Compound traditional Chinese medicine composition for improving cerebral ischemia-reperfusion nerve injury and application

Abstract

The invention belongs to the technical field of traditional Chinese medicine, and particularly relates to a compound traditional Chinese medicine composition for improving cerebral ischemia-reperfusion nerve injury and application. The compound traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 288 to 435 parts of radix astragali seu hedysari, 120 to 180 parts of radix angelicae sinensis, 80 to 120 parts of rhizoma chuanxiong, 80 to 120 parts of radix paeoniae rubra, 80 to 120 parts of semen persicae, 80 to 120 parts of flos carthami, 80 to 120 parts of pericarpium citri reticulatae, 80 to 120 parts of rhizoma atractylodis macrocephalae, 80 to 120 parts of radix codonopsis, 80 to 120 parts of poria cocos, 32 to 48 parts of centipede, 80 to 120 parts of earthworm, 80 to 120 parts of bombyx batryticatus and 48 to 72 parts of liquorice root. The traditional Chinese medicine composition has the advantages that the traditional Chinese medicine composition is mainly used for tonifying qi and promoting blood circulation to jointly achieve the effects of regulating qi and promoting blood circulation, and dispersing blood stasis and promoting coronary circulation, is reasonable in formula compatibility, is mutually associated, is scientifically prepared, has very good beneficial technical effects through experiments, and has a remarkable effect of improving cerebral ischemia-reperfusion nerve injury.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicine, and specifically relates to a compound Chinese medicine composition for improving cerebral ischemia-reperfusion nerve injury and an application thereof. Background Art

[0002] Ischemic stroke (IS), also known as cerebral infarction, is a common cerebrovascular disease with transient or permanent ischemia and hypoxia in the brain, which leads to ischemia and hypoxic necrosis of local brain tissue, and a clinical syndrome of rapid development of corresponding neurological deficits. Ischemic stroke is the most common type of cerebrovascular disease. Patients mainly show focal neurological deficits, such as hemiplegia, sensory impairment, aphasia, ataxia, etc., and may also have headaches, vomiting, coma, etc. The prognosis is good for mild cases, but life is endangered in severe cases.

[0003] At present, the treatment of ischemic stroke is determined according to different causes, pathogenesis, clinical types, onset time, etc., and individualized treatment is implemented. The general treatment methods are 1) oxygen inhalation and ventilation support, 2) cardiac monitoring and treatment of cardiac lesions: routine electrocardiogram examination should be performed within 24 hours after onset, and electrocardiogram monitoring can be performed according to the condition if conditions permit, 3) temperature control, 4) blood pressure and blood sugar control, 5) nutritional support. Vomiting and dysphagia after onset can cause dehydration and malnutrition, leading to slower recovery of neurological function. Attention should be paid to the assessment of fluid and nutritional status. On the basis of general supportive treatment, measures such as improving cerebral circulation, brain protection, anti-cerebral edema, and reducing intracranial pressure should be used as appropriate. The specific treatment methods for ischemic stroke are mainly intravenous thrombolysis and intravascular interventional therapy. Intravenous thrombolysis therapy with tissue-type plasminogen activator within 3 hours of onset is the only drug treatment method that has been proven to have significant efficacy in rigorous clinical scientific trials and approved for use in acute stroke, but due to the limitation of the time window, it has certain limitations in clinical practice. However, the resulting cerebral ischemia reperfusion injury (CI / RI) further hinders the recovery of patients' neurological function and is currently an important stumbling block in the rehabilitation of ischemic stroke. Therefore, how to provide neuroprotection during the reperfusion period after ischemic stroke is of great significance for disease management.

[0004] CI / RI does not have a specific name in traditional Chinese medicine books, but according to the onset characteristics and clinical manifestations, it can be classified as a "stroke" in traditional Chinese medicine. Its pathogenesis lies in the imbalance of yin and yang, disorder of qi and blood, and direct attack on the brain. Insufficient qi and blood or liver and kidney yin deficiency are the root causes of the disease, resulting in blockage of brain veins or blood overflowing outside the brain veins.

[0005] Traditional Chinese medicine follows the principle of holistic syndrome differentiation and treatment, has a complex chemical composition, and has unique advantages such as multiple components, multiple targets, and improved microcirculation. It is also highly praised for its good clinical efficacy, diverse treatment methods, few side effects, and high safety.

[0006] Therefore, it is of great practical significance to develop Chinese herbal preparations for preventing and treating cerebral ischemic injury and further enrich and improve the scientific connotation of the "stroke" theoretical system of traditional Chinese medicine. Summary of the invention

[0007] In view of the deficiencies in the prior art, the present invention provides a compound Chinese medicine composition for improving cerebral ischemia-reperfusion nerve injury and its application.

[0008] In order to achieve the purpose of the present invention, the technical solution adopted is as follows:

[0009] A compound Chinese medicine composition for improving cerebral ischemia-reperfusion nerve injury, characterized in that the raw materials of the Chinese medicine composition include the following original components in parts by weight: 288-435 parts of astragalus, 120-180 parts of angelica, 80-120 parts of chuanxiong, 80-120 parts of red peony root, 80-120 parts of peach kernel, 80-120 parts of safflower, 80-120 parts of tangerine peel, 80-120 parts of atractylodes, 80-120 parts of codonopsis, 80-120 parts of tuckahoe, 32-48 parts of centipede, 80-120 parts of earthworm, 80-120 parts of bombyx batryticatus and 48-72 parts of liquorice.

