CN104922097A - 替普瑞酮在制备预防和/或治疗阿片类毒品复吸药物中的应用 - Google Patents
替普瑞酮在制备预防和/或治疗阿片类毒品复吸药物中的应用 Download PDFInfo
- Publication number
- CN104922097A CN104922097A CN201510274523.XA CN201510274523A CN104922097A CN 104922097 A CN104922097 A CN 104922097A CN 201510274523 A CN201510274523 A CN 201510274523A CN 104922097 A CN104922097 A CN 104922097A
- Authority
- CN
- China
- Prior art keywords
- teprenone
- morphine
- readdiction
- gga
- medicine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000003814 drug Substances 0.000 title claims abstract description 41
- DJAHKBBSJCDSOZ-AJLBTXRUSA-N (5z,9e,13e)-6,10,14,18-tetramethylnonadeca-5,9,13,17-tetraen-2-one;(5e,9e,13e)-6,10,14,18-tetramethylnonadeca-5,9,13,17-tetraen-2-one Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\CC\C(C)=C/CCC(C)=O.CC(C)=CCC\C(C)=C\CC\C(C)=C\CC\C(C)=C\CCC(C)=O DJAHKBBSJCDSOZ-AJLBTXRUSA-N 0.000 title claims abstract description 25
- 229950006156 teprenone Drugs 0.000 title claims abstract description 25
- 229940079593 drug Drugs 0.000 title claims abstract description 19
- 229940127240 opiate Drugs 0.000 title abstract description 4
- 239000004081 narcotic agent Substances 0.000 title abstract 3
- 239000008896 Opium Substances 0.000 claims description 13
- 229960001027 opium Drugs 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 7
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 abstract description 34
- 229960005181 morphine Drugs 0.000 abstract description 17
- 230000001143 conditioned effect Effects 0.000 abstract description 10
- 102000034527 Retinoid X Receptors Human genes 0.000 abstract description 7
- 108010038912 Retinoid X Receptors Proteins 0.000 abstract description 7
- 238000002474 experimental method Methods 0.000 abstract description 7
- 208000008013 morphine dependence Diseases 0.000 abstract description 5
- 206010012335 Dependence Diseases 0.000 abstract description 3
- 238000012360 testing method Methods 0.000 abstract description 2
- 241000699670 Mus sp. Species 0.000 description 14
- 102000004169 proteins and genes Human genes 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 238000003304 gavage Methods 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 230000007613 environmental effect Effects 0.000 description 5
- GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 description 4
- 241000725303 Human immunodeficiency virus Species 0.000 description 4
- 229960002069 diamorphine Drugs 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 3
- 229920001213 Polysorbate 20 Polymers 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 239000007928 intraperitoneal injection Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 3
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 3
