A Chinese medicine composition for treating sequelae caused by cerebral thrombosis or cerebral hemorrhage

Abstract

The invention relates to a traditional Chinese medicine composition for treating sequelae caused by cerebral thrombosis or cerebral hemorrhage. The composition comprises 120-400 parts of chuanxiong, 200-450 parts of stir-fried guanyin seeds, 100-450 parts of santalin and 2-10 parts of borneol. The raw materials are mixed in appropriate proportions to enable the traditional Chinese medicine composition to have outstanding therapeutic effects on sequelae caused by cerebral thrombosis and cerebral hemorrhage, transient cerebral ischemia, central retinal vein occlusion and the like. The preparation method of the traditional Chinese medicine composition is simple and the composition is suitable for large-scale production and promotion.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicines, and in particular relates to a traditional Chinese medicine composition for treating sequelae caused by cerebral thrombosis or cerebral hemorrhage. Background Art

[0002] Stroke is a central nervous system disease in which brain tissue is damaged due to blockage of cerebral blood vessels or sudden rupture of blood vessels. It is characterized by high morbidity, high mortality, high disability rate and high economic burden. Studies have shown that stroke is the second leading cause of death worldwide, accounting for 11.6% of the total number of deaths, and is also the third leading cause of disability. Stroke is divided into ischemic stroke (IS) and hemorrhagic stroke (CH), of which IS has a higher incidence, accounting for 60% to 80% of the total number of strokes. Ischemic stroke is mainly caused by intracranial artery occlusion, involving complex brain neuropathological changes, including excitotoxicity, oxidative stress, neuroinflammation and blood-brain barrier destruction, which eventually lead to brain parenchyma necrosis and neurological deficits. Clinical manifestations include neurological deficits such as hemiplegia, dysphasia, facial paralysis and impaired consciousness. At present, thrombolysis and interventional therapy are the most effective treatments, but the cost of treatment is high, and there is a thrombolysis time window and thrombolysis risk. Therefore, there is an urgent need for a relatively effective and economical treatment strategy to reduce the burden of stroke on society and families. Summary of the invention

[0003] In order to solve the above technical problems, the present invention provides a Chinese medicine composition for treating sequelae caused by cerebral thrombosis or cerebral hemorrhage.

[0004] The technical scheme adopted by the invention is: a traditional Chinese medicine composition comprising 120-400 parts of chuanxiong, 200-450 parts of stir-fried guanyin seeds, 100-450 parts of santalin and 2-10 parts of borneol.

[0005] Preferably, it comprises 240-260 parts of Chuanxiong, 400-450 parts of stir-fried Cnidium monnieri seeds, 200-220 parts of Santalum album and 6-8 parts of borneol.

[0006] Preferably, it comprises 255.3 parts of Chuanxiong, 425.6 parts of stir-fried Cnidium monnieri seeds, 212.8 parts of Santalum album, and 6.4 parts of borneol.

[0007] Application of a Chinese medicine composition in medicine for treating sequelae caused by cerebral thrombosis or cerebral hemorrhage, transient cerebral ischemia or central retinal vein occlusion.

[0008] A method for preparing a drug for treating sequelae caused by cerebral thrombosis or cerebral hemorrhage, wherein a Chinese medicine composition is prepared into a drug preparation; the specific steps are as follows:

[0009] Step 1: Take half of the weight of Chuanxiong and sandalwood, crush and sieve to obtain fine powder A for later use;

[0010] Step 2: Take the other half of the weight of Chuanxiong and sandalwood, mix with stir-fried arborvitae, add water and boil, combine the decoctions, filter and concentrate the filtrate under reduced pressure to prepare a clear paste, mix the clear paste with fine powder A, dry and crush into fine powder, add auxiliary materials and then spray into the borneol solution to mix evenly. Among them, the auxiliary materials can be selected from common categories according to the type of preparation.

[0011] Preferably, in step 1, the powder is sieved through an 80-mesh sieve after being crushed.

[0012] Preferably, in step 2, the relative density of the prepared clear paste when tested at 60°C is 1.36-1.38.

