Traditional Chinese medicine composition for treating or improving cerebral arterial thrombosis

Abstract

The invention provides a traditional Chinese medicine composition for treating or improving cerebral arterial thrombosis, and relates to the technical field of traditional Chinese medicine pharmacy. The traditional Chinese medicine composition is prepared from radix astragali, radix notoginseng, radix angelicae lateralis preparata, radix scrophulariae, radix achyranthis bidentatae, cortex moutan, rhizoma corydalis, rhizoma curcumae longae, radix curcumae, radix gentianae macrophyllae, radix polygalae preparata and radix glycyrrhizae. According to the traditional Chinese medicine composition disclosed by the invention, the qi-tonifying medicine and the blood-activating and blood-stasis-removing medicine are used together, and the effects of activating blood, removing blood stasis, tonifying qi and nourishing yin are achieved together through simultaneous application of dispersing and deficiency tonifying, so that qi deficiency is tonified, meridians and collaterals are dredged, qi is tonified without stagnation, both symptoms and root causes are treated, and the cerebral arterial thrombosis is effectively treated. The traditional Chinese medicine composition disclosed by the invention can be used for remarkably improving the neurological function impairment symptom of a patient suffering from cerebral arterial thrombosis, helping to recover and improve the living activity ability of the patient, remarkably relieving and improving the clinical symptoms such as upper limb paralysis, lower limb paralysis, mouth and tongue deflection, sluggish speech or speech loss and the like of the patient, and remarkably improving the total effective rate of treating the cerebral arterial thrombosis.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine pharmaceutical preparation, and in particular to a traditional Chinese medicine composition for treating or improving ischemic stroke. Background Art

[0002] Ischemic stroke (IS) is an acute cerebrovascular disease caused by stenosis or blockage of cerebral arteries and carotid arteries, resulting in insufficient blood supply to local brain tissue, thus forming cerebral infarction. Its pathogenesis is complex, involving vascular endothelial damage, thrombosis, neurovascular unit damage, and pathological processes such as inflammatory response, oxidative stress and cell apoptosis. Clinically, it often manifests as symptoms such as hemiplegia, hemiplegia, and speech dysfunction. It is characterized by high incidence, high recurrence rate, high disability rate, and high mortality rate. It often occurs in the middle-aged and elderly population, and has a trend of younger people in recent years, seriously threatening the health and life of the middle-aged and elderly.

[0003] For patients with ultra-early and acute IS, the best treatment options are intravenous injection of tissue plasminogen activator and intravascular thrombectomy to relieve large vessel occlusion and save the ischemic penumbra through rapid reflow. Tissue plasminogen activator is the only thrombolytic drug approved by the US Food and Drug Administration and is widely used worldwide. However, its treatment time window is narrow, and patients must undergo thrombolytic therapy within 4.5 hours after stroke. A large number of patients cannot receive timely treatment due to missing the treatment time window or due to their own reasons. Even for patients who have received acute thrombolytic thrombectomy, although reperfusion can restore blood oxygen supply, the free radicals produced will trigger a series of inflammatory cascade reactions, further aggravating tissue damage, causing varying degrees of neurological damage and behavioral dysfunction, and seriously affecting the quality of life of patients.

[0004] The characteristics of Chinese medicine with multiple components, multiple pathways and multiple targets make it unique in the treatment of IS. Many studies have shown that Chinese medicine compound preparations have a certain effect in the treatment of ischemic stroke, which is mainly through inhibiting related inflammatory reactions and some brain oxidative stress mechanisms, improving the environment around brain tissue and nerve tissue, repairing damage, promoting nerve regeneration and unblocking blocked blood vessels, improving local brain ischemia, thereby improving the pathological state of patients with ischemic stroke. The present invention aims to provide a Chinese medicine composition with definite efficacy for treating or improving ischemic stroke. Summary of the invention

[0005] 1. Technical issues to be solved

[0006] In view of the deficiencies in the prior art, the present invention provides a Chinese medicine composition for treating or improving ischemic stroke.

[0007] (II) Technical solution

[0008] To achieve the above objectives, the present invention is implemented through the following technical solutions:

[0009] The invention provides a traditional Chinese medicine composition for treating or improving ischemic stroke. The traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 20-40 parts of astragalus, 10-30 parts of notoginseng, 1-15 parts of radix radix et rhizoma radix, 5-20 parts of scrophulariae, 5-20 parts of achyranthes, 1-15 parts of moutan bark, 1-15 parts of corydalis, 1-10 parts of turmeric, 1-10 parts of curcuma, 1-10 parts of gentiana macrophylla, 1-10 parts of processed polygala, and 1-15 parts of liquorice.

[0010] Furthermore, the Chinese medicine composition is composed of the following raw materials in parts by weight: 25-35 parts of Astragalus, 15-25 parts of Panax notoginseng, 5-10 parts of Radix Angelicae Sinensis, 5-15 parts of Scrophulariae, 10-20 parts of Achyranthes bidentata, 1-10 parts of Paeonia suffruticosa, 1-10 parts of Corydalis yanhusuo, 1-6 parts of Curcuma longa, 1-6 parts of Curcuma aromatica, 1-6 parts of Gentiana macrophylla, 1-6 parts of processed Polygala tenuifolia, and 5-10 parts of Licorice.

