JP2006083131A - Aldose reductase inhibitor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an aldose reductase inhibitor for preventing or treating diabetic complications which is highly safe, has no problems from the viewpoint of stable supply and compliance, and can be daily and continually used. <P>SOLUTION: The aldose reductase inhibitor comprises as effective ingredients ellagic acid and other natural-derived substances contained in solvent extracts of plants such as oaks belonging to the genus Quercus serrata of the family of Fagaceae. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to an aldose reductase inhibitor. In more detail, this invention relates to the food-drinks or pharmaceutical which have the aldose reductase inhibitory effect containing the solvent extract of the beech family Quercus genus plant.

  Nutritional fulfillment is the primary value of products in the food field, but in addition to that, taste, visual and olfactory impressions have been pursued. In recent years, in addition to the conventional nutritional value for energy satisfaction, biological construction, and biological function maintenance, additional values such as biological function regulation and homeostasis disturbance prevention have been demanded. This tendency is strong in luxury products. Especially for alcoholic beverages, red wine's biooxidative stress-inhibiting effect, Japanese sake lees' cell growth promoting effect, etc. are well known. The effect of red wine is derived from the grape seed coat, and grapes are also a product of the organism.

  Whiskey gains unique taste, visual and olfactory merit by aging in oak barrels due to its manufacturing method, but this aging is nothing other than extracting oak with distilled alcohol, The unique component of the oak plant greatly contributes to its characteristics. Therefore, aging whiskey is expected to have a unique physiological effect derived from oak ingredients.

  On the other hand, in diabetes, it is known that complications (typically diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy) result in a serious medical condition. The enzyme involved in the exacerbation of this complication is aldose reductase. This enzyme is involved in a process in which a polyol metabolic pathway, which is one of intracellular glucose metabolic pathways, is abnormally enhanced to cause diabetic complications such as neuropathy. More specifically, glucose uptake in peripheral nerve Schwann cells, kidney mensagium cells, vascular endothelial cells, retinal vascular pericytes, and lens epithelial cells in tissues that cause diabetic complications is insulin-independent, The intracellular glucose concentration increases in proportion to the blood glucose level, and the glycolytic initial enzyme becomes saturated under high blood glucose, and glucose flows into the polyol pathway (FIG. 1). Sorbitol produced by the action of aldose reductase on this glucose accumulates in the cell because of its slow metabolism. This accumulation increases intracellular osmotic pressure, and thus damages systematically and functionally. NADPH consumption also causes oxidative stress because it makes it difficult to regenerate reduced glutathione.

Therefore, aldose reductase inhibitors are expected to be used as therapeutic agents for diabetic complications. However, Epalrestat, a diabetic neuropathy treatment, which is the only drug that has been put into practical use as this type of drug, may cause side effects of liver damage if not used under the control of a doctor. There is a problem that it cannot be used on a daily basis.
Folia Pharmacol. Jpn. (1998) 111; 137-145 Recent Res. Devel. In Agricultural & Biological Chem. (1997) 1; 147-160

  The present inventors aimed at the preventive effect of lifestyle-related diseases, and in particular for the purpose of searching for effective functions and components in physiological reactions related to diabetes in whiskey or oak components, As a cause of diabetic complications, we investigated the ability to suppress the enhancement of the polyol pathway secondary to the hyperglycemic state, and investigated the aldose reductase inhibitory active substance that is the central catalyst of this pathway.

  Therefore, the subject of the present invention is derived from whiskey or a beech family Quercus genus plant (for example, oak) used for the production thereof, which is highly safe, has no problem with stable supply, and is sufficient in terms of compliance. Another object of the present invention is to provide an aldose reductase inhibitor that can be used daily or continuously as a food, drink, cosmetic or pharmaceutical product.

  A further object of the present invention is to provide a diabetic complication, particularly diabetic retinopathy, diabetes, comprising the above-mentioned aldose reductase inhibitor, or ellagic acid and / or isoquercitrin found in the inhibitor as an active ingredient. It is to provide a preventive or therapeutic agent for diabetic nephropathy and diabetic neuropathy.

