JPH0326172B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to an anti-inflammatory agent whose main component is a protein polysaccharide derived from a basidiomycete belonging to the genus Corsicolor, and more particularly to an anti-inflammatory agent comprising PSK. The PSK has already been provided to society as an antitumor agent, has extremely low toxicity, and can be administered for a long period of time without worrying about disturbance of intestinal flora. Also,
It does not affect mutagenicity or allergic reactions, and therefore does not cause teratogenesis in healthy people.
It is an extremely safe substance with no risk of allergic reactions. The present inventors have discovered that the protein polysaccharide of the present invention has an anti-inflammatory pharmacological effect in addition to an antitumor effect, leading to the present invention. The protein polysaccharide which is the active ingredient of the anti-inflammatory agent of the present invention is disclosed in, for example, Japanese Patent Publication No. 46-17149, Japanese Patent Publication No. 51-1987,
Publication No. 36322, Special Publication No. 14274, Publication No. 14274, Special Publication No. 14274
It is a known substance described in Publication No. 14276, Japanese Patent Publication No. 56-39288, etc., and is obtained by culturing basidiomycetes belonging to the genus Corsicolor in hot water of mycelium, broth, or fruiting body. Or an extract with an alkaline aqueous solution, containing about 18 to 38% protein and having a molecular weight of 5,000 to 300,000 (ultracentrifugation measurement). Among the protein polysaccharides of the present invention, Coriolus mycelium [FERM-P2412 (ATCC
20547)], the protein polysaccharide derived from
It is commonly referred to as PSK, or is commercially available under the trade name Krestin (Recent New Drugs Vol. 28, pp. 14-16, 1977 and Vol. 29, pp. 96-19).
Page 101, 1978, Pharmaceutical Directory Page 1346,
(May 6th edition, 1978, published by Yakugyo Jihosha, Medical Drugs, Japan Pharmaceutical Collection, 7th edition, page 240, 1983, published by Yakugyo Jihosha), and some of its properties are as follows. The sugar moiety of the main fraction is β-D-glucan, and the structures of this glucan moiety are 1→3, 1→4 and 1→
It has a branched structure containing 6 bonds, and the amino acids that make up the protein are mostly acidic amino acids such as aspartic acid and glutamic acid, and neutral amino acids such as valine and leucine, and few basic amino acids such as lysine and arginine. Soluble in water, almost insoluble in methanol, pyridine, chloroform, benzene, and hexane. Gradually decomposes from about 120℃. The protein polysaccharide of the present invention has a carrageenan edema suppressing effect, a granuloma suppressing effect, an anti-exudation effect, and an adjuvant arthritis suppressing effect, and is useful as an anti-inflammatory agent. Each effect will be explained below. 1. Edema inhibitory effect of carrageenan When the edema inhibition rate was determined using rats according to the method of Van Arman et al (1963), it was 50.6% after oral administration of 1000 mg/Kg. 2. Granuloma inhibitory effect When the inhibition rate was determined using rats according to the method of Winter et al (1963), it was 49.9% after oral administration of 1000 mg/Kg. 3. Anti-exudation effect When the inhibition rate was determined in rats using the method of Baris et al (1965), oral administration of 1000 mg/Kg showed that
It showed an inhibition rate of 39.7%. 4 Suppressive effect on arthritis of adjuband When the suppression rate was determined in rats using the method of Fujiwara (1971) et al., oral administration of 1000 mg/Kg was 35.9%.
showed a suppression rate of The protein polysaccharide of the present invention is known to be an extremely safe substance for living organisms, having extremely low toxicity and causing almost no side effects. The acute toxicity values of the protein polysaccharide of the present invention are shown in Table 1 below.

