Lomustine_COA_09380_MedChemExpress
肝靶向十六酸拉咪呋啶酯固体脂质纳米粒抗乙肝病毒的研究
肝靶向十六酸拉咪呋啶酯固体脂质纳米粒抗乙肝病毒的研究王九平;白雪帆;张三奇;李谨革;张颖;张岩;薛克昌;顾宜;王平忠;骆抗先【期刊名称】《世界华人消化杂志》【年(卷),期】2003(11)2【摘要】目的:探讨肝靶向十六酸拉咪呋啶酯固体脂质纳米粒抗HBV的作用.方法:以半乳糖苷为载体,构建十六酸拉咪呋啶酯固体脂质纳米粒(PLN-LAGS),将其靶向导入2.2.15细胞,共同温育10d后,观察对细胞的毒性作用;同时将LAP-GSLN尾静脉注入小鼠体内,RP-HPLC测定拉米呋定(lamivudine,LA)在血清、肝、肾、肺及脾中的分布,用ELISA和荧光定量PCR检测多个时期培养上清中HBsAg,HBeAg 和HBVDNA.结果:LAP-GSLN在肝脏中具有靶向性,LAP-GSLN组肝脏的含药量为LA组的3.3倍;导向后4d出现对HBV-DNA的抑制,在药物浓度10.0mg/L时LAP-GSLN组HBVDNA<1.11×107拷贝/L,而单纯LA组则为5.06×109拷贝/L;6d出现对HBsAg,HBeAg抑制,在药物浓度0.01mg/L时,LAP-GSLN,LA组对HBsAg,HBeAg抑制率分别为52.9%,53.9%;32.2%,31.1%;在药物浓度10.0mg/L 时,LAP-GSLN,LA组对HBsAg,HBeAg抑制率分别为67.2%,69.0%;45.1%,41.0%.未发现对2.2.15细胞的毒性作用.结论:小剂量半乳糖介导十六酸拉米呋定脂质纳米粒能快速有效的抑制HBV抗原表达和DNA复制.【总页数】4页(P191-194)【关键词】肝靶向十六酸拉咪呋啶酯固体脂质纳米粒;乙型肝炎;治疗;疗效【作者】王九平;白雪帆;张三奇;李谨革;张颖;张岩;薛克昌;顾宜;王平忠;骆抗先【作者单位】中国人民解放军第四军医大学唐都医院全军感染病诊疗中心;中国人民解放军第四军医大学西京医院药剂科;中国人民解放军第一军医大学南方医院传染科【正文语种】中文【中图分类】R512.62;R978.7【相关文献】1.丁香苦苷固体脂质纳米粒抗鸭乙肝病毒的实验研究 [J], 张喜武;李永吉;方建;窦金金2.十六酸拉米夫定酯固体脂质纳米粒的肝靶向研究 [J], 薛克昌;张三奇;顾宜;蒋永培3.乳糖化多聚赖氨酸拉咪呋啶在慢性乙型病毒肝炎小鼠体内的肝靶向性研究 [J], 孔令斌;杨景玉;孙志4.十六酸拉米夫定酯固体脂质纳米粒的制备 [J], 薛克昌;顾宜;张三奇;蒋永培;吴道澄因版权原因，仅展示原文概要，查看原文内容请购买。
化学重要的英文网站
化学的研究生必须知道的网站1． ScienceDirect (SD)网址：/(1) Catalysis Communications （催化通讯）(2) Journal of Molecular Catalysis A: Chemical （分子催化A：化学）(3) Tetrahedron (T) （四面体）(4) Tetrahedron: Asymmetry (TA) （四面体：不对称）(5) Tetrahedron Letters (TL) （四面体快报）(6) Applied Catalysis A: General （应用催化A）2． EBSCOhost数据库网址：/(1) Synthetic Communcations （合成通讯）(2) Letters in Organic Chemistry (LOC)(3) Current Organic Synthesis(4) Current Organic Chemistry3. Springer数据库网址：http:// /(1) Molecules （分子）(2) Monatshefte für Chemie / Chemical Monthly （化学月报）(3) Science in China Series B: Chemistry （中国科学B）(4) Catalysis Letts （催化快报）4. ACS Publications (美国化学会)网址：/(1) Journal of the American Chemical Society (JACS) （美国化学会志）(2) Organic Letters (OL) （有机快报）(3) The Journal of Organic Chemistry (JOC) （美国有机化学）(4) Journal of Medicinal Chemistry (JMC) （美国药物化学）(5) Chemical Reiew （化学评论）5. Royal Society of Chemistry (RSC) (英国皇家化学会)网址：/Publishing/Journals/Index.asp(1) Green Chemistry （绿色化学）(2) Chemical Communications (CC) （化学通讯）(3) Chemical Society Reviews （化学会评论）(4) Journal of the Chemical Society （化学会志）Journal of the Chemical Society, Perkin Transactions 1 (1972-2002)Journal of the Chemical Society, Perkin Transactions 2 (1972-2002)Journal of the Chemical Society B: Physical Organic (1966-1971)Journal of the Chemical Society C: Organic (1966-1971)(5) Organic & Biomolecular Chemistry (OBC) （有机生物化学）/publishing/jo ... p?type=CurrentIssue6. Wiley网址：/(1) Advanced Synthesis & Catalysis (ASC) （先进合成催化）(2) Angewandte Chemie International Edition （德国应用化学）(3) Chemistry - A European Journal （欧洲化学）(4) Chinese Journal of Chemistry （中国化学）(5) European Journal of Organic Chemistry （欧洲有机化学）(6) Helvetica Chimica Acta （瑞士化学）(7) Heteroatom Chemistry （杂原子化学）7. Ingent网址：/(1) Journal of Chemical Research (JCR) （化学研究杂志）(2) Canadian Journal of Chemistry （加拿大化学）(3) Current Organic Chemistry(4) Mini-Reviews in Organic Chemistry(5) Phosphorus, Sulfur, and Silicon and the Related Elements （磷、硫、硅和相关元素）(6) Letters in Organic Chemistry8. Taylor & Francis数据库网址：http://www.journalsonline.tandf. ... sp?referrer=default(1) Synthetic Communications(2) Journal of Sulfur Chemistry（硫化学杂志）(3) Phosphorus, Sulfur, and Silicon and the Related Elements9. Thieme数据库网址：/(1) Synlett （合成快报）(2) Synthesis （合成）10. 日本化学会网址：(1) Chem. Lett. (CL) （化学快报）http://www.jstage.jst.go.jp/browse/cl/_vols(2) Bull. Chem. Soc. Jpn. http://www.csj.jp/journals/bcsj/index.html11. 澳大利亚化学会（Australian Journal of Chemistry）http://www.publish.csiro.au/nid/52.htm12．巴西化学会.br/13．Molecules/molecules/14．韩国化学会http://journal.kcsnet.or.kr/15．印度化学会http://www.niscair.res.in/Scienc ... hin.htm&d=test816．国际有机制备和程序（Organic Preparations and Procedures International，OPPI）/17．有机化学/index.htm有机合成：Organic Syntheses(有机合成手册), John Wiley & Sons (免费)/Named Organic Reactions Collection from the University ofOxford (有机合成中的命名反应库) (免费)/thirdyearcomputing/NamedOrganicReac...有机化学资源导航Organic Chemistry Resources Worldwide/有机合成文献综述数据库Synthesis Reviews (免费)/srev/srev.htmCAMEO (预测有机化学反应产物的软件)/products/cameo/index.shtmlCarbohydrate Letters (免费,摘要)/Carbohydrate_Letters/Carbohydrate Research (免费,摘要)/locate/carresCurrent Organic Chemistry (免费,摘要)/coc/index.htmlElectronic Encyclopedia of Reagents for Organic Synthesis (有机合成试剂百科全书e-EROS) /eros/European Journal of Organic Chemistry (免费,摘要)/jpages/1434-193X/Methods in Organic Synthesis (MOS,有机合成方法)/is/database/mosabou.htmOrganic Letters (免费,目录)/journals/orlef7/index.htmlOrganometallics (免费,目录)/journals/orgnd7/index.htmlRussian Journal of Bioorganic Chemistry (Bioorganicheskaya Khimiya) (免费,摘要)http://www.wkap.nl/journalhome.htm/1068-1620Russian Journal of Organic Chemistry (Zhurnal Organicheskoi Khimii) (免费,摘要)http://www.maik.rssi.ru/journals/orgchem.htmScience of Synthesis: Houben-Weyl Methods of Molecular Transformation/Solid-Phase Synthesis database (固相有机合成)/chem_db/sps.htmlSynthetic Communications (免费,摘要)/servlet/product/productid/SCCSyntheticPages (合成化学数据库) (免费)/The Complex Carbohydrate Research Center (复杂碳水化合物研究中心)/合成材料老化与应用 (免费,目录)/default.html金属卡宾络合物催化的烯烃复分解反应 (免费)/html/books/O61BG/b1/2002/2.6%20.htm上海化学试剂研究所/英国化学数据服务中心CDS (Chemical Database Service)/cds/cds.html英国皇家化学会碳水化合物研究组织 (Carbohydrate Group of the Royal Society of Chemistry) /lap/rsccom/dab/perk002.htm有机反应催化学会 (ORCS, Organic Reaction Catalysis Society)/有机合成练习 (免费)/中国科学院成都有机化学研究所：催化与环境工程研究发展中心/MainIndex.htm金属有机及元素有机化学：CASREACT - Chemical Reactions Database(CAS的化学反应数据库)/CASFILES/casreact.html日本丰桥大学 Jinno实验室的研究数据库(液相色谱、多环芳烃/药物/杀虫剂的紫外谱、物性) (免费) http://chrom.tutms.tut.ac.jp/JINNO/ENGLISH/RESEARCH/research...A New Framework for Porous Chemistry (金属有机骨架) (免费)/alchem/articles/1056983432324.htmlActa Crystallographica Section B (免费,摘要)/b/journalhomepage.htmlActa Crystallographica Section E (免费,摘要)/e/journalhomepage.htmlBibliographic Notebooks for Organometallic Chemistryhttp://www.ensc-lille.fr/recherche/cbco/bnoc.htmlBiological Trace Element Research (生物痕量元素研究杂志) (免费,摘要)/JournalDetail.pasp?issn=0163-4984...Journal of Organometallic Chemistry (免费,摘要)/locate/jnlabr/jomOrganic Letters (免费,目录)/journals/orlef7/index.htmlOrganometallics (免费,目录)/journals/orgnd7/index.htmlSyntheticPages (合成化学数据库) (免费)/金属卡宾络合物催化的烯烃复分解反应 (免费)/html/books/O61BG/b1/2002/2.6%20.htm金属有机参考读物：The Organometallic HyperTextBook by Rob Toreki/organomet/index.html金属有机化学国家重点实验室，中国科学院上海有机所/元素有机化学国家重点实验室（南开大学）/在线网络课程：有机金属反应和均相催化机理 (Dermot O'Hare 主讲)/icl/dermot/organomet/药物化学：Fisher Scientific/PubMed: MEDLINE和PREMEDLINE (免费)/PubMed/生物医药:BioMedNet: The World Wide Club for the Biological and Medical Community /AIDSDRUGS (艾滋病药物) (免费)/pubs/factsheets/aidsinfs.htmlautodock (分子对接软件) (免费)/pub/olson-web/doc/autodock/DIRLINE (卫生与生物医药信息源库) (免费)/HISTLINE (医药史库) (免费)/TOXNET (化合物毒性相关数据库系列) (免费)/日本药典，第14版 (免费)http://jpdb.nihs.go.jp/jp14e/index.html小分子生物活性数据库ChemBank (免费)/Ashley Abstracts Database (药物研发、市场文献摘要) (免费)/databases/ashley/search.aspBIOSIS/BIOSIS/ONLINE/DBSS/biosisss.html从检索药物交易信息库PharmaDeals (部分免费)/从ChemWeb检索有机药物用途及别名库Negwer: organic-chemical drugs and their synonyms (部分免费)/negwer/negwersearch.html美国常用药品索引库RxList (免费)/美国国家医学图书馆NLM的免费在线数据库 (免费)/hotartcl/chemtech/99/tour/internet.html制药公司目录(Pharmaceutical Companies on Virtual Library: Pharmacy Page)/company.html37℃医学网/AAPS PharmSci (免费,全文)/Abcam Ltd.有关抗体、试剂的销售，抗体的搜索)/Acta Pharmaceutica (免费,摘要)http://public.srce.hr/acphee/Advanced Drug Delivery Reviews (免费,摘要)http://www.elsevier.nl/locate/drugdelivAmerican Journal of Drug and Alcohol Abuse (免费,摘要)/servlet/product/productid/ADAAmerican Journal of Pharmaceutical Education (AJPE) (免费,全文)/Amgen Inc. (医药)/Anita's web picks (药学与药物化学信息导航)http://wwwcmc.pharm.uu.nl/oyen/webpicks.htmlAnnals of Clinical Microbiology and Antimicrobials (免费,全文)/Annual Review of Pharmacology and Toxicology (免费,摘要)/Anti-Cancer Drug Design (免费,摘要)/antcan/生物有机化学：ScienceDirect: 在线访问Elsevier的1100种期刊全文 (免费目录) (免费)/生命、环境科学综合性资源TheScientificWorld (sciBASE)/生物医药:BioMedNet: The World Wide Club for the Biological and Medical Community /BIOETHICSLINE (BIOETHICS onLINE) (免费)/BIOME (生命科学资源导航)/browse/Directory of P450-containing Systems(P450酶系目录)http://p450.abc.hu/DIRLINE (卫生与生物医药信息源库) (免费)/百名最佳生物技术网站列表 (Top 100 Biotechnology WWW Sites)/top100.asp从ChemWeb检索《化学工程与生物技术文摘》库CEABA (部分免费)/课程材料：MIT生物学超文本教材:8001/esgbio/7001main.html生物材料网 (Biomaterials Network)/生物信息学资源导航，上海生物化学所/bio/index.htm小分子生物活性数据库ChemBank (免费)/英国剑桥医学研究委员会：分子生物学实验室LMB/biology site of the network./生物有机化学：ScienceDirect: 在线访问Elsevier的1100种期刊全文 (免费目录) (免费)/生命、环境科学综合性资源TheScientificWorld (sciBASE)/生物医药:BioMedNet: The World Wide Club for the Biological and Medical Community /BIOETHICSLINE (BIOETHICS onLINE) (免费)/BIOME (生命科学资源导航)/browse/Directory of P450-containing Systems(P450酶系目录)http://p450.abc.hu/DIRLINE (卫生与生物医药信息源库) (免费)/百名最佳生物技术网站列表 (Top 100 Biotechnology WWW Sites) /top100.asp从ChemWeb检索《化学工程与生物技术文摘》库CEABA (部分免费) /课程材料：MIT生物学超文本教材:8001/esgbio/7001main.html生物材料网 (Biomaterials Network)/生物信息学资源导航，上海生物化学所/bio/index.htm小分子生物活性数据库ChemBank (免费)/英国剑桥医学研究委员会：分子生物学实验室LMB/biology site of the network./。
低聚甘露糖醛酸或其药用盐在制备防治白细胞减少症药物中的应用[
专利名称：低聚甘露糖醛酸或其药用盐在制备防治白细胞减少症药物中的应用
专利类型：发明专利
发明人：管华诗,李春霞,李海花,胡婷,李全才,于广利
申请号：CN201210439029.0
申请日：20121106
公开号：CN102920729A
公开日：
20130213
专利内容由知识产权出版社提供
摘要：本发明提供了一种低聚甘露糖醛酸或其药用盐在制备防治白细胞减少症药物中的应用。
在体外细胞实验中，低聚甘露糖醛酸能明显促进CFU-GM的形成，同时能促进骨髓基质细胞的增殖，促进骨髓基质细胞分泌GM-CSF，促进脾淋巴细胞分泌白介素-3。
体内实验进一步表明低聚甘露糖醛酸能明显抑制环磷酰胺所致的小鼠白细胞的减少，提高小鼠的骨髓有核细胞数量，提高CFU-GM的形成。
实验结果证明本发明提供的低聚甘露糖醛酸可以开发成为一种临床上有效的防治白细胞减少症的药物。
申请人：中国海洋大学
地址：266003 山东省青岛市市南区鱼山路5号
国籍：CN
代理机构：青岛联智专利商标事务所有限公司
代理人：崔滨生
更多信息请下载全文后查看。
稳定性英文版
HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationFLUOXETINE HClC17H18F3NO•HClM.W. = 345.79CAS — 59333-67-4STABILITY INDICATINGA S S A Y V A L I D A T I O NMethod is suitable for:ýIn-process controlþProduct ReleaseþStability indicating analysis (Suitability - US/EU Product) CAUTIONFLUOXETINE HYDROCHLORIDE IS A HAZARDOUS CHEMICAL AND SHOULD BE HANDLED ONLY UNDER CONDITIONS SUITABLE FOR HAZARDOUS WORK.IT IS HIGHLY PRESSURE SENSITIVE AND ADEQUATE PRECAUTIONS SHOULD BE TAKEN TO AVOID ANY MECHANICAL FORCE (SUCH AS GRINDING, CRUSHING, ETC.) ON THE POWDER.ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationTABLE OF CONTENTS INTRODUCTION........................................................................................................................ PRECISION............................................................................................................................... System Repeatability ................................................................................................................ Method Repeatability................................................................................................................. Intermediate Precision .............................................................................................................. LINEARITY................................................................................................................................ RANGE...................................................................................................................................... ACCURACY............................................................................................................................... Accuracy of Standard Injections................................................................................................ Accuracy of the Drug Product.................................................................................................... VALIDATION OF FLUOXETINE HCl AT LOW CONCENTRATION........................................... Linearity at Low Concentrations................................................................................................. Accuracy of Fluoxetine HCl at Low Concentration..................................................................... System Repeatability................................................................................................................. Quantitation Limit....................................................................................................................... Detection Limit........................................................................................................................... VALIDATION FOR META-FLUOXETINE HCl (POSSIBLE IMPURITIES).................................. Meta-Fluoxetine HCl linearity at 0.05% - 1.0%........................................................................... Detection Limit for Fluoxetine HCl.............................................................................................. Quantitation Limit for Meta Fluoxetine HCl................................................................................ Accuracy for Meta-Fluoxetine HCl ............................................................................................ Method Repeatability for Meta-Fluoxetine HCl........................................................................... Intermediate Precision for Meta-Fluoxetine HCl......................................................................... SPECIFICITY - STABILITY INDICATING EVALUATION OF THE METHOD............................. FORCED DEGRADATION OF FINISHED PRODUCT AND STANDARD..................................1. Unstressed analysis...............................................................................................................2. Acid Hydrolysis stressed analysis..........................................................................................3. Base hydrolysis stressed analysis.........................................................................................4. Oxidation stressed analysis...................................................................................................5. Sunlight stressed analysis.....................................................................................................6. Heat of solution stressed analysis.........................................................................................7. Heat of powder stressed analysis.......................................................................................... System Suitability stressed analysis.......................................................................................... Placebo...................................................................................................................................... STABILITY OF STANDARD AND SAMPLE SOLUTIONS......................................................... Standard Solution...................................................................................................................... Sample Solutions....................................................................................................................... ROBUSTNESS.......................................................................................................................... Extraction................................................................................................................................... Factorial Design......................................................................................................................... CONCLUSION...........................................................................................................................ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationBACKGROUNDTherapeutically, Fluoxetine hydrochloride is a classified as a selective serotonin-reuptake inhibitor. Effectively used for the treatment of various depressions. Fluoxetine hydrochloride has been shown to have comparable efficacy to tricyclic antidepressants but with fewer anticholinergic side effects. The patent expiry becomes effective in 2001 (US). INTRODUCTIONFluoxetine capsules were prepared in two dosage strengths: 10mg and 20mg dosage strengths with the same capsule weight. The formulas are essentially similar and geometrically equivalent with the same ingredients and proportions. Minor changes in non-active proportions account for the change in active ingredient amounts from the 10 and 20 mg strength.The following validation, for the method SI-IAG-206-02 , includes assay and determination of Meta-Fluoxetine by HPLC, is based on the analytical method validation SI-IAG-209-06. Currently the method is the in-house method performed for Stability Studies. The Validation was performed on the 20mg dosage samples, IAG-21-001 and IAG-21-002.In the forced degradation studies, the two placebo samples were also used. PRECISIONSYSTEM REPEATABILITYFive replicate injections of the standard solution at the concentration of 0.4242mg/mL as described in method SI-IAG-206-02 were made and the relative standard deviation (RSD) of the peak areas was calculated.SAMPLE PEAK AREA#15390#25406#35405#45405#55406Average5402.7SD 6.1% RSD0.1ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::PRECISION - Method RepeatabilityThe full HPLC method as described in SI-IAG-206-02 was carried-out on the finished product IAG-21-001 for the 20mg dosage form. The method repeated six times and the relative standard deviation (RSD) was calculated.SAMPLENumber%ASSAYof labeled amountI 96.9II 97.8III 98.2IV 97.4V 97.7VI 98.5(%) Average97.7SD 0.6(%) RSD0.6PRECISION - Intermediate PrecisionThe full method as described in SI-IAG-206-02 was carried-out on the finished product IAG-21-001 for the 20mg dosage form. The method was repeated six times by a second analyst on a different day using a different HPLC instrument. The average assay and the relative standard deviation (RSD) were calculated.SAMPLENumber% ASSAYof labeled amountI 98.3II 96.3III 94.6IV 96.3V 97.8VI 93.3Average (%)96.1SD 2.0RSD (%)2.1The difference between the average results of method repeatability and the intermediate precision is 1.7%.HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationLINEARITYStandard solutions were prepared at 50% to 200% of the nominal concentration required by the assay procedure. Linear regression analysis demonstrated acceptability of the