A compound medicine of Zhuang Yao medicine, preparation method and application thereof in treatment of acute ischemic stroke

Abstract

The application belongs to the field of Zhuang and Yao medicine treatment of acute ischemic stroke, and discloses a Zhuang and Yao medicine compound medicine, a preparation method and application thereof in treating acute ischemic stroke. The Zhuang and Yao medicine compound medicine comprises the following raw materials in parts by weight: Ficus tikoua 55-62 parts, Camptotheca acuminata 12-17 parts, Ilex hainanensis 26-35 parts and Saposhnikovia divaricata 13-18 parts. The four raw materials are put into clean water, and the raw materials are prepared into a medicinal liquid to obtain the Zhuang and Yao medicine compound medicine. The Zhuang and Yao medicine compound medicine is cheap, convenient to use, has remarkable curative effect, can dredge the dragon road and the toxic evil and toxic side effects of the fire road, and has a simple preparation process.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of Zhuang and Yao medicine treatment of acute ischemic stroke, and particularly relates to a Zhuang and Yao medicine compound, a preparation method and application thereof in the treatment of acute ischemic stroke. TECHNICAL BACKGROUND

[0002] Acute ischemic stroke (AIS), also known as acute cerebral infarction in modern medicine, is a clinically common critical and severe cerebrovascular disease. After acute ischemia, blood circulation in the lesion local area of the brain tissue is impaired, and blood supply is insufficient, thereby causing ischemic and anoxic necrosis and dysfunction of the nervous system. Clinically, it can be seen that the limbs are paralyzed, speech is blocked or even aphasia, and severe consciousness disorders occur. It causes serious burden to the family and society. China is one of the high-incidence areas of cerebrovascular disease, and is currently the second leading cause of death. The incidence of acute ischemic stroke in the elderly population in recent years is significantly higher, especially in the elderly population. The older the age, the more serious the underlying diseases such as hypertension and coronary heart disease, and the higher the incidence of ischemic stroke. This disease has a high mortality and disability rate, and has a serious impact on the life safety and self-care ability, quality of life, and the like of patients. Common measures for the treatment of acute ischemic stroke include thrombolytic therapy, surgical treatment, and interventional therapy. Among them, thrombolytic therapy and surgical treatment have a relatively high usage rate in clinical practice. Thrombolytic therapy includes arterial thrombolysis and intravenous thrombolysis. Both of them have a significant effect on improving the symptoms of stroke and infarction in patients, but the risk of arterial thrombolysis is relatively high. Surgical treatment mainly refers to thrombectomy, which can improve the blood circulation of the brain by timely eliminating the symptoms of thrombosis and promoting the function of the brain tissue as much as possible. Various treatment methods and effects are different, therefore, timely and effective intervention of acute ischemic stroke, promotion of the recovery of the nervous function of patients, and minimization of the impact of disability are of great significance for the early return of patients to their families and society.

[0003] The blood-brain barrier (BBB) is mainly composed of endothelial cells, pericytes, astrocytes and extracellular matrix, etc. Its high selective permeability can avoid the damage of harmful substances such as pathogens and inflammatory factors to the central nervous system (CNS), thereby protecting and maintaining the normal function and homeostasis of the central nervous system. The damage of BBB is the most important initiating factor of cerebral ischemia-reperfusion injury, and is also the main cause of inducing various complications. The BBB has a high "selectivity" to the surrounding substances, which can ensure the normal material exchange and charge balance between CNS and blood, and ensure the normal physiological function of neurons. In addition, the BBB can block the large molecular substances such as pathogens, immune cells and toxins in the blood to protect the neural tissue. In the process of cerebral ischemia-reperfusion injury, the BBB is damaged before the surrounding neurons, and then the brain vascular permeability increases, the selectivity to substances is lost, so as to cause various intravascular contents to penetrate into the neural tissue, induce vasogenic cerebral edema, intracranial pressure rise, and severe intracranial hemorrhage transformation. In addition, many neurotoxic substances (such as thrombin, glutamate, albumin, etc.) in the blood vessels can enter the brain tissue through the damaged BBB, further aggravating the nerve damage. Therefore, the protection of BBB is the key treatment point in the process of cerebral ischemia-reperfusion injury.

[0004] Since the damage of BBB after cerebral ischemia-reperfusion is related to free radical damage, inflammatory infiltration, calcium overload, neural apoptosis, excitatory amino acid toxicity and other pathological mechanisms, the pathological process formed is extremely complex and variable. At present, modern medicine often uses the above single pathological factor as a treatment target to prevent and treat cerebral ischemia-reperfusion injury, which is difficult to achieve satisfactory clinical efficacy. In recent years, research has found that traditional Chinese medicine, as a natural compound, can treat diseases through multiple pathways and multiple targets, especially the compound preparation of multi-flavor drugs highlights the characteristics of traditional Chinese medicine in treating this disease, and its efficacy is better than that of single western medicine.

[0005] For example, Chinese patent document (publication number: CN108567920A) discloses a traditional Chinese medicine composition for treating acute ischemic stroke, which is composed of effective components and medically acceptable excipients, wherein the effective components are made of raw medicinal materials in the following weight percentages: 10.4-11.5% of rhubarb, 10.4-11.5% of silvertree, 26.0-28.7% of gardenia, 1.6-1.7% of artificial ox gall, 10.4-11.5% of yellow earth, 10.4-11.5% of magnolia, 10.4-11.5% of red peony root, 15.6-17.2% of giant knotweed. The traditional Chinese medicine composition can be tablets, granules or capsules, and the traditional Chinese medicine composition can treat acute ischemic stroke. However, the drug formula has many drawbacks. First, the formula contains many drug components, some of which are expensive, and the volatile is strong during decoction, so the decoction requirements are very strict and the process is complex. Second, the multi-component formula makes the effective components relatively lack. Many drug components may interfere with each other, making it difficult for effective components to fully play a role, and thus leading to poor treatment effect.

