TW201900195A - Herbal composition for preventing or alleviating ischemic stroke - Google Patents

Abstract

The present invention relates to an herbal composition, comprising Ligusticum chuanxiong, Angelica dahurica, Spatholobus suberectus Dunn, Equisetum hiemale L., Carthamus tinctorius L., and green tea, and methods for its preparation. The present invention further relates to a use of preparing the herbal composition for preventing or alleviation of thrombotic and related diseases.

Description

 Prevent or improve ischemic stroke in herbal compositions  

The present invention provides a Chinese herbal medicine composition comprising Chuanxiong, Angelica, Spatholobus, Equisetum, Saffron, Green Tea or a combination thereof; the present invention further provides for preparing the Chinese herbal composition for preventing or ameliorating thrombosis or thrombosis-related diseases. Use, and a preparation method of the Chinese herbal medicine composition.

Stroke is also called acute cerebrovascular disease, which is the second leading cause of death in Taiwan after cancer. If cancer is ranked according to different types, stroke is the first cause of death for all single diseases. Brain stroke is a vascular disease. When the blood vessels of the brain are blocked by blood plugs and the blood cannot supply oxygen and nutrients to the brain normally, a stroke will occur. Once the blood supply to the brain is insufficient, it is short. Within a few seconds, the cells in the brain begin to die. The types of stroke are mainly divided into two categories: ischemic and hemorrhagic. According to statistics, 80% of stroke patients have ischemic stroke, and hemorrhagic stroke accounts for about 20%.

Chuanxiong has a certain effect on the treatment of headache. "Shen Nong's Herbal Classic" said: "The main stroke has a headache, cold and cold." Li Dongyuan, a member of the Jinyuan Four, is also a member of Yunchuan. However, Chuanxiong is dry and only suitable for people with partial cold.

Chuanxiong and white peony have a long history of treatment. "Materia Medica" has pointed out that "white 芷 is the (Chuan-chuan)." Both Baiqi and Chuanxiong are hurricane painkillers, white peony and dehumidification, and sharing with Chuanxiong can enhance the efficacy of Chuanxiong.

Unless otherwise specifically defined, the terms used in this description will have the ordinary and common meanings that are known to those skilled in the art. As used throughout the application, the following terms have the meanings set forth below: The term "individual" means an animal. Preferably, the animal is a mammal, such as a mouse, a rat, a human, a dog, a cat, and the like. In a preferred embodiment, the system is human.

The invention combines Chuanxiong and Baiqi, and adds a combination of Chinese herbal medicines such as activating blood composition to form a new formula, taking the brain as the main target, and evaluating the curative effect of preventing ischemic stroke by animal experiments.

The object of the present invention is to provide a Chinese herbal medicine composition comprising about 0.5 to 1.5 parts by weight of the dry weight of the material, about 0.5 to 1.5 parts by weight of the white peony, about 1.5 to 4.5 parts by weight of the spatholobus, and about 0.5 to 1.5 for the thief. The weight is about 0.2 to 1 part by weight of the safflower, and about 0.5 to 1.5 parts by weight of the green tea or a combination thereof. Preferably, the Chinese herbal medicine composition comprises about 1 part by weight of Rhizoma Chuanxiong, about 1 part by weight of white peony, about 3 parts by weight of spatholobus, about 1 part by weight of squid, about 0.5 weight of safflower, and green tea. About 1 part by weight.

In a specific embodiment of the invention, the herbal composition is used to prevent or ameliorate thrombosis or thrombosis related diseases. In another specific embodiment, the thrombosis-related disease refers to a cardiovascular disease or a cerebrovascular disease. In a more specific embodiment, the cerebrovascular disease refers to an ischemic stroke.