[0010] Among the above medicinal flavors,

[0011] Astragalus: sweet, slightly warm. Enters the lung and spleen meridians. Replenishes qi and raises yang, strengthens the body's defense system, promotes diuresis and reduces swelling, promotes the production of body fluids and nourishes blood, relieves stagnation and relieves arthritis, removes toxins and discharges pus, and heals sores and promotes tissue regeneration. It is an important medicine for replenishing the middle qi and replenishing qi, and is used for spleen and lung qi deficiency syndrome, qi deficiency and spontaneous sweating syndrome; it also replenishes qi to promote blood circulation, and is used for arthritis and sequelae of stroke.

[0012] Angelica: Sweet, pungent, warm. Enters the liver, heart, and spleen meridians. Nourishes blood and activates blood circulation, moistens the intestines and promotes bowel movements. Good at nourishing blood, it is a sacred medicine for nourishing blood, used for various symptoms of blood deficiency, abdominal pain due to deficiency and cold, injuries from falls, carbuncles, sores, and pain due to wind and cold.

[0013] Chuanxiong: pungent, warm. Enters the liver, gallbladder, and pericardium meridians. It promotes blood circulation and qi, dispels wind and relieves pain. It is a "qi medicine in the blood", which can not only promote blood circulation and remove blood stasis, but also promote qi and relieve pain, and treat chest pain caused by blood stasis in the heart vessels; it can also "go up to the head", dispel wind and relieve pain, and is an important medicine for treating headaches. Regardless of wind-cold, wind-heat, rheumatism, blood deficiency, or blood stasis headaches, it can be used in combination according to the symptoms. Li Dongyuan said, "Headache needs Chuanxiong."

[0014] Red Peony Root: bitter, slightly cold. Enters the Liver Channel. Clears heat and cools blood, dissipates blood stasis and relieves pain. Enters the blood of the Liver Channel, has the function of promoting blood circulation, dissipating blood stasis and relieving pain, and treats the pain in the ribs caused by liver depression and blood stasis. Used for heat entering the blood, fever and toxicity, vomiting blood and bleeding, red and swollen eyes, liver depression and pain in the ribs, amenorrhea, dysmenorrhea, abdominal pain due to lumps and masses, injuries from falls, carbuncles, sores and ulcers.

[0015] Peach kernel: bitter, sweet, neutral. Enters the heart, liver, and large intestine meridians. It activates blood circulation and removes blood stasis, moistens the intestines and promotes bowel movements, relieves cough and asthma. It is good at relieving blood stasis and has strong blood stasis removal ability. It is a commonly used medicine for treating various blood stasis diseases. It is used for various blood stasis diseases and activates blood circulation and removes blood stasis to eliminate carbuncle.

[0016] Safflower: pungent, warm. It enters the heart and liver meridians. It promotes blood circulation and relieves pain. It is an important medicine for promoting blood circulation and removing blood stasis, relieving pain. It is good at treating heart and abdomen pain caused by blood stasis, chest pain and heart pain. It is also good at promoting blood circulation, reducing swelling and relieving pain. It is used for headache caused by blood stasis, dizziness, and hemiplegia caused by stroke.

[0017] Tangerine peel: bitter, pungent, warm. Enters the lung and spleen meridians. Regulates qi and strengthens the spleen, dries dampness and resolves phlegm. Has the functions of promoting qi and relieving pain, strengthening the spleen and harmonizing the middle. Because it is bitter, warm and dry, it is most suitable for treating qi stagnation in the middle due to cold and dampness. It is good at regulating qi, smoothing the middle jiao and making it rise and fall in an orderly manner, and can promote qi and relieve numbness and relieve pain.

[0018] Atractylodes macrocephala: bitter, sweet, warm. Enters the spleen and stomach meridians. Strengthens the spleen and replenishes qi, dries dampness and promotes diuresis, stops sweating, and calms the fetus. With the main function of strengthening the spleen and drying dampness, it was praised by the predecessors as "the first medicine for replenishing qi and strengthening the spleen". Its effect is similar to that of Astragalus but slightly weaker. It is used for spleen deficiency, poor appetite, fatigue, phlegm and fluid, dizziness and palpitations, and spontaneous sweating due to qi deficiency.

[0019] Codonopsis: sweet, neutral. Enters the spleen and lung meridians. Replenishes spleen and lung qi, replenishes blood, produces body fluid, and strengthens the body and eliminates evil. It mainly enters the spleen and lung meridians, and its main function is to replenish the qi of the spleen and lung. It can replenish qi and blood, and is often used for qi and blood deficiency syndromes such as qi deficiency that cannot produce blood, or blood deficiency that cannot transform qi. It can also strengthen the body and eliminate evil, so that the evil is attacked without hurting the body qi, and is used to treat qi deficiency, external infection, or internal heat accumulation and qi and blood deficiency, and other syndromes of evil excess and body deficiency.