[0006] For example, Chinese patent application document (publication number: CN112791117A) discloses a formula for treating acute ischemic stroke, which is prepared from raw medicinal materials angelica and salvia miltiorrhiza. The invention can be used for treating acute ischemic stroke by traditional Chinese medicine composition, but the component is only two kinds, and there is also the problem of poor treatment effect. SUMMARY

[0007] The present application is aimed at the deficiencies of existing western medicines for treating acute ischemic stroke and the poor treatment effect of existing traditional Chinese medicines, and provides a Zhuang and Yao medicine compound, a preparation method and its application in treating acute ischemic stroke. The Zhuang and Yao medicine compound is cheap, convenient to use, has significant effect, can dredge the dragon road, the poison evil and toxic side effects of the road, and has simple preparation process.

[0008] To achieve the above-mentioned purpose, the technical scheme adopted by the present application is as follows:

[0009] A Zhuang and Yao medicine compound, comprising the following raw materials by weight: Ficus pumila 55-62 parts, iron drill 12-17 parts, Ilex hainanensis 26-35 parts, silvertree 13-18 parts.

[0010] The technical principle of the present application is as follows:

[0011] The properties of each raw medicinal material used are as follows:

[0012] Five-finger Ficus: The root of *Ficus simplicissima* Lour., a plant in the Moraceae family. *Ficus simplicissima* is distributed in Fujian, Guangdong, Guangxi, Hainan, Guizhou, and Yunnan provinces of China, and also in Vietnam and Cambodia. It has a sweet taste and neutral properties. It enters the spleen, lung, and liver meridians. Functions: Strengthens the spleen and lungs, promotes qi circulation and eliminates dampness, relaxes muscles and tendons. Indications: Spleen deficiency edema, poor appetite and weakness, pulmonary tuberculosis cough, night sweats, leukorrhea, postpartum agalactia, rheumatic pain, edema, ascites due to cirrhosis, hepatitis, and traumatic injuries.

[0013] Iron Drill: [Yao language] Jia Duan, [Yao language transliteration] hlieqc nzunx, [Other names] Long Teng, [Source] The root of Fissistigma oldhamii (Hemsl.) Merr., a plant of the Annonaceae family. Distributed in Fujian, Taiwan, Guangdong, Hunan, Jiangxi, Yunnan, Guangxi, and other places, specifically in Jinxiu, Rongshui, Lingchuan, Quanzhou, Fuchuan, and Cenxi in Guangxi. [Properties and Effects] Classified as a medicinal herb. Pungent and warm in nature. It has the effects of dispelling wind and dampness, relieving pain and swelling, and promoting blood circulation and removing blood stasis. Used to treat acute stroke, arthritis, and sciatica.

[0014] Ilex pubescens Hook. et Am. (Yao language): [Yao language] chū gōng láng, [Yao language transliteration] couh gong ndiangx, [Other names] huō lóu mǔ, wū wěi dīng, máo pī shù, xī yè dōng qīng, shān xǒng dān, suān wěi mǔ, ā mǐ shù, xiāo bāi jié, [Source] The whole plant of Ilex pubescens Hook. et Am. (Hormonece family). [Properties and effects] Bitter and astringent in taste, cool in nature. Clears heat and detoxifies, invigorates blood and unblocks meridians, reduces swelling and relieves pain. Used for colds with fever, pharyngitis, hepatitis, pneumonia, cough due to lung heat, rheumatic heart disease, coronary heart disease, thromboangiitis obliterans, acute suppurative inflammation of the skin, stomach pain, dysentery, erysipelas, traumatic swelling and pain, burns, scalds, and acute stroke.

[0015] *Saposhnikovia divaricata* (Turcz.) Schishk., a perennial herb belonging to the genus *Saposhnikovia* in the family Apiaceae. The taproot is conical and pale yellowish-brown. The stem is solitary. The petals are white and obovate. The fruit is narrowly elliptical or elliptical, slightly flattened on the back, with spongy, tuberculate protuberances on young fruits. Properties and Channels: Pungent and sweet in taste, slightly warm in nature. It enters the bladder, spleen, and liver channels. Functions: Dispels wind and releases the exterior, eliminates dampness and relieves pain, stops spasms. Indications: Acute phase of stroke, external pathogenic factors, urticaria and itching, rheumatic arthralgia, tetanus, spleen deficiency with dampness.

[0016] The five-finger peach, iron drill, hairy holly and saposhnikovia in the Zhuang-Yao medicine compound work together to exert a unique and effective effect, and together they are dedicated to the treatment of acute ischemic stroke.

[0017] As the main medicine, Ficus hirta plays a crucial role in the prescription. It has the function of replenishing qi, and can target the upward movement of ministerial fire caused by the deficiency of invisible qi, thus avoiding the consumption and injury of human qi and blood. Qi is the commander of blood, and visible blood depends on invisible qi for generation. Ficus hirta helps the primordial qi, enabling the generation of qi and blood to have a source, and can also dredge the dragon meridian, guiding all the medicines directly to the delicate acupoints, regulating the core hub of the human spirit, emotion and qi and blood circulation, laying a foundation for the whole prescription to strengthen the healthy qi and consolidate the root, and guide the meridian to dredge the pulse.

[0018] As the male medicine, Smilax china belongs to the category of attacking medicines and has a powerful effect of promoting blood circulation and removing blood stasis. In the acute stage of stroke, qi and blood stasis is an important pathological link. Smilax china can break through blood stasis obstruction and improve cerebral blood circulation disorders. In combination with Ficus hirta, one replenishes and the other dredges, enabling qi and blood to be promoted by qi replenishment while the blood stasis is dissipated, effectively relieving the stasis of the dragon meridian and fire meridian, and restoring the smooth flow of qi and blood.