The present invention further provides a use for preparing a Chinese herbal medicine composition for preventing or ameliorating a thrombosis or a thrombosis-related disease, wherein the Chinese herbal medicine composition comprises about 0.5 to 1.5 parts by weight of the sorghum, and about 0.5 to 1.5 parts by weight of the white peony. The spatholobus is about 1.5~4.5 weight points, the wood thief is about 0.5~1.5 weight points, the safflower is about 0.2~1 weight, the green tea is about 0.5~1.5 weight points or a combination thereof. Preferably, the Chinese herbal medicine composition comprises about 1 part by weight of Chuanxiong, about 1 part by weight of white peony, about 3 parts by weight of spatholobus, about 1 part by weight of squid, about 0.5 weight of safflower, and about about 50 parts by weight of green tea. 1 weight point.

The invention further provides a method for preparing a Chinese herbal medicine composition, which comprises: cooking 0.5~1.5 weight of Chuanxiong with 0.5~1.5 parts by weight of white peony for half an hour to form a first pot of cooking liquor; 1.5~4.5 weighting of spatholobus sinensis The second pot of cooking liquid is boiled with 0.5~1.5 weight of wood thief for two hours; the second pot cooking liquid is heated by adding 0.2~1 weight of safflower and 0.5~1.5 weight green tea for half an hour; and the first pot The second pot and the third pot of cooking liquid are mixed to form a solution of the Chinese herbal medicine composition.

In one embodiment, the solution of the Chinese herbal composition is further concentrated to form a concentrate of a Chinese herbal composition. Preferably, the concentrate of the Chinese herbal medicine composition is further spray-dried to form a powder of a Chinese herbal medicine composition.

The Chinese herbal medicine composition of the present invention was tested in a cerebral artery occlusion/reperfusion stroke mode mouse, and the results of the stroke test showed that the herbal composition of the present invention can effectively prevent brain damage caused by ischemic stroke. a), as well as improving the neurological deficits caused by stroke (Figure 2).

The composition of the present invention may be in the form of a solid, a solution, an emulsion, a dispersion, a micelle, a liposome, and other composition products containing, as an active ingredient, one or more of the ingredients of the present invention, or with an organic or inorganic carrier or The excipients are mixed for application to enteral or parenteral administration. The active ingredient may be mixed, for example, in a pharmaceutically acceptable usually non-toxic vehicle such as a tablet, pill, capsule, suppository, solution, emulsion, suspension, and any other suitable form for use. Carriers which may be used include glucose, lactose, gum arabic, gelatin, mannitol, starch paste, magnesium tricaprate, talc, corn starch, keratin, colloidal cerium oxide, potato starch, urea, medium chain length triglycerides. , dextran, and other carriers suitable for the preparation of the formulation, solid, semi-solid or liquid form. In addition, stabilizers, thickeners and colorants and perfumes may also be used as an aid.

The compositions of the present invention may be administered orally, for example, as tablets, troches, lozenges, aqueous or oily suspensions, dispersible powders or granules, emulsions, hard or soft capsules, or syrups or elixirs. Compositions for oral use can be prepared according to various known pharmaceutical composition preparation methods, and the compositions may contain one or more sweeteners such as sucrose, lactose or saccharin, such as mint, wintergreen or cherry. Colorants and preservatives provide pharmaceutical aesthetics and mouthfeel. Tablets mixed with the active ingredient and a pharmaceutically acceptable non-toxic excipient can also be produced by known methods. Excipients which may be used are, for example, (1) inert diluents such as calcium carbonate, lactose, calcium phosphate or sodium phosphate; (2) granulating agents and disintegrating agents such as corn starch, potato starch or alginic acid; Adhesives such as tragacanth, corn starch, gelatin or gum arabic, and (4) lubricants such as magnesium stearate, stearic acid or talc. The tablets may be uncoated or may be coated by known techniques to delay disintegration and absorption in the gastrointestinal tract, thereby providing a sustained action over a longer period of time. For example, a time delay material such as glyceryl monostearate or glyceryl distearate may be employed, or may be coated by techniques such as those described in U.S. Patent Nos. 4,256,108; 4,160,452; and 4,265,874, to produce controlled release. Osmotic treatment tablets.

In some cases, the compositions for oral use can be in the form of hard gelatin capsules in which the active ingredient is mixed with an inert solid diluent such as calcium carbonate, calcium phosphate or kaolin. They may also be in the form of soft gelatin capsules in which the active ingredient is mixed with water or oil medium, such as peanut oil, liquid paraffin or olive oil.

