JP2649296B2 - Composition for reducing uremic substances - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a composition for reducing uremic substances.

[0002]

2. Description of the Related Art In chronic renal failure, renal function gradually decreases,
It is a syndrome that causes a decrease in the amount of glomerulus and it is known to follow irreversible progression. The symptoms worsen on a monthly or yearly basis, and acute renal failure is significantly different from progression on an hourly or daily basis. In recent years, basic research on chronic renal failure has gradually elucidated the factors that progress the symptoms, but there is no effective treatment yet, and it depends on diet, hemodialysis, kidney transplantation, etc. It is the current situation.

[0003]

SUMMARY OF THE INVENTION In view of the above situation, it has been proposed to reduce uremic substances which cause the progression of chronic renal failure,
There is a demand for the development of a composition for reducing uremic substances that can avoid dialysis, can be used continuously for a long time, can be mass-produced at low cost, and is effective for improving chronic renal failure.

[0004]

Means for Solving the Problems The present inventors have conducted intensive studies in order to solve the above problems, and as a result, (−) −
We have discovered that epigallocatechin 3-O-gallate (hereinafter referred to as EGCg) has an effect of reducing uremic substances, and completed the present invention. That is, the present invention relates to EG
It is a composition for reducing uremic substances containing Cg as an active ingredient. EGCg, which is an active ingredient of the present invention, is a tea (Cammellia sine) which we serve for daily drinking.
nsis) by extraction, purification, etc., but other raw materials and chemically synthesized products may be used. When tea leaves are used as raw materials, they can be at any stage of the normal tea-making process, from fresh leaves to finished tea (dried tea), and can be used as unfermented tea, semi-fermented tea, or fermented tea regardless of the degree of fermentation. it can. A typical method for preparing these compounds is described in Patents filed by the present inventors (JP-A-64-90124 and JP-A-1-265023).
Is disclosed.

[0005] Next, the following describes test examples in which EGCg, which is an active ingredient of the present invention, has a uremic substance reducing action and safety. Effect on Adenine-Induced Chronic Renal Failure Rats (1) Preparation of Chronic Renal Failure Model Rats Wistar male rats (weight: about 200 g) were treated with 18
% Casein synthetic feed, and after pre-breeding for one week,
24 with 18% casein synthetic feed containing 0.75% adenine
They were bred for days, and rats with chronic renal failure were produced. The breeding environment was performed at a temperature of 22 ± 1 ° C. and a humidity of about 60% RH.
The feed composition was as follows: 100 g, casein 18 g, α-corn starch 57.9 g, sucrose 15 g, soybean oil: liver oil (4: 1) 2 g, mineral mixture 4 g, vitamin mixture 1
g, 2 g of cellulose powder and 0.1 g of choline chloride. Adenine-containing feed is 18% casein synthetic feed 1
0.75% adenine was added to 00g.

(2) Chronic renal insufficiency improving effect EGCg, which is an active ingredient of the present invention, is dissolved in water from day 20 after the start of adenine administration to the rats shown in (1).
After continuous oral administration until the 34th day, the urinary content of the uremic substance methylguanidine (MG) was determined. For the determination of methylguanidine (MG), a sample obtained by adding 2 ml of a 15% trichloroacetic acid solution to 0.5 ml of urine and removing protein was used. After centrifugation (3000 rpm, 10 minutes), the supernatant was filtered through a membrane filter (0.45 μm).
Using an automatic guanidine analyzer (manufactured by JASCO Corporation), the mixture was reacted with 9,10, -phenanthrenequinone under alkaline conditions, and measured with a fluorometer. Table 1 shows the amount of uremic substance (methylguanidine) in urine.

[0007]

[Table 1]

[0008] As shown in the above results, the administration group of EGCg which is the active ingredient of the present invention,
Compared with the control group, the amount of methylguanidine, which is a uremic substance, is reduced, which is considered to be effective in improving the symptoms of chronic renal failure caused by these uremic substances.

Test Example 2 Acute toxicity test EDCg, an active ingredient of the present invention, suspended in saline was added to 10 ddy male mice per group at a constant temperature (23 ± 1).
℃) and constant humidity (55 ± 5% RH), and an acute toxicity test was performed. As a result, no death occurred at 1000 mg / kg.

Test Example 3 Mutagenicity test An Ames test was performed using salmonella (S. typhimurium) as a marker for reversion from histidine auxotrophy to non-auxotrophy. As test bacteria, Sanemonella typhimurium TA100 and Salmonella typhimurium TA9
8, a direct test and a metabolic activation test were performed. As a result, EGCg, which is an active ingredient of the present invention, was determined to have no mutagenicity (negative) without an increase in mutant colonies in direct tests and metabolic activation tests.

