Traditional Chinese medicine preparation for cerebral arterial thrombosis

Abstract

The invention provides a traditional Chinese medicine preparation for cerebral arterial thrombosis, and belongs to the technical field of traditional Chinese medicine pharmacy, the traditional Chinese medicine preparation is prepared from gentiana macrophylla, divaricate saposhnikovia root, mulberry leaf, radix scrophulariae, ruddle, bulbus fritillariae cirrhosae, bamboo juice, selfheal, poria with hostwood and szechwan chinaberry fruit, and the whole formula has the effects of calming liver and suppressing yang, calming endogenous wind and relieving convulsion, eliminating phlegm and inducing resuscitation. The traditional Chinese medicine preparation has a remarkable improvement effect on the neurological function of a cerebral ischemia reperfusion injury model rat, can effectively reduce the water content of brain tissue and the cerebral infarction volume of the rat, remarkably improves the levels of GSH and SOD in serum of the rat and reduces the MDA level, and has the effect of improving oxidative stress induced by cerebral ischemia reperfusion. The traditional Chinese medicine preparation can effectively relieve neurological function loss of a patient suffering from cerebral arterial thrombosis, help to recover life functions of the patient and relieve clinical symptoms of the patient, is definite and remarkable in curative effect and can be used as a new medicine for treating cerebral arterial thrombosis.

Description

Technical Field

[0001] The invention relates to the technical field of traditional Chinese medicine pharmaceutical preparations, and in particular to a traditional Chinese medicine preparation for ischemic stroke. Background Art

[0002] Cerebral vascular accident (CVA) is a common clinical sudden disease with high morbidity, high disability rate, high recurrence rate and high mortality rate. CVA is divided into ischemic stroke (IS) and hemorrhagic stroke (SA). IS is the main type in clinical practice, accounting for about 85% of the incidence of CVA. Therefore, the prevention and treatment of IS is also a major problem that needs to be solved in the field of medical research. IS is mainly caused by hypoxia and ischemia due to cerebral blood circulation disorders, which leads to localized brain tissue softening or necrosis. IS will cause blood supply, oxygen supply and energy supply dysfunction of brain tissue in the arterial supply area, causing secondary vascular endothelial damage and autonomic dysfunction. The key to the treatment of IS lies in how to improve blood microcirculation, promote angiogenesis, reduce nerve function damage, and then restore the body's normal metabolism.

[0003] Currently, Western medicine mainly uses thrombolytic therapy to treat IS. Although thrombolytic therapy can effectively improve the clinical outcome 3 months after treatment, the time window for thrombolysis is limited to 6 hours after onset. Most patients often miss the best treatment opportunity and are left with serious sequelae. Long-term use of Western medicine such as anticoagulants and nerve repair drugs has poor efficacy and serious side effects.

[0004] In recent years, traditional Chinese medicine has gradually appeared in clinical research on IS and has achieved very clear therapeutic effects. Some studies have even confirmed that the total effective rate of comprehensive treatment of traditional Chinese medicine is higher than that of Western medicine. Compared with single chemical drugs, traditional Chinese medicine has a synergistic regulatory effect of multiple components, multiple targets, and multiple pathways in the treatment of IS. Studies have confirmed that traditional Chinese medicine can alleviate the damage caused by cerebral ischemia by improving factors such as oxidative stress, apoptosis, inflammatory response, and calcium overload, and has unique efficacy and development value in the treatment of IS. Traditional Chinese medicine believes that ischemic stroke belongs to the category of "stroke", and the main pathogenesis is blood stasis blocking the brain and blood stasis blocking. The treatment should be based on promoting blood circulation and removing blood stasis, and opening the orifices and activating the collaterals. At present, many traditional Chinese medicine compound prescriptions for the treatment of IS have been disclosed, such as Publication No. CN103550702A and Publication No. CN105232813A, but most of them have unclear mechanisms of action, unclear therapeutic effects, and complex ingredients. Therefore, it is very important to provide a safe, effective, and effective traditional Chinese medicine compound preparation for the treatment or prevention of IS. Summary of the invention

[0005] 1. Technical issues to be resolved

[0006] In view of the deficiencies in the prior art, the present invention provides a traditional Chinese medicine preparation for ischemic stroke.

[0007] (II) Technical solution

[0008] To achieve the above objectives, the present invention is implemented through the following technical solutions:

[0009] The invention provides a traditional Chinese medicine preparation for ischemic cerebral stroke. The traditional Chinese medicine preparation is prepared from the following raw materials in parts by weight: 5-20 parts of gentiana macrophylla, 5-20 parts of siler, 5-20 parts of mulberry leaves, 10-30 parts of scrophulariae, 10-30 parts of magnetite, 5-20 parts of fritillaria cirrhosa, 5-20 parts of bamboo juice, 5-20 parts of selfheal, 5-20 parts of poria, and 5-20 parts of toosendan.

[0010] Furthermore, the Chinese medicine preparation is made of the following raw materials in parts by weight: 10-20 parts of Gentiana macrophylla, 10-20 parts of Saposhnikovia divaricata, 5-15 parts of mulberry leaves, 15-25 parts of Scrophularia ningpoensis, 10-20 parts of magnetite, 5-15 parts of Fritillaria cirrhosa, 5-15 parts of bamboo juice, 5-15 parts of Prunella vulgaris, 5-15 parts of Poria cocos, and 5-15 parts of Toosendan fruit.