method for quantitative analysis over the concentration range required. Y-Intercept was found to be insignificant.RANGEDifferent concentrations of the sample (IAG-21-001) for the 20mg dosage form were prepared, covering between 50% - 200% of the nominal weight of the sample.Conc. (%)Conc. (mg/mL)Peak Area% Assayof labeled amount500.20116235096.7700.27935334099.21000.39734463296.61500.64480757797.52000.79448939497.9(%) Average97.6SD 1.0(%) RSD 1.0ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::RANGE (cont.)The results demonstrate linearity as well over the specified range.Correlation coefficient (RSQ)0.99981 Slope11808.3Y -Interceptresponse at 100%* 100 (%) 0.3%ACCURACYACCURACY OF STANDARD INJECTIONSFive (5) replicate injections of the working standard solution at concentration of 0.4242mg/mL, as described in method SI-IAG-206-02 were made.INJECTIONNO.PEAK AREA%ACCURACYI 539299.7II 540599.9III 540499.9IV 5406100.0V 5407100.0Average 5402.899.9%SD 6.10.1RSD, (%)0.10.1The percent deviation from the true value wasdetermined from the linear regression lineHPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::ACCURACY OF THE DRUG PRODUCTAdmixtures of non-actives (placebo, batch IAG-21-001 ) with Fluoxetine HCl were prepared at the same proportion as in a capsule (70%-180% of the nominal concentration).Three preparations were made for each concentration and the recovery was calculated.Conc.(%)Placebo Wt.(mg)Fluoxetine HCl Wt.(mg)Peak Area%Accuracy Average (%)70%7079.477.843465102.27079.687.873427100.77079.618.013465100.0101.0100%10079.6211.25476397.910080.8011.42491799.610079.6011.42485498.398.6130%13079.7214.90640599.413080.3114.75632899.213081.3314.766402100.399.618079.9920.10863699.318079.3820.45879499.418080.0820.32874899.599.4Placebo, Batch Lot IAG-21-001HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::VALIDATION OF FLUOXETINE HClAT LOW CONCENTRATIONLINEARITY AT LOW CONCENTRATIONSStandard solution of Fluoxetine were prepared at approximately 0.02%-1.0% of the working concentration required by the method SI-IAG-206-02. Linear regression analysis demonstrated acceptability of the method for quantitative analysis over this range.ACCURACY OF FLUOXETINE HCl AT LOW CONCENTRATIONThe peak areas of the standard solution at the working concentration were measured and the percent deviation from the true value, as determined from the linear regression was calculated.SAMPLECONC.µg/100mLAREA FOUND%ACCURACYI 470.56258499.7II 470.56359098.1III 470.561585101.3IV 470.561940100.7V 470.56252599.8VI 470.56271599.5(%) AverageSlope = 132.7395299.9SD Y-Intercept = -65.872371.1(%) RSD1.1HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationSystem RepeatabilitySix replicate injections of standard solution at 0.02% and 0.05% of working concentration as described in method SI-IAG-206-02 were made and the relative standard deviation was calculated.SAMPLE FLUOXETINE HCl AREA0.02%0.05%I10173623II11503731III10103475IV10623390V10393315VI10953235Average10623462RSD, (%) 5.0 5.4Quantitation Limit - QLThe quantitation limit ( QL) was established by determining the minimum level at which the analyte was quantified. The quantitation limit for Fluoxetine HCl is 0.02% of the working standard concentration with resulting RSD (for six injections) of 5.0%. Detection Limit - DLThe detection limit (DL) was established by determining the minimum level at which the analyte was reliably detected. The detection limit of Fluoxetine HCl is about 0.01% of the working standard concentration.ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::VALIDATION FOR META-FLUOXETINE HCl(EVALUATING POSSIBLE IMPURITIES)Meta-Fluoxetine HCl linearity at 0.05% - 1.0%Relative Response Factor (F)Relative response factor for Meta-Fluoxetine HCl was determined as slope of Fluoxetine HCl divided by the slope of Meta-Fluoxetine HCl from the linearity graphs (analysed at the same time).F =132.7395274.859534= 1.8Detection Limit (DL) for Fluoxetine HClThe detection limit (DL) was established by determining the minimum level at which the analyte was reliably detected.Detection limit for Meta Fluoxetine HCl is about 0.02%.Quantitation Limit (QL) for Meta-Fluoxetine HClThe QL is determined by the analysis of samples with known concentration of Meta-Fluoxetine HCl and by establishing the minimum level at which the Meta-Fluoxetine HCl can be quantified with acceptable accuracy and precision.Six individual preparations of standard and placebo spiked with Meta-Fluoxetine HCl solution to give solution with 0.05% of Meta Fluoxetine HCl, were injected into the HPLC and the recovery was calculated.HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::META-FLUOXETINE HCl[RECOVERY IN SPIKED SAMPLES].Approx.Conc.(%)Known Conc.(µg/100ml)Area in SpikedSampleFound Conc.(µg/100mL)Recovery (%)0.0521.783326125.735118.10.0521.783326825.821118.50.0521.783292021.55799.00.0521.783324125.490117.00.0521.783287220.96996.30.0521.783328526.030119.5(%) AVERAGE111.4SD The recovery result of 6 samples is between 80%-120%.10.7(%) RSDQL for Meta Fluoxetine HCl is 0.05%.9.6Accuracy for Meta Fluoxetine HClDetermination of Accuracy for Meta-Fluoxetine HCl impurity was assessed using triplicate samples (of the drug product) spiked with known quantities of Meta Fluoxetine HCl impurity at three concentrations levels (namely 80%, 100% and 120% of the specified limit - 0.05%).The results are within specifications:For 0.4% and 0.5% recovery of 85% -115%For 0.6% recovery of 90%-110%HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::META-FLUOXETINE HCl[RECOVERY IN SPIKED SAMPLES]Approx.Conc.(%)Known Conc.(µg/100mL)Area in spikedSample Found Conc.