[0011] Furthermore, the Chinese medicine composition is composed of the following raw materials in parts by weight: 30 parts of Astragalus, 20 parts of Panax notoginseng, 6 parts of Radix Angelicae Sinensis, 8 parts of Scrophulariae, 12 parts of Achyranthes bidentata, 5 parts of Paeonia suffruticosa, 5 parts of Corydalis yanhusuo, 3 parts of Curcuma, 3 parts of Curcuma, 3 parts of Gentiana macrophylla, 4 parts of processed Polygala, and 6 parts of Licorice.

[0012] The Chinese medicine composition provided by the present invention is used to prepare a drug for treating or improving ischemic stroke. The drug is prepared into an oral dosage form according to a conventional preparation method, and the dosage form includes oral liquid, granules, suspensions, powders, decoctions, pills, tablets, capsules, freeze-dried powders, etc.

[0013] Astragalus: sweet, slightly warm. Enters the lung and spleen meridians. It has the effects of tonifying qi and raising yang, consolidating the exterior and stopping sweating, promoting diuresis and reducing swelling, promoting fluid and nourishing blood, relieving stagnation and relieving arthritis, expelling toxins and expelling pus, and healing sores and promoting tissue regeneration. It is mainly used for qi deficiency and fatigue, poor appetite and loose stools, sinking of qi in the middle, chronic diarrhea and prolapse of the anus, bloody stool and metrorrhagia, spontaneous sweating due to exterior deficiency, edema due to qi deficiency, internal heat and thirst, sallow complexion due to blood deficiency, hemiplegia, pain and numbness, carbuncle that is difficult to heal, and carbuncle that does not heal for a long time.

[0014] Panax notoginseng: sweet, slightly bitter, warm in nature. Enters the liver and stomach meridians. Its main effects are to disperse blood stasis and stop bleeding, reduce swelling and relieve pain. It is mainly used clinically for hemoptysis, hematemesis, epistaxis, bloody stool, metrorrhagia, traumatic bleeding, chest and abdominal pain, and swelling and pain caused by falls.

[0015] Radix Angelicae Sinensis: sweet, pungent, warm in nature. It enters the liver, heart, and spleen meridians. Its main effects are to nourish blood and activate blood circulation, regulate menstruation and relieve pain, and moisten the intestines and relieve constipation. It is used for blood deficiency and sallow complexion, dizziness and palpitations, irregular menstruation, amenorrhea and dysmenorrhea, abdominal pain due to deficiency and cold, rheumatic arthralgia, injuries from falls, carbuncle, ulcers, and constipation due to dry intestines. Wine angelica activates blood circulation and regulates menstruation. It is mainly used to treat amenorrhea and dysmenorrhea, rheumatic arthralgia, and injuries from falls.

[0016] Scrophularia: Sweet, bitter, salty, slightly cold. Enters the lung, stomach, and kidney meridians. Its efficacy is to clear away heat and cool blood, nourish yin and reduce fire, and detoxify and disperse stagnation. It is mainly used clinically for heat entering the blood, fever toxicity causing spots, febrile disease damaging yin, red tongue and thirst, body fluid damage and constipation, bone steaming and fatigue cough, red eyes, sore throat, diphtheria, scrofula, carbuncle, swelling and ulcer.

[0017] Achyranthes bidentata: sweet, bitter, sour, neutral in nature. Enters the liver and kidney meridians. Its main functions are to remove blood stasis and dredge menstruation, nourish the liver and kidney, strengthen tendons and bones, promote diuresis and relieve stranguria, and guide blood downward. It is mainly used to treat blood stasis, amenorrhea, dysmenorrhea, soreness of waist and knees, weakness of tendons and bones, headache, dizziness, toothache, mouth sores, and vomiting blood.

[0018] Corydalis yanhusuo: pungent, bitter, warm in nature. Enters the liver and spleen meridians. Its efficacy is to promote blood circulation, promote qi circulation, and relieve pain. It is mainly used to treat chest and flank pain, abdominal pain, chest obstruction and heart pain, amenorrhea, dysmenorrhea, postpartum blood stasis, and swelling and pain due to falls.

[0019] Turmeric: pungent, bitter, warm in nature. Enters the spleen and liver meridians. It has the effects of breaking blood and promoting qi, dredges the menstrual passages and relieves pain. It is mainly used clinically to treat chest and flank pain, chest obstruction and heart pain, amenorrhea, dysmenorrhea, masses, rheumatic shoulder and arm pain, and swelling and pain caused by falls.

[0020] Curcuma: pungent, bitter, cold in nature. Enters the liver, heart, and lung meridians. It has the effects of promoting blood circulation and relieving pain, promoting qi and relieving depression, clearing the heart and cooling blood, promoting bile and relieving jaundice. It is mainly used to treat chest and flank pain, chest obstruction and heart pain, amenorrhea and dysmenorrhea, breast pain, febrile coma, epilepsy and madness, and vomiting and bleeding due to blood heat.

[0021] Peony bark: bitter, pungent, slightly cold. Enters the heart, liver, and kidney meridians. It has the effects of clearing away heat and cooling blood, promoting blood circulation and removing blood stasis. It is used for heat entering the blood, fever and rashes, vomiting blood and epistaxis, night heat and morning coolness, no sweating and bone steaming, amenorrhea and dysmenorrhea, injuries and pains from falls, carbuncles, sores and ulcers.

[0022] Gentiana macrophylla: pungent, bitter, neutral in nature. Enters the stomach, liver, and gallbladder meridians. Its main functions are to dispel rheumatism, clear damp-heat, stop pain, and relieve deficiency-heat. It is mainly used for rheumatic pain, hemiplegia due to stroke, muscle spasm, joint pain, damp-heat jaundice, bone steaming and tidal fever, and fever due to malnutrition in children.

