JPS6045526A - Improver for ischemic heart desease - Google Patents

Abstract

PURPOSE:An extremely safe improver for ischemic heart disease, useful for coronary arteriosclerosis, myocardial infarction, angina pectoris, arrhythmia, cardiac incompetence, etc., comprising protein polysaccharide derived from Basidiomyces belonging to the genus Coriolus versicolor as a main component. CONSTITUTION:An improver for ischemic heart disease comprising protein polysaccharide, an extract of a mycelium culture obtained by cultivating Basidiomyces belong to the genus Coriolus versicolor or its fruit body with hot water or 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 method), 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 an ischemic heart disease ameliorating agent containing as a main component a protein polysaccharide derived from a basidiomycete belonging to the genus Corsicolor, and more particularly to an ischemic heart disease ameliorating agent comprising crestin. Krestin has already been provided to society as an anti-liver tumor agent,
It has extremely low toxicity and there is no need to worry about disrupting the intestinal flora.
Long-term administration is possible. It also affects mutagenicity and allergic reactions, so it is an extremely safe substance with no risk of teratogenicity or allergic reactions compared to healthy people.

The present inventors have discovered that the protein polysaccharide of the present invention has, in addition to its antitumor effect, a pharmacological effect as an agent for improving ischemic heart disease, leading to the present invention.

The protein polysaccharide which is the active ingredient of the present invention improving agent for ischemic heart disease 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 No. Sho 56-14276, Special Publication No. Sho 56-3928
It is a known substance described in Publication No. 8, etc., and is a mycelium culture ([3roth) obtained by culturing basidiomycetes belonging to the genus Corsicolor or an extract of the fruiting body with hot water or an alkaline solution. It contains about 18-38% protein and has a molecular weight of 5,00'0-300,000 (ultracentrifugation measurement). Among the protein polysaccharides of the present invention, Kawarataku mycelium [FERM-P24'12
(ATCC20547)] is commercially available under the trade name Krestin (Recent New Drugs Vol. 28, pp. 14-16), as mentioned above.
1977 and Volume 29, pp. 96-101, 19
1978, Pharmaceutical Handbook, page 1346, May 1978, 6th edition, published by Yakugyo Jihosha, Medical Drugs Japan Pharmaceutical Dictionary, 7th edition, page 240.

(Published by Yakugyo Jihosha in 1983) and is also called 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 amino acids that constitute the protein include aspartic acid, glutamic acid, etc. There are many acidic amino acids and neutral amino acids such as valine and leucine, and there are few basic amino acids such as lysine and arginine. It is soluble in water, but hardly soluble in methanol, pyridine, chloroform, benzene, and hexylene. The temperature is gradually increased from about 120°C.

The protein polysaccharide of the present invention has an effect of increasing coronary blood flow and is useful as an agent for improving ischemic heart disease. That is, when a heart-lung specimen was prepared using a normal Pegle-sized animal and the protein polysaccharide was injected through the superior human artery, an increase in coronary flow rate was observed, indicating its effectiveness as an agent for improving ischemic heart disease.

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 1 The acute toxicity values shown in Table 1 above were determined using the following test method.

Mice are I CR-J CL strain, 4-5 weeks old, weight 21
~24 (for I, rats are 6 dragons, 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 to treat general symptoms,
Mortality and body weight were observed, and a slaughter autopsy was performed after the observation period.

As shown in Table 1, no deaths were observed even at the maximum doses that could be administered to rats and mice, and the results of this study are so great that it is virtually impossible to determine the [-D5o value]. The protein polysaccharide of the 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 agent for improving ischemic heart disease since it exhibits an effect of increasing coronary blood flow. The drug of the present invention is used for coronary artery sclerosis, acute or chronic myocardial infarction, stable or unstable angina, and arrhythmia.

It is effective for open cases such as heart failure.

When the protein polysaccharide of the present invention is used as an agent for improving ischemic heart disease, it can be made into any dosage form.

Moreover, administration is also performed by each route.

In the case of oral administration, tablets, granules,
Powders, Cabrel agents, etc. may contain additives such as binders, inclusion agents, excipients, lubricants, disintegrants, and wetting agents commonly used in pharmaceutical formulations in their compositions. When used as a liquid preparation for daily use, it may be in the form of an oral solution, a shaken mixture, a suspension, an emulsion, or a syrup, or it may be in the form of a dry product that is redissolved before use. Deatsu-C is also good. Additionally, such liquid formulations may contain any commonly used additives and preservatives.

When used for injection, the composition may contain additives such as stabilizers, buffers, preservatives, tonicity agents, etc., in unit-dose ampoules, or in multi-dose containers. Middle C provided.

The composition may be in the form of an aqueous solution, suspension, solution, emulsion in an oily or aqueous vehicle,
Alternatively, the active ingredient may be in powder form for reconstitution with a suitable vehicle, eg, sterile pyrogen-free water, before use.

The agent for improving ischemic heart disease 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.

Administration of the ischemic heart disease improving agent of the present invention! ``Im is influenced by animals and humans, as well as by age, individual differences, medical conditions, etc., so in some cases it may be necessary to administer ω outside the range below, but in general, when humans are considered as animals, The oral dosage of the active substance of the invention is 10 to 100 per 10 kg of body weight.
0mg, 'M? Preferably 20 to 60 mg (administer 1 mg in 1 to 3 divided doses).

In addition, the ischemic heart disease improving agent of the present application can be used in combination with amyl nitrite, 21-glyrelin, etc. during an attack.
Or, during non-seizures, nitrites, quintin preparations, pababerine, dipyridamole prenylamine, Penzi A Daron, carbochromene, efloxe 1-, MAOII
II harmful agent, 2,6-pyricinsimethanol-bis(N-
methylcarbame-1), beta receptor blockers, verapamil, coronary dilators such as nicotinic acid, phenobarbital, meprobame-1, chlordiazepoxide, reserpine.

V1 effects can be expected when used in combination with sedatives such as chlorpromazine. It can also be used in combination with an anti-arteriosclerotic agent.

Example 1 Measurement of the effect of increasing coronary blood flow m Cardiopulmonary specimens were prepared using three normal peagles from each city.
Coronary blood flow patterns were recorded using an electromagnetic flowmeter 1 (Starim SF'-2202) inserted into the right atrium and into the coronary vein side of the M0raWity canicule. After dissolving Krestin in physiological saline, 1-100
m! J/kG was injected from the -L vena cava. The results are in the table-
2, the increase in the mean blood flow after administration (111) relative to the mean blood flow (2) before administration was expressed as perlen 1.

Preparation of Capsules Using a pressure-type automatic filling machine, 330 mg of Crestin was filled into a No. 0 hard cabrel to prepare capsules.

Representative Patent Attorney Hajime Imamura

Claims (1)

[Claims] (1) A hot water or alkaline solution extract of mycelia or fruiting bodies obtained by culturing Basidiomycetes belonging to the genus Corsicolor, containing approximately 18 to 38% protein and having a molecular weight of 5,000 to 300. ,000 (Ultracentrifugation measurement method) An ischemic heart disease improving agent containing a protein polysaccharide as an active ingredient. (2=) The agent for improving ischemic heart disease according to claim 1, wherein the protein polysaccharide is Krestin.