  Furthermore, examples of preservatives include benzoate, salicylate, sorbate, dehydroacetate, paraoxybenzoate, 2,4,4′-trichloro-2′-hydroxydiphenyl ether, 3,4,4 ′. -Trichlorocarbanilide, benzalkonium chloride, hinokitiol, resorcin, ethanol, etc. can be exemplified, and humectants include glycerin, erythritol, xylitol, maltitol glycerin, propylene glycol, 1,3-butylene glycol, sorbitol Polyglycerin, polyethylene glycol, dipropylene glycol, polyhydric alcohols such as 1,2-pentanediol, isoprene glycol, NMF components such as amino acids, sodium lactate, sodium pyrrolidonecarboxylate, xyloglucan, quinine Seed, carrageenan, pectin, mannan, curdlan, galactan, dermatan sulfate, glycogen, keratan sulfate, chondroitin, mucoitin sulfate, keratosulfate, locust bean gum, succinoglucan, caronic acid, hyaluronic acid, heparan sulfate, sodium hyaluronate, Examples thereof include water-soluble polymer substances such as collagen, mucopolysaccharide and chondroitin sulfate, silicones such as dimethylpolysiloxane and methylphenylsiloxane, and culture supernatants such as lactic acid bacteria and bifidobacteria.

  Furthermore, examples of thickeners include sodium alginate, xanthan gum, aluminum oxalate, quince seed extract, gum arabic, hydroxyethyl guar gum, carboxymethyl guar gum, guar gum, dextran, tragacanth gum, starch, chitin, chitosan, carboxymethyl Natural polymeric substances such as chitin and agar; semi-synthetic polymeric substances such as cellulose, hydroxypropylcellulose, methylhydroxypropylcellulose, methylcellulose, carboxymethylcellulose, hydroxyethylcellulose, soluble starch, cationized cellulose; carboxyvinyl polymer, polyvinyl alcohol, Examples thereof include synthetic polymer substances such as polyvinylpyrrolidone and vinyl alcohol / vinyl acetate copolymers.

  Furthermore, examples of antioxidants include dibutylhydroxytoluene, butylhydroxyanisole, propyl gallate, ascorbic acid, etc., and chelating agents include disodium edetate, ethylenediaminetetraacetate, pyrophosphate, hexametaphosphate Citric acid, tartaric acid, gluconic acid and the like, and examples of the pH adjusting agent include sodium hydroxide, triethanolamine, citric acid, sodium citrate, boric acid, borax, potassium hydrogen phosphate and the like.

  Examples of UV absorbers / scatterers include paraaminobenzoic acid UV absorbers, anthranilic acid UV absorbers, salicylic acid UV absorbers, cinnamic acid UV absorbers, benzophenone UV absorbers, sugar UV absorbers, 3- (4′-methylbenzylidene) -d-camphor, 3-benzylidene-d, 1-camphor, urocanic acid, urocanic acid ethyl ester, 2-phenyl-5-methylbenzoxazole, 2,2′-hydroxy- 5-methylphenylbenzotriazole, 2- (2′-hydroxy-5′-t-octylphenyl) benzotriazole, 2- (2′-hydroxy-5′-methylphenylbenzotriazole), dibenzalazine, dianisoylmethane, 4- Methoxy-4′-tert-butyldibenzoylmethane, 5- (3,3-dimethyl) 2-norbornylidene) -3-pentan-2-one, 2-hydroxy-4-methoxybenzophenone, octyl dimethyl p-aminobenzoate, ethylhexyl p-methoxycinnamate Saina formate, titanium oxide, can be exemplified kaolin, talc and the like.

The vitamins include vitamin A and its derivatives, vitamin B ₆ hydrochloride, vitamin B ₆ tripalmitate, vitamin B ₆ dioctanoate, vitamin B ₂ and its derivatives, vitamin B ₁₂ , vitamin B ₁₅ and its derivatives, etc. Vitamin Bs, ascorbic acid, ascorbic acid sulfate and its salts, ascorbic acid phosphates and their salts, ascorbic acid dipalmitates, ascorbic acid glucoside, acylascorbic acid glucoside and other vitamin Cs, α-tocopherol, β-tocopherol , Γ-tocopherol, vitamin E such as vitamin E acetate, vitamin D, vitamin H, pantothenic acid, panthetin, vitamin F, vitamin K, vitamin P, vitamin U, carnitine, ferulic acid, γ-oryzanol, α Lipoic acid, can be exemplified orotic acid and their derivatives.

