Medicine for treating cerebral arterial thrombosis

Abstract

The invention belongs to the technical field of traditional Chinese medicine preparation, and particularly relates to a medicine for treating cerebral arterial thrombosis, the medicine is prepared from the following raw materials in parts by weight: 10-15 parts of angelica sinensis, 6-10 parts of ligusticum wallichii, 10-15 parts of salvia miltiorrhiza, 6-10 parts of frankincense, 6-10 parts of myrrh, 3-6 parts of leech, 10-15 parts of centella asiatica and 10-15 parts of sculellaria barbata, experiments show that the medicine can effectively improve neurological functions; the cerebral infarction volume of the rat can be obviously reduced; in the aspect of brain tissue pathological damage, after the medicine is added for intervention, pathological changes such as nerve cell degeneration and necrosis occurring in a model group can be relieved to different degrees; under the condition of neuron apoptosis, the number of apoptotic cells of a model group is increased, and the medicine can reduce the number of apoptotic cells; in general, the medicine provided by the invention has a remarkable treatment effect on patients suffering from cerebral arterial thrombosis.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicine preparation, and particularly relates to a medicine for treating ischemic stroke. Background Art

[0002] Ischemia stroke (IS) is an acute cerebrovascular disease caused by stenosis or occlusion of the cerebral and carotid arteries, leading to inadequate localized brain blood supply and consequent cerebral infarction. Its pathogenesis is complex, involving endothelial injury, thrombosis, neurovascular unit damage, inflammation, oxidative stress, and apoptosis. Clinically, it often presents with symptoms such as hemiplegia, hemiplegia, and speech dysfunction. It is characterized by high morbidity, recurrence, disability, and mortality rates. It often occurs in middle-aged and elderly individuals, with a recent trend toward younger onset, posing a serious threat to their health and well-being.

[0003] For patients with very early and acute IS, the optimal treatment is intravenous injection of tissue plasminogen activator and endovascular thrombectomy to relieve large vessel occlusion and salvage the ischemic penumbra through rapid revascularization. Tissue plasminogen activator is the only thrombolytic drug approved by the US Food and Drug Administration and is widely used worldwide. However, its therapeutic window is narrow, requiring patients to receive thrombolytic therapy within 4.5 hours of stroke. Many patients miss this window or are unable to receive timely treatment due to personal reasons. Even for patients who have received acute thrombolytic therapy and thrombectomy, although reperfusion can restore blood oxygenation, the free radicals generated can trigger a series of inflammatory cascades, further exacerbating tissue damage and causing varying degrees of neurological impairment and behavioral dysfunction, severely impacting patients' quality of life.

[0004] In this context, seeking effective drugs to treat ischemic stroke has become a research focus in the medical community. Summary of the Invention

[0005] In view of this, the present invention provides a drug for treating ischemic stroke.

[0006] To achieve the above objectives, this application adopts the following scheme: A medicine for treating ischemic stroke, comprising the following raw materials in parts by weight: 10-15 parts of Chinese Angelica sinensis, 6-10 parts of Chuanxiong, 10-15 parts of Salvia miltiorrhiza, 6-10 parts of frankincense, 6-10 parts of myrrh, 3-6 parts of Hirudo, 10-15 parts of Centella asiatica, and 10-15 parts of Scutellaria barbata.

[0007] Preferably, it is composed of the following raw materials by weight: 12 parts of Chinese Angelica sinensis, 10 parts of Chuanxiong, 15 parts of Salvia miltiorrhiza, 6 parts of frankincense, 6 parts of myrrh, 3 parts of Hirudo, 15 parts of Centella asiatica, and 15 parts of Scutellaria barbata.

[0008] Preferably, the preparation method of the drug comprises the following steps: S10 weigh the above parts by weight of each raw material; S20. The weighed raw materials were added to about 10 times the distilled water and soaked at room temperature for the first time; S30. After soaking, bring to a boil over high heat and then simmer for a second time. S40. After decoction, the mixture is filtered, the residue is added with water and boiled, and then simmered for the second time. After decoction, the residue is filtered and discarded. The two filtrates are combined and filtered again with gauze, and evaporated and concentrated to obtain the drug.