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- AVWQQPYHYQKEIZ-UHFFFAOYSA-K trisodium;2-dodecylbenzenesulfonate;3-dodecylbenzenesulfonate;4-dodecylbenzenesulfonate Chemical compound [Na+].[Na+].[Na+].CCCCCCCCCCCCC1=CC=C(S([O-])(=O)=O)C=C1.CCCCCCCCCCCCC1=CC=CC(S([O-])(=O)=O)=C1.CCCCCCCCCCCCC1=CC=CC=C1S([O-])(=O)=O AVWQQPYHYQKEIZ-UHFFFAOYSA-K 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 102000018932 HSP70 Heat-Shock Proteins Human genes 0.000 description 2
- 108010027992 HSP70 Heat-Shock Proteins Proteins 0.000 description 2
- 208000018526 Narcotic-Related disease Diseases 0.000 description 2
- 102000002933 Thioredoxin Human genes 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 206010008118 cerebral infarction Diseases 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 201000005040 opiate dependence Diseases 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000000630 rising effect Effects 0.000 description 2
- 108060008226 thioredoxin Proteins 0.000 description 2
- 229940094937 thioredoxin Drugs 0.000 description 2
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
- 208000009304 Acute Kidney Injury Diseases 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 101100507655 Canis lupus familiaris HSPA1 gene Proteins 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- FMGYKKMPNATWHP-UHFFFAOYSA-N Cyperquat Chemical compound C1=C[N+](C)=CC=C1C1=CC=CC=C1 FMGYKKMPNATWHP-UHFFFAOYSA-N 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 1
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 1
- 241000700721 Hepatitis B virus Species 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- 229940121954 Opioid receptor agonist Drugs 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 208000033626 Renal failure acute Diseases 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 201000011040 acute kidney failure Diseases 0.000 description 1
- 208000012998 acute renal failure Diseases 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000007844 bleaching agent Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 230000001120 cytoprotective effect Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000001784 detoxification Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 210000004307 hair cells vestibular Anatomy 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 210000005240 left ventricle Anatomy 0.000 description 1
- 239000012160 loading buffer Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229960005195 morphine hydrochloride Drugs 0.000 description 1
- XELXKCKNPPSFNN-BJWPBXOKSA-N morphine hydrochloride trihydrate Chemical compound O.O.O.Cl.O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O XELXKCKNPPSFNN-BJWPBXOKSA-N 0.000 description 1
- 230000016273 neuron death Effects 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000003402 opiate agonist Substances 0.000 description 1
- 239000003401 opiate antagonist Substances 0.000 description 1