(µg/100mL)Recovery (%)[0.4%]0.4174.2614283182.66104.820.4174.2614606187.11107.370.4174.2614351183.59105.36[0.5%]0.5217.8317344224.85103.220.5217.8316713216.1599.230.5217.8317341224.81103.20[0.6%]0.6261.3918367238.9591.420.6261.3920606269.81103.220.6261.3920237264.73101.28RECOVERY DATA DETERMINED IN SPIKED SAMPLESHPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::REPEATABILITYMethod Repeatability - Meta Fluoxetine HClThe full method (as described in SI-IAG-206-02) was carried out on the finished drug product representing lot number IAG-21-001-(1). The HPLC method repeated serially, six times and the relative standard deviation (RSD) was calculated.IAG-21-001 20mg CAPSULES - FLUOXETINESample% Meta Fluoxetine % Meta-Fluoxetine 1 in Spiked Solution10.0260.09520.0270.08630.0320.07740.0300.07450.0240.09060.0280.063AVERAGE (%)0.0280.081SD 0.0030.012RSD, (%)10.314.51NOTE :All results are less than QL (0.05%) therefore spiked samples with 0.05% Meta Fluoxetine HCl were injected.HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::Intermediate Precision - Meta-Fluoxetine HClThe full method as described in SI-IAG-206-02 was applied on the finished product IAG-21-001-(1) .It was repeated six times, with a different analyst on a different day using a different HPLC instrument.The difference between the average results obtained by the method repeatability and the intermediate precision was less than 30.0%, (11.4% for Meta-Fluoxetine HCl as is and 28.5% for spiked solution).IAG-21-001 20mg - CAPSULES FLUOXETINESample N o:Percentage Meta-fluoxetine% Meta-fluoxetine 1 in spiked solution10.0260.06920.0270.05730.0120.06140.0210.05850.0360.05560.0270.079(%) AVERAGE0.0250.063SD 0.0080.009(%) RSD31.514.51NOTE:All results obtained were well below the QL (0.05%) thus spiked samples slightly greater than 0.05% Meta-Fluoxetine HCl were injected. The RSD at the QL of the spiked solution was 14.5%HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationSPECIFICITY - STABILITY INDICATING EVALUATIONDemonstration of the Stability Indicating parameters of the HPLC assay method [SI-IAG-206-02] for Fluoxetine 10 & 20mg capsules, a suitable photo-diode array detector was incorporated utilizing a commercial chromatography software managing system2, and applied to analyze a range of stressed samples of the finished drug product.GLOSSARY of PEAK PURITY RESULT NOTATION (as reported2):Purity Angle-is a measure of spectral non-homogeneity across a peak, i.e. the weighed average of all spectral contrast angles calculated by comparing all spectra in the integrated peak against the peak apex spectrum.Purity Threshold-is the sum of noise angle3 and solvent angle4. It is the limit of detection of shape differences between two spectra.Match Angle-is a comparison of the spectrum at the peak apex against a library spectrum.Match Threshold-is the sum of the match noise angle3 and match solvent angle4.3Noise Angle-is a measure of spectral non-homogeneity caused by system noise.4Solvent Angle-is a measure of spectral non-homogeneity caused by solvent composition.OVERVIEWT he assay of the main peak in each stressed solution is calculated according to the assay method SI-IAG-206-02, against the Standard Solution, injected on the same day.I f the Purity Angle is smaller than the Purity Threshold and the Match Angle is smaller than the Match Threshold, no significant differences between spectra can be detected. As a result no spectroscopic evidence for co-elution is evident and the peak is considered to be pure.T he stressed condition study indicated that the Fluoxetine peak is free from any appreciable degradation interference under the stressed conditions tested. Observed degradation products peaks were well separated from the main peak.1® PDA-996 Waters™ ; 2[Millennium 2010]ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationFORCED DEGRADATION OF FINISHED PRODUCT & STANDARD 1.UNSTRESSED SAMPLE1.1.Sample IAG-21-001 (2) (20mg/capsule) was prepared as stated in SI-IAG-206-02 and injected into the HPLC system. The calculated assay is 98.5%.SAMPLE - UNSTRESSEDFluoxetine:Purity Angle:0.075Match Angle:0.407Purity Threshold:0.142Match Threshold:0.4251.2.Standard solution was prepared as stated in method SI-IAG-206-02 and injected into the HPLC system. The calculated assay is 100.0%.Fluoxetine:Purity Angle:0.078Match Angle:0.379Purity Threshold:0.146Match Threshold:0.4272.ACID HYDROLYSIS2.1.Sample solution of IAG-21-001 (2) (20mg/capsule) was prepared as in method SI-IAG-206-02 : An amount equivalent to 20mg Fluoxetine was weighed into a 50mL volumetric flask. 20mL Diluent was added and the solution sonicated for 10 minutes. 1mL of conc. HCl was added to this solution The solution was allowed to stand for 18 hours, then adjusted to about pH = 5.5 with NaOH 10N, made up to volume with Diluent and injected into the HPLC system after filtration.Fluoxetine peak intensity did NOT decrease. Assay result obtained - 98.8%.SAMPLE- ACID HYDROLYSISFluoxetine peak:Purity Angle:0.055Match Angle:0.143Purity Threshold:0.096Match Threshold:0.3712.2.Standard solution was prepared as in method SI-IAG-206-02 : about 22mg Fluoxetine HCl were weighed into a 50mL volumetric flask. 20mL Diluent were added. 2mL of conc. HCl were added to this solution. The solution was allowed to stand for 18 hours, then adjusted to about pH = 5.5 with NaOH 10N, made up to volume with Diluent and injected into the HPLC system.Fluoxetine peak intensity did NOT decrease. Assay result obtained - 97.2%.ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationSTANDARD - ACID HYDROLYSISFluoxetine peak:Purity Angle:0.060Match Angle:0.060Purity Threshold:0.099Match Threshold:0.3713.BASE HYDROLYSIS3.1.Sample solution of IAG-21-001 (2) (20mg/capsule) was prepared as per method SI-IAG-206-02 : An amount equivalent to 20mg Fluoxetine was weight into a 50mL volumetric flask. 20mL Diluent was added and the solution sonicated for 10 minutes. 1mL of 5N NaOH was added to this solution. The solution was allowed to stand for 18 hours, then adjusted to about pH = 5.5 with 5N HCl, made up to volume with Diluent and injected into the HPLC system.Fluoxetine peak intensity did NOT decrease. Assay result obtained - 99.3%.SAMPLE - BASE HYDROLYSISFluoxetine peak:Purity Angle:0.063Match Angle:0.065Purity Threshold:0.099Match Threshold:0.3623.2.Standard stock solution was prepared as per method SI-IAG-206-02 : About 22mg Fluoxetine HCl was weighed into a 50mL volumetric flask. 