制备舒血宁注射液的废弃物中银杏内酯的回收方法

目的探索从制备舒血宁注射液的废弃物中回收银杏内酯的可行方法。方法舒血宁注射液制备过程中的废弃物经过柱层析法分离得到银杏内酯,并计算银杏内酯的回收率。结果经大孔吸附树脂制备舒血宁所产生的废弃物回收银杏内酯的回收率为每kg银杏叶提取液的水沉物可回收0.428 3 g银杏内酯,经阳树脂制备舒血宁所产生的废弃物回收银杏内酯的回收率为每1 kg阳树脂可回收0.373 8 g银杏内酯。结论两种方法制备舒血宁所产生的废弃物中均可回收到银杏内酯。     

舒血宁注射液配伍禁忌文献研究

舒血宁注射液为银杏叶提取物制成的中药制剂,主要成分是银杏黄酮醇苷和银杏内酯,其功能主要是扩张血管、改善微循环,用于治疗缺血性心脑血管疾病,如冠心病、心绞痛、脑栓塞及脑血管痉挛等。近年来,随着舒血宁注射液临床应用的逐渐广泛,关于该药品的配伍禁忌报道也逐渐增多。笔者对舒血宁注射液的配伍禁忌文献进行了整理研究,希望为舒血宁注射液的临床安全使用提供参考。     

银杏注射制剂疑似药品不良反应监测数据分析

目的:比较来自于河南省药品不良反应监测自发报告系统的银杏注射制剂(舒血宁注射液、银杏达莫注射液、银杏提取物注射液、银杏内酯注射液、杏芎氯化钠注射液、银杏二萜内酯葡胺注射液)的不良反应发生情况,为临床合理用药及药品风险评估提供参考依据。方法:对2014—2021年河南省药品不良反应自发报告系统收集的疑似银杏注射制剂不良反应监测数据进行对比分析。结果和结论:银杏注射制剂不良反应报告主要来自于医疗机构;人群性别分布总体较均匀;患者年龄集中分布在60岁以上;不良反应表现以一般不良反应为主,表现为瘙痒、皮疹、恶心、潮红、发热等;新的药品不良反应有呼吸困难、心悸、静脉炎、失眠等。对于新的药品不良反应,建议药品上市许可持有人加强监测,积极开展信号监测及风险评估工作。     

舒血宁注射液治疗急性脑梗死

舒血宁注射液是银杏叶提取物，主要成分是银杏黄酮醇苷、银杏内酯和白果内酯，这些成分具有多种生物学功效，我院于2005年1月-2006年3月应用舒血宁注射液治疗急性脑梗死患者82例，并进行评价，疗效显著，现报告如下：     

银杏达莫注射液致过敏性休克二例

银杏达莫注射液为国产第四代银杏叶提取物,其主要含有白果内酯2.9%,银杏苦内酯3.1%及银杏黄酮苷24%[1].其为复方制剂,含银杏总黄酮9.0～11.0 mg、双嘧达莫3.6～4.4 mg.近年来间断报道此药出现过敏性反应[2-3],甚至出现过敏性休克[4-6].我院发生2例银杏达莫注射液过敏性休克,现报告如下.     

舒血宁葡萄糖注射液对实验性心脑缺血的保护作用

目的:研究舒血宁葡萄糖注射液对动物实验性心脑缺血的保护作用。方法:采用大鼠心肌缺血、局灶性脑梗死、血小板聚集及小鼠脑循环障碍等模型,观察舒血宁葡萄糖注射液的药效作用。结果:舒血宁葡萄糖注射液可改善心肌缺血大鼠的心电图,对大鼠局灶性脑梗死和行为障碍有明显的保护作用,能延长小鼠脑循环障碍存活时间,并能明显抑制大鼠血小板的聚集率。结论:舒血宁葡萄糖注射液对动物实验性心脑缺血和局灶性脑梗死具有保护作用。     

2种联合用药方案治疗缺血性脑梗死的成本-效果分析

目的:评价不同药物治疗方案在缺血性脑梗死治疗中的临床疗效及经济学效果。方法:60例缺血性脑梗死患者随机分为银杏达莫组与舒血宁组,每组30例,在常规疗法的基础上,分别给予银杏达莫注射液、舒血宁注射液静脉滴注,运用成本-效果分析法进行分析和比较。结果:银杏达莫组与舒血宁组的成本分别为10773.53、10935.43元,总有效率分别为83.33%、76.67%(P>0.05),成本-效果比分别为12928.75、14262.98。2组各出现1例消化道出血,经治疗痊愈,未见颅内出血者。结论:银杏达莫组方案较佳。     

