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 the brain tissue of the rat and the cerebral infarction volume, remarkably improves the levels of GSH and SOD in the brain tissue of the rat, 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 present 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, sudden clinical illness characterized by high morbidity, disability, recurrence, and mortality. CVA is categorized into ischemic stroke (IS) and hemorrhagic apoplexy (SA). IS is the most common clinical type, accounting for approximately 85% of CVA incidence. Therefore, the prevention and treatment of SA remains a major challenge in medical research. SA primarily results from impaired cerebral blood circulation, leading to hypoxia and ischemia, which in turn causes localized brain softening or necrosis. SA impairs blood, oxygen, and energy supply to the arterial supply zone, causing secondary endothelial damage and autonomic dysfunction. The key to the treatment of SA lies in improving microcirculation, promoting angiogenesis, minimizing neurological damage, and ultimately restoring normal metabolic function.

[0003] Currently, Western medicine primarily treats IS with thrombolysis. Although thrombolysis can effectively improve clinical outcomes three months after treatment, the window for thrombolysis is limited to six hours after onset. Most patients miss the optimal treatment window, leaving them with serious sequelae. Long-term use of Western medicine, including anticoagulants and neurorepair drugs, is ineffective and often carries significant side effects.

[0004] In recent years, Traditional Chinese Medicine (TCM) therapies have gradually emerged in clinical research on IS, demonstrating clear efficacy. Some studies have even confirmed that the overall efficacy of comprehensive TCM treatments is higher than that of Western medicine. Compared to single chemical drugs, TCM treatments for IS utilize multiple components, multiple targets, and multiple pathways for synergistic regulation. Studies have demonstrated that TCM can alleviate damage caused by cerebral ischemia by improving factors such as oxidative stress, apoptosis, inflammation, and calcium overload, offering unique therapeutic efficacy and development value in the treatment of IS. Currently, numerous TCM compound formulas for the treatment of IS have been published, such as Publication No. CN103550702A and Publication No. CN105232813A. However, most suffer from unclear mechanisms of action, limited therapeutic effects, and complex and numerous ingredients. Therefore, it is crucial to provide a safe, effective, and therapeutically effective TCM compound preparation for the treatment or prevention of IS. Summary of the Invention

[0005] (1) Technical problems solved

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

[0007] (2) 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 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 figwort, 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 fruit.

[0010] Furthermore, the traditional Chinese medicine preparation is made from 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 sap, 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 from 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 sap, 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 excipients.

[0013] Gentiana macrophylla: pungent and bitter in taste, neutral in nature, enters the stomach, liver, and gallbladder meridians; has the effects of dispelling rheumatism, clearing damp-heat, relieving arthralgia, and relieving deficiency-heat; used for rheumatic arthralgia, hemiplegia caused by stroke, muscle spasms, joint pain, damp-heat jaundice, hot flashes due to bone steaming, and fever caused by malnutrition in children; Gentiana macrophylla 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, and antioxidant 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 overcoming dampness; mainly treats exogenous wind-cold, general pain, wind-cold-dampness arthritis, joint pain and other symptoms; the more clearly 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 are bitter and sweet, with a cold nature. They enter the lung and liver meridians and have the effects of dispersing wind-heat, clearing the lungs and moistening dryness, calming the liver and improving eyesight, cooling the blood and stopping bleeding. They are used to treat wind-heat colds, the early stages of febrile diseases, lung-heat coughs, and red and blurred vision. Mulberry leaves contain flavonoids, alkaloids, amino acids, and polysaccharides, which have the following pharmacological effects: protecting the nerves and cardiovascular system, protecting the liver and improving digestion, protecting the kidneys, fighting tumors, regulating blood sugar and lipid metabolism, and providing anti-inflammatory and antioxidant benefits.

[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 resolves stagnation. Treats febrile diseases, harmonizing 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; carbuncles and ulcers. "Pharmaceutical Chemistry": "Dai Ren said that the kidney is originally cold, and it will become hot if it is weak. If you indulge in lust and consume your essence, the true yin will be depleted, which will cause 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 of 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 big 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 cool and moistening medicine nourishes the kidney alone, and its function is better than that of Zhi and Bai, and it is especially the king medicine for the kidney."

