Application of sessilazine methyl ether and pharmaceutical composition thereof in preparation of medicine for preventing or treating brain injury
Sesamin methyl ether addresses the treatment challenges of ischemic stroke and hemorrhagic transformation by inhibiting acetylcholinesterase and regulating the MAPK/ERK signaling pathway, significantly reducing the area of cerebral infarction and hemorrhage, and improving neurological function.
Patent Information
- Application Number
- CN202511479211.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-10-16
- Publication Date
- 2025-12-12
AI Technical Summary
Existing treatments for ischemic stroke, such as rt-PA thrombolysis, have a narrow time window, are expensive, and have safety concerns. Conventional treatment interventions have limited efficacy, and there is a lack of effective drugs to prevent hemorrhagic transformation.
Using Geissoschizine methyl ether (GM) as the drug component, it reduces the hydrolysis of acetylcholine by inhibiting acetylcholinesterase (AChE) activity, thereby increasing the level of acetylcholine in the brain, reducing the level of reactive oxygen species (ROS), regulating the MAPK/ERK signaling pathway, and alleviating oxidative stress damage to nerve cells.
Sesamin methyl ether significantly reduces the infarct area and hemorrhage area in ischemic stroke and hemorrhagic transformation, improves neurological function, and provides a new direction for the treatment of brain injury.
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Abstract
Description
TECHNICAL FIELD
[0001] The present application belongs to the technical field of medicine, and particularly relates to the use of suture seedazine methyl ether and a pharmaceutical composition thereof in the preparation of a medicament for preventing or treating brain injury. BACKGROUND
[0002] Stroke is a refractory disease that seriously endangers human health and life safety in the world today, and is the second leading cause of death and disability worldwide, causing 5.5 million deaths each year. Studies have shown that the incidence of stroke has been on the rise in recent years, and nearly one in four people in the world has experienced a stroke in their lifetime. The disability-adjusted life years (DALY) caused by ischemic stroke is 51.9 million years per year, and about 34% of the total medical expenses worldwide are related to the treatment of stroke, highlighting the enormous economic and social impact of this disease. Ischemic stroke is caused by stenosis or occlusion of the cerebral blood supply artery, leading to cerebral tissue necrosis and neurological dysfunction. Currently, the only approved treatment for ischemic stroke by the US Food and Drug Administration is rt-PA thrombolytic therapy. However, due to the narrow treatment time window (<4.5 h), high cost and safety concerns involving increased risk of cerebral hemorrhage and neurotoxicity, only a small number of stroke patients can receive rt-PA therapy. Conventional treatment interventions, including drug therapy, rehabilitation therapy and secondary prevention, have been observed to have limited efficacy, and therefore, more effective treatment methods need to be discovered.
[0003] Hemorrhagic transformation (HT) refers to bleeding caused by reperfusion of blood vessels in the infarcted area after cerebral ischemia, and is a common complication of thrombolytic therapy and mechanical thrombectomy for ischemic stroke. About 10%-40% of patients with ischemic stroke develop hemorrhagic transformation after intravenous thrombolysis or thrombectomy. Studies have shown that delayed use of rt-PA for thrombolytic therapy, insufficient reperfusion after thrombectomy, high blood glucose levels, and hypertension significantly increase the probability of hemorrhagic transformation in ischemic stroke. When HT occurs, it affects the normal treatment and recovery process of stroke, aggravates brain injury, increases the morbidity and mortality of stroke, and increases the risk of other complications related to stroke, and therefore, prevention of HT is very important for the prognosis and rehabilitation of stroke patients. Current treatment targets for hemorrhagic transformation in ischemic stroke mainly focus on reducing reactive oxygen species, inhibiting the expression of metal matrix proteinases, and maintaining the stability of the blood-brain barrier. Although some drugs such as minocycline have shown certain efficacy in animal models of hemorrhagic transformation in ischemic stroke, no drug has been successfully translated into clinical use. Therefore, it is of great significance to study effective treatment methods and compounds for controlling hemorrhagic transformation for the treatment and rehabilitation of the ischemic stroke patient population. SUMMARY
[0004] The present application aims to find a drug that can treat both ischemic stroke and hemorrhagic transformation of ischemic stroke.