  A further object of the present invention is to provide health foods and cosmetics and cosmetics suitable for the prevention and / or treatment of diabetic complications, to which the aldose reductase inhibitor or ellagic acid and / or isoquercitrin is added. .

  In accordance with the present invention, it has been found that whiskey contains an aldose reductase inhibitor and the amount of this inhibitor component increases with the aging period of the whiskey. Therefore, it is considered that the aldose reductase inhibitor is extracted from oak wood that makes barrels for ripening whiskey.

  Therefore, this invention is an aldose reductase inhibitor containing the solvent extract of the beech family Quercus plant in the 1st aspect.

  Examples of the plant of the genus Fagaceae Quercus sp used as a raw material for producing the aldose reductase inhibitor of the present invention include, for example, Mizunara (scientific name: Q. mongolica Fisch. Ex Turcz. Var. Grosseserrata ( Bl.) Rehd. Et Wils.), Kashiwa (scientific name: Quercus dentata Thunb), Konara (scientific name: Quercus serrata Thunb), Kunigi (scientific name: Quercus acutissima Carruth), Shirakashi (scientific name: Quercus myrsinaefolia Bl.), White oak (scientific name: Quercus serrata Thunb) Scientific name: Quercus alba L.), Common oak (also known as Limousin oak, French oak or Spanish oak. Scientific name: Quercus robur L.), Cecil oak (scientific name: Quercus petraea (Mattuschka) Lieblein), Cork oak (scientific name: Quercus suber L.) and the like. Since ancient times, many plants that have been used as raw materials for barrels for manufacturing and storing whiskeys and brandies belong to this genus. Particularly preferred are plants called oaks. The oak as used in the present invention refers to a plant group used as a raw material for barrels for production and storage of whiskey, brandy, etc., among plants belonging to the genus Quercus. In the present invention, these oaks can be preferably used. Among these, white oak, common oak, cecil oak and mizunara can be particularly preferably used.

  For these plants, the part used as a raw material is not particularly limited, and trunks, leaves, branches, bark, flowers, fruits and the like can be used. Moreover, they may be used immediately after collection or after drying. If necessary, it can be used after being subjected to processing such as pulverization, cutting, chopping and molding. Chips, wood flour, barrels and the like obtained from the wood of such plants are listed as processed products. The barrel is preferably subjected to a heat treatment such as baking the inner surface before being used for solvent extraction.

  As a solvent used for extraction of an aldose reductase inhibitor component, an aqueous solution of a lower alcohol can be preferably used. Examples of the lower alcohol include linear or branched alcohols having 1 to 4 carbon atoms (for example, methanol, ethanol, propanol, butanol, etc.). It is important that the concentration of the lower alcohol in the aqueous solution is a concentration at which an extract having a strong aldose reductase inhibitory action can be obtained. Specifically, the concentration of the lower alcohol in the aqueous solution of the lower alcohol is usually about 10 to 10. 100% by volume, preferably about 30-99% by volume. Considering that it can finally be blended with food and drink, etc., it is preferable to use an aqueous ethanol solution as the extraction solvent from the viewpoint of safety. The extraction solvent here may contain other components in addition to the lower alcohol and water as long as the extraction efficiency is not significantly impaired. For example, water-soluble components such as saccharides, salts or amino acids and various other solvents (for example, ethyl acetate and acetone) may be contained as desired.

  Accordingly, when ethanol is used as the lower alcohol, for example, an aqueous ethanol solution obtained by mixing an industrial reagent with water may be used, or various alcohol products and work-in-process products thereof may be used. For example, brandy, whiskey, shochu, sake, beer, sparkling liquor, spirits, vodka or work in progress thereof can be mentioned. These production methods may follow conventional methods. When a barrel is formed from plant raw materials and extraction is performed by injecting a solvent therein, a product obtained by distilling an ethanol-containing material can be suitably used as the solvent. The term “distilled ethanol-containing material” as used herein refers to a distillate obtained by distilling a solution containing ethanol. Specifically, an ethanol-containing product obtained by saccharification and fermentation using malt, rice, grapes and the like as a part of raw materials can be obtained by single distillation or double distillation. For example, it is preferable to use shochu, vodka, raw whiskey pre-storage liquor (new pot of malt whiskey original liquor, new make of gren whiskey original liquor), or brandy pre-storage raw liquor (nouvelle). Among them, whiskey pre-stored liquor and brandy pre-stored raw liquor can be preferably used. These production methods may follow conventional methods. In this case, the extraction condition is preferably about half a year to 30 years at room temperature, but there is no substantial upper limit to the extraction time.