[0009] Preferably, the first duration is 18 hours and the second duration is 1 hour.

[0010] Preferably, the dosage of the drug is 7.2 g / kg-14.4 g / kg.

[0011] Preferably, the drug includes pharmaceutical excipients acceptable in traditional Chinese medicine pharmacy or is prepared into a pharmaceutical dosage form suitable for clinical use.

[0012] The above-mentioned drug for treating ischemic stroke, as shown in the modeling results below, was successfully established in all groups of rats. After drug administration, the Longa scores of all experimental groups decreased, but the decrease in the drug group provided in the present application was the most significant, close to that of the normal group, indicating that it can effectively improve neurological function; in terms of cerebral infarction volume, the experimental group can significantly reduce the cerebral infarction volume of rats, and the effect is better than that of the drug pair group and the positive control group; in terms of brain tissue pathological damage, after intervention with the drug provided in the present application, the pathological changes such as nerve cell degeneration and necrosis in the model group can be alleviated to varying degrees; in terms of neuronal apoptosis, the number of apoptotic cells in the model group increased, while the drug provided in the present application can reduce the number of apoptotic cells; in general, the drug provided in the present application has a significant therapeutic effect on patients with ischemic stroke. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 This is the Longa score chart of rats on the first day of modeling in this application.

[0014] Figure 2 This is the Longa score chart of rats on the seventh day of modeling in this application.

[0015] Figure 3 This is a TTC staining picture of rat brain tissue in this application.

[0016] Figure 4 This is the HE staining result of brain tissue of rats in different treatment groups in this application.

[0017] Figure 5These are the Tunel staining results of brain tissues of rats in different treatment groups in this application.

[0018] Figure 1 and Figure 2 Middle: CON (normal group), M (model group), YD (drug pair group), Y (experimental group), E (positive control group); Figure 3 Middle: C (normal group), M (model group), YD (drug pair group), Y (experimental group), E (positive control group); Figure 4 and Figure 5 Middle: CON (normal group), MOD (model group), YD (drug pair group), Y (experimental group), E (positive control group). DETAILED DESCRIPTION

[0019] To make the objectives and technical solutions of the present invention more clearly understood, the present invention is further described in detail through experiments. However, it should not be understood that the present invention is limited to the following experiments within the scope of the above-mentioned subject matter. Any corresponding substitutions or modifications made according to common technical knowledge and customary means in the art without departing from the above-mentioned technical premise are included in the present invention.

[0020] In one embodiment provided herein, a drug for treating ischemic stroke is composed of the following raw materials in parts by weight: 10-15 parts of Chinese Angelica sinensis, 6-10 parts of Chuanxiong, 10-15 parts of Salvia miltiorrhiza, 6-10 parts of frankincense, 6-10 parts of myrrh, 3-6 parts of Hirudo, 10-15 parts of Centella asiatica, and 10-15 parts of Scutellaria barbata.

[0021] In this formula, the distinct roles of the main, secondary, adjuvant, and envoy herbs are clearly defined, working synergistically to invigorate blood circulation, remove stasis, detoxify, and dredge the meridians. Specifically, angelica and salvia miltiorrhiza serve as the main herbs, complementing each other. Angelica tonifies blood, invigorates blood circulation, regulates menstruation, and relieves pain, while salvia miltiorrhiza activates blood circulation, removes stasis, dredges menstruation, and relieves pain. Together, these herbs exert their core functions of invigorating blood circulation, removing stasis, dredge the meridians, and relieve pain, laying a solid foundation for the treatment of ischemic stroke.

