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Application of a class of nucleoside analogs in the preparation of drugs for preventing and/or treating cerebrovascular diseases
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A drug and ischemic stroke technology, applied in the field of medicine, to achieve the effect of reducing neurological deficit score and infarct focus
Active Publication Date: 2022-07-08
LANZHOU UNIVERSITY
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Patent CN111741967A discloses nucleotide analogs, preparation methods and their applications in nucleic acidsequence determination, etc., which mainly relate to preparation methods of nucleoside analogs, etc.; patent CN109790196A discloses the use of reversibly blocked nucleoside analogs for nucleic acid detection Method; patent CN108671235A discloses a functional nucleic acid with nucleoside analog drugs integrated in its backbone and its derivatives and its preparation method, as well as the use of gene therapy and chemotherapy for combined treatment of diseases; patent CN104211742A discloses cyclophosphoryl Phosphoric acid N-fatty acid that is modified by the N-yl group and connected to the fatty chain is used for the treatment of viral hepatitis and liver cancer; patent CN110643609A discloses drug aptamers, preparation methods and applications of nucleoside analog drug molecules; however, At present, there is no literature on the application of nucleoside analogs to cerebrovascular diseases, nor any literature suggesting that nucleoside analogs have new uses for the treatment of cerebrovascular diseases
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[0049] SPF grade healthy male SD rats, weighing 200-240g, have not used any drugs before the experiment, provided by Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, animal license number is SCXK (gan)-2020-0002, adaptive feeding for one week, Animals were given chow and water ad libitum and were then grouped for experiments.
[0051] 2. Preparation and administration time of MCAO model: After one week of adaptive feeding, all SD rats were randomly divided into 4 groups, and the grouping and administration doses were as follows:
[0070] SPF grade healthy male SD rats, weighing 200-240g, have not used any drugs before the experiment, provided by Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, license number is SCXK (gan)-2020-0002, adaptive rearing for one week, given Animals were fed food and water ad libitum before being grouped for the experiment.
[0072] Drugs and reagents: Zidovudine (Zidovudine, AZT, HPLC≥98%), purchased from Aladdin Biotechnology Co., Ltd.; Acyclovir (Acyclovir, ACV, HPLC≥98%), purchased from McLean Biotechnology Co., Ltd. Company; Butylphthalide Soft Capsules (NBP, NBP), purchased from NBP Pharmaceutical Co., Ltd. of CSPC; 2,3,5-triphenyltetrazolium chloride (TTC), purchased from Solarbio Company .
[0073] 3. The preparation of the animal model and the method for detecting the i...
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Abstract
The invention relates to the technical field of medicine, in particular to the application of nucleoside analogs in the preparation of medicines for preventing or treating cerebrovascular diseases. The general structural formula of the nucleoside analogs of the present invention is shown in formula (I), wherein X and Y are respectively selected from any one of S, O, NH or alkoxy, and R is limited to cytosine, thymine, Either adenine or guanine, R 1 For OH, NH 2 , CH 3 , CH 3 O, halogen, C 1 ‑C 6 Alkyl, metal ions, etc.; R 2 For OH, NH 2 , CH 3 , CH 3 O, halogen, C 1 ‑C 6 Alkyl, metal ions, etc.; 0≤n≤3. The nucleoside analog has significant curative effect on ischemic cerebral apoplexy, can significantly improve nerve function damage, reduce infarct size, and has a good clinical application prospect in clinic.
Description
technical field [0001] The present invention relates to the field of medical technology, and also relates to a class of novel small molecular compounds that can be used for cerebrovascular diseases, and more particularly to the preparation of nucleoside analogs such as lamivudine, zidovudine and acyclovir for cerebrovascular diseases. The use of drugs in vascular diseases. Background technique [0002] Cerebrovascular disease refers to various diseases of the brain blood vessels, including atherosclerosis, thrombosis, stenosis, occlusion, cerebral arteritis, cerebral artery injury, cerebral aneurysm, intracranial vascular malformation, cerebral aneurysm The common feature of venous fistula is to cause brain tissueischemia or hemorrhagic accident. Typical cerebrovascular diseases include cerebral thrombosis, cerebral ischemia, and cerebral infarction. [0003] Cerebral thrombosis is based on cerebral atherosclerosis and plaque. Under the conditions of slow blood flow and l...
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