JP2002255837A - Aldose reductase inhibitor - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a safe and effective aldose reductase inhibitor preventing several kinds of complications of diabetes. SOLUTION: This aldose reductase inhibitor is obtained by formulating the extract of one or more of the aboveground parts of Filipendula ulmaria, the flowers and stems of Ilex paraguarienesis and Arnica montana, the aboveground parts of Allium schoenoprasum, the leaves of Pimenta dioicalis, Rubus suavissims S. Lee and Psidium guayava, the aboveground parts of lagerstroemia speciosa and the flowers and stems of Tanacetum vulgare.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to aldose reductase inhibitors which prevent various complications of diabetes.

[0002]

2. Description of the Related Art In Japan, there are about 6 million diabetic patients, including those who tend to have this tendency, 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] Medu sweet (Natsuyuki snow)
The name Filipendula ulmaria is a plant native to Europe and Asia, and is used for food and for medicinal purposes such as hyperacidity and heartburn. Mate tea is distributed in South America under the scientific name Ilex paraguarienesis, and has been used as mate tea since ancient times.

[0004] Arnica
ca montana is a perennial plant of the Asteraceae family which is produced in alpine warm regions such as the Alps, Himalayas and Rockies, and has long been used in Europe as an anti-inflammatory. Chabir (Asatsuki) Scientific name is Allium schoenoprasum and is used for food. All Spice (Pimento) is scientific name Pimenta dio
Called icalis, a plant native to Central America, Mexico and the West Indies, its seeds are widely used as spices. Ten tea (tencha) is widely consumed as tea, but is recently used as effective for allergic rhinitis and hay fever.

[0005] The guava scientific name Psidium guayava is called a bunjirou or gypsophile, and is a plant belonging to the genus Bunjiro in the family Myrtaceae, and its scientific name is Psidium guayava.
guajaba L.). Generally, the berries are eaten raw, jam, juice, or the like. It is native to tropical America, but is widely cultivated in tropical and subtropical areas, cultivated in southern Kyushu in Japan, and wild in the Ryukyu Islands.
Guava is used as a drug for enteritis, dysentery, and indigestive diarrhea, and leaves are used as a substitute for tea. Further, in Japanese Patent Application Laid-Open No. 5-246837 filed by the applicant of the present application, use of a solvent extract of guava leaves as a cosmetic material is intended to use for whitening, prevention of rough skin, and the like.

[0006] Lagerstroemia sp.
eciosa is a semi-deciduous tree that grows in India and is a plant belonging to the genus Lagerstroemia in the family Sorrelidae. The roots of this sedge are used for diarrhea and the bark and leaves are used as laxatives. The tansy is called Tanacetum vulgare and is widely used for food.

[0007]

2. Description of the Related Art In tissues such as the lens, the 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. Excess glucose that cannot be metabolized in the glycolysis pathway of the 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 (which promotes the conversion of fructose into the alternative pathway into fructose) is slow. Increased internal osmotic pressure causes cell swelling and cell membrane degeneration, 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 for diabetic complications. Thus, the purpose was to obtain a more effective drug or food.

[0008]

As a result of various studies on safe and effective aldose reductase-inhibiting active ingredients, the present inventors have found that the above-ground parts of Medu Sweet, yerba mate, flowers or stems of Arnica, the above-ground parts of charble, The inventors have found that one or more extracts of spices, marten tea, guava leaves, above-ground parts of the labaceae, tansy flowers or stems have high inhibitory activity, and 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. This step may be added as needed, as heating also increases the extraction rate.

[0010] The above-ground parts of the medu suite extracted above, mate tea, arnica flowers or stems, above-ground parts of charbles, allspice, marble tea, guava leaves, above-ground parts of Ohanasrassberg, tansy flowers or stems The solvent can be distilled off from the extract as necessary, and the extract 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 healthy 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 and yacon, gymneva sylvester, siberian ginseng, etc. , Ginseng, propolis, villasala and the like, which are preferably used in combination with foods for preventing diabetes, and this medicine or foods are 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.

[0012]

EXAMPLES The present invention will be described more specifically with reference to the following production examples and examples. However, it goes without saying that the present invention is not limited to these production examples and examples.

[Production Example 1-1] 10 g of the above-ground portion (dried product) of Medu Sweet was pulverized, and then 300 ml of a 50% ethanol aqueous solution was added, and the mixture was left for 5 days with occasional stirring.
After filtration, evaporation and freeze-drying. After freeze-drying.

[Production Example 1-2] 10 g of the above-ground part (dried product) of Medu Sweet was pulverized, and then 300 ml of purified water was added thereto and heated for 5 hours with occasional stirring. After allowing to cool, it was filtered and freeze-dried.

[Production Example 2-1] 10 g of mate tea (dried product)
After grinding, 300 ml of ethanol was added, and the mixture was left for 5 days with occasional stirring. After filtration, evaporation and freeze-drying.

[Production Example 2-2] 10 g of mate tea (dried product)
After grinding, 300 ml of a 50% aqueous ethanol solution was added, and the mixture was left for 5 days with occasional stirring. After filtration, evaporation and freeze-drying.