[0013] Preferably, in step 2, an appropriate amount of borneol dissolved in ethanol is sprayed into the mixture.

[0014] Preferably, the product prepared in step 2 can be further made into a preparation, and the preparation type is tablets, capsules, lozenges, granules, pills, powders, pills, suspensions, solutions, injections, suppositories, sprays, drops, pills or patches.

[0015] A pharmaceutical preparation prepared by a method for preparing a drug for treating sequelae caused by cerebral thrombosis or cerebral hemorrhage.

[0016] The advantages and positive effects of the present invention are as follows: the Chinese medicine composition consists of four herbs, namely, rhizoma chuanxiong, fried cnidium, sandalwood and borneol; pharmacological studies have shown that the composition of the present invention can effectively improve neurological function, relieve cerebral infarction and increase cerebral blood flow; the medicine composition can improve cerebral ischemia-reperfusion injury, reduce inflammatory response, and regulate intestinal flora and differential metabolites; and the medicine composition has outstanding therapeutic effects by mixing the raw materials in appropriate proportions. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Fig. 1 Neurological deficit scores of mice in each group;

[0018] Figure 2 TTC staining of mice in each group; white represents the cerebral infarction area, and red represents the normal tissue;

[0019] Figure 3 Statistical bar graph of cerebral infarction area in each group of mice; Comparison between the model group and the sham operation group, # P<0.05, ## P<0.01, ### P < 0.001, ####P<0.0001; there was no significant difference between the embodiment group and the model group, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001, ns (not significant). DETAILED DESCRIPTION

[0020] The embodiments of the present invention are described below with reference to the accompanying drawings.

[0021] The present invention relates to a Chinese medicine composition for treating sequelae caused by cerebral thrombosis or cerebral hemorrhage, and the medicine composition can be used for treating sequelae caused by cerebral thrombosis or cerebral hemorrhage, transient cerebral ischemia and central retinal vein occlusion. The raw materials involved in the Chinese medicine composition include chuanxiong, stir-fried guanyin seeds, sandalwood and borneol. In the field of traditional Chinese medicine, the amount of medicine is the mark of the medicine's strength. If there is no amount in the prescription, there is medicine but no prescription, and no amount cannot explain its exact efficacy. When the Chinese medicine composition specifically includes 120-400 parts of chuanxiong, 200-450 parts of stir-fried guanyin seeds, 100-450 parts of sandalwood and 2-10 parts of borneol, it can produce a significant improvement effect on sequelae caused by cerebral thrombosis and cerebral hemorrhage; preferably, 240-260 parts of chuanxiong, 400-450 parts of stir-fried guanyin seeds, 200-220 parts of sandalwood and 6-8 parts of borneol.

[0022] Ligusticum chuanxiong Ligusticum striatum DC. Dried rhizome of Ligusticum chuanxiong. Pungent, warm. Enters the liver, gallbladder, and pericardium meridians. Used for chest pain, chest and flank pain, swelling and pain from falls, irregular menstruation, amenorrhea, dysmenorrhea, abdominal pain due to symptoms, headache, and rheumatic pain. Ferulic acid is a key component of Ligusticum chuanxiong, which can reduce memory impairment and provide protection against oxidative stress and apoptosis caused by cerebral ischemia / reperfusion injury. Animal experimental studies have shown that Ligustrazine can reduce infarct size, neurological scores, and brain edema in permanent and transient cerebral ischemic injury models.

[0023] Leonurus japonicus Leonurus japonicus Houtt. The dried mature fruit of the herb. Pungent, bitter, slightly cold. Enters the pericardium and liver meridians. Used for irregular menstruation, amenorrhea, dysmenorrhea, conjunctivitis, cataracts, dizziness and pain in the head. Stir-fried Cnidium monnieri is a processed product of Cnidium monnieri. Take the clean Cnidium monnieri and stir-fry until there is a popping sound, the surface is slightly bulging, and the color deepens. Take it out and let it cool. The main ingredient is leonurine, which can reduce the concentration of active oxygen in mitochondria extracted from ischemic cortex.