20mL Diluent was added. 2mL of 5N NaOH was added to this solution. The solution was allowed to stand for 18 hours, then adjusted to about pH=5.5 with 5N HCl, made up to volume with Diluent and injected into the HPLC system.Fluoxetine peak intensity did NOT decrease - 99.5%.STANDARD - BASE HYDROLYSISFluoxetine peak:Purity Angle:0.081Match Angle:0.096Purity Threshold:0.103Match Threshold:0.3634.OXIDATION4.1.Sample solution of IAG-21-001 (2) (20mg/capsule) was prepared as per method SI-IAG-206-02. An equivalent to 20mg Fluoxetine was weighed into a 50mL volumetric flask. 20mL Diluent added and the solution sonicated for 10 minutes.1.0mL of 30% H2O2 was added to the solution and allowed to stand for 5 hours, then made up to volume with Diluent, filtered and injected into HPLC system.Fluoxetine peak intensity decreased to 95.2%.ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationSAMPLE - OXIDATIONFluoxetine peak:Purity Angle:0.090Match Angle:0.400Purity Threshold:0.154Match Threshold:0.4294.2.Standard solution was prepared as in method SI-IAG-206-02 : about 22mg Fluoxetine HCl were weighed into a 50mL volumetric flask and 25mL Diluent were added. 2mL of 30% H2O2 were added to this solution which was standing for 5 hours, made up to volume with Diluent and injected into the HPLC system.Fluoxetine peak intensity decreased to 95.8%.STANDARD - OXIDATIONFluoxetine peak:Purity Angle:0.083Match Angle:0.416Purity Threshold:0.153Match Threshold:0.4295.SUNLIGHT5.1.Sample solution of IAG-21-001 (2) (20mg/capsule) was prepared as in method SI-IAG-206-02 . The solution was exposed to 500w/hr. cell sunlight for 1hour. The BST was set to 35°C and the ACT was 45°C. The vials were placed in a horizontal position (4mm vials, National + Septum were used). A Dark control solution was tested. A 2%w/v quinine solution was used as the reference absorbance solution.Fluoxetine peak decreased to 91.2% and the dark control solution showed assay of 97.0%. The difference in the absorbance in the quinine solution is 0.4227AU.Additional peak was observed at RRT of 1.5 (2.7%).The total percent of Fluoxetine peak with the degradation peak is about 93.9%.SAMPLE - SUNLIGHTFluoxetine peak:Purity Angle:0.093Match Angle:0.583Purity Threshold:0.148Match Threshold:0.825 ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationSUNLIGHT (Cont.)5.2.Working standard solution was prepared as in method SI-IAG-206-02 . The solution was exposed to 500w/hr. cell sunlight for 1.5 hour. The BST was set to 35°C and the ACT was 42°C. The vials were placed in a horizontal position (4mm vials, National + Septum were used). A Dark control solution was tested. A 2%w/v quinine solution was used as the reference absorbance solution.Fluoxetine peak was decreased to 95.2% and the dark control solution showed assay of 99.5%.The difference in the absorbance in the quinine solution is 0.4227AU.Additional peak were observed at RRT of 1.5 (2.3).The total percent of Fluoxetine peak with the degradation peak is about 97.5%. STANDARD - SUNLIGHTFluoxetine peak:Purity Angle:0.067Match Angle:0.389Purity Threshold:0.134Match Threshold:0.8196.HEAT OF SOLUTION6.1.Sample solution of IAG-21-001-(2) (20 mg/capsule) was prepared as in method SI-IAG-206-02 . Equivalent to 20mg Fluoxetine was weighed into a 50mL volumetric flask. 20mL Diluent was added and the solution was sonicated for 10 minutes and made up to volume with Diluent. 4mL solution was transferred into a suitable crucible, heated at 105°C in an oven for 2 hours. The sample was cooled to ambient temperature, filtered and injected into the HPLC system.Fluoxetine peak was decreased to 93.3%.SAMPLE - HEAT OF SOLUTION [105o C]Fluoxetine peak:Purity Angle:0.062Match Angle:0.460Purity Threshold:0.131Match Threshold:0.8186.2.Standard Working Solution (WS) was prepared under method SI-IAG-206-02 . 4mL of the working solution was transferred into a suitable crucible, placed in an oven at 105°C for 2 hours, cooled to ambient temperature and injected into the HPLC system.Fluoxetine peak intensity did not decrease - 100.5%.ED. N0: 04Effective Date:APPROVED::。
PHA-793887_DataSheet_MedChemExpress
Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:PHA–793887 is a novel pan–cdk inhibitor, including cdk1, cdk2, cdk4, cdk5, cdk7, and cdk9 with IC50 in the 5 to 140 nM range.IC50 Value: 8 nM (CDK2), 5 nM(CDK5), 10 nM (CDK7)Target: CDKsin vitro: PHA–793887 is cytotoxic for leukemic cell lines, including K562, KU812, KCL22, and TOM1, with IC50 of 0.3–7 μM, but it is not cytotoxic for normal unstimulated peripheral blood mononuclear cells or CD34+ hematopoietic stem cells. In colony assays,PHA–793887 shows very high activity against leukemia cell lines with IC50 less than 0.1 μM. PHA–793887 induces cell–cycle arrest,inhibits Rb and nucleophosmin phosphorylation, and modulates cyclin E and cdc6 expression at 0.2–1 μM and induces apoptosis at 5μM. PHA–793887 has low activity against CDK1, CDK4, CDK9 and GSK3β with IC50 of 60 nM, 62 nM, 138 nM and 79 nM, respectively.PHA–793887 inhibits cell proliferation of many tumor cell lines, including A2780, HCT–116, COLO–205, C–433, DU–145, A375, PC3,MCF–7, and BX–PC3, with IC50 of 88 nM–3.4 μM. PHA–793887 (1 μM) shows a decrease in the S phase, a subsequent increase of the G1 phase and a slight accumulation of G2/M phase in A2780 cells. PHA–793887 (3 μM) significantly increases G2/M phase and reduces DNA synthsis.in vivo: PHA–793887 (20 mg/kg) is effective in xenograft models of K562 and HL60 cells, primary leukemic disseminated model, and a high–burden disseminated ALL–2 model derived from a relapsed Philadelphia–positive acute lymphoid leukemia patient. PHA–793887(10–30 mg/kg) shows good efficacy in the human ovarian A2780, colon HCT–116, and pancreatic BX–PC3 carcinoma xenograft models.PROTOCOL (Extracted from published papers and Only for reference)Animal administration [1]A2780 human ovarian adenocarcinoma–bearing CD–1 nude mice (Charles River Breeding