[0022] Chuanxiong and Hirudo are both assistant herbs. Chuanxiong, with its pungent, dispersing, warming, and unblocking properties, invigorates blood circulation and promotes the flow of qi and blood, while Hirudo, with its potent blood-dissolving power, promotes the flow of blood, dispels stasis, and resolves symptoms. Together, the two herbs further enhance the efficacy of invigorating blood circulation, removing stasis, unblocking meridians, and dissolving symptoms, empowering the main herb to achieve greater results.

[0023] Frankincense and myrrh, as adjuvants, not only enhance the effects of promoting blood circulation and qi, but also reduce swelling and relieve pain. Their synergy allows the drug to effectively promote blood circulation and dissipate blood stasis, while also effectively alleviating the pain and swelling caused by ischemic stroke.

[0024] Centella asiatica and Scutellaria barbata act as guiding herbs. Centella asiatica clears heat and detoxifies, promotes blood circulation and promotes urination, helping to eliminate heat and toxins from the body and promote blood circulation. Scutellaria barbata clears heat and detoxifies, promotes blood circulation and blood stasis, and relieves swelling and pain, further enhancing the detoxification and meridian-opening effects of the herbs. The two herbs complement each other, guiding the herbs directly to the affected area for optimal therapeutic effect.

[0025] In summary, these eight Chinese herbs are carefully combined to form a unique formula with synergistic effects of "activating blood circulation, detoxifying and unblocking meridians". This formula effectively improves the blood circulation of patients with ischemic stroke, reduces inflammatory response, and protects nerve cells through the comprehensive effects of multiple pathways and multiple targets, thereby showing significant clinical effects in the treatment of ischemic stroke. The following experiments also show that it can effectively improve neurological function; in terms of cerebral infarction volume, the experimental group can significantly reduce the cerebral infarction volume of rats, and the effect is better than that of the drug pair group and the positive control group; in terms of brain tissue pathological damage, after intervention with the drugs provided in this application, the pathological changes such as nerve cell degeneration and necrosis in the model group can be alleviated to varying degrees; in terms of neuronal apoptosis, the number of apoptotic cells in the model group increased, while the drugs provided in this application can reduce the number of apoptotic cells; in general, the drugs provided in this application have significant therapeutic effects on rats with ischemic stroke.

[0026] The following specific experimental examples further illustrate the technical solutions and technical effects of the present invention. It should be noted that the inventors conducted relevant pharmacodynamic studies to prove the efficacy of the drugs for treating ischemic stroke in the present invention. It should be noted that the following experimental studies were all conducted on the basis of proving the safety of the drugs, and the dosages in the experimental studies were all within the safe dosage range. The drugs selected for the following pharmacodynamic tests are drugs obtained by the representative formulas and preparation methods of the present invention; the inventors of other drugs also conducted pharmacodynamic experiments, and the experimental results showed that they had the same or similar effects, but due to space limitations, they are not listed here one by one.

[0027] 1. Pharmaceutical materials Centella asiatica and leech extract (prepared in the laboratory of the Medical University); An extract prepared according to the method provided in this application (prepared in the laboratory of Medical University) contains 12 parts of Angelica sinensis, 10 parts of Chuanxiong, 15 parts of Salvia miltiorrhiza, 6 parts of Frankincense, 6 parts of Myrrh, 3 parts of Hirudo, 15 parts of Centella asiatica, and 15 parts of Scutellaria barbata.

[0028] 2 Construction of ischemic stroke rat model 2.1 Experimental Animals SPF-grade Sprague-Dawley rats weighing 260-300 g were provided by the Experimental Animal Center of the Medical University. They were maintained in a ventilated, dry animal room with a room temperature of 22-25°C and a humidity of 50%-70% with free access to water and a fixed diet.

[0029] 2.2 Animal grouping Sixty SPF adult male SD rats aged 6-8 weeks that passed quarantine were randomly divided into five groups, namely normal group, model group, drug pair group, experimental group and positive control group, with 12 rats in each group.

