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

Abstract

The invention belongs to the field of treatment of acute ischemic stroke by Yao-strengthening medicines, and discloses a Yao-strengthening medicine compound medicine, a preparation method and application of the Yao-strengthening medicine compound medicine in treatment of acute ischemic stroke, the Yao-strengthening medicine compound medicine is prepared from the following raw materials in parts by weight: 55-62 parts of radix fici simplicissimae, 12-17 parts of radix aconiti, 26-35 parts of radix ilicis pubescentis and 13-18 parts of radix saposhnikoviae. After the four raw materials are put into clear water, liquid medicine is prepared from the raw materials, and the Zhuang Yao medicine compound medicine is obtained. The Zhuang Yao medicine compound medicine has the characteristics of low price, convenience in use, remarkable curative effect, dredging of toxic and pathogenic stasis of a dragon road and a fire road, small toxic and side effects and simple preparation process.

Description

Technical Field

[0001] The invention belongs to the field of Zhuang-Yao medicine for treating acute ischemic stroke, and specifically relates to a Zhuang-Yao medicine compound medicine, a preparation method and application thereof in treating acute ischemic stroke. Technical Background

[0002] Acute ischemic stroke (AIS), known as acute cerebral infarction in modern medicine, is a common clinically critical cerebrovascular disease. After acute ischemia, the brain tissue has local blood circulation disorders and insufficient blood supply, which leads to ischemic hypoxic necrosis and dysfunction of the nervous system. Clinically, limb paralysis, speech blockage or even aphasia, and consciousness disorders in severe cases can be seen, which imposes a serious burden on families and society. my country is one of the high-incidence areas of cerebrovascular disease, and it is currently the second leading cause of death2. The incidence of acute ischemic stroke has been significantly higher in the middle-aged and elderly population in recent years, especially in the elderly population. The older they are, the more serious their underlying diseases such as hypertension and coronary heart disease are, and the higher the incidence of ischemic stroke. This disease has a high mortality rate and disability rate, which has a serious impact on the patient's life safety, self-care ability, and quality of life. Common measures for the treatment of acute ischemic stroke include thrombolytic therapy, surgical treatment, and interventional treatment, among which thrombolytic therapy and surgical treatment are relatively frequently used in clinical practice. Thrombolytic therapy includes arterial thrombolytic therapy and intravenous thrombolytic therapy. Although both have a significant effect on improving patients' stroke and infarction symptoms, arterial thrombolytic therapy has a relatively high risk. Surgical treatment mainly refers to intravascular embolectomy, which can timely eliminate the patient's thrombosis symptoms to fully improve the blood circulation in the brain and protect the brain tissue function as much as possible. Various treatment measures have different treatment methods and effects. Therefore, it is of great significance to intervene in acute ischemic stroke in a timely and effective manner, promote the recovery of patients' neurological function, minimize the impact of disability, and enable patients to return to their families and society as soon as possible.

[0003] The blood-brain barrier (BBB) ​​is mainly composed of endothelial cells, pericytes, astrocytes and extracellular matrix. Its highly selective permeability can prevent harmful substances such as pathogens and inflammatory factors from damaging the central nervous system (CNS), thereby protecting and maintaining the normal function and homeostasis of the CNS. Damage to the BBB is the most important initiating factor for cerebral ischemia-reperfusion injury and the main cause of various complications. The high "selectivity" of the BBB for surrounding substances can ensure the normal exchange of substances and charge balance between the CNS and the blood, and ensure that neurons can perform their physiological functions normally. In addition, the BBB can also block macromolecules such as pathogens, immune cells and toxins in the blood to protect nerve tissue. In the process of cerebral ischemia-reperfusion injury, the BBB is damaged before the surrounding neurons, which then increases the permeability of cerebral blood vessels and loses selectivity for substances, resulting in the infiltration of various vascular contents into the nerve tissue, causing vasogenic cerebral edema and increased intracranial pressure. In severe cases, intracranial hemorrhage may occur. In addition, many neurotoxic substances in blood vessels (such as thrombin, glutamate, albumin, etc.) can enter the brain tissue through the damaged BBB, further aggravating nerve damage. Therefore, protecting the BBB is the key treatment point in preventing cerebral hemorrhage-reinjection injury.

[0004] Since the damage of BBB after cerebral ischemia-reperfusion is related to multiple pathological mechanisms such as free radical damage, inflammatory infiltration, calcium ion overload, neural apoptosis, excitatory amino acid toxicity, etc., the pathological process formed is extremely complex and changeable. At present, modern medicine often uses the above single pathological factors as therapeutic targets to prevent and treat cerebral ischemia-reperfusion injury, which makes it difficult to achieve satisfactory clinical efficacy. Recent studies have found that Chinese medicine, as a natural compound, can treat diseases through multiple pathways and multiple targets, especially compound preparations of multiple drugs, which highlight the characteristics of Chinese medicine in treating this disease, and its efficacy is also better than that of single use of Western medicine.