[0024] Santalum album Santalum album L. Heartwood of the trunk. Pungent, warm. Enters the spleen, stomach, heart, and lung meridians. Used for cold stagnation and qi stagnation, chest discomfort, chest pain, abdominal pain, vomiting and loss of appetite. Sandalwood can enhance antioxidant enzyme activity, scavenge oxygen free radicals, and has been shown to regulate intestinal microbiota.

[0025] Borneolum serratum Dryobalanops aromatica CFGaertn. Resin processed products. Pungent, bitter, slightly cold. Enters the heart, spleen, and lung meridians. Revitalizes the mind, clears away heat and relieves pain. Used for fever, coma, convulsions, stroke, phlegm, qi stagnation, coma, chest pain, red eyes, mouth sores, sore throat, pus in the ear canal. Borneol can inhibit inflammatory factors, reduce oxidative stress, and maintain brain function.

[0026] Chuanxiong is the main drug, which is warm in nature and is a qi drug in the blood. When qi moves, blood moves, and when blood moves, wind will be eliminated. It can remove wind from the top of the head and promote blood circulation, remove blood stasis and relieve pain. Stir-fried Cnidium monnieri is the assistant drug, which tastes slightly cold and can promote blood circulation and remove blood stasis to clear the liver and improve eyesight; it can nourish yin and benefit essence, promote blood circulation and have the effect of nourishing. Chuanxiong and stir-fried Cnidium monnieri are combined, one is warm and the other is cold, one is dispersing and the other is clearing, and they can promote circulation while replenishing, and they can play the role of dispelling wind, promoting blood circulation and removing blood stasis to help regulate qi and blood in the head and eyes. Sandalwood and borneol are adjuvants. Sandalwood is pungent and warm in nature. It can dispel cold and regulate the middle, help promote the circulation of phlegm and qi stasis in the middle jiao caused by unclear orifices and unfavorable spirit, and promote qi circulation and relieve pain. Borneol can open the orifices and wake up the mind, improve eyesight and remove cataracts. The four drugs are used together to achieve the effect of promoting qi and promoting blood circulation, removing blood stasis and opening the orifices.

[0027] The preparation of the above-mentioned pharmaceutical composition comprises the following steps:

[0028] Step 1: Take half of the weight of Chuanxiong and sandalwood, grind them, pass through an 80-mesh sieve to form fine powder A, and set aside;

[0029] Step 2: add water to the other half of the weight of Chuanxiong, sandalwood and stir-fried safflower seed and boil twice, the first time for 2 hours, the second time for 1.5 hours, combine the decoctions, filter, and concentrate the filtrate under reduced pressure until a clear paste with a relative density of 1.36-1.38 (60°C) is formed; mix it with the fine powder A prepared in step 1, dry it, and grind it into fine powder; in some embodiments of the present invention, a flavoring agent can also be added as needed, such as adding an appropriate amount of sucrose fine powder and ethanol to make granules, drying, spraying borneol dissolved in an appropriate amount of ethanol, mixing evenly, pressing into 1000 tablets, and coating with sugar to obtain.

[0030] The pharmaceutical composition can be made into a Chinese medicine preparation, preferably a unit dose pharmaceutical preparation. When the Chinese medicine preparation is made, in step 2, when the clear paste is mixed with the fine powder A, an auxiliary material can be added. The selection of the auxiliary material can be determined according to the type of preparation. The auxiliary material has the functions of excipient, inclusion and dilution. The oral preparation is selected from one of tablets, capsules, granules, dripping pills, concentrated pills, oral liquid and mixture; the injection is selected from one of freeze-dried powder injection, injection liquid and water injection.

[0031] Orally administered preparations may contain conventional excipients such as binders, fillers, diluents, tableting agents, disintegrants, colorants, lubricants, flavoring agents and wetting agents, and the tablets may be coated if necessary. Suitable fillers include cellulose, mannitol, lactose and other similar fillers. Suitable disintegrants include starch, polyvinyl pyrrolidone and starch derivatives, such as sodium starch glycolate. Suitable lubricants include, for example, magnesium stearate. Suitable pharmaceutically acceptable wetting agents include sodium lauryl sulfate.