  The extraction method using a plant solvent used as a raw material in the present invention is not particularly limited, and the extraction is performed by bringing the solvent into contact with the plant raw material. The raw material may be immersed in a solvent, or a container such as a barrel may be formed using a plant raw material, and the solvent may be injected therein. It may be stored at rest, and the extraction mode such as heating under reflux and immersion extraction can be appropriately set according to the known means as desired. Extraction may be performed at room temperature or by heating. The extraction temperature is not particularly limited, but is preferably not higher than the boiling point of the solvent in operation. The time required for extraction is usually about 30 minutes to 30 years, although it depends on temperature conditions and extraction method. However, there is no practical upper limit on the extraction time.

  According to the present invention, after the above extraction, the extract containing the aldose reductase inhibiting component is separated from the beech family Quercus plant, its processed product or its processed product according to a method known per se. As the separation means, known means may be used, and examples thereof include centrifugation and filtration. The extract may be used as it is as an aldose reductase inhibitor, or a concentrate or dried product (concentrated and dried product) of the extract may be used as an aldose reductase inhibitor. Concentration is performed under normal pressure or reduced pressure. Concentration may reduce the volume of the concentrate to about 5-70% by volume, preferably about 10-50% by volume. The dried product is obtained by evaporating the solvent from the extract containing the aldose reductase inhibitor component, preferably under reduced pressure.

  Furthermore, the solvent extract of the present invention includes a product obtained by further fractionating and purifying the extract obtained by the extraction by, for example, column chromatography. The solvent extract thus obtained can be used as an extract after completion of the extraction operation, a concentrate obtained by partially removing the solvent of the extract, or a dry product obtained by completely removing the solvent. From the viewpoint of storage stability and ease of carrying, it is preferably used as a dried product. The solvent extract referred to in the present invention refers to these extract, concentrate and dried product. The solvent extract may be used as it is as an aldose reductase inhibitor, and further, for example, an appropriate liquid or solid additive such as titanium oxide, calcium carbonate, distilled water, lactose, starch or the specific examples described in the following examples. A form or bulking agent may be added to the aldose reductase inhibitor. The mixing ratio of the solvent extract in the aldose reductase inhibitor is not particularly limited, but is, for example, in the range of about 0.01 to 100% by weight, depending on the properties of the extract (extract, concentrate, or dry product). It can be set appropriately.

  The aldose reductase inhibitor of the present invention may be prepared as it is in foods and drinks, cosmetics and pharmaceuticals, but may be used as additives or compounding agents in foods and drinks, cosmetics and pharmaceuticals. The additive or compounding agent for foods and beverages, cosmetics or pharmaceuticals referred to in the present invention is an additive or compounding agent usually used for foods, beverages, cosmetics or pharmaceuticals, such as fragrances, pigments and antioxidants. This refers to a mixture of a solvent extract and an agent. What is necessary is just to set a mixing ratio suitably. The mixing ratio is, for example, about 0.01 to 100% by weight, preferably 0.1 to 80% by weight. Examples of additives or compounding agents for foods, beverages, cosmetics or pharmaceuticals used here include various additives described below.

  The amount to be added to foods and beverages, cosmetics and pharmaceuticals when used as an additive or a compounding agent is not particularly limited, but is, for example, about 0.01 to 100% by weight, preferably about 0.1% based on the solvent extract. It can set suitably in the range of 1 to 80 weight%. In setting the blending amount when the solvent extract itself is blended as an aldose reductase inhibitor, the nature of the extract (extract, concentrate, or dried product) is also considered.