[0011] Furthermore, the Chinese medicine preparation is made of the following raw materials in parts by weight: 12 parts of Gentiana macrophylla, 12 parts of Saposhnikovia divaricata, 10 parts of mulberry leaves, 18 parts of Scrophularia ningpoensis, 14 parts of magnetite, 10 parts of Fritillaria cirrhosa, 10 parts of bamboo juice, 8 parts of Prunella vulgaris, 8 parts of Poria cocos, and 8 parts of Toosendan fruit.

[0012] The Chinese medicine preparation provided by the present invention is used to prepare a medicine for treating ischemic stroke. The Chinese medicine preparation is prepared into granules, powders, oral liquids, pills, decoctions or other pharmaceutically acceptable oral dosage forms according to conventional pharmaceutical preparation methods in pharmacy and with medically acceptable adjuvants.

[0013] Qinjiao: It tastes pungent and bitter, is neutral in nature, and enters the stomach, liver, and gallbladder meridians; it has the effects of removing rheumatism, clearing damp-heat, relieving arthralgia and relieving deficiency fever; it is used for rheumatic arthralgia, hemiplegia caused by stroke, muscle spasm, joint pain, damp-heat jaundice, bone steaming and hot flashes, and fever caused by malnutrition in children; Qinjiao mainly contains cyclopentane ether terpenes, triterpenes, lignans, flavonoids, alkaloids, steroids, polysaccharides and other types of ingredients, and its pharmacological effects mainly include anti-inflammatory, analgesic, antibacterial, antiviral, anti-tumor, immunomodulatory, liver protection, antioxidant and other pharmacological activities.

[0014] Saposhnikovia divaricata: spicy, slightly sweet, warm in nature, enters the bladder, spleen, lung and liver meridians; has the effects of dispelling wind, stopping spasms and removing dampness; mainly treats exogenous wind-cold, general pain, wind-cold-dampness arthralgia, joint pain and other symptoms; the more obvious active ingredients in Saposhnikovia divaricata include chromones, polysaccharides, volatile oils, polyacetylenes and coumarins. Modern pharmacological research shows that Saposhnikovia divaricata has antioxidant, antipyretic and analgesic, anti-inflammatory and anti-tumor effects.

[0015] Mulberry leaves: bitter, sweet, cold in nature; enter the lung and liver meridians; have the effects of dispersing wind-heat, clearing the lungs and moistening dryness, calming the liver and improving eyesight, cooling blood and stopping bleeding; used for wind-heat colds, early onset of febrile diseases, lung-heat coughs, red and blurred eyes, etc. Mulberry leaves contain chemical components such as flavonoids, alkaloids, amino acids, and polysaccharides, which mainly have pharmacological effects such as protecting nerves and cardiovascular and cerebrovascular vessels, protecting the liver and improving digestion, protecting the kidneys, anti-tumor, regulating blood sugar and blood lipid metabolism, anti-inflammatory and anti-oxidation.

[0016] Scrophularia: sweet, bitter, salty, slightly cold. Enters the spleen, stomach, and kidney meridians. Clears heat and cools blood; nourishes yin and reduces fire; detoxifies and disperses stagnation. Treats febrile diseases, heat and blood circulation; fever; thirst; red tongue; rash; bone steaming and fatigue cough; insomnia; constipation due to loss of body fluid; blurred vision; sore throat; scrofula and phlegm nodules; carbuncle and ulcer. "Pharmaceutical Chemistry": "Dai Ren said that the kidney is originally cold, and it will become hot when it is weak. If you indulge in lust and consume your essence, your true yin will be depleted, causing the virtual fire to rise. Use Scrophularia ningpoensis to nourish yin and suppress fire. All headaches, heat toxins, tinnitus, sore throat, laryngeal wind, scrofula, yang toxins from typhoid fever, and upset under the heart are caused by rootless floating fire. This medicine has the function of clearing the upper and lower parts. There are great differences in the treatment of kidney deficiency. If the kidney meridian is weak, it will be cold and damp, and it should be warmed and supplemented; if the kidney organs are weak, it will be hot and dry, and it should be cooled and supplemented. This alone cools and moistens the kidney, and its function is better than that of Zhi and Bai, so it is the main medicine for the kidney."

[0017] Daizheshi: It is an oxidized corundum mineral hematite ore, bitter and sweet, slightly cold in nature, and enters the liver, stomach, and heart meridians; it has the effects of calming the liver and suppressing yang, calming the adverse, cooling blood and stopping bleeding. It is often used for headaches, dizziness, palpitations, madness, epilepsy, vomiting, belching, hiccups, choking, coughing, asthma, vomiting blood, epilepsy, metrorrhagia, blood in the stool, and blood in the urine.

[0018] Fritillaria cirrhosa: sweet and bitter in taste; slightly cold in nature; enters the lung and heart meridians; has the effects of clearing heat and moistening the lungs, resolving phlegm and relieving cough, dispersing nodules and reducing swelling; mainly treats lung deficiency, chronic cough, cough due to consumptive disease, dryness and heat cough, lung abscess, scrofula, carbuncle, breast abscess, etc. The main chemical components of Fritillaria cirrhosa are alkaloids. In addition to the traditional antitussive and antiasthmatic activities, Fritillaria cirrhosa also has antihypertensive, anti-inflammatory, anti-tumor and antioxidant activities.

