A Chinese medicine composition, Chinese medicine preparation and application thereof

Abstract

The invention discloses a Chinese medicine composition, a Chinese medicine preparation and its application, and relates to the technical field of drug production. The Chinese medicine composition comprises the following raw materials in parts by weight: 5-20 parts of ephedra; 5-30 parts of cassia twig; 1-10 parts of fish oil; 3-25 parts of angelica; 3-25 parts of chuanxiong; 5-20 parts of peach kernel; 5-20 parts of codonopsis; 5-20 parts of ginger; 5-30 parts of licorice; and 10-100 parts of gypsum. The Chinese medicine composition of the invention has the characteristics of multiple targets and small toxic and side effects. It plays a role in treating cerebral infarction mainly by improving blood rheology, inhibiting thrombosis, enhancing body immunity, inhibiting the activation of microglia in the brain and the damage of mature neurons, and improving neuronal apoptosis.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical production, and particularly relates to a traditional Chinese medicine composition, a traditional Chinese medicine preparation and their applications. Background Art

[0002] Cerebral infarction (CI) is the main manifestation of ischemic stroke, which is caused by local cerebral tissue ischemic necrosis or softening due to cerebral blood supply disorder, ischemia and hypoxia. The common clinical types of cerebral infarction include cerebral thrombosis, lacunar infarction and cerebral embolism, etc. Cerebral infarction accounts for 80% of all strokes. The clinical manifestations are mainly characterized by sudden fainting, unconsciousness, hemiplegia, speech disorder and intellectual disorder.

[0003] Western medicine has obvious advantages in the acute stage of treating stroke. Clinically, thrombolysis, antiplatelet aggregation, anticoagulation, promoting brain metabolism, nourishing cranial nerves and other symptomatic treatments are often given. Early thrombolytic therapy can significantly reduce sequelae and improve the prognosis of patients. However, thrombolytic therapy has relatively strict indications and a short thrombolytic time window. Most patients cannot be sent to the hospital in time and miss the best period of thrombolysis. 70% of the surviving patients after treatment have different degrees of disability, bringing a heavy burden to their families and society.

[0004] In addition, although western medicine is commonly used in the clinical treatment of cerebral infarction, western medicine has large side effects, poor effects, and cannot fundamentally solve the cause and prevent cerebral infarction. Summary of the Invention

[0005] The main object of the present invention is to propose a traditional Chinese medicine composition, a traditional Chinese medicine preparation and their applications, aiming to solve the problems of large side effects, poor treatment effects and inability to prevent cerebral infarction of western medicine in the prior art.

[0006] To achieve the above object, the present invention proposes a traditional Chinese medicine composition, comprising the following raw materials in parts by weight:

[0007] Ephedra 5 - 20 parts;

[0008] Ramulus Cinnamomi 5 - 30 parts;

[0009] Fish oil 1 - 10 parts;

[0010] Angelica sinensis 5 - 25 parts;

[0011] Ligusticum wallichii 5 - 25 parts;

[0012] Peach kernel 5 - 20 parts;

[0013] Codonopsis pilosula 5 - 20 parts;

[0014] Fresh ginger 5 - 20 parts;

[0015] 5 - 30 parts of roasted licorice root; and 10 - 100 parts of gypsum.

[0016] In one embodiment, the traditional Chinese medicine composition further comprises the following raw materials in parts by weight: 1 - 10 parts of aconite, 5 - 15 parts of pinellia.

[0017] In one embodiment, the traditional Chinese medicine composition comprises the following raw materials in parts by weight: 5 - 15 parts of ephedra;

[0018] 5 - 15 parts of cassia twig;

[0019] 2 - 5 parts of fish oil;

[0020] 5 - 10 parts of angelica sinensis;

[0021] 5 - 10 parts of ligusticum wallichii;

[0022] 5 - 15 parts of peach kernel;

[0023] 5 - 10 parts of codonopsis pilosula;

[0024] 5 - 10 parts of ginger;

[0025] 5 - 15 parts of roasted licorice root; and 20 - 50 parts of gypsum.

[0026] In one embodiment, the traditional Chinese medicine composition comprises the following raw materials in parts by weight: 10 parts of ephedra;

[0027] 10 parts of cassia twig;

[0028] 5 parts of fish oil;

[0029] 9 parts of angelica sinensis;

[0030] 9 parts of ligusticum wallichii;

[0031] 10 parts of peach kernel;

[0032] 9 parts of codonopsis pilosula;

[0033] 9 parts of ginger;

[0034] 9 parts of roasted licorice root;

[0035] 30 parts of gypsum;

[0036] 9 parts of aconite; and,

[0037] 9 parts of pinellia.

[0038] In one embodiment, the fish oil contains EPA and DHA, and the mass ratio of the sum of the masses of EPA and DHA in the fish oil is greater than or equal to 70%.

[0039] In one embodiment, the type of aconite includes black prepared aconite or white prepared aconite; and / or,

[0040] The peach kernels include the processed product, stir-fried peach kernels; and / or,

[0041] The gypsum includes raw gypsum; and / or,

[0042] The pinellia includes the processed pinellia or the prepared pinellia.

[0043] The present invention also provides a traditional Chinese medicine preparation, which comprises the above traditional Chinese medicine composition.

[0044] In one embodiment, the type of the traditional Chinese medicine preparation includes mixture, concentrated decoction, pill or capsule.

[0045] The present invention also provides an application of the above traditional Chinese medicine composition or traditional Chinese medicine preparation in the preparation of an inhibitor for cerebral infarction.

[0046] In one embodiment, the cerebral infarction includes ischemic cerebral infarction.