[0019] Ilex pubescens is the adjuvant medicine. Its effect of promoting blood circulation and dredging meridians can further enhance the fluidity of blood, synergistically with Smilax china to strengthen the effect of promoting blood circulation and removing blood stasis. At the same time, it also has the functions of detumescence and pain relief, and clearing heat and detoxifying. It can clear the cerebral edema, local pain and heat toxin caused by qi and blood stasis that may accompany ischemic stroke, and act on the dragon meridian and fire meridian together with Ficus hirta and Smilax china to improve various symptoms caused by toxin stasis.

[0020] As the guiding medicine, Saposhnikovia divaricata, although it has the effects of pain relief and spasmolysis itself, its more important characteristic is that it is a moistening agent among the wind medicines. It can guide all the medicines to reach the affected area and enhance the resistance and treatment effect of the whole prescription against wind pathogens. Whether it is exogenous wind invasion or endogenous wind disturbance (such as endogenous wind caused by qi and blood disharmony), Saposhnikovia divaricata can cooperate with other medicines to disperse exogenous wind and calm endogenous wind, achieving the effect of "when blood circulates smoothly, wind will disappear by itself", enabling the whole prescription to not only target exogenous pathogens but also regulate the wind movement caused by abnormal internal qi and blood.

[0021] In terms of dosage, the amount of Ficus hirta is controlled at 55 - 62 parts. As the main medicine, its dosage is relatively large to give full play to its leading role in replenishing qi and dredging meridians and guiding all the medicines. If the dosage is too small, it will be difficult to shoulder the heavy responsibility of the main medicine and cannot effectively replenish qi and assist the primordial qi and dredge the dragon meridian; if the dosage is too large, it may lead to qi excess and stagnation, affecting the balance and coordination of qi and blood. The dosage of Smilax china is 12 - 17 parts, which can not only ensure the exertion of its effect of promoting blood circulation and removing blood stasis, but also will not cause excessive blood-breaking and consumption of healthy qi due to excessive dosage. The dosage of Ilex pubescens is 26 - 35 parts, and this dosage can moderately exert its effects of promoting blood circulation and dredging meridians, detumescence and detoxification, synergistically with Ficus hirta and Smilax china. Improper dosage may affect the overall synergy and efficacy balance. The dosage of Saposhnikovia divaricata is 13 - 18 parts. An appropriate amount of Saposhnikovia divaricata can just right guide the medicine to reach the affected area and regulate wind-related diseases. Too little will result in insufficient guiding and wind-dispelling power, and too much may lead to excessive dryness of the wind medicine and injury to yin and consumption of blood.

[0022] Through precise dosage control and synergistic effects of these four herbs, the entire formula works together to clear the "dragon's path" and "fire path," restoring the normal functioning of the "two paths," regulating the opening and closing balance of the "three channels," promoting the orderly rise and fall of Yin and Yang in the body, and harmonizing Qi and blood. In the treatment of acute ischemic stroke, it overcomes the shortcomings of Western medicine, such as large side effects and easy drug resistance, and brings forward the advantages of traditional Chinese medicine, achieving remarkable and unexpected technical effects. It provides an innovative and effective drug combination scheme for the symptom improvement and disease rehabilitation of patients with ischemic stroke.

[0023] Preferably, the Zhuang-Yao medicine compound medicine comprises the following raw materials in parts by weight: 56 parts of five-finger peach, 12 parts of iron drill, 27 parts of hairy holly, and 13 parts of saposhnikovia.

[0024] Preferably, the Zhuang-Yao medicine compound medicine comprises the following raw materials in parts by weight: 59 parts of five-finger peach, 16 parts of iron drill, 28 parts of hairy holly, and 15 parts of saposhnikovia.

[0025] Preferably, the Zhuang-Yao medicine compound medicine comprises the following raw materials in parts by weight: 60 parts of five-finger peach, 15 parts of iron drill, 30 parts of hairy holly, and 15 parts of saposhnikovia.

[0026] Preferably, the Zhuang-Yao medicine compound medicine comprises the following raw materials in parts by weight: 58 parts of five-finger peach, 14 parts of iron drill, 28 parts of hairy holly, and 14 parts of saposhnikovia.

[0027] Preferably, the Zhuang-Yao medicine compound medicine comprises the following raw materials in parts by weight: 61 parts of five-finger peach, 17 parts of iron drill, 34 parts of hairy holly, and 18 parts of saposhnikovia.

[0028] This invention also provides a method for preparing a Zhuang-Yao medicine compound, comprising the following steps: weighing five-finger peach, iron drill, hairy holly, and saposhnikovia according to the weight proportions, and then putting the above four raw materials into water to make a medicinal liquid.

[0029] Preferably, the amount of water is 500ml.

[0030] This invention also provides the application of a Zhuang-Yao medicine compound in the treatment of acute ischemic stroke. The resulting liquid is taken orally twice a day, 100ml each time.

[0031] Preferably, a course of treatment lasts one month.

[0032] Compared with the prior art, the present invention has the following technical advantages:

[0033] 1. Unique treatment philosophy and remarkable efficacy

[0034] This invention focuses on clearing blockages and stagnation of toxins and pathogens in the "dragon" and "fire" pathways, demonstrating remarkable efficacy in the acute phase of ischemic stroke. In traditional medicine, the "dragon" and "fire" pathways are considered vital energy channels in the human body; when these channels are blocked by toxins and pathogens, various diseases can result. The medicine of this invention effectively improves the symptoms of ischemic stroke patients by precisely clearing these pathways.