- 239000004031 partial agonist Substances 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 238000000197 pyrolysis Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- 210000005245 right atrium Anatomy 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明公开了替普瑞酮的新用途，即在制备预防和/或治疗阿片类毒品复吸药物中的应用，涉及医药技术领域；实验结果显示：口服替普瑞酮7天后，对吗啡成瘾消退后复吸点燃小鼠进行条件性位置偏爱测试；发现预先口服GGA，能够显著抑制吗啡复吸引起的小鼠条件性位置偏爱，且在分子水平上GGA显著抑制了吗啡复吸点燃诱导的NAc区NR2B的表达升高，替普瑞酮可用于制备预防和/或治疗阿片类毒品复吸的药物。
Description
技术领域
本发明涉及医药技术领域，涉及一种替普瑞酮的医药用途，具体为替普瑞酮在制备预防和/或治疗阿片类毒品复吸药物中的应用。
背景技术
药物复吸是国际性公害，是长期的世界性问题，它已经成为21世纪人类的主要敌人之一，且引起了各国研究人员的广泛重视。复吸是指药物依赖者在戒药一段时间后，由于某些因素的激发，重现觅药和用药的行为，是药物成瘾的重要特征。药物复吸的影响涉及社会文化、政治、行为等多个领域，可引起一系列的社会和公共卫生问题，如人类免疫缺陷病毒（Human Immunodeficiency Virus，HIV）、乙型肝炎病毒的感染的主要原因之一。成瘾药物滥用者一旦成瘾，脱毒戒毒十分困难，戒毒后的复吸率仍高达95%。阿片类毒品是成瘾药物中的一种，常见的阿片类毒品包括吗啡、海洛因和鸦片等。现代医学可用于阿片类复吸的药物，有阿片受体拮抗剂和阿片受体激动剂和部分激动剂，但多存在着副作用大、疗效不肯定、成本高等局限性，但到目前为止，现有的防复吸药物仍不能满足预防或治疗需要。
替普瑞酮（geranylgeranylacetone, GGA）,即6，10，14，18-四甲基-5，9，13，17-十九烷四烯-2-酮的单顺式和全反式异构体的混合物，现已被广泛应用于消化道溃疡的治疗中。近年研究发现，GGA可以通过诱导热休克蛋白70和硫氧还蛋白减轻化学物质引起的细胞毒害(Bai J, Nakamura H, Hattori I, Tanito M, Yodoi J. Thioredoxin suppresses 1-methyl-4-phenylpyridinium-induced neurotoxicity in rat PC12 cells, Neurosci Lett 2002; 321, 81-4; Takumida M, Anniko M. Heat shock protein 70 delays gentamicin-induced vestibular hair cell death. Acta Otolaryngol.2005;125:23-8)。同时，GGA对光损伤、缺血性肾衰竭、癫痫和脑梗塞等具有保护作用(Tanito M, Kwon Y.W, Kondo N, Bai J, Masutani H, Nakamura H, Fujii J, Ohira A, Yodoi J. Cytoprotective effects of geranylgeranylacetone against retinal photooxidative damage, J Neurosci 2005; 25, 2396-404; Suzuki S, Maruyama S, Sato W, Morita Y, Sato F, Miki Y, Kato S, Katsuno M, Sobue G, Yuzawa Y, Matsuo S. geranylgeranylacetone ameliorates ischemic acute renal failure via induction of Hsp70. Kidney Int 2005;67:2210-20; Fujiki M, Kobayashi H, Inoue R, Tatsuya R, Ishii K. Single oral dose of geranylgeranylacetone for protection against delayed neuronal death induced by transient ischemia. Brain Res 2004;1020:210-213; Yasuda H, Shichinohe H, Kuroda S, Ishikawa T, Iwasaki Y. Neuroprotective effect of a heat shock protein inducer, geranylgeranylacetone in permanent focal cerebral ischemia. Brain Res 2005;1032:176-182)。替普瑞酮是否可以用于阿片类毒品复吸的预防或治疗尚未见报道。大鼠海洛因复吸时可以观察到PFC投射到NAc区有长时程增强样突触增强，在海洛因药物寻求恢复前阻断NR2B表达，可以阻断长时程增强样变化且抑制了复吸（Shen H, Moussawi K, Zhou W, Toda S, Kalivas PW. Heroin relapse requires long-term potentiation-like plasticity mediated by NMDA2b-containing receptors[J]. Proc Natl Acad Sci U S A, 2011, 108(48): 19407-19412）。
发明内容
本发明的目的是提供替普瑞酮（geranylgeranylacetone，GGA）的新用途，即在制备预防和/或治疗阿片类毒品复吸药物中的应用。
本发明所述的应用是以GGA为活性成分在制备预防和/或治疗阿片类毒品复吸药物中的应用。
本发明所述应用中还可以加入一种或多种药物上可接受的辅料，所述辅料包括药学领域常规的填充剂、稀释剂、粘合剂、赋形剂、吸收促进剂、填充剂、表面活性剂和稳定剂等，必要时还可加入香味剂、色素和甜味剂等。
本发明所述应用除制成胶囊外，还可以制成丸剂、粉剂、片剂、粒剂、口服液和注射液等多种形式。
本发明公开了GGA的一种新用途，即在制备预防和/或治疗阿片类毒品复吸药物中的应用。动物实验结果：口服替普瑞酮7天后，对吗啡成瘾消退后复吸点燃小鼠进行条件性位置偏爱测试。发现预先口服GGA，能够显著抑制吗啡复吸引起的小鼠条件性位置偏爱，且在分子水平上GGA显著抑制了吗啡复吸点燃诱导的NAc区NR2B的表达升高。因此，替普瑞酮可用于制备预防和/或治疗阿片类毒品复吸的药物。