[0017] Daizheshi: An oxidized corundum-type mineral, hematite, it has a bitter and sweet taste and a slightly cold nature. It enters the liver, stomach, and heart meridians. It calms the liver and suppresses yang, calms the stomach and suppresses adverse reactions, and cools the blood and stops bleeding. It is commonly used to treat headaches, dizziness, palpitations, mania, epilepsy, vomiting, belching, hiccups, choking, coughs, asthma, hematemesis, epistaxis, metrorrhagia, bloody stools, and hematuria.

[0018] Fritillaria cirrhosa: Sweet and bitter in flavor; slightly cold in nature; enters the Lung and Heart meridians; clears heat and moistens the lungs, resolves phlegm and relieves cough, and dissipates stagnation and swelling. It is used to treat lung deficiency, chronic coughs, coughs due to consumptive disease, coughs caused by dryness and heat, lung abscesses, scrofula, carbuncles, and mastitis. Alkaloids are the primary chemical components of Fritillaria cirrhosa. In addition to its traditional antitussive and antiasthmatic properties, it also exhibits antihypertensive, anti-inflammatory, antitumor, and antioxidant activities.

[0019] Bamboo juice: It is the light yellow clear liquid that flows out of the fresh stems of the grass plant light bamboo 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 opening the orifices, nourishing yin and unblocking the meridians; it is often used clinically to treat lung heat, cough with excessive phlegm, asthma and chest tightness, tongue stiffness in 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 antiasthmatic, anti-inflammatory, anti-tumor, and antibacterial.

[0020] Prunella Vulgaris: It is pungent, bitter and cold in nature, and enters the liver and gallbladder meridians; it has the effects of clearing the liver and purging fire, improving eyesight, dispersing stagnation and reducing swelling; it is used for symptoms such as red and swollen eyes, night pain in the eyeballs, headache and dizziness; the main chemical components of Prunella Vulgaris include triterpenes, sterols, flavonoids, organic acids, coumarins and other active 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: It tastes sweet, is slightly warm in nature, and enters the spleen and lung meridians; it has the effects of replenishing qi and strengthening the exterior, detoxifying and draining pus, diuresis, and tissue regeneration; it is used for symptoms such as qi deficiency and fatigue, long-term diarrhea and prolapse of the anus, spontaneous sweating, edema, uterine prolapse, proteinuria in chronic nephritis, diabetes, and long-term wound healing; Astragalus contains active ingredients such as carbohydrates, multiple amino acids, proteins, choline, betaine, folic acid, vitamin P, amylase, and multiple trace elements, which have the effects of enhancing immunity and antiviral.

[0021] Fu Shen (Chinese herbal medicine) is the white part of the sclerotium of the Polyporaceae plant, Poria cocos, which naturally contains pine roots (also known as Fu Shen wood). It has a sweet and light flavor, is neutral in nature, and enters the Heart and Spleen meridians. Its main functions include calming the mind, tranquilizing the nerves, and promoting diuresis. It treats palpitations caused by heart palpitations, forgetfulness, insomnia, epilepsy, and dysuria. Fu Shen contains triterpenes, sterol derivatives, flavonoids, ditans, and fatty acids, which have pharmacological activities such as anti-tumor, diuresis, kidney protection, immunomodulation, and hypoglycemic and lipid-lowering properties.

[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 circulation and relieving pain, and killing insects; is used for symptoms such as liver depression and fire transformation, chest and flank, abdominal distension and pain, hernia pain, and abdominal pain caused by worm accumulation; 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] (3) Beneficial effects