Embodiments of the compositions of the invention may also be in the form of a sterile injectable suspension. This suspension may be formulated according to known methods using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent, for example as a solution in 1,3-butanediol. Sterile, fixed oils are usually employed as a solvent or suspension medium. For this purpose, any mild fixed oil can be used, including synthetic mono- or diglycerides, fatty acids (including oleic acid), naturally occurring vegetable oils such as sesame oil, coconut oil, peanut oil, cottonseed oil, etc., or synthetic fatty acid carriers. Such as ethyl oleate or the like. Buffering agents, preservatives, antioxidants, and the like can be combined as needed.

Embodiments of the compositions of the invention may also be administered in the form of a suppository in the rectal cavity. By combining the drug with a suitable non-irritating excipient, such as a synthetic glyceride of cocoa butter or polyethylene glycol, the composition is solid at room temperature but liquefied and/or dissolved in the rectal cavity. To release the drug.

Since individual subjects may exhibit broad variations in the severity of the symptoms, and each drug has its own unique therapeutic profile, the composition of the present invention should be performed by the physician to determine the subject's response to the treatment and to vary the dosage accordingly. .

Figure 1 is an analysis of the degree of brain injury after treatment of stroke in Chinese herbal medicine composition - infarct size and edema degree analysis. Pre-fed C57BL/6 mouse vehicle (CMC suspending agent) (control group, CT) or different multiple human dose (two times: 1.2 grams per kilogram per day, 2x; or five times: 3 grams per kilogram per day, 5x) One month after the herbal composition of the present invention, the mice were subjected to middle cerebral artery infarction, and 24 hours later, the changes in the area of brain infarction (A and B) and (C) the degree of edema were evaluated using an imaging system. The number of animals in each group is 4-6. *** represents a P value of less than 0.001.

Figure 2 is an evaluation of the degree of brain injury after treatment of stroke in Chinese herbal medicine composition of the present invention--analysis of animal behavior patterns. Pre-fed C57BL/6 mouse vehicle (CMC suspending agent) (control group, CT) or different multiple human dose (two times: 1.2 grams per kilogram per day, 2x; or five times: 3 grams per kilogram per day, 5x) One month after the herbal composition of the present invention, the mice were subjected to middle cerebral artery infarction, and the degree of neurological deficit behavior was evaluated after 1 hour and 24 hours, respectively. The number of animals in each group is 5-10.

It is an object of the present invention to provide a Chinese herbal medicine composition for use in preventing or ameliorating a thrombosis or a thrombosis-related disease, and a preparation method thereof. Wherein, the Chinese herbal medicine composition comprises Chuanxiong, Baiji, Spatholobus, Equisetum, Chuanhonghua, green tea or a combination thereof.

The following examples are not intended to be limiting, but merely to present various aspects of the invention.

Example 1. Preparation method of Chinese herbal medicine composition.

10 grams of Chuanxiong and 10 grams of white peony are cooked for half an hour into the first pot of cooking liquid; 30 grams of spatholobus and 10 grams of squid are boiled for 2 hours into a second pot of cooking liquid; 5 grams of safflower and 10 grams of green tea are heated for half an hour. The third pot of cooking liquid. The first pot, the second pot, and the third pot of cooking liquor are mixed, concentrated, and spray dried to a powder.

Example 2: Evaluation of the degree of brain injury after stroke treatment.

The middle cerebral artery occlusion/reperfusion stroke pattern in mice.

Six-week-old C57BL/6 strain mice (body weight 20-25 g) were anesthetized with a 3% isoflurane (isofluran, dissolved in 95% O ₂ and 5% CO ₂ ) gas mixer and 2% isoflurane (isoflurane) ) Maintain anesthesia. The skin of the neck is cut from the midline to find the right common carotid artery, the external carotid artery, and the internal carotid artery. The wire plug is inserted through the external carotid artery. The carotid artery, which causes the ischemia of the right middle cerebral artery, then sutures the wound, allowing the mouse to naturally wake up. Behavioral testing was used to confirm that the mouse was on a successful single side of the brain ischemia. Twenty-four hours later, brain tissue was removed for further analysis. The body temperature of the mice was maintained at 37 °C during the operation.