[0023] Processed Polygala: bitter, pungent, warm in nature. Enters the heart, kidney, and lung meridians. Its effects are to calm the mind and improve intelligence, connect the heart and kidney, remove phlegm, and reduce swelling. It is used to treat insomnia, dreaminess, forgetfulness, palpitations, confusion, coughing up phlegm, sores, swelling, and breast pain caused by disharmony between the heart and kidney.

[0024] Licorice: sweet, neutral. Enters the heart, lung, spleen, and stomach meridians. It nourishes the spleen and replenishes qi, clears away heat and detoxifies, removes phlegm and relieves cough, relieves pain, and harmonizes various medicines. It is used for spleen and stomach weakness, fatigue, palpitations and shortness of breath, cough with sputum, abdominal and limb cramps and pain, carbuncle, sore and ulcer, and relieves drug toxicity and potency.

[0025] (III) Beneficial effects

[0026] The present invention takes TCM syndrome differentiation and treatment as the principle, comprehensively considers the symptoms and etiology and pathogenesis of the patient, and provides a Chinese medicine composition for treating or improving ischemic stroke, wherein the Chinese medicine composition is composed of astragalus, notoginseng, Radix Angelicae Sinensis, Radix Achyranthis Bidentatae, Cortex Moutan, Rhizoma Corydalis, Curcuma Longa, Radix Curcumae, Radix Gentianae Macrophyllae, Radix Polygalae Preparata, and Radix Glycyrrhizae. Astragalus and notoginseng are used in the prescription, which are sweet, warm and nourishing, good at replenishing qi and removing stagnation, and the amount is taken to be large, which greatly replenishes the vital energy, makes qi vigorous and promotes blood circulation, and eliminates blood stasis without hurting the body; notoginseng is bitter, purging, warming and unblocking, good at promoting blood circulation and removing blood stasis, dredges the meridians and relieves pain, and the two are the main medicines for dispersing blood stasis. Angelicae Sinensis tail guides the drug power directly to the diseased area, dispersing blood stasis while taking into account nourishing blood, so that blood stasis is removed without hurting blood, which not only helps astragalus to promote blood circulation, but also because it has the ability to nourish blood, it can prevent the use of a large amount of blood-activating and blood-removing drugs from hurting blood; Scrophulariae is bitter, cold and clear, sweet and salty, nourishes and enters the blood, is good at nourishing yin, cooling blood and clearing heat, and promotes blood circulation without hurting the body. Angelica root and Scrophularia are both ministerial drugs, which can not only help the monarch drug to disperse blood stasis, but also nourish qi, nourish yin and promote body fluid, and at the same time make up for the blood deficiency caused by blood stasis in the meridians. Peony bark, Achyranthes bidentata, Corydalis yanhusuo, Curcuma longa, Curcuma zedoaria and Gentiana macrophylla are all adjuvant drugs. Among them, Peony bark can clear away heat and cool blood, promote blood circulation and remove blood stasis, promote blood circulation and remove blood stasis, and can not only promote blood circulation and remove blood stasis to help the monarch and ministerial drugs, but also cool blood, clear the heart and relieve troubles; Achyranthes bidentata leads blood stasis downward to promote the rise and fall of qi and blood; Corydalis yanhusuo, Curcuma zedoaria and Curcuma longa have the effects of promoting blood circulation and removing blood stasis, promoting qi and relieving pain; Gentiana macrophylla can dredge the meridians and relieve pain. Polygala tenuifolia and Licorice are all guiding drugs. Polygala tenuifolia can calm the mind and improve intelligence, connect the heart and kidney, and improve the symptoms of patients with confusion and insomnia caused by brain lesions. At the same time, its role in connecting the heart and kidney helps to adjust the functions of the human organs, so that the whole prescription can treat qi deficiency and blood stasis while taking into account abnormalities in consciousness; Licorice harmonizes the various drugs, alleviates the strong nature of the drugs, and makes the medicinal properties of the whole prescription more coordinated. The Chinese medicine composition of the present invention uses a qi-tonifying drug and a blood-activating and blood-stasis-removing drug together, and dispersing and tonifying the deficiency are used simultaneously, so as to jointly achieve the functions of activating blood circulation and removing blood stasis, invigorating qi and nourishing yin, so that qi deficiency can be replenished, meridians can be unblocked, qi can be replenished without stagnation, and both the symptoms and the root causes are treated, thereby achieving effective treatment of ischemic stroke.

[0027] The Chinese medicine composition of the present invention can significantly reduce the rate of reduction of brain microvascular flow in ischemic stroke mice induced by photochemical treatment, has a significant inhibitory effect on the formation of microthrombi, significantly reduces the level of vWF in the serum of ischemic stroke mice, and increases the level of PGI2 in the serum; at the same time, it significantly improves the neurological function damage of ischemic stroke mice, reduces the volume of brain tissue infarction, and improves brain tissue pathological changes. The Chinese medicine composition of the present invention has a significant therapeutic effect on ischemic stroke mice induced by photochemical treatment, and can be used as a potential drug for treating or improving ischemic stroke.

[0028] The Chinese medicine composition of the present invention significantly improves the symptoms of neurological function damage in patients with ischemic cerebral stroke, helps to restore and improve the patients' ability to carry out daily activities, significantly alleviates and improves the patients' clinical symptoms such as upper limb paralysis, lower limb paralysis, crooked mouth and tongue, slurred speech or aphasia, and significantly improves the total effective rate of ischemic stroke treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 The following are the pathological images of brain tissues of mice in each group.