[0024] The invention provides a traditional Chinese medicine preparation for ischemic stroke. The traditional Chinese medicine preparation is prepared from gentiana, siler, mulberry leaf, scrophularia, daizheshi, fritillaria cirrhosa, bamboo juice, prunella vulgaris, poria and toosendan fruit. In the prescription, the scrophularia is the main medicine for clearing heat and cooling blood, nourishing yin and reducing fire, and is supplemented by daizheshi to calm the liver and suppress yang, calm the stomach and reduce adverse reactions, cool blood and stop bleeding; gentiana is pungent and slightly cold, pungent and dispersing, bitter but not dry, and can dispel rheumatism, dredge tendons and meridians, and stop pain, and can promote externalization and internal guidance, clear away deficiency heat, and eliminate damp heat; siler is pungent, sweet and slightly warm, and has a dispersing nature, and is good at It circulates throughout the body, is slightly warm but not dry, sweet and slow but not harsh, and is a moisturizing agent for wind, 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, purges fire and detoxifies. Most stroke patients have hyperactivity of liver yang, which manifests as symptoms of interweaving of internal and external wind. Daizheshi, a heavy sedative, can extinguish internal wind, and is combined with Qinjiao and Saposhnikovia to dispel external wind to treat internal and external wind together. Toosendan fruit is good at guiding liver qi downward, and Fritillaria cirrhosa and bamboo juice can clear away heat and resolve phlegm. The whole formula can calm the liver and suppress yang, stop wind and stop convulsions, and resolve phlegm and open the orifices.

[0025] The Chinese medicinal preparation of the present invention significantly improves the neurological function of rats with cerebral ischemia-reperfusion injury model, effectively reduces brain tissue water content and cerebral infarction volume in rats with cerebral ischemia-reperfusion injury model, significantly increases GSH and SOD levels in the brain tissue of rats with cerebral ischemia-reperfusion injury model, reduces MDA levels, and has the effect of improving oxidative stress induced by cerebral ischemia-reperfusion. The Chinese medicinal preparation of the present invention has a significant therapeutic effect on rats with cerebral ischemia-reperfusion injury model, and its efficacy is comparable 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 for ischemic stroke patients, significantly reduce patients' NIHS scores and TCM symptom scores, and significantly improve patients' ADL scores. The Chinese medicine preparation of the present invention can effectively alleviate the neurological deficits of ischemic stroke patients, help restore their functional abilities, and alleviate their clinical symptoms. It has a definite and significant therapeutic effect and can be used as a new drug for the treatment of ischemic stroke. DETAILED DESCRIPTION

[0027] To make the objectives, technical solutions, and advantages of the embodiments of the present invention more clear, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. All other embodiments obtained by ordinary technicians in this field based on the embodiments of the present invention without making any creative efforts shall fall 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 leaf, 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 fruit.

[0030] 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, with medically acceptable excipients.

[0031] Example 2

[0032] The difference between this embodiment and embodiment 1 is that the traditional 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 mulberry leaves, 30 parts of Scrophularia ningpoensis, 30 parts of magnetite, 20 parts of Fritillaria cirrhosa, 20 parts of bamboo juice, 5-20 parts of Prunella vulgaris, 20 parts of Poria cocos, and 20 parts of Toosendan fruit.

[0033] Example 3

[0034] The difference between this embodiment and embodiment 1 is that the traditional Chinese medicine preparation is made from the following raw materials in parts by weight: 16 parts of Gentiana macrophylla, 18 parts of Saposhnikovia divaricata, 16 parts of mulberry leaves, 28 parts of Scrophularia ningpoensis, 22 parts of magnetite, 16 parts of Fritillaria cirrhosa, 18 parts of bamboo sap, 16 parts of Prunella vulgaris, 16 parts of Poria cocos, and 16 parts of Toosendan fruit.

[0035] Example 4

[0036] The difference between this embodiment and embodiment 1 is that the traditional Chinese medicine preparation is made from the following raw materials in parts by weight: 10 parts of Gentiana macrophylla, 10 parts of Saposhnikovia divaricata, 5 parts of mulberry leaves, 15 parts of Scrophularia ningpoensis, 10 parts of magnetite, 5 parts of Fritillaria cirrhosa, 5 parts of bamboo juice, 5 parts of Prunella vulgaris, 5 parts of Poria cocos, and 5 parts of Toosendan fruit.

[0037] Example 5

[0038] The difference between this embodiment and embodiment 1 is that the traditional 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 mulberry leaves, 25 parts of Scrophularia ningpoensis, 20 parts of magnetite, 15 parts of Fritillaria cirrhosa, 15 parts of bamboo sap, 15 parts of Prunella vulgaris, 15 parts of Poria cocos, and 15 parts of Toosendan fruit.

