Traditional Chinese medicine preparation for ischemic stroke

Abstract

The application provides a traditional Chinese medicine preparation for ischemic cerebral stroke, and belongs to the technical field of traditional Chinese medicine preparation. The traditional Chinese medicine preparation is prepared from Gentiana macrophylla Pall, Saposhnikovia divaricata, Morus alba, Scrophularia ningpoensis, red ocher, Fritillaria delavayi Franch, bamboo juice, Prunella vulgaris, Hericium, and Melia toosendan. The traditional Chinese medicine preparation has the functions of calming liver and hiding yang, calming wind and stopping convulsion, and removing phlegm and opening orifices. The traditional Chinese medicine preparation has a significant improvement effect on the nerve function of a cerebral ischemia-reperfusion injury model rat, can effectively reduce the brain tissue water content and cerebral infarction volume of the rat, significantly increase the GSH and SOD levels in the brain tissue of the rat, and reduce the MDA level, and has an effect of improving the oxidative stress induced by cerebral ischemia-reperfusion. The traditional Chinese medicine preparation can effectively relieve the nerve function loss of a patient with ischemic cerebral stroke, help restore the life function of the patient, and reduce the clinical symptoms of the patient, and has a definite and significant curative effect, and can be used as a new drug for treating ischemic cerebral stroke.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine pharmaceutical technology, specifically to traditional Chinese medicine preparations for ischemic stroke. Background Technology

[0002] Cerebral vascular accident (CVA) is a common, sudden-onset clinical disease characterized by high incidence, high disability rate, high recurrence rate, and high mortality rate. CVA is divided into ischemic stroke (IS) and sanguineous apoplexy (SA), with IS being the predominant type, accounting for approximately 85% of CVA cases. Therefore, the prevention and treatment of IS is a major issue urgently needing to be addressed in the field of medical research. IS is mainly caused by cerebral circulatory disorders leading to hypoxia and ischemia, resulting in localized softening or necrosis of brain tissue. IS causes dysfunction in the blood supply, oxygen supply, and energy supply to the brain tissue in the arterial supply area, leading to secondary vascular endothelial damage and autonomic dysfunction. The key to the treatment of IS lies in improving blood microcirculation, promoting angiogenesis, reducing neurological damage, and thereby restoring normal metabolism.

[0003] Currently, Western medicine primarily treats IS with thrombolytic therapy. Although thrombolysis can effectively improve clinical outcomes 3 months after treatment, the time window for thrombolysis is limited to within 6 hours of onset, often causing most patients to miss the optimal treatment window and suffer from serious sequelae. Long-term use of anticoagulants and nerve repair drugs in Western medicine has poor efficacy and significant side effects.

[0004] In recent years, Traditional Chinese Medicine (TCM) therapies have gradually appeared in clinical research on Inflammatory Disorder (IS) and have achieved clear efficacy. Some studies have even confirmed that the overall effective rate of TCM comprehensive treatment is higher than that of Western medicine. Compared with single chemical drugs, TCM treatment for IS has a synergistic regulatory effect involving multiple components, multiple targets, and multiple pathways. Studies have confirmed that TCM can alleviate damage caused by cerebral ischemia by improving factors such as oxidative stress, apoptosis, inflammatory response, and calcium overload, demonstrating unique efficacy and development value in the treatment of IS. Currently, many TCM compound preparations for IS treatment have been published, such as publication numbers CN103550702A and CN105232813A, but most of them suffer from unclear mechanisms of action, insignificant therapeutic effects, and numerous and complex components. Therefore, it is crucial to provide a safe, effective, and definite TCM compound preparation for the treatment or prevention of IS. Summary of the Invention

[0005] (a) Technical problems to be solved

[0006] To address the shortcomings of existing technologies, this invention provides a traditional Chinese medicine preparation for ischemic stroke.

[0007] (II) Technical Solution

[0008] To achieve the above objectives, the present invention provides the following technical solution:

[0009] This invention provides a traditional Chinese medicine preparation for ischemic stroke, which is made from the following raw materials in parts by weight: Gentiana macrophylla 5-20 parts, Saposhnikovia divaricata 5-20 parts, Morus alba leaf 5-20 parts, Scrophularia ningpoensis 10-30 parts, Hematite 10-30 parts, Fritillaria cirrhosa 5-20 parts, Bambusa textilis sap 5-20 parts, Prunella vulgaris 5-20 parts, Poria cocos 5-20 parts, and Melia toosendan 5-20 parts.