[0035] Compared to Western medicine, the formula of this invention is simple yet delivers powerful therapeutic effects. Western medicine often has significant side effects when treating ischemic stroke, such as gastrointestinal discomfort and liver and kidney damage. Furthermore, long-term use of Western medicine can easily lead to drug resistance, gradually reducing its effectiveness. In contrast, the medicine of this invention fully utilizes the advantages of traditional Chinese medicine, with fewer side effects and a lighter burden on the patient's body. Simultaneously, due to its unique mechanism of action, it is less likely to induce drug resistance, providing patients with long-term and stable therapeutic effects.

[0036] 2. Excellent clinical efficacy and high safety profile

[0037] This invention presents a unique clinical formula composed of Zhuang and Yao medicinal herbs that clear blockages and stagnation of toxins and pathogens in the blood and energy pathways. This formula has demonstrated remarkable efficacy in treating the acute phase of ischemic stroke. Extensive clinical practice has proven that this formula can significantly improve patients' symptoms, such as limb numbness, speech difficulties, and dizziness. Its efficacy is definite and stable, bringing tangible health benefits to patients.

[0038] In terms of safety, the medicine of this invention has unparalleled advantages. Because it uses natural Zhuang and Yao medicines and contains no chemical components, it has no toxic side effects. Patients do not need to worry about adverse effects on their bodies during use and can receive treatment with peace of mind. This is undoubtedly a great boon for patients who are physically weak or have poor drug tolerance.

[0039] 3. It has outstanding comprehensive advantages and broad application prospects.

[0040] The Zhuang-Yao herbal compound medicine of this invention has many advantages, making it promising for the treatment of acute ischemic stroke. Firstly, the medicine is inexpensive, alleviating the financial burden on patients. This advantage is particularly important given the current rising medical costs. Secondly, its ease of use is another key feature. Patients can choose from various methods such as oral administration or topical application, based on their doctor's advice, without requiring complicated procedures.

[0041] Furthermore, the drug of this invention exhibits significant therapeutic effects, rapidly alleviating patients' symptoms and improving their quality of life. Simultaneously, its mechanism of action in clearing blockages and stagnation of toxins and pathogens in the meridian pathways provides new insights and methods for treating other diseases related to meridian obstruction. Finally, the drug's preparation process is simple and easy for large-scale production. This not only ensures drug quality and supply but also reduces production costs, further improving drug accessibility.

[0042] In summary, this invention possesses significant technical advantages in treating the acute phase of ischemic stroke. Its unique treatment concept, excellent clinical efficacy, high safety profile, and comprehensive advantages make it a treatment method with broad application prospects. It is believed that in future clinical practice, this invention will bring hope and benefits to more patients with ischemic stroke. Attached Figure Description

[0043] Figure 1 This is a functional analysis diagram of differentially expressed mRNAs in the brain tissue of rats with cerebral ischemia-reperfusion injury induced by Zhuang-Yao compound drugs. Detailed Implementation

[0044] The technical solutions in the preferred embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0045] In this embodiment of the invention, a Zhuang-Yao medicine compound for treating the acute phase of ischemic stroke comprises the following raw materials in parts by weight: 55-62 parts of *Ficus hirta*, 12-17 parts of *Ilex cornuta*, 26-35 parts of *Ilex pubescens*, and 13-18 parts of *Saposhnikovia divaricata*. After adding the above four raw materials to 500ml of water to prepare the liquid, 200mL is taken orally twice daily after meals.

[0046] To make the present invention more fully disclosed, the present invention will be further explained below with reference to specific embodiments.

[0047] I. Examples and Comparative Examples

[0048] Example 1

[0049] A Zhuang-Yao medicine compound medicine includes the following raw materials in parts by weight: 56 parts of five-finger peach, 12 parts of iron drill, 27 parts of hairy holly, and 13 parts of saposhnikovia.

[0050] Preparation method: After adding 500ml of water, the raw materials are made into a medicinal liquid. Take 200mL and drink it warm twice a day after meals.

[0051] The method of use of this invention is as follows: take orally, twice a day, 100ml each time, for one month as a course of treatment.

[0052] Example 2

[0053] A Zhuang-Yao medicine compound medicine includes the following raw materials in parts by weight: 58 parts of five-finger peach, 14 parts of iron drill, 28 parts of hairy holly, and 14 parts of saposhnikovia.

[0054] Preparation method: After adding 500ml of water, the raw materials are made into a medicinal liquid. Take 200mL and drink it warm twice a day after meals.

[0055] The method of use of this invention is as follows: take orally, twice a day, 100ml each time, for one month as a course of treatment.

[0056] Example 3

[0057] A Zhuang-Yao medicine compound medicine includes the following raw materials in parts by weight: 60 parts of five-finger peach, 15 parts of iron drill, 30 parts of hairy holly, and 15 parts of saposhnikovia.

[0058] Preparation method: After adding 500ml of water, the raw materials are made into a medicinal liquid. Take 200mL and drink it warm twice a day after meals.

[0059] The method of use of this invention is as follows: take orally, twice a day, 100ml each time, for one month as a course of treatment.

[0060] Example 4

[0061] A Zhuang-Yao medicine compound medicine includes the following raw materials in parts by weight: 59 parts of five-finger peach, 16 parts of iron drill, 28 parts of hairy holly, and 15 parts of saposhnikovia.

[0062] Preparation method: After adding 500ml of water, the raw materials are made into a medicinal liquid. Take 200mL and drink it warm twice a day after meals.

[0063] The method of use of this invention is as follows: take orally, twice a day, 100ml each time, for one month as a course of treatment.

[0064] Example 5

[0065] A Zhuang-Yao medicine compound medicine includes the following raw materials in parts by weight: 61 parts of five-finger peach, 17 parts of iron drill, 34 parts of hairy holly, and 18 parts of saposhnikovia.

