Link:  Pharm/Biotech Resources

Title:  Composition of medicine for treating headache disease and process of preparation and uses thereof

United States Patent:  6,919,094

Issued:  July 19, 2005

Inventors:  Xiao; Wei (Jiangsu, CN)

Assignee:  Jiangsu Kanion Pharmaceutical Co., Ltd. (Lianyungang, CN)

Appl. No.:  380273

Filed:  September 12, 2000

PCT Filed:  September 12, 2000

PCT NO:  PCT/CN00/00272

371 Date:  July 23, 2003

102(e) Date:  July 23, 2003

PCT PUB.NO.:  WO02/22143

PCT PUB. Date:  March 21, 2002

This invention relates to a medicine combination used to treat headache, which is made up of Chuanxiong and Tianma in a certain scientific weight proportion. The medicine combination can be made into any commonly used dosage form. The invention also provides other applications of this medicine combination in the production of an anti-oxidative drug, an antihypertensive drug, a platelet antiaggregation drug, an antithrombosis drug and an anticoagulant.

FIELD OF THE INVENTION

This invention is related to a kind of combination of medicines to treat headache, especially a combination of medicines which are made from the Chinese herbal medicine that can cure headache. This invention is also related to the preparation of this medicine combination and applications in the pharmaceutical field-the traditional Chinese medicine field.

BACKGROUND OF THE INVENTION

Headache, especially the vascular headache, is a commonly encountered disease and frequently occurring disease. Vascular headache includes the type of vascular hemicrania and the type of vascular nonhemicrania. Based on the domestic and international statistical data, the incidence rate of vascular headache is about 4-6%, while the incidence rate in China is about 6.3%. Estimated on this data, the number of the patients suffering from the vascular headache in China is about 6,000,000-8,000,000, while the actual number may be even more. This disease seriously affects people's usual work, study, health and life.

In the recent decades, more and more attention was paid to this disease in the modern medicine. The majority of the scholars believe that the mechanism of vascular headache is related to the genetic factors, the dysfunction of the cerebrovascular relaxation-contraction movement, the vitium of the blood brain barrier, the dysfunction of the internal secretion, the concentration change of the bradykinin, 5-HT, histamine and the other vaso-active substances, the enhancement of the platelet aggregative function and adhesive function. By now, the main therapies of the vascular headache include: vasoconstrictor, antiserotonin, inhibitor of the platelet aggregation, antihistamine, β-receptor blocking agent, tranquilizer, several kinds of hormone, oxygen therapy in the high pressure situation and the surgical therapies such as the cutting off the sympathetic nerve and the ligation of the special vessels out of skull. But the effects are not very ideal, especially the effects in the future. Additionally, all these therapies have many side effects.

SUMMARY OF THE INVENTION

By taking advantage of the plentifulness of the Chinese herbal medicine in combination with the modem pharmacological, toxicological and clinical research findings of the Chinese herb medicine, we selected two herbs: Chuanxiongiong (Rhizome of chuanxiong)-with the function of activating blood circulation to dissipate blood stasis, and Tianma (Rhizome of tall gastrodia)-with the function of calming the wind and relieving convulsion and spasm, then searched out a scientific way of compatibility and an elaborate preparation method. On these bases we made out this invention's technical proposal.

The first purpose of this invention is to provide a medicine combination, which has a remarkable function of anticoagulant, antianoxic, depressurizing, calming and antalgic, to treat headache.

The second purpose of this invention is to provide the special preparation of this medicine combination.

The third purpose of this invention is to provide the application of this medicine combination in the manufacture of other medicines used to treat headache. These medicines include the drug to treat the vascular headache and the drug to treat the neural headache.

The fourth purpose of this invention is to provide the application of this medicine combination in the manufacture of the antianoxic drug.

The fifth purpose of this invention is to provide the application of this medicine combination in the manufacture of antihypertensive drug.

The sixth purpose of this invention is to provide the application of this medicine combination in the manufacture of the platelet anticoagulant.