[0010] Furthermore, the traditional Chinese medicine preparation is made from the following raw materials in parts by weight: Gentiana macrophylla 10-20 parts, Saposhnikovia divaricata 10-20 parts, Morus alba leaf 5-15 parts, Scrophularia ningpoensis 15-25 parts, Hematite 10-20 parts, Fritillaria cirrhosa 5-15 parts, Bambusa textilis sap 5-15 parts, Prunella vulgaris 5-15 parts, Poria cocos 5-15 parts, and Melia toosendan 5-15 parts.

[0011] Furthermore, the traditional Chinese medicine preparation is made from the following raw materials in parts by weight: Gentiana macrophylla 12 parts, Saposhnikovia divaricata 12 parts, Morus alba leaf 10 parts, Scrophularia ningpoensis 18 parts, Hematite 14 parts, Fritillaria cirrhosa 10 parts, Bamboo sap 10 parts, Prunella vulgaris 8 parts, Poria cocos 8 parts, and Melia toosendan 8 parts.

[0012] The traditional Chinese medicine preparation provided by this invention is used to prepare drugs for treating ischemic stroke. The traditional Chinese medicine preparation is prepared into granules, powders, oral liquids, pills, decoctions or other pharmaceutically acceptable oral dosage forms according to conventional pharmaceutical manufacturing methods and with medically acceptable excipients.

[0013] Gentiana macrophylla: It has a pungent and bitter taste, and is neutral in nature. It enters the stomach, liver, and gallbladder meridians. It has the effects of dispelling wind and dampness, clearing damp heat, relieving pain, and reducing deficiency heat. It is used for rheumatic pain, hemiplegia due to stroke, muscle spasms, joint pain, damp-heat jaundice, bone steaming fever, and infantile malnutrition fever. Gentiana macrophylla mainly contains iridoids, triterpenes, lignans, flavonoids, alkaloids, steroids, polysaccharides, and other types of components. Its pharmacological effects mainly include anti-inflammatory, analgesic, antibacterial, antiviral, antitumor, immunomodulatory, hepatoprotective, and antioxidant pharmacological activities.

[0014] Saposhnikovia divaricata: It has a pungent and slightly sweet taste, and is warm in nature. It enters the bladder, spleen, lung, and liver meridians. It has the effects of relieving exterior syndromes, dispelling wind, stopping spasms, and eliminating dampness. It is mainly used to treat exogenous wind-cold, general pain, wind-cold-dampness arthralgia, and joint pain. The more clearly active components in Saposhnikovia divaricata include chromones, polysaccharides, volatile oils, polyacetylenes, and coumarins. Modern pharmacological studies have shown that Saposhnikovia divaricata has antioxidant, antipyretic, analgesic, anti-inflammatory, and anti-tumor effects.

[0015] Mulberry leaves: bitter and sweet in taste, cold in nature; enters the lung and liver meridians; has the effects of dispersing wind-heat, clearing the lungs and moistening dryness, calming the liver and improving eyesight, cooling the blood and stopping bleeding; used for wind-heat colds, early stages of febrile diseases, lung-heat cough, red and blurred vision, etc. Mulberry leaves contain flavonoids, alkaloids, amino acids, polysaccharides and other chemical components, mainly with pharmacological effects such as protecting nerves and cardiovascular system, protecting the liver and improving digestion, protecting the kidneys, anti-tumor, regulating blood sugar and lipid metabolism, anti-inflammatory and antioxidant effects.

[0016] Scrophularia: Sweet, bitter, and salty; slightly cold. It enters the spleen, stomach, and kidney meridians. It clears heat and cools the blood; nourishes yin and reduces fire; detoxifies and dissipates nodules. It is used for febrile diseases with heat affecting the blood; fever; thirst; crimson tongue; rashes; steaming bone cough; insomnia due to deficiency; constipation due to fluid depletion; dry and blurred vision; sore throat; scrofula; carbuncles and boils. The "Medicinal Properties Explained" states: "Dai Ren said that the kidneys are inherently cold, but when deficient, they become hot. If one indulges in excessive sexual activity and depletes essence, the true yin will be deficient, leading to upward flaring of deficient fire. Scrophularia is used to nourish yin and suppress fire. All headaches, heat toxins, tinnitus, sore throat, sore throat, scrofula, typhoid fever with yang toxins, and restlessness in the chest are caused by rootless floating fire. This has the effect of clearing heat from above and below. There are great differences in the treatment of kidney deficiency. When the kidney meridian is deficient, it is cold and damp, and should be warmed and tonified. When the kidney organ is deficient, it is hot and dry, and should be cooled and tonified. This cooling and moistening kidney-tonifying medicine is superior to Anemarrhena asphodeloides and Phellodendron chinense, and is especially the chief medicine for the kidneys."

