JP4818549B2 - Aldose reductase inhibitor - Google Patents

Description

【００３５】
【効果】
ストロベリーリーフ、セージ、西河柳、仙鶴草、ミサキノハナの葉チャービルの葉、チャイブスの葉、大黄の抽出物の１種以上の抽出物を配合したアルドースレダクターゼ阻害剤は今まで食用とされた植物で安全性が高く、アルドースレダクターゼを阻害し、糖尿病の各種の合併症を防ぐことができる。[0001]
[Industrial application fields]
The present invention relates to an aldose reductase inhibitor that prevents various complications of diabetes.
[0002]
[Prior art]
In Japan, there are about 6 million diabetic patients, and even if people with such a tendency are included, it has reached 10% of Japan's population and is becoming the scale of national diseases. There are two types of diabetes, insulin-dependent and insulin-independent, and most Japanese patients have non-insulin-dependent diabetes. However, diabetes is said to cause various complications.
[0003]
Strawberry leaf is a leaf of strawberry (Fragaria vesca, F. viridis, F. mosahata, F. chiloensis, F. virginiana) and is drunk as tea.
[0004]
Sage (Salvia officinalis S. lavandulaefolia S. tribolaulmaria) is a plant native to the Mediterranean and widely distributed in Europe. Leaves are used for medicinal purposes, for anti-inflammatory and astringent purposes, and also for spices.
[0005]
Nishigayu is a young branch with leaves of a plant called Tamarix chinensis Lour, commonly known as Gyoryu. Although this plant is originally from China, it is a small deciduous tree that came to Japan for viewing and was planted in gardens. Applications include sweating, antipyretic, diuretic, antitussive, antibacterial (pneumococcus, α-streptococcus, white staphylococci, influenza).
[0006]
Sengakuso uses the whole plant. Its purpose is hemostasis, antistasis, anti-inflammation, tonic, and it is used for various bleeding symptoms such as vomiting, stool blood, urine blood, under collapse band, and dysentery. However, as cosmetics, they 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 from the Acatezaceae family and is often planted as a garden tree. The bark is dark gray and cracked. The leaves are oval to oblong, and the flowers are fertile and single, or bunch are small, pale yellow and star-shaped, and have a good fragrance. For chemical use, the bark is astringent and tonic, and is also prescribed for heat. The leaves are also used for treatment when bitten by a snake.
[0008]
Chervil (Anthriscus cerefolium) leaves are native to the Middle East / Eastern Russia and the Caucasus and are widely used in France. Use is for stomachic medicine.
[0009]
The leaves of Allium schoenoprasum (aka Asatsuki) are distributed in Europe and America and are used in cooking.
[0010]
Daio has long been used as an internal medicine and is made of water or ethanol extract, and its safety has been sufficiently confirmed. Daihuang uses a variety of plants. Examples include Rheum Palmatum Linne, Rheum tanguticum Maximowicz, Rheum officinale Baillon, Rheum coreanum Nakai, or interspecific hybrids such as Shinshu Daio. Daiki is the root of these plants.
[0011]
[Background Art and Problems to be Solved by the Invention]
Insulin-independent tissues such as the lens, retina, and peripheral nerves that take up glucose, intracellular glucose levels rise due to high blood sugar levels due to diabetes, and excess glucose that cannot be metabolized by the main glycolytic pathway Is converted to sorbitol by aldose reductase in the cell. Sorbitol is not easily released from the cell due to cell membrane charge, and sorbitol accumulates in the cell due to the slow processing speed of sorbitol dehydrase (which promotes conversion to fructose on the alternative pathway of polyol). Increased internal osmotic pressure causes cell swelling and cell membrane degeneration, and the resulting cell damage is thought to cause various diabetic complications such as diabetic complications such as retinopathy, nephropathy, and neuropathy. ing.
Conventionally, not only insulin and various antihyperglycemic agents have been used as a therapeutic agent for diabetes, but also sufficient attention must be paid for diabetic complications, so a substance that inhibits the activity of aldose reductase involved in this is included. The purpose was to obtain more effective chemicals or foods.
[0012]
[Means for Solving the Problems]
As a result of various investigations on safe and effective aldose reductase inhibitory active ingredients, the present inventors have extracted one or more of strawberry leaf, sage, Nishikawayanagi, Sentsukakusa, Misakinohana leaf, chervil leaf, chives leaf, and Daiki. It was found that the product has a high inhibitory activity, and reached the present invention.
[0013]
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.
Adding heat also increases this extraction rate, so this step is added if necessary.
[0014]
The extract of strawberry leaf, sage, Nishikawayanagi, Sentsukakusa, Misaki no Hana leaf, Chervil leaf, Chives leaf, Daihuang extract extracted in this way, if necessary, distill the solvent, various dosage forms for drugs and food Can be blended. For example, it can be in the form of pills, tablets, syrups, powders, health teas.
[0015]
In addition, since the present invention is used for the prevention of diabetic complications, naturally, antidiabetic drugs such as sulfonylureas, sulfonamides, biguanides, voglibose, acarbose, yacon, gymneba sylvesta, siberian ginseng, ginseng. In addition, it is preferable to use in combination with foods that prevent diabetes prevention such as propolis and villasala, and it is desirable to add ingredients effective for diabetes prevention such as hypoglycemic agents to these drugs or foods at the same time. It is also desirable to use so-called diet therapy.
[0016]
【Example】