[0039] Example 6

[0040] The difference between this embodiment and embodiment 1 is that the traditional Chinese medicine preparation is made from the following raw materials in parts by weight: 14 parts of Gentiana macrophylla, 14 parts of Saposhnikovia divaricata, 8 parts of mulberry leaves, 20 parts of Scrophularia ningpoensis, 16 parts of magnetite, 8 parts of Fritillaria cirrhosa, 12 parts of bamboo juice, 10 parts of Prunella vulgaris, 12 parts of Poria cocos, and 12 parts of Toosendan fruit.

[0041] Example 7

[0042] The difference between this embodiment and embodiment 1 is that the traditional Chinese medicine preparation is made from the following raw materials in parts by weight: 16 parts of Gentiana macrophylla, 12 parts of Saposhnikovia divaricata, 12 parts of mulberry leaves, 22 parts of Scrophularia ningpoensis, 14 parts of magnetite, 12 parts of Fritillaria cirrhosa, 8 parts of bamboo juice, 12 parts of Prunella vulgaris, 10 parts of Poria cocos, and 6 parts of Toosendan fruit.

[0043] Example 8

[0044] The difference between this embodiment and embodiment 1 is that the Chinese medicine preparation is made from 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.

[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 the following ingredients: 12 parts of gentiana macrophylla, 12 parts of siler, 10 parts of mulberry leaf, 18 parts of scrophulariae, 14 parts of magnetite, 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 parts by weight, washed, soaked in 3 times deionized water for 20 minutes, and then decocted for 30 minutes. The decoction is repeated for more than 2 times, and the decoction liquid is collected and concentrated to 1 g / mL (1 mL contains 1 g of the crude drug). The decoction liquid is stored at 4°C for standby use.

[0050] Western medicine control: Nimodipine

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

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

[0053] After one week of adaptive feeding, a rat model of cerebral ischemia-reperfusion was established. The rats were anesthetized and fixed in the supine position. A midline incision was made along the neck, and the right common, external, and internal carotid arteries were isolated. The common and external carotid arteries were ligated with a fine suture, and the distal end of the internal carotid artery was temporarily clamped with a micro-arteriolar clamp. A small incision was made approximately 4 mm from the bifurcation of the common carotid artery, and a suture plug was inserted into the internal carotid artery. The micro-arteriolar clamp was opened, and the suture plug was gently pushed with ophthalmic forceps until slight resistance was met. After 2 hours of ischemia, the suture plug was withdrawn until resistance was met. 25 units of penicillin were injected intramuscularly to prevent infection, and the wound was sutured. The sham-operated group underwent the same procedures as above, except that the suture plug was not inserted. After 22 hours of reperfusion, the Zea-Longa 5-grade scale was used to score the rats: ① No neurological deficit (0 points); ② Inability to fully flex the contralateral forepaw (1 point); ③ Turning toward the paretic side (2 points); ④ Falling toward the paretic side (3 points); ⑤ Inability to walk spontaneously and loss of 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 rats with cerebral ischemia-reperfusion model were 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 given equal amounts of normal saline by gavage, with 12 rats in each group, and each group was given the drug continuously for 7 days.

[0056] 1.4 Detection indicators

[0057] 1.4.1 Modified Neurological Deficit Score

[0058] After the final dose, behavioral assessments were performed on the animals in each group according to the mNSS scoring system. The total mNSS score is 18 points, with mild damage ranging from 0 to 6, moderate damage from 7 to 12, and severe damage from 13 to 18. The severity of neurological impairment increases with increasing scores. The scoring system 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 dose, rats were euthanized, and brain tissue was quickly removed. Residual blood on the surface of the brain tissue was wiped off with filter paper. The brain tissue was placed in tinfoil that had been weighed (A) and weighed on an analytical balance (B), which was the wet weight of the brain tissue (BA). The brain tissue was wrapped in tinfoil and dried in a 95°C oven for 24 hours. After being taken out and returned to room temperature, it was weighed (C), which was 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 rat brain infarct volume

[0066] After the last dose, rats were euthanized and brain tissue was quickly removed. 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. Continuous coronal sections were made from the occipital pole to the frontal pole, with a thickness of approximately 2 mm. The sections were placed in a 2% red tetrazolium (TTC) solution and incubated at 37°C in the dark for 30 minutes, gently turning over every 5 minutes to ensure sufficient staining. Normal brain tissue appears red, while 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 brain tissue infarct volume 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 Brain Tissue

[0069] After the last dose, rats were euthanized and brain tissue was quickly removed for the determination of GSH, SOD, and MDA levels in brain tissue. All procedures were strictly in accordance with the kit instructions.