[0017] Hematite: a mineral of the corundum group, it has a bitter and sweet taste, is slightly cold in nature, and enters the liver, stomach, and heart meridians. It has the effects of calming the liver and suppressing yang, sedating and descending rebellious qi, cooling the blood and stopping bleeding. It is commonly used for headaches, dizziness, palpitations, mania, epilepsy, vomiting, belching, hiccups, esophageal obstruction, cough, asthma, hematemesis, epistaxis, metrorrhagia, hematochezia, and hematuria.

[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 used for lung deficiency, chronic cough, consumptive cough, dry cough, lung abscess, scrofula, carbuncles, mastitis, etc. The main chemical components of Fritillaria cirrhosa are alkaloids. In addition to its traditionally recognized antitussive and antiasthmatic activities, Fritillaria cirrhosa also has antihypertensive, anti-inflammatory, antitumor, and antioxidant activities.

[0019] Bamboo sap: It is the pale yellow, clear liquid that flows out after the fresh stems of Phyllostachys edulis and closely related plants of the same genus are roasted over a fire; it is sweet and cold in nature, and enters the heart, liver, and lung meridians; it has the effects of clearing heat and detoxifying, resolving phlegm and relieving cough, calming the nerves and promoting urination, nourishing yin and unblocking the meridians; it is often used clinically to treat symptoms such as cough with excessive phlegm due to lung heat, shortness of breath and chest tightness, stiff tongue due to stroke, excessive phlegm, and infantile convulsions due to phlegm and heat; bamboo sap contains phenolic acids, amino acids, flavonoids and inorganic elements; it has pharmacological effects such as antitussive, expectorant, antiasthmatic, anti-inflammatory, antitumor, and antibacterial.

[0020] Prunella vulgaris: pungent, bitter, and cold in nature, it enters the liver and gallbladder meridians; it has the effects of clearing liver fire, improving eyesight, and dispersing nodules and reducing swelling; it is used for symptoms such as red and swollen eyes, night pain in the eyes, headache, and dizziness; the main chemical components of Prunella vulgaris include triterpenes, sterols, flavonoids, organic acids, coumarins, and other effective components, which have certain pharmacological activities in antibacterial, antiviral, anti-inflammatory, immune-regulating, antioxidant, free radical scavenging, antitumor, antihypertensive, hypoglycemic, and lipid-regulating aspects. Astragalus membranaceus: sweet in taste and slightly warm in nature, it enters the spleen and lung meridians; it has the effects of tonifying qi and consolidating the exterior, promoting pus drainage, diuresis, and tissue regeneration; it is used for symptoms such as qi deficiency and fatigue, chronic diarrhea and rectal prolapse, spontaneous sweating, edema, uterine prolapse, proteinuria in chronic nephritis, diabetes, and slow-healing sores; Astragalus membranaceus contains sugars, various amino acids, proteins, choline, betaine, folic acid, vitamin P, amylase, and various trace elements, which have the effects of enhancing immunity and antiviral activity.

[0021] Poria cocos (Fu Shen): This refers to the white part naturally containing pine roots (i.e., Fu Shen wood) in the center of the sclerotium of the fungus Poria cocos. It has a sweet and bland taste, is neutral in nature, and enters the heart and spleen meridians. Its functions and indications are: calming the mind, soothing the nerves, and promoting diuresis. It is used to treat palpitations due to heart deficiency, forgetfulness, insomnia, epilepsy, and difficulty urinating. Poria cocos mainly contains triterpenoids, sterol derivatives, flavonoids, diols, fatty acids, and other active ingredients, and has pharmacological activities such as anti-tumor, diuretic, kidney protection, immune regulation, and hypoglycemic and lipid-lowering effects.

[0022] Sichuan Chinaberry: Bitter in taste, cold in nature, and enters the liver, small intestine, and bladder meridians; it has the effects of soothing the liver and clearing heat, promoting qi circulation and relieving pain, and killing parasites; it is used for symptoms such as liver stagnation transforming into fire, chest and rib pain, abdominal distension and pain, hernia pain, and abdominal pain due to intestinal parasites; Sichuan Chinaberry mainly contains volatile oils, lignans, organic acids, flavonoids, limonene and other components, which have anti-inflammatory, analgesic, and neuroprotective effects on the central nervous system, as well as antioxidant, antitumor, antibacterial, antiviral, and insecticidal pharmacological effects.