Laboratories) were treated with 15 or 30mg/kg of PHA–793887 once a day by i.v. route for 2 days. Animals were sacrificed at 1.5, 6, and 24 hours after the last treatment, and tumor slices from mice treated with compound or vehicle (n = 9 animals per group) were collected and immediately soaked inRNAlater solution (Qiagen) for gene expression analysis. For pharmacokinetic analysis, plasma samples were collected from six animals at each time interval and analyzed by liquid chromatography–tandem mass spectrometry. Data were evaluated by nonlinear mixed effect modeling. Plasma levels of the compound were fitted using a two–compartment model with bolus input and first–order output mean, and random parameters were considered in the following equation: Pi = P.exp (η). The random effects were considered normal distributed with zero mean and variance ω2.References:[1]. Locatelli G et al Transcriptional analysis of an E2F gene signature as a biomarker of activity of the cyclin–dependent kinase inhibitor PHA–793887 inProduct Name:PHA–793887Cat. No.:HY-11001CAS No.:718630-59-2Molecular Formula:C 19H 31N 5O 2Molecular Weight:361.48Target:CDK Pathway:Cell Cycle/DNA Damage Solubility:10 mM in DMSOtumor and skin biopsies from a phase I clinical study. Mol Cancer Ther. 2010 May;9(5):1265–73.[2]. Massard C, Soria JC, Anthoney DA, Proctor A, Scaburri A, Pacciarini MA, Laffranchi B, Pellizzoni C, Kroemer G, Armand JP, Balheda R, Twelves CJ.A first in man, phase I dose–escalation study of PHA–793887, an inhibitor of multiple cyclin–dependent kinases (CDK2, 1 and 4) reveals unexpected hepatotoxicity in patients with solid tumors.Cell Cycle. 2011 Mar 15;10(6):963–70. Epub 2011 Mar 15.[3]. Alzani R, Pedrini O, Albanese C, Ceruti R, Casolaro A, Patton V, Colotta F, Rambaldi A, Introna M, Pesenti E, Ciomei M, Golay J.Therapeutic efficacy of the pan–cdk inhibitor PHA–793887 in vitro and in vivo in engraftment and high–burden leukemia models.Exp Hematol. 2010 Apr;38(4):259–269.e2. Epub 2010 Feb 16.[4]. Brasca MG, Albanese C, Alzani R, Amici R, Avanzi N, Ballinari D, Bischoff J, Borghi D, Casale E, Croci V, Fiorentini F, Isacchi A, Mercurio C, Nesi M, Orsini P, Pastori W, Pesenti E, Pevarello P, Roussel P, Varasi M, Volpi D, Vulpetti A, Ciomei M.Optimization of 6,6–dimethyl pyrrolo[3,4–c]pyrazoles: Identification of PHA–793887, a potent CDK inhibitor suitable for intravenous dosing.Bioorg Med Chem. 2010 Mar 1;18(5):1844–53. Epub 2010 Jan 25.[5]. Zoubir M, Flament C, Gdoura A, Bahleda R, Litvinova E, Soumelis V, Conforti R, Viaud S, Soria JC, Kroemer G, Zitvogel L, Chaput N.An inhibitor of cyclin–dependent kinases suppresses TLR signaling and increases the susceptibility of cancer patients to herpesviridae.Cell Cycle. 2011 Jan 1;10(1):118–26. Epub 2011 Jan 1.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。
GDC-0980_SDS_MedChemExpress
Inhibitors, Agonists, Screening LibrariesSafety Data Sheet Revision Date:May-24-2017Print Date:May-24-20171. PRODUCT AND COMPANY IDENTIFICATION1.1 Product identifierProduct name :GDC-0980Catalog No. :HY-13246CAS No. :1032754-93-01.2 Relevant identified uses of the substance or mixture and uses advised againstIdentified uses :Laboratory chemicals, manufacture of substances.1.3 Details of the supplier of the safety data sheetCompany:MedChemExpress USATel:609-228-6898Fax:609-228-5909E-mail:sales@1.4 Emergency telephone numberEmergency Phone #:609-228-68982. HAZARDS IDENTIFICATION2.1 Classification of the substance or mixtureGHS Classification in accordance with 29 CFR 1910 (OSHA HCS)Acute toxicity, Oral (Category 4)Skin irritation (Category 2)Eye irritation (Category 2A)Specific target organ toxicity - single exposure (Category 3).2.2 GHS Label elements, including precautionary statementsPictogramSignal word WarningHazard statement(s)H302 Harmful if swallowed.H315 Causes skin irritation.H319 Causes serious eye irritation.H335 May cause respiratory irritation.Precautionary statement(s)P261 Avoid breathing dust/ fume/ gas/ mist/ vapours/ spray.P264 Wash skin thoroughly after handling.P270 Do not eat, drink or smoke when using this product.P271 Use only outdoors or in a well-ventilated area.P280 Wear protective gloves/ eye protection/ face protection.P301 + P312 IF SWALLOWED: Call a POISON CENTER or doctor/ physician if you feel unwell.P302 + P352 IF ON SKIN: Wash with plenty of soap and water.¡¢P304 + P340 IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing.P305 + P351 + P338 IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do.Continue rinsing.2.3 Other hazardsNone.3. COMPOSITION/INFORMATION ON INGREDIENTS3.1 SubstancesSynonyms:GNE 390; GDC 0980; RG 7422Formula:C23H30N8O3SMolecular Weight:498.60CAS No. :1032754-93-04. FIRST AID MEASURES4.1 Description of first aid measuresEye contactRemove any contact lenses, locate eye-wash station, and flush eyes immediately with large amounts of water. Separate eyelids with fingers to ensure adequate flushing. Promptly call a physician.Skin contactRinse skin thoroughly with large amounts of water. Remove contaminated clothing and shoes and call a physician.InhalationImmediately relocate self or casualty to fresh air. If breathing is difficult, give cardiopulmonary resuscitation (CPR). Avoid mouth-to-mouth resuscitation.IngestionWash out mouth with water; Do NOT induce vomiting; call a physician.4.2 Most important symptoms and effects, both acute and delayedThe most important known symptoms and effects are described in the labelling (see section 2.2).4.3 Indication of any immediate medical attention and special treatment neededTreat symptomatically.5. FIRE FIGHTING MEASURES5.1 Extinguishing mediaSuitable extinguishing mediaUse water spray, dry chemical, foam, and carbon dioxide fire extinguisher.5.2 Special hazards arising from the substance or mixtureDuring combustion, may emit irritant fumes.5.3 Advice for firefightersWear self-contained breathing apparatus and protective clothing.6. ACCIDENTAL RELEASE MEASURES6.1 Personal precautions, protective equipment and emergency