Zhuang Yao medicine compound medicine, preparation method and application of Zhuang Yao medicine compound medicine in treatment of ischemic stroke in recovery period

Abstract

The invention discloses a Yao-strengthening medicine compound medicine, a preparation method and application of the Yao-strengthening medicine compound medicine in treatment of ischemic stroke in the recovery period, and belongs to the field of treatment of the ischemic stroke in the recovery period through Yao-strengthening medicines. The Zhuang Yao medicine compound medicine is prepared from the following raw materials in parts by weight: 26 to 33 parts of euonymus fortunei, 27 to 32 parts of Yin-Yang wind, 16 to 24 parts of radix et rhizoma dioscoreae nipponicae and 18 to 22 parts of kadsura coccinea. The four raw materials are put into clear water and prepared into liquid medicine through a scientific process. The clinical characteristic prescription composed of the Yao-strengthening medicine for dredging toxic pathogen stasis of the dragon road and the fire road in the ischemic stroke recovery period is good in effect, can improve the symptoms of patients in the ischemic stroke recovery period, and is definite and stable in curative effect and free of toxic and side effects.

Description

Technical Field

[0001] The present invention belongs to the field of treating the recovery period of ischemic stroke with Zhuang and Yao medicines, and particularly relates to a compound Zhuang and Yao medicine, a preparation method thereof, and an application thereof in treating the recovery period of ischemic stroke. Background Art

[0002] Stroke, commonly known as apoplexy, mainly includes two types: ischemic stroke and hemorrhagic stroke. Among them, ischemic stroke is the most common, accounting for more than 80% of all stroke patients. It is mainly caused by a reduction in cerebral blood flow, leading to obstruction of cerebral arteries, and thus causing damage to brain cells and neurons. In China and worldwide, the overall incidence of stroke shows an upward trend. And according to research statistics, it is predicted that the incidence of stroke in China will increase by 50% in 2030 compared with 2010. At the same time, the incidence of stroke patients has gradually become younger, and it has a high recurrence rate and disability rate. One month after the onset of the acute stage of stroke, it enters the recovery period, which is a critical stage for improving nerve function recovery. If the treatment is improper, it will seriously affect the quality of life of patients after returning home, bringing a huge psychological and economic burden to families, society and the country. Compound Zhuang and Yao medicines have good curative effects in treating ischemic stroke and play an important role in its treatment with advantages such as small side effects, low treatment costs, etc.

[0003] The blood-brain barrier (BBB) is mainly composed of endothelial cells, pericytes, astrocytes and extracellular matrix, etc. Its highly selective permeability can avoid damage to the central nervous system (CNS) caused by harmful substances such as pathogens and inflammatory factors, thus playing a role in protecting and maintaining the normal function and homeostasis of the central nervous system. The damage of the BBB is the most important initiating factor leading to cerebral ischemia-reperfusion injury and is also the main cause of inducing various complications. The high "selectivity" of the BBB for surrounding substances can ensure normal material exchange and charge balance between the CNS and the blood, and ensure that neurons can normally perform their physiological functions. In addition, the BBB can also block macromolecular substances such as pathogens, immune cells and toxins in the blood to protect nerve tissue. During the process of cerebral ischemia-reperfusion injury, the BBB is damaged prior to the surrounding neurons, and then the cerebrovascular permeability increases, losing its selectivity for substances, resulting in the infiltration of various vascular contents into nerve tissue, triggering vasogenic brain edema and increased intracranial pressure. In severe cases, intracranial hemorrhage transformation may occur. In addition, many neurotoxic substances in the blood (such as thrombin, glutamate, albumin, etc.) can enter the brain tissue through the damaged BBB, further aggravating nerve damage. Therefore, protecting the BBB is regarded as a key treatment point in the process of preventing cerebral ischemia-reperfusion injury.

[0004] Since the injury of the BBB after cerebral ischemia-reperfusion is related to multiple pathological mechanisms such as free radical injury, inflammatory infiltration, calcium ion overload, neuronal apoptosis, and excitatory amino acid toxicity, the resulting pathological process is extremely complex and variable. Currently, modern medicine often uses the above single pathological factors as treatment targets to prevent and treat cerebral ischemia-reperfusion injury, making it difficult to achieve satisfactory clinical efficacy. In recent years, studies have found that traditional Chinese medicine, as natural compounds, can treat diseases through multiple pathways and multiple targets. In particular, compound preparations formulated with multiple herbs highlight the characteristics of traditional Chinese medicine in treating this disease, and their efficacy is also superior to that of using western medicine alone.

[0005] For example, the Chinese patent application document (publication number: CN115779053A) discloses a traditional Chinese medicine composition for treating acute ischemic stroke. This invention relates to traditional Chinese medicine for the recovery period of ischemic stroke and is made from the following raw drugs by weight: 20-40 g of Astragalus membranaceus, 10-20 g of Codonopsis pilosula, 9-15 g of stir-fried Atractylodes macrocephala, 10-20 g of Taxillus chinensis, 10-20 g of Eucommia ulmoides, 20-40 g of Achyranthes bidentata, 20-40 g of Cistanche deserticola, 10-20 g of Alpinia oxyphylla, 10-20 g of Salvia miltiorrhiza, 10-20 g of Ligusticum wallichii, 10-20 g of Pheretima aspergillum, 1-3 pieces of Scolopendra subspinipes, 9-15 g of Acorus tatarinowii, 9-15 g of Polygala tenuifolia, and 2-4 g of roasted Glycyrrhiza uralensis. The said traditional Chinese medicine composition can treat acute ischemic stroke. However, there are quite a few defects in the actual application of this drug formula. On the one hand, there are too many herbs in the formula, and some are rare varieties that are difficult to buy on the market, making the raw material cost high. Moreover, precious herbs are very "fragile", with strong volatility during decoction, and are quite picky about the heat, time, and container. In terms of heat, strong heat is likely to volatilize the effective components, while weak heat cannot decoct thoroughly. One has to keep an eye on the whole process of decocting, and if there is the slightest carelessness, the medicinal effect will be greatly reduced. On the other hand, there are many types of herbs. When various components are put together, it instead dilutes the proportion of the effective components and interferes with each other, resulting in the components that should dissolve not being able to dissolve out. Doctors originally hoped that they could work together to treat diseases, but as a result, they each do their own thing, and the clinical effect is naturally not satisfactory.