[0005] Geissoschizine methyl ether (GM) (CAS No. 60314-89-8) is a natural indole alkaloid extracted from Uncaria rhynchophylla, which is the main active ingredient of Yishan San. Geissoschizine methyl ether is a potent acetylcholinesterase (AChE) inhibitor, and its inhibition of AChE is a reversible non-competitive inhibition. This compound can reduce the hydrolysis rate of acetylcholine (ACh) in the central nervous system by inhibiting AChE activity, thereby increasing the steady-state level of ACh in the brain and improving cognitive function. Therefore, it has potential therapeutic value in neurodegenerative diseases such as Alzheimer's disease, which are closely related to the decline of the acetylcholinergic system. In addition, studies have shown that geissoschizine methyl ether can significantly improve the survival activity of SH-SY5Y cells (a model of nerve cells) induced by glutamate (Glu) damage. Specifically, excessive Glu can induce a large accumulation of reactive oxygen species (ROS) in SH-SY5Y cells, while geissoschizine methyl ether can effectively down-regulate the intracellular ROS level, significantly reduce the content of lipid peroxidation product malondialdehyde (MDA), and increase the level of endogenous antioxidant glutathione (GSH), thereby exhibiting a clear neuroprotective effect. Further mechanism studies have shown that this compound can also inhibit the expression of cleaved-caspase-3, a key protein in apoptosis, in SH-SY5Y cells induced by Glu, while down-regulating the protein levels of p-ERK and p-p38, suggesting that it may regulate the ROS-MAPK / ERK signaling pathway to effectively reduce Glu-mediated neurotoxicity and oxidative stress damage.
[0006] From the pathological mechanism, when ischemic stroke occurs, brain tissue causes energy metabolism disorder due to hypoxia and ischemia, and then leads to a large number of abnormal release of Glu, further induces excessive generation of ROS; at the same time, ROS can consume endogenous antioxidants, aggravate oxidative stress damage. In addition, Glu excitotoxicity can also activate MAPK / ERK, p38 and other signaling pathways, promote the expression of cleaved-caspase-3, and ultimately lead to neuronal apoptosis, and aggravate the neurological impairment after cerebral ischemia. In the process of hemorrhagic transformation of ischemic stroke, the core secondary injury is caused by hemolysis products (such as hemoglobin, free iron ions): among them, iron ions can generate a large amount of ROS through Fenton reaction, induce oxidative stress; at the same time, the local brain tissue of the hemorrhagic area will appear Glu release increase, neuronal calcium overload, and then activate MAPK / ERK, p38 signaling pathway, ultimately leading to neuronal apoptosis, further worsening the nerve function.
[0007] So far, the activity of suture seedazine methyl ether in cerebrovascular diseases (especially ischemic stroke and hemorrhagic transformation of ischemic stroke) has not been clear. The core innovation of the present application is that it is first confirmed that suture seedazine methyl ether has potential application value in the treatment of brain injury (especially ischemic stroke and hemorrhagic transformation of ischemic stroke): through animal experiment verification, the compound can significantly reduce the cerebral infarction area and hemorrhagic area of the rat cerebral ischemia / hemorrhagic transformation model, and effectively improve the neurological impairment of the model animal. Based on the above findings, the present application provides the use of suture seedazine methyl ether in the preparation of a drug for preventing or treating brain injury, which provides a new direction and candidate molecule for the research and development of brain injury treatment drugs.
[0008] Technical scheme: The present application provides the use of suture seedazine methyl ether in the preparation of a drug for preventing and / or treating brain injury.
[0009] Further, the use of suture seedazine methyl ether in the preparation of a drug for preventing and / or treating brain injury caused by cerebrovascular diseases such as ischemic stroke and hemorrhagic transformation of ischemic stroke.