  Foods and beverages produced using or blending with the aldose reductase inhibitor of the present invention include strawberries, troches, gum, yogurt, ice cream, pudding, jelly, water candy, alcoholic beverages, coffee beverages, juices, fruit juice beverages An appropriate amount of a solvent extract can be added to a carbonated beverage, a soft drink, milk, a whey beverage, a lactic acid bacteria beverage, etc., and provided as a food or drink. These foods and drinks can be obtained according to conventional methods by blending various additives as necessary.

  When preparing these foods and drinks, for example, glucose, fructose, sucrose, maltose, sorbitol, stevioside, rubusoside, corn syrup, lactose, citric acid, tartaric acid, malic acid, succinic acid, lactic acid, L-ascorbic acid Dl-α-tocophenol, sodium erythorbate, glycerin, propylene glycol, glycerin fatty acid ester, polyglycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester gum arabic, carrageenan, casein, gelatin, pectin, Add the additives used as normal food ingredients such as agar, vitamin B, nicotinic acid amide, calcium pantothenate, amino acids, calcium salts, pigments, fragrances, preservatives, etc. Can be manufactured.

  The cosmetics referred to in the present invention include products called cosmetics and fragrance products. When these products are provided, they are lotions, cosmetic creams, emulsions, foundations, lipsticks, hair styling agents, hair tonics, hair restorers, shampoos. Prepare a cosmetic product by adding an appropriate amount of solvent extract to non-oral cosmetics such as rinsing, bathing agents, and oral cosmetics such as toothpastes, mouthwashes, mouthwashes, and oral fragrances. be able to.

  These cosmetics include, for example, oils and fats such as vegetable oils, waxes such as lanolin and beeswax, hydrocarbons, fatty acids, higher alcohols, esters, various surfactants, pigments, fragrances, vitamins, plants and Obtained according to conventional methods by appropriately blending additives used as usual cosmetic ingredients such as animal extract ingredients, ultraviolet absorbers, antioxidants, antiseptic / bactericides, and moisturizers (eg urea, hyaluronic acid) be able to.

  When preparing or blending the aldose reductase inhibitor of the present invention into a pharmaceutical product, various additives can be blended as necessary, and an appropriate amount of a solvent extract can be added to prepare the pharmaceutical product in various dosage forms. For example, as oral drugs such as tablets, capsules, granules, powders, syrups, extracts, etc., or ointments, eye ointments, lotions, creams, patches, suppositories, eye drops, nasal drops, injections, etc. It can be provided as an oral medicine. These pharmaceuticals may be produced according to conventional methods using various additives. The additive to be used is not particularly limited, and those commonly used can be used. Examples thereof include a solid carrier such as starch, lactose, sucrose, mannitol, carboxymethylcellulose, corn starch, inorganic salt, distilled water, and the like. , Physiological saline, aqueous glucose solution, alcohol such as ethanol, liquid carriers such as propylene glycol and polyethylene glycol, various animal and vegetable oils, oily carriers such as white petrolatum, paraffin, waxes, and the like.

  In addition, when preparing foods and drinks, cosmetics or pharmaceuticals using the aldose reductase inhibitor of the present invention, other aldose reductase inhibitors and melanin production inhibitors such as ascorbic acid, hydroquinone, kojic acid, It can be used in combination with placenta extract, arbutin, or plant extract components such as fire thorns, kyounin, karin, hinoki, jasmine, yaw pilpy. The blending ratio of such a plant extract component and the solvent extract of the present invention cannot be generally specified, but is usually about 1: 9 to 9: 1 by weight.

  According to the present invention, the active ingredient of the aldose reductase inhibitor in the solvent extract of the beech family Quercus spp.

Ellagic acid represented by the following formula:

(Where Rham represents a rhamnose residue)
The isoquercitrin represented by these is contained. The fact that ellagic acid has an aldose reductase inhibitory action is a new finding. Ellagic acid and isoquercitrin are aldose reductase inhibitory active ingredients found to date, and there is still a possibility that other inhibitory active ingredients may be present in the solvent extract of the beech family Quercus. Yes.