[0047] The present invention provides a traditional Chinese medicine composition, a traditional Chinese medicine preparation and their applications. According to the compatibility principles of traditional Chinese medicine, the traditional Chinese medicine composition uses ephedra and cassia twig as the monarch drugs to disperse the striae of the skin and dispel cold pathogens. The compatibility of aconite root and fresh ginger has the effects of reinforcing fire and recuperating yang, dispersing wind-cold and dredging collaterals. Cassia twig also has the function of regulating nutrient qi and defensive qi, warming yang and promoting qi transformation. The compatibility of fresh ginger and peach kernels has the effects of warming the lungs and relieving cough, and treating fluid-retention. The compatibility of angelica sinensis and codonopsis pilosula supplements the lung qi, nourishes blood and promotes blood circulation. Codonopsis pilosula and honey-fried licorice replenish qi and strengthen the spleen, promote the production of body fluid and harmonize the stomach, preventing damage to healthy qi due to sweating. Gypsum is cold in nature, clearing heat and purging fire, restricting the warm nature of other drugs to prevent yin injury, which is used as an assistant in the opposite way. Fish oil and ligusticum wallichii promote blood circulation and remove blood stasis. Ligusticum wallichii can also ascend to the head, leading other drugs to reach the vertex, and when combined with angelica sinensis and peach kernels, it enhances the effects of promoting blood circulation and removing blood stasis, dispelling wind and dredging collaterals to achieve the effect of "when blood circulates smoothly, wind will subside by itself". Honey-fried licorice can also harmonize the middle energizer and relieve spasm, and coordinate various drugs, jointly exerting the effects of expelling wind and strengthening healthy qi, warming and dredging collaterals, promoting qi and removing blood stasis, and protecting cerebral blood vessels. The traditional Chinese medicine composition of the present invention has the characteristics of multiple targets and low toxicity and side effects. Its treatment of cerebral infarction mainly plays a role in improving hemorheology, inhibiting thrombus formation, enhancing the body's immunity, inhibiting the activation of microglia in the brain and the damage of mature neurons, and improving neuronal apoptosis. BRIEF DESCRIPTION OF THE DRAWINGS

[0048] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required for the description of the embodiments or the prior art. Obviously, the following drawings are only some embodiments of the present invention. For those of ordinary skill in the art, other drawings can be obtained based on the structures shown in these drawings without creative efforts.

[0049] Figure 1Graph showing the results of the Zea Longa neurological function symptom scores for the traditional Chinese medicine compositions in Example 1, Example 2, and Comparative Example 1 provided by the present invention in animal experiments;

[0050] Figure 2 Graph showing the results of the cerebral infarction volume for the traditional Chinese medicine compositions in Example 1, Example 2, and Comparative Example 1 provided by the present invention in animal experiments;

[0051] Figure 3 Graph showing the results of 2,3,5-triphenyltetrazolium chloride (TTC) staining for the traditional Chinese medicine compositions in Example 1, Example 2, and Comparative Example 1 provided by the present invention in animal experiments;

[0052] Figure 4 Graph showing the results of the brain water content for the traditional Chinese medicine compositions in Example 1, Example 2, and Comparative Example 1 provided by the present invention in animal experiments;

[0053] Figure 5 Graph showing the results of the activated partial thromboplastin time (APTT) for the traditional Chinese medicine compositions in Example 1, Example 2, and Comparative Example 1 provided by the present invention in animal experiments;

[0054] Figure 6 Graph showing the results of the prothrombin time (PT) for the traditional Chinese medicine compositions in Example 1, Example 2, and Comparative Example 1 provided by the present invention in animal experiments;

[0055] Figure 7 Graph showing the results of the thrombin time (TT) for the traditional Chinese medicine compositions in Example 1, Example 2, and Comparative Example 1 provided by the present invention in animal experiments;

[0056] Figure 8 Graph showing the results of the fibrinogen (FIB) for the traditional Chinese medicine compositions in Example 1, Example 2, and Comparative Example 1 provided by the present invention in animal experiments;

[0057] Figure 9 Graph showing the results of the anti-apoptotic factor Bcl-2 for the traditional Chinese medicine compositions in Example 1, Example 2, and Comparative Example 1 provided by the present invention in animal experiments;

[0058] Figure 10 Graph showing the results of the pro-apoptotic factor Bax for the traditional Chinese medicine compositions in Example 1, Example 2, and Comparative Example 1 provided by the present invention in animal experiments;

[0059] Figure 11 Graph showing the results of the pro-apoptotic factor Caspase-3 for the traditional Chinese medicine compositions in Example 1, Example 2, and Comparative Example 1 provided by the present invention in animal experiments;

[0060] Figure 12The result diagram of the apoptosis-promoting factor AIF in animal experiments using the Chinese medicine composition in Example 1, Example 2 and Comparative Example 1 provided by the present invention;

[0061] Figure 13 This is a graph showing the NeuN results of neurons in the hippocampus of brain tissue in animal experiments using the Chinese medicine compositions in Example 1, Example 2 and Comparative Example 1 provided by the present invention.

[0062] The realization of the purpose, functional features and advantages of the present invention will be further explained in conjunction with the embodiments and with reference to the accompanying drawings. Specific implementation method

[0063] In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be described clearly and completely below. If the specific conditions are not specified in the embodiments, they shall be carried out under conventional conditions or the conditions recommended by the manufacturer. The reagents or instruments used without indicating the manufacturer are all conventional products that can be purchased commercially. In addition, the meaning of "and / or" appearing in the full text includes three parallel solutions. Taking "A and / or B" as an example, it includes solution A, solution B, or solutions that satisfy both A and B. In addition, the technical solutions between the various embodiments can be combined with each other, but they must be based on the ability of ordinary technicians in this field to implement them. When the combination of technical solutions is contradictory or cannot be implemented, it should be deemed that such a combination of technical solutions does not exist and is not within the scope of protection required by the present invention. Based on the embodiments in the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0064] Cerebral infarction (CI) is the main manifestation of ischemic stroke. It is caused by ischemic necrosis or softening of local brain tissue due to cerebral blood supply disorder, ischemia and hypoxia. Common clinical types of cerebral infarction include cerebral thrombosis, lacunar infarction and cerebral embolism. Cerebral infarction accounts for 80% of all strokes. The main clinical manifestations are sudden fainting, unconsciousness, hemiplegia, speech disorders and intellectual disabilities. Cerebral infarction, as a sudden brain disease, can occur at any age, and is more common in middle-aged and elderly people aged 45 to 70. The onset is relatively rapid, with no prodromal symptoms. Focal neurological signs reach a peak in minutes to hours, and often present as complete stroke, with clear consciousness or mild disturbance of consciousness. Embolism of the internal carotid artery or middle cerebral artery trunk leads to large-area cerebral infarction, which may cause severe cerebral edema, increased intracranial pressure, and even brain herniation and coma, and rarely epileptic seizures; vertebral basilar artery system embolism often leads to coma, and in some cases, focal signs are stable or improved for a time and then worsen, indicating recurrence of infarction or secondary bleeding, etc.