[0005] For example, a Chinese patent document (publication number: CN108567920A) discloses a Chinese medicine composition for treating acute ischemic stroke, which is composed of an effective ingredient and a medically acceptable excipient, wherein the effective ingredient is made of the following raw materials in percentage by weight: 10.4-11.5% of rhubarb, 10.4-11.5% of siler, 26.0-28.7% of gardenia, 1.6-1.7% of artificial bezoar, 10.4-11.5% of turmeric, 10.4-11.5% of magnolia bark, 10.4-11.5% of red peony root, and 15.6-17.2% of knotweed. The Chinese medicine composition described in the invention can be a tablet, a granule or a capsule, and the Chinese medicine composition can treat acute ischemic stroke. However, the drug formula has many disadvantages. First, the formula contains a variety of drug ingredients, some of the medicinal materials are expensive, and are highly volatile when decocted, which requires very strict decocting and the process is relatively complicated. Secondly, the multi-component formula makes the effective ingredients relatively scarce. The numerous drug ingredients may interfere with each other, making it difficult for the effective ingredients to fully exert their effects, which in turn leads to poor treatment effects.

[0006] For another example, a Chinese patent application document (publication number: CN112791117A) discloses a formula for treating acute ischemic stroke, which is prepared from raw medicinal materials Angelica sinensis and Salvia miltiorrhiza. The invention can be used to treat acute ischemic stroke through a Chinese medicine composition, but there are only two components and there is also a problem of poor treatment effect. Summary of the invention

[0007] The present invention aims at the deficiencies of various existing western medicines for treating acute ischemic stroke and the problem of poor therapeutic effects of existing traditional Chinese medicines, and provides a Zhuang-Yao medicine compound medicine, a preparation method and its application in treating acute ischemic stroke. The Zhuang-Yao medicine compound medicine is cheap, easy to use, has significant efficacy, can dredge the toxic evil blood stasis of dragon path and fire path, has little toxic and side effects, and has a simple preparation process.

[0008] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0009] A Zhuang-Yao medicine compound medicine comprises the following raw materials in parts by weight: 55-62 parts of five-fingered peach, 12-17 parts of iron diamond, 26-35 parts of hairy holly and 13-18 parts of siler.

[0010] Technical principle of the present invention:

[0011] The characteristics of the raw materials used are as follows:

[0012] Five-fingered ginseng: It is the root of Ficus simplicissima Lour., a plant of the Moraceae family. Ficus simplicissima Lour. is distributed in Fujian, Guangdong, Guangxi, Hainan, Guizhou, Yunnan and other places in China, and also in Vietnam and Cambodia. It tastes sweet and is neutral in nature. It enters the spleen, lung and liver meridians. Efficacy: invigorates the spleen and lungs, promotes qi and eliminates dampness, relaxes muscles and activates collaterals. Indications: edema due to spleen deficiency, loss of appetite and weakness, cough due to tuberculosis, night sweats, leucorrhea, postpartum alacrity, rheumatic arthralgia, edema, ascites due to liver cirrhosis, hepatitis, and traumatic injuries.

[0013] Tiezuan: [Yao language] Jiaduan, [Yao language transliteration] hlieqc nzunx, [alias] cage vine, [source] is the root of Fissistigma oldhamii (Hemsl.) Merr. of the Annonaceae family. It is distributed in Fujian, Taiwan, Guangdong, Hunan, Jiangxi, Yunnan, Guangxi and other places. In Guangxi, it is distributed in Jinxiu, Rongshui, Lingchuan, Quanzhou, Fuchuan, Cenxi and other places. [Nature, flavor and efficacy] It is a spray medicine. It tastes spicy 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. It is used to treat acute stroke, arthritis and sciatica.

[0014] Ilex pubescens Hook.etAm.: [Yao language] Qiu Gongliang, [Yao language transliteration] couh gong ndiangx, [alias] fire-burned wood, black-tailed lily, hairy tree, fine-leaved holly, mountain bear gall, sour wood, ant tree, small baijie, [source] the whole plant of Ilex pubescens Hook.etAm. of the Aquifoliaceae family. [properties and effects] bitter, astringent, cool in nature. Clears away heat and detoxifies, promotes blood circulation and dredges the meridians, reduces swelling and relieves pain. Used for colds and fever, pharyngitis, hepatitis, pneumonia, lung heat cough, rheumatic heart disease, coronary heart disease, thromboangiitis obliterans, acute suppurative inflammation of the skin, epigastric pain, dysentery, erysipelas, swelling and pain from falls, burns, scalds, and acute stroke.

[0015] Saposhnikovia divaricata (Turcz.) Schischk., a perennial herbaceous plant of the genus Saposhnikovia in the family Apiaceae. The taproot is conical and light yellow-brown. The stem is solitary. The petals are white and obovate. The fruit is narrowly elliptical or elliptical, with a slightly flat back, and the young fruit has spongy tumor-like protrusions. Nature and flavor: spicy and sweet, slightly warm. It enters the bladder, spleen, and liver meridians. Efficacy: dispel wind and relieve exterior symptoms, overcome dampness and relieve pain, and stop spasms. Indications: acute stroke, external symptoms, urticaria itching, rheumatic pain, tetanus, spleen deficiency and dampness.

[0016] The five-fingered peach, iron diamond, hairy holly and siler in the Zhuang and Yao medicine compound work together to play a unique and highly effective role, and are jointly dedicated to the treatment of the acute stage of ischemic stroke.

