CN113069460B - Application of halcinonide and derivatives thereof in preparation of drugs for treating and/or preventing cerebrovascular diseases - Google Patents
Application of halcinonide and derivatives thereof in preparation of drugs for treating and/or preventing cerebrovascular diseases Download PDFInfo
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Abstract
The invention relates to the technical field of medicines, in particular to application of halcinonide and derivatives thereof in preparing medicines for treating and/or preventing cerebrovascular diseases. The halcinonide and the derivatives thereof have the structural general formula shown in the formula (I), and the treatment effect on ischemic stroke is evaluated by an MCAO cerebral ischemia-reperfusion injury animal model. Experimental results show that the halcinonide and the derivatives prednisone and the testosterone propionate thereof can obviously improve animal neurological deficit scores and reduce the area of infarction foci, can be used for treating ischemic stroke, and have good application prospects in clinic.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to application of halcinonide and derivatives thereof in preparing medicines for treating and/or preventing cerebrovascular diseases.
Background
Stroke (Stroke) is a common clinical disease and a high morbidity, has the characteristics of high morbidity, high mortality and high disability rate, is the first cause of death in China and is the second most fatal disease in the world. Seriously affecting the life quality of patients and often causing hemiplegia after treatment, bringing huge economic and social burden. With the improvement of the aging level of the population in China, the incidence rate of cerebral apoplexy is gradually increased. The cerebral apoplexy is divided into ischemic stroke and hemorrhagic stroke, wherein the ischemic stroke accounts for 60 to 70 percent of the total number of the cerebral stroke, and the ischemic stroke is a general term for cerebral tissue necrosis caused by stenosis or occlusion of blood supply arteries (carotid artery and vertebral artery) of the brain and insufficient blood supply of the brain. Cerebral ischemia is dangerous, even after the dangerous period, various sequelae are left, and serious patients can cause disability. The restoration or opening of the diseased vessel within the effective time window to realize the reperfusion of the ischemic brain tissue is an important measure for treating the ischemic stroke in the acute stage. At present, the most common treatment method in clinic is thrombolytic treatment, and the final purpose is to open blood vessels and realize reperfusion of ischemic brain tissues. However, it has the disadvantage of being limited by the time window for thrombolysis and, in patients who have not received thrombolytic therapy, can only select drug therapy to reduce their neurological impairment. The therapeutic drugs for cerebral arterial thrombosis comprise a fiber-reducing drug, an anticoagulant drug, an anti-platelet aggregation drug and a neuroprotective drug, but because of the self-limitations of single components, single target points and the like, side effects such as bleeding, cerebral edema and the like can be caused, and no drug which has a remarkable curative effect clinically exists so far.
Halcinonide and its derivative are hormones produced by stimulation of adrenal cortex by adrenocorticotropic hormone secreted by anterior lobe of pituitary, and has antiinflammatory, anti-pruritus and vasoconstriction effects, and can be used for clinically resisting various inflammations and inhibiting proliferation of capillary and fibroblast at late stage of inflammation, and relieving sequelae. Patent CN201610366828.8 discloses the use of pharmaceutical composition of halcinonide for the treatment of hyperthyroidism; patent CN102641277A discloses that the composition of halcinonide can be used for treating gynecological diseases and skin diseases; patent CN106511505A discloses that halcinonide composition can be used for treating gastric ulcer. However, there is no literature on the application of halcinonide to cerebrovascular diseases at present, and there is no literature on any application of halcinonide to cerebrovascular diseases, which suggests that halcinonide has a function of treating cerebrovascular diseases.
The inventor unexpectedly discovers that the halcinonide has the effect of treating cerebrovascular diseases, particularly has a remarkable treatment effect on cerebral apoplexy in the experimental process, and researches on the derivatives of the halcinonide and discovers that the derivatives of the halcinonide also have the effect of treating cerebral apoplexy.