银杏内酯吸入剂对哮喘模型豚鼠气管嗜酸性粒细胞浸润的影响

目的:探讨银杏内酯吸入剂对哮喘模型豚鼠气道嗜酸性粒细胞浸润的影响。方法:将豚鼠随机分为7组,每组8只,分别为哮喘模型组,银杏内酯吸入剂低、中、高剂量组(剂量分别为5、10、20mg·kg-1),银杏内酯腹腔注射(ip)组(剂量为20mg·kg-1),地塞米松组(剂量为10mg·kg-1)和正常对照组,计数肺灌注液(BALF)和支气管中的嗜酸性粒细胞(EOS)数。结果:与正常对照组比较,模型组BALF中的EOS显著增多,银杏内酯吸入剂组可显著减少BALF和支气管中的EOS浸润数(P<0.05)。结论:银杏内酯吸入剂能对抗哮喘豚鼠气道嗜酸性粒细胞浸润,可作为治疗支气管哮喘的一种新方法。     

银杏内酯对CCl4诱导的小鼠肝损伤的作用研究

目的 探讨银杏内酯对CCl4诱导的小鼠肝损伤的保护作用及其机制.方法 随机将50只SD小鼠分为5组,分别为空白对照组、模型组、银杏内酯低剂量组、银杏内酯中剂量组和银杏内酯高剂量组.采用CC14腹腔注射和灌胃制作小鼠肝损伤模型.通过观察肝脏的解剖学形态,检测血丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）水平来评估银杏内酯对小鼠肝脏的保护作用.Real time-PCR检测孕烷X受体（PXR）、CYP3A 11、CYP3A13和RXRα的表达.结果 与空白对照组相比,模型组小鼠肝脏表面粗糙、轮廓萎缩;血清ALT和AST水平明显升高.与模型组相比,银杏内酯组小鼠肝脏表面光滑、轮廓清晰;血清ALT和AST水平明显降低,肝脏PXR、RXRα、CYP3A13和CYP3A11表达水平明显升高.结论 银杏内酯对CCl4诱导的小鼠肝损伤有一定的保护和修复作用,其保护效果呈明显剂量依赖性.PXR、RXRα、CYP3A13、CYP3A 11基因表达的上调可能在小鼠肝损伤保护中起重要作用.     

舒血宁注射液临床应用近况

舒血宁注射液系银杏叶提取物配制成的无菌水溶液，其有效成分主要是黄酮苷类和萜类内酯活性物质，包括：槲皮素、山茶素、银杏三酯、银杏内酯、苦内脂等。具有扩张心脑血管、改善微循环、抗血小板激活因子（PAF）、抗氧化清除和抑制氧自由基、抗病毒、抗菌消炎等药理作用。被应用于多种疾病，并取得显著效果。本文对近年国内期刊应用舒血宁注射液治疗临床各种疾病的论文回顾分析，综述如下。     

不同生长季节银杏叶中总黄酮醇苷和总内酯的含量变化

目的比较不同生长季节银杏叶中总黄酮醇苷和总内酯的含量。方法采用HPLC法对样品中总黄酮醇苷和总内酯进行定量分析。结果5月份总黄酮醇苷含量最高,9月份后含量有所降低,12月份含量最低;总内酯含量以6月份为最高,8月份含量开始显著下降,12月份含量最低。结论不同季节银杏叶中总黄酮醇苷和总内酯含量差异较大,此结果为适时采收、合理开发利用银杏叶提供依据。     

Inhibition of human cytochromes P450 by components of Ginkgo biloba

The extraction, isolation and characterization of 29 natural products contained in Ginkgo biloba have been described, which we have now tested for their in-vitro capacity to inhibit the five major human cytochrome P450 (CYP) isoforms in human liver microsomes. Weak or negligible inhibitory activity was found for the terpene trilactones (ginkgolides A, B, C and J, and bilobalide), and the flavonol glycosides. However 50% inhibitory activity (IC50) was found at concentrations less than 10 microg L(-1) for the flavonol aglycones (kaempferol, quercetin, apigenin, myricetin, tamarixetin) with CYP1A2 and CYP3A. Quercetin, the biflavone amentoflavone, sesamin, as well as (Z,Z)-4,4'-(1,4-pentadiene-1,5-diyl)diphenol and 3-nonadec-8-enyl-benzene-1,2-diol, were also inhibitors of CYP2C9. The IC50 of amentoflavone for CYP2C9 was 0.019 microg mL(-1) (0.035 microM). Thus, the principal components of Ginkgo biloba preparations in clinical use (terpene trilactones and flavonol glycosides) do not significantly inhibit these human CYPs in-vitro. However, flavonol aglycones, the biflavonol amentoflavone and several other non-glycosidic constituents are significant in-vitro inhibitors of CYP. The clinical importance of these potential inhibitors will depend on their amounts in ginkgo preparations sold to the public, and the extent to which their bioavailability allows them to reach the CYP enzymes in-situ.     