[0006] For another example, the Chinese patent application document (Publication No.: CN106913612A) discloses a pharmaceutical composition for treating the recovery period of qi deficiency and blood stasis type ischemic stroke and its sequelae, as well as its preparation method, preparation and application. The pharmaceutical composition for treating the recovery period of qi deficiency and blood stasis type ischemic stroke and its sequelae includes 180 - 720 parts by weight of astragalus membranaceus, 120 - 480 parts by weight of notoginseng, and 80 - 320 parts by weight of pheretima aspergillum, and is prepared through extraction, concentration, and drying steps. The preparation is a tablet, powder, capsule, granule or pill prepared by adding pharmaceutically acceptable excipients to the pharmaceutical composition for treating the recovery period of qi deficiency and blood stasis type ischemic stroke and its sequelae. The application is the application of the pharmaceutical composition for treating the recovery period of qi deficiency and blood stasis type ischemic stroke and its sequelae in the preparation of drugs for treating hemiplegia, hemiparalysis, numbness of the skin and unclear speech caused by the recovery period and sequelae period of qi deficiency and blood stasis type ischemic stroke. However, the involved drug formula, including astragalus membranaceus, notoginseng, and pheretima aspergillum, is expensive. The price of astragalus membranaceus fluctuates greatly due to variety and origin differences, and high-quality products can reach 100 yuan per catty; notoginseng is priced according to the number of heads, and the fewer the heads, the more expensive; the price of pheretima aspergillum is also stable at about 200 yuan per kilogram. And the production process is extremely cumbersome. From the screening, cleaning, and processing of medicinal materials to the precise proportioning and mixing, each step requires precise operation, consuming time and effort, and having high requirements for technology. Summary of the Invention

[0007] The clinical characteristic prescription composed of Zhuang and Yao medicines for dredging the toxin stasis in the dragon path and fire path in the recovery period of ischemic stroke of the present invention has good effects, can improve the symptoms of patients in the recovery period of ischemic stroke, has definite and stable curative effects, and has no toxic and side effects.

[0008] The present invention uses a compound Zhuang and Yao medicine to treat the recovery period of ischemic stroke and improve the clinical curative effect of the quality of life of ischemic stroke patients. The inventor is committed to the theory and clinical application of traditional Chinese medicine (ethnic medicine).

[0009] Based on the concepts of "dredging the dragon path and fire path" in Zhuang medicine and "the theory of balance between surplus and deficit" in Yao medicine, the compound Zhuang and Yao medicine has 4 medicinal materials: euonymus fortunei, polygonum perfoliatum l., kadsura interior, and kadsura coccinea. The theory of balance between surplus and deficit is an important pathogenesis theory for treating diseases in Yao medicine. Yao medicine believes that the occurrence of ischemic stroke is mainly due to long-term illness and weakness, and the imbalance between qi and blood surplus and deficit in the human body, which belongs to the category of internal wind syndrome in Yao medicine. In treatment, it is mainly to supplement with wind medicines and dispel pathogenic factors with beating medicines. In the formula, euonymus fortunei is sweet in taste and neutral in nature, replenishing qi and nourishing blood, and relaxing muscles and tendons; polygonum perfoliatum l. is sweet in taste and warm in nature, dispelling wind and dampness, and relaxing muscles and activating blood circulation, both of which are wind medicines for strengthening the healthy qi; kadsura coccinea is pungent, slightly bitter, and warm in nature, promoting qi circulation to relieve pain, and dispersing stasis and dredging collaterals; kadsura interior is pungent, bitter, and warm in nature, activating blood circulation and relaxing meridians, and dispelling wind and dredging collaterals. The two are both beating medicines for dispelling pathogenic factors. When combined, they can achieve the effects of strengthening the healthy qi and dispelling pathogenic factors, and taking both the root and symptoms into consideration.

[0010] The combined action of all ingredients dredges the dragon and fire channels, enables the "two channels" to operate normally, opens and clears the "three passages", maintains the mutual profit and loss balance, ensures the orderly rise and fall of yin and yang in the human body, harmonizes qi and blood, achieves the "profit and loss balance", and aims at the early recovery from stroke.

[0011] The above-mentioned Zhuang and Yao compound medicines are mainly used for the recovery period of ischemic stroke. By dredging the toxic stasis in the dragon and fire channels, they can improve the symptoms of ischemic stroke patients. The prescription is simple and has good curative effects. It not only overcomes the disadvantages of large side effects and easy generation of drug resistance of western medicines, but also carries forward the advantages of small side effects and difficult generation of drug resistance of traditional Chinese medicines.

[0012] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0013] A Zhuang and Yao compound medicine, comprising the following raw materials: Euonymus fortunei, Dendropanax dentiger, Kadsura interior, Saururus chinensis.

[0014] The technical principle of the present invention:

[0015] The characteristics of each raw material medicinal herb used are as follows

[0016] Euonymus fortunei: [Yao language] Feix gueix cing, [phonetic translation of Yao language], [alias] Parthenocissus tricuspidata, [source] the leafy stem branches of Euonymus fortunei (Turcz.) Hand.-Mazz. of the Celastraceae family. It is produced in Jiangsu, Zhejiang, Anhui, Jiangxi, Hubei, Hunan, Sichuan, Shaanxi and other provinces in China. In Guangxi, it is distributed in Luocheng, Guilin, Gongcheng, Rongshui, Ziyuan, Jinxiu and other places. [Properties and effects] Belongs to the "beating medicine". Bitter in taste, warm in nature. It has the effects of tonifying the kidney and strengthening the waist, relaxing tendons and activating collaterals, promoting blood circulation to remove stasis and stopping bleeding. It is used for treating kidney deficiency and lumbar soreness, hemiplegia, rheumatic arthralgia and other diseases.