  Amino acids include glycine, alanine, valine, leucine, isoleucine, serine, threonine, phenylalanine, tyrosine, asparagine, glutamine, taurine, tryptophan, cystine, cysteine, methionine, proline, hydroxyproline, aspartic acid, glutamic acid, arginine, histidine. And lysine and derivatives thereof.

  Examples of the antibacterial agent include benzoic acid, salicylic acid, sorbic acid, paraoxybenzoic acid alkyl ester, hexachlorophene and the like.

  As seaweed extracts, there are extracts from brown algae, red algae, green algae, cyanobacteria, etc., specifically, kombu, macabu, seaweed, cypress, proboscis, coral, palmaria, tsunomata, nori, aosa, ana aosa, ascophyllum, Examples include extracts from Hibamata, Mozuku, Okinawa Mozuku, Himantaria and the like.

  Various drugs include nicotinamide, benzyl nicotinate, γ-oryzanol, allantoin, glycyrrhizic acid (salt), glycyrrhetinic acid and its derivatives, hinokitiol, bisabolol, eucalptone, thymol, inositol, saikosaponin, carrot saponin, loofah Examples thereof include saponins such as saponin and muclodisaponin, pantothenyl ethyl ether, ethinyl estradiol, tranexamic acid, arbutin, cephalanthin, and placenta extract.

  As a preferred form of the Maillard reaction product decomposition agent or Maillard reaction inhibitor of the present invention, specifically, basic cosmetics such as lotion, milky lotion, moisturizing cream, cleansing cream, massage cream, face wash cream, pack, cosmetic liquid, Various forms such as bath cosmetics such as bath additives, makeup cosmetics such as foundations, and special cosmetics such as sunscreens can be exemplified.

  Furthermore, since the Maillard reaction inhibitor or Maillard reaction product decomposition agent of the present invention contains a plant extract with food experience as an active ingredient, it can be incorporated into various foods and drinks. For example, after adding an appropriate auxiliary agent to the extract of scented scent, it may be used for edible by using conventional means and forming it into an edible form, for example, granular, granular, tablet, capsule, paste, etc. Often used in addition to various foods such as processed foods such as ham and sausage, processed fishery products such as kamaboko and chikuwa, bread and confectionery, and beverages such as water, fruit juice, milk and soft drinks It may be added to and used.

  EXAMPLES Next, although an Example is given and demonstrated in more detail, this invention is not restrict | limited at all by these Examples.

Example 1
Manufacture of water clove extract:
2000 g of 50% 1,3-butylene glycol aqueous solution was added to 100 g of water scented scent (water scented stalk cut), extracted at 25 ° C. for 2 weeks, and then filtered to obtain an extract. In this extract, 0.37% (3,700 μg / mL) of water scent extract (hereinafter sometimes referred to as “water scent incense 1,3BG extract”) was contained as a dry solid content.

Example 2
Maillard reaction product concentration reduction effect:
Using pentosidine known as the Maillard reaction product as a sample, the pentosidine concentration-reducing effect of the water clove extract (water clove 1,3BG extract) prepared in Example 1 was examined as follows.

  First, 45 μl of 100 mM sodium phosphate buffer (pH 7.4) was added to 5 μl of 5 μg / ml pentosidine. As shown in the table below, 5 μl of a test sample solution obtained by diluting the water clove 1,3BG extract of Example 1 using 100 mM sodium phosphate buffer (pH 7.4) was added, and the mixture was heated at 60 ° C. for 24 hours. did. As a comparison, a 1 mM aminoguanidine hydrochloride solution was used in place of the water clove 1,3BG extract, and water was used as a control in the same manner using water instead of the water clove 1,3BG extract. In addition, the blank used the buffer solution which does not contain pentosidine.

  After completion of heating, each specimen was irradiated with 330 nm excitation light, the resulting fluorescence intensity at 390 nm was measured, and the remaining amount of pentosidine was calculated as the fluorescence amount. From this fluorescence intensity, the pentosidine concentration reduction rate was calculated by the following formula. The results are shown in Table 1.