[0032] The pharmaceutical composition can be prepared into a solid oral composition by conventional methods such as mixing, filling, and tableting. Repeated mixing allows the active substance to be distributed throughout those compositions that use a large amount of fillers. The oral liquid preparation can be in the form of, for example, a solution, an emulsion, an aqueous or oily suspension, a syrup or an elixir, or can be a dry product that can be reconstituted with water or other suitable carriers before use. Such liquid preparations may contain conventional additives, such as suspending agents, such as syrup, sorbitol, methylcellulose, gelatin, hydroxyethylcellulose, carboxymethylcellulose, aluminum stearate gel or hydrogenated edible fats, emulsifiers, such as lecithin, sorbitan monooleate or gum arabic; non-aqueous carriers (which may include edible oils), such as fractionated coconut oil, almond oil, oily esters such as glycerol esters, propylene glycol or ethanol; preservatives, such as methyl paraben or propyl paraben or sorbic acid, and, if desired, conventional flavoring agents or coloring agents. For injections, the prepared liquid unit dosage form contains the active substance of the present invention and a sterile carrier. Depending on the vehicle and concentration, the compound may be suspended or dissolved. Solutions are usually prepared by dissolving the active substance in a vehicle, filter sterilizing it before filling it into a suitable vial or ampoule, which is then sealed. Excipients such as a local anesthetic, preservatives and buffers may also be dissolved in the vehicle. To improve its stability, the composition may be frozen after filling into the vial and the water removed under vacuum.

[0033] The pharmaceutical composition can be selectively added with a suitable pharmaceutically acceptable carrier when it is prepared into a medicament. The pharmaceutically acceptable carrier is selected from the group consisting of: vitamin C, mannitol, sorbitol, sodium pyrosulfite, methionine, sodium bisulfite, sodium thiosulfate, cysteine ​​hydrochloride, thioglycolic acid, disodium EDTA, calcium sodium EDTA, carbonates, acetates, phosphates of monovalent alkali metals or their aqueous solutions, hydrochloric acid, acetic acid, sulfuric acid, phosphoric acid, amino acids, sodium chloride, potassium chloride, sodium lactate, xylitol, maltose, glucose, fructose, dextran, glycine, lactose, mannitol, silicon derivatives, starch, sucrose, cellulose and its derivatives, alginate, gelatin, polyvinyl pyrrolidone, glycerol, soil temperature 80, agar, calcium carbonate, calcium bicarbonate, polyethylene glycol, dextrin, cyclodextrin, surfactants, β-cyclodextrin, phospholipid materials, kaolin, talc, calcium stearate, magnesium stearate, etc. Flavoring agents are used to improve the taste of granules, among which sweeteners commonly used are aspartame, sucralose, stevia, etc.

[0034] The scheme of the present invention is described below in conjunction with the accompanying drawings, wherein the experimental methods without specific operating steps are all carried out in accordance with the corresponding product instructions, and the instruments, reagents, and consumables used in the examples can all be purchased from commercial companies unless otherwise specified.

[0035] Main instruments and reagents: thread plug (0621, Henan Yushun); TTC staining solution (2%) (G3005, Beijing Solebow Technology Co., Ltd.); 4% tissue cell fixative (P1110, Beijing Solebow Technology Co., Ltd.); 0.5% CMC-Na (C8621, Beijing Solebow Technology Co., Ltd.); Olympus microscope #CX31.

[0036] Example 1

[0037] The medicine composition comprises 127.1 g of chuanxiong, 213.7 g of stir-fried guanyin seeds, 105.4 g of santalin and 2.6 g of borneol.

[0038] Take half of the weight of Chuanxiong and sandalwood, grind them, pass through an 80-mesh sieve to form fine powder for later use; add water to the other half of the weight of Chuanxiong, sandalwood and stir-fried arborvitae, decoct twice, the first decoction is 2 hours, the second decoction is 1.5 hours, the decoction is combined and filtered, the filtrate is concentrated under reduced pressure, and concentrated to a clear paste with a relative density of 1.36-1.38 measured at 60°C; mix the clear paste with the above fine powder, dry, grind into fine powder, add appropriate amount of powdered sucrose and ethanol to make granules, dry, spray borneol ethanol solution, mix evenly, press into 1000 tablets, and coat with sugar to obtain.