由于替普瑞酮在制备预防和/或治疗阿片类毒品复吸药物中的应用是发明人的首次发现，因此，无论是GGA单独使用为活性成分制成的药剂，还是利用GGA预防和/或治疗阿片类毒品复吸的作用与其他活性成分配合使用制成的药剂，均在本申请的保护范围之内。与目前临床上常用的预防药物成瘾及复吸的药物相比，本发明的药物具有以下优点：（1）疗效显著；（2）安全性高，无成瘾性；（3）价格低廉，可以减轻病人的经济负担。
附图说明
图1是替普瑞酮抑制吗啡成瘾戒断后复吸点燃小鼠的条件性位置偏爱结果。
图2是替普瑞酮抑制吗啡复吸引起的NAc区NR2B表达升高的实验分析结果。
具体实施方式
下面通过附图和实施例对本发明作进一步详细说明，但本发明的保护范围不局限于所述内容，所用方法如无特别说明均为常规方法。
1、实验动物：SPF级C57BL/6小鼠：雄性，体重19-22g，由重庆医科大学实验动物中心提供。小鼠饲喂专用饲料，自由饮食和饮水。
2、药品：替普瑞酮（日本卫材公司生产，分子量330.55）；盐酸吗啡注射液（东北制药集团公司沈阳第一制药厂）。
实施例1：替普瑞酮拮抗吗啡诱发的条件性位置偏爱实验
采用小动物自主活动检测装置测定，小鼠分成4组，每组10只小鼠。对照组（C）连续7天灌胃给予生理盐水；吗啡组（Mor）连续7天生理盐水灌胃；GGA和吗啡GGA组（GGA+Mor）连续7天灌胃给予GGA (800 mg/kg)。第8天测条件性位置偏爱实验初始时间15 min。之后分别在第9、11、13、15天，C组，腹腔注射生理盐水，GGA和GGA+Mor组灌胃给予GGA (800 mg/kg)，Mor组和GGA+Mor组腹腔注射吗啡20 mg/kg，在第10、12、14、16天各组分别灌胃及腹腔注射生理盐水。在第17天进行条件性位置偏爱实验15 min，记录伴药箱时间。在第18至25天对小鼠停止给药，之后第26天，进行条件性位置偏爱实验15 min，记录伴药箱时间，检测位置偏爱是否消退。在第27天复吸点燃，C组和GGA组腹腔注射生理盐水，Mor组和GGA+Mor组腹腔注射吗啡（10 mg/kg），2 h后进行条件性位置偏爱实验15 min，记录伴药箱时间。图1结果显示，Mor组小鼠经吗啡成瘾消退后给予低剂量的吗啡，小鼠偏爱于伴药箱（p＜0.05，与C组小鼠对比）；而GGA+Mor组小鼠经GGA预先灌胃后，可以拮抗吗啡成瘾消退后给予低剂量的吗啡点燃诱发的伴药箱偏爱(p＜0.05，与Mor组小鼠对比)。
实施例2：替普瑞酮抑制吗啡复吸诱导的NAc区NR2B的表达升高
组织取材及保存：将小鼠颈椎脱臼处死后，开胸，将右心房的静脉血管端剪开，用1×PBS缓冲液经左心室灌流，流速为20转/分，待各脏器失血变白后停止。然后取NAc区组织，分装放入液氮中速冻，做好标记，保存于-80 ℃冰箱中。
脑组织中蛋白质的提取：取出冻存于-80 ℃冰箱的NAc区组织，分别用镊子取出相同部位、相同大小的组织，放入玻璃研磨器中充分研磨成分散的细胞，加入适量的细胞裂解液，再将混合液吸出放入1.5 ml eppendorf离心管，再每隔10min冰浴进行裂解50 min后，15000 rpm、4 ℃离心15分钟，取上清液放于另外标记好的1.5 ml eppendorf离心管中并保存于-80℃冰箱中，以用于Western bloting检测
蛋白免疫印迹：总蛋白加样量为20 μg，与补足反应体系的1XPBS、起聚沉及前沿指示作用的2X loading buffer混合后，95℃热变性5min，用15%的SDS-PAGE胶电泳分离后，将蛋白条带用电转移到PVDF膜上，用10%脱脂牛奶4℃封闭过夜；取出PVDF膜，用含0.1% Tween-20的TPBS冲洗后，加入2000倍稀释的一抗室温孵育60 min；用含0.1% Tween-20的TPBS冲洗，加入5000倍稀释的二抗室温孵育60 min；用含0.1% Tween-20 的TPBS冲洗，将PVDF膜浸入发光底物溶液中反应1 min，X射线胶片曝光。
数据分析：蛋白条带灰度分析：使用扫描仪将曝光获得的蛋白条带扫描采集并保存至计算机，使用ImageJ、SPSS等软件对蛋白条带灰度值进行显著性差异分析。
图2结果显示：吗啡复吸点燃小鼠NAc区的NR2B表达升高，经过GGA预处理后显著抑制了吗啡成瘾消退后给予低剂量的吗啡点燃诱发的NR2B的表达水平。
Claims (1)
1.替普瑞酮在制备预防和/或治疗阿片类毒品复吸药物中的应用。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510274523.XA CN104922097A (zh) | 2015-05-26 | 2015-05-26 | 替普瑞酮在制备预防和/或治疗阿片类毒品复吸药物中的应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510274523.XA CN104922097A (zh) | 2015-05-26 | 2015-05-26 | 替普瑞酮在制备预防和/或治疗阿片类毒品复吸药物中的应用 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104922097A true CN104922097A (zh) | 2015-09-23 |
Family
ID=54109759
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510274523.XA Pending CN104922097A (zh) | 2015-05-26 | 2015-05-26 | 替普瑞酮在制备预防和/或治疗阿片类毒品复吸药物中的应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104922097A (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110893180A (zh) * | 2018-09-12 | 2020-03-20 | 厦门信力康生物技术有限公司 | 替普瑞酮及其衍生物作为制备治疗毒品成瘾和防止复吸药物的应用 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102266312A (zh) * | 2011-06-23 | 2011-12-07 | 昆明理工大学 | 替普瑞酮在制备预防和/或治疗阿片类毒品成瘾药物中的应用 |