[0011] As shown in the above results, EGCg, which is an active ingredient of the present invention, has no toxicity, is extremely safe, and can be said to provide a highly effective composition for reducing uremic substances. . Next, the present invention will be described in detail with application examples. EGCg, which is an active ingredient of the present invention, is a common food such as candy, caramel, chocolate, jelly, ice cream, yogurt, chewing gum, baked confectionery, rice cake, bread, confectionery such as fresh confectionery, coffee, tea, juice, milk, etc. It can be added to beverages such as beverages, alcoholic beverages, sprinkles, boiled soy sauce, prepared dishes, dressings, mayonnaise, soy sauce, sauces, ketchup, miso soup, soups, and cooked rice. Also, it can be taken orally as tablets, capsules, granules, fine granules, powders, liquids and the like. It is necessary to take into account the degree of excretion of uremia, age and body weight,
It is preferable to take g to 10 g several times a day. In addition to oral ingestion, administration by injection, liquid for external use, soft pepper, suppository, etc. is also possible. It is desirable to administer separately. Raw materials and manufacturing methods for preparing foods or pharmaceuticals can be manufactured without any change from ordinary ones.

[0012]

【Example】

Example 1 sugar 40 g starch syrup 25 g water 25 ml perfume small amount EGCg 2 g Yield 60 g (finished) According to the above formula, is heated and completely dissolved. Once this was boiled down to about 43 degrees Baume
The mixture is further boiled in a vacuum pan, cooled, mixed, kneaded well, cooled to about 70 ° C., and placed in a mold. EGCg, which is an active ingredient of the present invention, is added to 3 g of this candy.
0 mg is contained.

Example 2 Agar 12 g Sugar 500 g Water syrup 300 g Water 500 ml Fragrance and Western liquor Small amount EGCg 9.5 g Yield 950 g (finished) According to the above formula, put in, heat and dissolve.
While sequentially adding. Boil down to 103 ° C,
Add, cool and solidify. Cut to appropriate size. 20 mg of this agar jelly contains 200 mg of EGCg, which is an active ingredient of the present invention.

Example 3 300 g of flour 300 g of sugar 300 g of butter A small amount of fragrance 7.2 g of EGCg Yield: 720 g (done) Whisk the mixture according to the method described above and add the mixture in small portions. Next, is mixed homogeneously and is added as appropriate. After the mixed dough is cooled in a refrigerator, the thickness of the mixed dough is extended to a constant value, and the mold is cut out. Baking at 180 ~ 200 ℃ 7 ~
Perform for 10 minutes. 10 g of this cookie contains 100 mg of EGCg, which is an active ingredient of the present invention.

Example 4 Spray-dried lactose 188 g Corn starch 18.8 g Polyvinylpyrrolidone 3.2 g EGCg 30 g According to a total of 240 g above,-was mixed uniformly, and gelatin capsules were each filled with 400 mg of the mixture. One capsule contains 50 mg of EGCg, which is an active ingredient of the present invention.
It is contained.

Example 5 Corn starch 19 mg Crystalline cellulose 30 mg Magnesium stearate 1 mg Lactose 80 mg EGCg 20 mg Yield 150 mg According to the above-mentioned formula, after mixing uniformly, compression molding is performed to obtain a tablet of 150 mg per tablet. This tablet contains 20 mg of EGCg, which is an active ingredient of the present invention.

Example 6 350 g of sugar 200 g of sorbitol 200 g of methyl paraoxybenzoate 0.2 g of propyl paraoxybenzoate 0.15 g of sodium citrate 8 g of citric acid 1.2 g of fragrance a small amount of EGCg 2 g of purified water 438 g Yield 1000 g According to the above formula, is dissolved and mixed to obtain a syrup solution. 50 g of this syrup solution contains 1000 mg of EGCg, which is an active ingredient of the present invention.

[0018]

EGCg, which is an active ingredient of the present invention, has a uremic substance-lowering effect and has been shown to be useful for diseases caused by uremic substances. In addition, this ingredient, which shows its effectiveness in a very small amount, is a tea ingredient that has been drunk since ancient times, so its safety is high,
It is possible to supply a large amount of the composition for reducing uremic substances, and it is considered to be extremely useful in industry.

──────────────────────────────────────────────────の Continuation of front page (51) Int.Cl. ⁶ Identification code Agency reference number FI Technical indication location // C07D 311/62 C07D 311/62 (56) References JP-A-4-26624 (JP, A ) Nephron, 58 [2] (1991. 2) p. 155-160

Claims (1)

(57) [Claims] 1. A composition for reducing a uremic substance, comprising (-)-epigallocatechin 3-O-gallate as an active ingredient.