[0039] Example 2

[0040] The pharmaceutical composition comprises 255.3 g of Chuanxiong, 425.6 g of stir-fried Cnidium monnieri seeds, 212.8 g of Santalum album and 6.4 g of Borneol. Tablets are prepared according to the method of Example 1.

[0041] Example 3

[0042] The pharmaceutical composition comprises 380.9 g of Chuanxiong, 430.8 g of stir-fried Cnidium monnieri seeds, 104.8 g of Santalum album and 4.2 g of Borneol. The tablets were prepared according to the method of Example 1.

[0043] Example 4

[0044] The pharmaceutical composition comprises 381.6 g of Chuanxiong, 428.6 g of stir-fried Cnidium monnieri seeds, 428.4 g of Santalum album and 9.5 g of Borneol. Tablets were prepared according to the method of Example 1.

[0045] Example 5

[0046] The pharmaceutical composition comprises 522.2 g of Chuanxiong, 432.1 g of stir-fried Cnidium monnieri seeds, 210.9 g of Santalum album, and 5.9 g of Borneol. Tablets were prepared according to the method of Example 1.

[0047] Example 6

[0048] The pharmaceutical composition comprises 131.1 g of Chuanxiong, 429.2 g of stir-fried Cnidium monnieri seeds, 422.9 g of Santalum album, and 12.0 g of Borneol. Tablets were prepared according to the method of Example 1.

[0049] The composition of each raw material of the pharmaceutical composition disclosed in Examples 1-6 is shown in Table 1.

[0050] Table 1

[0051]

[0052] Example 7

[0053] The pharmaceutical composition comprises 240 g of Chuanxiong, 400 g of stir-fried Cnidium monnieri seeds, 200 g of Santalum album, and 6 g of Borneol. Tablets were prepared according to the method of Example 1.

[0054] Example 8

[0055] The pharmaceutical composition comprises 260 g of Chuanxiong, 450 g of stir-fried Cnidium monnieri seeds, 220 g of Santalum album, and 8 g of Borneol. Tablets were prepared according to the method of Example 1.

[0056] Example 9

[0057] The pharmaceutical composition comprises 120 g of Chuanxiong, 200 g of stir-fried Cnidium monnieri seeds, 100 g of Santalum album, and 2 g of Borneol. Tablets were prepared according to the method of Example 1.

[0058] Example 10

[0059] The pharmaceutical composition comprises 400 g of Chuanxiong, 450 g of stir-fried Cnidium monnieri seeds, 450 g of Santalum album, and 10 g of Borneol. Tablets were prepared according to the method of Example 1.

[0060] In some other embodiments of the present invention, other types of oral preparations or injection preparations can be prepared according to the mass ratio of each component in Examples 1-10, and the product after adding auxiliary materials and spraying borneol is further processed according to the conventional preparation method of each type of pharmaceutical preparation to obtain different types of pharmaceutical preparations including the above-mentioned pharmaceutical composition. The oral preparation can be one of tablets, capsules, granules, dripping pills, concentrated pills, oral liquids and mixtures; the injection can be one of freeze-dried powder injections, injection solutions, and water injections.

[0061] Example 11: Effects of different compositions of pharmaceutical compositions on cerebral ischemia-reperfusion mice

[0062] 11.1 Construction of model animals

[0063] 6-8 week old SPF male C57BL / 6 mice, weighing about 20 g, were purchased from Beijing Weitong Lihua Experimental Animal Technology Co., Ltd., with a production license of SCXK (Beijing) 2021-0006. Before the experiment, they were kept in the SPF animal room of the Institute of Neurology, Tianjin Medical University General Hospital, and were adaptively raised for 1 week in an environment with a temperature of 22-25°C, a humidity of 40%-60%, and a light duration of 12 h. The experimental animals had free access to food and water. The experimental process was carried out in strict accordance with the regulations on the management of experimental animals.

