JPS5849314A - Remedy for hypoadrenocorticalism - Google Patents

Abstract

PURPOSE:To obtain the titled remedy effective to rheumatoid arthritis, gout, allergic rhinitis, etc., by using ginseng-C20-R (or S)-prosapogenin or ginseng- C20-R (or S)-sapogenin as an active component. CONSTITUTION:Ginseng-C20-R- or C20-S-prosapogenin or ginseng-C20-R- or C20- S-sapogenin is used as an active component of the titled remedy. It is administered orally or parenterally in the form of powder, granules, tablet, capsule, injection, etc., by mixing with medical carrier, vehicle or diluent. Dose: e.g. 30-1,000mg, preferably 50-300mg daily for adult in 1-3 doses orally or by injection. The above active components can be prepared by breaking the C20 glycoside bond of ginsenoside Rb1, Rb2, Rb3, Rc or Rd which are the kinds of saponins contained in ginseng, by acid hydrolysis.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides ginseng-020-R- or C20-8-prosapogenin or ginseng-C20-R or C2
The present invention relates to an anti-open kidney cortical hypofunction agent containing 0-8-savogenin as an active ingredient.

The active ingredient of the present invention, ginseng-prosapogenin or ginseng saponin, is derived from ginsengside Rh, Rb2. Rb,.

It is obtained by acid hydrolyzing Re and Rd to cleave the glycosidic bond at the C20 position.

In this acid hydrolysis, epimerization occurs and two stereoisomers C2O-R- and C20-8 are formed. C
2O-R prosapogenin and C205-prosapogenin were isolated by the present inventors and their chemical structures were confirmed, and of course they do not exist in nature.

(Arzneim Forsch, 30 936
(1980)) Medicinal ginseng has been known to have a wide variety of pharmacological actions1. In addition, various components of medicinal ginseng have been recently isolated, and their relationship with medicinal efficacy is gradually being clarified. The present inventors previously succeeded in pure isolation of various ginseng saponin components, among which ginsenoside (Gin-aenoside) Rbl, R
b2r Re, Rd, and Re were found to have adrenocortical hormone secretion promoting effects (Medicinal Ginseng Seminar 1979 (Hiroshima), Endocrinol
Japan 26° (1979)) L Kashi 1 Not all of the isolated carrot saponins have such pharmacological actions, and the relationship between chemical structure and pharmacological action has hardly been elucidated.

The present inventors investigated all sugar chains of carrot saponin.

Or is it partially cleaved and retains the − portion of the sugar chain?

Alternatively, C2O-R- or C20-8-prosapogenin and C2O-R- or C20-8-sapogenin, which are aglycone moieties in which all sugar chains have been cleaved, have been found to have the effect of improving adrenal cortical dysfunction. .

This is the first time that aglycones, in which the sugar chains of carrot saponin are partially or completely cleaved, have been found to have such pharmacological effects.
The pharmacological effects of the type isomers are completely unexpected.

=Nnnnoczo4--/Rosaboge=n =7jin-C20-8-pu. Sapogenin (C20-R-propanaxadiol) (C20-8-propanaxadiol) Carrot-C20-R-sapogenin
Carrot-C20-5-sapogenino (C20-R-protopanaxadiol) (C211-8-protopanaxadiol) As a method for investigating the above pharmacological effects of prosapogenin or sapogenin used in the present invention, rat A method of measuring the cornacosterone content in the plasma of patients is adopted. The measurement results are shown below along with the test method. In addition.

Cortisone is the most secreted adrenocortical hormone in humans, but in rats there is almost no partial pressure of this component, so corticosterone, which is secreted in the highest amount, can be used as an indicator for measuring adrenocortical hormone secretion in rats. f Experiment that was measured 1. Rat Plasma Corticosterone Concentration Increase Test Wistar male runts weighing 130-150 g were provided with water and feed ad libitum, at room temperature of 24 tZ', with light from 6 a.m. to 6 p.m. and darkness thereafter. The animals were kept under an artificial lighting cycle for more than 6 days.

