生脉注射液中人参皂苷Rc在心绞痛患者体内的PK-PD相关性

目的 评价生脉注射液中人参皂苷Rc在心绞痛患者体内的药代动力学-药效动力学（PK-PD）相关性。方法 10名稳定性心绞痛受试者连续静脉滴注生脉注射液14 d,分别于给药后不同时间点采集血浆样品,采用液相色谱-串联质谱（LC-MS）法测定血浆中人参皂苷Rc的血药浓度,绘制药-时曲线,进行非房室模型拟合并计算PK参数;以受试者的收缩压（SBP）、舒张压（DBP）及心率（HR）作为药效指标,进行PK-PD结合模型的拟合,计算PK-PD参数。结果 人参皂苷Rc在心绞痛受试者体内的PK符合二室模型,其降压及加快HR的效应滞后于血药浓度,不与血药浓度直接相关;效应室浓度与药效之间具有良好的相关性,血压和HR的效应模型分别符合Inhibitory Effect Sigmoid I_max和Sigmoid E_max模型。结论 成功建立了生脉注射液中人参皂苷Rc在心绞痛患者体内的PK-PD结合模型,可有效地用于预测其血药浓度和效应,评价药效物质基础。     

生脉注射液的可见异物控制与研究

摘 要 目的：了解生脉注射液中可见异物的基本情况,对其可见异物的控制及检查方法进行研究。方法: 对收集到的生脉注射液样品,分别采用灯检法及光散射法进行可见异物检查,汇总结果,并予以分析;同时考察生脉注射液的可见异物成因中外源性因素及内源性因素的影响。结果:市面上流通的生脉注射液样品可见异物检查的阳性检出率较低。光照、温度、pH等因素对生脉注射液的可见异物影响不大。结论:各生产企业在生脉注射液的可见异物控制方面措施有效,质量控制较好。     

基于脑卒中治疗作用的清开灵注射液生物活性质控方法的建立

目的 从清开灵注射液的临床应用出发，依据其改善氧化应激在治疗脑卒中过程中发挥的作用，建立基于生物活性的清开灵注射液的质量控制新方法。方法 考察清开灵注射液对超氧阴离子、羟自由基、DPPH自由基的清除以及其总抗氧化能力这4种生物活性指标的作用强度，选择线性关系和灵敏度最佳的生物指标进行方法学考察，并以该法测定3个批次的清开灵注射液样品的生物活性，比较其质量优劣。结果 与另外3种方法相比，清开灵注射液的总抗氧化能力与其浓度之间的线性关系良好、灵敏度高，且符合方法学对于日内精密度、日间精密度和稳定性的要求。3个批次的清开灵注射液生物活性之间无显著差异，以水溶性维生素E当量代表的三者的质量相当接近。结论 总抗氧化能力适用于评价清开灵注射液在与此活性相关的应用（如脑卒中）中质量的优劣，此法可作为现行质量控制方式的有益补充，从而应用到清开灵注射液的质量控制工作中。     

生脉注射液治疗缺血性中风有效性和安全性的Meta分析

摘 要 目的：采用Meta分析方法评价生脉注射液治疗缺血性中风的有效性和安全性。方法：计算机检索PubMed、Medline、Embase、the Cochrane Library、中国知网（CNKI）、万方数据库、维普数据库（VIP）等电子数据库中应用生脉注射液治疗缺血性中风患者的随机对照试验(RCTs)。使用Cochrane协作网工具评价纳入文献的方法学质量,采用RevMan 5.3.3软件进行Meta分析。结果：共纳入8个RCT,累计745例缺血性中风患者,纳入的8篇文献均为中低质量研究。Meta分析结果显示,在缺血性中风的常规治疗基础上,联用生脉注射液可明显提高总有效率(RR=1.24,95%CI：1.15~1.33,P<0.000 01,n_RCT=7)、降低神经功能缺损程度评分(MD=-4.51,95%CI：-6.02~-3.00,P<0.000 01,n_RCT=5)及提高日常生活活动能力评分（n_RCT=2）。结论：常规治疗基础上联用生脉注射液治疗缺血性中风具有一定的疗效,且不增加不良反应。但由于本Meta分析纳入研究质量不高,有必要开展更多设计严谨、大样本、多中心RCT加以验证。     