[0023] (III) Beneficial Effects

[0024] This invention provides a traditional Chinese medicine preparation for ischemic stroke. The preparation is made from Gentiana macrophylla, Saposhnikovia divaricata, Morus alba leaf, Scrophularia ningpoensis, Hematite, Fritillaria cirrhosa, Bamboo sap, Prunella vulgaris, Poria cocos, and Melia toosendan. Scrophularia ningpoensis, with its clearing heat and cooling blood, nourishing yin and reducing fire, is the principal herb. Hematite is used to calm the liver and subdue yang, suppress rebellious qi, cool the blood and stop bleeding. Gentiana macrophylla is bitter, pungent, and slightly cold; its pungent nature allows it to disperse, and its bitterness does not cause dryness. It can dispel wind-dampness, unblock meridians, and relieve pain, as well as clear deficiency heat and eliminate damp heat. Saposhnikovia divaricata is pungent, sweet, and slightly warm; its nature is ascending and dispersing, and it is good at... It acts throughout the body, is slightly warm without being drying, and sweet without being harsh. It is a moisturizing agent for wind, with the functions of dispelling wind and relieving exterior symptoms, eliminating dampness and relieving pain, and stopping spasms. When used together, one of the herbs is slightly cold and the other is slightly warm, which is suitable for both. It dispels wind and dampness, relaxes muscles and tendons and unblocks collaterals. 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 stops cough. Bamboo sap clears heat and resolves phlegm, calms fright and opens the orifices. The two herbs together can treat stroke with phlegm coma, epilepsy and 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. Melia toosendan clears heat and dries dampness, drains fire and detoxifies. Stroke patients often have hyperactivity of liver yang, which manifests as a combination of internal and external wind. Hematite can calm internal wind, and when combined with herbs such as Gentiana macrophylla and Saposhnikovia divaricata to dispel external wind, the internal and external winds are treated together. Melia toosendan is good at guiding liver qi downward, and Fritillaria cirrhosa and bamboo sap are added to clear heat and resolve phlegm. The whole formula works together to calm the liver and subdue yang, stop wind and spasms, resolve phlegm and open the orifices.

[0025] The traditional Chinese medicine preparation of this invention has a significant effect on improving the neurological function of rats with cerebral ischemia-reperfusion injury. It can effectively reduce the water content and infarct volume of brain tissue in rats with cerebral ischemia-reperfusion injury, significantly increase the levels of GSH and SOD in the brain tissue of rats with cerebral ischemia-reperfusion injury, and reduce the level of MDA, thus improving the oxidative stress induced by cerebral ischemia-reperfusion injury. The traditional Chinese medicine preparation of this invention has a significant therapeutic effect on rats with cerebral ischemia-reperfusion injury, and its efficacy is comparable to that of the Western medicine nimoxicillin.

[0026] The traditional Chinese medicine preparation of this invention can significantly improve the overall effective rate of treatment for patients with ischemic stroke, significantly reduce the NIHS score and TCM syndrome score, and significantly improve the ADL score. This traditional Chinese medicine preparation can effectively alleviate the neurological deficits in patients with ischemic stroke, help restore their daily living functions, and reduce clinical symptoms. Its efficacy is definite and significant, and it can be used as a new drug for the treatment of ischemic stroke. Detailed Implementation

[0027] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of 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 some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0028] Example 1

[0029] A traditional Chinese medicine preparation for ischemic stroke, the preparation being made from the following raw materials in parts by weight: Gentiana macrophylla 5 parts, Saposhnikovia divaricata 5 parts, Morus alba leaf 5 parts, Scrophularia ningpoensis 10 parts, Hematite 10 parts, Fritillaria cirrhosa 5 parts, Bamboo sap 5 parts, Prunella vulgaris 5 parts, Poria cocos 5 parts, and Melia toosendan 5 parts.

[0030] The traditional Chinese medicine preparations are formulated into granules, powders, oral liquids, pills, decoctions, or other pharmaceutically acceptable oral dosage forms by using conventional pharmaceutical methods and adding medically acceptable excipients.

[0031] Example 2

[0032] 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: 20 parts of Gentiana macrophylla, 20 parts of Saposhnikovia divaricata, 20 parts of Morus alba leaf, 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 cocos, and 20 parts of Melia toosendan.

[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: Gentiana macrophylla 16 parts, Saposhnikovia divaricata 18 parts, Morus alba leaf 16 parts, Scrophularia ningpoensis 28 parts, Hematite 22 parts, Fritillaria cirrhosa 16 parts, Bamboo sap 18 parts, Prunella vulgaris 16 parts, Poria cocos 16 parts, and Melia toosendan 16 parts.

[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 Gentiana macrophylla, 10 parts Saposhnikovia divaricata, 5 parts Morus alba leaves, 15 parts Scrophularia ningpoensis, 10 parts Hematite, 5 parts Fritillaria cirrhosa, 5 parts Bamboo sap, 5 parts Prunella vulgaris, 5 parts Poria cocos, and 5 parts Melia toosendan.