[0017] As the main drug, the five-fingered ginseng occupies a key position in the prescription. It has the function of replenishing qi, and can target the indiscriminate movement of the phase fire caused by the invisible qi deficiency, thereby avoiding the loss of qi and blood in the human body. Qi is the leader of blood, and the visible blood depends on the invisible qi for production. The five-fingered ginseng helps the vital energy, making the qi and blood biochemical active, and can open the dragon path, guide all the medicines directly to the clever place, regulate the human body's mental emotions and the core hub of qi and blood circulation, and lay the foundation for the whole prescription to strengthen the body and guide the meridians.

[0018] As a public medicine, Tiezuan belongs to the category of spray medicine, and has a strong power to promote blood circulation and remove blood stasis. In the acute stage of stroke, blood stasis is an important pathological link. Tiezuan can break the blockage of blood stasis and improve the blood circulation disorder in the brain. In combination with Wuzhimaotao, one replenishes and one clears, so that blood stasis can be dissipated while qi and blood are promoted, so that the stasis of dragon and fire paths can be effectively relieved, and the smooth flow of qi and blood can be restored.

[0019] The herb is made of hollyhock, which can further enhance blood circulation and cooperate with the herb to enhance the effect of promoting blood circulation and removing blood stasis. At the same time, it also has the functions of reducing swelling and relieving pain, clearing away heat and detoxifying, and can clear away brain edema, local pain and heat toxins caused by blood stasis that may accompany ischemic stroke. It works together with five-fingered ginseng and herb to improve various symptoms caused by toxic evil stasis.

[0020] As a guide drug, although Saposhnikovia divaricata itself has the effect of relieving pain and relieving spasms, its more important characteristic is its property as a lubricant for wind-clearing drugs. It can guide all drugs to the diseased area and enhance the resistance and treatment effect of the whole prescription against wind evil. Whether it is an invasion of external wind or internal wind disturbance (such as internal wind caused by qi and blood imbalance), Saposhnikovia divaricata can cooperate with other drugs to evacuate external wind and calm internal wind, achieving the effect of "blood circulation and wind extinguishing itself", so that the whole prescription can not only target external evil, but also regulate the wind movement caused by internal qi and blood abnormalities.

[0021] In terms of dosage, the dosage of five-fingered ginseng is controlled at 55-62 parts. As the main drug, its dosage is relatively large to give full play to its leading role in replenishing qi and unblocking meridians and guiding various drugs. If the dosage is too small, it will be difficult to bear the heavy responsibility of the main drug, and it will not be able to effectively replenish qi and help the essence and unblock the dragon road; if the dosage is too much, it may cause qi stagnation and affect the balance and coordination of qi and blood. The dosage of 12-17 parts of iron drill can not only ensure its blood circulation and stasis effect, but also will not break blood too much due to excessive dosage, which will damage the positive energy. 26-35 parts of hairy holly, this dosage can moderately exert its effects of promoting blood circulation and unblocking meridians, reducing swelling and detoxification, and synergize with five-fingered ginseng and iron drill. Improper dosage may affect the overall synergy and balance of drug efficacy. 13-18 parts of fangfeng, the right amount of fangfeng can just lead the medicine to the diseased area and regulate wind-related symptoms. Too little will lead the medicine and dispel wind insufficiently, and too much may cause the wind medicine to be too dry and damage yin and consume blood.

[0022] Through the precise dosage control and synergistic effect of these four herbs, the whole formula works together to unblock the dragon path and the fire path, allowing the "two paths" to resume normal operation, regulating the balance of the "three paths", promoting the orderly rise and fall of yin and yang in the human body, and harmonizing qi and blood. In the treatment of the acute stage of ischemic stroke, it overcomes the defects of Western medicine such as large side effects and easy drug resistance, carries forward the advantages of traditional Chinese medicine, and achieves remarkable and unexpected technical effects, providing an innovative and effective drug combination solution for symptom improvement and disease recovery in patients with ischemic stroke.

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

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

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

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

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

[0028] The present invention also provides a method for preparing a Zhuang-Yao medicine compound, comprising the following steps: weighing five-fingered peach, iron diamond, hairy holly, and siler according to weight, and then putting the above four raw materials into clear water to prepare a medicinal liquid.

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

[0030] The present invention also provides an application of a Zhuang-Yao medicine compound medicine in treating acute ischemic stroke. The obtained medicine liquid is taken orally, twice a day, with 100 ml taken orally each time.

[0031] Preferably, the treatment course is one month.

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

[0033] 1. Unique treatment concept and significant efficacy

[0034] The present invention takes the dredging of the toxic evil stagnation of the dragon path and the fire path as the core of treatment, and has excellent therapeutic effect on the acute stage of ischemic stroke. In traditional medicine, the dragon path and the fire path are regarded as important energy channels of the human body. When these channels are blocked by toxic evil stagnation, various diseases will be caused. The medicine of the present invention can effectively improve the symptoms of ischemic stroke patients by accurately dredging these channels.

[0035] Compared with Western medicine, the prescription of the present invention is simple but can exert a powerful therapeutic effect. Western medicine often has the problem of large side effects when treating ischemic stroke, such as gastrointestinal discomfort, liver and kidney damage, etc. Moreover, long-term use of Western medicine is also prone to drug resistance, which gradually reduces the therapeutic effect. The medicine of the present invention gives full play to the advantages of traditional Chinese medicine, has few side effects, and has a lighter physical burden on patients. At the same time, due to its unique mechanism of action, it is not easy to produce drug resistance, and can provide patients with long-term and stable therapeutic effects.

