新型降脂药物的研究进展  

Research progress of new lipid lowering drugs

作　　者：俞婷婷 李静 YU Tingting;LI Jing(Department of Pharmacy,the 903rd Hospital of Joint Logistics Support Force,PLA,Hangzhou 310004,China;Department of Pharmacy of Zhongshan Hospital Affiliated to Fudan University,Shanghai 200032,China)

机构地区：[1]中国人民解放军联勤保障部队第903医院药剂科,杭州310004 [2]复旦大学附属中山医院药剂科,上海200032

出　　处：《上海医药》2021年第24期3-7,共5页Shanghai Medical & Pharmaceutical Journal

摘　　要：目前对于他汀类药物不耐受、无反应或治疗不达标患者以及家族性高脂血症患者的调脂治疗较为棘手,亟须研发更安全、有效、经济、方便使用的新型降脂药物。根据目前研究,未来的新型降脂药物主要是基于反义疗法,使用特定的寡核苷酸序列阻断所选蛋白的翻译或RNA沉默技术。相关药物目前正处于临床研究的不同阶段,包括抑制胆固醇合成的三磷酸腺苷柠檬酸裂解抑制剂Nexletol、复方降胆固醇药物Nexlizet和胆固醇酯转移蛋白抑制剂Anacetrapib;影响极低密度脂蛋白生成的反义寡核苷酸抑制剂Kynamro和微粒体三酰甘油转移蛋白抑制剂JUXTAPID以及影响其代谢的血管生成素样蛋白3单抗Evinacmab、载脂蛋白C-Ⅲ合成抑制剂反义寡核苷酸药物Waylivra和AKCEA-APOCⅢ-LRx及小干扰RNA ARO-APOC3;还有影响脂蛋白(a)生成的AKCEA-Apo(a)-LRX。其中一些已在国外上市应用。这些新型降脂药物将有望提高血脂水平的达标率。本文讨论了新型降脂药物的研究进展。At present,it is difficult to treat patients with statin intolerance,no response or not achieving treatment goal,as well as with familial hyperlipidemia,and it is urgent to develop new lipid-lowering drugs that are more safe,effective,economical and convenient to use.According to the current research,the new lipid-lowering drugs in the future are mainly based on antisense therapy,which use specific oligonucleotide sequences to block the translation of selected proteins or RNA silencing technology.Currently,the related drugs are in different stages of clinical research,including the drugs which inhibit cholesterol synthesis such as Nexletol,a citrate cleavage inhibitor of adenosine triphosphate,Nexlizet,a compound cholesterol lowering drug and Anacetrapib,a cholesterol ester transfer protein inhibitor;the drugs which affect the production of very low density lipoprotein(VLDL) such as Kynamro,an antisense oligonucleotide inhibitor,and Juxtapid,a microsomal triglyceride transfer protein inhibitor;the drugs which affect the metabolism such as Evinacmab,an angiopoietin like protein 3 monoclonal antibody,and Waylvra,and AKCEA-APOCⅢ-LRx,the apolipoprotein C-Ⅲ synthesis inhibitors and small interfering RNA ARO-APOC3;the drugs which affect the production of lipoprotein(a) such as AKCEA-Apo(a)-LRX.Some of them have been put on the market abroad.These new lipid-lowering drugs are expected to improve the rate of reaching target lipid goal.This paper discusses the research progress of new lipid-lowering drugs.

关 键 词：脂质异常 低密度脂蛋白胆固醇 血脂调节药 

分 类 号：R743.3[医药卫生—神经病学与精神病学]