Pentosidine concentration reduction rate (%) =
((Ec-Eb)-(Es-Eb)) / (Ec-Eb) × 100
Es: Sample fluorescence intensity
Ec: Control fluorescence intensity
Eb: Blank fluorescence intensity

<Result>

  As a result, it was confirmed that pentosidine disappeared in a concentration-dependent manner with the water clove incense extract, and it was revealed that this water cinder incense extract has Maillard reaction product concentration lowering activity. On the other hand, aminoguanidine, which is known to have a Maillard reaction inhibitory effect, had a low effect of reducing the pentosidine concentration.

Example 3
Maillard reaction suppression effect:
By the following method, the Maillard reaction inhibitory effect of the water clove extract was examined. That is, a substrate solution prepared by mixing 50 mM ribose, 50 mM lysine hydrochloride, 50 mM arginine hydrochloride and 100 mM sodium phosphate buffer (pH 7.4) in equal amounts was prepared. Next, a test sample solution obtained by diluting the water clove 1,3BG extract of Example 1 with 100 mM sodium phosphate buffer (pH 7.4) was added to the substrate solution, and the substrate solution: test sample solution was 1: 4. It mixed so that it might become, and it was made to react for 24 hours in a 60 degreeC thermostat. The reaction was carried out in the same manner using 1 mM aminoguanidine hydrochloride solution as a positive target instead of water clove 1,3BG extract and water as a control instead of water clove 1,3BG extract. As a blank, a buffer solution containing no ribose, lysine or arginine was used.

  After completion of the reaction, each specimen was irradiated with 330 nm excitation light, the resulting fluorescence intensity of 390 nm was measured, and the amount of Maillard reaction product (pentosidine) produced was calculated as the amount of fluorescence. Furthermore, the inhibition rate of the Maillard reaction was calculated by the following formula. The results are shown in Table 2.

Inhibition rate (%) = ((Ec−Eb) − (Es−Eb)) / (Ec−Eb) × 100
Es: Sample fluorescence intensity
Ec: Control fluorescence intensity
Eb: Blank fluorescence intensity

<Result>

  As a result, it was found that the Mail-Taka incense 1,3BG extract suppressed the Maillard reaction in a concentration-dependent manner, and it was revealed that the Water-Ting incense extract has Maillard reaction-inhibiting activity.

Example 4
Preparation of lotion:
A lotion was prepared with the composition described in Table 3. The lotion was prepared by adding 1 to 6 to 7 and stirring sufficiently.

Example 5
Emulsion preparation:
An emulsion was prepared with the composition described in Table 4. The emulsion was prepared by adding 7, 8, and 10 to 11 and heating, adding 1 to 6 at 80 ° C. to emulsify, then adding 9 and stirring, followed by cooling to 25 ° C. It was.

Example 6
Cream preparation:
A cream was prepared with the composition described in Table 5. The cream was prepared by adding 9, 10 and 12 to 13 and warming, adding 1 to 8 at 80 ° C. to emulsify, then adding 11 and stirring, and cooling to 25 ° C. It was.

  The water scent extract used in the present invention is highly safe, and as described above, it has both the concentration lowering effect of the Maillard reaction product and the inhibitory effect of the Maillard reaction. Skin external preparations and the like are extremely effective for ameliorating and treating symptoms caused by or related to the Maillard reaction.

  That is, the extract of scented scent of the present invention is applied to the skin, for example, to suppress the Maillard reaction to prevent the generation of the Maillard reaction product, and for the Maillard reaction product that has already occurred. Since the concentration is lowered, the Maillard reaction product can be strongly removed as compared with the conventional Maillard reaction inhibitor. That is, according to the present invention, not only the Maillard reaction can be suppressed, but the Maillard reaction product can be expected to restore the elasticity of skin collagen and the like that has already hardened, and to improve the dullness of the skin.

Thus, the present invention is extremely effective as a Maillard reaction inhibitor or a Maillard reaction product concentration reducing agent.

Claims (6)

Maillard reaction inhibitor which uses as an active ingredient the extract of the solvent which contains 1, 3- butylene glycol of water clove and water in the ratio of 30 : 70-50 : 50 . Maillard reaction inhibitor according to claim 1 is the use of a stem Mizuhinoto incense as MizuChoKaoru. The Maillard reaction inhibitor according to claim 1 or 2, which has a pentosidine production inhibitory action. The Maillard reaction inhibitor according to any one of claims 1 to 3 , which is a skin external preparation. An extract of a solvent containing 1,3-butylene glycol of water scent and water in a ratio of 30:70 to 50:50 . The extract according to claim 5 , wherein a stalk of mizucense is used as the scented scent.