[0036] 2. Excellent clinical efficacy and high safety

[0037] The clinical characteristic prescription composed of Zhuangyao medicine for dredging the stagnation of toxic evil in the dragon path and the fire path has shown remarkable effects in treating acute ischemic stroke. A large number of clinical practices have proved that the prescription can significantly improve the symptoms of patients, such as limb numbness, speech difficulties, dizziness, etc. Its efficacy is accurate and stable, and can bring real health benefits to patients.

[0038] In terms of safety, the drug of the present invention has an incomparable advantage. Since it uses natural Zhuang Yao medicine and does not contain any chemical components, it has no toxic side effects. Patients do not need to worry about the adverse effects of the drug on the body during use and can receive treatment with confidence. This is undoubtedly a great blessing for those patients who are physically weak and have poor tolerance to drugs.

[0039] 3. Outstanding comprehensive advantages and broad application prospects

[0040] The Zhuangyao medicine compound medicine of the present invention has many advantages, which makes it have broad application prospects in the treatment of acute ischemic stroke. First, the medicine is low in price and can reduce the economic burden for the majority of patients. In the context of the current rising medical expenses, this advantage is particularly important. Secondly, it is easy to use. Patients can choose a variety of methods such as oral administration and external application for treatment according to the doctor's advice, without the need for complicated operations.

[0041] In addition, the drug of the present invention has significant curative effect, can quickly relieve the patient's symptoms, and improve the patient's quality of life. At the same time, its mechanism of action of dredging the stagnation of toxic evil in the dragon path and the fire path also provides new ideas and methods for treating other diseases related to meridian obstruction. Finally, the preparation process of the drug is simple and easy to mass produce. This can not only ensure the quality and supply of the drug, but also reduce production costs and further improve the accessibility of the drug.

[0042] In summary, the present invention has significant technical advantages in treating acute ischemic stroke. Its unique treatment concept, excellent clinical efficacy, high safety and comprehensive advantages make it a treatment method with broad application prospects. It is believed that in future clinical practice, the present invention will bring hope and good news to more ischemic stroke patients. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 This is a functional analysis diagram of differentially expressed mRNA in the brain tissue of rats with cerebral ischemia-reperfusion injury caused by Zhuang-Yao medicine compound drugs. DETAILED DESCRIPTION

[0043] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the preferred examples. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0044] In an embodiment of the present invention, a Zhuang-Yao medicine compound for treating acute ischemic stroke comprises the following raw materials in parts by weight: 55-62 parts of five-fingered peach, 12-17 parts of iron diamond, 26-35 parts of hairy holly, and 13-18 parts of windproof. After the above four raw materials are put into 500 ml of clean water, the raw materials are made into a liquid medicine, and 200 ml is taken warm twice a day after meals in the morning and evening.

[0045] In order to make the disclosure of the present invention more complete, the present invention is further illustrated below in conjunction with specific embodiments.

[0046] 1. Examples and Comparative Examples

[0047] Example 1

[0048] A Zhuang-Yao medicine compound medicine comprises the following raw materials in parts by weight: 56 parts of five-fingered peach, 12 parts of iron diamond, 27 parts of hairy holly and 13 parts of siler.

[0049] Preparation method: After adding 500ml of clean water, after the raw materials are made into liquid medicine, take 200ml and take it warm twice a day, morning and evening, after meals.

[0050] The method of using the invention is: oral administration, twice a day, 100 ml each time, and one month as a course of treatment.

[0051] Example 2

[0052] A Zhuang-Yao medicine compound medicine comprises the following raw materials in parts by weight: 58 parts of five-fingered peach, 14 parts of iron diamond, 28 parts of hairy holly, and 14 parts of siler.

[0053] Preparation method: After adding 500ml of clean water, after the raw materials are made into liquid medicine, take 200ml and take it warm twice a day, morning and evening, after meals.

[0054] The method of using the invention is: oral administration, twice a day, 100 ml each time, and one month as a course of treatment.

[0055] Example 3

[0056] A Zhuang-Yao medicine compound medicine comprises the following raw materials in parts by weight: 60 parts of five-fingered peach, 15 parts of iron diamond, 30 parts of hairy holly and 15 parts of siler.

[0057] Preparation method: After adding 500ml of clean water, after the raw materials are made into liquid medicine, take 200ml and take it warm twice a day, morning and evening, after meals.

[0058] The method of using the invention is: oral administration, twice a day, 100 ml each time, and one month as a course of treatment.

[0059] Example 4

[0060] A Zhuang-Yao medicine compound medicine comprises the following raw materials in parts by weight: 59 parts of five-fingered peach, 16 parts of iron diamond, 28 parts of hairy holly and 15 parts of siler.

[0061] Preparation method: After adding 500ml of clean water, after the raw materials are made into liquid medicine, take 200ml and take it warm twice a day, morning and evening, after meals.

[0062] The method of using the invention is: oral administration, twice a day, 100 ml each time, and one month as a course of treatment.

[0063] Example 5

[0064] A Zhuang-Yao medicine compound medicine comprises the following raw materials in parts by weight: 61 parts of five-fingered peach, 17 parts of iron diamond, 34 parts of hairy holly and 18 parts of siler.