[0017] Dendropanax dentiger: [Yao language] Yiemh yaanghbuerng, [phonetic translation of Yao language], [alias] Dendropanax chevalieri, [source] the stem of Dendropanax dentiger (Harms) Merr. of the Araliaceae family. This product is distributed in provinces and regions south of the Yangtze River. In Guangxi, it is distributed in Lingyun, Jinxiu, Gongcheng, Shanglin, Rongshui, Guiping, Hezhou, Zhongshan, Quanzhou and other places. [Properties and effects] Belongs to the "beating medicine". Bitter in taste, warm in nature. It has the effects of dispelling wind and dampness, relaxing tendons and activating collaterals, promoting blood circulation and regulating menstruation. It is used for migraine, rheumatoid arthritis and hemiplegia and other diseases.

[0018] Rush into the Mountains Tiger:

Yao language

Yao language transliteration

Alias

Source

Properties and effects

[0019] Big Drilling:

Yao language

Yao language transliteration

Alias

Source

Properties and effects

[0020] In the compound medicine of Zhuang and Yao medicines, Euonymus fortunei, Yin Yang Feng, Rush into the Mountains Tiger, and Big Drilling cooperate with each other, play a unique and efficient role, and jointly contribute to the treatment of the recovery period of ischemic stroke.

[0021] Specific effects of each raw material:

[0022] Euonymus fortunei: As a common medicinal plant, Euonymus fortunei has a significant effect of relaxing tendons and activating collaterals. In the treatment of ischemic stroke, it can effectively improve the condition of blocked meridians caused by cerebral vascular occlusion. Modern research shows that various active ingredients contained in Euonymus fortunei, such as flavonoid compounds, can promote blood circulation, increase cerebral blood perfusion, and help the damaged nerve tissue recover blood supply. At the same time, it also has a certain effect of stopping bleeding and dissipating stasis, which can reduce the occurrence of microvascular bleeding and blood stasis accumulation in the brain after stroke, and create a good internal environment for the repair of nerve cells.

[0023] Yin-Yang Wind: Yin-Yang Wind is outstanding in dispelling wind and removing dampness. Patients with ischemic stroke often suffer from symptoms such as limb numbness and limited movement, which are closely related to the invasion of wind pathogen and the blockage of damp pathogen in the meridians. Through its property of dispelling wind and removing dampness, Yin-Yang Wind can effectively disperse wind pathogen in the body, resolve damp pathogen in the meridians, and make the qi and blood flow more smoothly. From a pharmacological perspective, Yin-Yang Wind may contain some substances that can regulate the function of the nervous system and improve the flexibility of muscles and joints, helping to relieve the stiffness and numbness of the limbs of stroke patients and promoting the recovery of limb function.

[0024] Mountain-Climbing Tiger: Mountain-Climbing Tiger has the effects of dispelling wind and dredging collaterals, reducing swelling and alleviating pain. In the pathological process of ischemic stroke, cerebrovascular lesions can cause local tissue ischemia and hypoxia, which in turn lead to pain and meridian blockage. The active ingredients in Mountain-Climbing Tiger can stimulate the body's nerve regulation mechanism and relieve the pain sensation. At the same time, it can also dilate blood vessels, improve the blood circulation of the brain and limbs, and further dredge the meridians damaged by stroke. In addition, its swelling-reducing effect helps to reduce local edema in the brain and limbs, lower tissue pressure, and promote the recovery of nerve function.

[0025] Large Drilling Root: Large Drilling Root has the dual effects of promoting qi circulation to relieve pain and activating blood circulation to dissipate stasis. The effect of promoting qi circulation can promote the circulation of qi and blood in the body. In the case of ischemic stroke, it helps to improve the insufficient blood supply to the brain caused by qi and blood stasis. Its effect of activating blood circulation to dissipate stasis can directly act on the stasis area, disperse the stasis, and restore the patency of blood vessels. Some chemical components in Large Drilling Root may have the effect of inhibiting platelet aggregation and reducing blood viscosity, thereby reducing the risk of thrombus formation, which is also of great significance for preventing the recurrence of ischemic stroke.

[0026] Synergistic effect among raw materials:

[0027] Multi-link regulation of blood circulation: Euonymus fortunei focuses on promoting overall blood circulation and increasing blood supply to the brain; Large Drilling Root further improves the power and stasis state of qi and blood circulation through promoting qi circulation and activating blood circulation; Mountain-Climbing Tiger synergistically acts from the perspective of dilating blood vessels and improving local blood circulation. The three cooperate with each other to comprehensively regulate blood circulation, ensure sufficient blood supply to the brain and tissues throughout the body, and provide a material basis for the repair and functional recovery of nerve cells.

[0028] Synergism between dispelling wind and removing dampness and dredging collaterals to relieve pain: The effect of dispelling wind and removing dampness of Yin-Yang Wind corresponds to the effects of dispelling wind and dredging collaterals, reducing swelling and alleviating pain of Mountain-Climbing Tiger. Yin-Yang Wind first disperses wind pathogen and resolves damp pathogen, creating conditions for the patency of meridians, and Mountain-Climbing Tiger further dredges the meridians, relieves pain and limb numbness. This synergistic effect can effectively improve the limb motor function and pain symptoms of stroke patients and improve the quality of life of patients.