[0065] ​Cerebral infarction belongs to the category of "stroke" in traditional Chinese medicine. Traditional Chinese medicine believes that the etiology and pathogenesis of ischemic stroke are complex, mainly including external deficiency, fire, wind, phlegm, qi, blood, etc., that is, it is closely related to internal injury accumulation, improper diet, obesity with phlegm abundance, qi deficiency with pathogenic factor invasion, etc. Its main causes are internal stirring of liver wind, insufficient blood supply to cerebral blood vessels, stagnant blood circulation, sequelae of stroke hemorrhage or trauma, resulting in anoxic necrosis of brain cells after concussion, blocked meridians, obstructed collaterals, emotional depression, phlegm turbidity obscuring the clear orifices, blood stasis blocking collaterals, coma, dementia, paralysis, inability to move the limbs, loss of memory or blindness due to cataract, headache, dizziness or unconsciousness, blood vessel sclerosis, hyperplasia, calcification, plaque formation with small thrombi, leading to insufficient oxygen supply, hemiplegia, aphasia, difficulty in eating and swallowing, disturbance of consciousness, etc. The internal carotid artery can cause blindness in the ipsilateral eye, but due to vascular diseases, there are sequelae such as hemiplegia, movement disorders, memory decline, abnormal gait, bedridden, inability to take care of oneself, muscle atrophy, joint stiffness and deformation, equinovarus, valgus foot, walking unsteadily, inability to bend fingers, etc.

[0066] In Western medicine theory, the coagulation function plays a key role in the pathogenesis of cerebral infarction. After the intima of the blood vessel wall is damaged, the formed elements in the blood are more likely to adhere and deposit, stimulating the release of more coagulation factors. Coupled with abnormal glucose and lipid metabolism in patients, the levels of lipoprotein, cholesterol, fibrinogen, etc. increase, comprehensively reducing the blood flow velocity and enhancing the blood coagulation state. Therefore, for patients with cerebral infarction, improving the hypercoagulable state of the blood is of great significance for restoring cerebral blood perfusion, restoring cerebral oxygen supply, promoting the rehabilitation of damaged nerve tissues, and reducing the complication rate.

[0067] Currently, drugs used to improve the hypercoagulable state of the blood include aspirin, etc., and its treatment mechanism lies in antiplatelet aggregation. However, 47% of aspirin takers will develop drug resistance, and long-term use will cause adverse reactions such as gastrointestinal damage, liver and kidney function damage, and impaired coagulation function. At the same time, aspirin only has a certain relieving effect and a role in preventing recurrence after the onset of cerebral infarction. It has no benefit for the treatment and prevention of ischemic stroke, but significantly increases the risk of bleeding, and it has no obvious repair effect on cerebral infarction tissue.

[0068] Therefore, although most cases of hemiplegia due to cerebral infarction are currently treated with Western medicine, Western medicine has large side effects, poor effects, and cannot fundamentally solve the etiology and effectively prevent cerebral infarction.

[0069] In view of this, the present invention provides a traditional Chinese medicine composition, comprising the following raw materials in parts by weight:

[0070] Ephedra 5 - 20 parts;

[0071] Ramulus Cinnamomi 5 - 30 parts;

[0072] Fish oil 1 - 10 parts;

[0073] 5 - 25 parts of Angelica sinensis;

[0074] 5 - 25 parts of Ligusticum wallichii;

[0075] 5 - 20 parts of Prunus persica;

[0076] 5 - 20 parts of Codonopsis pilosula;

[0077] 5 - 20 parts of Zingiber officinale;

[0078] 5 - 30 parts of roasted Glycyrrhiza uralensis Fisch.; and,

[0079] 10 - 100 parts of Gypsum fibrosum.

[0080] In the above formula, Ephedra: is the herbaceous stem of Ephedra sinica Stapf, Ephedra equisetina Bunge or Ephedra intermedia Schrenk ex Mey. of the Ephedraceae family, pungent, slightly bitter, warm in nature. It belongs to the lung and bladder meridians. It has the effects of inducing sweating and dispelling cold, dispersing the lung qi and relieving asthma, promoting diuresis and reducing swelling.

[0081] Ramulus Cinnamomi: is the dry tender branch of Cinnamomum cassia Presl of the Lauraceae family, pungent, sweet, warm in nature. It belongs to the heart, lung and bladder meridians. It has the effects of inducing sweating and releasing the muscles, warming and dredging the meridians, promoting yang qi transformation, and calming the rebellious qi.

[0082] Prunus persica: is the dry and mature seed of Prunus persica or Prunus davidiana of the Rosaceae family.

[0083] Angelica sinensis: is the dry root of Angelica sinensis (Oliv.) Diels of the Umbelliferae family, sweet, pungent, warm in nature. It belongs to the liver, heart and spleen meridians. It has the effects of enriching blood and promoting blood circulation, regulating menstruation and relieving pain, and moistening the intestines and promoting defecation.

[0084] Ligusticum wallichii: is the dry rhizome of Ligusticum sinense 'Chuanxiong' of the Umbelliferae family, pungent, warm in nature. It belongs to the liver, gallbladder and pericardium meridians. It has the effects of promoting blood circulation and qi movement, dispelling wind and relieving pain.