[0019] Bamboo juice: It is the light yellow clear liquid that flows out of the fresh stems of the Poaceae plant Bambusa gracile and closely related plants after being roasted over fire; it tastes sweet and is cold in nature, and enters the heart, liver, and lung meridians; it has the effects of clearing away heat and detoxifying, resolving phlegm and relieving cough, calming the nerves and relieving orifices, nourishing yin and unblocking meridians; it is often used clinically to treat lung heat, cough with excessive phlegm, asthma and chest tightness, tongue stiffness due to stroke, excessive phlegm, and phlegm-heat convulsions in children; bamboo juice contains phenolic acids, amino acids, flavonoids, and inorganic elements; it has pharmacological effects such as antitussive, expectorant, and anti-asthmatic, anti-inflammatory, anti-tumor, and antibacterial.

[0020] Prunella Vulgaris: pungent, bitter, cold in nature, enters the liver and gallbladder meridians; has the effects of clearing the liver and purging fire, improving eyesight, dispersing nodules and reducing swelling; used for symptoms such as red and swollen eyes, night pain in the eyeballs, headaches and dizziness; the main chemical components of Prunella Vulgaris include triterpenes, sterols, flavonoids, organic acids, coumarins and other effective ingredients, which have certain pharmacological activities in antibacterial, antiviral, anti-inflammatory, immune regulation, antioxidant, free radical scavenging, anti-tumor, blood pressure reduction, blood sugar reduction, and blood lipid regulation. Astragalus: sweet in taste, slightly warm in nature, enters the spleen and lung meridians; has the effects of invigorating qi and strengthening the exterior, supporting toxins and draining pus, diuresis, and promoting tissue regeneration; used for symptoms such as qi deficiency and fatigue, chronic diarrhea and prolapse of the anus, spontaneous sweating, edema, uterine prolapse, chronic nephritis proteinuria, diabetes, and long-term non-healing of wounds; Astragalus contains effective ingredients such as carbohydrates, various amino acids, proteins, choline, betaine, folic acid, vitamin P, amylase, and various trace elements, which have the effects of enhancing immunity and antiviral.

[0021] Fu Shen: It is the white part of the sclerotium of the plant Poria cocos of the Polyporaceae family, which naturally holds pine roots (i.e., Fu Shen wood). It tastes sweet and light, is neutral in nature, and enters the heart and spleen meridians. Its functions and indications are: calming the mind, tranquilizing the nerves, and promoting diuresis. It can treat palpitations caused by heart deficiency, forgetfulness, insomnia, epilepsy, and difficulty urinating. Fu Shen mainly contains active ingredients such as triterpenes, sterol derivatives, flavonoids, ditans, and fatty acids, and has pharmacological activities such as anti-tumor, diuresis, kidney protection, immunomodulation, and hypoglycemic and lipid-lowering.

[0022] Toosendan fruit: bitter in taste, cold in nature, enters the liver, small intestine, and bladder meridians; has the effects of soothing the liver and relieving heat, promoting qi and relieving pain, and killing insects; used for liver depression and fire transformation, chest and flank, abdominal distension and pain, hernia pain, abdominal pain caused by worms; Toosendan fruit mainly contains volatile oils, lignans, organic acids, flavonoids, limonoids and other ingredients, which have anti-inflammatory, analgesic, and neuroprotective effects on the central nervous system, and also have antioxidant, anti-tumor, antibacterial, antiviral, and anti-insect pharmacological effects.

[0023] (III) Beneficial effects

[0024] The invention provides a traditional Chinese medicine preparation for ischemic cerebral stroke. The traditional Chinese medicine preparation is prepared from qinjiao, fangfeng, mulberry leaf, xuanning, daiheshi, chuanbeimu, bamboo juice, prunella vulgaris, fushen and chuanlianzi. In the prescription, xuanning is a main medicine for clearing heat and cooling blood, nourishing yin and reducing fire, and daiheshi is used to calm the liver and suppress yang, calm down the adverse reaction, cool blood and stop bleeding. qinjiao is pungent, pungent and slightly cold, pungent and dispersing, bitter but not dry, and can dispel rheumatism, dredge tendons and collaterals, and stop arthralgia and pain, and can also promote external and internal, clear away deficiency heat, and eliminate dampness and heat. fangfeng is pungent, sweet and slightly warm, and has a dispersing nature. It circulates throughout the body, is slightly warm but not dry, sweet and slow but not harsh, and is a wind-moistening agent with the functions of dispelling wind and relieving exterior symptoms, overcoming dampness and relieving pain, and stopping spasms. The two medicines are used together, one is slightly cold, the other is slightly warm, with a suitable combination of cold and warm, which can dispel wind and dampness, relax muscles and tendons and dredge meridians; mulberry leaves disperse wind-heat, clear the lungs and moisten dryness, clear the liver and improve eyesight; Fritillaria cirrhosa clears heat and resolves phlegm, moistens the lungs and relieves cough, while bamboo juice clears heat and resolves phlegm, calms the nerves and relieves cough, and the two medicines are used together to treat stroke, epilepsy, mania, and excessive heat and phlegm. Prunella vulgaris clears liver fire; Poria cocos calms the mind and soothes the nerves, promotes diuresis and eliminates dampness; Toosendan fruit clears heat and dries dampness, and purges fire and detoxifies. Most stroke patients suffer from hyperactivity of liver yang, which manifests as symptoms of interweaving of internal and external wind. Daizheshi, a heavy sedative, can extinguish internal wind, and combined with Qinjiao and Saposhnikovia divaricata to dispel external wind, internal and external wind can be treated together. Chuanlianzi is good at leading liver qi downward, and Fritillaria cirrhosa and Zhuli can clear away heat and resolve phlegm. The whole formula can calm the liver and suppress yang, calm wind and stop convulsions, and resolve phlegm and open the orifices.