[0029] Overall regulation and neuroprotection in synergy: The combined effects of Euonymus fortunei, Piper hancei Maxim., Kadsura interior A. C. Smith, and Saurauia tristyla DC. not only improve blood circulation and the smoothness of meridians but also have a certain protective effect on nerve cells. They may reduce nerve cell damage and promote the repair and regeneration of nerve cells by regulating mechanisms such as inflammatory responses and antioxidant stress in the body. This synergistic effect from overall regulation to neuroprotection can more comprehensively address the complex pathophysiological process of ischemic stroke and achieve better therapeutic effects.

[0030] The necessity and importance of controlling the dosage of raw materials:

[0031] Ensuring the efficacy: Each raw material can exert its best efficacy within a specific dosage range. For example, if the dosage of Euonymus fortunei is too low, it may not be able to fully promote blood circulation and achieve the effect of improving cerebral blood supply; if the dosage is too high, it may cause some adverse reactions, such as bleeding tendency caused by excessive blood activation. Only by precisely controlling the dosage can the efficacy of each raw material be fully exerted to achieve the best therapeutic effect.

[0032] Maintaining the synergistic balance: The synergistic effect among raw materials depends on the appropriate dosage ratio. If the dosage of a certain raw material is too high or too low, it may disrupt the synergistic balance among them. For example, if the dosage of Piper hancei Maxim. is too large, it may lead to too strong a wind-expelling effect and damage healthy qi; if the dosage of Kadsura interior A. C. Smith is insufficient, it may not be able to dredge the meridians effectively in synergy with other raw materials. Therefore, strictly controlling the dosage is crucial for maintaining the synergistic balance among raw materials and ensuring the stability and reliability of therapeutic effects.

[0033] Reducing adverse reactions: Reasonably controlling the dosage of raw materials can effectively reduce the occurrence of adverse reactions. Each raw material has its safe dosage range, and exceeding this range may cause various adverse reactions. By precisely controlling the dosage, both the therapeutic effect of the drug can be ensured and the risk of adverse reactions can be minimized to the greatest extent, improving the safety and compliance of patients' medication.

[0034] In the treatment during the recovery period, Euonymus fortunei promotes neural plasticity and angiogenesis, Piper hancei Maxim. continuously regulates microcirculation and improves cerebral tissue perfusion, Kadsura interior A. C. Smith clears residual thrombus and inhibits the formation of secondary embolism, and Saurauia tristyla DC. repairs the damaged mitochondrial function and stabilizes the neuronal membrane potential. The four herbs in synergy not only accelerate the recovery of nerve function deficits such as movement and language but also reconstruct the overall coordination of the brain-limb-viscera by regulating the balance of the three physiological elements of qi, blood, and body fluid. Compared with the "stagnation of healthy qi due to the removal of stasis" or "retention of pathogenic factors due to supplementation" that are prone to occur in the conventional method of supplementing qi and activating blood circulation, this scheme innovatively achieves the dynamic balance of "removing stasis without consuming qi and dredging collaterals without damaging yin", providing a precise intervention strategy with both ethnic medicine characteristics and modern scientific connotations for the recovery period of stroke and an innovative and effective drug combination plan for the symptom improvement and disease recovery of ischemic stroke patients.

[0035] Preferably, the Zhuang and Yao ethnic medicine compound medicine comprises the following raw materials in parts by weight: 26-33 parts of Euonymus fortunei, 27-32 parts of Polygonum perfoliatum, 16-24 parts of Kadsura interior, and 18-22 parts of Saurauia tristyla DC.

[0036] Preferably, the Zhuang and Yao ethnic medicine compound medicine comprises the following raw materials in parts by weight: 26 parts of Euonymus fortunei, 27 parts of Polygonum perfoliatum, 23 parts of Kadsura interior, and 22 parts of Saurauia tristyla DC.

[0037] Preferably, the Zhuang and Yao ethnic medicine compound medicine comprises the following raw materials in parts by weight: 33 parts of Euonymus fortunei, 31 parts of Polygonum perfoliatum, 16 parts of Kadsura interior, and 18 parts of Saurauia tristyla DC.

[0038] Preferably, the Zhuang and Yao ethnic medicine compound medicine comprises the following raw materials in parts by weight: 30 parts of Euonymus fortunei, 30 parts of Polygonum perfoliatum, 20 parts of Kadsura interior, and 20 parts of Saurauia tristyla DC.

[0039] Preferably, the preparation method of the Zhuang and Yao ethnic medicine compound medicine comprises: mixing the raw materials, adding clear water, soaking, and then decocting.

[0040] The present invention also provides a preparation method of a Zhuang and Yao ethnic medicine compound medicine, comprising the following steps: mixing the raw materials, adding clear water, soaking, and then decocting to obtain the Zhuang and Yao ethnic medicine compound medicine.

[0041] Preferably, the decocting is carried out in two times. After the first decocting, the decoction liquid and the residue are filtered and collected; for the second time, clear water is added to the residue, and then it is decocted, filtered, and the two decoction liquids are combined.

[0042] Preferably, the first decocting is carried out for 60-90 minutes.

[0043] Preferably, the second decocting is carried out for 40-60 minutes.

[0044] Preferably, after the decocting is completed, the decoction liquid is quickly cooled to 20-30 °C.

[0045] The present invention also provides an application of the Zhuang and Yao ethnic medicine compound medicine in the treatment of the recovery period of ischemic stroke.

[0046] Compared with the prior art, the present invention has the following technical advantages:

[0047] (1) Rapidly improving limb function: The prescription composed of Euonymus fortunei, Polygonum perfoliatum, Kadsura interior, and Saurauia tristyla DC. used in the present invention can often significantly improve the limb motor function of ischemic stroke patients in a relatively short time. The numbness of the patients' limbs is reduced, and the activity flexibility is significantly improved, and this effect exceeds the expectation of using conventional treatment means alone.

