JPH04360831A - Composition for reducing uremic substance - Google Patents

Abstract

PURPOSE:To obtain an inexpensive mass-producible composition, useful for reducing uremic substances and capable of suppressing the progress of chronic renal insufficiency, avoiding dialytic introduction and suppressing deterioration of the chronic renal insufficiency without any problems even in continuous use for a long period. CONSTITUTION:A composition for reducing uremia substances containing (-)- epiqallocatechin theta3-O-Rallate (EGCg) as an active ingredient. Thereby, the aforementioned composition, useful for reducing the uremic substances and capable of reducing the amount of methylguanidine which is a uremic substance, effective in improving symptoms of chronic renal insufficiency caused by the uremic substances and having a high safety is obtained. The above-mentioned active ingredient is prepared by using operation such as extraction or purification from green tea; however, the active ingredient derived from other raw materials or chemically synthesized substances may be used. If green tea leaves are used as the raw material, the tea leaves in any stages of raw leaves to finished green tea (dried green tea) may be used. Furthermore, any of unfermented tea, semifermented tea or fermented tea can be used. In addition, the chronic renal insufficiency is irreversible diseases and relies on therapeutic methods such as alimentary therapy, hemodialysis or renal transplanting.

Description

[Detailed description of the invention]

0001

FIELD OF THE INVENTION The present invention relates to a composition for reducing uremic substances.

0002

[Prior Art] Chronic renal failure is a gradual decline in renal function.
It is a syndrome that causes excessive glomerular filtration, and is known to progress irreversibly. The symptoms worsen over months or years, which is very different from acute renal failure, which progresses over hours or days. In recent years, basic research on chronic renal failure has gradually begun to elucidate the factors that cause the symptoms to progress, but there is still no effective treatment, and treatment remains dependent on diet therapy, hemodialysis, kidney transplantation, etc. This is the current situation.

0003

[Problems to be solved by the invention] In response to this current situation, a new method has been developed that reduces uremic substances that cause the progression of chronic renal failure, avoids the need for dialysis, can be used continuously for a long period of time, and can be manufactured in large quantities at low cost. It is desired to develop a composition for reducing uremic substances that is effective in improving chronic renal failure.

0004

[Means for Solving the Problems] In order to solve the above problems, the present inventors have conducted intensive research and found that (-)-epigallocatechin 3-O-gallate (hereinafter referred to as EGCg) is a uremic substance. The present invention was completed based on the discovery that there is an effect of reducing the That is, the present invention provides EG
This is a composition for reducing uremic substances containing Cg as an active ingredient. EGCg, which is the active ingredient of the present invention, is derived from tea (Cammelia sinus) that we drink daily.
It can be obtained by extraction, purification, and other operations from P. ensis, but it may also be derived from other raw materials or chemically synthesized. When using tea leaves as raw materials, they can be from any stage of the normal tea manufacturing process, from fresh leaves to finished tea (dried tea), and regardless of the degree of fermentation, unfermented tea,
Both semi-fermented tea and fermented tea can be used. Typical methods for preparing these compounds are disclosed in patents previously filed by the present inventors (JP-A-64-90124 and JP-A-1-265023).

Next, Test Example 1 will explain the fact that EGCg, which is the active ingredient of the present invention, has a uremic substance reducing effect and its safety. Effects on adenine-induced chronic renal failure rats (1) Preparation method of chronic renal failure model rats Wistar male rats (body weight: approximately 200 g) were fed with 18% casein synthetic diet, and after being prefed for one week, 0.75% Rats with chronic renal failure were produced by raising them on a 18% casein synthetic diet containing adenine for 24 days. The breeding environment is a temperature of 22±1℃.
, humidity was around 60% RH. The feed composition was 18 g of casein, 57.9 g of α-corn starch, 15 g of sucrose, soybean oil: cod liver oil (in 100 g).
4:1) 2g, mineral mixture 4g, vitamin mixture 1g,
Contains 2g of cellulose powder and 0.1g of choline chloride. Adenine-containing feed is 18% casein synthetic feed 100
0.75% adenine was added to the g.

(2) Chronic renal failure improving effect EGCg, which is the active ingredient of the present invention, is dissolved in water and continuously administered orally to the rats shown in (1) from the 20th day after the start of adenine administration until the 34th day. The uremic substance methylguanidine (M
The urinary content of G) was determined. Methylguanidine (M
For the quantitative determination of G), a sample was used which had been deproteinized by adding 2 ml of 15% trichloroacetic acid solution to 0.5 ml of urine. Centrifugation (
3000 rpm for 10 minutes), the supernatant was ▲filtered through a membrane filter (0.45 μm), and analyzed under alkaline conditions using a guanidine automatic analyzer (manufactured by JASCO Corporation).
,10,-phenanthrenequinone and measured using a fluorophotometer. Table 1 shows the amount of uremic substance (methylguanidine) in urine.

[0007]

[Table 1]

[0008] As shown in the above results, the group administered with EGCg, which is the active ingredient of the present invention, at any dose,
It is thought to be effective in reducing the amount of methylguanidine, a uremic substance, compared to the control group, and improving symptoms of chronic renal failure caused by these uremic substances.

Test Example 2. Acute toxicity test EGCg, the active ingredient of the present invention, suspended in physiological saline was administered to 10 male DDY mice at a constant temperature (23±1°C).
), and an acute toxicity test was conducted by oral administration under conditions of constant humidity (55±5% RH). As a result, there were no fatal cases with administration of 1000 mg/kg.