[0010] Among them, the chemical structural formula of the suture seedazine methyl ether is as follows:
[0011] Among them, the suture seedazine methyl ether is used in the preparation of a drug for preventing and / or treating brain injury by significantly reducing the cerebral infarction area and behavior score under the middle cerebral artery occlusion model.
[0012] Among them, the suture seedazine methyl ether is used in the preparation of a drug for preventing and / or treating brain injury by significantly improving the brain hemorrhage area, hemorrhage score and behavior score under the acute hyperglycemia combined with middle cerebral artery occlusion model.
[0013] The present application also provides a pharmaceutical composition for preventing and / or treating brain injury, which comprises a therapeutically effective amount of geissoschizine methyl ether or a pharmaceutically acceptable salt thereof.
[0014] The present application also provides the use of the pharmaceutical composition for preparing a medicament for preventing and / or treating brain injury.
[0015] Further, the use of the pharmaceutical composition for preparing a medicament for preventing and / or treating brain injury caused by ischemic stroke and hemorrhagic transformation of ischemic stroke.
[0016] In some embodiments, the pharmaceutical composition for preventing and / or treating brain injury comprises geissoschizine methyl ether or a pharmaceutically acceptable salt or solvate thereof and a pharmaceutically acceptable carrier.
[0017] The present application also provides a pharmaceutical preparation, which comprises a therapeutically effective amount of geissoschizine methyl ether and a pharmaceutically acceptable carrier, adjuvant or vehicle.
[0018] The present application also provides the use of the pharmaceutical preparation for preparing a medicament for preventing and / or treating brain injury.
[0019] Further, the dosage form of the pharmaceutical preparation is a capsule, a powder, a tablet, a granule, a pill, an injection, a syrup, an oral liquid, an inhalant, a cream, an ointment, a suppository or a patch.
[0020] The amount of geissoschizine methyl ether is 1, 5 or 10 mg / kg in animal experiments.
[0021] In animal models, 1, 5 or 10 mg / kg of geissoschizine methyl ether (GM) can significantly reduce the cerebral infarction area of rats in a middle cerebral artery occlusion (tMCAO) model, and 1 mg / kg of geissoschizine methyl ether can significantly improve the behavioral score of rats in the tMCAO model; 1 mg / kg of geissoschizine methyl ether administered 10 min before reperfusion, 1 h after reperfusion and 3 h after reperfusion can significantly reduce the cerebral infarction area of rats in the tMCAO model, and administration 1 h after reperfusion can significantly reduce the behavioral score of rats in the tMCAO model; 1 mg / kg of geissoschizine methyl ether administered 1 h after reperfusion can significantly reduce the brain hemorrhage area and hemorrhage score of rats in an acute hyperglycemia combined tMCAO model, and administration 1 h after reperfusion can significantly improve the behavioral score of rats in the acute hyperglycemia combined tMCAO model.
[0022] The present application is a new functional compound discovered through random screening, and the main mechanism of action may be to reduce the damage of brain microvascular endothelial cells under ischemia and hypoxia conditions, thereby protecting the blood-brain barrier and improving brain ischemia and brain hemorrhage damage.
[0023] Advantages: Compared with the prior art, the present application has the following advantages: The present application provides, for the first time, the use of geissoschizine methyl ether in the preparation of a drug for preventing and / or treating brain damage, and geissoschizine methyl ether has a significant effect in preventing and / or treating brain damage, especially brain damage caused by ischemic stroke and hemorrhagic transformation of ischemic stroke, and can significantly reduce brain damage caused by ischemic stroke and hemorrhagic transformation of ischemic stroke.