The seventh purpose of this invention is to provide the application of this medicine combination in the manufacture of the anti-thrombosis drug.

The eighth purpose of this invention is to provide the application of this medicine combination in the manufacture of the anticoagulant.

The medicine combination mentioned in this invention was composed by the herbs of the special weight as following:

Chuanxiongiong 10 g-25 g

Tianma 1.5 g-8 g

The better weight proportion of the two herbs is that:

Chuanxiongiong 8 g-15 g

Tianma 2 g-6 g

The best weight proportion of the two herbs is that:

Chuanxiongiong 10 g

Tianma 2.5 g

According to the special compatibility of the herbs mentioned above and by the regular pharmaceutics method, the medicine combination in this invention can be made into any of the normal dosage forms, such as the capsule, the water-soluble powder, the tablet, the pellet, the oral liquid and the drop pills. The optimal form is the capsule. In the producing process, a regular excipient such as amylo and silicon dioxide can be added in the medicine combination.

The preparation of the medicine combination of the present invention is that: in the proportion of the present invention, Chuanxiongiong and Tianma of the special weight are dehydrated, smashed and mixed together. The mixed powder is extracted in the cycling 90% alcohol solution. The extracted liquids are merged and filtrated. Then the extracted solution is condensed to the clear cream at the relative density of 1.27 and at the degree ranged from 55° C. to 60° C. The gruffs are cooked in water, and then the extracted water solutions are merged and filtrated. The solution is condensed to the clear cream at the relative density of 1.27 and at the temperature ranging from 55° C. to 60° C. and then all the clear cream is combined together. The excipient is added into the mixed cream, and then the new cream is dehydrated in the vacuum, smashed and filtrated. Capsule the medicine powder and obtain the final medicine capsule.

In the preparation mentioned, the 90% alcohol solution can be used twice to extract the mixed raw herbs powder, and each time for 2 hours. The gruffs can be cooked twice, and each time for 1 hour.

The invention medicine has the function of curing the wind syndrome of head, the dizziness and blurred vision. It is also good at dispelling the wind and cold in the Yang channel, dispersing and expelling the phlegm in the chest, and treating the splitting and normal headache. It can also relieve the body constriction and listlessness, refresh the mind, and open the orifice. It has an obvious effect on the cardiovascular system, the blood system and the central nervous system. The effects on these systems are as follows:

1. The effect on the cardiovascular system: (1) the antianoxic function: The invention medicine can enhance the mouse's tolerance to the anoxic situation in the normal atmosphere pressure, and prolong the time of death in the oxygen free environment. It can lower the heart's time-tension index (TTI) of the anesthetic dog, and reduce the cardiac muscle's oxygen consumption. (2) The function of lowering BP: Not only can it lower the BP of the normal rat and dog in the anesthetic condition, but also lowers the BP, renin activity and the aldosterone concentration of the renal hypertension rat (Goldblatt rat) and the spontaneous hypertension rat. The fact indicates that the effect of lowering the BP is accomplished by regulating the RAS system.

2. The effect on the blood system: (1) The function of inhibiting the platelet aggregation: This invention medicine can not only suppress the rabbit's and rat's platelet aggregation induced by the ADP, but suppress the rat's experimental thrombosis. (2) The function of anticoagulation: the medicine can prolong the rat's thrombin time (TT) and the kaolin partial thrombin time (KPTT), and enhance the anticoagulation activity of the plasma.

3. The effect on the central nervous system: (1) The function of tranquilizing; (2) The function of antalgic: it can relieve the pain caused by the heat, the electricity and the chemical reagent.