[0020] Poria: sweet, light, neutral. Enters the heart, lung, spleen, and kidney meridians. It can promote diuresis and eliminate dampness, strengthen the spleen, and calm the mind. It tastes sweet and light, has a mild medicinal property, can dispel evil, and can strengthen the body, promote diuresis without hurting the body's vital energy. It is an important medicine for promoting diuresis and reducing swelling, and can be used to treat various edemas caused by cold, heat, deficiency, and excess; it can benefit the heart and spleen and calm the mind and tranquilize the nerves. It can be used to treat palpitations, insomnia, and forgetfulness caused by deficiency of both the heart and spleen, and insufficient qi and blood.

[0021] Centipede: pungent, warm; poisonous. Enters the liver meridian. It can extinguish wind and calm convulsions, attack toxins and dissipate stagnation, and dredge meridians and relieve pain. It is an important medicine for extinguishing wind, treating spasms and convulsions caused by various reasons, has good effects of dredging meridians and relieving pain, and is used to treat stubborn headaches.

[0022] Earthworm: salty, cold. Enters the liver, spleen, and bladder meridians. Clears heat and calms the nerves, dredges the meridians, relieves asthma, and promotes diuresis. Used for high fever and coma, epilepsy and convulsions, joint pain, limb numbness, hemiplegia, lung heat and cough, edema and oliguria. Clears heat and calms the nerves, dredges the meridians, relieves asthma, and promotes diuresis. It can extinguish wind and stop spasms, and is good at clearing heat and calming the nerves. It is suitable for coma and delirium, spasms and convulsions or epilepsy, convulsions, etc. caused by extreme heat and wind. It is good at clearing the meridians and is used to treat qi deficiency and blood stasis, and hemiplegia.

[0023] Bombyx Batryticatus: salty, pungent, neutral. Enters the liver, lung, and stomach meridians. Calms wind and stops spasms, dispels wind and calms convulsions, resolves phlegm and disperses stagnation. It can not only extinguish wind and stop spasms, but also resolve phlegm and calm convulsions. It is especially suitable for convulsions, epilepsy and phlegm-heat. It can dispel wind, resolve phlegm, and dredge meridians. It is used to treat wind-heat headaches.

[0024] Licorice: sweet and mild in nature, it enters the heart, lung, spleen, and stomach meridians. Licorice is sweet, nourishing, moistening, and slow in action. It is cool when raw, and warm when roasted. It mainly enters the spleen and lung meridians, and also enters the stomach and heart meridians. It nourishes the spleen and replenishes qi, removes phlegm and relieves cough, relieves urgency and relieves pain, clears away heat and detoxifies, and harmonizes various medicines. It can replenish the heart qi and restore the pulse. It is mainly used for those with insufficient heart qi that causes pulse knotting and palpitations. It is good at entering the middle jiao and has the power to replenish the spleen. Because of its mild effect, it is suitable for use as an auxiliary medicine, which can "help ginseng and astragalus to achieve the function of qi deficiency."

[0025] Preferably, the raw materials of the compound Chinese medicine composition include the following components in parts by weight: 320-400 parts of astragalus, 120-155 parts of angelica, 80-100 parts of chuanxiong, 80-100 parts of red peony root, 80-100 parts of peach kernel, 80-100 parts of safflower, 80-100 parts of tangerine peel, 80-100 parts of atractylodes, 80-100 parts of codonopsis, 80-100 parts of poria, 35-44 parts of centipede, 80-100 parts of earthworm, 80-100 parts of bombyx batryticatus and 48-60 parts of liquorice.

[0026] Preferably, the raw materials of the compound Chinese medicine composition include the following components in parts by weight: 435 parts of astragalus, 180 parts of angelica, 120 parts of chuanxiong, 120 parts of red peony root, 120 parts of peach kernel, 120 parts of safflower, 120 parts of tangerine peel, 120 parts of atractylodes, 120 parts of codonopsis, 120 parts of poria, 48 parts of centipede, 120 parts of earthworm, 120 parts of bombyx batryticatus and 72 parts of liquorice.

[0027] Preferably, the raw materials of the composition include the following original components in parts by weight: 320-400 parts, 135-165 parts of angelica sinensis, 90-110 parts of chuanxiong, 90-110 parts of red peony root, 90-110 parts of peach kernel, 90-110 parts of safflower, 90-110 parts of tangerine peel, 90-110 parts of atractylodes macrocephala, 90-110 parts of codonopsis pilosula, 90-110 parts of poria, 35-44 parts or 15-25 centipedes, 90-110 parts of earthworm, 90-110 parts of bombyx batryticatus and 50-66 parts of liquorice.

[0028] Preferably, the raw materials of the composition include the following original components in parts by weight: 320-400 parts, 115-155 parts of angelica sinensis, 80-100 parts of chuanxiong, 80-100 parts of red peony root, 80-100 parts of peach kernel, 80-100 parts of safflower, 80-100 parts of tangerine peel, 80-100 parts of atractylodes macrocephala, 80-100 parts of codonopsis pilosula, 80-100 parts of poria, 35-44 parts of centipede, 80-100 parts of earthworm, 80-100 parts of bombyx batryticatus and 40-60 parts of liquorice.