  Therefore, in the second aspect of the present invention, an aldose reduction comprising, as active ingredients, ellagic acid represented by the above formula, optionally isoquercitrin represented by the above formula, and further a further aldose reductase inhibitor component Enzyme inhibitors are also provided. Any of the compounds of the above formula may be present in the aldose reductase inhibitor of the present invention as a precursor that decomposes in the living body to produce the compound of the above formula.

  The aldose reductase inhibitor of the second aspect of the present invention can be used for the preparation of foods, drinks, cosmetics or pharmaceuticals, just like the aldose reductase inhibitor of the first aspect.

EXAMPLES Hereinafter, the present invention will be specifically described with reference to examples, but these examples do not limit the scope of the present invention.
Experimental methods and samples Single casks and oak chips of each age were procured from the applicant's whiskey production site. Various compounds contained in whiskey and oak (FIG. 2) were purchased from Sigma, Wako Pure Chemicals, Tokyo Kasei. Pig eyeballs were purchased from Nippon Ham, and Wister male rats were purchased from Shimizu Experimental Materials.

Aldose reductase was prepared by a method already published in the paper from pig eyeballs (see Recent Res. Devel. In Agricultural & Biological Chem. (1997) 1; 147-160, 148, “Preparation of Lens Aldose Reductase”). Recombinant human aldose reductase was purchased from Wako Pure Chemicals, reacted with substrate (glyceraldehyde) and coenzyme (NADPH), and NADPH consumption (oxidation rate) was measured at 340 nm (aldose reduction). For details of the method of measuring enzyme activity, see Recent Res. Devel. In Agricultural & Biological Chem. (1997) 1; 147-160, p. 149, “Assay of Reductase Activity”).
Example 1 Inhibition of aldose reductase by whiskey A 18-year-old whiskey, oolong tea, beer and green tea congener (powder from which water was removed and alcohol was also removed from alcohol) in an amount of 5 μl / ml In addition, aldose reductase (AR) inhibitory activity was examined against a control in which a buffer was added instead of congener. As a result, 80 to 90% AR inhibitory activity was observed in whiskey, and about 40% inhibitory activity was observed in oolong tea, but no inhibitory activity was observed in beer and green tea (FIG. 3).

Next, with respect to whiskey, shochu, beer, red wine, and sake, the inhibitory action of each liquor congener was compared when the AR inhibitory action of the whiskey congener was taken as 100. The results are shown in FIG. Whiskey's aldose reductase inhibitory action was overwhelmingly stronger than other liquors.
Example 2 Correlation between aldose reductase inhibitory activity and age of whiskey barrel aging Whiskey single casks with different aging periods (whiskey stock solution from one barrel) were added to the reaction solution of aldose reductase, aging period and aldose The relationship of reductase inhibitory action was investigated. Single casks were added to 1% of the total reaction solution. As a control, 60% EtOH was used at 1%. The% AR inhibition of the control was 0. The relationship between the aging period and the inhibition rate is shown in FIG.
Example 3 Aldose reductase inhibitory active ingredient in whiskey Spanish oak is also called common oak, its scientific name is Quercus robur L., American oak is also called white oak, its scientific name is Quercus alba, Mizunara's scientific name is Quercus crispula BLUME. An aldose reductase inhibitor was searched from compounds found in whiskey and Q. robur and Q. alba. Among the compounds known to be included in these literatures, compounds represented by the following structural formulas were obtained, and the aldose reductase inhibitory action was examined.

  According to the results found to date, ellagic acid has an inhibitory action, and the test system described immediately before Example 1 showed an inhibitory activity of 65% at a concentration of 100 M.

Quercus plants contain tannins with many complex structures. Since these are adsorbed with proteins, aldose reductase inhibition is also considered. In addition, isoquercitrin has been found in Q. robur, and such flavonoid glycosides have an aldose reductase inhibitory action. It may also be necessary to examine the presence or absence of flavonoids and coumarins.
Example 4
A pharmaceutical product containing the solvent extract of the present invention was produced by the following method.
Tablet :
1 kg of white oak chips was placed in a stainless steel container, 30 L of an aqueous solution having an ethanol concentration of 60 vol% was added, and the mixture was stirred at 60 ° C. for 3 hours. The solvent was removed from the resulting extract to obtain 15 g of white oak extract (dried product).