[0025] The Chinese medicine preparation of the present invention has a significant improvement effect on the neurological function of rats with cerebral ischemia-reperfusion injury model, can effectively reduce the brain tissue water content and cerebral infarction volume of rats with cerebral ischemia-reperfusion injury model, significantly improves the levels of GSH and SOD in the serum of rats with cerebral ischemia-reperfusion injury, reduces the level of MDA, and has the effect of improving oxidative stress induced by cerebral ischemia-reperfusion. The Chinese medicine preparation of the present invention has a significant therapeutic effect on rats with cerebral ischemia-reperfusion injury model, and the drug efficacy is equivalent to that of the Western medicine nimozepine.

[0026] The Chinese medicine preparation of the present invention can significantly improve the total effective rate of treatment of ischemic stroke patients, significantly reduce the NIHS score and TCM symptom score of the patients, and significantly improve the ADL score of the patients. The Chinese medicine preparation of the present invention can effectively alleviate the neurological deficit of ischemic stroke patients, help restore the patients' life functions, and alleviate the patients' clinical symptoms. The curative effect is definite and significant, and can be used as a new drug for treating ischemic stroke. DETAILED DESCRIPTION

[0027] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention will be clearly and completely described in combination with the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0028] Example 1

[0029] A traditional Chinese medicine preparation for ischemic stroke is prepared from the following raw materials in parts by weight: 5 parts of gentiana macrophylla, 5 parts of siler, 5 parts of mulberry leaves, 10 parts of scrophulariae, 10 parts of magnetite, 5 parts of fritillaria cirrhosa, 5 parts of bamboo sap, 5 parts of selfheal, 5 parts of poria, and 5 parts of toosendan.

[0030] The Chinese medicine preparation is prepared into granules, powders, oral liquids, pills, decoctions or other pharmaceutically acceptable oral dosage forms by conventional pharmaceutical preparation methods and with medically acceptable adjuvants.

[0031] Example 2

[0032] The difference between this embodiment and embodiment 1 is that the Chinese medicine preparation is made of the following raw materials in parts by weight: 20 parts of Gentiana macrophylla, 20 parts of Saposhnikovia divaricata, 20 parts of Morus alba, 30 parts of Scrophularia ningpoensis, 30 parts of Hematite, 20 parts of Fritillaria cirrhosa, 20 parts of Bamboo Sap, 5-20 parts of Prunella Vulgaris, 20 parts of Poria, and 20 parts of Toosendan fruit.

[0033] Example 3

[0034] The difference between this embodiment and embodiment 1 is that the Chinese medicine preparation is made of the following raw materials in parts by weight: 16 parts of Gentiana macrophylla, 18 parts of Saposhnikovia divaricata, 16 parts of Morus alba, 28 parts of Scrophularia ningpoensis, 22 parts of Hematite, 16 parts of Fritillaria cirrhosa, 18 parts of Bamboo Sap, 16 parts of Prunella Vulgaris, 16 parts of Poria, and 16 parts of Toosendan fruit.

[0035] Example 4

[0036] The difference between this embodiment and embodiment 1 is that the Chinese medicine preparation is made of the following raw materials in parts by weight: 10 parts of Gentiana macrophylla, 10 parts of Saposhnikovia divaricata, 5 parts of Morus alba, 15 parts of Scrophularia ningpoensis, 10 parts of Hematite, 5 parts of Fritillaria cirrhosa, 5 parts of Bamboo Sap, 5 parts of Prunella Vulgaris, 5 parts of Poria, and 5 parts of Toosendan fruit.

[0037] Example 5

[0038] The difference between this embodiment and embodiment 1 is that the Chinese medicine preparation is made of the following raw materials in parts by weight: 20 parts of Gentiana macrophylla, 20 parts of Saposhnikovia divaricata, 15 parts of Morus alba, 25 parts of Scrophularia ningpoensis, 20 parts of Hematite, 15 parts of Fritillaria cirrhosa, 15 parts of Bamboo Sap, 15 parts of Prunella Vulgaris, 15 parts of Poria, and 15 parts of Toosendan Fructus.

[0039] Example 6

[0040] The difference between this embodiment and embodiment 1 is that the Chinese medicine preparation is made of the following raw materials in parts by weight: 14 parts of Gentiana macrophylla, 14 parts of Saposhnikovia divaricata, 8 parts of Morus alba, 20 parts of Scrophularia ningpoensis, 16 parts of Hematite, 8 parts of Fritillaria cirrhosa, 12 parts of Bamboo Sap, 10 parts of Prunella Vulgaris, 12 parts of Poria, and 12 parts of Toosendan Fructus.

[0041] Example 7

[0042] The difference between this embodiment and embodiment 1 is that the Chinese medicine preparation is made of the following raw materials in parts by weight: 16 parts of Gentiana macrophylla, 12 parts of Saposhnikovia divaricata, 12 parts of Morus alba, 22 parts of Scrophularia ningpoensis, 14 parts of Hematite, 12 parts of Fritillaria cirrhosa, 8 parts of Bamboo Sap, 12 parts of Prunella Vulgaris, 10 parts of Poria, and 6 parts of Toosendan Fructus.

[0043] Example 8

[0044] The difference between this embodiment and embodiment 1 is that the Chinese medicine preparation is made of the following raw materials in parts by weight: 12 parts of Gentiana macrophylla, 12 parts of Saposhnikovia divaricata, 10 parts of Morus alba, 18 parts of Scrophularia ningpoensis, 14 parts of Hematite, 10 parts of Fritillaria cirrhosa, 10 parts of Bamboo Sap, 8 parts of Prunella Vulgaris, 8 parts of Poria, and 8 parts of Toosendan fruit.