[0037] Example 5

[0038] 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: 20 parts of Gentiana macrophylla, 20 parts of Saposhnikovia divaricata, 15 parts of Morus alba leaf, 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 cocos, and 15 parts of Melia toosendan.

[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: Gentiana macrophylla 14 parts, Saposhnikovia divaricata 14 parts, Morus alba leaf 8 parts, Scrophularia ningpoensis 20 parts, Hematite 16 parts, Fritillaria cirrhosa 8 parts, Bamboo sap 12 parts, Prunella vulgaris 10 parts, Poria cocos 12 parts, and Melia toosendan 12 parts.

[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 Morus alba leaves, 22 parts of Scrophularia ningpoensis, 14 parts of Haematitum, 12 parts of Fritillaria cirrhosa, 8 parts of Phyllostachys nigra juice, 12 parts of Prunella vulgaris, 10 parts of Poria cum Radix Pini, and 6 parts of Toosendan fruit.

[0043] Embodiment 8

[0044] 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: 12 parts of Gentiana macrophylla, 12 parts of Saposhnikovia divaricata, 10 parts of Morus alba leaves, 18 parts of Scrophularia ningpoensis, 14 parts of Haematitum, 10 parts of Fritillaria cirrhosa, 10 parts of Phyllostachys nigra juice, 8 parts of Prunella vulgaris, 8 parts of Poria cum Radix Pini, and 8 parts of Toosendan fruit.

[0045] Test Example 1

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

[0047] 1 Materials and methods

[0048] 1.1 Experimental drugs

[0049] The traditional Chinese medicine preparation of the present invention: 12 parts of Gentiana macrophylla, 12 parts of Saposhnikovia divaricata, 10 parts of Morus alba leaves, 18 parts of Scrophularia ningpoensis, 14 parts of Haematitum, 10 parts of Fritillaria cirrhosa, 10 parts of Phyllostachys nigra juice, 8 parts of Prunella vulgaris, 8 parts of Poria cum Radix Pini, and 8 parts of Toosendan fruit. Weigh each raw material according to the above parts by weight, wash them, soak them in 3 times deionized water for 20 minutes, then decoct for 30 minutes, repeat decocting more than 2 times, collect the decoction, concentrate the decoction to 1 g / mL (1 mL contains 1 g of crude drug content), and store it at 4°C for standby.

[0050] Western medicine control: Nimodipine

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

[0052] SPF-grade SD rats, male, weighing 160 - 180 g, were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd., and 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 specific method was as follows: After anesthetizing the rats, they were fixed in a supine position. The right common carotid artery, external carotid artery, and internal carotid artery were separated along the midline of the neck. The common carotid artery and external carotid artery were ligated with fine sutures. The distal end of the internal carotid artery was temporarily clamped with a micro-artery clamp. A small incision was made about 4 mm from the bifurcation of the common carotid artery, and the suture plug was inserted into the internal carotid artery. The micro-artery clamp was opened, and the suture plug was gently pushed with ophthalmic forceps until slight resistance was encountered. After 2 hours of ischemia, the suture plug was withdrawn until resistance was encountered. 25 units of penicillin were injected intramuscularly to prevent infection, and the wound was sutured. The sham-operated group followed the same steps as above except that no suture plug was inserted. 22 hours after reperfusion, the Zea-Longa 5-point scoring criteria were used: ① No signs of neurological deficit (0 points); ② Inability to fully flex the contralateral forepaw (1 point); ③ Turning towards the paralyzed side (2 points); ④ Leaning towards the paralyzed side (3 points); ⑤ Inability to walk spontaneously and loss of consciousness (4 points). Rats scoring 1-3 were considered to have successfully established the model 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 traditional Chinese medicine preparation of this invention (hereinafter referred to as the high-dose group, 20 g / kg), and a low-dose group of the traditional Chinese medicine preparation of this invention (hereinafter referred to as the low-dose group, 10 g / kg). The sham-operated group and the model group were given an equal volume of physiological saline by gavage. There were 12 rats in each group, and each group was administered the medicine for 7 consecutive days.

[0056] 1.4 Detection Indicators

[0057] 1.4.1 Modified Neurological Deficit Scoring

[0058] Behavioral scores were assessed in each group of experimental animals after the last administration of medication, according to the mNSS scoring criteria. The total mNSS score was 18 points, with mild impairment scored as 0–6 points, moderate impairment as 7–12 points, and severe impairment as 13–18 points. The degree of neurological impairment increased with the score. The scoring criteria are shown in Table 1.