[0064] The mice were randomly divided into 8 groups, namely, sham operation group, model group, and Example 1-6 group, with 12 mice in each group. The tablets made of the pharmaceutical composition in Examples 1-6 were ground into powder, dissolved in 0.5% CMC-Na, and used for gavage. The dosage of the tablets made of the pharmaceutical composition was 0.026 g per mouse per day. Gavage administration began before modeling. The Example group was continuously gavaged for 7 days, once a day, and continuously intervened for 1 week; the sham operation group and the model group were continuously gavaged with an equal volume of 0.5% CMC-Na for 7 days.

[0065] Surgery was performed 1 hour after the last administration. The middle cerebral artery occlusion / reperfusion (MCAO / R) model proposed by Zea-Longa was used as a reference. Mice were fasted for 12 hours before surgery and were only allowed to drink water freely. Mice were anesthetized with isoflurane, shaved, and placed in a supine position. An incision was made along the midline of the neck to expose the left common carotid artery (CCA), external carotid artery (ECA), and internal carotid artery (ICA). The ECA and the proximal end of the CCA were separated and ligated, and the suture was inserted into the ICA through the CCA incision. When resistance was encountered, the suture was stopped. The length of the inserted suture was about 0.9 cm. The mice were then placed on a 37°C heating pad for warmth. After 1 hour of ischemia, the suture was carefully withdrawn to form reperfusion, and the incision skin was sutured. In the sham operation group, only anesthesia, exposure, and separation of blood vessels were performed, and no suture insertion was performed.

[0066] 11.2 Neurological Behavioral Scores

[0067] In order to verify the effect of the composition on cerebral ischemia-reperfusion, we evaluated the neurological deficit scores of mice 24 hours after MCAO / R modeling. Neurological behavioral scores were performed on the 8 groups of mice after modeling. The neurological function score was scored using the Zea Longa scoring method. The neurological function of each group of mice was scored 24 hours after ischemia-reperfusion, with a total score of 4 points. No neurological deficit, 0 points; the front paw on the paralyzed side could not be fully extended, 1 point; turning in circles to the paralyzed side when walking, 2 points; leaning to the paralyzed side when walking, 3 points; inability to walk automatically, and loss of consciousness, 4 points.

[0068] The rating results are as follows Figure 1 As shown, the neurological behavior scores of mice in the model group were significantly higher than those in the sham operation group (P<0.0001). Compared with the model group, the neurological behavior scores of mice in each group of Examples 1-4 (P<0.001, P<0.0001, P<0.001, P<0.001) were all lower, indicating that the compositions of Examples 1-4 of the present invention can significantly improve the neurological behavior of MCAO / R mice. In addition, compared with the model group, the neurological behavior scores of mice in Groups 5-6 of Examples did not change significantly (P>0.05), indicating that Groups 5-6 of Examples of the present invention did not have a good improvement effect on the neurological behavior of MCAO / R mice.

[0069] 11.3 TTC staining

[0070] The whole brain of each group of mice was placed in a refrigerator at -20℃ for 20 minutes, and then the brain was cut into 5 slices with a thickness of 2mm using a blade. The brain slices were placed in 2% TTC solution and placed at 37℃ for 30min. During this period, the brain slices were turned over to ensure uniform staining. Then they were fixed in 4% paraformaldehyde and photographed. Finally, the area of ​​infarct tissue was measured using Image J software and the infarct area was calculated by integration. Infarction rate (%) = infarct area / total brain area × 100%. ImageJ and GraphPad Prism (9.5) were used to draw and statistically analyze the experimental results. GraphPad Prism used a one-way analysis of variance (ANOVA) test. When P<0.05, it was considered that there was a significant difference between the groups.

[0071] Slice color image as Figure 2 As shown in the figure, white is the cerebral infarction area and red is normal tissue. The TTC staining results of brain tissue sections showed that there was no cerebral infarction in the sham operation group, while there was a significant cerebral infarction area in the model group. Figure 3 As shown, the histogram of cerebral infarction area shows that the sham operation group has no cerebral infarction, while the model group has obvious cerebral infarction (P<0.0001). Compared with the model group, the proportion of cerebral infarction area in Examples 1-4 is significantly reduced (P<0.0001), and the effect of Example 2 is particularly obvious; while there is no significant difference between Examples 5-6 and the model group (P>0.05).