[0024] The present application finds that geissoschizine methyl ether (GM) has a significant effect of reducing the brain infarction area and behavior score of rats under a middle cerebral artery occlusion (tMCAO) model ( Figure 1 ), 2) geissoschizine methyl ether (GM) has a significant effect of reducing the hemorrhage area, hemorrhage score and behavior score under an acute hyperglycemia combined with middle cerebral artery occlusion (tMCAO+HG) model ( Figure 3 ). And the pharmaceutical composition comprising geissoschizine methyl ether (GM) of the present application can become a new drug for preventing and / or treating brain damage, treating various cerebrovascular diseases including ischemic stroke. BRIEF DESCRIPTION OF DRAWINGS
[0025] Figure 1 The effects of different concentrations of geissoschizine methyl ether (GM) on the brain infarction area and behavior score of rats under a transient middle cerebral artery occlusion (tMCAO) model, wherein *** P<0.001 vs Sham; ## P<0.01 , ### P<0.001 vs Vehicle, (Graphpad 9.5, One-way ANOVA); Figure 2 The effects of 1 mg / kg of geissoschizine methyl ether (GM) given at different time points on the brain infarction area and behavior score of rats under a transient middle cerebral artery occlusion (tMCAO) model, wherein *** P<0.001vs Sham; ## P<0.01 , ### P<0.001 vs Vehicle, (Graphpad 9.5, One-way ANOVA); Figure 3 Effects of Geissoschizine methyl ether (GM) on the brain hemorrhage area, brain hemorrhage score and behavior score of acute high glucose combined with transient middle cerebral artery occlusion (tMCAO+HG) model rats; wherein *** P<0.001 vs Sham; ## P<0.01 , ### P<0.001 vs Vehicle, (Graphpad 9.5, One-way ANOVA). DETAILED DESCRIPTION
[0026] The present application will be further described in conjunction with the accompanying drawings, and the examples are only used to explain the present application, and are not used to limit the scope of the present application.
[0027] Drugs and reagents: Geissoschizine methyl ether (GM) used in the examples was purchased from Chengdu Manst Biological Technology Co., Ltd. (CAS No. 60314-89-8, product No. A1060), and other reagents were commercially available analytical reagents.
[0028] Male SD rats were purchased from Spabio Biotechnology Co., Ltd. (Suzhou) (License No. SCXK (Su) 2024-0001).
[0029] Example 1: Effects of different concentrations of Geissoschizine methyl ether administration on the brain infarction area and behavior of middle cerebral artery occlusion (tMCAO) rats.
[0030] (1) Establishment of rat tMCAO model The rat tMCAO model refers to the internal carotid line embolism method of Longa et al. The main operation steps are as follows: after weighing the male SD rats with a body weight of about 280 g, the rats are placed in an anesthesia induction box, and 3%-4% isoflurane is given to induce anesthesia. After the rats are anesthetized, the rats are fixed in a supine position on the operation table. The rats are given a breathing mask, and 1.0%-2.0% isoflurane is given to maintain an anesthetic state. The rat's neck skin is wiped with a 75% alcohol cotton ball, the skin is incised in the middle of the neck, and the muscles and soft tissues are bluntly separated with a curved forceps to expose the right common carotid artery, and a nylon line is prepared. The soft tissues are bluntly separated along the common carotid artery towards the head of the rat to expose the external carotid artery and the internal carotid artery, and attention should be paid to avoid damaging the vagus nerve. The common carotid artery and the internal carotid artery are clamped with an artery clamp, and the external carotid artery is cauterized with an electrocoagulation pen. A small oblique cut is made on the free end of the external carotid artery, a silicone thread embolism is inserted into the external carotid artery, and then the external carotid artery stump is pulled into a straight line with the internal carotid artery, and the thread embolism is smoothly pushed into the internal carotid artery. The internal carotid artery clamp is loosened, and the thread embolism is pushed along the internal carotid artery into the brain. When a slight resistance is felt, the right brain blood flow is reduced to 25% or less of that before modeling, and the modeling is considered successful. The external carotid artery is ligated to fix the thread embolism and prevent bleeding, the muscles and skin are sutured, and the rats are placed in a 37 ℃ incubator to maintain body temperature. After 120 minutes of ischemia, the rats are anesthetized with isoflurane, the thread embolism is slowly pulled out, the external carotid artery stump is ligated, the right brain blood flow is increased to 75% or more of that before modeling, and the reperfusion is considered successful. The rats in the sham operation group are operated on in the same way as the modeling group, but the thread embolism should be pulled out immediately after insertion.
