JPH0469612B2 - - Google Patents

Description

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

Conventional technology The pharmacological mechanism of the antiplatelet aggregation agents currently in use is clear, and many of them have excellent antiplatelet aggregation effects, but on the other hand, they have side effects such as fire extinguisher ulcer formation and allergies (hives, asthma). There are quite a few. 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 for Solving the Problem The present inventors have conducted research on the anti-platelet aggregation effect of various Chinese herbal prescriptions, and have found that they are composed of other herbal medicines, such as huang, peony, chuan, dangki, huang, huangbai, huanglian, and sanbanzi. We discovered that a Chinese herbal medicine prescription, ie, hot water, has an antiplatelet aggregation effect. Therefore, hot drinks with anti-platelet aggregation effects 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. This is something that never happened. 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 peonies,
Decoct 3g of Kawa, 3g of Toki, 1.5g of Huang, 1.5g of Huangbai, 1.5g of Huangren, and 1.5g of Sanshuzi in 600ml of water to make 350ml.
It is possible to remove the lees and take it in three doses as an antiplatelet aggregation agent, but in order to make it easier to take and carry, a Chinese herbal medicine extract preparation is used as an antiplatelet aggregation agent. It can also be used. For example, 3 to 4 parts by weight of rhizome, 3 to 4 parts by weight of peonies
4 parts by weight, 3 to 4 parts by weight of Kawa, 3 to 4 parts by weight of Dangki, 1.5 to 3 parts of Huang, 1.5 to 2 parts of Huanglian, 1.5 to 2 parts by weight of Yamashu. The extract obtained by hot extraction with 10 parts of water is filtered and dried to obtain a powder of the dry extract, which is an antiplatelet aggregation agent. It can be prepared into powders, granules, tablets, capsules, etc. by adding adjuvants and the like according to conventional methods for manufacturing pharmaceuticals.

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

Specific example 1 3 g of rhizogen, 3 g of peony, 3 g of river, 3 g of toki, 1.5 g of huang, 1.5 g of huang, 1.5 g of huang, 1.5 g
10 times the amount of water (180 ml) was added to the herbal medicine mixture and extracted by heating at 100° C. for 1 hour. The resulting extract was filtered and spray-dried to obtain 2.1 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 Experimental animals are 5-week-old Wistars.
Male rats (purchased from Japan Charles River Co., Ltd., weighing approximately 100 g) were used.

Experimental method: 100 mg of the antiplatelet aggregation agent of the present invention was administered to rats twice.
The drug was suspended in distilled water and orally administered at 200 mg per week for one month once a day in the morning, and fasted for 24 hours from the end of administration on the final day until the treatment. Furthermore, the rats were subjected to laparotomy under ether anesthesia, the inferior vena cava was exposed, and pre-injected with 3.8% sodium citrate.
Venous blood (7.2 ml/rat) was collected into a polypropylene injection syringe containing 0.8 ml. The collected blood was centrifuged at 800 rpm for 10 minutes, and the supernatant was obtained as platelet-rich plasma (PRP).
After centrifugation at 3000 rpm 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.

Aggregation measurement Aggregation measurement is performed using an aggregometer (manufactured by Peito).
aggregation module, Model 600B),
This was investigated using turbidimetry. After heating 0.45 ml of PRP at 37°C for 1 minute, changes in plasma permeability due to platelet aggregation were recorded at 950 rpm and 37°C. The platelet aggregation-inducing substance used was adenosine diphosphate (ADP).

PRP uses PPP to reduce the platelet count to approximately 400,000/
0.45ml diluted to μ for 1 minute
After warming at 37°C, the mixture was incubated at 37°C with constant stirring at 950 rpm. After 2 minutes, add 50μ of ^14-4 MADP solution.
Platelet aggregation ability was measured using transmittance as an index. That is, the more platelets in plasma aggregate, the more the plasma permeability 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 two weeks, the transmittance was 28.2%.
Antiplatelet aggregation effect was observed compared to 36.3% of control. In addition, in the group administered with 200 mg of the antiplatelet aggregation agent of the present invention for one month, the transmittance was
28.3%, and a similar effect 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 the antiplatelet aggregation agent of the present invention by oral administration was conducted using male ddY mice and male Wistar rats. The flocculant is
No deaths occurred even after oral administration of 15 g/Kg (dose limit). Thus, the antiplatelet aggregation agent of the present invention has extremely low toxicity.
Incidentally, Onseindrink has been used by humans as a Chinese herbal medicine since ancient times to the present, and its effectiveness has been ensured, as well as the fact that it has few side effects, which has been proven through clinical application results. Considering the results of the experimental data of the present invention, the effective dose of the antiplatelet aggregation agent of the present invention varies depending on the patient's age, weight, and severity of symptoms, but is usually an adult dose as a dry extract powder amount. It is considered appropriate to take a daily dose of 1 to 10 g divided into three times a day depending on the symptoms.

Next, examples will be shown and concretely explained,
The present invention is not limited thereby.

Example 1 200 g of the drug produced in Example 1 above was mixed with 89 g of lactose and 1 g of magnesium stearate, and this mixture was compressed using a single-shot tablet machine to form slug tablets with a diameter of 20 mm and a weight of approximately 2.3 g. This is crushed using an oscillator, rectified, and sieved.
A good granule of 20-50 mesh particles was obtained.

This granule is available in a single dose of 0.5 to 4.5 depending on the symptoms.
g (equivalent to 0.34 to 3.10 g of dry extract powder weight of the antiplatelet aggregation agent of the present invention) three times a day.

Example 2 200 g of the drug produced in Example 1 above was mixed with 20 g of microcrystalline cellulose and 5 g of magnesium stearate, and this mixture was compressed using a single-shot tablet machine to produce tablets with a diameter of 7 mm and a weight of 225 mg. did. One tablet of the present invention contains 200 mg of the dry extract powder of the antiplatelet aggregation agent of the present invention. This tablet is taken in doses of 2 to 6 tablets three times a day, depending on the symptoms.

Example 3 500 mg of the drug produced according to Example 1 above was filled into hard capsules. This capsule is taken in 2 to 20 capsules three times a day, depending on the symptoms.

Claims (1)

[Claims] 1. Anti-platelet aggregation agent in hot drink