[0072] It can be seen from the above experimental data that the pharmaceutical composition prepared by using Chuanxiong, stir-fried Cnidium monnieri, Santalum album and borneol in a suitable mixing ratio has an improvement effect on cerebral ischemia-reperfusion model mice, especially the pharmaceutical composition obtained by the mass ratio in Example 2, which has a better improvement effect on the neurological behavior and cerebral infarction area control of mice compared with other groups.

[0073] In addition, for the above-mentioned groups of mice, cerebral cortical blood flow detection (laser speckle technology), neuronal cell pathology detection in the cerebral cortex, hippocampus and striatum (HE staining technology), and expression level detection of inflammatory factors TNF-α, IL-6 and IL-1β in peripheral blood (ELISA detection technology) were also performed; in addition, the changes in the intestinal flora and metabolites of mice (flora sequencing technology and non-targeted metabolomics) and the genetic changes in mouse brain tissue (transcriptomics) were also studied.

[0074] In various tests, the model mice in group 2 of Example 2 showed the best therapeutic effect in improving neurological function, relieving cerebral infarction, increasing cerebral blood flow, and reducing inflammatory response, while the effect of group 1 was second; the therapeutic effect of groups 5-6 was not as good as that of other groups. In addition, in terms of regulating intestinal flora and differential metabolites, the mice in group 2 of Example 2 also showed the best effect, which was significantly better than other groups.

[0075] Example 12: Clinical application of Chinese medicine composition

[0076] 12.1 Patient Condition

[0077] The patient is a 88-year-old female retired worker.

[0078] Chief complaint: difficulty in right limb movement and slurred speech for 2 months, and was admitted to the hospital due to "dizziness and headache for 1 day".

[0079] Current medical history: The patient suddenly had difficulty in right limb movement and slurred speech 2 months ago, and was diagnosed with cerebral thrombosis by the hospital. After treatment with Western medicine, the condition stabilized, but the patient still had difficulty in right limb movement and slurred speech, so he came to seek treatment from a traditional Chinese doctor.

[0080] 12.2 Diagnosis and treatment

[0081] Western medicine diagnosis: Cerebral thrombosis (called cerebral infarction in Western medicine) is an ischemic stroke. According to the third revised standard of the Second National Cerebrovascular Disease Academic Conference of the Chinese Medical Association in 1986, patients often develop the disease in a quiet state, and most of them do not have obvious headaches and vomiting. The onset can be slow, and it often progresses gradually or in stages, and is often related to cerebral atherosclerosis. The patient's symptoms and signs can be summarized as brain function defects in a certain cerebral artery blood supply area, and there is usually no obvious disturbance of consciousness, and the cerebrospinal fluid is normal, which should be considered as cerebral thrombosis, and cranial CT can help confirm the diagnosis.

[0082] Syndrome differentiation in Chinese medicine: According to the patient's symptoms and signs, combined with the theory of Chinese medicine, the patient belongs to the category of "stroke", and the syndrome differentiation is "blood stasis blocking collaterals". The patient has been ill for a long time, and blood stasis blocks the clear orifices, qi and blood stasis, resulting in poor limb movement, poor tongue collaterals, and unclear speech. The blood is stagnant and the meridians are unfavorable, resulting in tingling in the head and right limbs. The liver blood cannot nourish the eyes, resulting in stagnation of eyes or unclear vision. Phlegm and blood stasis cover the orifices, the spirit is out of harmony, the connection between yin and yang is unfavorable, the qi cannot circulate blood, and blood stasis is blocked inside, resulting in dark complexion, purple tongue, petechiae on the edge of the tongue, and deep and sluggish pulse. The cerebral thrombosis diagnosed by Western medicine is diagnosed by Chinese medicine as blood stasis blocking collaterals (meridians in stroke, blood stasis blocking collaterals syndrome or blood stasis blocking collaterals syndrome in stroke), and the two are unified in diagnosis of blood circulation disorder and local brain tissue ischemia.