[0045] Test Example 1

[0046] Effect of the Chinese medicine preparation of the present invention on cerebral ischemia-reperfusion rat model

[0047] 1 Materials and methods

[0048] 1.1 Experimental drugs

[0049] The Chinese medicine preparation of the present invention comprises: 12 parts of gentiana macrophylla, 12 parts of siler, 10 parts of mulberry leaf, 18 parts of scrophularia, 14 parts of daizheshi, 10 parts of fritillaria cirrhosa, 10 parts of bamboo sap, 8 parts of selfheal, 8 parts of poria and 8 parts of toosendan fruit. The raw materials are weighed according to the above weight parts, washed, soaked in 3 times of deionized water for 20 minutes, then decocted for 30 minutes, the decocting is repeated for more than 2 times, the decoction is collected, the decoction is concentrated to 1g / mL (1mL contains 1g of crude drug), and stored at 4°C for standby use.

[0050] Western medicine control: Nimodipine

[0051] 1.2 Experimental animals and preparation of rat models of cerebral ischemia-reperfusion

[0052] SPF grade SD rats, male, weighing 160-180 g, were purchased from Beijing Weitonglihua Laboratory Animal Technology Co., Ltd., with the laboratory animal production license number: SCXK (Beijing) 2016-0006.

[0053] After 1 week of adaptive feeding, the rat model of cerebral ischemia-reperfusion was prepared. The specific method was as follows: after anesthesia, the rats were fixed in the supine position, and the right common carotid artery, external carotid artery and internal carotid artery were separated along the midline incision of the neck; the common carotid artery and external carotid artery were ligated with a thin thread, the distal end of the internal carotid artery was temporarily clamped with a micro-arteriolar clamp, a small incision was made about 4 mm away from the bifurcation of the common carotid artery, the thread plug was inserted into the internal carotid artery, the micro-arteriolar clamp was opened, and the thread plug was gently pushed with ophthalmic forceps until slight resistance was encountered; after 2 hours of ischemia, the thread plug was withdrawn until resistance was encountered, 25 units of penicillin were injected intramuscularly to prevent infection, and the wound was sutured; the sham operation group did not insert the thread plug, and the rest of the steps were the same as above. After 22 hours of reperfusion, the Zea-Longa 5-level scoring criteria were performed: ① no signs of neurological deficit (0 points); ② unable to fully flex the contralateral forepaw (1 point); ③ turning to the paralyzed side (2 points); ④ falling to the paralyzed side (3 points); ⑤ unable to walk spontaneously and lose consciousness (4 points). Rats with scores of 1-3 were considered to have successfully established models and were used for subsequent studies.

[0054] 1.3 Animal grouping and treatment

[0055] The rat model of cerebral ischemia-reperfusion was randomly divided into a model group, a western medicine control group (nimodipine, 20 mg / kg), a high-dose group of the Chinese medicine preparation of the present invention (referred to as the high-dose group, 20 g / kg), and a low-dose group of the Chinese medicine preparation of the present invention (referred to as the low-dose group, 10 g / kg); the sham operation group and the model group were intragastrically administered with an equal amount of normal saline, with 8 rats in each group, and each group was administered with medication for 7 consecutive days.

[0056] 1.4 Detection indicators

[0057] 1.4.1 Modified Neurological Deficit Score

[0058] The behavioral scores of the experimental animals in each group were performed according to the mNSS scoring standard after the last administration. The total mNSS score is 18 points, of which mild damage is 0-6 points, moderate damage is 7-12 points, and severe damage is 13-18 points. The degree of neurological damage increases with the increase of the score. The scoring standard is shown in Table 1.

[0059] Table 1mNSS scoring criteria

[0060]

[0061]

[0062] 1.4.2 Water content of rat brain tissue

[0063] After the last administration, rats were quickly decapitated and the brain tissue was taken. The residual blood on the surface of the brain tissue was wiped off with filter paper, and the brain tissue was placed in tin foil that had been weighed (A). The brain tissue was weighed on an analytical balance (B) to obtain the wet weight of the brain tissue (BA). The brain tissue was wrapped in tin foil and dried in a 95°C oven for 24 hours. The brain tissue was taken out and returned to room temperature and weighed (C) to obtain the dry weight of the brain tissue (CA). The water content of the brain tissue was calculated according to the following formula:

[0064]

[0065] 1.4.3 Determination of infarct volume in rat brain tissue

[0066] After the last administration, rats were quickly decapitated and brain tissue was taken. The residual blood on the surface of the brain tissue was wiped off with filter paper and frozen in a -20°C refrigerator for 30 minutes. The lower brainstem, olfactory brain and cerebellum were removed, and continuous coronal sections were made from the occipital pole to the frontal pole with a thickness of about 2 mm. The sections were placed in a 2% red tetrazolium (TTC) solution and incubated at 37°C for 30 minutes in the dark. The sections were gently turned over every 5 minutes to ensure sufficient staining. Normal brain tissue appears red, and brain tissue in the infarcted area appears grayish white. After taking pictures, the infarct area was calculated using Image J software. The sum of the infarct areas of each brain slice multiplied by the thickness (2 mm) was the total infarct volume. The infarct volume of brain tissue was calculated according to the following formula:

[0067] Infarct volume ratio = infarct area × thickness) / (∑ whole brain slice area × thickness

[0068] 1.4.4 Detection of GSH, SOD and MDA levels in rat serum

[0069] After the last administration, blood was collected from the abdominal aorta, and after the blood was left to stand for 1 hour, it was centrifuged at 3800 rpm / min for 15 minutes, and the upper serum was collected and stored in a -20°C refrigerator for the detection of serum LDH, SOD and MDA levels. The operation was strictly in accordance with the requirements of the kit.