[0029] Preferably, the mass ratio of the centipede, earthworm and silkworm is: 1:1.5-3.5:1.5-3.5.

[0030] Preferably, the raw materials of the composition include the following original components in parts by weight: the raw materials of the composition include the following original components in parts by weight: 360 parts of Astragalus, 120 parts of Angelica, 80 parts of Ligusticum chuanxiong, 80 parts of Red Peony Root, 80 parts of Peach Kernel, 80 parts of Carthamus tinctorius, 80 parts of Tangerine Peel, 80 parts of Atractylodes macrocephala, 80 parts of Codonopsis pilosula, 80 parts of Poria, 40 parts of Scolopendra, 80 parts of Pheretima, 80 parts of Bombyx batryticatus and 48 parts of Licorice.

[0031] The second object of the present invention is to provide a method for preparing the above-mentioned compound Chinese medicine composition, which comprises mixing all the components of the compound Chinese medicine composition, decocting with water, and filtering to obtain a filtrate.

[0032] Preferably, the amount of water used is 5-10 times the total mass of all components, the number of decoctions is 1-3 times, and the time of each decoction is 0.5-2 hours.

[0033] Preferably, the filtration is through a 60-100 mesh sieve;

[0034] Preferably, the filtrate is further concentrated and dried, and the concentration is to concentrate the filtrate under reduced pressure at 60-70° C. to a relative density ≥1.03.

[0035] The third object of the present invention is to provide a pharmaceutical preparation, which comprises the Chinese medicine composition according to any one of claims 1 to 3 and pharmaceutically acceptable excipients.

[0036] Preferably, the dosage form of the pharmaceutical preparation is a mixture, pill, capsule, granule, powder, tablet or paste.

[0037] Another object of the present invention is to provide the use of the above-mentioned Chinese medicine composition in a drug for improving cerebral ischemia-reperfusion neural injury.

[0038] Compared with the prior art, the present invention has the following beneficial effects:

[0039] (1) This prescription contains 14 Chinese medicinal herbs, including Astragalus, Angelica, and Chuanxiong. Astragalus is sweet and warm, and can strengthen the superficial Qi, make Qi strong to promote blood circulation, and remove blood stasis and unclog the collaterals. It is the main herb. Since the Qi is weak, the nutrient blood is easily deficient, so Angelica is the auxiliary herb, which can nourish the nutrient blood, activate blood circulation and unclog the collaterals. Since "blood is the home of Qi", it can make the Qi to be replenished have something to attach to. Red Peony Root, Chuanxiong, Peach Kernel, and Safflower assist Angelica in activating blood circulation and removing blood stasis. Codonopsis is sweet and warm, and can replenish Qi and tonify the middle. Atractylodes is Invigorate the spleen and dry out dampness, dried tangerine peel promotes qi and invigorates the spleen, and Poria penetrates dampness and invigorates the spleen. All the other medicines are adjuvants, making it tonifying without being harsh, warming without being dry, and promoting movement while invigorating. When qi moves, the Ying and Wei are unobstructed, and when the Ying and Wei are unobstructed, the evil will not stagnate, making blood stasis disappear, the collaterals unblocked, and pain stopped; centipede and silkworm are adjuvants, calming the wind and stopping spasms, resolving phlegm and dispersing knots, so as to calm the internal movement of liver wind; earthworms unblock the meridians and activate the collaterals, and their power is specialized and good at moving, and they lead the power of all the other medicines directly to the collaterals. Licorice harmonizes all the other medicines, and both are adjuvants. The whole prescription emphasizes tonifying qi, supplemented by promoting blood circulation, and together they play the role of regulating qi, promoting blood circulation, removing blood stasis and unblocking the meridians.

[0040] (2) The prescription of the present invention is reasonable in composition and compatibility, and is interrelated with each other. It is scientifically prepared and has achieved very good beneficial technical effects through experiments. It can improve neurological dysfunction after cerebral ischemia, significantly reduce the reduced blood flow, and has a neuroprotective effect. It can also significantly reduce the infarct volume and has a significant effect on improving cerebral ischemia-reperfusion neural damage.

[0041] (3) Clinical studies have shown that the combination of the present invention and aspirin tablets and atorvastatin tablets in the treatment of patients with cerebral ischemic reperfusion injury of Qi deficiency and blood stasis type has a marked efficacy of 85% and a total efficacy of 97%. BRIEF DESCRIPTION OF THE DRAWINGS

[0042] Figure 1 This is a comparison chart of cerebral blood flow of mice in the dosage groups in Example 1, from left to right are the cerebral blood flow before modeling, after modeling, and 24 hours after modeling.

[0043] Figure 2 The bar graph shows the percentage of cerebral blood flow reduction in each group of mice compared with that before modeling, where ## represents P<0.01 compared with the sham operation group, and ** represents P<0.01 compared with the model group.