[0030] 2.3 Model Building The Longa suture method was used to establish a MCAO model in rats in the normal, model, drug-drug combination, experimental, and positive control groups. Rats were weighed, anesthetized intraperitoneally, and placed supine on a surgical board. The anterior neck hair was shaved, and after disinfection with iodine, an incision was made along the left side of the neck. The common, external, and internal carotid arteries were isolated. The common carotid artery was ligated proximally at the bifurcation of the external carotid artery, and an artery clamp was placed at the bifurcation of the internal carotid artery. A 0.24 mm suture was inserted through the puncture hole in the common carotid artery. The clamp was released and the artery was inserted 18-22 mm until resistance was felt. The suture was then ligated and the wound was cleaned. In the normal group, the arteries were isolated without ligation or suture insertion.

[0031] 2.4 Administration The normal group and the model group (administered with normal saline by gavage) were given once a day at a dose of 0.63 g / kg for 7 consecutive days; The drug pair group (Centella asiatica and Leech extract) was given once a day at a dose of 0.63 g / kg for 7 consecutive days; The experimental group (the extract provided by this application) was administered once a day at a dose of 14.4 g / kg for 7 consecutive days; The positive control group (edaravone) was given once a day at a dose of 4.55 g / kg for 7 consecutive days.

[0032] 3. Experimental Results 3.1 Longa Rating Evaluation of rat MCAO model: The Longa rat neurobehavioral score is an internationally recognized scoring standard for rat MCAO model, as shown in Table 1. Therefore, the Longa rat neurobehavioral score was used to evaluate whether the rat MCAO model was successfully established.

[0033] Table 1 Neurobehavioral score of Longa rats

[0034] As shown in Table 1, MCAO rats with a postoperative neurological behavioral score of 1-3 were considered to have a successful model. This means that after waking up from anesthesia, the rats showed left limb paralysis, unstable standing position, and turned to one side when the tail was lifted. Figure 1 ) and the seventh day ( Figure 2 ) Longa score situation.

[0035] 3.2 TTC staining of rat brain tissue After killing the animal by decapitation, the brain is quickly removed (within 10 minutes), transferred to a 0-4°C PBS solution, and then placed in a -20°C refrigerator for 30 minutes to freeze the brain slightly for easy slicing. The thickness of the coronal sections of rat brain tissue is controlled at 2 mm. Place the slices in a 2% red tetrazolium solution and incubate in a light-proof water bath or incubator at 37°C for 15-30 minutes. During this period, shake the container slightly every 5 minutes or turn the brain slices over in the middle to ensure that the slices are fully stained. After staining, remove the brain slices and wash them with PBS solution for 3-5 minutes. The brain slices can be fixed with 10% neutral formaldehyde, 4% paraformaldehyde or 4% formalin solution. Choose a suitable background and angle, use a camera or pathological image analysis system to take pictures of the stained brain slices, and obtain TTC staining pictures of rat brain tissue, as shown below. Figure 3 shown.

[0036] 3.3 H&E staining The pathological changes of brain tissue in each group of rats were analyzed by H&E staining: the embedded brain tissue specimens were placed on a microtome and cut into 4 μm slices. The dried slices were dewaxed with xylene, immersed in hematoxylin staining solution, and then separated with 1% hydrochloric acid alcohol, stained with eosin staining solution, rinsed with distilled water, and then dehydrated and immersed in xylene and sealed with resin glue. The brain tissue structure was observed under an optical microscope and photographed. Figure 4 shown.

[0037] 3.4 Tunel staining Tunel staining was used to analyze neuronal apoptosis in the brain tissue of each group of rats: Tunel apoptosis detection kit was used to detect neuronal apoptosis in the brain tissue of each group of mice. The brain tissue was made into coronal paraffin sections, stained with TUNEL working solution, and incubated at 37°C in the dark for 1 hour. Then, the antibiotic protein streptavidin HRP working solution was applied to the sections and incubated for another 30 minutes. Subsequently, DAPI was used for cell nuclei staining; finally, the sections were observed under a microscope and photographed, as shown in the following figure. Figure 5 The neuronal apoptosis rate in mouse brain tissue was calculated based on the quantitative fluorescence intensity. The neuronal apoptosis rate was calculated as: number of apoptotic neurons / total number of neurons × 100%.