To 5 g of this dried product, 490 g of lactose and 5 g of magnesium stearate were mixed, and tableted with a single tableting machine to produce a tablet having a diameter of 10 mm and a weight of 300 mg.
Granules :
The above tablets were pulverized, sized and sieved to obtain 20-50 mesh granules.
Example 5
A white oak extract was prepared in the same manner as in Example 4, and various foods and drinks containing the solvent extract of the present invention were produced with the composition shown below. The white oak extract (dried product) in the following composition was obtained in Example 4.
飴 :
(Composition) (Parts by weight)
Powdered sorbitol 99.7
Fragrance 0.2
White oak extract (dried product) 0.05
Sorbitol seed 0.05
Total 100
Candy :
(Composition) (Parts by weight)
Sugar 47.0
Minamata 49.76
Fragrance 1.0
Water 2.0
White oak extract (dry product) 0.24
Total 100
Lozenge :
(Composition) (Parts by weight)
Arabic gum 6
Glucose 73
White oak extract (dried product) 0.05
Potassium phosphate 0.2
Potassium phosphate 0.1
Lactose 17
Fragrance 0.1
Magnesium stearate 3.55
Total 100
Gum :
(Composition) (Parts by weight)
Gum base 20
Calcium carbonate 2
Stevioside 0.1
White oak extract (dried product) 0.05
Lactose 76.85
Fragrance 1
Total 100
Caramel :
(Composition) (Parts by weight)
Granulated sugar 32.0
Minamata 20.0
Milk powder 40.0
Hardened oil 4.0
Salt 0.6
Perfume 0.02
Water 3.22
White oak extract (dry product) 0.16
Total 100
Jelly (coffee jelly) :
(Composition) (Parts by weight)
Granulated sugar 15.0
Gelatin 1.0
Coffee extract 5.0
Water 78.93
White oak extract (dry product) 0.07
Total 100
Ice cream :
(Composition) (Parts by weight)
Fresh cream (45% fat) 33.8
Nonfat dry milk 11.0
Granulated sugar 14.8
Sweetened egg yolk 0.3
Vanilla extract 0.1
Water 39.93
White oak extract (dry product) 0.07
Total 100
Custard pudding :
(Composition) (Parts by weight)
Milk 47.51
Whole egg 31.9
Super white sugar 17.1
Water 3.4
White oak extract (dry product) 0.09
Total 100
Mizuyokan :
(Composition) (Parts by weight)
Akao Ann 24.8
Powder agar 0.3
Salt 0.1
Super white sugar 24.9
White oak extract (dry product) 0.1
Water 49.8
Total 100
Juice :
(Composition) (Parts by weight)
Frozen and concentrated Wenzhou orange juice 5
Fructose glucose liquid sugar 11
Citric acid 0.2
L-ascorbic acid 0.02
White oak extract (dried product) 0.05
Fragrance 0.2
Dye 0.1
Water 83.43
Total 100
Carbonated drink :
(Composition) (Parts by weight)
Granulated sugar 8.0
Concentrated lemon juice 1.0
L-ascorbic acid 0.10
Citric acid 0.06
Sodium citrate 0.05
Coloring agent 0.05
Fragrance 0.15
Carbonated water 90.55
White oak extract (dried product) 0.04
Total 100
Lactic acid bacteria beverage :
(Composition) (Parts by weight)
Milk solid content 21% fermented milk 14.76
Fructose dextrose liquid sugar 13.31
Pectin 0.5
Citric acid 0.08
Fragrance 0.15
Water 71.14
White oak extract (dry product) 0.06
Total 100
Coffee drink :
(Composition) (Parts by weight)
Granulated sugar 8.0
Nonfat dry milk 5.0
Caramel 0.2
Coffee extract 2.0
Fragrance 0.1
Polyglycerin 0.05
Fatty acid ester salt 0.05
Water 84.56
White oak extract (dried product) 0.04
Total 100
Alcoholic beverages :
(Composition) (Parts by weight)
50% ethanol 32%
Sugar 8.4