Determination of the infarct size.

After 24 hours of blood reperfusion, 200 mg of anesthetized mice per kiloliter of chloral hydrate were used to remove the brain tissue under low temperature and oxygen, and the crown was sliced to a thickness of 2 mm. Dyeing with 2% 2,3,5-triphenyltetrazolium chloride (TTC) at 37 ° C, the cells will metabolize to red and accumulate if the cells survive. In the cells, the cells that died in the opposite direction showed white color, and after 30 minutes, they were fixed in a 10% formaldehyde solution. The next day, brain slices were photographed with a digital camera (Nikon Coolpix 5000), and finally the percentage of cerebral infarction volume (% infarction volume) was calculated by Image-Pro Plus. The contralateral hemisphere of the experiment was controlled. Group, and converted the survival rate of brain cells to evaluate the efficacy of drugs in the treatment of brain damage caused by ischemic cerebral infarction. A: undamaged area of the ipsilateral cerebral hemisphere (right brain); B: area of the contralateral hemisphere (left brain); cerebral infarction rate after calibration: (B-A) / B × 100%.

Neurological deficits.

To assess the extent of motor nerve damage after stroke in mice. When the blood is reperfused for the first hour and the twenty-fourth hour, the bystander first determines the behavior pattern of the mouse, and then the mouse is subjected to other experiments. This grading system is detailed below. If mice present a more severe grade, they are classified by a more severe grade. The neurological examination process lasted 3 to 5 minutes. The experimental procedure is as follows: firstly, hold the mouse tail gently and hang it one meter away from the ground to observe the bending of the forefoot. If the two forefoot of the mouse can be extended to the ground in a balanced manner, and no other nerve defects are observed, it is a normal mouse, indicating level 0. Mice with cerebral infarction contract the forelimbs concentrically to the contralateral side of the brain injury hemisphere; while forelimb contractions vary with the degree of injury, such as wrist flexion, shoulder adduction, and elbow stiffness. More severe contraction causes the wrist and elbow to bend completely and the shoulder to adduct and rotate inward. When the mouse has the above-mentioned degree of forelimb contraction and no other abnormalities, the mouse is classified as the first level. When the mouse is placed on a counter-protection paper (Kimberly Clarke), the paper is held tightly by the claws. Grab the tail of the mouse with your hand and apply force from behind the shoulder until the forelimb of the mouse slides a few inches. According to this procedure, the operation is performed several times in different directions. Rats with normal or slight stroke have the same resistance to the pulling force in different directions. The lateral force exerted by the severely stroked mouse on the side of the paralysis body will reduce the resistance, and is classified as the first level 2. Then let the mouse move freely and observe its behavior around the circle. If the mouse moves to the side of the paralysis, it is classified as level 3. If the mouse loses walking or is difficult to walk, it is classified as level 4.

The administration of the experiment was designed to be administered orally to mice in different doses of the Chinese herbal medicine composition of the present invention for one month before the operation; the experimental grouping was divided into: (1) no operation control group (sham group), (2) surgery However, the unadministered group, (3) the low dose of the Chinese herbal medicine composition group of the present invention, and (4) the high dose of the Chinese herbal medicine composition group of the present invention were observed for the brain injury area and the indicators of cerebral infarction.

The experimental data were expressed as mean ± standard error (mean ± S. E. M.), the difference between the control group and the experimental group, and the experimental statistics were analyzed by one-way ANOVA. If there is a meaningful difference, then the Newman-Keuls method is used to compare the differences between the groups. If the P value is less than 0.05, it means a meaningful difference.

The experimental results showed that feeding the Chinese herbal composition of the present invention to 1.2 gram per kilogram per day or 3 gram per kilogram per day can effectively prevent brain damage caused by ischemic stroke surgery (Fig. 1). And improve the neurological deficits caused by stroke (Figure 2).