Test Example 3. Mutagenicity Test An Ames test was conducted using a reversion mutation from auxotrophic to non-auxotrophic histidine in Salmonella (Salmonella Typhimurium) as an indicator. As test bacteria, Sanemonella typhimurium TA100 and Salmonella typhimurium T
Direct tests and metabolic activation tests were conducted using A98. As a result, EGCg, which is the active ingredient of the present invention, did not show an increase in mutant colonies in the direct test or the metabolic activation test, and was determined to have no mutagenicity (negative).

[0011] As shown in the above results, EGCg, which is the active ingredient of the present invention, is not toxic, and it can be said that it has become possible to provide a composition for reducing uremic substances that is extremely safe and highly effective. . Next, the present invention will be explained in detail using application examples. EGCg, which is the active ingredient of the present invention, is commonly used in foods,
For example, candy, caramel, chocolate, jelly, ice cream, yogurt, chewing gum,
Sweets such as baked sweets, mochi, bread, and fresh sweets, coffee,
It can be added to drinks such as tea, juice, milk drinks, alcoholic drinks, furikake, tsukudani, side dishes, dressings, mayonnaise, soy sauce, sauces, ketchup, miso soup, soups, and cooked rice. It can also be taken orally in the form of tablets, capsules, granules, fine granules, powders, liquids, etc. The optimal intake should take into account the degree of uremic substance excretion, age, and body weight, but it is usually between 100 mg and 100 mg.
It is preferable to take 0g in divided doses several times a day. In addition to taking it orally, it can also be administered through injections, external solutions, soft pills, suppositories, etc. For parenteral administration, the dose is 1 mg to 250 mg several times a day. It is advisable to administer the drug separately. The raw materials and manufacturing methods used to form foods or formulations can be manufactured without any change from usual ones.

0012

【Example】

Example 1 ■Sugar
40g
■Mizuame
25 g ■Water

25 ml ■Fragrance
Small amount ■EGCg

2g



Yield 60
g (Complete) Heat ■, ■, ■ according to the above recipe to completely dissolve. This is boiled down to about 43 degrees Celsius, filtered, further boiled in a vacuum pot, cooled, mixed with ■ and ■, thoroughly kneaded, cooled to about 70 degrees Celsius, and poured into molds. 3 g of this candy contains 100 mg of EGCg, which is the active ingredient of the present invention.

Example 2 ■Agar
12g
■Sugar
500g
■Mizuame
300g ■
water
500ml
■Fragrances/Western liquor
Small amount ■EGCg

9.5 g



Yield: 950
g (Complete) According to the above recipe, put (1) into (2), heat and dissolve, and then heat while adding (2) and (2) sequentially. 103
Boil down to ℃, add ■, ■, ■, cool and solidify. Cut to appropriate size. 20 g of this agar jelly contains 200 mg of EGCg, which is the active ingredient of the present invention.

Example 3 ■ Weak flour
300g
■Sugar
150g ■
butter
300 g ■Fragrance
Small amount ■EGCg

7.2 g



Yield 720
g (Complete) According to the above method, whisk (1) and add (2) mixed with (2) little by little. Next, mix ■ homogeneously,
Add ① appropriately. After cooling the mixed dough in the refrigerator, roll it out to a uniform thickness and cut it out. Grilled food costs 180~
This is carried out at 200°C for 7-10 minutes. 10 g of this cookie contains 100 mg of EGCg, which is the active ingredient of the present invention.

Example 4 ■ Spray-dried lactose
1
88 g ■Corn starch

18.8 g ■Polyvinylpyrrolidone
3.2 g ■E
GCg
3
0g




240 g in total Mix ① to ① uniformly according to the above, and put 400 g of each mixture into gelatin capsules.
Filled with mg. One capsule contains 50 mg of EGCg, which is the active ingredient of the present invention.

Example 5 ■Corn starch
19
mg ■Crystalline cellulose

30 mg ■Magnesium stearate
1 mg ■Lactose
80
mg ■EGCg

20mg




Yield: 150 mg According to the above recipe, ① to ③ are mixed uniformly and compressed to form tablets each weighing 150 mg. This tablet contains 20 mg of EGCg, which is the active ingredient of the present invention.

Example 6 ■Sugar

350 g ■Sorbitol

200g ■
Methyl paraoxybenzoate
0.2 g
■Propyl paraoxybenzoate
0.15
g ■Sodium citrate
8
g ■Citric acid

1.2 g ■Fragrance
Small amount ■EGCg

2 g ■Purified water

438g




Yield 1000
g According to the above recipe, dissolve and mix ① to ② to make a syrup solution. 50 g of this syrup liquid contains 1000 mg of EGCg, which is the active ingredient of Honpoho.

[0018]

EFFECT OF THE INVENTION EGCg, which is the active ingredient of the present invention, exhibits a uremic substance-lowering effect and has been shown to be useful for diseases caused by uremic substances. In addition, this ingredient, which is effective in extremely small amounts, is a component of tea that has been drunk since ancient times, so it is highly safe and it is possible to supply a large amount of the composition for reducing uremic substances. It is considered to be extremely useful industrially.

Claims (1)

[Claims] [Claim 1] (-)-epigallocatechin 3-O
- A composition for reducing uremic substances characterized by containing gallate as an active ingredient