Another advantage of this invention medicine lies in that that Chuanxiong has the function of activating blood circulation to dissipate blood stasis and meliorating the blood circulation of the brain, and that Tianma has the function of relieving the pain caused by contracture and spasm and meliorating the vascular function. When the two herbs are used together, they can create a synergetic effect. Chuanxiong, which can activate blood circulation and dissipate blood stasis, makes the blood flow smoothly in the vessel. Additionally, it can promote circulation of Qi to relieve the pain. It is the king medicine in the invention medicine combination. Tianma, which has the even nature and the sweet flavor, can calm the wind and arrest convulsion. It is good at curing the dizziness, the wind syndrome of head, the headache and the numbness of the limbs. It is good at going to the upper orifices and makes up the best compatibility with Chuanxiong to treat vascular headache. The combination of the two herbs has a good effect to relieve the tendencies of "dense, congregate, stasis", that is the characteristic of the blood-stasis-type patients. The compound has a better effect than the single herb. Toxicology experiments indicated that: the Daxiong (made by the method of the present invention and named after Daxiong capsule) capsule's LD₅₀ amounts by single administration on mouse are as follows: intravenous injection (4.01±0.41 g/kg); intraabdominal injection (14.03±1.12 g/kg); stomach douche (52.19±6.36 g/kg). The Daxiong capsule's LD50 amount by single administration on rat by oral administration is 57.36±4.82 g/kg. Rats which have taken the Daxiong capsule continuously on the amount of 7.5, 15.0 g/kg for 3 months showed no toxic reaction. This amount is 10-20 times of the clinical dosage.

In addition, the clinical experiment proved that: the Daxiong capsule's total effective rate is 89.05%, which is remarkable higher than 72% effective rate of the commonly used similar medicine-"Yuntongding". The total effective rate in patients with hyperactivity of liver-yang is 90.91%, while the rate in the patients of internal accumulation of blood stasis is 72%. The effective rate is obviously higher than that of the "yuntongding".

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Practice Example 1

Chuanxiongiong 784 g and Tianma 196 g were taken, then the raw herbs were dehydrated, smashed and mixed. The powder was extracted with the 90% alcohol solute twice, each time for 2 hours. The extracted solution was collected, then filtered and the colature condensed to the clear cream at the relative density of 1.27 (55-60° C.) The gruffs were cooked in the water twice, each time for 1 hour. The extracting solution was collected and filtered then the solution was condensed to the clear cream at the relative density of 1.27(55-60° C.). The clear cream was mixed together with the cream mentioned above, then silicon dioxide 49 g was added to it. The medicine

Claim 1 of 13 Claims

1. A method for preparing a pharmaceutical composition made of herbs based on the following weight proportion:

rhizome of chuanxiong 10 g-25 g, and

rhizome of tall gastrodia 1.5 g-8 g;

the method comprising:

(1) dehydrating, smashing, and mixing together rhizome of chuanxiong and rhizome of tall gastrodia to obtain a mixed powder of rhizome of chuanxiong and rhizome of tall gastrodia;

(2) reflux extracting the mixed powder of rhizome of chuanxiong and rhizome of tall gastrodia with 90% alcohol solution at least once to extract at least one reflux extracted solution;

(3) if the mixed powder of rhizome of chuanxiong and rhizome of tall gastrodia is reflux extracted more than once, then the reflux extracted solutions are merged into one reflux extracted solution;

(4) filtering the reflux extracted solution to obtain a reflux filtrate;

(5) condensing the reflux filtrate to a clear cream at a relative density of 1.27 and at a temperature ranging from 55° C. to 60° C.;

(6) cooking the gruffs remaining from the alcohol extraction of step (2) of rhizome of chuanxiong and rhizome of tall gastrodia with water at least once to obtain at least one cooked extracted solution;

(7) if the gruffs of rhizome of chuanxiong and rhizome of tall gastrodia arc cooked more than once, then the cooked extracted solutions are merged into one cooked extracted solution;

(8) filtering the cooked extracted solution to obtain a cooked filtrate;

(9) condensing the cooked filtrate to clear cream at a relative density of 1.27 and at a temperature ranging from 55° C. to 60° C.;

(10) combining the clear creams from steps (5) and (9) together;

(11) adding excipient to the combined clear cream; and

(12) vacuum dehydrating; smashing; and filtering the cream.

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