[0059] Table 1. mNSS Scoring Criteria

[0060]

[0061]

[0062] 1.4.2 Water content of rat brain tissue

[0063] After the last administration, rats were euthanized, and brain tissue was quickly harvested. Residual blood on the surface of the brain tissue was wiped away with filter paper. The brain tissue was placed in pre-weighed (A) aluminum foil and weighed again using an analytical balance (B) to obtain the wet weight (BA) of the brain tissue. The brain tissue was then wrapped in aluminum foil and dried in a 95°C oven for 24 hours. After being removed and allowed to return to room temperature, it was weighed again (C) to obtain the dry weight (CA) of the brain tissue. The water content of the brain tissue was calculated using the following formula:

[0064]

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

[0066] After the last administration, rats were euthanized, and brain tissue was quickly harvested. Residual blood on the surface of the brain tissue was wiped away with filter paper, and the tissue was frozen at -20°C for 30 minutes. The lower brainstem, olfactory brain, and cerebellum were removed. Continuous coronal sections, approximately 2 mm thick, were prepared from the occipital to the frontal pole. The sections were then placed in 2% red tetrazolium (TTC) solution and incubated at 37°C for 30 minutes in the dark, gently turning the sections every 5 minutes to ensure thorough staining. Normal brain tissue appeared red, while infarcted brain tissue appeared grayish-white. After photographing, the infarct area was calculated using ImageJ software. The total infarct volume was calculated by multiplying the sum of the infarct areas of each brain slice by the thickness (2 mm). The infarct volume of the brain tissue was calculated using 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] Rats were euthanized after the last administration, and brain tissue was rapidly harvested for the detection of GSH, SOD, and MDA levels. All procedures were strictly performed according to the kit instructions.

[0070] 1.5 Statistical Analysis

[0071] Statistical analysis was performed using SPSS 21.0. One-way ANOVA was used for comparisons between groups. Results are expressed as mean ± standard deviation. Data were presented in t-test format. P < 0.05 was considered statistically significant.

[0072] 2 Results

[0073] 2.1 Effects of the herbal preparation of this invention on neurological function in rats with cerebral ischemia-reperfusion injury

[0074] The results are shown in Table 2. Compared with the sham-operated 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 high-dose and low-dose groups of the traditional Chinese medicine preparation of this invention were significantly decreased (P<0.01).

[0075] Table 2. Effects of the traditional Chinese medicine preparation of this invention on the neurological function scores of rats with cerebral ischemia-reperfusion model (n=12)

[0076] Group mNSS rating Sham surgery 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 surgery group. ** P<0.01; compared with the model group, ## P<0.01.

[0078] 2.2 Effects of the herbal preparation of this invention on the water content of brain tissue in rats with cerebral ischemia-reperfusion injury

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

[0080] Table 3. Effects of the traditional Chinese medicine preparation of this invention on brain tissue water content in rats with cerebral ischemia-reperfusion injury (n=3)

[0081] Group Brain tissue water content (%) Sham surgery 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 surgery group. ** P<0.01; compared with the model group, # P<0.05; ## P<0.01.

[0083] 2.3 Effects of the herbal preparation of this invention on the infarct volume in rats with cerebral ischemia-reperfusion injury

[0084] The results are shown in Table 4. Compared with the sham surgery 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 rats in the high-dose and low-dose groups of the traditional Chinese medicine preparation of this invention was significantly reduced (P<0.01), compared with the Western medicine control group.

[0085] Table 4. Effects of the traditional Chinese medicine preparation of this invention on the infarct volume in rats with cerebral ischemia-reperfusion injury (n=3)

[0086] Group Cerebral infarction volume (%) Sham surgery 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 surgery group. ** P<0.01; compared with the model group, ## P<0.01.

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

[0089] The results are shown in Table 5. Compared with the sham-operated group, the levels of GSH and SOD in the brain tissue of rats in the model group were significantly decreased (P<0.01, P<0.01), while the level of MDA was significantly increased (P<0.01). Compared with the model group, the levels of GSH and SOD in the brain tissue of rats in the Western medicine control group were significantly increased (P<0.01, P<0.01), while the level of MDA in the brain tissue was significantly decreased (P<0.01). In the high-dose group of the traditional Chinese medicine preparation of this invention, the levels of GSH and SOD in the brain tissue of rats were significantly increased (P<0.01, P<0.01), while the level of MDA in the brain tissue was significantly decreased (P<0.01). In the low-dose group of the traditional Chinese medicine preparation of this invention, the levels of GSH and SOD in the brain tissue of rats were significantly increased (P<0.01, P<0.01), while the level of MDA in the brain tissue was significantly decreased (P<0.01).