[0065] Preparation method: After adding 500ml of clean water, after the raw materials are made into liquid medicine, take 200ml and take it warm twice a day, morning and evening, after meals.

[0066] The method of using the invention is: oral administration, twice a day, 100 ml each time, and one month as a course of treatment.

[0067] Comparative Example 1

[0068] A Zhuang-Yao medicine compound medicine comprises the following raw materials in parts by weight: 30 parts of five-fingered peach, 6 parts of iron diamond, 50 parts of hairy holly and 25 parts of siler.

[0069] Preparation method: After adding 500ml of clean water, after the raw materials are made into liquid medicine, take 200ml and take it warm twice a day, morning and evening, after meals.

[0070] The method of using the invention is: oral administration, twice a day, 100 ml each time, and one month as a course of treatment.

[0071] Comparative Example 2

[0072] A Zhuang-Yao medicine compound medicine comprises the following raw materials in parts by weight: 70 parts of five-fingered peach, 6 parts of iron diamond, 50 parts of hairy holly, and 7 parts of siler.

[0073] Preparation method: After adding 500ml of clean water, after the raw materials are made into liquid medicine, take 200ml and take it warm twice a day, morning and evening, after meals.

[0074] The method of using the invention is: oral administration, twice a day, 100 ml each time, and one month as a course of treatment.

[0075] Comparative Example 3

[0076] A Zhuang-Yao medicine compound medicine comprises the following raw materials in parts by weight: 70 parts of five-fingered peach, 30 parts of iron diamond, 15 parts of hairy holly and 6 parts of siler.

[0077] Preparation method: After adding 500ml of clean water, after the raw materials are made into liquid medicine, take 200ml and take it warm twice a day, morning and evening, after meals.

[0078] The method of using the invention is: oral administration, twice a day, 100 ml each time, and one month as a course of treatment.

[0079] 2. Application Examples

[0080] Zhang, male, 68 years old, from Liuzhou, suffered from hemiplegia, crooked mouth and tongue, and choking when drinking water. The patient was clinically diagnosed with ischemic stroke. After one course of treatment according to Example 1 of the present invention, the hemiplegia and choking when drinking water were alleviated.

[0081] Gan, male, 58 years old, from Hezhou City, had slurred speech, crooked mouth and tongue, and squinting eyes. He was clinically diagnosed with ischemic stroke. After one course of medication treatment according to Example 2 of the present invention, the slurred speech and crooked mouth and tongue of the affected part were alleviated.

[0082] Cai, female, 64 years old, from Nanning, suffered from hemiplegia, slurred speech and headache. The patient was clinically diagnosed with ischemic stroke. After one course of treatment according to Example 3 of the present invention, the affected part had slurred speech and the headache was relieved.

[0083] 3. Animal Experiments

[0084] 1. Experimental Materials

[0085] 1.1 Experimental animals

[0086] 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, 21 rats. The animals were raised under specific pathogen free (SPF) safety conditions. The breeding environment was maintained at 22±2℃, the relative humidity was maintained at 50%-60%, the artificial light imitated the natural conditions of light and dark for 12h each, and sufficient food and drinking water were given during breeding. All experimental operators have the "Certificate of Qualification of Professional Technical Examination for Laboratory Animals". All animal experiments comply with the relevant provisions of the "Ethics Certificate for Laboratory Animals". The experimental animal production license number is SCXK (Xiang) 2019-0004, approved by the Ethics Committee of Guangxi University of Chinese Medicine (Ethics Number DW20200511-078).

[0087] 1.2 Drug preparation

[0088] The Zhuang-Yao medicine compound medicine of Example 3: 60 parts of five-fingered peach, 15 parts of iron diamond, 30 parts of hairy holly, and 15 parts of windproof; all medicines are single-flavor Chinese medicine concentrated granules, provided by Peili (Nanning) Pharmaceutical Co., Ltd., each package of granules, i.e., 1 pair of Zhuang-Yao medicine compound medicine pieces with the same conversion ratio, and the batch numbers are: A200151410, A210055200, A210163010, A210848210, A210173610, A190031032, A200113610, and A210175010.

[0089] Nimodipine tablets: provided by Sichuan Kelun Pharmaceutical Co., Ltd., item number B210301B21, specification is 20mg*50 tablets / bottle.

[0090] 2 Experimental methods

[0091] 2.1 Experimental Animal Grouping

[0092] The reference algorithm for the dosage of Zhuang-Yao medicine compound drugs is as follows: based on an adult (60kg) taking 156g of the original Zhuang-Yao medicine compound drug per day, and referring to the calculation method of the weight dose conversion coefficient between animals and humans, the dose for rats (weighing about 280-300g) is converted to 22g / kg, so 44g / kg is set as the high dose of Zhuang-Yao medicine compound drugs.

[0093] (1) Sham operation group: Rats underwent middle cerebral artery ischemia surgery, but no suture was inserted. They were kept normally and had free access to water.

[0094] (2) Model group: The model was established according to the following animal modeling method. Two hours after successful modeling, the rats were gavaged with an equal volume of saline to that in the Zhuang-Yao medicine compound drug intervention group. The rats were kept normally for 7 consecutive days and were allowed to drink water freely.

[0095] (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 gavaged at a dose of 44 g / kg / d for 7 consecutive days, once a day.