【table】

[Table] The acute toxicity values shown in Table 1 above were determined using the following test method. Mice are ICR-JCL strain, 4-5 weeks old, weight 21~
A 24 g sample was used, and the rats were 4- to 5-week-old, weighing 100 to 150 g. The protein polysaccharide of the present invention was administered through four routes: intravenous, subcutaneous, intraperitoneal, and oral. The protein polysaccharide of the present invention was dissolved in physiological saline and administered, and the animals were observed for general symptoms, death, and body weight for 7 days, and after the observation period, they were sacrificed and autopsied. As shown in Table 1, no cases of death were observed in both rats and mice even at the maximum dose that could be administered, and the protein _{polysaccharide} of the present invention is extremely safe for living organisms. In other words, the protein polysaccharide of the present invention has extremely low acute toxicity, is a safe drug, and is useful as an anti-inflammatory agent as it exhibits carrageenan edema suppressing effect, granuloma suppressing effect, anti-exudation effect, adjuvant arthritis suppressing effect, etc. be. The protein polysaccharide of the present invention can be made into any dosage form when used as an anti-inflammatory agent. Moreover, administration is also performed by each route. When the drug of the present invention is used in combination with other anti-inflammatory agents, such as steroids, non-steroids, and anti-inflammatory enzymes, a combined effect can be seen. In the case of oral administration, the tablets applied thereto;
Granules, powders, capsules, etc. contain binders, encapsulating agents,
It may contain additives such as excipients, lubricants, disintegrants, and wetting agents, and when used as oral liquid preparations, oral solutions, shaken mixtures, suspensions, emulsions, It may be in the form of a syrup or as a dry product which is redissolved before use. Additionally, such liquid formulations may contain any commonly used additives and preservatives. When used for injection, the composition may include stabilizers,
They may also contain additives such as buffers, preservatives, tonicity agents, and are presented in unit-dose ampoules or multi-dose containers. It should be noted that the compositions may be in the form of aqueous solutions, suspensions, solutions, emulsions in oily or aqueous vehicles, wherein the active ingredient is dissolved in a suitable vehicle, e.g., a pyrogen-free, sterile vehicle, before use. It may also be a powder that is redissolved in water. The anti-inflammatory agent of the present invention can be administered orally or parenterally to humans and animals, but oral administration is preferred.
Oral administration includes sublingual administration. Parenteral administration includes injections such as subcutaneous, intramuscular, intravenous, infusion, and the like. The dosage of the anti-inflammatory agent of the present invention depends on whether it is an animal or a human being, and is influenced by age, individual differences, medical conditions, etc., so in some cases, it may be necessary to administer an amount outside the following range, but in general, it may be administered to humans. For subjects, the oral dosage of the active substance of the present invention is 1 kg body weight per day.
10-1000mg, preferably 20-600mg once to three times
Administer in divided doses. Example 1 1 Carrageenin edema inhibitory effect 1 According to the method of Van Arman et al. (1963)
A group of 10 rats received 1000 mg/Kg of Crestin by gavage, and 1 hour after administration, 1 dose was administered to the right hind foot pad.
0.1 ml of %Carrageenin saline suspension was injected, the footpad volume was measured over time, and the inhibition rate was calculated using the following formula. (1-T/C) x 100 = IR (%) T: Average footpad volume of the administration group C: Control group footpad volume (no Krestin administration) As a result, the edema suppression rate by Krestin was 50.6
%, indicating that it has an excellent anti-inflammatory effect. 2. Granuloma suppression effect According to the method of Winter et al. (1963), 30±
Two 1 mg cotton wool pellets were implanted, and Krestin was orally administered for 7 consecutive days. On the 8th day, the granulation was removed, the dry weight was measured, and the inhibition rate was determined in the same manner as in 1) above. As a result, the weight of granulation was smaller in the Crestin administration group than in the control group, indicating an inhibitory effect, with an inhibition rate of 49.9%. 3 Anti-exudation effect According to the method of Baris et al. (1965), group 16
A pouch was created by injecting air subcutaneously into the back of one rat, and 1% Croton oil (in sesame oil) was added to the pouch.
Krestin was orally administered for 5 consecutive days by injecting 0.5 ml, and on the 6th day, the amount of exudate in the pouch was measured, and the inhibition rate was determined in the same manner as in 1) above. As a result, the suppression rate was 39.7% in the Crestin administration group, indicating an anti-exudation effect. 4 Adjuvant anti-arthritis effect According to the method of Fujiwara (1971) et al., mycobacterium tuberculosis (mycobacterium
On the 14th day, rats with similar hindlimb volumes were selected, and from the 15th day, 1000 mg/Kg of Crestin was orally administered continuously for 7 days.
The hindlimb volume was measured, and the inhibition rate was determined in the same manner as in 1) above. As a result, the suppression rate was 35.9% in the Crestin administration group, demonstrating remarkable medicinal efficacy against adjuvant arthritis. Example 2 Using a pressure-type automatic filling machine, 330 mg of Crestin was filled into No. 0 hard capsules to produce capsules.

Claims (1)

[Scope of Claims] 1. A hot water or alkaline aqueous extract of mycelia or fruiting bodies obtained by culturing Basidiomycetes belonging to the genus Corsicolor, containing about 18 to 38% protein and having a molecular weight of 5000. ~300000 (Ultracentrifugation measurement method)
An anti-inflammatory agent whose active ingredient is a protein polysaccharide. 2. The anti-inflammatory agent according to claim 1, wherein the protein polysaccharide is obtained from Corsicolor versicolor.