[0044] Figure 3 Schematic diagram of hematoxylin-eosin (HE) staining for the experimental results of the effects of each group of Chinese medicine compositions on brain tissue damage and brain neurons in mice with cerebral ischemia-reperfusion injury, from left to right are the sham operation group, the model group, the low-dose group of Example 1, the medium-dose group of Example 1, the high-dose group of Example 1 and the positive drug group.

[0045] Figure 4 This is a schematic diagram of Nissl staining of the experimental results of the effects of each group of Chinese medicine compositions on brain tissue damage and brain neurons in mice with cerebral ischemia-reperfusion injury, from left to right are the sham operation group, the model group, the low-dose group of Example 1, the medium-dose group of Example 1, the high-dose group of Example 1 and the positive drug group.

[0046] Figure 5 The present invention is a schematic diagram of the experimental results of the effect of the compound Chinese medicine composition on the cerebral infarction volume of mice with cerebral ischemia-reperfusion injury, which is a mouse TTC staining diagram, wherein each column is a group, from left to right are the sham operation group, the model group, the example 1 group, the example 2 group, the example 3 group and the positive drug group.

[0047] Figure 6 The present invention is a schematic diagram of the experimental results of the effect of the compound Chinese medicine composition on the cerebral infarction volume of mice with cerebral ischemia-reperfusion injury, which is a mouse TTC staining diagram, wherein each column is a group, from left to right are the sham operation group, the model group, the low-dose group of Example 1, the medium-dose group of Example 1, the high-dose group of Example 1 and the positive drug group.

[0048] Figure 7 The present invention is a schematic diagram of the experimental results of the effect of the compound Chinese medicine composition on the cerebral infarction volume of mice with cerebral ischemia-reperfusion injury, which is a mouse TTC staining diagram, wherein each column is a group, from left to right are sham operation group, model group, comparative example 1 group, embodiment 1 group, comparative example 2 group, comparative example 3 group, comparative example 4 group and positive drug group.

[0049] Figure 8 The figure is a bar graph of the cerebral infarction volume in each group of mice.

[0050] Fig. 9 The neurological scores of mice in each group, where ## represents P<0.01 compared with the sham operation group, ** represents P<0.01 compared with the model group, and * represents P<0.05 compared with the model group. DETAILED DESCRIPTION

[0051] The present invention will be further described below in conjunction with specific implementation modes.

[0052] Example 1

[0053] A compound Chinese medicine composition for improving cerebral ischemia-reperfusion nerve injury, comprising the following raw materials in parts by weight: 36g of astragalus, 12g of angelica, 8g of chuanxiong, 8g of tangerine peel, 8g of atractylodes, 8g of red peony root, 8g of peach kernel, 8g of safflower, 8g of tuckahoe, 8g of codonopsis, 8g of earthworm, 4g (2 pieces) of centipede, 8g of bombyx batryticatus, and 4.8g of liquorice.

[0054] The preparation method comprises the following steps: adding 10 times the total weight volume of water to the crude drug raw material, boiling the raw material twice, each time for 1 hour, combining the filtrates, filtering through an 80-mesh sieve, and concentrating under reduced pressure at 65° C. to a relative density of 1.03.

[0055] Example 2

[0056] A compound Chinese medicine composition for improving cerebral ischemia-reperfusion nerve injury is prepared from the following raw materials in parts by weight: 28.8 parts of astragalus, 15 parts of angelica, 10 parts of chuanxiong, 10 parts of red peony root, 10 parts of peach kernel, 10 parts of safflower, 10 parts of tangerine peel, 10 parts of atractylodes, 10 parts of codonopsis, 10 parts of tuckahoe, 3.2 parts of centipede, 10 parts of earthworm, 10 parts of bombyx batryticatus and 6 parts of liquorice.

[0057] The preparation method comprises the following steps: adding 8 times the total weight volume of water to the crude drug raw material, boiling for 3 times, each time for 0.5 h, combining the filtrate, filtering through an 80-mesh sieve, and concentrating under reduced pressure at 70° C. to a relative density of 1.03.

[0058] Example 3

[0059] A compound Chinese medicine composition for improving cerebral ischemia-reperfusion nerve injury is prepared from the following raw materials in parts by weight: 43.5 parts of astragalus, 18 parts of angelica, 12 parts of chuanxiong, 12 parts of red peony root, 12 parts of peach kernel, 12 parts of safflower, 12 parts of tangerine peel, 12 parts of atractylodes, 12 parts of codonopsis, 12 parts of tuckahoe, 4.8 parts of centipede, 12 parts of earthworm, 12 parts of bombyx batryticatus and 7.2 parts of liquorice.

[0060] The preparation method comprises the following steps: adding water of 10 times the total weight volume to the crude drug and boiling for 2 hours, combining the filtrate, filtering through an 80-mesh sieve, and concentrating under reduced pressure at 60° C. to a relative density of 1.05.

[0061] Comparative Example 1

[0062] The difference between this comparative example and Example 1 is that the mass ratio of Astragalus to Angelica is 1:1, each of which is 24 g.

[0063] Comparative Example 2

[0064] The difference between this comparative example and Example 1 is that the mass ratio of astragalus to angelica is 5:1, with 40 g of astragalus and 8 g of angelica.