Fruit juice 2.4
White oak extract (dry product) 0.2
Purified water 57.0
Example 6
A white oak extract was prepared in the same manner as in Example 4, and various cosmetics containing the solvent extract of the present invention were produced with the composition shown below. The white oak extract (dried product) in the following composition was obtained in Example 4.
Dentifrice :
(Composition) (Parts by weight)
Dicalcium phosphate 42
Glycerin 18
Carrageenan 0.9
Sodium lauryl sulfate 1.2
Saccharin sodium 0.09
Butyl paraoxybenzoate 0.005
White oak extract (dried product) 0.05
Fragrance 1
Water 36.755
Total 100
Mouthwash :
(Composition) (Parts by weight)
Sodium lauryl sulfate 0.8
Glycerin 7
Sorbitol 5
Ethyl alcohol 15
White oak extract (dried product) 0.05
1-menthol 0.05
Perfume 0.04
Saccharin sodium 0.1
Water 71.96
Total 100
Soft cosmetics (weakly acidic) :
(Composition) (Parts by weight)
Glycerin 5.0
Propylene glycol 4.0
Sodium hyaluronate 0.1
White oak extract (dried product) 0.05
Polyoxyethylene sorbitan monolaurate (20 EO) 1.5
Polyoxyethylene lauryl ether (20 EO) 0.5
Ethanol 10.0
Fragrance 0.1
Dye Trace amount Preservative amount Trace amount UV absorber Trace amount Purified water 78.75
Emollient cream :
(Composition) (Parts by weight)
Beeswax 2.0
Stearyl alcohol 5.0
Stearic acid 8.0
Squalane 10.0
Self-emulsifying propylene glycol 3.0
Monostearate Polyoxyethylene cetyl ether 1.0
(20 EO)
Fragrance 0.5
Antioxidant Trace amount Preservative Trace amount Propylene glycol 4.8
Glycerin 3.0
Sodium hyaluronate 0.1
White oak extract (dry product) 0.1
Triethanolamine 1.0
Purified water 61.5
Emollient lotion :
(Composition) (Parts by weight)
Stearic acid 2.0
Cetanol 1.5
Vaseline 3.0
Lanolin alcohol 2.0
Liquid paraffin 10.0
Polyoxyethylene monooleic acid 2.0
Ester (10 EO)
Fragrance 0.5
Antioxidant Trace amount Preservative Trace amount Propylene glycol 4.8
Glycerin 3.0
Sodium hyaluronate 0.1
White oak extract (dry product) 0.1
Triethanolamine 1.0
Purified water 70.0
Emulsion foundation :
(Composition) (Parts by weight)
Stearic acid 2.4
Propylene monostearate 2.0
Glycol cetostearyl alcohol 0.2
Liquid lanolin 2.0
Liquid paraffin 3.0
Isopropyl myristate 8.5
Propyl paraoxybenzoate Trace amount Purified water 64.1
Sodium carboxymethylcellulose 0.2
Bentonite 0.5
Propylene glycol 3.8
Sodium hyaluronate 0.1
White oak extract (dry product) 0.1
Triethanolamine 1.1
Methyl paraoxybenzoate Trace amount Titanium oxide 8.0
Talc 4.0
Coloring content Trace amount Fragrance amount Trace amount
Hair growth hair tonic :
(Composition) (Parts by weight)
Ethanol 70.0
Assembly extract 0.2
Vitamin E 0.2
L-Menthol 0.4
Glycyrrhizin 0.1
White oak extract (dry product) 0.1
Salicylic acid 0.5
Glycerin 0.5
Fragrance Trace amount Purified water 28.0
Shampoo :
(Composition) (Parts by weight)
Alkyl ether sulfuric acid 16.0
Sodium (AES-Na)
Lauric acid diethanolamide 4.0
Propylene glycol 1.9
White oak extract (dry product) 0.1
Preservative Trace amount Pigment Trace amount Fragrance Trace amount Purified water 78.0
Rinse :
(Composition) (Parts by weight)
Stearyl dimethyl chloride 1.4
Benzyl ammonium stearyl alcohol 0.6
Glycerol monostearate 1.5
Salt 0.1
White oak extract (dry product) 0.1
Purified water 96.3