[0066] Preparation method: After adding 500ml of water, the raw materials are made into a medicinal liquid. Take 200mL and drink it warm twice a day after meals.

[0067] The method of use of this invention is as follows: take orally, twice a day, 100ml each time, for one month as a course of treatment.

[0068] Comparative Example 1

[0069] A Zhuang-Yao medicine compound medicine includes the following raw materials in parts by weight: 30 parts of five-finger peach, 6 parts of iron drill, 50 parts of hairy holly, and 25 parts of saposhnikovia.

[0070] Preparation method: After adding 500ml of water, the raw materials are made into a medicinal liquid. Take 200mL and drink it warm twice a day after meals.

[0071] The method of use of this invention is as follows: take orally, twice a day, 100ml each time, for one month as a course of treatment.

[0072] Comparative Example 2

[0073] A Zhuang-Yao medicine compound medicine includes the following raw materials in parts by weight: 70 parts of five-finger peach, 6 parts of iron drill, 50 parts of hairy holly, and 7 parts of saposhnikovia.

[0074] Preparation method: After adding 500ml of water, the raw materials are made into a medicinal liquid. Take 200mL and drink it warm twice a day after meals.

[0075] The method of use of this invention is as follows: take orally, twice a day, 100ml each time, for one month as a course of treatment.

[0076] Comparative Example 3

[0077] A Zhuang-Yao medicine compound medicine includes the following raw materials in parts by weight: 70 parts of five-finger peach, 30 parts of iron drill, 15 parts of hairy holly, and 6 parts of saposhnikovia.

[0078] Preparation method: After adding 500ml of water, the raw materials are made into a medicinal liquid. Take 200mL and drink it warm twice a day after meals.

[0079] The method of use of this invention is as follows: take orally, twice a day, 100ml each time, for one month as a course of treatment.

[0080] II. Application Examples

[0081] Mr. Zhang, male, 68 years old, from Liuzhou City, presented with hemiplegia, facial paralysis, and choking when drinking. He was clinically diagnosed with ischemic stroke. After one course of treatment according to Example 1 of this invention, the hemiplegia and choking when drinking were alleviated.

[0082] Mr. Gan, male, 58 years old, from Hezhou City, had difficulty speaking, facial paralysis, and unresponsive eyes. He was clinically diagnosed with ischemic stroke. After one course of treatment with medication according to Example 2 of this invention, his difficulty speaking and facial paralysis were relieved.

[0083] Cai Moumou, female, 64 years old, from Nanning. The patient had hemiplegia, slurred speech, and headache. The clinical diagnosis was ischemic stroke. After 1 course of treatment with the medicine according to Example 3 of the present invention, the slurred speech and headache at the affected area were alleviated.

[0084] III. Animal experiments

[0085] 1. Experimental materials

[0086] 1.1 Experimental animals

[0087] The animals were from the Scientific Experiment Center of Guangxi University of Chinese Medicine. The Sprague Dawley (SD) rats used in the experiment were male, SPF grade, about 8 weeks old, and there were 21 of them. The animals were raised under specific pathogen free (SPF) safety conditions. The breeding environment was maintained at 22±2°C, the relative humidity was maintained at 50%-60%, the artificial light mimicked the natural conditions with 12 hours of light and 12 hours of darkness each, and sufficient food and water were provided during feeding. All experimental operators had the "Certificate of Qualification for Experimental Animal Professional Technology Examination". All animal experiments complied with the relevant regulations of the "Ethical Certificate for Experimental Animals". The production license number of the experimental animals was SCXK(Xiang)2019-0004, and it was approved by the Ethics Committee of Guangxi University of Chinese Medicine (Ethical number DW20200511-078).

[0088] 1.2 Drug preparation

[0089] The Zhuang and Yao medicine compound preparation of Example 3: 60 parts of Ficus hirta, 15 parts of Vitis heyneana, 30 parts of Ilex pubescens, 15 parts of Saposhnikovia divaricata; all the drugs were single-herb concentrated granules provided by Peili (Nanning) Pharmaceutical Co., Ltd. Each pack of granules was equivalent to the same conversion ratio of one dose of the Zhuang and Yao medicine compound preparation slices, and the batch numbers were: A200151410, A210055200, A2101630'10, A210848210, A210173610, A190031032, A200113610, A210175010.

[0090] Nimodipine tablets: provided by Sichuan Kelun Pharmaceutical Co., Ltd., product number B210301B21, specification 20mg*50 tablets / bottle.

[0091] 2 Experimental methods

[0092] 2.1 Grouping of experimental animals

[0093] The dosage reference algorithm for Zhuang-Yao compound medicine is as follows: Based on the adult (60kg) taking 156g of raw Zhuang-Yao compound medicine per day, and referring to the conversion factor between animal and human body weight, the dosage for rats (weighing about 280-300g) is 22g / kg. Therefore, 44g / kg is set as the high dose of Zhuang-Yao compound medicine.

[0094] (1) Sham surgery group: Rats underwent ischemic surgery of the middle cerebral artery, but no suture was inserted. They were fed normally and had free access to water.

[0095] (2) Model group: The following animal modeling method was used to establish the model. After successful modeling, the rats were gavaged for 2 hours and injected with the same volume of physiological saline as the Zhuangyao compound drug intervention group. After 7 consecutive days, the rats were fed normally and allowed free access to water.

[0096] (3) Zhuang and Yao medicine compound drug intervention group: The high-dose group was modeled according to the following animal modeling method. Two hours after modeling, the Zhuang and Yao medicine compound drug was administered by gavage at a dose of 44g / kg / d for 7 consecutive days, once a day.

[0097] Rats were grouped by labeling their tails. All three groups required successful model establishment, and rats that did not meet the inclusion and exclusion criteria were excluded. Animal observation was conducted after the required interventions for each group were completed.

