JPS61167623A - Agent for inhibiting coagulation of platelet - Google Patents

Abstract

PURPOSE:To use ONSEIIN which is Chinese herb tea composd of JIOU, SHAKUYAKU, SENKYU, TOUKI, OUGON, OUBAKU, OUREN, and KUCHINASHI, as a platelet coagulation inhbiting agent having low side effect. CONSTITUTION:ONSEIIN prepared by decocting 3g of JIOU (root of Rehmannia glutinosa), 3g of SHAKUYAKU (root of Paeonia albiflora), 3g of SENKYU (rhizome of Cnidium officinale), 3g of TOUKI (root of Angelica acutiloba), 1.5g of OUGON (root of Scutellaria baicalensis), 1.5g of OUGAKU (bard of Phellodendron amurense), 1.5g of OUREN (rhizome of Coptis japonia) and 1.5g of KUCHINASHI (fruit of Gardenia jasminoides) with 600ml of water to obtain 350ml of decocted liquid, and removing the grounds therefrom. It is administered thrice a day as a platelet coagulation inhibiting agent. It may be used as a Chinese drug extract preparation. A dried ONSEIIN extract powder can be obtained e.g. by extracting 3-4pts.wt. each of JIOU, SHAKUYAKU, SENKYU and TOUKI, 1.5-3pts.wt. of OUGON, 1.5-2pts.wt. of OUBAKU, 1.5-2pts.wt. of OUREN and 1.5-2pts.wt. of KUCHINASHI with 10 times wieght of the hot water, filtering the extract, and drying the product, and the powder is formed to a drug preparation by conventional method. It is effective to arteriosclerosis, hyperlipemia, cardiac infarction, etc.

Description

[Detailed description of the invention] Industrial applications The present invention relates to antiplatelet aggregation agents.

Conventional technology The pharmacological mechanisms of the antiplatelet aggregants currently in use are clear, and many of them have excellent antiplatelet aggregation effects.
On the other hand, gastrointestinal ulcer formation, allergies (hives,
There are many side effects such as asthma. Therefore, it is desired to develop an antiplatelet aggregation agent with fewer side effects.

Problems to be Solved by the Invention The present invention provides an antiplatelet aggregation agent with few side effects.

Means to Solve the Problem The present inventors conducted research on the anti-platelet aggregation effect of various Chinese herbal prescriptions, and as a result, found that the results of research on the anti-platelet aggregation effects of various Chinese herbal prescriptions were found to be effective.
It was discovered that a Chinese herbal medicine prescription consisting of Buyer, Huangbai, Huanglian, and Yamatateshi, that is, hot water, has an antiplatelet aggregation effect. But? Onsendan, which has an antiplatelet aggregation effect, can be used for diseases such as arteriosclerosis, hyperlipidemia, and myocardial infarction. The constituent herbal medicines, dosage, extraction method, etc. of Onseindoke are described in the classic Chinese herbal prescription (Wanbyou Kaishun), and it is used for menopausal disorders, but it has not been previously known that it has an antiplatelet aggregation effect. That was not the case. The present invention is based on this knowledge, and is an anti-platelet aggregation agent made of hot water.

Oncheongdrink is made according to the classics, with 3g of rhizome, 3g of Chinese medicine, and 3g of kawau.
, Dangki 3g, Huanglui 1.5g, Huangbai 1.5g, Huanglian 1.5
It is also possible to boil 1.5 g of Sanjizi with 600-g of water, remove the residue and take it as an anti-platelet aggregation agent in three doses, but it is difficult to take easily and with a mobile phone. For convenience, a Chinese herbal medicine preparation can also be used as an antiplatelet aggregation agent. For example, Jhiang 3~
4 parts by weight, 3 to 4 parts by weight of medicine, 3 to 4 parts by weight of bow, 3 to 4 parts of toki! part, Buyer 1.5-3 parts by weight, Huangbai 1.5-2 parts
1.5 to 2 parts by weight, 1.5 to 2 parts by weight of Huangren, and 1.5 to 2 parts by weight of Sanshuzi are heated and extracted with 10 times the amount of water.The resulting extract is aterated and dried to produce an antiplatelet agent. Obtain a hot dry extract powder, which is a flocculant, and add appropriate excipients, adjuvants, etc. used in ordinary formulations to form formulations such as powders, granules, tablets, and capsules according to conventional formulation manufacturing methods. It can be done.

A specific example of the production of the antiplatelet aggregation agent of the present invention is as follows.

Specific example 1: 3 g of Jihuang, 3 g of Chinese medicine, 3 g of Yokyu, 3 g of Dangki, 1.5 g of Ori
Add 10 times the amount of water, i.e. 180-g, to a mixed herbal medicine of 1.5 g of Huangbai, 1.5 g of Huanglian, and 1.5 g of Yamateshi, heat and extract at 100°C for 1 hour, and extract the resulting extract. I was removed and spray dried to obtain 2''g of dry extract powder.