[0030] Figure 2 Representative pictures of cerebral infarction volume in each group of mice, in which normal tissue is red and infarcted tissue is white. DETAILED DESCRIPTION

[0031] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention will be clearly and completely described below in combination with the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0032] Example 1

[0033] A traditional Chinese medicine composition for treating or improving ischemic stroke, the traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 20 parts of astragalus, 10 parts of panax notoginseng, 4 parts of radix radix et rhizoma radix, 6 parts of scrophulariae, 8 parts of achyranthes bidentata, 3 parts of moutan bark, 3 parts of corydalis, 2 parts of turmeric, 2 parts of curcuma, 2 parts of gentiana macrophylla, 2 parts of processed polygala, and 4 parts of liquorice.

[0034] Example 2

[0035] A traditional Chinese medicine composition for treating or improving ischemic stroke, the traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 40 parts of astragalus, 30 parts of panax notoginseng, 15 parts of radix radix et rhizoma radix, 20 parts of scrophulariae, 20 parts of achyranthes bidentata, 15 parts of moutan bark, 15 parts of corydalis, 10 parts of turmeric, 10 parts of curcuma, 10 parts of gentiana macrophylla, 10 parts of processed polygala, and 15 parts of liquorice.

[0036] Example 3

[0037] A traditional Chinese medicine composition for treating or improving ischemic stroke, the traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 22 parts of astragalus, 14 parts of panax notoginseng, 4 parts of radix radix et rhizoma radix, 4 parts of scrophulariae, 6 parts of achyranthes bidentata, 4 parts of moutan bark, 3 parts of corydalis, 2 parts of turmeric, 2 parts of curcuma, 4 parts of gentiana macrophylla, 3 parts of processed polygala, and 5 parts of liquorice.

[0038] Example 4

[0039] A traditional Chinese medicine composition for treating or improving ischemic stroke, the traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 36 parts of astragalus, 26 parts of panax notoginseng, 12 parts of radix radix et rhizoma radix, 16 parts of scrophulariae, 16 parts of achyranthes bidentata, 11 parts of moutan bark, 11 parts of corydalis, 7 parts of turmeric, 8 parts of curcuma, 4 parts of gentiana macrophylla, 7 parts of processed polygala, and 12 parts of liquorice.

[0040] Example 5

[0041] A traditional Chinese medicine composition for treating or improving ischemic stroke, the traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 25 parts of astragalus, 15 parts of panax notoginseng, 5 parts of radix radix et rhizoma radix, 5 parts of scrophulariae, 10 parts of achyranthes bidentata, 4 parts of peony bark, 3 parts of corydalis, 3 parts of turmeric, 3 parts of curcuma, 2 parts of gentiana macrophylla, 3 parts of processed polygala, and 5 parts of liquorice.

[0042] Example 6

[0043] A traditional Chinese medicine composition for treating or improving ischemic stroke, the traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 35 parts of astragalus, 25 parts of panax notoginseng, 10 parts of radix radix et rhizoma radix, 15 parts of scrophulariae, 20 parts of achyranthes bidentata, 10 parts of moutan bark, 10 parts of corydalis, 6 parts of turmeric, 6 parts of curcuma, 6 parts of gentiana macrophylla, 6 parts of processed polygala, and 10 parts of liquorice.

[0044] Example 7

[0045] A traditional Chinese medicine composition for treating or improving ischemic stroke, the traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 28 parts of astragalus, 22 parts of panax notoginseng, 7 parts of radix radix et rhizoma radix, 10 parts of scrophulariae, 14 parts of achyranthes bidentata, 7 parts of moutan bark, 7 parts of corydalis, 5 parts of turmeric, 5 parts of curcuma, 4 parts of gentiana macrophylla, 5 parts of processed polygala, and 8 parts of liquorice.

[0046] Example 8

[0047] A traditional Chinese medicine composition for treating or improving ischemic stroke, the traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 30 parts of astragalus, 20 parts of panax notoginseng, 6 parts of radix radix et rhizoma radix, 8 parts of scrophulariae, 12 parts of achyranthes bidentata, 5 parts of moutan bark, 5 parts of corydalis, 3 parts of turmeric, 3 parts of curcuma, 3 parts of gentiana macrophylla, 4 parts of processed polygala, and 6 parts of liquorice.

[0048] Test Example 1

[0049] 1 Materials and methods

[0050] 1.1 Experimental animals

[0051] SPF grade 8-week-old male C57 / BL6J mice with a body weight of (20±2) g were selected and raised in an environment of 20-25°C, 12h light-dark cycle, 50%-70% relative humidity, and sufficient food and water. The experiment began after 7 days of adaptive feeding.

[0052] 1.2 Drugs and preparation

[0053] The Chinese medicine stock solution of the invention comprises 30 parts of astragalus, 20 parts of notoginseng, 6 parts of Radix Angelicae Sinensis, 8 parts of Scrophulariae, 12 parts of Achyranthes Bidentatae, 5 parts of Paeonia Suffruticosae, 5 parts of Corydalis, 3 parts of Curcuma, 3 parts of Curcuma, 3 parts of Gentiana Macrophyllae, 4 parts of processed Polygala and 6 parts of Licorice. The raw materials are weighed according to the above weight parts, washed, soaked in 4 times of water for 30 minutes, then decocted for 30 minutes, filtered, decocted in 3 times of water for 30 minutes, combined the two decoctions, concentrated to a drug content of 1 g / mL (equivalent to 1 mL containing 1 g of the raw drug), and stored at 4°C for standby use.