[0038] After the experiment, the above results were analyzed. Figure 1 The results showed that the models of rats in the above groups were successfully established. Figure 2 The results showed that after drug administration, the Longa scores of each group decreased to varying degrees, and the score of the experimental group decreased most significantly, closer to that of the normal group.

[0039] Depend on Figure 3It can be seen that compared with the normal group (CON), the percentage of cerebral infarction volume in the model group (MOD) rats was significantly increased, and compared with the model group, the percentage of cerebral infarction volume in the experimental group (Y) rats was reduced, and the effect was better than that of the drug pair group (YD) and the positive control group (E), indicating that the modified Huoluo Xiaoling Dan provided in this application can effectively reduce the cerebral infarction volume in rats with ischemic stroke.

[0040] Depend on Figure 4 HE staining results showed that in the ischemic core area of ​​the model group (MOD), a large number of nerve cells were observed to be degenerated, necrotic, loose, and structurally lost, presenting a sieve-like pattern; scattered neuronal death was observed in the ischemic peripheral area, and some neurons showed reversible changes such as cytoplasmic red staining and cell body shrinkage, while the tissue structure was basically intact; after intervention with the drug extract provided in this application, the above-mentioned pathological changes could be alleviated to varying degrees, indicating that the drug provided in this application can improve pathological damage to brain tissue.

[0041] Depend on Figure 5 Tunel staining results showed that very few apoptotic nerve cells were observed in the brain tissue of the model group (MOD) rats, and the number of apoptotic cells in the model group rats was significantly increased; after intervention with the drug extract provided by this application and the positive control drug, the number of apoptotic cells decreased.

[0042] In summary, the drug provided in this application has a significant therapeutic effect on rats with ischemic stroke.

[0043] The above description is only a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any technician familiar with this technical field can easily think of various equivalent modifications or replacements within the technical scope disclosed by the present invention, and these modifications or replacements should all be included in the scope of protection of the present invention.

Claims

1. A drug for treating ischemic stroke, characterized in that: The composition is composed of the following raw materials by weight: 10-15 parts of Chinese Angelica sinensis, 6-10 parts of Chuanxiong, 10-15 parts of Salvia miltiorrhiza, 6-10 parts of frankincense, 6-10 parts of myrrh, 3-6 parts of Hirudo, 10-15 parts of Centella asiatica, and 10-15 parts of Scutellaria barbata.

2. The drug for treating ischemic stroke according to claim 1, characterized in that The composition is composed of the following raw materials by weight: 12 parts of Chinese Angelica sinensis, 10 parts of Chuanxiong, 15 parts of Salvia miltiorrhiza, 6 parts of frankincense, 6 parts of myrrh, 3 parts of Hirudo, 15 parts of Centella asiatica, and 15 parts of Scutellaria barbata.

3. The drug for treating ischemic stroke according to claim 1, characterized in that The preparation method of the medicine comprises the following steps: S10 weigh the above parts by weight of each raw material; S20. The weighed raw materials were added to about 10 times the distilled water and soaked at room temperature for the first time; S30. After soaking, boil over high heat and simmer for the second time; S40. After decoction, the mixture is filtered, the residue is added with water and boiled, and then simmered for the second time. After decoction, the residue is filtered and discarded. The two filtrates are combined and filtered again with gauze, and evaporated and concentrated to obtain the drug.

4. The drug for treating ischemic stroke according to claim 3, characterized in that The first duration is 18 hours, and the second duration is 1 hour.

5. The drug for treating ischemic stroke according to claim 1, wherein The dosage of the drug is 7.2 g / kg-14.4 g / kg.

6. The drug for treating ischemic stroke according to claim 1, characterized in that The medicine includes pharmaceutical excipients acceptable in traditional Chinese medicine pharmacy or is prepared into a pharmaceutical dosage form suitable for clinical use.

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