[0048] (2) Alleviating brain symptoms: The Zhuang and Yao medicine compound of the present invention has a significant effect on alleviating brain symptoms such as headache and dizziness in patients with ischemic stroke. By improving cerebral blood circulation and reducing nerve damage, the degree of headache in patients is reduced, and the frequency of dizziness attacks is decreased, which helps to improve the cognitive function and self-care ability of patients.

[0049] (3) Improving quality of life: Using Euonymus fortunei (Turcz.) Hand.-Mazz., Polygala paniculata L., Kadsura interior (Lem.) A. C. Smith, and Saurauia tristyla DC. to treat ischemic stroke in the present invention can comprehensively improve the quality of life of patients. Patients can return to normal life faster, reduce dependence on others, and re-participate in social activities, which is of great significance to the physical and mental health of patients and the stability of family and social relationships.

[0050] (4) The clinical characteristic prescription composed of Zhuang and Yao medicines for dredging the toxin stasis in the dragon and fire paths during the recovery period of ischemic stroke in the present invention has good effects, can improve the symptoms of patients during the recovery period of ischemic stroke, has definite and stable curative effects, and has no toxic and side effects. Detailed implementation manners

[0051] Next, in combination with the embodiments of the present invention, the technical solutions in the preferred examples will be clearly and completely described. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

[0052] In the embodiments of the present invention, a Zhuang and Yao medicine compound for treating the recovery period of ischemic stroke includes the following raw materials in parts by weight: 26-33 parts of Euonymus fortunei (Turcz.) Hand.-Mazz., 27-32 parts of Polygala paniculata L., 16-24 parts of Kadsura interior (Lem.) A. C. Smith, and 18-22 parts of Saurauia tristyla DC.

[0053] The preparation method of the Zhuang and Yao medicine compound includes the following steps: Mix the raw materials, add clear water, soak, and then decoct to obtain the Zhuang and Yao medicine compound.

[0054] The decoction is carried out in two times. After the first decoction for 60-90 minutes, filter to collect the decoction liquid and the filter residue; for the second time, add clear water to the filter residue, decoct for 40-60 minutes, filter and combine the two decoction liquids, and quickly cool the decoction liquid to 20-30 °C.

[0055] The usage method of the Zhuang and Yao medicine compound of the present invention is: Take orally, warm it twice a day in the morning and evening, take 100 ml each time, and 1 month is a course of treatment.

[0056] In order to make the disclosure of the present invention more sufficient, the present invention will be further illustrated below in combination with specific embodiments.

[0057] I. Examples and comparative examples

[0058] Example 1

[0059] A compound Zhuang and Yao medicine, comprising the following raw materials in parts by weight: 26 parts of Euonymus fortunei, 27 parts of Polygonum perfoliatum, 23 parts of Kadsura interior, and 22 parts of Saurauia tristyla.

[0060] The preparation method of the compound Zhuang and Yao medicine comprises the following steps: mixing the raw materials, adding clear water, soaking, and then decocting to obtain the compound Zhuang and Yao medicine.

[0061] The decocting is carried out in two times. After the first decocting for 80 minutes, the decoction liquid and the residue are filtered and collected; for the second time, clear water is added to the residue, decocted for 50 minutes, filtered, and the two decoction liquids are combined, and the decoction liquid is quickly cooled to 27 °C.

[0062] The usage method of the compound Zhuang and Yao medicine of the present invention is: taking orally, taking it warm twice a day, morning and evening, 100 ml each time, and 1 month is a treatment course.

[0063] Example 2

[0064] A compound Zhuang and Yao medicine, comprising the following raw materials in parts by weight: 30 parts of Euonymus fortunei, 30 parts of Polygonum perfoliatum, 20 parts of Kadsura interior, and 20 parts of Saurauia tristyla.

[0065] The preparation method and the usage method of the compound Zhuang and Yao medicine are the same as those in Example 1.

[0066] Example 3

[0067] A compound Zhuang and Yao medicine, comprising the following raw materials in parts by weight: 33 parts of Euonymus fortunei, 31 parts of Polygonum perfoliatum, 16 parts of Kadsura interior, and 18 parts of Saurauia tristyla.

[0068] The preparation method and the usage method of the compound Zhuang and Yao medicine are the same as those in Example 1.

[0069] Comparative Example 1

[0070] A compound Zhuang and Yao medicine, comprising the following raw materials in parts by weight: 13 parts of Euonymus fortunei, 13 parts of Polygonum perfoliatum, 22 parts of Kadsura interior, and 21 parts of Saurauia tristyla.

[0071] The preparation method and the usage method of the compound Zhuang and Yao medicine are the same as those in Example 1.

[0072] Comparative Example 2

[0073] A compound Zhuang and Yao medicine, comprising the following raw materials in parts by weight: 32 parts of Euonymus fortunei, 30 parts of Polygonum perfoliatum, 8 parts of Kadsura interior, and 9 parts of Saurauia tristyla.

[0074] The preparation method and the usage method of the compound Zhuang and Yao medicine are the same as those in Example 1.

[0075] Comparative Example 3

[0076] A compound Zhuang and Yao medicine, comprising the following raw materials in parts by weight: 16 parts of Euonymus fortunei, 35 parts of Polygonum perfoliatum, 12 parts of Kadsura interior, and 25 parts of Saurauia tristyla.

[0077] The preparation method and usage method of the compound Zhuang and Yao medicine are the same as those in Example 1.

[0078] II. Application Examples

[0079] In clinical application observations, 3 patients with ischemic stroke showed positive curative effects after being treated with different embodiments of the present invention, specifically as follows:

[0080] Li Moumou, a 62-year-old male from Wuzhou City, showed hemiplegia, deviation of the mouth and tongue, and choking cough when drinking water at the time of admission. After being clinically diagnosed with ischemic stroke, he was treated with the medicine in Example 1 of the present invention for 1 course of treatment. The hemiplegic motor function of the patient improved, and the symptom of choking cough when drinking water was significantly alleviated.