[0054] Western medicine control drug: Clopidogrel tablets, 25 mg / tablet, prepared into 11.38 mg / mL suspension with distilled water and used immediately after preparation.

[0055] 1.3 Construction of ischemic stroke mouse model

[0056] The ischemic stroke mouse model was prepared by photochemical induction. The specific method is: after intraperitoneal injection of 0.5% sodium pentobarbital anesthesia, the mouse was fixed on a brain stereotaxic instrument, the mouse scalp was cut, and the anterior fontanel and lambdoid suture were exposed. The Z axis of the brain stereotaxic instrument was positioned at the center of the anterior fontanel, and the 20mm centered at 3mm posterior and 2mm to the right of the anterior fontanel was exposed. 2 The light-irradiated area and the rest of the area were covered with black cloth. 15 mg / mL rose red dye solution was intraperitoneally injected into the mouse, with an injection volume of 10 μL / g. Turn on the cold light source and irradiate 1.5 cm above the skull for 10 minutes. After the irradiation, the wound was sutured.

[0057] The mice not injected with rose bengal dye were used as sham operation group, and the rest of the operations were the same as above.

[0058] 1.4 Grouping and Dosing

[0059] 50 mice were randomly divided into sham operation group, model group, positive control group, low-dose group of Chinese medicine composition of the present invention (referred to as low-dose group), and high-dose group of Chinese medicine composition of the present invention (referred to as high-dose group), with 10 mice in each group. Pre-administration was performed for 3 days before modeling, and administration was performed for 2 days after modeling. The positive control group was administered with 11 mg / kg of clopidogrel suspension, the low-dose group was administered with 5 g / kg of Chinese medicine stock solution of the present invention, the high-dose group was administered with 15 g / kg of Chinese medicine stock solution of the present invention, and the sham operation group and the model group were gavaged with 10 μL / g of normal saline. Each group was administered once a day.

[0060] 1.5 Observation indicators and detection methods

[0061] 1.5.1 Laser Doppler examination of mouse cerebral microvascular blood flow

[0062] During modeling, the laser Doppler optical fiber was glued to the edge of the irradiation range before illumination to record the cerebral microvascular blood flow before modeling. After recording, illumination was performed to induce ischemic stroke. After illumination, laser Doppler was used to collect the cerebral microvascular blood flow at the same position after modeling, and the reduction rate of cerebral microvascular blood flow after modeling was calculated to evaluate the inhibitory effect of the drug on microthrombi.

[0063] 1.5.2 Longa scoring method to evaluate the neurological function of mice

[0064] Neurological function was evaluated by Longa scoring method 24 hours after the light-induced ischemic stroke model was established. The scoring criteria were 0 points: normal mice, no significant neurobehavioral damage symptoms. 1 point: increased muscle tension of the left forepaw or decreased grip of the left forepaw. 2 points: the mouse showed left-side circling when moving on the platform. 3 points: the mouse showed left-side circling and a tendency to fall when moving on the platform. 4 points: the mouse had no obvious autonomous activity.

[0065] 1.5.3ELISA test

[0066] After the last administration, the mice in each group were anesthetized with 0.5% sodium pentobarbital, and blood was collected from the heart. The levels of vWF and PGI2, which are related indicators of ischemic stroke thrombosis, in the mouse serum were detected using the EILSA kit.

[0067] 1.5.4 HE staining

[0068] The mouse brain tissue was taken on ice, and part of the mouse brain tissue was fixed in 4% paraformaldehyde for 24 h. After washing and dehydration, it was embedded and prepared into 5 μm thick paraffin sections. It was stained with hematoxylin and eosin in sequence, and the pathological changes of brain tissue after ischemic stroke in each group were observed under a microscope.

[0069] 1.5.5TTC staining

[0070] Take the mouse brain tissue on ice, put part of the mouse brain tissue into a mold, freeze it at -20℃ for 20min, and cut the mouse brain into 5 2mm thick coronal slices using the mouse brain tissue mold. Put the brain slices into 2% TTC staining solution and stain them at 37℃ for 20min in the dark. Normal brain tissue is red, and necrotic brain tissue is white. Put the brain slices into 4% paraformaldehyde for fixation, take pictures, and calculate the proportion of cerebral infarction volume.

[0071] 1.6 Statistical analysis

[0072] IBM SPSS Statistics 19.0 software was used for statistical analysis. One-way analysis of variance was used for inter-group comparison. If the variances were equal, the LSD test was used; if the variances were unequal, the GamesHowell test was used. The results are expressed as mean ± standard deviation. P < 0.05 was considered statistically significant.

[0073] 2 Results

[0074] 2.1 Effect of the Chinese medicine composition of the present invention on local microvascular blood flow in mice with photochemically induced ischemic stroke

[0075] As shown in Table 1, compared with the sham operation group, the reduction rate of cerebral microvascular flow in the model group mice was significantly increased (P<0.05); compared with the model group, the reduction rate of cerebral microvascular flow in the positive control group, low-dose group and high-dose group mice was significantly reduced (P<0.05), among which the reduction rates of cerebral microvascular flow in the low-dose group and high-dose group mice were significantly lower than those in the positive control group. The results show that the inhibitory effect of the Chinese medicine composition of the present invention on microthrombi is better than that of clopidogrel.