[0070] 1.5 Statistical analysis

[0071] SPSS 21.0 was used for statistical analysis, and one-way analysis of variance was used for comparison between groups. The results were expressed as mean ± standard deviation ( ) format, and the t test was used. 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 the rats in the model group were significantly increased (P<0.01); compared with the model group, the behavioral scores 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 decreased (P<0.01).

[0075] Table 2 Effects of the Chinese medicinal preparation of the present invention on neurological function scores in rats with cerebral ischemia-reperfusion model (n=12)

[0076] Group mNSS score Sham operation group 0.58±0.66 Model Group <![CDATA[13.25±1.54 ** ]]> High-dose group <![CDATA[3.08±0.66 ## ]]> Low-dose group <![CDATA[4.91±0.66 ## ]]> Western medicine control group <![CDATA[2.75±1.21 ## ]]>

[0077] Note: Compared with the sham operation group, ** P<0.01; compared with the model group, ## 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 the brain tissue of the rats in the model group was significantly increased (P<0.01); compared with the model group, the water content of the brain tissue of the rats in the western medicine control group, the high-dose group and the low-dose group of the Chinese medicine preparation of the present invention were significantly decreased (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] Group Brain tissue water content (%) Sham operation group 78.78±2.08 Model Group <![CDATA[85.44±1.80 ** ]]> High-dose group <![CDATA[79.11±2.84 ## ]]> Low-dose group <![CDATA[80.63±2.25 # ]]> Western medicine control group <![CDATA[79.85±2.76 # ]]>

[0082] Note: Compared with the sham operation group, ** P<0.01; compared with the model group, # P < 0.05; ## P<0.01.

[0083] 2.3 Effect of the Chinese medicine preparation of the present invention on the cerebral infarction volume in rats with cerebral ischemia-reperfusion

[0084] 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).

[0085] Table 4 Effect of the Chinese medicinal preparation of the present invention on the cerebral infarction volume in rats with cerebral ischemia-reperfusion (n=3)

[0086] Group Cerebral infarction volume (%) Sham operation group 1.43±0.48 Model Group <![CDATA[49.89±2.50 ** ]]> High-dose group <![CDATA[15.15±1.05 ## ]]> Low-dose group <![CDATA[19.62±1.81 ## ]]> Western medicine control group <![CDATA[12.44±2.07 ## ]]>

[0087] Note: Compared with the sham operation group, ** P<0.01; compared with the model group, ## P<0.01.

[0088] 2.4 Effects of the Chinese herbal preparation of the present invention on the levels of GSH, SOD and MDA in the brain tissue of rats with cerebral ischemia-reperfusion

[0089] The results are shown in Table 5. Compared with the sham operation group, the GSH and SOD contents in the brain tissue of the rats in the model group were significantly reduced (P<0.01, P<0.01), and the MDA content was significantly increased (P<0.01). Compared with the model group, the GSH and SOD contents in the brain tissue of the rats in the western medicine control group were significantly increased (P<0.01, P<0.01), and the MDA content in the brain tissue of the rats was significantly reduced (P<0.01); the GSH and SOD contents in the brain tissue of the rats in the high-dose group of the Chinese medicine of the present invention were significantly increased (P<0.01, P<0.01), and the MDA content in the brain tissue of the rats was significantly reduced (P<0.01); the GSH and SOD contents in the brain tissue of the rats in the low-dose group of the Chinese medicine preparation of the present invention were significantly increased (P<0.01, P<0.01), and the MDA content in the brain tissue of the rats was significantly reduced (P<0.01).