近红外光谱法测定舒血宁注射液中总黄酮醇苷的含量

目的利用近红外光谱法快速测定舒血宁注射液中总黄酮醇苷的含量。方法采集舒血宁注射液NIR光谱,采用偏最小二乘法（PLS）进行回归,经内部交叉验证建立舒血宁注射液的NIR光谱与其主要成分总黄酮醇苷的HPLC法测定值之间的多元校正模型,预测总黄酮醇苷的含量。结果校正集样品浓度范围为0.760～0.890mg.mL-1。内部交叉验证决定系数（R2）为79.4,内部交叉验证均方差（RMSECV）为0.0154,外部验证均方差（RMSEP）为0.0233。结论本方法快速、简便,适用于药品的现场快检。     

银杏叶、银杏叶提取物及其制剂质量控制研究进展

目的为开展银杏叶类药品的研究提供参考。方法对银杏叶、银杏叶提取物及其制剂的国内外标准收录情况和质量控制方法进行了综述。结果与结论以总黄酮醇苷、萜类内酯和银杏酸为指标的质量控制体系已基本固定,指纹图谱分析、完型黄酮苷的测定和各类成分的同时检测成为新的研究热点。     

银杏总内酯抗血小板聚集与抗血栓作用

目的：探讨银杏总内酯抗血栓形成及抑制血小板聚集的作用.方法：采用大鼠动静脉旁路血栓模型和Chandler氏血栓形成法,利用血小板活化因子（platelet activating factor,PAF）、花生四烯酸（arachidonic acid,AA）和二磷酸腺苷（adenosine diphosphate,ADP）诱导家兔血小板聚集,测定血栓形成抑制率、血小板在不同时间点的聚集率以及最大聚集率.结果：银杏总内酯可不同程度地抑制大鼠动静脉旁路血栓和Chandler氏体外血栓形成,减轻血栓重量,血栓形成抑制率分别达到 41.58%和 59.31%;银杏总内酯可抑制PAF和ADP诱导的家兔血小板在不同时间点的聚集,降低其最大聚集率.结论：银杏总内酯可明显对抗血栓形成,并具有显著的抗PAF和ADP诱导血小板聚集作用.     

银杏叶总黄酮对小鼠脑缺血再灌注损伤的保护作用

目的:建立拟脑梗死模型,观察银杏叶总黄酮预处理对小鼠脑梗死的保护作用并分析其作用机制。方法:脑缺血再灌注方法制备拟脑梗死小鼠模型,将小鼠随机分为对照组、模型组、用药组(高、中、低3个剂量组)。用药组腹腔注射银杏叶总黄酮注射液,模型组和对照组在同一时间给予腹腔注射等量生理盐水。末次给药2h后进行脑缺血再灌注手术。最后测定血清超氧化物歧化酶(SOD)、丙二醛(MDA)的含量;取脑组织做苏木素-伊红染色。结果:脑缺血再灌注可造成小鼠脑梗死,同时使血清中SOD活性降低,MDA含量升高。给予银杏叶总黄酮预处理后,可提高血清中SOD活性,降低MDA含量。结论:银杏叶总黄酮对小鼠脑梗死具有一定的保护作用,其作用机制可能与银杏叶总黄酮抗氧化作用有关。     

Intestinal absorption and presystemic elimination of various chemical constituents present in GBE50 extract, a standardized extract of Ginkgo biloba leaves

The nature and level of systemic exposure to the active herbal constituents will profoundly affect their effects at action sites, which is fundamental in understanding their roles in the overall beneficial effects of a herbal medicine. The objective of this study is to gain a full picture of the systemic exposure to various putatively active ginkgo constituents after p.o. administration of GBE50 extract, a standardized extract of Ginkgo biloba leaves, to rats and understanding of the relevant mechanisms governing the intestinal absorption and presystemic elimination. To define the ginkgo compounds to be studied, literature informatics-guided chemical profiling revealed that GBE50 extract contained 72 ginkgo constituents, including terpene lactones, flavonols, flavones, an isoflavone, biflavones, flavanols, and carboxylic acids, at levels ranging from 0.01 to 55.3 mg/g. Among the ginkgo constituent groups were the terpene lactones and the flavonols that were significantly measurable in plasma after p.o. administration of GBE50 extract to rats. The intestinal absorption of terpene lactones appeared to be dictated by their intermediate membrane permeability, while the influences of MDR-1- and MRP-2- mediated intestinal efflux and the presystemic metabolism and biliary excretion might be relatively limited. Because of their deglycosylation absent in the small intestine and relatively slow presystemic elimination, many intact flavonol glycosides appeared in the rat plasma albeit with a limited extent of absorption. Colonic deglycosylation of the flavonol glycosides occurred and the glucuronides of flavonol aglycones were also measured in the plasma. Although some biflavones also had relatively high abundance in GBE50 extract, these ginkgo constituents were not measured in the rat plasma because of their poor solubility and poor permeability that hindered the intestinal absorption. The levels of the remaining ginkgo constituents in GBE50 extract were too low to be measured in the rat plasma. The current study enabled us to better understand the nature of systemic exposure to ginkgo compounds after p.o. administration of GBE50 extract and to more precisely implement multicomponent PK study of the extract.     