[The invention's effect]

  The present invention provides an aldose reductase inhibitor that can be used on a daily basis for the prevention or treatment of diabetic complications, which is highly safe, has no problem with stable supply, and is sufficient in terms of compliance. It was done.

  The aldose reductase inhibitor of the present invention is excellent in safety when taken orally when an aqueous ethanol solution is used as a solvent, or when an oak with abundant experience in eating and drinking with an extract is used as a raw material plant. Therefore, for the prevention or treatment of diabetic complications, it can be suitably used as a food / beverage product, oral medicine, or oral cosmetic. Therefore, whiskey and brandy, or concentrates and dried products thereof can be suitably used as solvent extracts for foods and drinks, oral pharmaceuticals, and oral cosmetics.

FIG. 1 shows the relationship between aldose reductase and polyol metabolic pathways. FIG. 2 is a list of various compounds contained in whiskeys and oaks whose aldose reductase inhibitory action was examined in the present invention. FIG. 3 is a graph comparing the aldose reductase inhibitory action of various luxury products. FIG. 4 is a graph showing the results of examining the aldose reductase inhibitor action for each alcoholic beverage. FIG. 5 is a graph showing the relationship between the aging period of whiskey and the inhibition rate of aldose reductase.

Claims (19)

An aldose reductase inhibitor comprising a solvent extract of a beech family Quercus. The aldose reductase inhibitor according to claim 1, wherein the extract is an extract, a concentrate of the extract or a dried product of the extract. The aldose reductase inhibitor according to claim 1 or 2, wherein the beech family Quercus is an oak. The aldose reductase inhibitor according to any one of claims 1 to 3, wherein the beech family Quercus is in the form of a chip made of oak wood or a whiskey or brandy aging barrel. The aldose reductase inhibitor according to any one of claims 1 to 4, wherein the solvent is an aqueous solution containing a lower alcohol. The aldose reductase inhibitor according to claim 5, wherein the lower alcohol is ethanol. The aldose reductase inhibitor according to claim 6, wherein the concentration of ethanol as a solvent during extraction is 10 to 100% by volume. The aldose reductase inhibitor according to claim 6 or 7, wherein the solvent is obtained by distilling an ethanol-containing material. The aldose reductase inhibitor according to any one of claims 1 to 8, wherein the solvate is obtained by contacting a product obtained by distilling ethanol-containing material with an oak barrel in an oak barrel. The aldose reductase inhibitor according to claim 9, wherein the contact is performed for 0.5 to 30 years. The aldose reductase inhibitor according to claim 1, wherein the aldose reductase inhibitor is one of whiskey, brandy, a concentrate or a dried product thereof. The following formula:

Ellagic acid or a lower carboxylic acid ester thereof or a salt thereof represented by the formula:

(Where Rham represents a rhamnose residue)
The aldose reductase inhibitor which contains the isoquercitrin represented by these, or its lower alcohol ester, or those salts as an active ingredient. It is food-drinks, cosmetics, or a pharmaceutical, The aldose reductase inhibitor of any one of Claims 1-12. The aldose reductase inhibitor according to claim 13, which is an oral cosmetic or oral medicine. The aldose reductase inhibitor according to claim 14, wherein the oral drug is a prophylactic or therapeutic agent for diabetic complications. The aldose reductase inhibitor according to claim 15, wherein the diabetic complication is selected from the group consisting of diabetic retinopathy, diabetic nephropathy and diabetic neuropathy. The aldose reductase inhibitor according to any one of claims 1 to 12, which is an additive to foods and drinks or cosmetics. A health food or drink or a cosmetic for preventing diabetic complications, to which the aldose reductase inhibitor according to claim 17 is added. Use of a solvent extract of a beech family Quercus for producing an aldose reductase inhibitor.

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