[0065] Comparative Example 3

[0066] The difference between this comparative example and Example 1 is that the centipede is replaced by the earthworm, and the tangerine peel is replaced by charred hawthorn, and the rest is the same as Example 1.

[0067] Comparative Example 4

[0068] The difference between this comparative example and Example 1 is that the mass ratio of centipede, silkworm and earthworm is 3:8:4.

[0069] Drug efficacy experiment

[0070] 1. Experimental Materials

[0071] 1.1 Experimental animals

[0072] 6-week-old SPF-grade C57BL / 6J male mice, weighing 22-25 g, were purchased from the Henan Experimental Animal Center (Animal Production License No. SCXK (Yu) 2022-0001), and the animal quality certificate No. 411006231100090737. The animals were kept in the Barrier Environment Experimental Animal Center of Luohe Central Hospital, with the Animal Use License No. SYXK (Yu) 2022-0011. The temperature was controlled at 20°C to 25°C, the relative humidity was controlled at 40% to 60%, and they were free to eat and drink. The lighting conditions were alternating every 12 hours (daytime) and observed for 5 days. The basic feed was provided by Henan Huanyu Hekang Biotechnology Co., Ltd. This animal experiment has been reviewed by the Experimental Animal Ethics Committee of Luohe Central Hospital (Animal Experiment Ethics No.: lhzxyy2309001).

[0073] 1.2 Drug preparation

[0074] The low-dose group, medium-dose group and high-dose group of the traditional Chinese medicine composition prepared in Example 1, the group in Example 2, the group in Example 3, and the traditional Chinese medicine compositions prepared in Comparative Examples 1, 2, 3 and 4.

[0075] Positive control group: Enteric-coated aspirin tablets were prepared at 1.428 mg / mL, equivalent to a drug content of 13 mg / kg.

[0076] Sham operation group and model group: distilled water.

[0077] 1.3 Reagents and instruments

[0078] The Chinese herbal medicines used in the experiment were all from Henan Hongbo Pharmaceutical Co., Ltd., enteric-coated aspirin tablets (Bayer Healthcare Co., Ltd., batch number: 20230227), isoflurane (Jiangsu Hengfengqiang Biotechnology Co., Ltd., batch number: 20230901), 4% paraformaldehyde universal tissue fixative (Beijing Lanjieke Technology Co., Ltd., batch number: 23257838), TTC (batch number: 240001001), hematoxylin and eosin (HE) staining kit and Nissl staining kit (methyl violet method) (Beijing Solebold Technology Co., Ltd.).

[0079] ZS-TS stereo microscope, ZS-MV-IV small animal anesthesia machine (Beijing Zhongshidichuang Technology Development Co., Ltd.), RFLSI ZW laser speckle blood flowmeter (Ruiwode Life Science Co., Ltd.), 303-0AB vertical electric heating incubator (Shanghai Jingqi Instrument Co., Ltd.), JM-23D-28 / 45 dual-frequency ultrasonic cleaning machine (Jiemeng Ultrasonic Technology Co., Ltd.).

[0080] 2. Experimental Methods

[0081] 2.1 Animal grouping, drug administration and modeling

[0082] Experiment 1: The mice were randomly divided into sham operation group, model group, Example 1 group (1.94 g / kg), Example 2 group (1.94 g / kg), Example 3 group (1.94 g / kg) and positive drug group aspirin enteric-coated tablets (13 mg / kg), 12 mice in each group, once a day for 14 consecutive days. At the same time, the sham operation group and the model group were given an equal volume of distilled water.

[0083] Experiment 2: The mice were randomly divided into sham operation group, model group, low-dose group of Example 1 (0.97 g / kg), medium-dose group of Example 1 (1.94 g / kg), high-dose group of Example 1 (3.88 g / kg) and positive drug group aspirin enteric-coated tablets (13 mg / kg), 12 mice in each group, once a day for 14 consecutive days. At the same time, the sham operation group and the model group were given an equal volume of distilled water.

[0084] Experiment 3: The mice were randomly divided into sham group (sham), model group (I / R), Example 1 group (1.94 g / kg), Comparative Example 1 group (1.94 g / kg), Comparative Example 2 group (1.94 g / kg), Comparative Example 3 group (1.94 g / kg), Comparative Example 4 group (1.94 g / kg) and positive drug group aspirin enteric-coated tablets (13 mg / kg), 12 mice in each group, once a day for 14 consecutive days. At the same time, the sham group and the model group were given an equal volume of distilled water.

[0085] One hour after the last administration of the above experiment, the left cerebral hemisphere of the mice in the model group and the drug group was subjected to a middle cerebral artery focal cerebral ischemia-reperfusion modeling operation. The entire operation was performed under a stereo microscope.

[0086] Laser speckle blood flow imaging was used to monitor the changes in brain blood flow in mice in real time. Brain blood flow was tested before, after and 24 hours after modeling.