[0085] Codonopsis pilosula: is Panax ginseng C.A.Mey. of the Araliaceae family, sweet, slightly bitter, slightly warm in nature. It belongs to the spleen, lung, heart and kidney meridians. It has the effects of greatly tonifying primordial qi, restoring pulse and securing collapse, invigorating the spleen and replenishing the lung, promoting fluid production and nourishing blood, and calming the mind and improving intelligence.

[0086] Ginger: It is the dried rhizome of the plant Zingiber officinale Rosc. of the Zingiberaceae family. It has a pungent taste and a hot nature. It belongs to the spleen, stomach, kidney, heart, and lung meridians. It has the effects of warming the middle-jiao to dispel cold, restoring yang and promoting blood circulation, and warming the lungs to resolve fluid-retention.

[0087] Prepared Licorice Root: It is obtained by honey-baking the plant Glycyrrhiza uralensis Fisch. of the Leguminosae family. It has a sweet taste and a neutral nature. It belongs to the heart, lung, spleen, and stomach meridians. It has the effects of strengthening the spleen and stomach, and replenishing qi and restoring the pulse.

[0088] Gypsum: Its scientific name is Gypsum Fibrosum. It is a kind of gypsum of the anhydrite group of sulfate minerals. It has a sweet and pungent taste and a very cold nature. It belongs to the lung and stomach meridians. It has the effects of clearing heat and purging fire, and relieving restlessness and quenching thirst.

[0089] Fish Oil: It is the oil extracted from different kinds of fish, especially the oil extracted from fish rich in Omega-3 fatty acids. It has a sweet taste and a warm nature. It has the effects of promoting blood circulation and reducing blood lipid.

[0090] In the technical solution of the present invention, according to the compatibility principle of traditional Chinese medicine, the traditional Chinese medicine composition uses Ephedra and Cinnamon Twig as the monarch drugs to open the pores and dispel pathogenic cold. When combined with Aconite Root and Ginger, it has the effects of reinforcing fire and restoring yang, dispersing wind-cold, and dredging the meridians. Cinnamon Twig also has the function of regulating nutrient qi and defensive qi, warming yang and promoting qi transformation. When combined with Ginger and Peach Kernel, it has the effects of warming the lungs and relieving cough, and treating fluid-retention. Angelica Sinensis and Codonopsis Pilosula are combined to supplement the lung qi, nourish blood and promote blood circulation. Codonopsis Pilosula and Prepared Licorice Root replenish qi and strengthen the spleen, generate body fluid and harmonize the stomach, preventing excessive sweating from damaging healthy qi. Gypsum is cold in nature, clearing heat and purging fire, restricting the warm nature of other drugs to prevent yin injury, which is used as an assistant drug for counteraction. Fish Oil and Chuanxiong Rhizoma promote blood circulation and remove blood stasis. Moreover, Chuanxiong Rhizoma can rise to the head, leading other drugs to reach the vertex. When combined with Angelica Sinensis and Peach Kernel, it promotes blood circulation and removes blood stasis, dispels wind and dredges the meridians to achieve the effect of "when blood circulates smoothly, wind will disappear by itself". Prepared Licorice Root harmonizes the middle-jiao and relieves spasm, and coordinates various drugs, jointly exerting the effects of expelling wind and strengthening the healthy qi, warming and dredging the meridians, promoting qi movement and removing blood stasis, and protecting the cerebral blood vessels. The traditional Chinese medicine composition of the present invention has the characteristics of multiple targets and small toxic and side effects. Its treatment of cerebral infarction mainly plays a role in improving hemorheology, inhibiting thrombus formation, reducing blood lipid, enhancing the body's immunity, inhibiting the activation of microglia in the brain and the damage of mature neurons, and improving neuronal apoptosis.

[0091] In some embodiments of the present invention, the traditional Chinese medicine composition further includes the following raw materials in parts by weight: 1-10 parts of Aconite Root, and 5-15 parts of Pinellia Tuber.

[0092] Aconite Root: It is the processed product of the lateral root of the plant Aconitum carmichaelii Debx of the Ranunculaceae family. It has a pungent and sweet taste and a hot nature; it is toxic. It belongs to the heart, kidney, and spleen meridians. It has the effects of restoring yang from collapse, reinforcing fire and assisting yang, and dispelling cold and relieving pain.

[0093] Pinellia: The tuber of Pinellia ternata (Thunb.) Breit. of the Araceae family, which has the effects of drying dampness and resolving phlegm, lowering adverse qi and stopping vomiting, and dissipating binds and nodules.

[0094] In the technical solution of the present invention, aconite regulates the nutrient qi and defensive qi, and can warm yang and transform qi. When combined with ginger, pinellia, and peach kernel, it has the effects of warming the lungs and relieving cough, and treating phlegm retention. The aconite is preferably processed aconite slices.

[0095] In some embodiments of the present invention, the traditional Chinese medicine composition comprises raw materials in the following parts by weight:

[0096] Ephedra 5 - 15 parts;

[0097] Ramulus Cinnamomi 5 - 15 parts;

[0098] Fish oil 2 - 5 parts;

[0099] Angelica sinensis 5 - 10 parts;

[0100] Rhizoma Chuanxiong 5 - 10 parts;

[0101] Peach kernel 5 - 15 parts;

[0102] Codonopsis pilosula 5 - 10 parts;

[0103] Fresh ginger 5 - 10 parts;

[0104] Honey - fried Licorice Root 5 - 15 parts; and,

[0105] Gypsum 20 - 50 parts.

[0106] Under this formula, the effect of treating cerebral infarction is better.