[0096] The rat tail number distinguishes the group. All three groups of rats must be successfully modeled, and rats that do not meet the conditions will be excluded according to the inclusion and exclusion criteria. After completing the required interventions for each group, animal observations were performed.

[0097] 2.2 Dosage regimen for experimental animals

[0098] Take 8 packets of Zhuangyao compound Chinese medicine granules, dissolve them in sterile water, and prepare a 100ml solution in a measuring cylinder, which is the high-dose oral administration drug of Zhuangyao compound medicine; each subsequent preparation is carried out according to the above method. The prepared solution is stored at 4℃. Take it out and restore it to room temperature 1h before use. According to the dosing plan of the experimental group, each rat is gavaged with 4.5mL once a day for 7 consecutive days.

[0099] 2.3 Animal model (MCAO method)

[0100] The MCAO model was established by embolizing the right middle cerebral artery of rats using the suture method. The modeling steps are briefly as follows:

[0101] (1) The experimental animals were anesthetized with sodium pentobarbital (40 mg / kg) by two people for intraperitoneal anesthesia. The hair on the neck was removed and the skin was prepared.

[0102] (2) The patient lies in the supine position on a fixation board, selects the midline of the neck, makes an incision, and separates three arteries along the inner edge of the sternocleidomastoid muscle, namely the left common carotid artery, external carotid artery, and internal carotid artery. Select the common carotid artery, and hang a thread at the left distal and proximal ends and the bifurcation of the external carotid artery for later use.

[0103] (3) Use a micro-arterial clamp to temporarily clamp the bifurcated internal carotid artery, and then use silk thread to ligate the proximal end of the left common carotid artery and the external carotid artery. Then cut a small hole 4 mm away from the bifurcation of the left common carotid artery, and just insert the ligature to the extent that it is pushed to the internal carotid artery. At this time, use the thin thread wrapped around the distal end of the left common carotid artery to fix its position and gently tie the ligature.

[0104] (4) Use fine ophthalmic forceps to gently push the ligature. When the insertion depth reaches 18 mm, the distance is measured from the bifurcation of the blood vessel and the thin wire at the distal end is tightly tied.

[0105] (5) Tie and fix the suture and external carotid artery for 40 minutes, pull out the suture to the external carotid artery, tie the external carotid artery again to prevent bleeding. Finally, suture the skin to achieve cerebral ischemia and reperfusion.

[0106] 3 Results

[0107] Functional analysis of differentially expressed mRNA in brain tissue of rats with cerebral ischemia-reperfusion injury induced by Zhuang-Yao medicine compound

[0108] Through GO functional enrichment analysis, it was found that after the intervention of Zhuangyao medicine compound drugs, the up-regulated differential genes in brain tissue were mainly enriched in Wnt pathway, DNA-binding transcription factor activity, nervous system development, G protein-coupled purinergic nucleotide receptor activity and other functions; the down-regulated differential genes were mainly enriched in inflammatory response, extracellular region, chemokine activity, cytokine receptor activity, virion assembly and other pathways, such as Figure 1 shown.

[0109] GO enrichment analysis

[0110] (A): Compared with the Model group, the GO enrichment of down-regulated genes in FYFH was higher than that in the Model group; (B): Compared with the Model group, the GO enrichment of up-regulated genes in FYFH was higher than that in the Model group.

[0111] IV. Clinical Research

[0112] 1. Medical records

[0113] 1.1 Number of people selected

[0114] A total of 120 patients with ischemic stroke were selected.

[0115] 1.2 Diagnostic criteria

[0116] 1.2.1 Diagnostic criteria for ischemic stroke

[0117] Refer to the "Disease Diagnosis Criteria in Stroke Diagnosis and Therapeutic Effect Evaluation Criteria" formulated by the Encephalopathy Emergency Collaboration Group of the Medical Administration Department of the State Administration of Traditional Chinese Medicine.

[0118] Diagnostic criteria for stroke:

[0119] (1) Main symptoms: hemiplegia, confusion, slurred speech or no speech, paresthesia on one side of the body, crooked mouth and tongue;

[0120] (2) Secondary symptoms: headache, dizziness, pupil changes, choking when drinking water, inability to blink, and ataxia;

[0121] (3) Onset: acute onset, often preceded by triggers and often with premonitory symptoms;

[0122] (4) Age of onset: mostly over 40 years old.

[0123] The diagnosis can be confirmed if there are two or more main symptoms, or one main symptom and two secondary symptoms, combined with the onset, triggering factors, precursor symptoms, age, and the results of imaging examinations.

[0124] 1.3 Case inclusion criteria

[0125] (1) Meet the diagnostic criteria of ischemic stroke in both traditional Chinese and Western medicine;

[0126] (2) Aged 45-75 years;

[0127] (3) No Chinese patent medicines, decoctions or related Western medicines for the treatment of stroke have been used since the onset of the disease;

[0128] (4) With the approval of the hospital ethics committee, each enrolled patient must sign an informed consent form.

[0129] 1.4 Case Exclusion Criteria

[0130] Except for those who have any of the following conditions:

[0131] (1)TIA;

[0132] (2) Hemorrhagic transformation after cerebral infarction;

[0133] (3) Patients with cerebral embolism caused by brain trauma, intracranial tumors, brain parasitic diseases, atrial fibrillation, etc.;

[0134] (4) People with allergic constitution;

[0135] (5) Patients with primary diseases of the liver, kidney, metabolic system, and blood system, making it difficult to evaluate the safety of the study;

[0136] (6) Mentally ill persons who are unable to express themselves accurately.