[0087] Neurological function scoring: Before sampling, the Zea-Longa scoring method was used to score the neurological function of mice. Scoring criteria: no signs of neurological deficit, 0 points; inability to fully flex the contralateral forepaw, 1 point; rotation to the paralyzed side, 2 points; tilting to the paralyzed side, 3 points; inability to walk spontaneously and loss of consciousness, 4 points. The scoring results of mice in each group were counted and their neurological function damage was analyzed. 24 hours after modeling, blood was collected from the fundus venous plexus of all mice, and the anesthetized mice were killed by cervical dislocation.

[0088] 2.2 Determination of cerebral infarction volume

[0089] TTC staining is a classic method to measure the degree of cerebral ischemia. Take the brain tissue of each group of mice and freeze it at -20℃ for 30 minutes. Cut the brain tissue into coronal slices with an average thickness of about 1mm on an ice box, put it into 2% TTC staining solution, incubate it at 37℃ in the dark for 30 minutes, fix it with 4% paraformaldehyde, arrange the fixed brain slices in order, and take pictures. Use Image J software to calculate the volume of cerebral infarction. Cerebral infarction volume ratio (%) = the sum of the white ischemic area of ​​each slice / the sum of the area of ​​each brain slice × the thickness of the brain slice (1mm) × 100%.

[0090] 2.3 Hematoxylin-eosin (HE) staining and Nissl staining

[0091] The brain tissue of each group of mice was sliced ​​2 mm in the coronal plane, immersed in 4% paraformaldehyde solution for fixation for 24 h, embedded in paraffin and cut into 3 μm slices, fixed by heating at 60 ° C for 30 min, then dewaxed with xylene and gradient ethanol, and finally stained with hematoxylin and eosin. Finally, the slices were transparent with xylene, and the morphological changes of the brain tissue of each group of mice were observed under an optical microscope; another 2 mm coronal slice of the brain tissue was routinely dewaxed to water, placed in tar violet working solution for staining, washed with water, and rapidly differentiated with Nissl body differentiation solution and 95% alcohol in turn, and finally rapidly dehydrated with anhydrous alcohol, dried and sealed. The damage of neurons in the mouse brain tissue was observed under a microscope.

[0092] 3. Results

[0093] 3.1 Morphological evaluation results

[0094] By laser speckle contrast imaging, the cerebral blood flow (CBF) in the left cerebral ischemic penumbra of mice after modeling was significantly decreased compared with that on the right side, and the blood flow recovered 24 hours after modeling. The results are shown in Table 1 and Figure 1-Figure 2 As shown. There was no significant change in the sham operation group. Compared with the sham operation group, the blood flow of mice in the model group decreased significantly; compared with the model group (45.80% ± 1.62%), the average values ​​of the reduced blood flow in the low, medium, high dose groups and the positive drug group in Example 1 were significantly reduced, with statistical differences (P < 0.01). This shows that the drug administration group can significantly reduce the reduced blood flow and has a neuroprotective effect.

[0095] Table 1

[0096]

[0097] 3.2 Results of hematoxylin-eosin (HE) staining and Nissl staining

[0098] HE staining results Figure 3Compared with the sham operation group, the tissue structure of the model group was clear and the cell morphology was good. Compared with the sham operation group, the tissue of the model group showed vacuolation, cell nucleus shrinkage, a significant decrease in the number of cells, and disordered arrangement. Compared with the model group, the cell morphology, number and pathological state of Examples 1, 2, 3 and the positive drug group were improved to varying degrees. The Nissl staining results are shown in Figure 4 Compared with the sham operation group, the number of Nissl bodies in the model group was significantly reduced. In addition, dissolved Nissl bodies appeared in the cytoplasm of some pyramidal cells, with blurred outlines and lighter staining. However, the above-mentioned damage was significantly reversed after the low, medium and high dose groups and positive drugs of Example 1 were given, and the number of Nissl bodies increased significantly. It shows that the embodiment has a certain protective effect on the mouse nerve cells injured by cerebral ischemia reperfusion.

[0099] 3.4 Results of cerebral infarction volume percentage (%)

[0100] TTC staining makes normal tissue appear red and infarcted area appear white. Figure 5-Figure 7 , the percentage of cerebral infarction volume (%) results are shown in Figure 8 and Table 2-3. The brain tissue sections of the sham operation group were red; compared with the sham operation group, the infarction volume of the model group mice was significantly increased; compared with the model group, the infarction volume of the low, medium, high dose groups and positive drug group in Example 1 gradually decreased, with statistical differences (P<0.01). It shows that the drug administration group can significantly reduce the percentage of infarction volume (%), and has the effect of improving the mouse model of cerebral ischemia-reperfusion injury.

[0101] Table 2

[0102]

[0103] Table 3

[0104]

[0105] 3.5 Neurological function score

[0106] The neurological function scores are shown in Table 4 and Fig. 9 shown.