[Production Example 2-3] Mate tea (dry product) 10 g
After pulverizing, 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 3-1] Arnica flower or stem (dry product) (10 g) was pulverized, and then 300 ml of a 50% ethanol aqueous solution was added.
After filtration, evaporation and freeze-drying.

[Preparation Example 4-1] 10 g of the above-ground portion (dried product) of the charble was crushed, and 300 ml of a 50% aqueous ethanol solution was added thereto. After filtration, evaporation and freeze-drying.

[Production Example 4-2] 10 g of the above-ground portion (dried product) of the charble was pulverized, and then 300 ml of purified water was added thereto, followed by heating for 5 hours with occasional stirring. After allowing to cool, it was filtered and freeze-dried.

[Production Example 5-1] After crushing 10 g of allspice (dry 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 5-2] 10 g of all-spice (dry product) was pulverized, and then 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 6-1] 10 g of ten tea (dried product)
After grinding, 300 ml of a 50% aqueous ethanol solution was added, and the mixture was left for 5 days with occasional stirring. After filtration, evaporation and freeze-drying.

[Production Example 7-1] Guava leaf (dried product) 1
After grinding 0 g, 300 ml of 50% ethanol aqueous solution
Was added and left for 5 days with occasional stirring. After filtration, evaporation and freeze-drying.

[Production Example 8-1] 10 g of the above-ground portion (dried product) of Prunus brassicae was ground, and 300 ml of a 50% aqueous ethanol solution was added thereto. After filtration, evaporation and freeze-drying.

[Production Example 9-1] 10 g of a tansy flower or stem (dried product) was pulverized, and 300 ml of a 50% aqueous ethanol solution was added thereto. The mixture was allowed to stand for 5 days with occasional stirring.
After filtration, evaporation and freeze-drying.

Example-1 Health food (tablets) A: 20.0% for yacon B: 10.0% for propolis C: 5.0% for vitamin E D: Production example 1-1 25.0% E: dextrin 25. 0% F: crystalline cellulose 22.5% G: sucrose fatty acid ester 2.0% H: starch 0.5% The manufacturing method weighs each of the components A to F and converts H into a binder solution using a fluidized bed granulator. Granulate as Thereafter, G is added and mixed uniformly, and made into tablets by a tableting machine.

Example 2 Healthy Food (Granules) A: Production Example 1-2 20.0% B: Production Example 2-1 20.0% C: Production Example 3-1 10.0% D: Erythritol 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 used as a binder solution in a fluidized bed granulator. Granulate as Thereafter, F is added and mixed uniformly to obtain granules.

Example-3 Soup (powder soup) A: Ginseng 20.0% B: Production Example 2-3 10.0% C: Production Example 4-1 5.0% D: Production Example 5-1-5 0.0% E: Soy protein 15.0% F: Powdered oil 13.0% G: Bouillon 11.0% H: Salt 6.0% I: Thickener (guar gum) 5.0% J: Milk protein 5 0.0% K: Seasoning (amino acids, etc.) 3.0% L: Flavor 2.0% In the manufacturing method, each component of A to L is weighed and uniformly mixed to obtain a powdered soup.

Example-4 Tea (powder type) A: Production Example 2-3 10.0% B: Production Example 4-2 10.0% C: Production Example 6-1 10.0% D: Banaba tea 25 0.0% 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 Health Food (Tablets) A: Gymneva Sylvester 20.0% B: Siberian Ginseng 10.0% C: Vitamin E 5.0% D: Production Example 7-1 15.0% D: Production Example 8-1 10.0% E: dextrin 25.0% F: crystalline cellulose 22.5% G: sucrose fatty acid ester 2.0% H: starch 0.5% The production method uses each component of A to F. Weigh and granulate H as binder solution in fluid bed granulator. Thereafter, G is added and mixed uniformly, and made into tablets by a tableting machine.

Example-6 Healthy Food (Granules) A: Production Example 9-1 20.0% B: Production Example 4-2 20.0% C: Production Example 7-1 10.0% D: Erythritol 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 used as a binder solution in a fluidized bed granulator. Granulate as 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 1 M aqueous glucose solution.
1.3 unit / ml aldose in 6 ml, 0.05 ml of sample solution, 0.15 ml of 2 mM aqueous NADPH 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 to which 0.4 ml of reductase has been added 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.

[0035]

[Effect] One of the above-ground parts of Medu Sweet, Yerba Mate, Arnica flower or stem, above-ground part of Chaburu, allspice, marbled tea, guava leaf, above-ground part of Ohanasasuruberi, Tanji flower or stem extract The aldose reductase inhibitor containing the above extract has high safety in plants that have been edible so far, inhibits aldose reductase, and can prevent various complications of diabetes.

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Claims (1)

[Claims] 1. An above-ground part of a medu suite, a mate tea, an arnica flower or stem, an above-ground part of a chabble, allspice, marten tea, guava leaves, an above-ground part of a giant crab, or a tansy flower or stem. Aldose reductase inhibitor containing an extract of