Hereinafter, the present invention will be described more specifically with reference to production examples and examples. However, it is needless to say that the present invention is not limited to these production examples and examples.
[0017]
[Production Example 1] After crushing 10 g of strawberry leaf (Fragaria vesca leaf) (dried product), 300 ml of purified water was added and heated for 5 hours with occasional stirring. This was allowed to cool, then filtered and lyophilized.
[0018]
[Production Example 2] After 10 g of sage (Salvia officinalis leaves) (dried product) was pulverized, 300 ml of 50% ethanol aqueous solution was added and allowed to stand for 5 days with occasional stirring. This was filtered, evaporated, and lyophilized.
[0019]
[Production Example 3] After 10 g of Nishikawayanagi (dried product) was pulverized, 300 ml of a 50% ethanol aqueous solution was added and left for 5 days with occasional stirring. This was filtered, evaporated, and lyophilized.
[0020]
[Production Example 4] After crushing 10 g of Sentsukakusa (dried product), 300 ml of 50% ethanol aqueous solution was added and left for 5 days with occasional stirring. This was filtered, evaporated, and lyophilized.
[0021]
[Production Example 5] After crushing 10 g of Misakinohana leaf (dried product), 300 ml of 50% ethanol aqueous solution was added and allowed to stand for 5 days with occasional stirring. This was filtered, evaporated, and lyophilized.
[0022]
[Production Example 6-1] After crushing 10 g of chervil leaves (dried product), 300 ml of a 50% ethanol aqueous solution was added and allowed to stand for 5 days with occasional stirring. This was filtered, evaporated, and lyophilized.
[0023]
[Production Example 6-2] After crushing 10 g of chervil leaves (dried product), 300 ml of purified water was added and heated for 5 hours with occasional stirring. This was allowed to cool, then filtered and lyophilized.
[0024]
[Production Example 7-1] After crushing 10 g of chives leaves (dried product), 300 ml of 50% aqueous ethanol solution was added and allowed to stand for 5 days with occasional stirring. This was filtered, evaporated, and lyophilized.
[0025]
[Production Example 7-2] After crushing 10 g of chives leaves (dried product), 300 ml of purified water was added and heated for 5 hours with occasional stirring. This was allowed to cool, then filtered and lyophilized.
[0026]
[Production Example 8] After 10 g of Rheum officinale Baillon (dried product) was pulverized, 300 ml of 50% ethanol aqueous solution was added and left for 5 days with occasional stirring. This was filtered, evaporated, and lyophilized.
[0027]
Example-1 Health food (tablet)
A: Yacon 20.0%
B: Propolis 10.0%
C: Vitamin E 5.0%
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%
In the production method, each component of A to F is weighed and granulated with H as a binder solution in a fluidized bed granulator. G is then added and mixed uniformly to form tablets with a tableting machine.
[0028]
Example-2 Health food (granule)
A: Production Example 2 20.0%
B: Production Example 3 20.0%
C: Production example 4 10.0%
D: Erythritol 30.0%
E: Crystalline cellulose 18.0%
F: Sucrose fatty acid ester 1.5%
G: Starch 0.5%
In the production method, each component of A to E is weighed and granulated with G as a binder solution in a fluidized bed granulator. Then F is added and mixed uniformly to form granules.
[0029]
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 oil and 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 acids, etc.) 3.0%
L: Fragrance 2.0%
In the production method, each component of A to L is weighed and mixed uniformly to obtain a powder soup.
[0030]
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: Pigeont 25.0%
F: Black tea 20.0%
In the production method, the components A to F are weighed and uniformly mixed to obtain a powder.
[0031]
Example-5 Health food (tablet)
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: Crystalline 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 granulated with H as a binder solution in a fluidized bed granulator. G is then added and mixed uniformly to form tablets with a tableting machine.
[0032]
Example-6 Health food (granule)
A: Production Example 4 20.0%
B: Production Example 5 20.0%
C: Production example 6-1 10.0%
D: Erythritol 30.0%
E: Crystalline cellulose 18.0%
F: Sucrose fatty acid ester 1.5%
G: Starch 0.5%
In the production method, each component of A to E is weighed and granulated with G as a binder solution in a fluidized bed granulator. Then F is added and mixed uniformly to form granules.
[0033]
The aldose reductase inhibition test test method is shown below.
1.5 ml of water, 0.6 ml of 500 mM potassium phosphate buffer (pH 6.0) containing 0.175% mercaptoethanol, 0.6 ml of 1M aqueous glucose solution, 0.05 ml of sample solution, 2 ml of 2 mM NADPH aqueous solution (pH 7.0) Mix 0.1 ml of a solution obtained by adding 0.4 ml of 1.3 unit / ml aldose reductase to 3.6 ml of 10 mM sodium phosphate buffer (pH 7.0) containing .15 ml and 0.035% mercaptoethanol. . Take time with enzyme addition.
Measure absorbance at 340 nm for 5 minutes while incubating at 37 ° C.
Since the absorbance when using water as a control decreases with time, the inhibition rate of the absorbance decrease for 1 minute of the sample was defined as the enzyme inhibition rate.
[0034]
The results are shown in the table.

[0035]
【effect】
An aldose reductase inhibitor that contains one or more extracts of strawberry leaf, sage, Nishikawayanagi, Sentsukakusa, Misakinohana leaf chervil leaf, chives leaf, Daihuang extract is safe in plants that have been eaten so far It is highly potent and can inhibit aldose reductase and prevent various complications of diabetes.

Claims (1)

An aldose reductase inhibitor containing an extract of Nishi-Hayanagi