proceduresUse full personal protective equipment. Avoid breathing vapors, mist, dust or gas. Ensure adequate ventilation. Evacuate personnel to safe areas.Refer to protective measures listed in sections 8.6.2 Environmental precautionsTry to prevent further leakage or spillage. Keep the product away from drains or water courses.6.3 Methods and materials for containment and cleaning upAbsorb solutions with finely-powdered liquid-binding material (diatomite, universal binders); Decontaminate surfaces and equipment by scrubbing with alcohol; Dispose of contaminated material according to Section 13.7. HANDLING AND STORAGE7.1 Precautions for safe handlingAvoid inhalation, contact with eyes and skin. Avoid dust and aerosol formation. Use only in areas with appropriate exhaust ventilation.7.2 Conditions for safe storage, including any incompatibilitiesKeep container tightly sealed in cool, well-ventilated area. 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PHYSICAL AND CHEMICAL PROPERTIES9.1 Information on basic physical and chemical propertiesAppearance White to yellow (Solid)Odor No data availableOdor threshold No data availablepH No data availableMelting/freezing point No data availableBoiling point/range No data availableFlash point No data availableEvaporation rate No data availableFlammability (solid, gas)No data availableUpper/lower flammability or explosive limits No data availableVapor pressure No data availableVapor density No data availableRelative density No data availableWater Solubility No data availablePartition coefficient No data availableAuto-ignition temperature No data availableDecomposition temperature No data availableViscosity No data availableExplosive properties No data availableOxidizing properties No data available9.2 Other safety informationNo data available.10. 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For more details, see section 2CarcinogenicityIARC: No component of this product present at a level equal to or greater than 0.1% is identified as probable, possible or confirmed human carcinogen by IARC.ACGIH: No component of this product present at a level equal to or greater than 0.1% is identified as a potential or confirmed carcinogen by ACGIH.NTP: No component of this product present at a level equal to or greater than 0.1% is identified as a anticipated or confirmed carcinogen by NTP.OSHA: No component of this product present at a level equal to or greater than 0.1% is identified as a potential or confirmed carcinogen by OSHA.Reproductive toxicityClassified based on available data. For more details, see section 2Specific target organ toxicity - single exposureClassified based on available data. For more details, see section 2Specific target organ toxicity - repeated exposureClassified based on available data. 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依达拉奉右莰醇通过铁死亡-脂质过氧化通路对脑出血大鼠神经保护的作用机制
实验研究依达拉奉右莰醇通过铁死亡-脂质过氧化通路对脑出血大鼠神经保护的作用机制毛权西，李作孝△摘要：目的探讨依达拉奉右莰醇对脑出血大鼠的神经保护作用及血肿周围脑组织脂质过氧化的影响。
方法将128只SD大鼠随机分为假手术组、脑出血组、依达拉奉组和依达拉奉右莰醇组，每组32只。
除假手术组外，其余组大鼠构建急性脑出血模型，依达拉奉组、依达拉奉右莰醇组于造模后分别腹腔注射依达拉奉6mg/kg、依达拉奉右莰醇7.5mg/kg，每12h注射1次，假手术组和脑出血组腹腔注射等量生理盐水。
术后1d、3d、7d和14d按Garcia评分标准进行神经功能评分，HE染色观察血肿周围脑组织病理变化，化学荧光法检测血肿周围脑组织活性氧（ROS）含量，微量酶标法检测血肿周围脑组织还原型谷胱甘肽（GSH）含量，蛋白免疫印迹法检测血肿周围脑组织谷胱甘肽过氧化物酶4（GPX4）、长链脂酰辅酶A合成酶4（ACSL4）和磷脂胆碱酰基转移酶3（LPCAT3）表达。
结果与假手术组比较，脑出血组大鼠神经功能评分降低，血肿周围脑组织出现大量炎性细胞浸润及神经细胞变性，ROS含量、ACSL4和LPCAT3蛋白表达水平升高，GSH含量、GPX4蛋白表达水平降低（P＜0.05）；与脑出血组比较，依达拉奉组和依达拉奉右莰醇组大鼠神经功能评分升高，血肿周围脑组织病理损伤明显减轻，ROS含量、ACSL4和LPCAT3蛋白表达水平降低，GSH含量、GPX4蛋白表达水平增加（P＜0.05）；依达拉奉右莰醇组干预效果优于依达拉奉组（P＜0.05）；除假手术组外，其余各组均在术后3d时变化最明显，术后7d、14d逐渐恢复（P＜0.05）。
结论依达拉奉右莰醇可能通过调节脑出血大鼠神经细胞铁死亡相关蛋白的表达，减少脑组织脂质过氧化，抑制神经细胞铁死亡，从而发挥脑保护作用。
关键词：依达拉奉右莰醇；依达拉奉；脑出血；铁死亡；脂质过氧化中图分类号：R743.34文献标志码：A DOI：10.11958/20221777Neuroprotective mechanism of edaravone dexborneol in rats with cerebral hemorrhage throughferroptosis-lipid peroxidation pathwayMAO Quanxi,LI Zuoxiao△Department of Neurology,the Affiliated Hospital of Southwest Medical University,Luzhou646000,China△Corresponding Author E-mail:Abstract:Objective To investigate the neuroprotective effect of edaravone dexborneol on cerebral hemorrhage in rats and the effect of lipid peroxidation on perihematomal brain tissue.Methods A total of128SD rats were randomly divided into the sham-operated group,the cerebral hemorrhage group,the edaravone group and the edaravone dexborneol group, with32rats in each group.The acute cerebral hemorrhage model was constructed in all groups except for the sham-operated group.The edaravone group and edaravone dexamphene group were injected intraperitoneally with6mg/kg of edaravone and edaravone dexamphene7.5mg/kg,one injection every12hours.The sham-operated group and the cerebral hemorrhage group were injected intraperitoneally with equal amounts of saline.The neurological function was scored according to Garcia score at1d,3d,7d,and14d after surgery.Brain tissue around hematoma was stained with HE staining.Chemo fluorescence assay was used to observe pathological changes and reactive oxygen species(ROS)content of brain tissue around hematoma.Micro enzyme labeling assay was used to detect glutathione(GSH)content of brain tissue around hematoma.The expression levels of glutathione peroxidase4(GPX4),long-chain lipid acyl-coenzyme A synthase4(ACSL4) and phospholipid choline acyltransferase3(LPCAT3)in brain tissue around hematoma were detected by protein immunoblotting.Results Compared with the sham-operated group,neurological function scores were decreased in the cerebral hemorrhage group.Massive inflammatory cell infiltration and neuronal degeneration in brain tissue around hematoma were found,and ROS content,ACSL4and LPCAT3protein expression level increased.GSH content and GPX4 protein expression level decreased in the cerebral hemorrhage group(P＜0.05).Compared with the cerebral hemorrhage group,neurological function scores were increased,histopathological damage around the hematoma was significantly基金项目：泸州市人民政府-西南医科大学科技战略合作基金项目（2018LZXNYD-ZK17）作者单位：西南医科大学附属医院神经内科（邮编646000）作者简介：毛权西（1990），男，硕士在读，主要从事神经免疫方向研究。