[0107] In some embodiments of the present invention, the traditional Chinese medicine composition comprises raw materials in the following parts by weight:

[0108] Ephedra 10 parts;

[0109] Ramulus Cinnamomi 10 parts;

[0110] Fish oil 5 parts;

[0111] Angelica sinensis 9 parts;

[0112] Rhizoma Chuanxiong 9 parts;

[0113] Peach kernel 10 parts;

[0114] Codonopsis pilosula 9 parts;

[0115] Fresh ginger 9 parts;

[0116] Honey - fried Licorice Root 9 parts;

[0117] Gypsum 30 parts;

[0118] 9 parts of aconite root; and,

[0119] 9 parts of pinellia tuber.

[0120] Among them, ephedra and cassia twig are monarch drugs, fish oil, chuanxiong rhizome, angelica sinensis, aconite root, etc. are ministerial drugs, and peach kernel, codonopsis pilosula, ginger, licorice root, gypsum, pinellia tuber, etc. are assistant and guiding drugs. This formula has the best effect in preventing and treating cerebral infarction.

[0121] In some embodiments of the present invention, the fish oil includes EPA and DHA, and the mass ratio of the sum of the masses of EPA and DHA in the fish oil is greater than or equal to 70%. Omega-3 unsaturated fatty acids in fish oil, such as eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), etc., have good application prospects in the prevention and treatment of various cardiovascular diseases. In the technical solution of the present invention, EPA may be used as a precursor substance of series 3 prostaglandin (PG), and under the action of lipoxygenase / cyclooxygenase, active substances such as PG inhibitor (PGI3) and thromboxane A3 (TXA3) are generated, playing a role in inhibiting platelet aggregation and prolonging bleeding time. At the same time, DHA may participate in brain function to achieve the prevention and treatment of cerebral infarction.

[0122] In some embodiments of the present invention, the types of aconite root include black processed aconite root or white processed aconite root.

[0123] Among them, black processed aconite root is one of the products obtained after special processing of aconite root. Usually, other adjuvants, such as vinegar, wine, licorice root, black beans, etc., are added during the processing to make its color turn black or dark brown. The medicinal effect of black processed aconite root is stronger. White processed aconite root is another common processed product of aconite root. Its processing process removes more impurities and toxic components, and its color is lighter, close to white or light yellow. The processing degree of white processed aconite root is deeper, the toxicity is weakened, and it is easy to decoct.

[0124] In some embodiments of the present invention, the peach kernel includes stir-fried peach kernel. Stir-fried peach kernel is a processed form of traditional Chinese medicine peach kernel. The stir-fried peach kernel is easier to digest and absorb. Stir-fried peach kernel is often used for promoting blood circulation to remove blood stasis, moistening the intestines and relieving constipation, etc.

[0125] In some embodiments of the present invention, the gypsum includes raw gypsum. Compared with other processed products, such as calcined gypsum (the main component becomes anhydrous calcium sulfate), the main component of raw gypsum is calcium sulfate dihydrate, which has the effect of enhancing clearing heat and detoxifying, promoting the production of body fluid and quenching thirst, and is more suitable for the symptoms of cerebral infarction.

[0126] In some embodiments of the present invention, the pinellia tuber includes qingbanxia or fahualixia. Qingbanxia is obtained by directly soaking the freshly collected pinellia tuber in clean water and changing the water several times until its taste becomes lighter; fahualixia is pinellia tuber processed by a specific processing method, usually including processing with adjuvants such as lime water or licorice root.

[0127] The present invention also provides a traditional Chinese medicine preparation, which comprises the above-mentioned traditional Chinese medicine composition.

[0128] The traditional Chinese medicine preparation comprises all the technical solutions of the pharmaceutical composition, and thus also has all the beneficial effects brought by the above solutions, which will not be elaborated herein one by one.

[0129] In some embodiments of the present invention, the types of the traditional Chinese medicine preparation include mixture, paste, pill or capsule. The types of the traditional Chinese medicine preparation can be changed according to specific usage scenarios to achieve the best therapeutic effect.

[0130] The present invention also provides an application of the above-mentioned traditional Chinese medicine composition or traditional Chinese medicine preparation in the preparation of an inhibitor for cerebral infarction.

[0131] The application comprises all the technical solutions of the pharmaceutical composition, and thus also has all the beneficial effects brought by the above solutions, which will not be elaborated herein one by one.

[0132] In some embodiments of the present invention, the cerebral infarction includes ischemic cerebral infarction. The traditional Chinese medicine composition or traditional Chinese medicine preparation of the present invention can significantly reduce the cerebral infarction volume and brain water content of model animals, improve brain edema and blood coagulation function, so as to regulate the phenomenon of poor blood circulation and repair necrotic brain tissue. Therefore, it can be used for the prevention and treatment of ischemic cerebral infarction, that is, ischemic stroke.

[0133] The technical solutions of the present invention will be further described in detail below with reference to specific embodiments and drawings. It should be understood that the following embodiments are only used to explain the present invention and are not used to limit the present invention.

[0134] Example 1

[0135] A traditional Chinese medicine composition, comprising:

[0136] 10 g of Ephedra, 10 g of Cinnamon Twig, 2 g of fish oil, 10 g of Peach Kernel, 6 g of Prepared Licorice Root, 9 g of Angelica Sinensis, 9 g of Chuanxiong Rhizome, 9 g of Codonopsis Pilosula, 9 g of Ginger, 10 g of Gypsum.

[0137] Example 2

[0138] A traditional Chinese medicine composition, comprising:

[0139] 10 g of Ephedra, 10 g of Cinnamon Twig, 5 g of fish oil, 10 g of Peach Kernel, 9 g of Prepared Licorice Root, 9 g of Angelica Sinensis, 9 g of Chuanxiong Rhizome, 9 g of Codonopsis Pilosula, 9 g of Ginger, 9 g of Aconite Lateralis Preparata, 20 g of Gypsum, 9 g of Pinellia Ternata.

[0140] Comparative Example 1

[0141] A traditional Chinese medicine composition, comprising:

[0142] Ephedra 10g, Cinnamon Twig 10g, Peach Kernel 10g, Prepared Licorice Root 6g, Angelica Sinensis 3g, Chuanxiong Rhizome 3g, Gypsum 5g.