[0076] Table 1 Decrease rate of cerebral microvascular blood flow in each group of mice after modeling

[0077]

[0078]

[0079] Note: # Compared with the model group, P < 0.05; * Compared with the sham operation group, P<0.05.

[0080] 2.2 Effect of the Chinese medicine composition of the present invention on neurological function in mice with photochemically induced ischemic stroke

[0081] As shown in Table 2, compared with the sham operation group, the mice in the model group showed obvious symptoms of neurobehavioral injury; compared with the model group, the neurological function scores of the mice in the positive control group, low-dose group and high-dose group were significantly reduced (P<0.05), and the neurobehavioral injury status of the mice in each group was improved.

[0082] Table 2 Neurological function scores of mice in each group

[0083] Group quantity Rating (score) Sham operation group 10 0±0 Model Group 10 <![CDATA[2.70±0.67 # ]]> Positive control group 10 <![CDATA[1.80±0.92 * ]]> Low dose group 10 <![CDATA[1.80±0.79 * ]]> High dose group 10 <![CDATA[1.70±0.82 * ]]>

[0084] Note: # Compared with the model group, P < 0.05; * Compared with the sham operation group, P<0.05.

[0085] 2.3 Effect of the Chinese medicine composition of the present invention on the levels of vWF and PGI2, indicators related to thrombosis in mice with photochemically induced ischemic stroke

[0086] Von Willebrand factor (vWF) is mainly produced and released by endothelial cells and plays an important role in platelet adhesion and aggregation as well as thrombosis. Elevated vWF levels indicate severe endothelial damage or dysfunction. vWF is the main factor in platelet aggregation and activation in narrow arteries, which can lead to acute thrombotic occlusion. PGI2 is an endothelial-derived relaxing factor, which is produced by arachidonic acid through the action of prostacyclin synthetase on endothelial cells. Its main function is to increase the cAMP content in platelets, ultimately playing an anti-platelet aggregation and vasodilation role. When endothelial cells are damaged, the PGI2 produced by local endothelial cells decreases, which in turn leads to platelet aggregation and promotes thrombosis.

[0087] As shown in Table 3, compared with the sham operation group, the content of vWF, a thrombosis-related index in the serum of mice in the model group was significantly increased (P<0.05), and the content of PGI2 was significantly decreased (P<0.05); compared with the model group, the content of vWF, a thrombosis-related index in the serum of mice in the positive control group, low-dose group and high-dose group were significantly decreased (P<0.05), and the content of PGI2 was significantly increased (P<0.05).

[0088] Table 3 vWF and PGI2 levels in serum of mice in each group

[0089]

[0090]

[0091] Note: # Compared with the model group, P < 0.05; * Compared with the sham operation group, P<0.05.

[0092] 2.4 Effect of the Chinese medicine composition of the present invention on brain tissue pathological changes and cerebral infarction volume in mice with photochemically induced ischemic stroke

[0093] like Figure 1 As shown, compared with the sham operation group, the model group mice had severe neuronal necrosis in the cerebral cortex, severe tissue damage in the infarction edge area, and disordered cell arrangement; compared with the model group, the necrosis of neuronal cells in the low-dose and high-dose groups of the Chinese medicine composition of the present invention were alleviated, the tissue damage in the infarction edge area was alleviated, and the cell arrangement was more regular.

[0094] like Figure 2As shown in Table 4, compared with the sham operation group, the mice in the model group had obvious necrotic brain tissue; compared with the model group, the cerebral infarction volume of the mice in the positive control group, low-dose group and high-dose group was significantly reduced (P<0.05).

[0095] The above results show that the Chinese medicine composition of the present invention can reduce the infarct volume of brain tissue, improve the pathological changes of brain tissue, and achieve the effect of improving ischemic stroke damage.

[0096] Table 4 Ratio of cerebral infarction volume in each group of mice

[0097] Grouping Cerebral infarction volume ratio (%) Sham operation group 0±0 Model Group <![CDATA[6.50±1.89 # ]]> Positive control group <![CDATA[2.76±0.84 * ]]> Low dose group <![CDATA[4.25±0.96 * ]]> High dose group <![CDATA[2.49±1.10 * ]]>

[0098] Note: # Compared with the model group, P < 0.05; * Compared with the sham operation group, P<0.05.

[0099] 3 Conclusion

[0100] According to the above results, the Chinese medicine composition of the present invention can significantly reduce the rate of decrease in brain microvascular flow in ischemic stroke mice induced by photochemical treatment, has a significant inhibitory effect on the formation of microthrombi, and can significantly reduce the level of vWF in the serum of ischemic stroke mice, and increase the level of PGI2 in the serum; at the same time, it can significantly improve the neurological function damage of ischemic stroke mice, reduce the volume of brain tissue infarction, and improve brain tissue pathological changes. The above results show that the Chinese medicine composition of the present invention has a significant therapeutic effect on ischemic stroke mice induced by photochemical treatment, and can be used as a potential drug for treating or improving ischemic stroke.