Systemic and cerebral exposure to and pharmacokinetics of flavonols and terpene lactones after dosing standardized Ginkgo biloba leaf extracts to rats via different routes of administration

BACKGROUND AND PURPOSE

Flavonols and terpene lactones are putatively responsible for the properties of Ginkgo biloba leaf extracts that relate to prevention and treatment of cardiovascular disease and cerebral insufficiency. Here, we characterized rat systemic and cerebral exposure to these ginkgo compounds after dosing, as well as the compounds’ pharmacokinetics.

EXPERIMENTAL APPROACH

Rats received single or multiple doses of ShuXueNing injection (prepared from GBE50 for intravenous administration) or GBE50 (a standardized extract of G. biloba leaves for oral administration). Brain delivery of the ginkgo compounds was assessed with microdialysis. Various rat samples were analysed using liquid chromatography/mass spectrometry.

KEY RESULTS

Slow terminal elimination features of the flavonols counterbalanced the influence of poor oral bioavailability on their systemic exposure levels, which also resulted in significant accumulation of the compounds in plasma during the subchronic treatment with ShuXueNing injection and GBE50. Unlike the flavonols, the terpene lactones had poor enterohepatic circulation due to their rapid renal excretion and unknown metabolism. The flavonol glycosides occurred as major forms in plasma after dosing with ShuXueNing injection, while the flavonol aglycone conjugates were predominant in plasma after dosing with GBE50. Cerebral exposure was negligible for the flavonols and low for the terpene lactones.

CONCLUSION AND IMPLICATIONS

Unlike the significant systemic exposure levels, the levels of cerebral exposure to the flavonols and terpene lactones are low. The elimination kinetic differences between the two classes of ginkgo compounds influence their relative systemic exposure levels. The information gained is relevant to linking ginkgo administration to the medicinal effects.     

栀子总苷对幽门结扎大鼠胃溃疡保护作用的实验研究

目的：研究栀子总苷（TGZ）对幽门结扎模型大鼠胃溃疡的影响,初步探讨其抗溃疡作用的机制。方法：采用大鼠幽门结扎的方法建立大鼠胃溃疡模型,收集胃液测定胃液游离酸和总酸、胃蛋白酶活性以及观察胃黏膜损伤指数。结果：TGZ灌胃70或140mg/kg5d能显著抑制幽门结扎大鼠胃溃疡的发生,抑制胃液量,降低胃液中游离酸度与总酸度,有效降低胃液中胃蛋白酶活性。结论：栀子总苷对幽门结扎所致的大鼠胃溃疡具有明显的保护作用,与其抑制胃酸分泌和胃蛋白酶的活性有关。     

银杏总内酯对衰老模型小鼠的作用银杏总内酯对衰老模型小鼠的作用

目的研究银杏总内酯(total lactones of ginkgo,TLG)对衰老模型小鼠的影响,探讨TLG的抗衰老作用机制。方法以D-半乳糖衰老模型小鼠和自然衰老模型小鼠为实验对象,以D-半乳糖衰老模型小鼠心、肝组织中脂褐素(LF)的含量及肝中羟脯氨酸(Hyp)的含量,脑组织中MAO,GSH-Px的活性和NO的含量以及自然衰老模型小鼠脑组织凋亡细胞数作为观察指标。结果TLG可减少D-半乳糖小鼠肝脏及心肌组织中LF的含量,升高肝脏组织中的Hyp的含量,并可提高脑组织中GSH-Px的活性,降低脑组织中NO的含量和MAO的活性;能明显减少自然衰老模型小鼠脑神经细胞凋亡的数目。结论TLG有明显的延缓衰老作用,其作用机理可能与抗氧化、抑制NO生成及细胞凋亡有关。