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

[0091]

[0092]

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

[0094] 3. Conclusion

[0095] Based on the above results, the traditional Chinese medicine preparation of this invention has a significant effect on improving the neurological function of rats with cerebral ischemia-reperfusion injury, effectively reducing the water content and infarct volume of brain tissue in rats with cerebral ischemia-reperfusion injury, significantly increasing the levels of GSH and SOD in the brain tissue of rats with cerebral ischemia-reperfusion injury, and decreasing the level of MDA, thus improving the oxidative stress induced by cerebral ischemia-reperfusion injury. These results indicate that the traditional Chinese medicine preparation of this invention has a significant therapeutic effect on rats with cerebral ischemia-reperfusion injury, and its efficacy is comparable to that of the Western medicine nimoxicillin, making it a potential drug for the treatment or prevention of ischemic stroke.

[0096] Experimental Example 2

[0097] Clinical efficacy observation of the traditional Chinese medicine preparation of this invention in ischemic stroke

[0098] 1. Materials and Methods

[0099] 1.1 Clinical Data

[0100] Seventy-two patients with ischemic stroke admitted to Lushan County Traditional Chinese Medicine Hospital from January 2023 to June 2024 were selected as the study subjects. They were randomly divided into an observation group and a control group, with 36 patients 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 statistically significant differences in general characteristics between the two groups (P>0.05), indicating comparability.

[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 Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2018: (1) Sudden onset, with sudden generalized or focal neurological deficits; (2) Acute infarction lesions can be seen on MRI or cranial CT, excluding space-occupying lesions, cerebral hemorrhage and other intracranial lesions.

[0104] Traditional Chinese Medicine Diagnosis: Refer to the diagnostic criteria for "stroke" in the "Guidelines for Diagnosis and Treatment of Common Diseases in Traditional Chinese Medicine Internal Medicine - Traditional Chinese Medicine Symptoms": (1) Main symptoms: sudden collapse, hemiplegia, unconsciousness, facial paralysis, and speech impairment; (2) In mild cases, there may be no collapse, only hemiplegia and facial paralysis.

[0105] 1.2.2 Inclusion Criteria

[0106] (1) Meets the relevant Western medicine diagnostic criteria mentioned above; (2) Meets the diagnostic criteria for "stroke" mentioned above in traditional Chinese medicine; (3) The patient and their family 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 loss of consciousness; (3) Patients allergic to the drugs studied; (4) Patients with severe heart, liver and kidney dysfunction; (5) Patients with a history of ischemic stroke; (6) Patients with dysphagia; (7) Patients with a history of mental illness.

[0109] 1.3 Treatment Methods

[0110] Control group: Patients received standardized treatment according to guidelines. The treatment was formulated in accordance with the "Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2018" and the "Chinese Guidelines for Secondary Prevention of Ischemic Stroke and Transient Ischemic Attack 2014." For patients with comorbidities such as hypertension, hyperglycemia, and hyperlipidemia, targeted treatment was provided. Aspirin + clopidogrel: Initially, aspirin 100mg / day and clopidogrel 300mg / day; from day 2 to day 21, aspirin 100mg / day and clopidogrel 75mg / day. If the patient had contraindications to aspirin, gravidarum tablets (90mg / day) could be substituted. Edaravone was administered intravenously, 30mg twice daily, for 4 weeks.

[0111] Observation group: In addition to the treatment of the control group, the patients were given oral Chinese medicine preparation of the present invention, specifically: 12 parts of Gentiana macrophylla, 12 parts of Saposhnikovia divaricata, 10 parts of Morus alba leaf, 18 parts of Scrophularia ningpoensis, 14 parts of Hematite, 10 parts of Fritillaria cirrhosa, 10 parts of Bambusa textilis sap, 8 parts of Prunella vulgaris, 8 parts of Poria cocos, and 8 parts of Melia toosendan. Each herb was weighed according to the above weight proportions, decocted in water, and one dose was taken daily, divided into two doses after breakfast and dinner, 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 according to the NIHSS, including level of consciousness, ability to answer questions, ability to follow instructions, eye movements, 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 score of 42 points. The higher the score, the more severe the neurological damage.

[0115] 1.4.2 Daily Activities of Daily Living

[0116] Activities of Daily Living (ADL) were assessed before and after treatment. ADL was assessed using the modified Barthel Index, which includes 10 items such as bathing, dressing, and climbing stairs, with a total score of 100. A score >95 indicates complete independence, and a higher score indicates better ADL.

[0117] 1.4.3 Traditional Chinese Medicine Symptom Scoring

[0118] Both before and after treatment, the diagnostic and efficacy evaluation criteria for stroke were followed, including speech impairment, hemiplegia, and oral and lingual impairment. Symptoms include strabismus, loss of consciousness, and ataxia. Each item is scored from 0 to 9 points, with higher scores indicating more severe symptoms.