[0137] 1.5 Rejection and shedding criteria

[0138] (1) Cases that do not meet the inclusion criteria or are mistakenly included;

[0139] (2) The subject's condition has not been controlled to the expected level within a period of time;

[0140] (3) Those that affect the determination of efficacy, such as failure to use the drug as prescribed or incomplete clinical data;

[0141] (4) The subject voluntarily requests to withdraw from the trial for various reasons;

[0142] (5) Patients with other serious complications during the study;

[0143] (6) Taking other drugs during the study that may affect the efficacy evaluation.

[0144] 2. Methods

[0145] 2.1 Treatment methods

[0146] A total of 330 patients with ischemic stroke were randomly divided into 11 groups, with 30 patients in each group.

[0147] Control group 1: oral administration of enteric-coated aspirin tablets (Bayer Pharmaceuticals, Germany, batch number: National Medicine Standard J20171021), 100 mg / time, once / day;

[0148] Control group 2: intravenous drip of edaravone injection (Nanjing Xiansheng Dongyuan Pharmaceutical Co., Ltd., batch number: National Medicine Standard H20031342), 10 mL / time, once / day;

[0149] Control group 3: oral administration of butylphthalide soft capsules (Shijiazhuang Pharmaceutical Group Enbi Pharmaceutical Co., Ltd., batch number: National Medicine Standard H20050299), 0.2 g / time, 3 times / day;

[0150] Control group 4: on the basis of control group 1, the Zhuang-Yao medicine compound medicine and method of comparative example 1 were used for treatment;

[0151] Control group 5: on the basis of control group 1, the Zhuang-Yao medicine compound medicine and method of comparative example 2 were added for treatment;

[0152] Control group 6: on the basis of control group 1, the Zhuang-Yao medicine compound medicine and method of comparative example 3 were used for treatment;

[0153] Observation group 1: on the basis of control group 1, the Zhuang-Yao medicine compound medicine and method of Example 1 of the present invention were used for treatment;

[0154] Observation group 2: on the basis of control group 1, the Zhuang-Yao medicine compound medicine and method of Example 2 of the present invention were used for treatment;

[0155] Observation group 3: on the basis of control group 1, the Zhuang-Yao medicine compound medicine and method of Example 3 of the present invention were used for treatment;

[0156] Observation group 4: on the basis of control group 1, the Zhuang-Yao medicine compound medicine and method of Example 4 of the present invention were used for treatment;

[0157] Observation group 5: Based on the treatment of control group 1, the Zhuang-Yao medicine compound drug and method of Example 5 of the present invention were added for treatment.

[0158] The treatment course for each control group or observation group was 8 weeks.

[0159] During the treatment, the diet should be light and spicy food should be avoided; any drugs that may interfere with the research results should be avoided.

[0160] 2.2 Observation indicators and scoring criteria

[0161] 2.2.1 Degree of neurological deficit

[0162] The neurological deficit severity score was based on the National Institutes of Health Stroke Scale (NIHSS) score.

[0163] 2.2.2 Activities of daily living

[0164] The scoring standard for daily living activities refers to the scoring standard of the Barthel (BI) index rating scale.

[0165] 2.2.3 Evaluation of disability level

[0166] The degree of disability was evaluated according to the modified Rankin Scale (mRS) scoring standard.

[0167] 2.2.4 Quality of life evaluation

[0168] The short quality of life scale recommended by WHO was used.

[0169] 2.2.5 TCM Syndrome Score

[0170] The scale was drawn up with reference to the Stroke Symptom Grading Quantitative Table in the Guiding Principles for Clinical Research of New Chinese Medicines: dizziness, headache, limb numbness, limb stiffness, shortness of breath and fatigue were used as evaluation indicators. No symptoms were scored 0 points, mild symptoms that were still tolerable were scored 2 points, severe symptoms that affected life were scored 4 points, and severe symptoms that were unbearable were scored 6 points.

[0171] 2.2.6 Blood lipids

[0172] TC, TG, HDL-C, and LDL-C levels were measured.

[0173] 2.1.7 Adverse Reactions

[0174] Observe the patients' blood, urine, stool routine, coagulation function, myocardial enzymes, liver and kidney function, electrocardiogram and other indicators.

[0175] 2.3 Efficacy determination

[0176] Refer to the scoring standard for neurological deficits in stroke patients developed at the Fourth National Cerebrovascular Academic Conference.

[0177] Cured: symptoms and signs basically disappear, the patient can take care of himself, and the disability level is 0;

[0178] Markedly effective: symptoms and signs improved significantly, the neurological deficit score decreased by ≥21 points, and the disability level was 1-3;

[0179] Effective: symptoms and signs improved significantly, and the neurological deficit score decreased by 8-20 points;

[0180] Ineffective: There was no significant improvement in symptoms and signs before and after medication, and the neurological deficit score decreased by <8 points.

[0181] Effective rate = (number of cured cases + number of markedly effective cases + number of effective cases) / total number of cases × 100%.

[0182] 2.4 Concomitant medication

[0183] Avoid using Chinese patent medicines for the treatment of ischemic stroke. Symptomatic medications may be used for other complications without affecting the efficacy evaluation of the study drug.