[0098] 2.2 Dosing regimen for experimental animals

[0099] Take 8 packets of Zhuang-Yao compound herbal medicine granules, dissolve them in sterile water, and dilute to 100ml in a graduated cylinder to prepare a high-dose oral administration solution. Subsequent preparations should follow the same method. Store the prepared solution at 4℃. Remove it 1 hour before use and allow it to reach room temperature. Administer 4.5ml orally to each rat according to the experimental grouping regimen, once daily for 7 consecutive days.

[0100] 2.3 Animal Modeling (MCAO Method)

[0101] A rat model of MCAO (middle cerebral artery aspiration disorder) was established by embolizing the right middle cerebral artery using the suture occlusion method. The modeling steps are briefly described below, referencing relevant literature and our laboratory methods:

[0102] (1) The experimental animals were anesthetized with sodium pentobarbital. Two people performed intraperitoneal anesthesia (40mg / kg). The neck was shaved and the skin was prepared.

[0103] (2) The patient is placed in a supine position and fixed to a fixation board. An incision is made along the midline of the neck, and the three arteries are separated along the inner edge of the sternocleidomastoid muscle: the left common carotid artery, the external carotid artery, and the internal carotid artery. The common carotid artery is selected, and sutures are placed at the distal and proximal ends on the left side and at the bifurcation of the external carotid artery for later use.

[0104] (3) Use a micro-artery clamp to briefly clamp the branched internal carotid artery, and then use silk thread to ligate the proximal ends of the left common carotid artery and external carotid artery. Then, make a small incision 4 mm away from the bifurcation of the left common carotid artery, just enough to insert the ligature, and push it to the internal carotid artery. At this time, use a thin thread wrapped around the distal end of the left common carotid artery to fix its position and gently tie the ligature.

[0105] (4) Use fine ophthalmic forceps to gently push the suture. When the insertion depth is 18mm, the distance is calculated from the bifurcation of the blood vessel. Tightly tie the thin suture at the distal end.

[0106] (5) Ligate and fix the suture plug and external carotid artery for 40 minutes, then pull out the suture plug to the external carotid artery and tighten the external carotid artery again to prevent bleeding. Finally, suture the skin to achieve cerebral ischemia-reperfusion.

[0107] 3 Results

[0108] Functional analysis of differentially expressed mRNAs in brain tissue of rats with cerebral ischemia-reperfusion injury induced by Zhuang-Yao herbal compound drugs

[0109] GO functional enrichment analysis revealed that after intervention with Zhuang-Yao herbal compound drugs, the upregulated differentially expressed genes in brain tissue were mainly enriched in the Wnt pathway, DNA-binding transcription factor activity, nervous system development, and G protein-coupled purinergic nucleotide receptor activity; while the downregulated differentially expressed genes were mainly enriched in pathways such as inflammatory response, extracellular region, chemokine activity, cytokine receptor activity, and virion assembly. Figure 1 As shown.

[0110] GO enrichment analysis

[0111] (A): Compared with the Model group, FYFH showed downregulated gene enrichment in GO; (B): Compared with the Model group, FYFH showed upregulated gene enrichment in GO.

[0112] IV. Clinical Research

[0113] 1. Medical records

[0114] 1.1 Number of participants

[0115] 120 patients with ischemic stroke were selected.

[0116] 1.2 Diagnostic criteria

[0117] 1.2.1 Diagnostic criteria for ischemic stroke

[0118] The diagnostic criteria for stroke shall be implemented in accordance with the "Diagnostic Criteria for Stroke" formulated by the Brain Disease Emergency Collaboration Group of the Department of Medical Administration of the State Administration of Traditional Chinese Medicine.

[0119] Diagnostic criteria for stroke:

[0120] (1) Main symptoms: hemiplegia, clouded consciousness, slurred speech or aphasia, abnormal sensation on one side of the body, and facial paralysis.

[0121] (2) Secondary symptoms: headache, dizziness, pupillary changes, choking when drinking water, unblinking eyes, ataxia;

[0122] (3) Onset: Acute onset, often with precipitating factors before onset, and often with prodromal symptoms;

[0123] (4) Age of onset: mostly over 40 years old.

[0124] A diagnosis can be made if two or more primary symptoms are present, or one primary symptom and two secondary symptoms are present, combined with the onset, triggering factors, prodromal symptoms, age, and imaging examination results.

[0125] 1.3 Case Inclusion Criteria

[0126] (1) Meets the diagnostic criteria for ischemic stroke in both traditional Chinese and Western medicine;

[0127] (2) Age between 45 and 75 years old;

[0128] (3) No traditional Chinese medicine preparations or decoctions or related Western medicines for treating stroke have been used since the onset of this illness;

[0129] (4) With the approval of the hospital's ethics committee, each enrolled patient must sign an informed consent form.

[0130] 1.4 Case Exclusion Criteria

[0131] Except for those who meet one of the following conditions:

[0132] (1) TIA;

[0133] (2) Patients who developed hemorrhage after cerebral infarction;

[0134] (3) Cerebral embolism caused by brain trauma, intracranial tumor, intracranial parasitic disease, atrial fibrillation, etc.

[0135] (4) Individuals with allergies;

[0136] (5) Individuals with underlying diseases of the liver, kidneys, metabolic system, and blood system, making it difficult to evaluate the safety of the study;

[0137] (6) Mentally ill patients who are unable to express themselves accurately.

[0138] 1.5 Rejection and Shedding Criteria

[0139] (1) Cases that do not meet the inclusion criteria or were mistakenly included;

[0140] (2) The subject's condition did not reach the expected level of control within a certain period of time;

[0141] (3) Factors that affect the determination of efficacy, such as failure to use medication as prescribed or incomplete clinical data;

[0142] (4) For various reasons, the subject requested to withdraw from the trial;

[0143] (5) Those who develop other serious complications during the research process;

[0144] (6) Taking other medications during the study that may affect the evaluation of efficacy.