[0119] 1.5 Efficacy Criteria

[0120] According to the "Guiding Principles for Clinical Research of New Traditional Chinese Medicine Drugs in the Treatment of Stroke". Significant effect: Clinical symptoms improve significantly, with a decrease in NIHSS score of 46%–90%; Effective: Clinical symptoms improve, with a decrease in NIHSS score of 18%–45%. Ineffective: Clinical symptoms do not improve or worsen, with no decrease or increase in NIHSS score.

[0121] 1.6 Adverse Reactions

[0122] Symptoms include headaches, dizziness, nausea, vomiting, and abnormal liver and kidney function.

[0123] 1.7 Statistical Analysis

[0124] SPSS 21.0 statistical software was used for analysis. Quantitative data were analyzed using (… Count data are expressed as (%) and tested using t-tests; categorical data are expressed as (%) and tested using χ². 2 The test showed that P < 0.05 was 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 examples Effective efficient invalid Overall 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 pre-treatment scores, the NIHSS scores of all groups were significantly reduced after treatment (P<0.01); among them, the NIHSS scores of the observation group were significantly lower than those of the control group after treatment (P<0.01).

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

[0133] Grouping Number of examples 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 pre-treatment level in this group. ** P < 0.01; compared with the control group after treatment, # P < 0.05 ## P < 0.01, the same applies below.

[0135] 2.3 Comparison of ADL scores

[0136] The results are shown in Table 8. Compared with the pre-treatment scores, the ADL scores of all groups were significantly improved after treatment (P<0.01); among them, the ADL scores of the observation group were significantly higher than those of the control group after treatment (P<0.01).

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

[0138] Grouping Number of examples 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 pre-treatment scores, the TCM symptom scores of the group were significantly reduced after treatment (P<0.01); among them, the ADL scores of the observation group were significantly lower than those of the control group after treatment (P<0.05).

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

[0142] Grouping Number of examples 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 Observation of adverse reactions

[0144] Adverse reactions were observed in both groups of patients during treatment. Neither group experienced adverse reactions such as nausea and vomiting, headache and dizziness, or abnormal liver and kidney function.

[0145] 3. Conclusion

[0146] The above results show that, compared with the control group, the traditional Chinese medicine preparation of this invention can significantly improve the overall effective rate of treatment for patients with ischemic stroke, significantly reduce the NIHS score and TCM syndrome score, and significantly improve the ADL score. These results indicate that the traditional Chinese medicine preparation of this invention can effectively alleviate the neurological deficits in patients with ischemic stroke, help restore their daily living functions, and reduce clinical symptoms. Its efficacy is definite and significant, and it 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, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A traditional Chinese medicine preparation for ischemic stroke, characterized in that, The traditional Chinese medicine preparation is made from the following raw materials in parts by weight: Gentiana macrophylla 5-20 parts, Saposhnikovia divaricata 5-20 parts, Morus alba leaf 5-20 parts, Scrophularia ningpoensis 10-30 parts, Hematite 10-30 parts, Fritillaria cirrhosa 5-20 parts, Bambusa textilis sap 5-20 parts, Prunella vulgaris 5-20 parts, Poria cocos 5-20 parts, and Melia toosendan 5-20 parts.

2. The traditional Chinese medicine preparation for ischemic stroke according to claim 1, characterized in that, The traditional Chinese medicine preparation is made from the following raw materials in parts by weight: Gentiana macrophylla 10-20 parts, Saposhnikovia divaricata 10-20 parts, Morus alba leaf 5-15 parts, Scrophularia ningpoensis 15-25 parts, Hematite 10-20 parts, Fritillaria cirrhosa 5-15 parts, Bambusa textilis sap 5-15 parts, Prunella vulgaris 5-15 parts, Poria cocos 5-15 parts, and Melia toosendan 5-15 parts.

3. The traditional Chinese medicine preparation for ischemic stroke according to claim 1, characterized in that, The traditional Chinese medicine preparation is made from the following raw materials in parts by weight: Gentiana macrophylla 12 parts, Saposhnikovia divaricata 12 parts, Morus alba leaf 10 parts, Scrophularia ningpoensis 18 parts, Hematite 14 parts, Fritillaria cirrhosa 10 parts, Bamboo sap 10 parts, Prunella vulgaris 8 parts, Poria cocos 8 parts, and Melia toosendan 8 parts.

4. The use of the traditional 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 traditional Chinese medicine preparations are formulated into granules, powders, oral liquids, pills, decoctions, or other pharmaceutically acceptable oral dosage forms by using conventional pharmaceutical methods and adding medically acceptable excipients.

Images