[0070] 1.5 Statistical analysis

[0071] SPSS 21.0 was used for statistical analysis, and one-way analysis of variance was used for inter-group comparisons. The results are expressed as mean ± standard deviation The data were analyzed using t-test. P < 0.05 was considered statistically significant.

[0072] 2 Results

[0073] 2.1 Effect of the Chinese medicine preparation of the present invention on neurological function in rats with cerebral ischemia-reperfusion

[0074] The results are shown in Table 2. Compared with the sham operation group, the behavioral scores of rats in the model group were significantly increased (P<0.01); compared with the model group, the behavioral scores of rats in the western medicine control group, the high-dose and low-dose groups of the Chinese medicine preparation of the present invention were significantly decreased (P<0.01, P<0.05, P<0.01).

[0075] Table 2 Effect of the Chinese medicine preparation of the present invention on the neurological function score of rats with cerebral ischemia-reperfusion model (n=8)

[0076] Group mNSS score Sham operation group 6.23±1.2 Model Group 11.57±3.4** High dose group <![CDATA[8.59±1.2 # ]]> Low dose group <![CDATA[6.22±3.4 ## ]]> Western medicine control group <![CDATA[6.89±2.2 ## ]]>

[0077] Note: Compared with the sham operation group, **P<0.01, compared with the model group, # P<0.05, ## P<0.01

[0078] 2.2 Effect of the Chinese medicine preparation of the present invention on the water content of brain tissue in rats with cerebral ischemia-reperfusion

[0079] The results are shown in Table 3. Compared with the sham operation group, the water content of brain tissue of rats in the model group was significantly increased (P<0.05); compared with the model group, the water content of brain tissue of rats in the western medicine control group, high-dose and low-dose groups of the Chinese medicine preparation of the present invention was significantly reduced (P<0.05, P<0.01, P<0.05).

[0080] Table 3 Effect of the Chinese medicine preparation of the present invention on the water content of brain tissue in rats with cerebral ischemia-reperfusion (n=3)

[0081]

[0082]

[0083] Note: Compared with the sham operation group, *P<0.05, compared with the model group, # P<0.05, ## P<0.01

[0084] 2.3 Effect of the Chinese medicine preparation of the present invention on the volume of cerebral infarction in rats with cerebral ischemia-reperfusion

[0085] The results are shown in Table 4. Compared with the sham operation group, the cerebral infarction volume of the experimental animals in the model group was significantly increased (P<0.01); compared with the model group, the cerebral infarction volume of the rats in the western medicine control group, the high-dose and low-dose groups of the Chinese medicine preparation of the present invention were significantly reduced (P<0.01, P<0.01, P<0.01).

[0086] Table 4 Effect of the Chinese medicine preparation of the present invention on the volume of cerebral infarction in rats with cerebral ischemia-reperfusion (n=3)

[0087] Group Cerebral infarction volume (%) Sham operation group 6.43±0.55 Model Group 49.56±0.44** High dose group <![CDATA[18.99±0.48 ## ]]> Low dose group <![CDATA[0.73±0.11 ## ]]> Western medicine control group <![CDATA[0.75±0.29 ## ]]>

[0088] Note: Compared with the sham operation group, **P<0.01, compared with the model group, ## P<0.01

[0089] 2.4 Effect of the Chinese medicine preparation of the present invention on the levels of GSH, SOD and MDA in the serum of rats with cerebral ischemia-reperfusion

[0090] The results are shown in Table 5. Compared with the sham operation group, the levels of GSH and SOD in the serum of the model group rats were significantly reduced (P<0.05, P<0.01), and the level of MDA was significantly increased (P<0.01). Compared with the model group, the levels of GSH and SOD in the serum of the western medicine control group rats were significantly increased (P<0.05, P<0.01), and the level of MDA in the serum of the rats was significantly reduced (P<0.05); the levels of GSH and SOD in the serum of the rats in the high-dose group of the Chinese medicine of the present invention were significantly increased (P<0.05, P<0.01), and the level of MDA in the serum of the rats was significantly reduced (P<0.05); the levels of GSH and SOD in the serum of the rats in the low-dose group of the Chinese medicine preparation of the present invention were significantly increased (P<0.05, P<0.05), and the level of MDA in the serum of the rats was significantly reduced (P<0.05).

[0091] Table 5 Effect of the Chinese medicine preparation of the present invention on the levels of LDH, SOD and MDA in the serum of rats with cerebral ischemia-reperfusion (n=8)

[0092]

[0093]

[0094] Note: Compared with the sham operation group, *P<0.05, **P<0.01, compared with the model group, # P<0.05, ## P<0.01

[0095] 3 Conclusion

[0096] According to the above results, the Chinese medicine preparation of the present invention has a significant improvement effect on the neurological function of rats with cerebral ischemia-reperfusion injury model, effectively reduces the brain tissue water content and cerebral infarction volume of rats with cerebral ischemia-reperfusion model, significantly increases the levels of GSH and SOD in the serum of rats with cerebral ischemia-reperfusion, reduces the level of MDA, and has the effect of improving oxidative stress induced by cerebral ischemia-reperfusion. The above results show that the Chinese medicine preparation of the present invention has a significant therapeutic effect on rats with cerebral ischemia-reperfusion injury model, and the drug efficacy is equivalent to that of the Western medicine nimozepine, and can be used as a potential drug for the treatment or prevention of ischemic stroke.