[0083] Treatment principle: Promote qi and blood circulation, remove blood stasis and open the orifices.

[0084] Treatment method: Take Chinese medicine orally.

[0085] Prescription: The composition prepared in Example 2, 4 tablets tid.

[0086] 12.3 Symptoms before and after treatment

[0087] Before treatment: The patient had difficulty moving his right limbs, occasional tingling in the head, slurred speech, blurred vision or dry eyes, dark complexion, dark purple tongue, petechiae on the edges of the tongue, and a deep and sluggish pulse.

[0088] After treatment: After oral treatment with Chinese medicine, the patient's limb movement ability will improve, speech function will gradually recover, complexion and tongue will tend to be normal, and pulse will tend to be peaceful. Adhere to treatment and have regular checkups to observe changes in the condition.

[0089] The embodiments of the present invention are described in detail above, but the contents described are only preferred embodiments of the present invention and cannot be considered to limit the scope of implementation of the present invention. All equivalent changes and improvements made within the scope of the present invention should still fall within the scope of the patent coverage of the present invention.

Claims

1. A Chinese medicine composition, characterized in that The invention is prepared from the following components in parts by weight: 120-400 parts of chuanxiong, 200-450 parts of stir-fried cnidii seeds, 100-450 parts of sandalwood and 2-10 parts of borneol.

2. The Chinese medicine composition according to claim 1, characterized in that: 240-260 parts of chuanxiong, 400-450 parts of stir-fried cnidii seeds, 200-220 parts of santalin and 6-8 parts of borneol.

3. The Chinese medicine composition according to claim 1, characterized in that: 255.3 parts of Chuanxiong, 425.6 parts of stir-fried Cnidium monnieri seeds, 212.8 parts of Santalum album, and 6.4 parts of borneol.

4. Use of the Chinese medicine composition according to any one of claims 1 to 3 in the preparation of a drug for treating sequelae caused by cerebral thrombosis or cerebral hemorrhage, transient cerebral ischemia or central retinal vein occlusion.

5. A method for preparing a drug for treating sequelae caused by cerebral thrombosis or cerebral hemorrhage, characterized in that: The Chinese medicine composition according to any one of claims 1 to 3 is prepared into a pharmaceutical preparation; the specific steps are as follows: Step 1: Take half of the weight of Chuanxiong and sandalwood, crush and sieve to obtain fine powder A for later use; Step 2: Take the other half of the weight of Chuanxiong and sandalwood, mix them with the stir-fried safflower seeds, add water and boil, combine the decoctions, filter and concentrate the filtrate under reduced pressure to prepare a clear paste, mix the clear paste with fine powder A, grind it into fine powder after drying, add auxiliary materials and then spray the borneol solution to mix evenly.

6. The method for preparing the drug for treating sequelae caused by cerebral thrombosis or cerebral hemorrhage according to claim 5, characterized in that: In step 1, the powder is crushed and passed through an 80-mesh sieve.

7. The method for preparing the drug for treating sequelae caused by cerebral thrombosis or cerebral hemorrhage according to claim 5, characterized in that: In step 2, when the prepared clear paste is tested at 60°C, its relative density is 1.36-1.

38.

8. The method for preparing the drug for treating sequelae caused by cerebral thrombosis or cerebral hemorrhage according to claim 7, characterized in that: In step 2, borneol dissolved in ethanol is sprayed in.

9. The method for preparing the drug for treating sequelae caused by cerebral thrombosis or cerebral hemorrhage according to any one of claims 5 to 8, characterized in that: The product prepared in step 2 can be further made into a preparation, and the preparation type is tablets, capsules, lozenges, granules, pills, powders, pills, suspensions, solutions, injections, suppositories, sprays, drops, pills or patches.

10. A pharmaceutical preparation obtained by the method for preparing a drug for treating sequelae caused by cerebral thrombosis or cerebral hemorrhage according to any one of claims 5 to 9.

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