[0031] (2) Dosing regimen Sewsisazine methyl ether 5.6 mg was weighed, first dissolved in 100 μL of dimethyl sulfoxide (DMSO), and then 250 μL of Solutol HS-15 and 650 μL of normal saline were added and mixed uniformly. The drug volume was calculated according to the body weight of each rat, and tail vein injection was performed 1 h after reperfusion. The drug concentration was 1, 5, and 10 mg / kg. The sham operation group and the model group were injected with the same volume of solvent in the tail vein at the time of reperfusion.
[0032] (3) Measurement of cerebral infarction area The TTC staining method was used to determine the brain infarction volume after tMCAO in rats. After 48 h of ischemia, the neurological behavior test was completed, and the rats were euthanized by cervical dislocation, the brain tissue was removed and immediately placed in a-80°C ultra-low temperature refrigerator. After 10 min of freezing, the brain tissue was cut into coronal sections with a knife, and each brain was cut into 5 pieces on average. The cut brain slices were gently placed in 2% TTC staining solution, protected from light, and incubated at 37°C for 10 min. The brain slices were gently removed from the staining solution, arranged neatly, and photographed for preservation. The TTC-stained brain slices showed normal tissue as red and infarcted tissue as white. The Image J software was used to calculate the infarct area and total brain area of the brain slices. The percentage of brain infarction area was the percentage of infarct area to total brain area, and the results are shown in Table 1 and Figure 1 .
[0033] Table 1 Reduction of brain infarction area in rats after tMCAO injury by different concentrations of Geissoschizine methylether
[0034] The experimental results on animal models showed that 1 mg / kg of Geissoschizine methylether (GM) had the most significant effect on reducing the brain infarction area of rats in the middle cerebral artery occlusion (tMCAO) model (Table 1 and Figure 1 ).
[0035] (4) Longa score After 48 h of reperfusion, the motor function of rats was evaluated according to the Zea-Longa method, and the higher the score, the more severe the neurological injury. The specific evaluation method is shown in the table below.
[0036] Longa score details
[0037] Table 2 Improvement of behavioral scores in rats after tMCAO injury by different concentrations of Geissoschizine methylether
[0038] The experimental results showed that the behavioral scores of rats after tMCAO injury were scored after 48 h of reperfusion, and Geissoschizine methylether could improve the behavioral scores of rats after tMCAO injury (Table 2 and Figure 1 ), the Longa score of rats in the Vehicle group was significantly higher than that in the Sham group; the improvement effect was the most significant when 1 mg / kg of Geissoschizine methylether was administered.
[0039] Example 2: Effect of Geissoschizine methylether administered at different time points on the brain infarction area and behavior of rats in the middle cerebral artery occlusion (tMCAO) model.
[0040] (1) Establishment of rat tMCAO model See Example 1 for details. (2) Dosing regimen Geissoschizine methyl ether 5.6 mg was weighed, first dissolved in 100 μL of dimethyl sulfoxide (DMSO), and after being fully dissolved, 250 μL of Solutol HS-15 and 650 μL of normal saline were added and mixed evenly. The dosing volume was calculated according to the body weight of each rat, and tail vein injection was performed at 10 min before reperfusion, 1 h after reperfusion, and 3 h after reperfusion, respectively. The dosing concentration was 1 mg / kg. The sham operation group and the model group were injected with the same volume of solvent through the tail vein at the time of reperfusion.
[0041] (3) Measurement of cerebral infarction area See Example 1 for details.
[0042] Table 3 Effect of administration of geissoschizine methyl ether at different time points on cerebral infarction area of rats after tMCAO injury
[0043] The experimental results on animal models showed that administration of geissoschizine methyl ether (GM) at different time points could significantly reduce the cerebral infarction area of rats in the middle cerebral artery occlusion (tMCAO) model (Table 3 and Figure 2 ).
