JPS6045527A - Hypotensor - Google Patents

Abstract

PURPOSE:An extremely safe hypotensor comprising protein polysaccharide derived from Basidiomyces belonging to the genus Coriolus versicolor as a main component. CONSTITUTION:A hypotensor comprising protein polysaccharide, an extract of a mycelium culture obtained by cultivating Basidiomyces belonging to the genus Coriolus versicolor or its fruit body with hot water and an alkali solution as an active ingredient. The protein polysaccharide (e.g., krestin) contains 18-38wt% protein, has 5,000-300,000 molecular weight (ultracentrifugation), its saccharide part is beta-D-glucan, constituent amino acids of protein are aspartic acid, leucine, etc., and it shows properties of solubility in water, etc. Oral administration is preferable, and a dose is 10-1,000mg/day/kg, preferably 20-600mg/day/kg.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a hypotensive agent containing a protein polysaccharide derived from a basidiomycete belonging to the genus Corsicolor as a main component, and more particularly to a hypotensive agent consisting of crestin. Krestin has already been provided to society as an antitumor agent, has extremely low toxicity,
In addition, there is no concern about disturbance of intestinal flora, and long-term administration is possible. Furthermore, it does not affect mutagenicity or allergic reactions, so it is an extremely safe substance with no risk of irritation or allergic reactions in healthy people.

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 anti-liver cancer effect, leading to the present invention.

The active ingredient C of the antihypertensive agent of the present invention, a certain protein polysaccharide, is disclosed in, for example, Japanese Patent Publications No. 46-17149 and Japanese Patent Publication No. 51-363.
Publication No. 22, Special Publication No. 56-14274, Komako Sho 5
It is a well-known substance described in Japanese Patent Publication No. 6-14276, Japanese Patent Publication No. 56-39288, etc., and is a mycelial culture obtained by culturing basidiomycetes belonging to the genus Corsicolor (Br.
otl+) or fruiting bodies in hot water or alkaline solution, containing about 18-38% protein and containing 5.
, 000-300,000 (ultracentrifugation measurement method). Among the protein polysaccharides of the present invention, Coriolus mycelium [FERM-P2412' (ATC
C20547) J-derived protein polysaccharide is, as mentioned above, commercially available under the trade name Krestin (Recent New Drugs Vol. 28, pp. 14-16, 197
7 and Volume 29, pages 96-101, 1978,
Pharmaceutical Handbook No. 1346, 6th edition, May 1978,
Published by Yakugyo Jihosha, Medical drugs l] This pharmaceutical collection 1st edition No. 24
0 pages.

(Published by Yakugyo Jihosha in 1983) and has been designated as PS-, 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 a branched structure containing 1→3, 1->4 and 1→6 bonds, and the constituent amino acids of the protein are aspartic acid, glutamic acid, It contains many acidic amino acids such as valine and leucine, and low amounts of salts such as lysine and arginine. Soluble in water, almost insoluble in methanol, pyridine, chloroborum, benzene, and hexane. It gradually decomposes from about 120°C.

The protein polysaccharide of the present invention was applied to spontaneously hypertensive rats SH, which are commonly used as a model for essential hypertension in humans.
R, 30ma/k (I to 300mo/ko17)
JTI was administered orally, and blood pressure was measured non-invasively over time.
Since a drop in blood pressure was observed, it was found that the drug had an effect on preventing a drop in blood pressure.

The protein polysaccharide of the present invention is known to be a very safe substance for living organisms, as its green bamboo has extremely low -C and causes almost no side effects. The acute toxicity values of the protein polysaccharide of the present invention are shown in Table 1 below.

Table 1 Note that the acute efficacy fili shown in Table 1 above was investigated using the test method described above.

Mice are ICR-J CL strain, 4-5 weeks old, age 2
1 to 240, Rat 1- is capacity type, 4 to 5 weeks old,
Those weighing 100 to 150 g were used. 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 general symptoms,
The animals were observed for death and body weight, and were sacrificed and necropsied after the observation period ended.

As shown in Table 1, no deaths were observed even at the maximum dose that could be administered to rats and mice.
The protein polysaccharide of the present invention is extremely safe for living organisms, as it is virtually impossible to determine the Ll)5o value statically.

1 In other words, the protein polysaccharide of the present invention has extremely low f1- for acute use, is a safe drug, and is a safe drug for patients with spontaneous hypertension.
It is useful as an antihypertensive agent since it exhibits the effect of preventing the lowering of the blood pressure of l-IR.

When the protein glycoside of the present invention is used as an antihypertensive agent,
It can be made into any dosage form. Throw again! (1) The drug of the present invention is a nodal blocker that is currently widely used as an antihypertensive agent.

Even with alkaloids, guanethidine, methyldopa, and thiazide agents (11), the efficacy is not reduced, and the combination with these other agents can be used as an effective means.

In the case of oral administration, tablets, granules,
Powders, capsules, etc. may contain additives commonly used in pharmaceutical formulations such as binders, encapsulating agents, excipients, lubricants, disintegrants, wetting agents, etc. When used as a daily liquid preparation, it may be in the form of an internal solution, shaken mixture, suspension emulsion, or syrup.
It may also be in the form of a dry product that is redissolved before use. Furthermore, such liquid formulations may contain any of the commonly used additives and preservatives.

When used for injection, the composition may contain additives such as stabilizers, buffers, preservatives, and tonicity agents.

The drug may be provided in unit-dose ampoules or multi-dose containers. It should be noted that the above compositions may be in the form of aqueous solutions, suspensions, solutions, emulsions in oily or aqueous vehicles, while the ingredients may be dissolved in a suitable vehicle, e.g. a pyrogen, before use. It may also be a powder that is redissolved in free sterile 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 intravenous, intramuscular, intravenous, infusion, and the like.

The dosage of the antihypertensive agent of the present invention is influenced by animal and human conditions, as well as age, individual differences, medical conditions, etc.; therefore, depending on the case, doses outside the following range may be administered. Generally, when administering to humans, the oral dose of the present photostimulant substance is 1 kg of body weight (10 to 1,000 mg per day, preferably 20 to 6 oomas per day, divided into 1 to 3 doses). .

Example 1 Blood pressure was measured using a blood pressure measuring device (Model US M-105R, manufactured by Ueda Seisakusho) using spontaneously hypertensive rats 1 to 1 (SHR).

To administer Krestin, dissolve Krestin in distilled water and
The oral dosage form was administered at 0 or 300mM kQ. The results are shown in Figure 1.

From the above results, it is understood that Krestin exerts an extremely excellent 1ζ effect on blood pressure. Incidentally, 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 1a1 machine, 330 mg of Krestin was filled into B4 hard Cazorel to prepare capsules.

[Brief explanation of drawings]

FIG. 1 is a graph showing changes in blood pressure reduction when the antihypertensive agent of the present invention is administered to spontaneously hypertensive rats (St-IR). Representative Patent Attorney Hajime Imamura

Claims (2)

[Claims] (1) A hot water or alkaline solution extract of the mycelium or fruiting body obtained by culturing Basidiomycetes belonging to the genus Corsicolor, which contains about 18 to 38% protein and has a molecular weight of 5,000 to 300. ,000 (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 Krestin.