JP2003081849A - Aldose reductase inhibitor - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an aldose reductase inhibitor derived from a plant, for preventing various kinds of complication of diabetes. SOLUTION: This aldose reductase inhibitor is obtained by formulating one or more kinds of extracts of leaves of Fragaria vesca or the like, Salvia officinalis or the like, Tamarix chinensis Lour, Agrimonia pilosa, leaves of Mimusops elengi, leaves of Anthriscus cerefolium, leaves of Allium schoenoprasum, and Rheum Palmatum Linne or the like. The components of the inhibitor is a plant eaten as a food up to now and has the high safety, and the inhibitor can inhibit the aldose reductase, and prevent the various kinds of the complication of the diabetes.

Description

Description: BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an aldose reductase inhibitor for preventing various complications of diabetes. [0002] In Japan, there are about 6 million diabetic patients, including those who tend to have it, reaching 10% of Japan's population, and the scale of national illness is increasing. There are two types of diabetes, insulin-dependent and non-insulin-dependent, and most Japanese patients have non-insulin-dependent diabetes. However, diabetes is said to cause various complications. [0003] Strawberry leaf is a strawberry (Fragaria v
esca, F. viridis, F. mosahata, F. chiloensis, F. virgi
niana) leaf, which is consumed as tea. [0004] Sage (Salvia officinalis S. lavandul)
aefolia S. tribolaulmaria) is a plant native to the Mediterranean, widely distributed in Europe, and its leaves are widely used as medicinal, anti-inflammatory and astringent purposes, and also as spices. [0005] Nishikawayanagi has given the scientific name of the genus Goryoli in the family Goryoliaceae to Tamarix chinensis roua.
s Lour), a shoot with leaves on a plant commonly known as Gory リ ュ. Although this plant is native to China, it is a deciduous small tree that has been introduced to Japan for appreciation and is planted in gardens and the like. It is used as perspiration, antipyretic, diuretic, antitussive, antibacterial (pneumococci, α-streptococci, staphylococcus, influenza). [0006] The whole plant is used for Senkaku. Its purpose is hemostasis, antidiarrhea, anti-inflammatory, tonic,
It is used for various bleeding symptoms such as urinary blood, cramps, and dysentery. However, cosmetics are only used as head cosmetics in JP-A-1-313414 and as bactericidal compositions in JP-A-60-184024. [0007] Mimusops elengi
Comes from India in the Tarai region of Nepal. It is an evergreen small tree of the Acate family, and is often planted as a garden tree called Misaki Nohana. The bark is dark gray with cracks. The leaves are elliptical to oblong and the flowers are axillary and solitary, or bunchy, small, pale yellow, star-shaped, and fragrant. For chemical use, bark is astringent and tonic, and is also prescribed for heat. The leaves are also used to treat snake bites. [0008] The chervil (Anthriscus cerefolium) leaf is native to the Middle East and Eastern Russia and the Caucasus and is widely used in France. Use is as a stomachic. [0009] The leaves of chives (Allium schoenoprasum) (also known as Asatsuki) are distributed in Europe and the United States and are used in cooking. Rhubarb has been used as an internal medicine since ancient times,
Water or ethanol extract is used, and its safety has been sufficiently confirmed. Various types of plants are used in rhubarb. Rhinoceros (Rheum Palm)
atum Linne, Rheum tanguticum
Maximowicz, Rhubarb (Rheum officinale Baillo)
n), Rheum coreanum Nakai or their interspecific hybrids, such as Shinshu Daio. Rhubarb used rhizomes of these plants. [0011] In tissues such as the lens, retina, and peripheral nerves that take up glucose independently of insulin, the intracellular glucose concentration increases due to a high blood glucose level due to diabetes. However, excess glucose that cannot be completely metabolized by the glycolysis of the main pathway is converted to sorbitol by aldose reductase in cells. Sorbitol is difficult to get out of the cell due to cell membrane charge, and the processing speed by sorbitol dehydratase (promotes the conversion of fructose to fructose on the alternative pathway) is slow. Increased internal osmotic pressure causes swelling of cells and degeneration of cell membrane, resulting in cell damage, retinopathy,
