JPS62240621A - Styptic - Google Patents

Abstract

PURPOSE:A styptic useful as a remedy for pulmonary hemorrhage, cerebral hemorrhage, purpura, etc., having higher hemostatic action than ethamsylate and tranexamic acid, containing pectolinarin extracted from Cirsium japonicum DC. for Chinese herbal remedy as an active ingredient. CONSTITUTION:A styptic containing pectolinarin shown by the formula as an active ingredient. The compound shown by the formula is obtained by extracting Cirsium japonicum DC. with hot water, treating the prepared extracted essence by counter current partition, removing water-soluble substances, then fractionating and purifying a prepared fraction by column chromatography and purifying an active fraction by recrystallization. The compound shown by formula is administered orally or parenterally. A dose is preferably 3-6mg/time by oral administration.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention - relates to a pharmaceutical composition containing vectorinarin extracted from Japanese radish as an active ingredient.

The raw material of the present invention, the large daisy, is from the genus Thistle (Clr.
slum japanlcum DC,), and is used in Chinese medicine as a hemostasis, blood thinner, detoxifier, and tonic.

Vectrinarin (I), which has been reported as a component contained in daikon daikon, is reported in Pharmaceutical Journal, υ-, 1338 (195
Although it is well known from a phantom, its pharmacological activity has not yet been elucidated.

OO 8 (° ゛.・ Therefore, an object of the present invention is to provide a useful pharmaceutical composition containing as an active ingredient pectrinarin (I), a pharmacologically active substance extracted from Japanese radish.

. ° Pectrinarin represented by the formula (I) in 2 is obtained by extracting Japanese radish with hot water, treating the obtained extract with countercurrent distribution to remove water-soluble substances, and then passing the obtained fraction through a column. It can be obtained by separating and purifying by chromatography and purifying the obtained active fraction by recrystallization.

Purified pectrinarin (I) is published in a pharmaceutical journal.

75.172 (1955); 79,1338 (1959
); 7-1 V* 7' 7 @Fy -""E+m+ 126 (193G); l Luc Intenochus (9th edition), 6862; Hiemiso/Ko Berichte.

74.1818 (+941) and the like.

However, these documents do not describe at all that pectolinarin has hemostatic activity, and only pectolinarin (Cirslum mlcrospIc)
atum), Clrslum 0ta
yae), Clrslum Yoshjz
avae), Lang Lang (Llnariajaponlc)
It is merely separated by IL from a) etc. In addition, pectolinarigenin (
Regarding n), Pharmaceutical Journal “, 80.820 (19GO
), there are only reports of antispasmodic effects.

OO As a result of intensive research into the pharmacological effects of pectolinarin (I), the present inventors discovered that this compound exerts a strong hemostatic effect, leading to the completion of the present invention.

That is, the present invention relates to a pharmaceutical composition containing pectrinarin (I) as a secondary active ingredient.

That is, the compound has a strong hemostatic effect and inhibits pulmonary hemorrhage.

It is extremely useful as a therapeutic agent for cerebral hemorrhage, epistaxis, retinal hemorrhage, purpura, aplastic anemia, etc.

Pectrinarin represented by formula (I) can be made into preparations such as tablets, powders, capsules, injections, or external preparations by conventional methods, and is clinically administered by oral or parenteral administration. The dosage depends on the symptoms to be treated and the administration method, but when administered orally to adults, it is usually administered once.
-10 mg, preferably 3-61 g.

In addition, the hemostatic activity test conducted in the examples was calculated using shoulder 1 constant according to the following method.

[Hemostatic activity test method] According to the method of Kodejima et al., 1% methylcellulose/physiological saline solution 0.51 was administered intraperitoneally to a ddY male mouse weighing 20 g. After 10 minutes, the mouse was fixed in a fixing box and the middle part of the tail was injected. Injure the nearby left leg vein with a scalpel to cause bleeding. Thereafter, a piece of filter paper is lightly applied to the wound at 30 second intervals, and the time until blood stops adhering to the filter paper is measured. This time is taken as the control bleeding time. After 4 hours, a test sample suspension suspended in 1% methylcellulose/physiological saline solution (0.51%) is intraperitoneally administered to the same mouse. After 10 minutes, the mouse is immobilized, the right leg vein near the middle of the tail is injured with a scalpel, and the bleeding time is measured in the same manner as in the control case. Perform the test twice on the same sample and use the average value.

Calculation method of hemostatic activity: Kyo11 P(0,01 Book * X books p (0,001 Hereinafter, the present invention will be explained by examples.

Example: After crushing 200g of Japanese radish using a crusher (NRK-R8 was used in Nippon Rikagaku Kiki 9 for crude drug use),
Extract with 1 liter of water under reflux for 1 hour. After cooling, collect by suction filtration,
The filtrate is lyophilized to obtain 19-8 g of extract.

Hemostatic activity of hot water extract: 39. O% small volume (dose 500
sag/Kg) After dissolving the hot water extract in 350 ml of water, 350 ml of n-butanol is added thereto, partitioning is performed, and the n-butanol layer is concentrated under reduced pressure to obtain 1.87 g of active fraction.

Hemostatic activity of active fraction: 35.5% of z (administration ff15
0g/Kg) 1.87g of the fraction was dissolved in methanol 501, and this was dissolved in Sephadex LH-20 (25g/Kg) prepared with methanol.
Column chromatography using 0g gel) was performed, and K
217 mg of active fraction of d 1.14-1.7G is obtained.

Hemostatic activity of active fraction: 27.9%
Peng/Kg) This fraction was mixed with chloroform/methanol/water (65:35
The active ingredient is purified by silica gel column chromatography (using 40 g) using the lower layer of 10) as an elution solvent. 100 g of the crude compound was obtained and further recrystallized with methanol to give a melting point of 241-244'' [Literature value (Pharmaceutical Journal, 95, 173 (1955)): 248-2.
50"] of pale yellow crystalline powder are obtained.

IR spectrum v ig2 cm-': 3400.2
93G, 1GlliO.

+11i40, 14GO, 1355, 1295, 11
80,835uv spectrum λtakiQ'nm (log
e):272(4,18).

327(4,33) NMR spectrum δpp theory (d6-D Seki So):8.
04 (2H, d.

J=8.8Hz), 7.111i(211,d, J=8
．． 8Hz), 8.92 (28,s).

5.6-4.2 (8H, m), 3.811i (3) I,
s), 3.77 (3H, s), 4.0-3.5 (2H,
m), 1.05 (31, d, J=2Hz) mass spectrum -/z:314.299,271.凰33
, [i9 high-resolution mass spectrum: 314.0799
(error-1,0M0) for C17H14
06 elemental analysis value C29H34015 theoretical value C,55,94; H,5,50 experimental value C,
55,67; H,5,57 The hemostatic activity of the thus obtained pectrinarin and the reprinted hemostatic agents ethanlate and tranexamic acid was tested. The results are shown in the table.

table

Claims (1)

[Claims] A hemostatic agent containing vectorinaline as an active ingredient, which is represented by the formula ▲There are mathematical formulas, chemical formulas, tables, etc.▼.