This invention has been described and illustrated in sufficient detail to enable a person of ordinary skill in the art to which this invention pertains. The various modifications, modifications, and improvements should be considered. It is no different from the spirit and scope of this invention.

It is obvious to those skilled in the art that the present invention can readily understand and achieve the objects of the present invention and obtain the results and advantages mentioned. The animals, materials, and processes and methods for producing the same are representative of the preferred embodiments and are exemplary in nature and are not intended to limit the scope of the invention. Modifications or other uses that may occur to those skilled in the art and in the art of making or using the art are encompassed within the spirit of the invention and are defined by the scope of the invention.

Claims (14)

 A Chinese herbal medicine composition comprising about 0.5 to 1.5 parts by weight of the dry weight of the material, about 0.5 to 1.5 parts by weight of the white peony, about 1.5 to 4.5 parts by weight of the spatholobus, and about 0.5 to 1.5 parts by weight of the squid. 0.2 to 1 part by weight, green tea about 0.5 to 1.5 parts by weight or a combination thereof.    For example, the herbal composition of claim 1 includes about 1 part by weight of Chuanxiong, about 1 part by weight of white peony, about 3 parts by weight of spatholobus, about 1 weight of squid, and about 0.5 of safflower. The weight, and green tea is about 1 part by weight.    For example, the herbal composition of claim 1 or 2 is used for preventing or ameliorating thrombosis or thrombosis-related diseases.    For example, the Chinese herbal medicine composition of claim 3, wherein the thrombosis-related disease refers to a cardiovascular disease or a cerebrovascular disease.    For example, the Chinese herbal medicine composition of claim 4, wherein the cerebrovascular disease refers to an ischemic stroke.    The herbal composition of claim 1 or 2, which is in the form of a tablet, a tablet, an aqueous or oily suspension, a dispersible powder or granule, an emulsion, a hard or soft capsule, a syrup or an elixir, or injection.    A use for preparing a herbal composition for preventing or ameliorating a disease associated with thrombosis or thrombosis, wherein the Chinese herbal medicine composition comprises about 0.5 to 1.5 parts by weight of the glutinous rice, and about 0.5 to 1.5 parts by weight of the white peony, and the spatholobus About 1.5 to 4.5 parts by weight, the thief is about 0.5 to 1.5 parts by weight, the safflower is about 0.2 to 1 part by weight, and the green tea is about 0.5 to 1.5 parts by weight or a combination thereof.    The use of the seventh item of the patent application includes about 1 part by weight of the dry material, about 1 part by weight of the white peony, about 3 parts by weight of the spatholobus, about 1 part by weight of the squid, and about 0.5 weight of the safflower. , and green tea about 1 weight point.    The use of the seventh or eighth aspect of the patent application, wherein the thrombosis-related disease refers to a cardiovascular disease or a cerebrovascular disease.    The use of the ninth aspect of the patent application, wherein the cerebrovascular disease refers to an ischemic stroke.    For use in the scope of claim 7 or 8, it is presented in the form of tablets, troches, aqueous or oily suspensions, dispersible powders or granules, emulsions, hard or soft capsules, syrups or elixirs, or injections.    A method for preparing a Chinese herbal medicine composition, which comprises: cooking 0.5~1.5 weight of Chuanxiong with 0.5~1.5 parts by weight of white peony for half an hour to form a first pot of cooking liquid; 1.5~4.5 parts by weight of spatholobus and 0.5~1.5 weight The thief is boiled for two hours to form a second pot of cooking liquor; the 0.2~1 weight of safflower and 0.5~1.5 parts of green tea are heated for half an hour to form a third pot of cooking liquor; and the first pot, the second pot, And the third pot cooking liquid is mixed to form a solution of the Chinese herbal medicine composition.    The method of claim 12, wherein the solution of the Chinese herbal composition is further concentrated to form a concentrate of a Chinese herbal composition.    The method of claim 13, wherein the concentrate of the Chinese herbal composition is further spray-dried to form a powder of a Chinese herbal composition.