[0081] Li Moumou, a 58-year-old male from Hezhou City, presented with speech slurring, deviation of the mouth and tongue, and fixed deviation of the eyes. He was diagnosed with ischemic stroke. After being treated with the medicine in Example 2 of the present invention for 1 course of treatment, the clarity of his speech expression improved, and the symptom of facial deviation was significantly relieved.

[0082] Zhang Moumou, a 74-year-old female from Nanning City, was admitted to the hospital with the main complaints of hemiplegia, speech impairment, and headache. She was diagnosed with ischemic stroke. After being treated with the medicine in Example 3 of the present invention for 1 course of treatment, not only the symptom of speech slurring was alleviated, but also the headache symptom was effectively controlled.

[0083] III. Animal Experiments

[0084] 1. Experimental Materials

[0085] 1.1 Experimental Animals

[0086] Twenty-one male SPF-grade Sprague Dawley (SD) rats used in this experiment were all provided by the Scientific Experiment Center of Guangxi University of Chinese Medicine, and the rat age was about 8 weeks. The whole experiment was carried out in accordance with the relevant regulations of the "Experimental Animal Ethics Certificate", and was approved by the Ethics Committee of Guangxi University of Chinese Medicine (Ethics No. DW20200511-078). The animal production license number was SCXK (Xiang) 2019-0004.

[0087] The rats were raised in an SPF-grade environment, with the temperature controlled at 22±2°C and the relative humidity maintained at 50%-60%. Artificial lighting with a 12h light-dark cycle was used to ensure sufficient food and water supply. All operators held the "Qualified Certificate for Experimental Animal Professional Technology" to ensure the standardization of experimental operations.

[0088] 1.2 Drug Preparation

[0089] Compound Zhuang and Yao medicine of Example 2: The single-herb concentrated granules were provided by Peili (Nanning) Pharmaceutical Co., Ltd. The prescription composition was 30 parts of Euonymus fortunei, 30 parts of Marsdenia multibracteata, 20 parts of Kadsura interior, and 20 parts of Saurauia tristyla. Each pack of granules was equivalent to 1 dose of the decoction pieces in terms of dosage, and the corresponding batch numbers were A200151410, A210055200, A210163010, A210848210, A210173610, A190031032, A200113610, and A210175010.

[0090] Nimodipine tablets: Produced by Sichuan Kelun Pharmaceutical Co., Ltd. (product number B210301B21), with a specification of 20 mg × 50 tablets / bottle.

[0091] 2. Experimental methods

[0092] 2.1 Grouping of experimental animals

[0093] Referring to the previous research and pre-experiment data of the research group, based on the fact that an adult (60 kg) takes 156 g of the crude drug of the compound Zhuang and Yao medicine of Example 2 per day as a benchmark, according to the conversion coefficient of the animal and human body weight dosage, the dosage of the drug for rats (weight 280 - 300 g) was determined to be 22 g / kg, and 44 g / kg was set as the drug dosage standard for the high-dose group. The specific grouping was as follows:

[0094] Sham operation group: The middle cerebral artery ischemia operation was performed, but the suture was not inserted, and the rats were normally raised after the operation.

[0095] Model group: The model was established by the suture method. After the model was successfully established for 2 h, the rats were intragastrically administered with an equal volume of normal saline for 7 consecutive days.

[0096] Compound Zhuang and Yao medicine intervention group of Example 2: After the model was successfully established for 2 h, the compound Zhuang and Yao medicine of Example 2 was intragastrically administered at a dose of 44 g / kg / d, once a day for 7 consecutive days.

[0097] Before the experiment, the groups were distinguished by tail marking, and the rats were strictly screened according to the inclusion and exclusion criteria to ensure that the experimental subjects met the requirements.

[0098] 2.2 Drug administration plan for experimental animals

[0099] Take 8 packs of the compound Zhuang and Yao medicine granules of Example 2, dissolve them in sterile water, and make up the volume to 100 ml in a measuring cylinder to prepare a high-dose intragastric solution. The solution was stored at 4 °C, and taken out 1 h before use and restored to room temperature. According to the grouping drug administration plan, each rat was intragastrically administered 4.5 mL per day for 7 consecutive days.

[0100] 2.3 Animal model establishment (MCAO method)

[0101] Referring to the reference literature and the mature methods in the laboratory, the middle cerebral artery occlusion (MCAO) model in rats was prepared by the suture occlusion method. The specific steps are as follows:

[0102] The rats were anesthetized intraperitoneally with sodium pentobarbital (40 mg / kg) by two people, and the hair on the neck was removed and the skin was prepared;

[0103] The rats were fixed supine, incised along the midline of the neck, and the left common carotid artery, external carotid artery and internal carotid artery were separated, and threads were hung at the corresponding positions for standby;

[0104] The internal carotid artery was clamped, the proximal ends of the common carotid artery and external carotid artery were ligated, an incision was made 4 mm at the bifurcation of the common carotid artery, and the suture was inserted into the internal carotid artery and fixed;

[0105] The suture was gently pushed to a depth of 18 mm (counting from the vascular bifurcation), and the distal end of the thin thread was tightened;

[0106] The suture was ligated and fixed to the external carotid artery. After 40 minutes of ischemia, the suture was withdrawn, and the external carotid artery was ligated again to stop bleeding, and the skin was sutured to complete cerebral ischemia-reperfusion.

[0107] 3. Results

[0108] Effect of the Zhuang and Yao compound medicine in Example 2 on the mRNA expression in the brain tissue of rats with cerebral ischemia-reperfusion injury.