The sample was dissolved in a small amount of DMSO and PyrogenF IJ
- Dispersed and prepared in physiological saline and administered intraperitoneally.

Plasma corticosterone level is determined by Murphy's method (binding protein antagonism method) Murphy, B, E, P, J, C
l1n, Endocrinol 27.97:3 (1
967).

Plasma corticosterone concentration in rats was adjusted to the morning basal value (re
sting 1 level) is 3-4μ/dt,
When physiological saline is administered intraperitoneally, 8 μg is temporarily released after 5 minutes.
/d l, but then after 10-45 minutes r
esting drops to 1 level. By intraperitoneal administration of the sample, plasma corticosterone increases linearly3.
It reaches almost the maximum value at 0 minutes.

It is dependent on the administration of the sample. Display the sample dose and plasma corticosterone concentration after 30 minutes.

Experiment 2. Acute toxicity test Carrot-C20-R (or C20-8>-Prosapogenin and Carrot-C20-R (or C20-8)-
Sapogenin was suspended in physiological saline and
500111 g/kg was administered intraperitoneally to 3 mice (week old, male),
Although the animals were observed for 7 days, there were no deaths.

As is clear from the above experiments, C2O-R,S-F.

Administration of rosapogenin or C2O-R,S-sapogenin significantly increases the plasma concentration of corticosterone, an adrenocortical hormone. This means that these ingredients are
It is thought that it promotes the secretion of ACTH (adrenocorticotropic hormone) from the pituitary gland and causes the secretion of adrenocortical hormone. Therefore, administration of one bottle of U+ is effective in improving various diseases requiring adrenocortical hormone therapy.

The main diseases treated with corticosteroids are rheumatoid arthritis, pain [, SLE, and rheumatic fever].

Allergic rhinitis, bronchial asthma, sarcoidosis.

These include hives, chronic active hepatitis, and ulcerative colitis.

In long-term corticosteroid hormones,
In addition to causing various side effects, it can also cause iatrogenic adrenocortical insufficiency, making treatment difficult, so it is useful to administer it as prescribed.

Savogenin or prosapogenin used in the present invention can be prepared as a powder, granules, 9 tablets, or capsules by itself or mixed with suitable carriers, excipients, and diluents for formulation.

It can be administered orally or parenterally in the form of an injection.

The dosage is, for example, for adults, 30 to 1000 doses per day.
(2) Preferably, 50 to 300 mg is administered orally or injected in 1 to 3 doses, but the dose may not be increased or decreased depending on age, age, body weight, symptoms, etc.

Patent Applicant Yamanouchi Pharmaceutical Co., Ltd. Agent Koji Sasaki Procedural Amendment Written by Commissioner of the Patent Office Shima 1) Haruki Tonol, Indication of Case Patent Application No. 147485, 1982
Title of the invention: Anti-open kidney cortical hypofunction agent 3 Relationship with the person making the amendment Patent applicant address: 2-5-1 Nihonbashi Honmachi, Chuo-ku, Tokyo Name (
667) Yamanouchi Pharmaceutical Co., Ltd. Representative Shigeru Morioka 4, Agent address 1-1-8-5 Azukizawa, Itabashi-ku, Tokyo Amendment χ
(Column 6 of “Detailed Description of the Invention” of the detailed description of the invention Contents of amendment (1) Position 120 of the fourth line from the bottom of the first page of the specification”)
Or add "C20th place and 03rd place".

(2) Add the following sentence at the end of the fourth line on page 2 of the same document. “Also, C20R-sapogenino and C20R-sapogenino
OS-sapogenin can also be obtained by our isolation method. (The Chemical Sgcie
ty of Japan '4'l th congre
ss, Tokyo) j (3) Correct J Wister J on page 4, line 11 to “Wistar J.

(41) Change “μ/dt” in the first line of page 5 to [μg/dtJ
Correct.

Claims (1)

[Claims] Carrot-C20-R- or C20-8-prosapogenin or Carrot-C20-R- or 20-8-
Anti-open kidney cortical hypofunction agent containing sapogenin as an active ingredient