[0143] Performance Test

[0144] Preparation of Traditional Chinese Medicine Composition: Weigh Ephedra, Cinnamon Twig, Angelica Sinensis, Chuanxiong Rhizome, Peach Kernel, Codonopsis Pilosula, Fresh Ginger, Prepared Licorice Root, Gypsum, Aconite Root, and Pinellia Ternata in Examples 1 - 2 and Comparative Example 1 according to the corresponding proportions, add 8 times the weight of water, soak for 30 - 40 minutes, bring to a boil over high heat, then simmer for 30 minutes. After filtering the medicinal liquid through a 200 - mesh sieve, conduct a second decoction in the same manner. Concentrate the medicinal liquid from the two decoctions into an extract, add fish oil in the corresponding proportion, and stir evenly to obtain 3 groups of traditional Chinese medicine compositions.

[0145] Drug Group: Take the 3 groups of traditional Chinese medicine compositions prepared above and prepare a medicinal liquid with a concentration of 1 g / mL using pure water.

[0146] Animal Grouping, Modeling, and Administration:

[0147] 1. Adaptation Period: 100 SPF - grade male SD rats, 6 - 7 weeks old, with a body weight of (250 ± 20) g, provided by Hunan Slack Jingda Experimental Animal Co., Ltd. The production license number of experimental animals is SCXK(Xiang)2019 - 0004 (valid until June 05, 2024), issued by the Hunan Provincial Department of Science and Technology. Observe the experimental rats for 7 days during the adaptation period, and enter the formal experimental period after no abnormalities are found.

[0148] 2. Modeling Period and Grouping: Middle cerebral artery occlusion (MCAO) is the most commonly used focal cerebral ischemia (ischemic stroke / cerebral infarction) model. In the MCAO model, the external carotid artery (ECA) and its branches are blocked first, and the pterygopalatine artery (PPA) is also blocked to cut off the collateral circulation blood flow from extracranial sources. Insert a nylon thread through the ECA, pass through the internal carotid artery (ICA) to the anterior cerebral artery (ACA), and mechanically block the blood supply at the origin of the middle cerebral artery (MCA) to establish a middle cerebral artery ischemia model. This model can remove the nylon thread under non - anesthetic conditions to restore blood flow and achieve reperfusion. The suture method has the advantages of not opening the skull, definite effect, and accurate control of ischemia and reperfusion time. It is ideal for studying the sensitivity and tolerance of neurons to ischemia, observing drug efficacy, as well as reperfusion injury and treatment time window. At the same time, it also has the characteristics of little impact on the whole body and long animal survival time, and is suitable for the study of chronic brain injury. By controlling the variable factors, the instability of experimental results can be avoided.

[0149] Fifteen cases were randomly selected as the sham operation group, and the remaining 85 cases were used for MCAO model establishment. A fish line was inserted into the middle cerebral artery of the ICA. After model preparation, scoring was performed according to the 5-point method of Zea Longa. Animals with a first score of 1-3 were considered to have successfully established the model. At least 60 modeled animals were selected and then grouped into a model group, Comparative Example 1, Example 2, and Example 3, with at least 15 animals in each group.

[0150] Table 1 Zea Longa Neurological Function Symptom Scoring Table

[0151] Score Neurological symptoms 0 No neurological deficit symptoms 1 Mild focal neurological deficit, that is, the left forepaw cannot be extended when lifting the tail and suspending in the air 2 Moderate focal neurological deficit, that is, walking in circles to the left 3 Moderate focal neurological deficit, that is, difficulty walking and falling to the left

[0152] 3. Administration of drugs: After model establishment and grouping, the animals in each group were given intragastric administration of drugs. The administration volume was 10 mL / kg, once a day for 14 consecutive days. The blank group and the model control group were given an equal volume of pure water, and the drug groups were given drugs according to the set doses.

[0153] 4. Index determination and final treatment: Zea Longa scores were performed before drug administration and on the 14th day of drug administration. After the neurological function symptom scoring was completed on the 14th day of drug administration, the animals were euthanized by drawing blood from the abdominal aorta after anesthesia. After blood collection, the serum was separated and divided into 2 parts. One part was used to measure the four coagulation items, namely prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB); one part was stored at -80 °C for subsequent detection. After the final treatment, the brain tissues of 7 animals in each group were used to measure the percentage of cerebral infarction volume and the percentage of brain water content; the remaining brain tissues of the animals in each group were homogenized and used to detect the expression levels of apoptosis-related factors Bcl-2, Bax, Caspase-3, AIF, and NeuN proteins.

[0154] Method for measuring the percentage of cerebral infarction volume: Place the rat brain tissue in a glass dish and cut it into 5 slices with a blade, cutting one slice every 2 mm. The first cut is at the midpoint of the line connecting the anterior pole of the brain and the optic chiasm, the second cut is at the optic chiasm, the third cut is at the infundibulum, and the fourth cut is between the infundibulum and the caudal pole of the posterior lobe; place the brain slices in a glass dish containing 1% TTC solution, cover them with tin foil to avoid light, and place them in a 37 °C constant temperature incubator to avoid light for 20 min. Turn the brain slices once at the 10th minute, and be careful and gentle when turning to make them evenly contact the staining solution; after TTC staining, place the brain slices in 10% formaldehyde solution to fix them in the dark for 24 h and then take them out for photography; use Image J image analysis software to analyze the cerebral infarction area. The normal part is red and the infarcted part is white. Calculate the cerebral infarction volume according to the volume calculation formula. In order to reduce the influence of brain swelling and individual differences on the experimental results, the results are expressed as the ratio of cerebral infarction volume; calculate and statistically analyze according to the following formula:

[0155] Infarct volume: V = (A1 + A2 + … + An)t / 2

[0156] Note: t is the slice thickness. A1 and A2 respectively represent the infarct areas at the rostral and caudal ends of the cut block. Infarct volume ratio (%) = infarct volume / ipsilateral cerebral hemisphere volume × 100%