[0109] Through GO functional enrichment analysis, it was shown that after the intervention of the Zhuang and Yao compound medicine in Example 2, the up-regulated differential genes in the rat brain tissue were mainly enriched in functions such as Wnt pathway, DNA-binding transcription factor activity, nervous system development, G protein-coupled purine nucleotide receptor activity, etc.; the down-regulated differential genes were mainly concentrated in pathways such as inflammatory response, extracellular region, chemokine activity, cytokine receptor activity, viral particle assembly, etc.

[0110] IV. Clinical research

[0111] 1. Medical records

[0112] 1.1 Research subjects

[0113] A total of 270 patients with ischemic stroke were included in this study.

[0114] 1.2 Diagnostic criteria

[0115] Referring to the "Diagnosis and Efficacy Evaluation Criteria for Stroke" formulated by the Encephalopathy Emergency Collaboration Group of the Medical Administration Department of the State Administration of Traditional Chinese Medicine:

[0116] Main symptoms: hemiplegia, loss of consciousness, speech difficulty or aphasia, abnormal hemisensory, deviation of the mouth and tongue;

[0117] Sub-symptoms: headache, dizziness, pupil changes, choking when drinking water, non-blinking of the eyes, ataxia;

[0118] Onset characteristics: Acute onset, often with predisposing factors and prodromal symptoms before the onset;

[0119] Age of onset: Mostly over 40 years old.

[0120] Meeting 2 or more major symptoms, or 1 major symptom and 2 minor symptoms, and combined with the onset situation, predisposing factors, prodromal symptoms, age, and imaging examination results, the diagnosis can be confirmed.

[0121] 1.3 Inclusion criteria for cases

[0122] (1) Meeting the Chinese and Western medicine diagnostic criteria for ischemic stroke;

[0123] (2) Aged 45 - 75 years old;

[0124] (3) Not having used Chinese or Western medicines related to stroke after this onset;

[0125] (4) Approved by the hospital ethics committee, and the patient signed the informed consent form.

[0126] 1.4 Exclusion criteria for cases

[0127] (1) Transient ischemic attack (TIA);

[0128] (2) Hemorrhagic transformation after cerebral infarction;

[0129] (3) Cerebral embolism caused by brain trauma, intracranial tumor, cerebral parasitosis, atrial fibrillation, etc.;

[0130] (4) Allergic constitution;

[0131] (5) Complicated with severe primary diseases such as liver, kidney, metabolism, and blood system, affecting safety assessment;

[0132] (6) Mental illness or those who cannot express accurately.

[0133] 1.5 Exclusion and dropout criteria

[0134] (1) Cases that do not meet the inclusion criteria or are misclassified;

[0135] (2) The condition fails to reach the expected control;

[0136] (3) Affecting the judgment of curative effect (such as non-standard medication, incomplete clinical data);

[0137] (4) The subject withdraws actively;

[0138] (5) Severe concurrent diseases occur during the study;

[0139] (6) Taking other drugs that affect the evaluation of curative effect.

[0140] 2. Methods

[0141] 2.1 Treatment methods

[0142] A total of 270 patients with ischemic stroke were randomly divided into 9 groups, with 30 patients in each group.

[0143] Control group 1: oral administration of enteric-coated aspirin tablets (Bayer Pharmaceuticals, Germany, batch number: National Medicine Standard J20171021), 100 mg / time, once / day;

[0144] 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;

[0145] 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.

[0146] 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;

[0147] 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;

[0148] 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;

[0149] 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;

[0150] 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;

[0151] 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;

[0152] The treatment course for each control group or observation group was 8 weeks.

[0153] 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.

[0154] 2.2 Observation indicators and scoring criteria

[0155] 2.2.1 Degree of neurological deficit

[0156] The National Institutes of Health Stroke Scale (NIHSS) scoring standard is used to quantitatively evaluate the degree of neurological deficit in patients, providing an objective basis for diagnosis of the disease and judgment of treatment effects.

[0157] 2.2.2 Activities of daily living

[0158] Using the Barthel Index (BI) rating scale, score the patient from dimensions such as daily self-care ability and activity ability to accurately measure the improvement of their activities of daily living.

[0159] 2.2.3 Evaluation of disability degree

[0160] According to the scoring criteria of the modified Rankin scale (mRS), conduct a systematic assessment of the patient's disability degree to clarify the progress of the patient in functional recovery and disability status.

[0161] 2.2.4 Quality of life evaluation

[0162] Use the WHO-recommended Quality of Life-BREF to comprehensively evaluate the patient's quality of life from multiple aspects such as physical, psychological, and social functions, and comprehensively understand the impact of treatment on the patient's living status.

[0163] 2.2.5 Traditional Chinese medicine syndrome score

[0164] Referring to the "Quantification Table of Stroke Symptoms" in the "Guiding Principles for Clinical Research of New Chinese Medicines", select 5 core symptoms of dizziness, headache, limb numbness, limb stiffness, and shortness of breath and fatigue as evaluation indicators. The scoring criteria are: no symptoms are scored 0; mild symptoms that can still be tolerated are scored 2; severe symptoms that affect life are scored 4; extremely severe symptoms that are difficult to tolerate are scored 6, so as to quantify the changes in traditional Chinese medicine syndromes.

[0165] 2.2.6 Blood lipids

[0166] Measure the levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in the patient, monitor the blood lipid metabolism, and assist in judging the impact of treatment on the patient's blood lipid indicators.

[0167] 2.2.7 Adverse reactions

[0168] Closely observe the patient's blood, urine, and stool routine, coagulation function, myocardial enzymes, liver and kidney functions, and electrocardiogram and other indicators, comprehensively evaluate the safety during the treatment process, and promptly detect and record possible adverse reactions.