Disclosure of Invention
In view of the above technical problems, the present invention provides a new use of halcinonide and its derivatives, and specifically provides an application of halcinonide and its derivatives in preparing drugs for treating and/or preventing cerebrovascular diseases, wherein the halcinonide and its derivatives have a general structural formula shown in formula (i):
wherein, the halcinonide and the derivatives thereof can be in the forms of tautomers, mesomers, racemates, enantiomers, diastereomers or the mixture thereof, or pharmaceutically acceptable salts thereof;
R1and R2Each independently selected from H, -C ═ C;
R3selected from H or halogen;
R4selected from H, -OH or-C ═ OH;
R5and R6Each independently selected from H, -OH, -NH2、C1-6Alkyl radical, C1-6Alkoxy radical, C1-6Alcoxyl acyl radical, C2-6Alkenyl radical, C2-6Alkynyl, C1-6Alkyl acyl, aromatic acyl, C6-10Aryl radical, C5-6Cycloalkyl, or R5And R6Linked to form saturated or unsaturatedA 5-or 6-membered carbocyclic or heterocyclic group or an alkyl-substituted carbocyclic or heterocyclic group, wherein R is5And R6Wherein the alkyl group is substituted with 1 to 3 substituents selected from the group consisting of: hydroxyl, halogen.
Preferably, R is5And R6Each independently selected from H, -OH, -NH2、C1-6Alkyl radical, C1-4Alkoxy radical, C1-4Alcoxyl acyl radical, C2-4Alkenyl radical, C2-4Alkynyl, C1-4Alkyl acyl, phenyl, C5-6Cycloalkyl, or R5And R6Linked to form a saturated or unsaturated 5-or 6-membered carbocyclic or heterocyclic group or an alkyl-substituted carbocyclic or heterocyclic group, wherein R is5And R6Wherein said alkyl group may be substituted with 1 to 3 substituents as follows: hydroxyl, halogen.
Preferably, R is5And R6Are respectively selected from H, -OH and-NH2、-COH、CH3CO-、-CO-CH2OH、-O-C(O)CH2CH3、-CH2-C≡CH、-(CH2)5CH3、-(CH2)4CF3Cyclohexyl-, -CH2-(CH2)3-CH2-、-C(O)-CF3-c (o) -Ph, wherein the alkyl is substituted with 1-3 of the following substituents: hydroxyl, halogen.
Preferably, the halcinonide and the derivatives thereof are selected from the following compounds: pregn-4-ene-3,20-dione,21-chloro-9-fluoro-11-hydroxy-16,17- [ (1-methythylidene) bis (oxy) -, (11 β,16 α) -; pregn-4-ene-3,20-dione, 21-hydroxy-; androst-4-en-3-one,17- (1-oxopropoxy) -, (17 β) -; pregn-4-ene-3,11,20-trione,17, 21-dihydroxy-; pregn-4-ene-3,20-dione,11,17,21-trihydroxy-, (11 β) -; pregna-1,4-diene-3,20-dione,11,17,21-trihydroxy-, (11 β) -; pregna-1,4-diene-3,11,20-trione,17, 21-dihydroxy-; pregna-1,4-diene-3,20-dione,9-fluoro-11,17,21-trihydroxy-16-methyl-, (11 β,16 α) -; pregna-1,4-diene-3,20-dione,9-fluoro-11,16,17,21-tetrahydroxy-, (11 β,16 α) -; pregna-1,4-diene-3,20-dione,9-fluoro-11,21-dihydroxy-16,17- [ (1-methythyidiene) bis (oxy), (11 β,16 α) -; androst-4-en-3-one; andrst-4-en-3-one, 17-methyl-; androst-4-ene-3, 17-dione; androst-4-ene-3, 16-dione; hydrost-4-en-3-one, 17-hydroxy-, (17 α) -; androst-4-ene-3, 11-dione; androst-4-en-3-one,17 β -amino-; androst-4-en-3-one,17-chloro-, (17 α) -; androst-4-ene-3,11, 16-trione; pregn-4-en-20-yn-3-one, (17 α) -.
Preferably, the compounds are halcinonide, prednisone and testosterone propionate.
Preferably, the cerebrovascular disease is cerebral apoplexy, cerebral ischemia, cerebral infarction.
Preferably, the stroke comprises hemorrhagic stroke and/or ischemic stroke.
Preferably, the stroke is ischemic stroke.
The second purpose of the invention is to provide the application of halcinonide and derivatives thereof in preparing the medicines for treating and/or preventing cerebral ischemia-reperfusion injury.
The third purpose of the invention is to provide the application of the composition containing halcinonide and the derivatives thereof in preparing the drugs for treating and/or preventing cerebrovascular diseases.
The fourth purpose of the invention is to provide the application of halcinonide and derivatives thereof in preparing medicines for treating and/or preventing nerve function damage.
