JPH0326175B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a hypoglycemic agent whose main component is a protein polysaccharide derived from a basidiomycete belonging to the genus Corsicolor, and more particularly to a hypoglycemic 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 not only an antitumor effect but also a pharmacological effect of hypoglycemic effect, which led to the present invention. The protein polysaccharide which is the active ingredient of the hypoglycemic 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, it is an aqueous alkali extract containing about 18 to 38% protein and has 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, pages 14-16, 1977 and Vol. 29, 96).
~Page 101, 1978, Pharmaceutical Directory No. 1346,
May 1974 6th edition, published by Yakugyo Jihosha, medical drugs
(Japan Pharmaceutical Collection, 7th edition, page 240, 1983, published by Yakugyo Jihosha), some of its properties are as follows. The sugar moiety of the main fraction is β-D-glucan, and the structure of this glucan moiety is 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 was administered to diabetic rats prepared using streptozotocin at doses ranging from 30 mg/Kg to 300 mg/Kg.
When administered orally at a dose of mg/Kg, 50 mg/dl to
A decrease in blood sugar levels of 100 mg/dl was observed, indicating that the drug has a blood sugar lowering effect. 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] 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 a hypoglycemic agent since it exhibits the effect of lowering blood sugar in diabetic animals. That is, it is effective for diabetes. When the protein polysaccharide of the present invention is used as a hypoglycemic agent, it can be made into any dosage form. Moreover, administration is also performed by each route. Furthermore, the drug of the present invention is
Even when used in combination with sulfonylurea drugs, which are currently widely used as hypoglycemic agents, the efficacy is not reduced, and the combination with these other drugs can be used as an effective means. 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 is 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 hypoglycemic 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 dose of the hypoglycemic agent 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. 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 Streptozotocin 60 mg/Kg was intraperitoneally administered to a Wistar rat, and after about one week positive urine sugar and blood sugar were confirmed, and further, regular insulin administration showed a decrease in urine sugar and blood sugar. A few days later, only those animals in which hyperglycemia and hyperglycemia were confirmed again were used as diabetic model animals for the following test. Krestin dissolved in distilled water 30 or 300mg/Kg
amount was administered orally. Blood was collected from the tail vein, and glucose was measured by an enzymatic method (RaBA kit). The results are shown in Figure 1. From the above results, administration of Crestin clearly lowers blood glucose, proving that it is useful as a hypoglycemic agent. In view of the above-mentioned toxicological and pharmacological properties of Krestin, it will be understood that Krestin is of practical use as a hypoglycemic agent. Example 2 Using a pressure-type automatic filling machine, 330 mg of Crestin was filled into No. 0 hard capsules to produce capsules.

[Brief explanation of the drawing]

FIG. 1 is a graph showing the amount of change in blood glucose level over time when the drug of the present invention is administered to rats with hyperuricemia and hyperglycemia.

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)
A hypoglycemic agent whose active ingredient is a protein polysaccharide. 2. The hypoglycemic agent according to claim 1, wherein the protein polysaccharide is obtained from Corsicolor versicolor.