Effects of the Invention The antiplatelet aggregation effect of the antiplatelet aggregation agent of the present invention will be explained by giving experimental examples.

Experimental Example ■ Animals Used The experimental animals used were 5-week old Wistar (W1star) male rats (purchased from Japan Charles River Co., Ltd., weighing approximately 100 g).

■Experimental method 100 mg of the antiplatelet aggregation agent of the present invention was administered to rats for 2 weeks.
200 mg was suspended in distilled water and administered orally once a day for 1 month in the morning, and from the end of administration on the last day until treatment.
I fasted for 4 hours. Furthermore, the rats were subjected to laparotomy under ether anesthesia, the vena cava was exposed, and 7.2 d/rat of venous blood was collected into a polypropylene injection syringe containing 3.8% sodium citrate in advance. The collected blood was centrifuged for 10 minutes at 80 Or, p, i, and the supernatant was obtained as platelet-rich plasma (P RP ), which was further centrifuged for 3
After centrifugation at 000 r, p, m for 15 minutes, the supernatant was obtained as platelet-poor plasma (PPP), stored at room temperature, and used within 2 hours.

Rats used as controls were not administered the antiplatelet aggregation agent of the present invention, but were administered only distilled water.

■Agglutination measurement Aggregation measurement is performed using an Alibometer (Aggregation manufactured by Bait 7).
registration node, model
600 B), and was investigated by the ratio-subtraction method. P
After heating RPO, 45d at 37℃ for 1 minute, 950
Changes in plasma permeability associated with platelet aggregation were recorded at r, La+, and 37°C. The platelet aggregation-inducing substance used was adenosine diphosphate (ADP).

PRP is diluted with PPP to a platelet count of approximately 400,000/ml, heated at 37°C for 1 minute, and then heated at 37°C, 950 r, p, m, constant rate. The treatment was carried out under stirring. After 2 minutes, 50 doses of IOMADP solution was added, and platelet aggregation ability was measured using transmittance as an index. That is, the more platelets in the plasma aggregate, the more the permeability of the plasma increases, and the permeability becomes a larger value.

As a result, in the group to which 100 mg of the antiplatelet aggregation agent of the present invention was administered for 2 weeks, the transmittance was 28.2%, which was compared to 36.3% in the control, and an antiplatelet aggregation effect was observed. Furthermore, in the group to which 200+ng of the antiplatelet aggregation agent of the present invention was administered for one month, the transmittance was 28.3%, and similar patterning was observed compared to 38.5% in the control. From this, it was confirmed that the antiplatelet aggregation agent of the present invention has an antiplatelet aggregation effect.

Next, an acute toxicity test of oral administration of the antiplatelet aggregation agent of the present invention was conducted on ddY male mice and Wistar (W 1s) mice.
Specific Example 1
The antiplatelet aggregation agent of the present invention obtained in 1 did not cause any deaths even when administered orally at 15 g/kg (dosage limit). Thus, the antiplatelet aggregation agent of the present invention has extremely low toxicity. Incidentally, hot water has been used by humans as a Chinese herbal medicine since ancient times to the present, and its effectiveness has been confirmed, as well as the fact that it has few side effects has been proven from clinical application results. Considering the results of the experimental data of the present invention, the effective dosage of the antiplatelet aggregation agent of the present invention varies depending on the age, weight, and severity of symptoms of the patient, but is usually an adult dose per day as a dry extract powder amount. It is considered appropriate to take a dose of 1 to IQg divided into three times a day depending on the symptoms.

Next, examples will be shown and specifically explained, but the present invention is not limited thereto.

Example 1 200g of the drug produced according to the above specific example 1 was mixed with 89g of lactose.
g and magnesium stearate tg, and this mixture was compressed into tablets using a single-shot key press to form tablets with a diameter of 20IllIn.
Slug tablets each weighing approximately 2.3 g were prepared, pulverized with an oscillator, sized, and sieved to obtain good granules of 20 to 50 mesh particles.

This granule has a dosage of 0.5 to 4.5 g depending on the symptoms.
(equivalent to 0.34 to 3.10 g as a dry extract powder of the antiplatelet aggregation agent of the present invention) is taken three times a day.

Example 2 200 g of the drug produced according to Example 1 above was mixed with 20 g of microcrystalline cellulose and 5 g of magnesium stearate, and this mixture was compressed into tablets with a single-shot key press to form tablets with a diameter of 7.
Tablets with a weight of 225 mg were produced. Each tablet contains 200% of the dry extract powder of the antiplatelet aggregation agent of the present invention.
Contains mg. This tablet is divided into 1 equal amount and 2. ~
Take 16 tablets three times a day.

Example 3 500 mg of the drug produced according to Example 1 above was filled into hard capsules. This capsule takes 2 to 2 doses depending on the symptoms.
Take 0 capsules in 3 divided doses a day.

Claims (1)

[Claims] Antiplatelet aggregation agent consisting of hot drink