[0044] (4) Longa score See Example 1 for details. Table 4 Effect of administration of geissoschizine methyl ether at different time points on behavioral score of rats after tMCAO injury
[0045] The experimental results showed that the behavioral score of rats after tMCAO injury was scored at 48 h after reperfusion, and administration of geissoschizine methyl ether at different time points could improve the behavioral score of rats after tMCAO injury, and administration at 1 h after reperfusion was the most significant (Table 4 and Figure 2 ).
[0046] Example 3: Establishment of rat ischemic stroke hemorrhagic transformation model induced by acute hyperglycemia in rats and measurement of hemorrhagic area, hemorrhagic score, and behavioral score.
[0047] (1) Preparation of acute hyperglycemia-induced ischemic stroke hemorrhagic transformation model in rats According to the relevant literature, we construct the rat ischemic stroke hemorrhagic transformation model by inducing acute hyperglycemia in rats and rat middle cerebral artery occlusion (tMCAO) model. Intraperitoneal injection of 50% glucose solution (6 mL / kg) 30 min before the preparation of rat tMCAO model induces acute hyperglycemia in rats. According to the method of Longa et al. for preparing rat tMCAO model, the main operation steps are as follows. The surgical instruments are sterilized before the experiment, and the rats are anesthetized with 3% isoflurane, then the rats are fixed in a supine position on the operation table, and the rats are maintained in an anesthetized state with 2% isoflurane. The rat neck skin is wiped with 75% alcohol cotton, and the skin is cut with a surgical knife at the midline of the neck. The muscles and soft tissues are separated by blunt forceps, the left common carotid artery is exposed, and the nylon thread is prepared. Then the soft tissue is separated along the left common carotid artery, and the vagus nerve is carefully avoided to expose the external carotid artery and internal carotid artery, and the nylon thread is prepared. The thread is prepared and ligated at the distal and proximal ends of the external carotid artery, and the blood vessel is cut with ophthalmic scissors between the two ligation points. The left common carotid artery and internal carotid artery are clamped, then a small opening is cut with ophthalmic scissors at the residual end of the external carotid artery, the thread plug is inserted into the residual end of the external carotid artery, then it is pushed into the internal carotid artery, and further pushed into the middle cerebral artery, until a slight resistance is felt, and the ischemic time is recorded. The residual end of the external carotid artery is ligated, the thread plug is fixed, the muscles and skin are sutured, and the rat is placed on a 37℃ warming blanket to maintain body temperature until the rat wakes up. After 2 hours of ischemia, the rats are anesthetized with 3% isoflurane, the residual end of the external carotid artery is exposed, the thread plug is slowly pulled out, the residual end of the external carotid artery is ligated, and the rat's brain blood perfusion is restored. Then the muscles and skin are sutured, and the rat is placed on a 37℃ warming blanket until it wakes up. The rats in the sham operation group are operated on in the same way as the model group, but the thread plug is pulled out immediately after insertion.
[0048] (2) Dosing regimen Sewziaine methylether 5.6 mg was weighed, first dissolved in 100 μL of dimethyl sulfoxide (DMSO), and then 250 μL of Solutol HS-15 and 650 μL of normal saline were added and mixed uniformly. According to the body weight of each rat, the volume of the drug was calculated, and the tail vein injection was performed 1 h after reperfusion, with a concentration of 1 mg / kg. The sham operation group and the model group were injected with the same volume of solvent in the tail vein at the time of reperfusion.
[0049] (3) Measurement of hemorrhagic area and hemorrhagic score After 24 h of modeling, the rats were anesthetized with 5% isoflurane and then perfused with pre-cooled 1xPBS solution through the heart, and the brain was taken. The brain tissue was coronally sectioned, about 2 mm per section, and the brain sections were photographed by a camera and the hemorrhagic area was calculated by Image J. The total hemorrhagic area was equal to the sum of the hemorrhagic area of each brain section. Hemorrhagic area percentage (%) = total hemorrhagic area / total brain area x 100%. The rat brain hemorrhagic transformation score was referred to the literature related to the Heidelberg ECASS hemorrhage grading, and the specific scoring details are shown in the table below.