Preferably, the halcinonide and the derivatives thereof can be powder, tablets, granules, capsules, solutions, emulsions, suspensions and injections.
The invention has the beneficial effects that: the invention provides a new application of halcinonide and derivatives thereof, and particularly provides an application of halcinonide and derivatives thereof in preparing a medicine for treating and/or preventing cerebrovascular diseases, wherein the cerebrovascular diseases are ischemic stroke, the treatment effect of halcinonide and derivatives thereof on ischemic stroke is evaluated through an MCAO cerebral ischemia reperfusion injury animal model, and experimental results show that all of halcinonide, prednisone and testosterone propionate can obviously improve animal neurological deficit scores and reduce the area of an infarction focus, so that the halcinonide, the prednisone and the derivatives thereof can be used for treating ischemic stroke, and have good application prospects in clinic.
Drawings
FIG. 1 is a histogram of the neurological scores of rats in each administration group provided by the present invention;
wherein the "SHAM" is a SHAM operation group, the "IR" (ischemic reperfusion) is an ischemic reperfusion model control group, the "NBP" (butyl phthalide) is a positive drug group, and the "Halcinonide" is a Halcinonide group. In contrast to the SHAM group "SHAM",###p<0.001; compared with "IR". about.p<0.05
FIG. 2 is a TTC staining pattern of rats of each administration group according to the present invention;
wherein the "SHAM" is a SHAM operation group, the "IR" (ischemic reperfusion) is an ischemic reperfusion model control group, the "NBP" (butyl phthalide) is a positive drug group, and the "Halcinonide" is a Halcinonide group. FIG. 3 shows the results of the cerebral infarction volume evaluation of each group of rats provided by the present invention
Wherein the "SHAM" is a SHAM operation group, the "IR" (ischemic reperfusion) is an ischemic reperfusion model control group, the "NBP" (butyl phthalide) is a positive drug group, and the "Halcinonide" is a Halcinonide group.
Compared with the false operation of 'SHAM',###p<0.001, compared to "IR". about.p<0.01 and<0.001
FIG. 4 is a histogram of the neurological scores of rats in each administration group provided by the present invention;
wherein "SHAM" is a SHAM group, "IR" (Ischemia-reperfusion) is an Ischemia-reperfusion model control group, "NBP" (butyl phthalide) is a positive drug control group, "Prednisone" is a Prednisone group, and "Testosterone Propionate" is a Testosterone Propionate group.
Compared with SHAM group 'SHAM', the # p is less than 0.001; p <0.05 and p <0.01 compared to "IR
FIG. 5 shows the results of the cerebral infarction volume evaluation of each group of rats provided by the present invention
Wherein "SHAM" is a SHAM group, "IR" (Ischemia-reperfusion) is an Ischemia-reperfusion model control group, "NBP" (butyl phthalide) is a positive drug control group, "Prednisone" is a Prednisone group, and "Testosterone Propionate" is a Testosterone Propionate group.
Compared to SHAM operation "SHAM" ### p <0.001, compared to "IR" # # p <0.01 and 0.001
FIG. 6 is a TTC staining pattern of rats in each administration group according to the present invention
Wherein "SHAM" is a SHAM group, "IR" (Ischemia-reperfusion) is an Ischemia-reperfusion model control group, "NBP" (butyl phthalide) is a positive drug control group, "Prednisone" is a Prednisone group, and "Testosterone Propionate" is a Testosterone Propionate group.
Detailed Description
The technical solutions in the examples of the present invention will be described more fully with reference to the accompanying drawings in the examples of the present invention, and it is obvious that the described examples are only a part of the examples of the present invention, but not all examples, and simultaneously protect the therapeutic effects of halcinonide and its derivatives in all cerebrovascular diseases, including different dosage forms, dosages, etc. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without any creative effort, shall fall within the protection scope of the present invention.
It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the subject matter herein. In this application, it must be noted that, unless the context clearly dictates otherwise, as used in this specification and the claims, the singular forms "a," "an," and "the" include plural referents. It should also be noted that the use of "or", "or" means "and/or" unless stated otherwise. Furthermore, the term "comprising" as well as other forms, such as "includes," "including," and "containing," are used without limitation.