[0157] Method for measuring the percentage of brain water content: Immediately weigh the brain after removal, which is the wet brain weight. After TTC staining, place the brain slices in a glass dish lined with tin foil paper and dry them in an oven until constant weight, which is the dry brain weight. Calculate and statistically analyze according to the following formula:

[0158] Percentage of brain water content = (wet brain weight - dry brain weight) / wet brain weight × 100%

[0159] 5. Data processing: After the data is processed by ECGAUTO software, it is statistically analyzed using SPSS 17.0 statistical software. The measurement data of each group are expressed as x-±sem. Each experimental group is compared with that before drug administration using the Student-T test (paired T test) for statistics. Before comparing between experimental groups, one-way ANOVA (F-test) is performed first. When the variances between groups are homogeneous, the Student-T test (unpaired T test) is used for comparison between groups. When the variances between groups are not homogeneous, the corrected Student-T test is used for statistical analysis.

[0160] Experimental results

[0161] 1. Zea Longa neurological function scores of rats in each group before and after treatment

[0162] It can be seen from Figure 1 that compared with the blank group, the Zea Longa score of the model group increased significantly (P < 0.01), and there was no significant change before and after treatment (P > 0.05), indicating that the MCAO rat model was successfully established and the disease model was stable. After 14 days of drug treatment, the results showed that there were significant differences between Comparative Example 1, Example 1 and Example 2 and the model group (P < 0.05), which could significantly improve the neurobehavior of MCAO rats. Among them, the statistical difference of Example 2 was the most significant, preliminarily indicating that Example 1 and Example 2 had good therapeutic effects on rats with cerebral infarction.

[0163] Figure 1 Among them, ** indicates a very significant difference compared with the blank group (P < 0.01); # indicates a significant difference compared with the model group (P < 0.05), and ## indicates a very significant difference compared with the model group (P < 0.01).

[0164] 2. Results of infarct volume of rats in each group

[0165] As Figure 2 and Figure 3As shown: After TTC staining, it was found that the TTC staining of the brain tissue of rats in the blank group was normal without abnormal necrosis; the left brain tissue of rats in the model group was severely necrotic with a large infarct area in the brain tissue (white area); there was no significant difference between Comparative Example 1 and the model group, indicating that it had no obvious therapeutic effect on the treatment of cerebral infarction. Both Example 1 and Example 2 had a certain therapeutic effect on rats with cerebral infarction. Among them, the therapeutic effect of Example 2 was the most significant, the infarct area of TTC staining was significantly reduced, which could effectively improve the necrosis of rat brain tissue and had a good protective effect on the brain tissue. It shows that the formula compatibility of Example 2 is scientific and effective, and the therapeutic effect is remarkable.

[0166] Figure 2 Among them, ** indicates a very significant difference compared with the blank group (P < 0.01); # indicates a significant difference compared with the model group (P < 0.05), and ## indicates a very significant difference compared with the model group (P < 0.01).

[0167] 3. Water content of brain tissue in each group of rats

[0168] By measuring the water content of brain tissue in different groups of rats, the results are as Figure 4 shown: After modeling, it was found that the water content of the brain of rats in the model group increased significantly (P < 0.01), showing the phenomenon of brain edema, indicating that the brain tissue of rats in the model group presented pathological damage. After treatment with the traditional Chinese medicine composition, the brain water volume showed a downward trend, indicating that after drug treatment, the brain edema state of rats with cerebral infarction was alleviated to a certain extent; among them, there was a significant difference between Example 1 and Example 2 compared with the model group, and the statistical difference of Example 2 was the most obvious, indicating that it had a good therapeutic effect on the brain edema caused by cerebral infarction and had a certain protective effect on the brain tissue.

[0169] Figure 4 Among them, ** indicates a very significant difference compared with the blank group (P < 0.01); # indicates a significant difference compared with the model group (P < 0.05), and ## indicates a very significant difference compared with the model group (P < 0.01).

[0170] 4. Determination of four coagulation items in each group of rats

[0171] By measuring the four coagulation items of blood in different groups of rats, the results are as Figure 5 、 Figure 6 、 Figure 7 and Figure 8Shown as follows: Compared with the blank group, the contents of PT, APTT and TT in the blood of the model group decreased significantly, while the content of FIB increased significantly, indicating that blood coagulation and thrombosis occurred in MCAO rats, resulting in obstruction of cerebral blood flow and cerebral ischemia. After treatment with the traditional Chinese medicine group, the coagulation indexes were improved to varying degrees, indicating that traditional Chinese medicine has a good regulatory effect on the poor blood circulation caused by cerebral infarction. Compared with the model group, the contents of PT, APTT and TT in Examples 1 and 2 increased significantly, while the content of FIB decreased significantly, which can effectively treat blood coagulation and thrombosis after cerebral infarction, regulate the blood circulation of the heart and brain, and thus play the effects of promoting blood circulation to remove blood stasis and promoting qi and nourishing blood.

[0172] Figures 5 to 8 In the figure, ** indicates a very significant difference compared with the blank group (P<0.01); # indicates a significant difference compared with the model group (P<0.05), and ## indicates a very significant difference compared with the model group (P<0.01).

[0173] 5. Expression of cell necrosis and apoptosis-related factors in the brain tissues of each group

[0174] By detecting the contents of cell necrosis and apoptosis-related factors in the brain tissues of rats in different groups, the results are as Figure 9 、 Figure 10 、 Figure 11 and Figure 12 shown as follows: Compared with the blank group, the anti-apoptotic factor Bcl-2 in the model group decreased significantly, while the pro-apoptotic factors Bax, Caspase-3 and AIF increased significantly, indicating that the apoptosis of brain tissue cells in rats with cerebral infarction was aggravated, resulting in a deeper degree of cerebral infarction and the inability of the infarcted tissue to be repaired normally. After treatment with the traditional Chinese medicine group, Comparative Example 1 had a regulatory effect on the expression trends of apoptosis-related factors Bcl-2, Bax, Caspase-3 and AIF. Examples 1 and 2 could significantly increase Bcl-2 and decrease the contents of Bax, Caspase-3 and AIF. Among them, the effect of Example 2 was the most significant, indicating that it could effectively inhibit the apoptosis and necrosis process of brain tissue cells, promote the repair of necrotic brain tissue, had a good repair effect on the necrotic brain tissue of rats with cerebral infarction, and could effectively protect the tissue.