It is considered that various diabetic complications such as diabetic complications such as nephropathy and neuropathy occur. Conventionally, as a therapeutic agent for diabetes, not only insulin and various hypoglycemic agents are used, but also sufficient attention is required regarding diabetic complications. Therefore, a substance that inhibits the activity of aldose reductase involved in this is compounded. Thus, the purpose was to obtain a more effective drug or food. Means for Solving the Problems The present inventors have conducted various studies on aldose reductase inhibitory active ingredients which are safe and effective. As a result, strawberry leaf, sage, Nishikawayanagi, sensurugusa, Misakinohana leaf, chervil leaf , Chives leaves, and one or more extracts of rhubarb have high inhibitory activity, and have reached the present invention. These plants are extracted with water or a water-soluble organic solvent or a mixture of a water-soluble organic solvent and water. As the water-soluble organic solvent, methanol, ethanol, glycerin, propylene glycol, or a mixture thereof can be used. Heating also increases the extraction rate, so this step is added if necessary. The strawberry leaf thus extracted,
Extracts of sage, Nishikawayanagi, Senkaku-so, Misakinohana leaf, chervil leaf, chives leaf, and rhubarb extract can be distilled off the solvent if necessary, and can be incorporated into medicines and foods in various dosage forms. For example, it can be in the form of pills, tablets, syrups, powders, and health tea. Since the present invention is used for the prevention of complications of diabetes, it should be understood that diabetes preventives such as sulfonylureas, sulfonamides, biguanides, voglibose and acarbose, yacon, gymneva sylvestre, siberian ginseng, etc. , Ginseng, propolis, villasala and the like, which are preferably used in combination with foods for preventing diabetes, and the medicine or the food is desirably combined with a component effective for preventing diabetes, such as a hypoglycemic agent. It is also desirable to use a so-called diet therapy together. EXAMPLES The present invention will be described more specifically with reference to production examples and examples, but it is needless to say that the present invention is not limited to these production examples and examples. [Production Example 1] Strawberry leaf (Fragar
After crushing 10 g of ia vesca leaf) (dried product), 300 ml of purified water was added, and the mixture was heated for 5 hours with occasional stirring.
After allowing to cool, it was filtered and freeze-dried. [Production Example 2] Sage (Salvia officinalis)
Leaves) (dried product) (10 g) was pulverized, and 300 ml of a 50% aqueous ethanol solution was added thereto, and the mixture was left for 5 days with occasional stirring. After filtration, evaporation and freeze-drying. [Production Example 3] 10 g of Nishikawayanagi (dried product) was pulverized, and then 300 ml of a 50% aqueous ethanol solution was added. The mixture was left for 5 days with occasional stirring. After filtration, evaporation and freeze-drying. [Preparation Example 4] 10 g of dried sardines were ground, and 300 ml of a 50% aqueous ethanol solution was added. The mixture was allowed to stand for 5 days with occasional stirring. After filtration, evaporation and freeze-drying. [Production Example 5] Misakinohana leaf (dried product)
After crushing 10 g, a 50% aqueous ethanol solution 300
ml was added and left for 5 days with occasional stirring. After filtration, evaporation and freeze-drying. [Production Example 6-1] After crushing 10 g of chervil leaves (dried product), a 50% aqueous ethanol solution 3
After adding 00 ml, the mixture was left for 5 days with occasional stirring. After filtration, evaporation and freeze-drying. [Production Example 6-2] After crushing 10 g of chervil leaves (dried product), 300 ml of purified water was added, and the mixture was heated for 5 hours with occasional stirring. After letting it cool,
Filtered and lyophilized. [Production Example 7-1] After crushing 10 g of chives leaves (dried product), a 50% aqueous ethanol solution 3
