[发明专利]注射用益气复脉(冻干)或鲁斯可皂苷元预防药物性器官出血的用途

说明书

本发明公开注射用益气复脉(冻干)或鲁斯可皂苷元预防药物性器官出血新用途。本发明使用达沙替尼诱导小鼠胃肠出血模型验证了注射用益气复脉(冻干)或鲁斯可皂苷元对达沙替尼诱导小鼠胃肠出血的改善作用。此外本发明还使用达沙替尼损伤HUVEC细胞模型验证了注射用益气复脉(冻干)或鲁斯可皂苷元对细胞通透性的改善作用。

技术领域

本发明涉及中药复方及天然药物领域，具体涉及注射用益气复脉(冻干)或鲁斯可皂苷元预防药物性器官出血副作用。

背景技术

鲁斯可皂苷元(Ruscogenin，RUS)，是中药麦冬中的主要皂苷元和有效成分之一，又名假叶树苷元。具有显著的抗炎、抗血栓、抗肿瘤、降低毛细血管通透性等作用((1)KouJ,Sun Y,Lin Y,et al.Anti-inflammatory Activities of Aqueous Extract fromRadix Ophiopogon japonicus and Its Two Constituents[J].Biol Pharm Bull.2005,28(7):1234-1238.(2)Cheng ZH,Wu T,Yu BY.Steroidal glycosides from tubers ofOphiopogon japonicus[J].J Asian Nat Prod Res.2006,8(6):555-559.(3)Kou J,TianY,Tang Y.Antithrombotic Activities of Aqueous Extract from RadixOphiopogonjaponicus and Its Two Constituents[J].Biol Pharm Bull.2006,29(6):1267-1270.(4)Huang YL,Kou JP,Ma L,et al.Possible Mechanism of the Anti-inflammatory Activity of Ruscogenin:Role of Intercellular Adhesion Molecule-1and Nuclear Factor-κB[J].JPharmacol Sci.2008,108(2):198-205.(5)Liang H,XingY,Chen J,et al.Antimicrobial activities of endophytic fungi isolated fromOphiopogon japonicus(Liliaceae)[J].BMC Complement Altern Med.2012,12:238.(6)马爱珍.鲁斯可皂苷元对人肺癌A549和H460细胞的作用机理研究[D].南京:南京中医药大学，2014.(7)Wang Kui-Wu,zhang hong,shen lianqing,et al.Novel steroidalsaponins from Liriope graminifolia(Linn.)Baker with anti-tumoractivities.CARBOHYDRATE RESEARCH.2011,346(2):253-258)。达沙替尼通常与出血性并发症有关，它通过ROCK途径磷酸化MLC，诱导F-actin结构发生聚合现象，使得细胞骨架重构；达沙替尼诱导内皮细胞之间VE-cadherin结构发生改变，增加内皮细胞的通透性，导致血管渗漏，因此发生胃肠道出血等副作用。达沙替尼通过RhoA-ROCK途径诱导细胞骨架重构，增加肺微血管通透性，引发胸腔积液等副作用((8)Dasatinib reversibly disruptsendothelial vascular integrity by increasing non-muscle Myosin IIcontractility in a ROCK-dependent manner[J].Clin Cancer Res,2017,23(21):6697-6707.(9)Dasgupta SK,Le A,Vijayan KV,et al.Dasatinib inhibits actin fiberreorganization and promotes endothelial cell permeability through RhoA-ROCKpathway[J].Cancer Med,2017,6(4):809-818.(10)Gover PA,Granot G,Pasmanik CM,etal.Bosutinib,dasatinib,imatinib,nilotinib,and ponatinib differentially affectthe vascular molecular pathways and functionality of human endothelial cells[J].Leuk Lymphoma,2019,60(1):189-199.(11)Phan C,Jutant EM,Tu L,etal.Dasatinib increases endothelial permeability leading to pleural effusion[J].Eur Respir J,2018,51(1))。血为气之配，气虚会引起血液循环紊乱，可引起微血管高渗透性，导致出血，气虚不足，统摄血液的生理功能减弱，血即离经而外溢，溢于胃肠，即为便血。治疗上以益气补气之法恢复统摄的功能，达到止血的目的。注射用益气复脉(冻干)是根据经典名方“生脉散”制成的冻干粉针剂，由红参﹑麦冬﹑五味子三味药组成，本方具有补益气血﹑益气复脉的功效，是治疗气阴两虚证的代表方，临床用于治疗心血管疾病和气阴两虚型心绞痛，疗效显著((12)Han JY,Li Q,Ma ZZ,et al.Effects and mechanisms ofcompound Chinese medicine and major ingredients on microcirculatorydysfunction and organ injury induced by ischemia/reperfusion[J].PharmacolTher,2017,177:146-173.(13)齐东.补气血偏方[J].中华养生保健,2009(4):13-13.(14)孙宗发.益气活血法对脏器保护作用的研究现状[J].中医药临床杂志,2011,23(10):939-940)。