[0101] Test Example 2

[0102] 1 Materials and methods

[0103] 1.1 Research subjects

[0104] A total of 70 patients with ischemic stroke who were hospitalized in the Department of Neurology, the First Affiliated Hospital of Henan University of Traditional Chinese Medicine from January 2024 to December 2024 were selected as the research subjects and divided into a control group and an observation group using a random number table method, with 35 cases in each group. Control group: 19 males and 16 females; average age (57.94±7.11) years old. Observation group: 21 males and 14 females, average age (59.23±5.69) years old. There was no significant difference in the general information of the two groups of patients (P>0.05)

[0105] Inclusion criteria: (1) diagnosed with ischemic stroke by Western medicine; (2) diagnosed with stroke according to TCM standards; (3) no more than 14 days since the first onset of the disease; (4) aged 45-75 years; (5) NIHSS score 4-20 points; (6) the patient or his / her legal guardian was fully informed and agreed to participate and signed the corresponding informed consent form.

[0106] Exclusion criteria: (1) women who are pregnant or breastfeeding; (2) those who have had cerebral hemorrhage in the past 6 months; (3) those who have been diagnosed with stroke caused by brain tumors, brain injuries, blood system diseases, infections, genetic diseases, autoimmune diseases, etc.; (4) those who suffer from serious diseases of the liver, kidney, blood, endocrine system, etc.; (5) those who have limb movement disorders that affect the assessment of neurological function, such as claudication, osteoarthritis, rheumatoid arthritis, gouty arthritis, etc.; (6) those who have mental health problems; (7) those who have a history of stroke with significant residual symptoms; (8) those who are currently participating in clinical trials of other drugs.

[0107] 1.2 Methods

[0108] Control group: Guideline-standardized treatment was adopted. The treatment was formulated with reference to the "Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke in China 2018" and the "Guidelines for the Secondary Prevention of Ischemic Stroke and Transient Ischemic Attack in China 2014". Targeted treatment can be carried out for patients with hypertension, hyperglycemia, hyperlipidemia and other diseases. The first aspirin was 100 mg / d and clopidogrel was 300 mg / d; from the next day to the 21st day, aspirin was 100 mg / d and clopidogrel was 75 mg / d; if the patient had contraindications to taking aspirin, ticagrelor tablets could be taken orally at 90 mg / d; edaravone was intravenously dripped, 30 mg / time, twice / d.

[0109] Observation group: On the basis of standardized treatment according to the guidelines, the patients were given the Chinese medicine composition of the present invention. Specifically, the composition includes 30 parts of Astragalus, 20 parts of Panax notoginseng, 6 parts of Radix Angelicae Sinensis, 8 parts of Scrophulariae, 12 parts of Achyranthes Bidentatae, 5 parts of Paeonia Suffruticosae, 5 parts of Corydalis, 3 parts of Curcuma, 3 parts of Curcuma, 3 parts of Gentiana Macrophyllae, 4 parts of Polygala Tenuifolia, and 6 parts of Licorice, 1 dose per day, decocted in water to 400 mL, taken twice a day in the morning and evening.

[0110] The treatment observation period for both is 14 days.

[0111] 1.3 Observation indicators

[0112] 1.3.1 Neurological impairment score (National Institute of Health stroke scale, NIHSS)

[0113] It includes 11 items, including level of consciousness, ability to answer questions, ability to follow instructions, eye movement, visual field, facial muscle strength, upper limb motor kinetics, lower limb motor function, limb coordination, sensory function, language, articulation, and sensory neglect, with a total of 42 points. The higher the score, the more severe the nerve damage.

[0114] 1.3.2 Scoring of activities of daily living

[0115] The assessment was based on the Barthel scale for activities of daily living (ADL) provided in the Chinese Guidelines for the Prevention and Treatment of Cerebrovascular Disease. It included eating, grooming, cleansing, bathing, toileting, dressing, defecation control, urination control, moving between bed and chair, walking 45 meters on flat ground, and climbing stairs, a total of 11 activities. The assessment was based on the Barthel index scoring system (full score 100): (1) independent completion, 100 points; (2) mild dependence, 75-95 points; (3) moderate dependence, 50-70 points; (4) severe dependence, 25-45 points; (5) complete dependence, 0-20 points.

[0116] 1.3.3 TCM symptom scoring

[0117] Main symptoms: upper limb paralysis, lower limb paralysis, crooked mouth and tongue, slurred speech or aphasia; secondary symptoms: limb numbness, dizziness, and sticky sputum; no score for no symptoms, 2 points for mild, 4 points for moderate, and 6 points for severe main symptoms, 1 point for mild, 2 points for moderate, and 3 points for severe secondary symptoms. Add the scores of the main and secondary symptoms together, and the higher the score, the more severe the symptom.

[0118] 1.3.4 Clinical efficacy

[0119] Basically cured: clinical symptoms and signs basically disappear, and the score reduction rate reaches more than 95%;

[0120] Markedly effective: clinical symptoms and signs improved, with the score reduction rate reaching ≥70% and <95%;

[0121] Effective: clinical symptoms and signs have improved to varying degrees, with the score reduction rate reaching ≥30% and <70%;

[0122] Ineffective: The decrease in the total symptom score is less than 30%, and all TCM symptoms and signs have not been significantly improved, and have a tendency to worsen.

[0123] 1.4 Statistical analysis

[0124] SPSS 21.0 statistical software was used for analysis. t test was used for the expression of count data (%) and χ test was used for the expression of count data (%). 2 Test, P < 0.05 was considered statistically significant.

[0125] 2 Results

[0126] 2.1 Comparison of NIHSS scores between the two groups before and after treatment

[0127] Before treatment, there was no significant difference in NIHSS scores between the two groups (P>0.05). Compared with before treatment, the NIHSS scores of the two groups after treatment were significantly reduced, with significant differences (P<0.05); among them, the NIHSS score of the observation group after treatment was significantly lower than that of the control group, with significant differences (P<0.05). The results are shown in Table 5.