The compound according to the invention is selected from the following compounds numbered from co.1 to co.20;
Co.1：Pregn-4-ene-3,20-dione,21-chloro-9-fluoro-11-hydroxy-16,17-[(1-methylethylidene)bis(oxy)]-,(11β,16α)-；
Co.2：Pregn-4-ene-3,20-dione,21-hydroxy-；
Co.3：Androst-4-en-3-one,17-(1-oxopropoxy)-,(17β)-；
Co.4：Pregn-4-ene-3,11,20-trione,17,21-dihydroxy-；
Co.5：Pregn-4-ene-3,20-dione,11,17,21-trihydroxy-,(11β)-；
Co.6：Pregna-1,4-diene-3,20-dione,11,17,21-trihydroxy-,(11β)-；
Co.7：Pregna-1,4-diene-3,11,20-trione,17,21-dihydroxy-；
Co.8：Pregna-1,4-diene-3,20-dione,9-fluoro-11,17,21-trihydroxy-16-methyl-,(11β,16α)-；
Co.9：Pregna-1,4-diene-3,20-dione,9-fluoro-11,16,17,21-tetrahydroxy-,(11β,16α)-；
Co.10：Pregna-1,4-diene-3,20-dione,9-fluoro-11,21-dihydroxy-16,17-[(1-methylethylidene)bis(oxy)]-,(11β,16α)-；
Co.11：Androst-4-en-3-one；
Co.12：Androst-4-en-3-one,17-methylene-；
Co.13：Androst-4-ene-3,17-dione；
Co.14：Androst-4-ene-3,16-dione；
Co.15：Androst-4-en-3-one,17-hydroxy-,(17α)-；
Co.16：Androst-4-ene-3,11-dione；
Co.17：Androst-4-en-3-one,17β-amino-；
Co.18：Androst-4-en-3-one,17-chloro-,(17α)-；
Co.19：Androst-4-ene-3,11,16-trione；
Co.20：Pregn-4-en-20-yn-3-one,(17α)-；
or a pharmaceutically acceptable salt, solvate, e.g. hydrate, lipid, prodrug thereof.
The TTC dyeing of the invention refers to 2, 3, 5-triphenyltetrazolium chloride dyeing.
In the following examples of the present invention, butylphthalide is used to treat mild or moderate acute ischemic stroke. In the embodiment of the invention, butylphthalide is used as a positive drug.
In the following examples of the invention, MCAO is Middle Cerebral Artery ischemia, Middle Cerebral Artery ischemia.
The inventor uses Halcinonide (Co.1), Prednisone (Co.7) and Testosterone Propionate (Co.3) small molecular compounds to score the nerve function of SD (Sprague-Dawley) rats and measure the cerebral infarction volume under different feeding conditions, and proves that Halcinonide and derivatives thereof have the effect of treating ischemic cerebral apoplexy.
Example I study of the Effect of halcinonide on treating ischemic Stroke
1. Laboratory animal
SPF male SD rats of 3 months age are selected, and the body weight of the male SD rats is 200 +/-20 g. Provided by the Lanzhou veterinary research institute of the Chinese academy of agricultural sciences. No drug was used before the experiment. The experimental animals are adaptively raised for one week in an environment with 24-26 ℃ and 12h/12h of alternate diurnal rules, the animals are fed with diet and water freely, and then the experiments are carried out in groups.
2. Drugs and agents
Halcinonide (Halcinonide), available from shanghai mclin biochemical technologies ltd, lot No.: c11650940 with molecular weight formula of C24H32ClFO5Molecular weight of 454.96
Butylphthalide soft capsules (NBP) available from Enbip pharmaceutical Co., Ltd;
2, 3, 5-Triphenyltetrazolium chloride (TTC), available from Sigma.
Sodium Carboxymethylcellulose (CMC-Na) was purchased from Michelin corporation
3. Experimental grouping and intragastric dosing
Male 3-month-old SD rats were randomly divided into 4 groups of 9 animals, and divided and administered at the following doses:
SHAM group (SHAM, gavage given an equal volume of 0.5% CMC-Na);
model control group (IR, gavage given equal volume of 0.5% CMC-Na);
positive drug group (NBP, 20mg/kg/d butylphthalide for intragastric administration);
halcinonide group (Halcinonide, gavage dose 2mg/kg/d)
The administration time is one week after adaptive feeding, all SD rats are administered 24h before molding, and are administered 24h again after molding.