[0050] ECASS hemorrhage grading details
[0051] Table 5 Geissoschizine methyl ether reduces the brain hemorrhagic area of rats after tMCAO+HG injury
[0052] Table 6 Geissoschizine methyl ether reduces the brain hemorrhagic score of rats after tMCAO+HG injury
[0053] The experimental results show that 1 mg / kg of geissoschizine methyl ether (GM) can significantly reduce the brain hemorrhagic area and brain hemorrhagic score of rats in the acute hyperglycemia combined with middle cerebral artery occlusion (tMCAO+HG) model, and significantly reduce the occurrence of hemorrhagic transformation of ischemic stroke (Table 5, Table 6 and Figure 3 ).
[0054] (4) Longa score The detailed scoring details are shown in Example 1.
[0055] Table 7 Geissoschizine methyl ether reduces the behavioral score of rats after tMCAO+HG injury
[0056] The experimental results show that 1 mg / kg of geissoschizine methyl ether (GM) can significantly reduce the behavioral score of rats in the acute hyperglycemia combined with middle cerebral artery occlusion (tMCAO+HG) model, and can significantly improve the neurological impairment after hemorrhagic transformation of ischemic stroke (Table 7 and Figure 3 ).
[0057] Through the above examples, the application evaluates the effect of geissoschizine methylether on ischemic stroke and hemorrhagic transformation of ischemic stroke. The experimental results show that 1 mg / kg of geissoschizine methylether (GM) significantly reduces the cerebral infarction area of a middle cerebral artery occlusion (tMCAO) model rat and improves the behavior score; 1 mg / kg of geissoschizine methylether (GM) significantly reduces the brain hemorrhage area and brain hemorrhage score of an acute hyperglycemia combined with middle cerebral artery occlusion (tMCAO+HG) model rat and improves the behavior score. This further indicates that geissoschizine methylether has the potential to prevent or treat brain injury-related diseases, including ischemic stroke, hemorrhagic transformation of ischemic stroke and other cerebrovascular diseases.
Claims
1. Use of styrax methyl ether in the preparation of drugs for the prevention and / or treatment of brain injury.
2. The use according to claim 1, characterized in that, Use of the styrax methyl ether in the preparation of medicaments for the prevention and / or treatment of ischemic stroke and brain injury caused by hemorrhagic transformation of ischemic stroke.
3. The use according to claim 1 or 2, characterized in that, The chemical structural formula of the methamidophos methyl ether is as follows: 。 4. The use according to claim 1 or 2, characterized in that, The use of the styrax methyl ether in the preparation of drugs for the prevention and / or treatment of brain injury by significantly reducing the infarct area and behavioral score in a middle cerebral artery occlusion model.
5. The use according to claim 1 or 2, characterized in that, The use of the styrax methyl ether in the preparation of drugs for the prevention and / or treatment of brain injury by significantly improving the hemorrhage area, hemorrhage-related scores, and behavioral scores of post-stroke hemorrhage transformation.
6. A pharmaceutical composition for the prevention and / or treatment of brain injury, characterized in that, It contains a therapeutically effective amount of styrax methyl ether or a pharmaceutically acceptable salt thereof.
7. Use of the pharmaceutical composition of claim 6 in the preparation of a medicament for the prevention and / or treatment of brain injury.
8. The use according to claim 7, characterized in that, Use of the pharmaceutical composition in the preparation of a medicament for the prevention and / or treatment of ischemic stroke and brain injury resulting from hemorrhagic transformation of ischemic stroke.
9. A pharmaceutical preparation comprising a therapeutically effective amount of styrax methyl ether and a pharmaceutically acceptable carrier, adjuvant, or mediator.
10. Use of the pharmaceutical preparation of claim 9 in the preparation of a medicament for the prevention and / or treatment of brain injury.