After adding 00 ml, the mixture was left for 5 days with occasional stirring. After filtration, evaporation and freeze-drying. [Production Example 7-2] 10 g of chives leaves (dried product) was pulverized, and 300 ml of purified water was added thereto, followed by heating for 5 hours with occasional stirring. After letting it cool,
Filtered and lyophilized. [Production Example 8] Rhubarb (Rheum officinale Bai
llon) (dry product) (10 g) was pulverized, and 300 ml of a 50% aqueous ethanol solution was added thereto. The mixture was left for 5 days with occasional stirring. After filtration, evaporation and freeze-drying. Example-1 Health food (tablet) A: 20.0% of yacon B: 10.0% of propolis C: 5.0% of vitamin E D: Production example 1 25.0% E: Dextrin 25.0% F: crystalline cellulose 22.5% G: sucrose fatty acid ester 2.0% H: starch 0.5% The production method weighs each of the components A to F, and granulates H as a binder solution using a fluidized bed granulator. Become Thereafter, G is added and mixed uniformly to form tablets with a tableting machine. Example 2 Healthy Food (Granules) A: Production Example 2 20.0% B: Production Example 3 20.0% C: Production Example 4 10.0% D: Erythritol 30.0% E: Microcrystalline cellulose 18.0% F: Sucrose fatty acid ester 1.5% G: Starch 0.5% In the manufacturing method, each component of A to E is weighed, and G is granulated as a binder solution by a fluidized bed granulator. Thereafter, F is added and mixed uniformly to obtain granules. Example-3 Soup (powder soup) A: Ginseng 20.0% B: Production Example 5 10.0% C: Production Example 6-1 5.0% D: Production Example 6-2 5.0 % E: soy protein 15.0% F: powdered fat 13.0% G: bouillon 11.0% H: salt 6.0% I: thickener (guar gum) 5.0% J: milk protein 5.0 % K: Seasoning (amino acid etc.) 3.0% L: Flavor 2.0% In the manufacturing method, each component of A to L is weighed and uniformly mixed to make a powder soup. Example-4 Tea (powder type) A: Production Example 7-2 10.0% B: Production Example 8 10.0% C: Production Example 1 10.0% D: Banaba tea 25.0% E : Pigeon wheat 25.0% F: Black tea 20.0% In the manufacturing method, each component of A to F is weighed and uniformly mixed to obtain a powder. Example-5 Healthy Food (Tablets) A: Gymneva Sylvester 20.0% B: Siberian Ginseng 10.0% C: Vitamin E 5.0% D: Production Example 2 15.0% D: Production Example 3 10.0% E: Dextrin 25.0% F: Microcrystalline cellulose 22.5% G: Sucrose fatty acid ester 2.0% H: Starch 0.5% In the production method, each component of A to F is weighed and fluidized. Granulate H as a binder solution in a bed granulator. Thereafter, G is added and mixed uniformly to form tablets with a tableting machine. Example-6 Healthy Food (Granules) A: Production Example 4 20.0% B: Production Example 5 20.0% C: Production Example 6-1 10.0% D: Erythritol 30.0% E: Microcrystalline cellulose 18.0% F: Sucrose fatty acid ester 1.5% G: Starch 0.5% In the manufacturing method, each component of A to E is weighed, and G is granulated as a binder solution by a fluidized bed granulator. . Thereafter, F is added and mixed uniformly to obtain granules. Aldose reductase inhibition test The test method is described below. 1.5 ml of water, 0.6 ml of 500 mM potassium phosphate buffer (pH 6.0) containing 0.175% mercaptoethanol, and 0.1 ml of 1M aqueous glucose solution.
1.3 unit / ml aldose in 6 ml, 0.05 ml of sample solution, 0.15 ml of 2 mM NADPH aqueous solution (pH 7.0), and 3.6 ml of 10 mM sodium phosphate buffer (pH 7.0) containing 0.035% mercaptoethanol. 0.1 ml of a solution containing 0.4 ml of reductase is mixed in the above order. Time the addition of the enzyme. Measure the absorbance at 340 nm for 5 minutes while incubating at 37 ° C. Since the absorbance of water as a control decreases with time, the inhibition rate of the absorbance decrease of the sample for 1 minute was defined as the enzyme inhibition rate. The results are shown in the table. [Effect] An aldose reductase inhibitor containing at least one extract of strawberry leaf, sage, Nishikawayanagi, Senkaku grass, Misaki nohana leaf chervil leaf, chives leaf, and rhubarb extract has been used up to now. The plant is highly safe, inhibits aldose reductase, and can prevent various complications of diabetes.

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Claims (1)

[Claim 1] An aldose reductase inhibitor containing one or more extracts of strawberry leaf, sage, Nishikawayanagi, Senkaku-hana, Misakinohana leaf, chervil leaf, chives leaf, and rhubarb.