JPH0326171B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to an antipyretic analgesic agent whose main ingredient is a protein polysaccharide derived from a basidiomycete belonging to the genus Corsicolor, and more particularly to an antipyretic analgesic agent comprising PSK. The PSK
has already been provided to society as an antitumor agent,
It has extremely low toxicity and can be administered for a long period of time without worrying about disturbance of intestinal flora. Furthermore, it has no effect on mutagenicity or allergic reactions, and is therefore extremely safe, with no risk of teratogenicity or allergic reactions in healthy people. The present inventors have discovered that the protein polysaccharide of the present invention has pharmacological effects such as antipyretic and analgesic effects in addition to antitumor effects, leading to the present invention. The protein polysaccharide that is the active ingredient of the present invention has analgesic and antipyretic effects, and is useful as an analgesic or an antipyretic. The protein polysaccharide which is the active ingredient of the antipyretic analgesic of the present invention is disclosed in, for example, Japanese Patent Publication No. 46-17149, Japanese Patent Publication No. 51
-36322 Publication, Special Publication No. 56-14274, Special Publication Sho
It is a known substance described in Japanese Patent Publication No. 56-14276, Japanese Patent Publication No. 56-39288, etc., and is a heat-generating mycelium, broth, or fruiting body obtained by culturing basidiomycetes belonging to the genus Coriolis. It is a water or alkaline aqueous extract containing about 18-38% protein and has a molecular weight of 5,000-300,000 (ultracentrifugation measurement). Among the protein polysaccharides of the present invention, C. versicolor mycelium [FERM-P2412
(ATCC20547)], as mentioned above, is commonly called PSK or is commercially available under the trade name Krestin (Recent New Drugs Vol. 28, pages 14-16, 1977 and Volume 29, pages 96-101, 1978, Pharmaceutical Directory No.
1346 pages, May 1974 6th edition, published by Yakugyo Jihosha, Medical Drugs Japan Pharmaceutical Collection 7th Edition 240 pages,
(Published by Yakugyo Jihosha in 1983), 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 analgesic and antipyretic effects of the central nervous system depressant of the present invention will be explained below. 1) Analgesic effect When the analgesic effect of the active substance of the protein polysaccharide of the present invention was investigated using mechanical stimulation method (pressure stimulation method) and chemical stimulation method using mice, it was found that the protein polysaccharide
Oral administration of 1000 mg/Kg caused a rise in pressure and a prolongation of the time until the appearance of a pseudo-escape response, respectively.
and a decrease in the number of writings. 2) Antipyretic effect Using brewer's yeast subcutaneous administration method in rats,
When we investigated the antipyretic effect of the protein polysaccharide of the present invention, we found that
Oral administration of 1000 mg/Kg of the active substance showed a fever suppressing effect, and a decrease in body temperature to the level of rats not treated with brewer's yeast was observed. 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. That is, the protein polysaccharide of the present invention has extremely low acute toxicity, is a safe drug, and is useful as an antipyretic analgesic because it exhibits analgesic effects against chemical and physical stimuli and antipyretic effects caused by brewer's yeast. When the protein polysaccharide of the present invention is used as an antipyretic analgesic, it can be made into any dosage form. Moreover, administration is also performed by each route. The antipyretic analgesic of the present invention and other antipyretic analgesics, such as narcotic analgesics, non-narcotic analgesics, salicylic acid,
When used in combination with pyrazolone-based, indole-based, phenylacetic acid-based, anthranilic acid-based, thienopyridine-based, pyrimidine-based, pyrimidinyl pyrazole-based, benzotriazine-based and benzothiazolinone-based analgesic, antipyretic, and anti-inflammatory agents, a combined effect can be seen. It will be done. 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. For injection, the compositions may contain additives such as stabilizers, 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 antipyretic analgesic of the present invention can be given to humans and animals orally or parenterally, but oral administration is preferred. Oral administration includes sublingual administration. Parenteral administration includes injections such as subcutaneous, intramuscular, intravenous, infusion, and the like. The dose of the antipyretic analgesic of the present invention depends on whether it is an animal or a human, and is influenced by age, individual differences, medical conditions, etc., so in some cases, doses outside the following range may be administered, but in general, 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) Analgesic Mechanical Stimulation Method (Pressure Stimulation Method) A pressure stimulation device (manufactured by Natsume Seisakusho) by Takagi and Kameyama et al. was used. The test animals used were ICR mice (♀).
Apply pressure to the ridge of the mouse, and the pain tolerance value is 50 to 80.
Those exhibiting mmHg were selected and each group consisted of 10 animals. After oral administration of Krestin 1000 mg/Kg, measurements were taken over time to determine the pressure and time required (seconds) until the test animal showed a pseudo-escape response, and the pressure and time required were used to provide analgesia. The effectiveness was determined. In all of the Crestin-administered groups, when the pseudo-escape reaction appeared, the pressure was higher than that of the control group, and the appearance time also tended to be longer than that of the control group, confirming the analgesic effect.

[Table] Chemical stimulation method ICR mice, 1 group of 5-6 week old (♀) mice
30 minutes after orally administering 1000 mg/Kg of Krestin to 10 animals according to the method of Kostet et al (1959).
A 0.6% acetic acid solution was intraperitoneally injected per 0.1 ml/10 g of mouse body weight, and the number of writings occurring in the mouse was counted for 10 minutes after 10 minutes, and the inhibition rate (%) relative to the control group was determined using the following formula. (1-T/C)×100=IR (%) T: Average number of writings in the administration group C: Average number of writings in the control group With the administration of Krestin, the number of writings clearly decreased compared to the control group. , the suppression rate is
A significant analgesic effect of 52.1% was obtained. 2) Antipyretic effect According to the method of Winter et al (1961), a 20% brewer's yeast suspension was administered subcutaneously to 6 rats per group.
After fasting for 10 hours, Krestin was orally administered at 1000 mg/Kg, and the rectal temperature was measured over time to examine the fever-suppressing effect of Krestin. As a result, administration of Crestin showed an antipyretic effect, lowering the body temperature of rats with fever to almost the level of untreated rats.

[Table] 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 antipyretic analgesic whose active ingredient is a protein polysaccharide. 2. The antipyretic and analgesic agent according to claim 1, characterized in that the protein polysaccharide is obtained from C. versicolor.