[0090] Table 5 Effects of the Chinese medicinal preparation of the present invention on the levels of GSH, SOD and MDA in the brain tissue of rats with cerebral ischemia-reperfusion (n=6)

[0091]

[0092]

[0093] Note: Compared with the sham operation group, ** P<0.01; compared with the model group, ## P<0.01.

[0094] 3 Conclusion

[0095] The above results indicate that the Chinese herbal preparation of the present invention significantly improves the neurological function of rats with cerebral ischemia-reperfusion injury, effectively reduces brain tissue water content and cerebral infarction volume in rats with cerebral ischemia-reperfusion injury, significantly increases GSH and SOD levels in the brain tissue of rats with cerebral ischemia-reperfusion injury, and reduces MDA levels, thereby improving oxidative stress induced by cerebral ischemia-reperfusion injury. The above results demonstrate that the Chinese herbal preparation of the present invention has a significant therapeutic effect on rats with cerebral ischemia-reperfusion injury, and its efficacy is comparable to that of the Western medicine nimoxipine, suggesting that it may be a potential drug for the treatment or prevention of ischemic stroke.

[0096] Test Example 2

[0097] Observation on the clinical efficacy of the Chinese medicine preparation of the present invention in ischemic stroke

[0098] 1 Materials and Methods

[0099] 1.1 Clinical Data

[0100] Methods: 72 patients with ischemic stroke admitted to Lushan County Hospital of Traditional Chinese Medicine between January 2023 and June 2024 were enrolled in the study. They were randomly divided into an observation group and a control group, with 36 cases in each group. The observation group consisted of 20 males and 16 females with a mean age of (61.97±8.09) years; the control group consisted of 19 males and 17 females with a mean age of (63.07±7.48) years. There were no significant differences in the general information between the two groups (P>0.05), indicating that the two groups were comparable.

[0101] 1.2 Selection criteria

[0102] 1.2.1 Diagnostic criteria

[0103] 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 cranial CT scans show acute infarction lesions, excluding other cranial lesions such as space-occupying and cerebral hemorrhage.

[0104] TCM diagnosis: Refer to the diagnostic criteria for stroke in the Guidelines for the Diagnosis and Treatment of Common Diseases in TCM Internal Medicine: (1) Main symptoms: sudden collapse, hemiplegia, unconsciousness, facial paralysis, and slurred speech; (2) Mild cases may not cause collapse, but only hemiplegia and facial paralysis.

[0105] 1.2.2 Inclusion criteria

[0106] (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 informed of this study and have signed a consent form.

[0107] 1.2.3 Exclusion criteria

[0108] (1) Patients with hemorrhagic stroke; (2) Patients with severe impaired consciousness; (3) Patients allergic to the study drugs; (4) Patients with severe heart, liver, and kidney dysfunction; (5) Patients with a history of ischemic stroke; (6) Patients with swallowing dysfunction; (7) Patients with a history of mental illness.

[0109] 1.3 Treatment

[0110] Control group: Guideline-based treatment was adopted. This was developed in accordance with 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 provided for patients with comorbidities such as hypertension, hyperglycemia, and hyperlipidemia. Aspirin plus clopidogrel was administered: 100 mg / day aspirin and 300 mg / day clopidogrel for the first time, followed by 100 mg / day aspirin and 75 mg / day clopidogrel from the next day to the 21st day. Patients with contraindications to aspirin could be switched to oral Glutarol tablets (90 mg / day). Edaravone was administered intravenously at a dose of 30 mg twice daily for four weeks.

[0111] The observation group was treated with the Chinese medicine preparation of the present invention on the basis of the treatment of the control group, 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 cocos, and 8 parts of Toosendan fruit. The medicinal materials were weighed according to the above weight parts, decocted in water, and taken once a day, twice a day, morning and evening after meals, for 4 consecutive weeks.

[0112] 1.4 Observation indicators

[0113] 1.4.1 Neurological function

[0114] The changes in the patient's neurological function were assessed with reference to the NIHSS, including the degree 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.

[0115] 1.4.2 Daily Activities

[0116] Activities of daily living (ADL) were assessed before and after treatment using the modified Barthel Index scale. ADL includes 10 items, including bathing, dressing, and climbing stairs. The total score is 100 points. A score >95 indicates complete independence, and higher scores indicate better ability to perform daily activities.