[0184] 2.5 Data processing

[0185] SPSS24.0 software package was used for statistical analysis. The measurement data were analyzed by t test, the count data were analyzed by chi-square test, and the rank data were analyzed by Ridit test. P greater than 0.05 indicated no significant difference, P less than 0.05 indicated significant difference, and P less than 0.01 indicated extremely significant difference.

[0186] 3. Results

[0187] 3.1 TCM symptom efficacy

[0188] After treatment, the quality of life scores and TCM syndrome scores of the four groups were significantly improved (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).

[0189] Group Cured / person Significant effect / person Effective / person Invalid / person Cure rate / % Effectiveness / % 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

[0190] It can be seen from the above table that: (1) On the basis of the control group, taking the Zhuangyao medicine compound medicine of the present invention in combination can significantly improve the cure rate and the effective rate. This phenomenon fully demonstrates that the combination of five-fingered ginseng, iron drill, hairy holly, and windproof can produce a synergistic effect, thereby greatly improving the efficacy of the medicine, so that the cure rate and the effective rate are significantly improved. Specifically, five-fingered ginseng has the effects of strengthening the spleen and lungs, promoting qi and removing dampness; iron drill can play a role in dispelling wind and dampness, promoting blood circulation and relieving pain; hairy holly has the effects of clearing away heat and detoxifying, promoting blood circulation and unblocking meridians; windproof can relieve the symptoms and dispel wind, overcome dampness and relieve pain. The characteristics of these medicines complement and promote each other, and together they play a more powerful therapeutic role, bringing better therapeutic effects to patients.

[0191] (2) Comparison of the cure rate and effective rate between the observation groups 1-5 and the control groups 4-6 shows that when the dosage ratio of Rhizoma Cibotii, Rhizoma Cibotii, Rhizoma Cibotii, and Rhizoma Cibotii is not in 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 shows that it is very critical that the prescription of the present invention strictly controls the dosage ratio of Rhizoma Cibotii, Rhizoma Cibotii, Rhizoma Cibotii, and Rhizoma Cibotii to be (55-62):(12-17):(26-35):(13-18). Only under this specific dosage ratio can these drugs give full play to their respective advantages, cooperate with each other, achieve the best therapeutic effect, and significantly improve the cure rate and effective rate. For example, if the dosage of five-fingered ginseng is too much or too little, it may affect the spleen-tonifying and lung-tonifying effect of the entire compound medicine, thus failing to provide a good foundation for the performance of other medicines; the inappropriate dosage of iron agarwood may weaken the effects of dispelling wind and dampness, promoting blood circulation and relieving pain, affecting the overall therapeutic effect; the improper dosage ratio of hairy holly and windproof will also make it impossible to fully exert the effects of clearing away heat and detoxification, promoting blood circulation and unblocking meridians, and dispelling wind and dampness, and relieving pain. Therefore, accurately controlling the dosage ratio of these medicines is crucial to improving the therapeutic effect.

[0192] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A Zhuang-Yao medicine compound medicine, characterized in that: The invention comprises the following raw materials in parts by weight: 55-62 parts of five-fingered peach, 12-17 parts of iron diamond, 26-35 parts of hairy holly and 13-18 parts of windproof.

2. The Zhuang-Yao medicine compound medicine according to claim 1, characterized in that: The invention comprises the following raw materials in parts by weight: 56 parts of five-fingered peach, 12 parts of iron diamond, 27 parts of hairy holly and 13 parts of siler.

3. The Zhuang-Yao medicine compound medicine according to claim 1, characterized in that: The invention comprises the following raw materials in parts by weight: 59 parts of five-fingered peach, 16 parts of iron diamond, 28 parts of hairy holly and 15 parts of siler.

4. The Zhuang-Yao medicine compound medicine according to claim 1, characterized in that: The invention comprises the following raw materials in parts by weight: 60 parts of five-fingered peach, 15 parts of iron diamond, 30 parts of hairy holly and 15 parts of windproof.

5. The Zhuang-Yao medicine compound medicine according to claim 1, characterized in that: The invention comprises the following raw materials in parts by weight: 58 parts of five-fingered peach, 14 parts of iron diamond, 28 parts of hairy holly and 14 parts of siler.

6. The Zhuang-Yao medicine compound medicine according to claim 1, characterized in that: The invention comprises the following raw materials in parts by weight: 61 parts of five-fingered peach, 17 parts of iron diamond, 34 parts of hairy holly and 18 parts of siler.

7. A method for preparing a Zhuang-Yao medicine compound according to any one of claims 1 to 6, characterized in that: The following steps are involved: Weigh five-fingered peach, iron diamond, hairy holly, and windproof according to weight, then put the above four raw materials into clean water, and make the raw materials into liquid medicine.

8. The method for preparing the Zhuang-Yao medicine compound according to claim 7, characterized in that: The amount of the clean water is 500 ml.

9. Use of a Zhuang-Yao medicine compound prepared according to the method of claim 7 or 8 in the treatment of acute ischemic stroke, characterized in that: The obtained medicinal solution is taken orally, twice a day, 100 ml each time.

10. The use of the Zhuang-Yao medicine compound medicine according to claim 9 in the treatment of acute ischemic stroke, characterized in that: The treatment course is one month.

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