[0175] Figures 9 to 12 In the figure, ** indicates a very significant difference compared with the blank group (P<0.01); # indicates a significant difference compared with the model group (P<0.05), and ## indicates a very significant difference compared with the model group (P<0.01).

[0176] 6. Expression of neuron cells - NeuN in the hippocampal region of the brain tissues of each group of rats

[0177] After cerebral infarction, it is accompanied by brain tissue death and focal neuronal damage. Neuronal nuclei (NeuN) is a neuron-specific nuclear protein, mainly expressed in mature neurons, and can be used as a reliable marker for mature neurons. On the basis of the above research, the effect of the drug on neuronal cells was further investigated by immunohistochemical determination of NeuN expression. The results are as Figure 13 shown: Compared with the blank group, the expression level of NeuN in the hippocampal region of the rats in the model group was significantly decreased, indicating significant neuronal necrosis or nerve injury in the cerebral infarction rats; compared with the model group, there was a tendency to increase the expression level of NeuN in Comparative Example 1, but there was no statistical difference. The expression levels of NeuN in Example 1 and Example 2 were significantly increased, and the effect of Example 2 was the most obvious, indicating that it could effectively restore neuronal injury in the brain, repair necrotic nerve cells and brain tissue, and thus effectively relieve the symptoms of cerebral infarction.

[0178] Figure 13 Among them, ** indicates a very significant difference compared with the blank group (P < 0.01); # indicates a significant difference compared with the model group (P < 0.05), and ## indicates a very significant difference compared with the model group (P < 0.01).

[0179] In summary, the traditional Chinese medicine composition provided by the present invention has a good therapeutic effect on the rat cerebral infarction (ischemic cerebral infarction) model induced by the MCAO method: (1) In terms of neurobehavior: significantly reduced the pathological behavior score of the model rats, improved the physiological state of the rats, and had a good therapeutic effect; (2) TTC staining: significantly reduced the cerebral infarction volume of the model rats, significantly reduced the brain water content of the model rats, and improved the brain edema of the model rats; (3) Significantly improved the coagulation index, indicating that the traditional Chinese medicine composition of the present invention has a good regulatory effect on the poor blood circulation caused by cerebral infarction; (4) The traditional Chinese medicine composition of the present invention can regulate the expression of apoptosis factors Bcl-2, Bax, Caspase-3, and AIF, has a good repair effect on the necrotic brain tissue of cerebral infarction rats, and can effectively protect tissues; (5) The traditional Chinese medicine composition of the present invention can effectively restore neuronal injury in the brain, repair necrotic nerve cells and brain tissue, further improve nerve function, and thus effectively relieve the symptoms of cerebral infarction.

[0180] The above are only the preferred embodiments of the present invention, and do not limit the patent scope of 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 in the patent protection scope of the present invention.

Claims

1. A Chinese medicine composition for ischemic cerebral infarction, characterized in that: It is composed of the following raw materials in parts by weight: Ephedra 5-20 parts; 5-30 parts of cinnamon twig; 1-10 portions of fish oil; 5-25 parts of Chinese Angelica; 5-25 parts of Chuanxiong; 5-20 portions of peach kernels; 5-20 parts of Codonopsis pilosula; 5~20 portions of ginger; 5-30 portions of roasted licorice root; 10~100 parts of gypsum; 1-10 parts of Aconite root; and 5 to 15 servings of Pinellia ternata.

2. The Chinese medicine composition according to claim 1, characterized in that The Chinese medicine composition is composed of the following raw materials in parts by weight: Ephedra 5-15 parts; 5-15 parts of cinnamon twig; 2-5 servings of fish oil; 5-10 parts of Chinese Angelica; 5-10 parts of Chuanxiong; 5-15 servings of peach kernels; 5-10 parts of Codonopsis pilosula; 5-10 portions of ginger; 5-15 parts of roasted licorice root; 20~50 parts of gypsum; 1-10 parts of Aconite root; and 5 to 15 servings of Pinellia ternata.

3. The Chinese medicine composition according to claim 1, characterized in that: The Chinese medicine composition is composed of the following raw materials in parts by weight: Ephedra 10 parts; 10 parts of cinnamon twig; 5 servings of fish oil; Angelica 9 parts; 9 parts of Chuanxiong; 10 portions of peach kernels; 9 parts of Codonopsis pilosula; 9 parts ginger; 9 parts of roasted licorice root; 30 parts of gypsum; 9 parts of Aconite root; and 9 servings of Pinellia ternata.

4. The Chinese medicine composition according to claim 1, characterized in that: The fish oil contains EPA and DHA, and the sum of the masses of EPA and DHA in the fish oil accounts for greater than or equal to 70% of the mass.

5. The Chinese medicine composition according to claim 1, characterized in that: The type of the aconite is Heishunpian or Baifupian; and / or, The peach kernel is a processed product, stewed peach kernel; and / or, The gypsum is raw gypsum; and / or, The pinellia ternata is Qing pinellia ternata or French pinellia ternata.

6. A Chinese medicine preparation, characterized in that: Made from the Chinese medicine composition according to any one of claims 1 to 5.

7. The Chinese medicine preparation according to claim 6, characterized in that: The type of the Chinese medicine preparation is mixture, ointment, pill or capsule.

8. Use of the Chinese medicine composition according to any one of claims 1 to 5 or the Chinese medicine preparation according to any one of claims 6 to 7 in the preparation of an inhibitor of ischemic cerebral infarction.

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