| CN103656645A (zh) * | 2013-10-27 | 2014-03-26 | 北京大学 | 治疗阿片成瘾新的分子靶点及其在药物开发中的应用 |
-
2015
- 2015-05-26 CN CN201510274523.XA patent/CN104922097A/zh active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102266312A (zh) * | 2011-06-23 | 2011-12-07 | 昆明理工大学 | 替普瑞酮在制备预防和/或治疗阿片类毒品成瘾药物中的应用 |
| CN103656645A (zh) * | 2013-10-27 | 2014-03-26 | 北京大学 | 治疗阿片成瘾新的分子靶点及其在药物开发中的应用 |
Non-Patent Citations (4)
| Title |
|---|
| LUO FU-CHENG等: "Geranylgeranylacetone protects against morphine-induced hepatic and renal damage in mice", 《MOLECULAR MEDICINE REPORTS》 * |
| 周连芳: "转录因子CREB在大鼠吗啡精神依赖过程中的作用研究", 《浙江大学硕士学位论文》 * |
| 李楠: "毁损双侧伏隔核对大鼠吗啡诱导复燃的影响", 《第四军医大学硕士学位论文》 * |
| 罗富成: "硫氧还蛋白诱导物抵抗甲醛和吗啡毒性作用分子机制研究", 《昆明理工大学博士学位论文》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110893180A (zh) * | 2018-09-12 | 2020-03-20 | 厦门信力康生物技术有限公司 | 替普瑞酮及其衍生物作为制备治疗毒品成瘾和防止复吸药物的应用 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Parikh et al. | Preventive analgesia: Effect of small dose of ketamine on morphine requirement after renal surgery | |
| Shinohara et al. | I. Stroke in general | |
| CN106963769A (zh) | 含pi3k抑制剂和perk抑制剂的药物组合物及其应用 | |
| CN107213149A (zh) | 青蒿素类衍生物在制备治疗或辅助治疗自身免疫性甲状腺疾病药物中的用途 | |
| Dobrev et al. | Vernakalant. | |
| Gomes et al. | Comparison of the sedative effects of morphine, meperidine or fentanyl, in combination with acepromazine, in dogs | |
| CN104922097A (zh) | 替普瑞酮在制备预防和/或治疗阿片类毒品复吸药物中的应用 | |
| Wang et al. | Amlodipine/valsartan fixed-dose combination treatment in the management of hypertension: A double-blind, randomized trial | |
| WO2020225283A1 (en) | Nk1 inhibitors for the treatment of malaria | |
| KR101793308B1 (ko) | 5-ｈｔ3 수용체 길항제인 사인 추출물을 포함하는 구토 또는 설사의 치료용 조성물 | |
| Osei et al. | Xylopic acid-amodiaquine and xylopic acid-artesunate combinations are effective in managing malaria in Plasmodium berghei-infected mice | |
| CN105596324A (zh) | 柚皮素在制备预防和/或治疗主动脉夹层的药物中的应用 | |
| Samad et al. | Intracerebral coinfection with Burkholderia pseudomallei and Cryptococcus neoformans in a patient with systemic lupus erythematosus | |
| CN104958281A (zh) | 替普瑞酮的新用途 | |
| US20120058961A1 (en) | Pharmaceutical Composition for Treating Cancers | |
| MX2011001631A (es) | Tratamiento de transtornos de ansiedad. | |
| CN102764249B (zh) | 替普瑞酮防治吗啡所致的肾脏损伤的用途 | |
| CN110898052A (zh) | 山萘酚在制备治疗脓毒症药物中的应用 | |
| Thomas et al. | Opiate withdrawal after tramadol and patient‐controlled analgesia. | |
| CN111228264A (zh) | 西达本胺联合cgb以及自体造血干细胞的应用及联合药物 | |
| CN113456643B (zh) | 一种含普那布林的药物组合及其应用 | |
| WO2017114215A1 (zh) | 重组人钙调磷酸酶b亚基的应用 | |
| Robson | Emergency surgery complicated by thyrotoxicosis and thyrotoxic periodic paralysis | |
| CN107582560A (zh) | 木通皂苷d的溶血栓作用及其应用 | |
| CN109674788B (zh) | 羧胺三唑与ido1抑制剂组合在抗肿瘤中的用途 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20150923 |
|
| RJ01 | Rejection of invention patent application after publication |