[0145] 2. Methods

[0146] 2.1 Treatment methods

[0147] 330 patients with ischemic stroke were randomly divided into 11 groups, with 30 patients in each group.

[0148] Control group 1: Aspirin enteric-coated tablets (Bayer Pharmaceuticals, Germany, batch number: J20171021) were administered orally, 100 mg once a day.

[0149] Control group 2: Intravenous infusion of edaravone injection (Nanjing Xiansheng Dongyuan Pharmaceutical Co., Ltd., batch number: National Drug Approval Number H20031342), 10mL / time, once a day;

[0150] Control group 3: Oral administration of butylphthalide soft capsules (CSPC Enbipu Pharmaceutical Co., Ltd., batch number: National Drug Approval Number H20050299), 0.2g / time, 3 times / day;

[0151] Control group 4: In addition to the treatment given to control group 1, the Zhuang-Yao medicine compound and treatment method of control group 1 were used.

[0152] Control group 5: In addition to the treatment given to control group 1, the Zhuang and Yao medicine compound drugs and methods of control group 2 were used for treatment;

[0153] Control group 6: In addition to the treatment given to control group 1, the Zhuang-Yao medicine compound and treatment method of control group 3 were used.

[0154] Observation group 1: In addition to the treatment given to control group 1, the Zhuang-Yao medicine compound and method of Example 1 of this invention were used for treatment;

[0155] Observation group 2: In addition to the treatment given to control group 1, the Zhuang-Yao medicine compound and method of Example 2 of this invention were used for treatment;

[0156] Observation group 3: In addition to the treatment given to control group 1, the Zhuang-Yao medicine compound drug and method of Example 3 of this invention were used for treatment;

[0157] Observation group 4: In addition to the treatment given to control group 1, the Zhuang-Yao medicine compound drug and method of Example 4 of this invention were used for treatment;

[0158] Observation group 5: In addition to the treatment given to control group 1, the Zhuang-Yao medicine compound drug and method of Example 5 of this invention were used for treatment.

[0159] Each control group or observation group received treatment for 8 weeks.

[0160] During treatment, a light diet is recommended, avoiding spicy and irritating foods; all medications that may interfere with the research results should be avoided.

[0161] 2.2 Observation indicators and scoring criteria

[0162] 2.2.1 Degree of neurological deficit

[0163] The scoring criteria for the degree of neurological deficit were based on the National Institutes of Health Stroke Scale (NIHSS) scoring criteria.

[0164] 2.2.2 Daily Living Skills

[0165] The scoring criteria for activities of daily living are based on the Barthel Index (BI) rating scale.

[0166] 2.2.3 Assessment of the degree of disability

[0167] The assessment of the degree of disability was based on the standard of the modified Rankin Scale (mRS).

[0168] 2.2.4 Quality of Life Assessment

[0169] The WHO-recommended quality of life scale was used.

[0170] 2.2.5 Traditional Chinese Medicine Syndrome Scoring

[0171] Based on the "Stroke Symptom Grading and Quantification Table" in the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines," the following evaluation indicators were proposed: dizziness, headache, limb numbness, limb stiffness, and shortness of breath and weakness. No symptoms were scored as 0 points; mild and tolerable symptoms as 2 points; severe symptoms affecting daily life as 4 points; and severe and unbearable symptoms as 6 points.

[0172] 2.2.6 Blood lipids

[0173] Measure the levels of TC, TG, HDL-C, and LDL-C.

[0174] 2.1.7 Adverse Reactions

[0175] Observe the patient's blood, urine, and stool routine tests, coagulation function, myocardial enzymes, liver and kidney function, electrocardiogram and other indicators.

[0176] 2.3 Evaluation of therapeutic effect

[0177] The scoring criteria for neurological deficits in stroke patients were developed with reference to the 4th National Conference on Cerebrovascular Diseases.

[0178] Cured: Symptoms and signs have basically disappeared, the person can take care of themselves, and the degree of disability is level 0;

[0179] Significant improvement: Symptoms and signs are significantly improved, the neurological deficit score is reduced by ≥21 points, and the degree of disability is grade 1-3;

[0180] Effective: Symptoms and signs significantly improved, and neurological deficit scores decreased by 8-20 points;

[0181] Ineffective: Symptoms and signs did not improve significantly before and after medication, and the neurological deficit score decreased by <8 points.

[0182] Effectiveness rate = (Number of cured cases + Number of cases with significant improvement + Number of cases with improvement) / Total number of cases × 100%.

[0183] 2.4 Combined medication

[0184] Avoid using traditional Chinese medicine preparations for treating ischemic stroke. Symptomatic treatment may be administered for other complications, provided it does not affect the evaluation of the efficacy of the research drug.

[0185] 2.5 Data Processing

[0186] Statistical analysis was performed using SPSS 24.0 software. t-tests were used for continuous data, chi-square tests for categorical data, and Ridit tests for ordinal data. A p-value greater than 0.05 was considered statistically insignificant, a p-value less than 0.05 was considered statistically significant, and a p-value less than 0.01 was considered highly significant.

[0187] 3. Results

[0188] 3.1 Symptoms and therapeutic effects in Traditional Chinese Medicine

[0189] After treatment, the quality of life scores and TCM syndrome scores of all four groups were significantly improved compared with those before treatment (P<0.05). The improvement in the observation group was better than that in the control group, and the difference was statistically significant (P<0.05).