[0097] Test Example 2

[0098] Clinical observation of the efficacy of the Chinese medicine preparation of the present invention in ischemic stroke

[0099] 1 Materials and methods

[0100] 1.1 Clinical Data

[0101] A total of 72 patients with ischemic stroke who were admitted to Lushan County Hospital of Traditional Chinese Medicine from January 2023 to June 2024 were selected as the research subjects. They were divided into an observation group and a control group by random number table method, with 36 cases in each group; the observation group: 20 males, 16 females, with an average age of (61.97±8.09) years old; the control group: 19 males, 17 females, with an average age of (63.07±7.48) years old. There was no significant difference in the general data of the two groups of patients (P>0.05), and they were comparable.

[0102] 1.2 Selection criteria

[0103] 1.2.1 Diagnostic criteria

[0104] Western medicine diagnosis: Refer to the diagnostic criteria for ischemic stroke in the "Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke in China 2018": (1) Acute onset, sudden global or focal neurological deficits; (2) MRI or head CT scans show acute infarction lesions, and other cranial lesions such as mass lesions and cerebral hemorrhage are excluded.

[0105] TCM diagnosis: Refer to the diagnostic criteria for stroke in the TCM Symptoms and Diagnosis Guidelines for Common Diseases in Internal Medicine of Traditional Chinese Medicine: (1) Main symptoms: sudden fainting, hemiplegia, unconsciousness, facial paralysis, and slurred speech; (2) Mild cases may not involve fainting, but only hemiplegia and facial paralysis.

[0106] 1.2.2 Inclusion criteria

[0107] (1) Meet the above-mentioned relevant Western medical diagnostic criteria; (2) Meet the above-mentioned Chinese medicine diagnostic criteria for "stroke"; (3) Patients and their families are aware of this study and have signed consent.

[0108] 1.2.3 Exclusion criteria

[0109] (1) Patients with hemorrhagic stroke; (2) Patients with severe impaired consciousness; (3) Patients who are allergic to the study drugs; (4) Patients with severe heart, liver, or kidney dysfunction; (5) Patients with a history of ischemic stroke; (6) Patients with swallowing dysfunction; (7) Patients with a history of mental illness.

[0110] 1.3 Treatment methods

[0111] Control group: Guideline-standardized treatment was adopted. The treatment was formulated with reference to the "Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke in China 2018" and the "Guidelines for the Secondary Prevention of Ischemic Stroke and Transient Ischemic Attack in China 2014". Targeted treatment can be carried out for patients with hypertension, hyperglycemia, hyperlipidemia and other diseases. Aspirin + clopidogrel, aspirin 100mg / d for the first time, clopidogrel 300mg / d, aspirin 100mg / d from the next day to 21 days, clopidogrel 75mg / d, if the patient has contraindications to taking aspirin, it can be changed to oral Glurerol tablets (90mg / d); edaravone intravenous drip, 30mg / time, 2 times / d, for 4 consecutive weeks.

[0112] Observation group: On the basis of the treatment of the control group, the Chinese medicine preparation of the present invention was taken orally, specifically: 12 parts of Gentiana macrophylla, 12 parts of Saposhnikovia divaricata, 10 parts of Morus alba, 18 parts of Scrophularia ningpoensis, 14 parts of Daizheshi, 10 parts of Fritillaria cirrhosa, 10 parts of Bamboo Sap, 8 parts of Prunella Vulgaris, 8 parts of Poria, and 8 parts of Toosendan Fructus. Each medicinal material was weighed according to the above weight parts, decocted in water, one dose per day, taken twice a day after meals, and the medication was continued for 4 weeks.

[0113] 1.4 Observation indicators

[0114] 1.4.1 Neurological function

[0115] The changes in the patient's neurological function were assessed with reference to the NIHSS, including level of consciousness, ability to answer questions, ability to follow instructions, eye movement, visual field, facial muscle strength, upper limb motor function, lower limb motor function, limb coordination, sensory function, language, articulation, and sensory neglect. There are 11 items in total, with a total of 42 points. The higher the score, the more severe the nerve damage.

[0116] 1.4.2 Daily Activities

[0117] The activities of daily living (ADL) scale was used to evaluate before and after treatment. ADL was evaluated using the modified Barthel index scale, which includes 10 items such as bathing, dressing, and going up and down stairs, with a total score of 100 points. A score of >95 points indicates complete independence, and the higher the score, the better the ability to perform daily activities.

[0118] 1.4.3 TCM symptom scoring

[0119] Before and after treatment, the stroke diagnosis and efficacy evaluation criteria were followed, including speech impairment, hemiplegia, oral and tongue Strabismus, confusion, ataxia, etc., each item is scored from 0 to 9, and the higher the score, the more severe the symptom.

[0120] 1.5 Efficacy criteria

[0121] According to the "Guidelines for Clinical Research on New Chinese Medicines for the Treatment of Stroke". Markedly effective: clinical symptoms improved significantly, NIHSS score decreased by 46% to 90%; effective: clinical symptoms improved, NIHSS score decreased by 18% to 45%. Ineffective: clinical symptoms did not improve or worsened, NIHSS score did not decrease or increase.