[0128] Table 5 NIHSS scores of the two groups of patients before and after treatment (points)

[0129] Group Number of cases Before treatment After treatment Control group 35 19.03±1.79 11.57±1.57* Observation Group 35 18.76±2.01 <![CDATA[8.03±1.84* # ]]>

[0130] Note: Within each group, compared with before treatment, *P<0.05; after treatment, compared with the control group, # P<0.05.

[0131] 2.2 Comparison of ADL scale (BI) scores before and after treatment between the two groups

[0132] Before treatment, there was no significant difference in the Barthel scores between the two groups (P>0.05). Compared with before treatment, the Barthel scores of the two groups after treatment were significantly increased, with significant differences (P<0.05); among them, the Barthel score of the observation group after treatment was significantly higher than that of the control group, with significant differences (P<0.05). The results are shown in Table 6.

[0133] Table 6 ADL scale (BI) scores of the two groups of patients before and after treatment (points)

[0134] Group Number of cases Before treatment After treatment Control group 35 43.18±4.87 63.44±5.07* Observation Group 35 42.87±4.19 <![CDATA[77.46±5.43* # ]]>

[0135] Note: Within each group, compared with before treatment, *P<0.05; after treatment, compared with the control group, # P<0.05.

[0136] 2.3 Comparison of TCM symptom scores between the two groups of patients before and after treatment

[0137] Before treatment, there was no significant difference in the TCM symptom scores between the two groups (P>0.05). Compared with before treatment, the TCM symptom scores of the two groups were significantly reduced after treatment, with significant differences (P<0.05); among them, the TCM symptom scores of the observation group after treatment were significantly lower than those of the control group, with significant differences (P<0.05). The results are shown in Table 7.

[0138] Table 7 TCM symptom scores of the two groups of patients before and after treatment (points)

[0139] Group Number of cases Before treatment After treatment Control group 35 18.47±1.77 10.58±2.01* Observation Group 35 18.91±1.83 <![CDATA[8.21±2.46* # ]]>

[0140] Note: Within each group, compared with before treatment, *P<0.05; after treatment, compared with the control group, #P<0.05.

[0141] 2.4 Comparison of clinical treatment efficacy between the two groups of patients

[0142] The total effective rate of the observation group was 88.57%, and the total effective rate of the control group was 62.86%. The total effective rate of the observation group was significantly higher than that of the control group, with a significant difference (P < 0.05). The results are shown in Table 8.

[0143] Table 8 Clinical treatment efficacy of both patients [n (%)]

[0144]

[0145] 3 Conclusion

[0146] The Chinese medicine composition of the present invention can significantly improve the symptoms of neurological function damage in patients with ischemic cerebral stroke, can help restore and improve the patients' ability to carry out daily activities, significantly alleviate and improve the patients' clinical symptoms such as upper limb paralysis, lower limb paralysis, crooked mouth and tongue, slurred speech or aphasia, and significantly improve the total effective rate of ischemic stroke treatment.

[0147] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that the technical solutions described in the aforementioned embodiments may still be modified, or some of the technical features may be replaced by equivalents. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A Chinese medicine composition for treating or improving ischemic stroke, characterized in that: The Chinese medicine composition is composed of the following raw materials in parts by weight: 20-40 parts of astragalus, 10-30 parts of panax notoginseng, 1-15 parts of radix radix et rhizoma, 5-20 parts of scrophulariae, 5-20 parts of achyranthes bidentata, 1-15 parts of moutan bark, 1-15 parts of corydalis, 1-10 parts of turmeric, 1-10 parts of curcuma, 1-10 parts of gentiana macrophylla, 1-10 parts of processed polygala, and 1-15 parts of liquorice.

2. A Chinese medicine composition for treating or improving ischemic stroke according to claim 1, characterized in that: The Chinese medicine composition is composed of the following raw materials in parts by weight: 25-35 parts of Astragalus, 15-25 parts of Panax notoginseng, 5-10 parts of Radix Angelicae Sinensis, 5-15 parts of Scrophulariae, 10-20 parts of Achyranthes Bidentatae, 1-10 parts of Paeonia Suffruticosa, 1-10 parts of Corydalis Seu Radix, 1-6 parts of Curcuma Longa, 1-6 parts of Curcuma Aromatica, 1-6 parts of Gentiana Macrophyllae, 1-6 parts of processed Polygala Tenuifolia, and 5-10 parts of Licorice.

3. A Chinese medicine composition for treating or improving ischemic stroke according to claim 1, characterized in that: The Chinese medicine composition is composed of the following raw materials in parts by weight: 30 parts of Astragalus, 20 parts of Panax notoginseng, 6 parts of Radix Angelicae Sinensis, 8 parts of Scrophulariae, 12 parts of Achyranthes Bidentatae, 5 parts of Paeonia Suffruticosa, 5 parts of Corydalis, 3 parts of Curcuma, 3 parts of Curcuma, 3 parts of Gentiana Macrophylla, 4 parts of processed Polygala, and 6 parts of Licorice.

4. Use of the Chinese medicine composition according to any one of claims 1 to 3 in the preparation of a medicament for treating or improving ischemic stroke, characterized in that: The medicine is prepared into oral dosage forms by the above-mentioned Chinese medicine composition according to conventional preparation methods, and the dosage forms include oral liquid, granules, suspensions, powders, decoctions, pills, tablets, capsules, and freeze-dried powders.

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