[0169] 2.3 Efficacy determination

[0170] According to the scoring standard of neurological deficit in stroke patients formulated by the Fourth National Cerebrovascular Academic Conference, the following efficacy determination rules are formulated:

[0171] Cured: Symptoms and signs basically disappear, the patient can take care of themselves, and the disability degree reaches grade 0;

[0172] Marked effect: Symptoms and signs are significantly improved, the neurological deficit score is reduced by ≥21 points, and the disability degree is at level 1-3;

[0173] Effective: Symptoms and signs are significantly improved, and the neurological deficit score is reduced by 8-20 points;

[0174] Ineffective: There is no obvious change in symptoms and signs before and after medication, and the neurological deficit score is reduced by <8 points.

[0175] The formula for calculating the effective rate is: Effective rate = (number of cured cases + number of markedly effective cases + number of effective cases) / total number of cases × 100%.

[0176] 2.4 Concomitant medications

[0177] During the study period, the use of traditional Chinese patent medicines for treating ischemic stroke was strictly avoided. On the premise of not interfering with the evaluation of the efficacy of the study drug, for other comorbidities of the patients, symptomatic medication can be carried out according to the actual situation.

[0178] 2.5 Data processing

[0179] SPSS 24.0 software package was used for statistical analysis. For measurement data, t-test was used; for count data, chi-square test was used; for ranked data, Ridit test was used. P>0.05 indicates no significant difference, P<0.05 indicates significant difference, and P<0.01 indicates extremely significant difference.

[0180] 3. Results

[0181] 3.1 Efficacy of traditional Chinese medicine symptoms

[0182] After treatment, the statistical results are as follows.

[0183]

[0184]

[0185] It can be seen from the above table that: (1) After treatment, the quality of life scores and traditional Chinese medicine syndrome scores of the 9 groups were significantly improved compared with before (P<0.05). The improvement of the observation group was better than that of the control group, and the difference was statistically significant (P<0.05).

[0186] (2) On the basis of the control group, taking the compound drug of the present invention can significantly improve the cure rate and total effective rate.

[0187] (3) Comparison of cure rates

[0188] The cure rate range of the control group was between 43.33% and 60%. Among them, the cure rate of control group 5 was the highest, at 60%; the cure rate of control group 1 was the lowest, at 43.33%. There were certain differences in the cure rates among the control groups, but the gap was not very significant.

[0189] The cure rate of the observation group was significantly higher than that of the control group, ranging from 70% to 80%. Among them, the cure rate of Observation Group 3 was the highest, reaching 80%; the cure rate of Observation Group 1 was 70%. This indicates that the treatment plan of the observation group is more effective than that of the control group in enabling patients to reach the cured state.

[0190] (4) Comparison of effective rates

[0191] The effective rate of the control group was between 73.33% and 86.67%. The effective rate of Control Group 5 was the highest, at 86.67%; the effective rate of Control Group 1 was the lowest, at 73.33%. Although the effective rates fluctuated among the control groups, they were generally at a similar level.

[0192] The effective rate of the observation group was in the relatively high range of 93.33% - 96.67%. Among them, the effective rate of Observation Group 3 was the highest, at 96.67%; the effective rates of Observation Group 1 and Observation Group 2 were both 93.33%. Thus, it can be seen that the treatment plan of the observation group has obvious advantages over the control group in effectively improving the condition of patients (including cure, marked effect, and effective).

[0193] (5) From the comparison of the cure rates and effective rates of Observation Groups 1 - 3 and Control Groups 4 - 6, when the dosage ratios of Euonymus fortunei, Polygala paniculata, Kadsura interior, and Saurauia tristyla are not in the range of (26 - 33 parts) : (27 - 32 parts) : (16 - 24) : (18 - 22), both the cure rate and the effective rate decrease significantly, further illustrating the necessity and importance of controlling the dosages of Euonymus fortunei, Polygala paniculata, Kadsura interior, and Saurauia tristyla in the present invention.

[0194] The above are only the preferred embodiments of the present invention and are not used to limit the present invention. For those skilled in the art, the present invention can have various changes and modifications. 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 Zhuang-Yao medicine compound medicine, characterized in that: The invention comprises the following raw materials in parts by weight: 26-33 parts of Euonymus fortunei, 27-32 parts of Phragmites australis, 16-24 parts of Polygonum multiflorum and 18-22 parts of Radix Codonopsis pilosulae.

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: 26 parts of Euonymus fortunei, 27 parts of Herba Lycopodii, 23 parts of Herba Polygoni Multiflori and 22 parts of Herba Dioscoreae.

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: 33 parts of Euonymus fortunei, 31 parts of Herba Lycopodii, 16 parts of Herba Polygoni Multiflori and 18 parts of Herba Dioscoreae.

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: 30 parts of Euonymus fortunei, 30 parts of Yin Yang Feng, 20 parts of Ornithogalum ruthenicum and 20 parts of Dalbergia fortunei.

5. A method for preparing a Zhuang-Yao medicine compound according to any one of claims 1 to 4, characterized in that: The following steps are involved: After mixing the raw materials, add clean water, soak, and then boil to obtain the Zhuang and Yao medicine compound medicine.

6. The method for preparing the Zhuang-Yao medicine compound medicine according to claim 5, characterized in that: The decoction is performed twice. After the first decoction, the decoction and the filter residue are collected by filtering; for the second decoction, clean water is added to the filter residue, and the two decoctions are decocted, filtered and combined.

7. The method for preparing the Zhuang-Yao medicine compound according to claim 6, characterized in that: The first decoction takes 60-90 minutes.

8. The method for preparing the Zhuang-Yao medicine compound according to claim 6, characterized in that: The second decoction is 40-60 minutes.

9. The method for preparing the Zhuang-Yao medicine compound medicine according to claim 6, characterized in that: After decoction is completed, the decoction is quickly cooled to 20-30℃.

10. Use of a Zhuang-Yao medicine compound prepared according to the method according to any one of claims 5 to 9 in the treatment of ischemic stroke recovery period.

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