[0107] Table 4

[0108]

[0109] 4. Clinical application

[0110] According to clinical statistics, the clinical cases of 111 patients with cerebral infarction of qi deficiency and blood stasis type are shown in Table 5, and the evaluation indicators are the neurological impairment (NIHSS) score, daily living ability index (Barthel), and blood lipid levels (Tc, TG, LDL-C) of the patients with therapeutic effect. The selected patients meet the diagnostic criteria of qi deficiency and blood stasis syndrome of cerebral infarction in Western medicine and stroke in traditional Chinese medicine, and the total cholesterol (TC) of the patients is ≥5.7mmol / L. The patients are given comprehensive treatment measures such as diet control, anti-infection, correction of electrolyte disorders, and exercise guidance, especially strict control of sodium salt intake in diet control. The patients are given Bayaspirin tablets 100mg, qd., for 14 consecutive days, atorvastatin tablets 20mg, qn., and on this basis, 50mL of the Chinese medicine composition mixture of the present invention is taken, bid, for 14 consecutive days. The clinical efficacy evaluation criteria are divided into basic cure (TCM symptoms and signs basically disappear, and the symptom score decreases by ≥90%), marked effect (TCM symptoms and signs significantly improve, and the symptom score decreases by ≥60%), effective (TCM symptoms and signs improve, and the symptom score decreases by ≥30%, but ≤60%), and ineffective (TCM symptoms and signs do not improve or even worsen, and the symptom score decreases by ≤30%). Total effective rate of treatment = (basic cure + marked effect + effective) / total number of cases × 100%

[0111] Statistical analysis showed that the effective rate of the Chinese medicine composition combined with aspirin tablets and atorvastatin tablets in treating patients with cerebral ischemic reperfusion injury of qi deficiency and blood stasis type was 85% (94 / 111), the ineffective rate was 3% (3 / 111), and the total effective rate was 97%.

[0112] Table 5

[0113]

Claims

1. A compound Chinese medicine composition for improving cerebral ischemia-reperfusion nerve damage, characterized in that: The raw materials of the compound Chinese medicine composition include the following components in parts by weight: 288-435 parts of astragalus, 120-180 parts of angelica, 80-120 parts of chuanxiong, 80-120 parts of red peony root, 80-120 parts of peach kernel, 80-120 parts of safflower, 80-120 parts of tangerine peel, 80-120 parts of atractylodes, 80-120 parts of codonopsis, 80-120 parts of tuckahoe, 32-48 parts of centipede, 80-120 parts of earthworm, 80-120 parts of bombyx batryticatus and 48-72 parts of liquorice.

2. The compound Chinese medicine composition according to claim 1, characterized in that: The raw materials of the compound Chinese medicine composition include the following components in parts by weight: 320-400 parts of astragalus, 120-155 parts of angelica, 80-100 parts of chuanxiong, 80-100 parts of red peony root, 80-100 parts of peach kernel, 80-100 parts of safflower, 80-100 parts of tangerine peel, 80-100 parts of atractylodes, 80-100 parts of codonopsis, 80-100 parts of poria, 35-44 parts of centipede, 80-100 parts of earthworm, 80-100 parts of bombyx batryticatus and 48-60 parts of liquorice.

3. The compound Chinese medicine composition according to claim 1, characterized in that: The mass ratio of the centipede, earthworm and silkworm is 1:1.5-3.5:1.5-3.

5.

4. The compound Chinese medicine composition according to claim 1, characterized in that: The raw materials of the compound Chinese medicine composition include the following components in parts by weight: 360 parts of astragalus, 120 parts of angelica, 80 parts of chuanxiong, 80 parts of red peony root, 80 parts of peach kernel, 80 parts of safflower, 80 parts of tangerine peel, 80 parts of atractylodes, 80 parts of codonopsis, 80 parts of tuckahoe, 40 parts of centipede, 80 parts of earthworm, 80 parts of bombyx batryticatus and 48 parts of licorice; or 435 parts of astragalus, 180 parts of angelica, 120 parts of chuanxiong, 120 parts of red peony root, 120 parts of peach kernel, 120 parts of safflower, 120 parts of tangerine peel, 120 parts of atractylodes, 120 parts of codonopsis, 120 parts of tuckahoe, 48 parts of centipede, 120 parts of earthworm, 120 parts of bombyx batryticatus and 72 parts of licorice.

5. A method for preparing the compound Chinese medicine composition according to any one of claims 1 to 4, characterized in that: The method comprises mixing all the components of the compound Chinese medicine composition, adding water to boil the mixture, and filtering the mixture to obtain the filtrate.

6. The preparation method according to claim 5, characterized in that: The amount of water used is 5-10 times the total mass of all components, the number of decoctions is 1-3 times, and the time of each decoction is 0.5-2 hours.

7. The preparation method according to claim 5, characterized in that: The filtration is through a 60-100 mesh sieve, and / or the filtrate is further concentrated and dried, and the concentration is to concentrate the filtrate under reduced pressure at 60-70° C. to a relative density ≥1.

00.

8. A pharmaceutical preparation, characterized in that The pharmaceutical preparation comprises the compound Chinese medicine composition according to any one of claims 1 to 4 and pharmaceutically acceptable excipients.

9. The pharmaceutical preparation according to claim 8, characterized in that The dosage form of the pharmaceutical preparation is a mixture, pill, capsule, granule, powder, tablet or paste.

10. Use of the traditional Chinese medicine composition according to any one of claims 1 to 4 for preparing a medicament for improving cerebral ischemia-reperfusion neural injury.

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