[0190] Group Cure / person Effective / person Effective / person Ineffective / person Cure rate / % Effective rate / % Control group 1 14 5 4 7 46.7 76.7 Control group 2 16 7 2 5 53.3 83.3 Control group 3 15 6 3 6 50.0 80.0 Control group 4 17 7 1 5 56.7 83.3 Control group 5 19 6 1 4 63.3 86.6 Control group 6 18 5 2 5 60.0 83.3 Observation group 1 22 4 1 3 73.3 90.0 Observation group 2 23 2 3 2 76.7 93.3 Observation group 3 25 3 1 1 83.3 96.7 Observation group 4 24 3 1 2 80.0 93.3 Observation group 5 23 1 3 3 76.7 90.0

[0191] As can be seen from the above table: (1) Based on the control group and combined with the Zhuangyao medicine compound of the present invention, the cure rate and effective rate can be significantly improved. This phenomenon fully demonstrates that the combination of Ficus hirta, Vitis flexuosa, Ilex pubescens, and Saposhnikovia divaricata can produce a synergistic effect, thereby greatly enhancing the medicinal efficacy and significantly increasing the cure rate and effective rate. Specifically, Ficus hirta has the effects of strengthening the spleen and tonifying the lung, promoting qi circulation and removing dampness; Vitis flexuosa can dispel wind and dampness, promote blood circulation and relieve pain; Ilex pubescens has the effects of clearing heat and detoxifying, promoting blood circulation and dredging meridians; Saposhnikovia divaricata can relieve exterior syndrome by dispelling wind, eliminating dampness and relieving pain. The characteristics of these several drugs complement and promote each other, jointly exerting a more powerful therapeutic effect and bringing better treatment effects to patients.

[0192] (2) From the comparison of the cure rate and effective rate between Observation Groups 1-5 and Control Groups 4-6, when the dosage ratio of Ficus hirta, Vitis flexuosa, Ilex pubescens, and Saposhnikovia divaricata is not within the range of (55-62):(12-17):(26-35):(13-18), the cure rate shows a very significant decline, and the effective rate also decreases. This result clearly indicates that it is crucial to strictly control the dosage ratio of Ficus hirta, Vitis flexuosa, Ilex pubescens, and Saposhnikovia divaricata in the formula of the present invention to be (55-62):(12-17):(26-35):(13-18). Only at this specific dosage ratio can these several drugs give full play to their respective advantages, cooperate with each other, achieve the best therapeutic effect, and significantly increase the cure rate and effective rate. For example, if the dosage of Ficus hirta is too much or too little, it may affect the effect of strengthening the spleen and tonifying the lung of the entire compound medicine, thus unable to provide a good basis for the play of other drugs; an inappropriate dosage of Vitis flexuosa may lead to a weakened effect of dispelling wind and dampness, promoting blood circulation and relieving pain, affecting the overall therapeutic effect; improper dosage ratios of Ilex pubescens and Saposhnikovia divaricata will also prevent the full play of the effects of clearing heat and detoxifying, promoting blood circulation and dredging meridians, and relieving exterior syndrome by dispelling wind, eliminating dampness and relieving pain. Therefore, precisely controlling the dosage ratio of these several drugs is crucial for improving the therapeutic effect.

[0193] The above description is only the preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention can have various modifications and changes. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. A preparation method of a Yao ethnic group's compound medicine for treating ischemic stroke in acute stage, characterized in that, It comprises the following steps: Take Ficus tikovii, iron drill, Ilex hainanensis, and Saposhnikovia divaricata by weight, then put the above four raw materials into 500ml of water, and the raw materials are made into medicinal liquid; The Zhuang Yao medicine compound medicine is composed of the following raw materials in weight: Ficus tikovii 60 parts, iron drill 15 parts, Ilex hainanensis 30 parts, and Saposhnikovia divaricata 15 parts.

2. A preparation method of a Yao medicinal compound for treating ischemic stroke in acute phase, characterized in that, It comprises the following steps: Take Ficus tikovii, iron drill, Ilex hainanensis, and Saposhnikovia divaricata by weight, then put the above four raw materials into 500ml of water, and the raw materials are made into medicinal liquid; The Zhuang Yao medicine compound medicine is composed of the following raw materials in weight: Ficus tikovii 56 parts, iron drill 12 parts, Ilex hainanensis 27 parts, and Saposhnikovia divaricata 13 parts.

3. A preparation method of a Yao medicinal compound for treating ischemic stroke in acute phase, characterized in that, It comprises the following steps: Take Ficus tikovii, iron drill, Ilex hainanensis, and Saposhnikovia divaricata by weight, then put the above four raw materials into 500ml of water, and the raw materials are made into medicinal liquid; The Zhuang Yao medicine compound medicine is composed of the following raw materials in weight: Ficus tikovii 59 parts, iron drill 16 parts, Ilex hainanensis 28 parts, and Saposhnikovia divaricata 15 parts.

4. A preparation method of a Yao medicinal compound for treating ischemic stroke in acute phase, characterized in that, It comprises the following steps: Take Ficus tikovii, iron drill, Ilex hainanensis, and Saposhnikovia divaricata by weight, then put the above four raw materials into 500ml of water, and the raw materials are made into medicinal liquid; The Zhuang Yao medicine compound medicine is composed of the following raw materials in weight: Ficus tikovii 58 parts, iron drill 14 parts, Ilex hainanensis 28 parts, and Saposhnikovia divaricata 14 parts.

5. A preparation method of a Yao medicinal compound for treating ischemic stroke in acute phase, characterized in that, It comprises the following steps: Take Ficus tikovii, iron drill, Ilex hainanensis, and Saposhnikovia divaricata by weight, then put the above four raw materials into 500ml of water, and the raw materials are made into medicinal liquid; The Zhuang Yao medicine compound medicine is composed of the following raw materials in weight: Ficus tikovii 61 parts, iron drill 17 parts, Ilex hainanensis 34 parts, and Saposhnikovia divaricata 18 parts.

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