JPH0331177B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to an antihypertensive agent containing a protein polysaccharide derived from a basidiomycete belonging to the genus Corsicolor as a main component, and more particularly to an antihypertensive agent consisting of crestin. Krestin 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 a pharmacological effect of lowering blood pressure in addition to an antitumor effect, leading to the present invention. The protein polysaccharide which is the active ingredient of the antihypertensive agent of the present invention is disclosed in, for example, Japanese Patent Publication No. 17149/1983, Japanese Patent Publication No. 51/1986,
Publication No. 36322, Special Publication No. 14274, Special Publication No. 1983
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, C. versicolor mycelium [FERM-P2412
(ATCC20547)] is commercially available under the trade name Krestin (Recent New Drugs Vol. 28, pp. 14-16), as mentioned above.
1977 and 29th edition, pages 96-101, 1978, Pharmaceutical Directory, page 1346, May 1978, 6th edition, published by Yakugyo Jihosha, Medical Drugs Japan Pharmaceutical Collection, 7th edition, page 240, 1983, It is also called PS-K (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 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 orally administered at a dose of 30 mg/Kg to 300 mg/Kg to spontaneously hypertensive rats SHR, which are widely used as a model of human essential hypertension, and blood pressure was monitored over time. As a result of blood pressure measurement, a drop in blood pressure of 15 mmHg to 25 mmHg was observed, indicating that it has a blood pressure 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 an antihypertensive agent since it exhibits the effect of lowering blood pressure in spontaneously hypertensive rats SHR. The protein polysaccharide of the present invention can be made into any dosage form when used as an antihypertensive agent. Moreover, administration is also performed by each route. Furthermore, the drug of the present invention is
Nodal blockers, which are currently widely used as antihypertensive agents,
Even when used in combination with alkaloids, guanethidine, methyldopa, and thiazides, the efficacy does not decrease, 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 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 antihypertensive 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 antihypertensive 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, but in general, when 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 Using a spontaneously hypertensive rat (SHR), blood pressure was measured using a blood pressure measuring device (Model USM-105R, manufactured by Ueda Seisakusho). Crestin was administered in an oral dosage form by dissolving Crestin in distilled water at a concentration of 30 or 300 mg/Kg. The results are shown in Figure 1. From the above results, it is understood that Krestin has an extremely excellent antihypertensive effect. Furthermore, since the spontaneously hypertensive rats (SHR) used in the above test correspond to essential hypertension in humans, Krestin can be said to be effective as a hypotensive 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]

Figure 1 shows spontaneously hypertensive rats (SHR).
2 is a graph showing changes in blood pressure lowering when the antihypertensive agent of the present invention is administered to patients.

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 antihypertensive agent whose active ingredient is a protein polysaccharide. 2. The antihypertensive agent according to claim 1, wherein the protein polysaccharide is obtained from C. versicolor.