4. Preparation of ischemic stroke model group
The anesthetized rats were fixed, prepped, disinfected with iodophor, and disinfected with surgical instruments, ready for ligation with No. 5 thread, and a longitudinal incision of about 1.5cm was made along the right midline of the neck. After the right carotid artery and vagus nerve were carefully isolated, the common carotid artery and internal carotid artery were ligated with surgical sutures, the common carotid artery was ligated at the position of 10mm from the bifurcation, and then a 0.32mm diameter plug was inserted into the internal carotid artery through the incision at the position of 5mm from the bifurcation of the common carotid artery, and when the depth of the plug was about 18-20mm, the plugging was stopped and the ligation was tied. After cleaning, layered sewing is performed. And removing the wire bolt after the animal is ischemic for 2h, naturally reviving the animal, and then perfusing the animal for 24h to perform related index detection.
The sham operation group is the same as the MCAO model operation group, and does not cause ischemic stroke except that a wire plug is not required to be inserted.
5. Detecting the index
(1) Neurological deficit scoring
24h after dosing treatment, rats with restored activity were scored according to Zea Longa grade 5, score 0: no neurological deficit; 1 minute: the front paw at the opposite side of the focus can not be fully extended; and 2, dividing: spontaneous rotation to the opposite side of the lesion; and 3, dividing: pouring to the opposite side of the focus; and 4, dividing: no spontaneous walking occurred and loss of consciousness occurred, after scoring was completed, brain tissue was isolated and TTC staining was performed.
(2) TTC dyeing
Separating brain tissue, removing olfactory bulb and brain stem, washing with physiological saline, freezing at-20 deg.C for 15min, continuously slicing brain tissue from frontal part of forebrain along coronal plane, quickly placing into 1.5% TTC staining solution, incubating at 37 deg.C in dark place for 45min, turning over every 15min, observing staining condition, wherein bright red is normal brain tissue, and pale white is infarction focus. The sections were then fixed in paraformaldehyde for 12h, and the cerebral infarct size was measured in each group of rats using Image Pro Plus 6.0 software, followed by calculation of the cerebral infarct volume. The formula is as follows:
cerebral infarction volume (sum of ischemic side area average value-sum of contralateral area average value) x infarcted brain tissue thickness
6. Results of the experiment
(1) Neurological deficit score assessment
SD rats are administrated for 1 day, after MCAO model ischemia for 2h, the rats are treated with the drug again, and after 24h of reperfusion, the behavioral scores of the nerve functions of the rats in each group are shown in figure 1. As shown in fig. 1, the neurological scores were significantly increased in the model group compared to the sham group (###p<0.001), indicating successful model construction, reduced neurofunctional behavioral scores (/ p) in the halcinonide group compared to the model group<0.05), indicating that the halcinonide has the function of treating ischemic cerebral apoplexy.
(2) TTC staining and cerebral infarction volume evaluation
TTC staining results and cerebral infarction volume results are shown in figures 2 and 3, the non-ischemic area of the brain tissue of the sham operation group is uniformly red, and ischemic white infarction foci are not seen, while white infarction foci of a large area can be seen on the ischemic side of the model group, which indicates that the model is successfully constructed. The cerebral infarct zone of the positive drug group was significantly reduced compared to the model group (× p < 0.001); the infarct zone was significantly reduced in the halcinonide group compared to the model group (× p <0.01), indicating that halcinonide has an effect on the treatment of ischemic stroke.
7. Conclusion of the experiment
In conclusion, the invention adopts the MCAO cerebral ischemia reperfusion injury animal model to evaluate the treatment effect of halcinonide on ischemic stroke, and proves that the halcinonide has the effect of treating ischemic stroke.
Since halcinonide belongs to a classical halcinonide derivative drug, the inventors speculate that other halcinonide derivatives besides halcinonide also have the effect of treating ischemic stroke, and in order to verify the above speculation, the inventors evaluated the therapeutic effect of prednisone and testosterone propionate on ischemic stroke, and the specific experimental process is as follows.
EXAMPLE two study on the Effect of prednisone in treating ischemic stroke
1. The specific implementation method is the same as the first embodiment.
Prednisone (Prednisone) was purchased from Shanghai Michelin Biochemical technology, Inc., lot number: c11008416, molecular formula C21H26O5And the molecular weight is 358.43. Experimental groups referring to example one, the halcinonide group was replaced with prednisone group, and the administration mode was intragastric administration at a dose of 20 mg/kg/d. The model preparation and detection indexes are the same as those in the first embodiment.