[0122] 1.6 Adverse Reactions

[0123] Including headache, dizziness, nausea and vomiting, abnormal liver and kidney function, etc.

[0124] 1.7 Statistical analysis

[0125] SPSS 21.0 statistical software was used for analysis. t test was used for the expression of count data (%) and χ test was used for the expression of count data (%). 2 Test, P < 0.05 was considered statistically significant.

[0126] 2 Results

[0127] 2.1 Comparison of clinical efficacy

[0128] The results are shown in Table 6. The total effective rate of the observation group was 91.67%, which was significantly higher than that of the control group (69.44%).

[0129] Table 6 Comparison of clinical efficacy between the two groups [cases (%)]

[0130] Grouping Number of cases Significant effect efficient invalid Total Effectiveness Control group 36 7(19.44) 18(50.00) 11(30.55) 69.44 Observation Group 36 16(44.44) 17(47.22) 3(8.33) 91.67

[0131] 2.2 Comparison of NIHSS scores

[0132] The results are shown in Table 7. Compared with the group before treatment, the NIHSS scores of the group after treatment were significantly reduced (P < 0.01); among them, the NIHSS score of the observation group after treatment was significantly lower than that of the control group (P < 0.01).

[0133] Table 7 Comparison of NIHSS scores between the two groups before and after treatment (points)

[0134] Grouping Number of cases Before treatment After treatment Control group 36 23.98±2.87 17.08±3.41** Observation Group 36 24.46±3.07 <![CDATA[10.87±2.68 ## ]]>

[0135] Note: Compared with the group before treatment, **P<0.01; compared with the control group after treatment, # P<0.05, ## P<0.01, the same below.

[0136] 2.3 Comparison of ADL scores

[0137] The results are shown in Table 8. Compared with before treatment, the ADL scores of the group after treatment were significantly improved (P < 0.01); among them, the ADL score of the observation group after treatment was significantly higher than that of the control group (P < 0.01).

[0138] Table 8 Comparison of ADL scores between the two groups before and after treatment (points)

[0139] Grouping Number of cases Before treatment After treatment Control group 36 38.49±6.07 62.71±7.20** Observation Group 36 39.08±8.41 <![CDATA[78.37±8.03 ## ]]>

[0140] 2.4 TCM symptom scoring

[0141] The results are shown in Table 9. Compared with the group before treatment, the TCM symptom scores of the group after treatment were significantly reduced (P < 0.01); among them, the ADL score of the observation group after treatment was significantly lower than that of the control group (P < 0.05).

[0142] Table 9 Comparison of TCM symptom scores between the two groups before and after treatment (points)

[0143] Grouping Number of cases Before treatment After treatment Control group 36 18.79±1.87 11.23±2.06** Observation Group 36 19.08±2.14 <![CDATA[8.86±2.51 # ]]>

[0144] 2.5 Adverse reaction observation

[0145] The adverse reactions of the two groups of patients during the treatment were observed, and both groups of patients experienced adverse reactions such as nausea and vomiting, headache and dizziness, and abnormal liver and kidney function.

[0146] 3 Conclusion

[0147] The above results show that compared with the control group, the Chinese medicine preparation of the present invention can significantly improve the total effective rate of treatment of ischemic stroke patients, significantly reduce the NIHS score and TCM symptom score of patients, and significantly improve the ADL score of patients. The results show that the Chinese medicine preparation of the present invention can effectively alleviate the neurological deficit of ischemic stroke patients, help restore the patient's life function, and alleviate the patient's clinical symptoms. The efficacy is definite and significant, and it can be used as a new drug for the treatment of ischemic stroke.

[0148] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that the technical solutions described in the aforementioned embodiments may still be modified, or some of the technical features may be replaced by equivalents. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A Chinese medicine preparation for ischemic stroke, characterized in that: The Chinese medicine preparation is prepared from the following raw materials in parts by weight: 5-20 parts of gentiana macrophylla, 5-20 parts of siler, 5-20 parts of mulberry leaves, 10-30 parts of scrophularia, 10-30 parts of magnetite, 5-20 parts of fritillaria cirrhosa, 5-20 parts of bamboo sap, 5-20 parts of selfheal, 5-20 parts of poria, and 5-20 parts of toosendan.

2. The Chinese medicine preparation for ischemic stroke according to claim 1, characterized in that: The Chinese medicine preparation is prepared from the following raw materials in parts by weight: 10-20 parts of gentiana macrophylla, 10-20 parts of siler, 5-15 parts of mulberry leaves, 15-25 parts of scrophularia, 10-20 parts of magnetite, 5-15 parts of fritillaria cirrhosa, 5-15 parts of bamboo sap, 5-15 parts of selfheal, 5-15 parts of poria, and 5-15 parts of toosendan.

3. The Chinese medicine preparation for ischemic stroke according to claim 1, characterized in that: The Chinese medicine preparation is prepared from the following raw materials in parts by weight: 12 parts of gentiana macrophylla, 12 parts of siler, 10 parts of mulberry leaf, 18 parts of scrophularia, 14 parts of magnetite, 10 parts of fritillaria cirrhosa, 10 parts of bamboo juice, 8 parts of selfheal, 8 parts of poria and 8 parts of toosendan.

4. Use of the Chinese medicine preparation according to any one of claims 1 to 3 in the preparation of a medicament for treating ischemic stroke, characterized in that: The Chinese medicine preparation is prepared into granules, powders, oral liquids, pills, decoctions or other pharmaceutically acceptable oral dosage forms by conventional pharmaceutical preparation methods and with medically acceptable adjuvants.

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