[0117] 1.4.3 Traditional Chinese Medicine Symptom Scoring

[0118] Before and after treatment, the stroke diagnosis and efficacy evaluation standards were referred to, including speech impairment, hemiplegia, oral and tongue paralysis, confusion, ataxia, etc. Each item is scored from 0 to 9 points, and the higher the score, the more severe the symptoms.

[0119] 1.5 Efficacy criteria

[0120] According to the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines for the Treatment of Stroke," markedly effective means clinical symptoms significantly improved, with a 46% to 90% decrease in NIHSS scores. Effective means clinical symptoms improved, with a 18% to 45% decrease in NIHSS scores. Ineffective means clinical symptoms did not improve or worsened, with no decrease or increase in NIHSS scores.

[0121] 1.6 Adverse Reactions

[0122] Including headache, dizziness, nausea and vomiting, abnormal liver and kidney function, etc.

[0123] 1.7 Statistical analysis

[0124] SPSS 21.0 statistical software was used for analysis, and the measurement data were analyzed by ( ) were expressed and t-test was used, and count data were expressed as (%) and χ 2 Test, P < 0.05 indicates that the difference is statistically significant.

[0125] 2 Results

[0126] 2.1 Comparison of clinical efficacy

[0127] 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%).

[0128] Table 6 Comparison of clinical efficacy between the two groups [cases (%)]

[0129] Grouping Number of cases Significant effect efficient invalid Total efficiency 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

[0130] 2.2 Comparison of NIHSS scores

[0131] 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).

[0132] Table 7 Comparison of NIHSS scores between the two groups before and after treatment (points)

[0133] Grouping Number of cases Before treatment After treatment control group 36 23.98±2.87 <![CDATA[17.08±3.41 ** ]]> Observation Group 36 24.46±3.07 <![CDATA[10.87±2.68 ## ]]>

[0134] 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.

[0135] 2.3 Comparison of ADL scores

[0136] The results are shown in Table 8. Compared with the group 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).

[0137] Table 8 Comparison of ADL scores before and after treatment between the two groups (points)

[0138] Grouping Number of cases Before treatment After treatment control group 36 38.49±6.07 <![CDATA[62.71±7.20 ** ]]> Observation Group 36 39.08±8.41 <![CDATA[78.37±8.03 ## ]]>

[0139] 2.4 Traditional Chinese Medicine Symptom Scoring

[0140] 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).

[0141] Table 9 Comparison of TCM symptom scores before and after treatment between the two groups (points)

[0142] Grouping Number of cases Before treatment After treatment control group 36 18.79±1.87 <![CDATA[11.23±2.06 ** ]]> Observation Group 36 19.08±2.14 <![CDATA[8.86±2.51 # ]]>

[0143] 2.5 Adverse reaction observation

[0144] The adverse reactions of the two groups of patients during 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.

[0145] 3 Conclusion

[0146] 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 for patients with ischemic stroke, significantly reduce patients' NIHS scores and TCM symptom scores, and significantly improve patients' ADL scores. These results indicate that the Chinese medicine preparation of the present invention can effectively alleviate the neurological deficits of patients with ischemic stroke, help restore patients' daily life functions, and alleviate their clinical symptoms. It has a definite and significant efficacy and can be used as a new drug for the treatment of ischemic stroke.

[0147] 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 they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. 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 various embodiments of the present invention.

Claims

1. A Chinese medicine preparation for ischemic stroke, characterized in that: 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 leaf, 10-30 parts of scrophulariae, 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 fruit.

2. The Chinese medicine preparation for ischemic stroke according to claim 1, characterized in that The traditional 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 scrophulariae, 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 fruits.

3. The Chinese medicine preparation for ischemic stroke according to claim 1, characterized in that The traditional 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 scrophulariae, 14 parts of magnetite, 10 parts of fritillaria cirrhosa, 10 parts of bamboo sap, 8 parts of selfheal, 8 parts of poria and 8 parts of toosendan fruit.

4. Use of the Chinese medicine preparation according to any one of claims 1 to 3 in preparing 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 according to conventional pharmaceutical preparation methods in pharmacy, with medically acceptable excipients.

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