2. Results of the experiment
(1) Neurological deficit score assessment
SD rats are administrated for 1 day, after MCAO model ischemia for 2h, the rats are treated with the drug again, and after 24h reperfusion, the behavioral scores of the nerve functions of the rats in each group are shown in figure 4. As shown in fig. 4, the neurological scores were significantly increased in the model group compared to the sham group(s) ((s))###p<0.001), indicating successful model construction, reduced neuro-functional behavioral scores (/ p) in the prednisone group compared to the model group<0.05), which shows that the prednisone has the function of treating the cerebral arterial thrombosis.
(2) TTC staining and cerebral infarction volume evaluation
TTC staining results and cerebral infarction volume results are shown in figures 5 and 6, and as can be seen from figure 6, the non-ischemic area of the brain tissue of the sham operation group is uniformly red, and ischemic white infarction foci are not seen, while the ischemic white infarction foci of a large area can be seen in the ischemia test of the model group, which indicates that the model is successfully constructed. The cerebral infarct zone of the positive drug group was significantly reduced compared to the model group (. about.. p < 0.01); compared with the model group, the infarct area of the prednisone group is obviously reduced (p <0.001), the prednisone is proved to have the function of treating the ischemic cerebral apoplexy, and the inhibition rate (77.26%) of the prednisone group cerebral infarction is stronger than that (53.07%) of the positive medicine group cerebral infarction, which indicates that the prednisone has better curative effect than the positive medicine.
EXAMPLE III study of the Effect of testosterone propionate on treating ischemic Stroke
1. See example one for a specific implementation.
Testosterone Propionate (Testosterone Propionate) was purchased from Shanghai Allantin Biotechnology, Inc., lot number: a1910098 with the molecular formula of C22H32O3And the molecular weight is 344.49. Experimental groups referring to example one, the halcinonide group was replaced with testosterone propionate group, and the administration mode was intragastric administration at a dose of 20 mg/kg/d. The model preparation and detection indexes are the same as those in the first embodiment.
2. Results of the experiment
(1) Neurological deficit score assessment
SD rats are administrated for 1 day, after MCAO model ischemia for 2h, the rats are treated with the drug again, and after 24h reperfusion, the behavioral scores of the nerve functions of the rats in each group are shown in figure 4. As shown in fig. 4, the neurological scores were significantly increased in the model group compared to the sham group(s) ((s))###p<0.001), indicating successful model construction, and decreased neurofunctional behavioral scores (. about.p) in the testosterone propionate group compared to the model group<0.01), which shows that the testosterone propionate has the function of treating ischemic stroke.
(2) TTC staining and cerebral infarction volume evaluation
TTC staining results and cerebral infarction volume results are shown in fig. 5 and fig. 6, the non-ischemic area of the brain tissue of the sham operation group is uniformly red, and ischemic white infarction foci are not seen, while the ischemia of the model group can be measured to see the white infarction foci of a large area, which indicates that the model is successfully constructed. The cerebral infarct zone of the positive drug group was significantly reduced compared to the model group (. about.. p < 0.01); compared with the model group, the infarct area of the testosterone propionate group is remarkably reduced (p <0.001), the testosterone propionate is proved to have the function of treating ischemic cerebral apoplexy, and the cerebral infarction inhibition rate (78.34%) of the testosterone propionate group is higher than that (53.07%) of the positive drug, so that the testosterone propionate has better curative effect than the positive drug.
In conclusion, the invention adopts the MCAO cerebral ischemia reperfusion injury animal model to evaluate the treatment effect of halcinonide, prednisone and testosterone propionate on ischemic stroke, and the experimental result shows that the halcinonide, prednisone and testosterone propionate have the effect of treating the ischemic stroke, and the halcinonide and the derivatives thereof also have the effect of treating the ischemic stroke, so the invention has wide clinical application prospect.
All technical solutions which can be derived by a person skilled in the art through logical analysis, inference and experiments according to the idea of the invention are within the scope of protection of the claims.
Claims (2)
1. Application of halcinonide in preparing medicine for preventing and/or treating cerebral arterial thrombosis.
2. The use according to claim 1, wherein the halcinonide is a powder, tablet, granule, capsule, solution, emulsion, suspension, injection.
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