润燥清肺膏止咳、抗炎、抑菌的药效学研究

目的 探讨润燥清肺膏的止咳、抗炎、抑菌的药效学作用。方法 将50 只小鼠及豚鼠各随机分为5 组,分别为模型组、阳性对照药急支糖浆组和润燥清肺膏高、中、低剂量组,采用氨水喷雾致咳小鼠模型及枸橼酸喷雾致咳豚鼠模型评价止咳作用;将60 只大鼠随机分为6 组,分别为正常组、模型组、阳性对照药急支糖浆组和润燥清肺膏高、中、低剂量组,采用脂多糖致急性支气管炎模型大鼠评价抗炎作用;将50 只小鼠随机分为5 组,分别为模型组、阳性对照药急支糖浆组和润燥清肺膏高、中、低剂量组,采用醋酸致小鼠腹腔毛细血管通透性增高及巴豆油致小鼠耳肿胀等模型评价其抗炎作用;采用体外抑菌实验,评价其抑菌作用。结果 润燥清肺膏高、中、低各剂量组豚鼠咳嗽潜伏期明显延长(P< 0.05、0.01)、咳嗽次数明显减少(P< 0.01);润燥清肺膏能减轻急性支气管炎大鼠模型黏膜上皮细胞的坏死和脱落,抑制黏膜层和黏膜下层炎性细胞浸润;润燥清肺膏高、中剂量组明显抑制醋酸所致小鼠腹腔毛细血管通透性的增高(P< 0.05、0.01);润燥清肺膏高、中、低各剂量组明显地抑制小鼠耳肿胀(P< 0.05、0.01)。润燥清肺膏对金黄色葡萄球菌、表皮葡萄球菌、肺炎克雷伯菌和大肠杆菌有不同程度的抑制作用。结论 润燥清肺膏对急性支气管炎模型大鼠支气管病变有抑制作用,具有明显的止咳、抗炎、抑菌作用。     

狗皮膏安全性评价研究

目的 对狗皮膏的皮肤用药安全性进行评价研究。方法 取不同厂家样品10批分别进行家兔急性皮肤刺激性试验和豚鼠皮肤过敏性试验,同时采用原子吸收分光光度法测定给药后家兔血铅浓度的变化。结果 10批样品中有7批出现皮肤刺激反应,除A厂家1批为中度刺激性,其余为轻度刺激性;10批样品均未见皮肤过敏反应;狗皮膏连续给药7 d后,给药组的血铅浓度与对照组相比差异有统计学意义（P＜0.01）,连续给药14 d后的血铅浓度与连续给药7 d相比差异有统计学意义（P＜0.05）。结论 狗皮膏引起皮肤刺激反应的风险较大,且不同厂家间、厂内批次间存在差异;久贴狗皮膏可引起血铅升高,建议改善制剂以减轻不良反应。     

基于网络药理学的生脉注射液作用机制研究

目的 基于网络药理学技术探索生脉注射液的体内药效物质基础和作用机制。方法 通过数据库及文献检索方法获取生脉注射液的有效成分,通过BATMAN-TCM构建的分子对接技术预测生脉注射液有效成分的体内作用靶标及相关通路,基于京都基因与基因组百科全书（KEGG）的通路富集分析功能,阐述生脉注射液的多成分-多通路作用机制。结果 通过上述方法共计发现295个有效成分,直接或间接涉及体内4 891个靶标,552种相关疾病。关键成分是,锦葵酸、腺苷、蝙蝠葛碱、维生素B12、十四醇、腺苷三磷酸肌醇。关键靶标是亚当金属肽酶结构域8、AKT丝氨酸/苏氨酸激酶1、ATP结合盒亚家族成员1、花生四烯酸15脂肪氧化酶、腺苷A1受体、缓激肽受体B2、一氧化氮合酶3、乙酰胆碱酯酶、丁酰胆碱酯酶。关键疾病是炎症反应、乳腺癌、心血管疾病、前列腺癌、哮喘、脓毒症、动脉粥样硬化、帕金森氏病、阿尔兹海默病、精神分裂症。涉及通路是糖酵解/糖异生、柠檬酸循环、磷酸戊糖途径、戊糖和葡糖醛酸盐相互转化、果糖与甘露糖代谢、半乳糖代谢、抗坏血酸与醛酸代谢、脂肪酸生物合成、脂肪酸伸长、脂肪酸降解。结论 生脉注射液主要通过多成分协同起效的机制起到抗炎、抗乳腺癌等疾病的作用。本研究结果初步验证了生脉注射液治疗疾病的有效成分和作用机制,为进一步深入揭示相关疾病的有效治疗方法开发奠定基础。     

灯盏生脉胶囊联合奥拉西坦治疗轻中度血管性痴呆的疗效观察

目的 探讨灯盏生脉胶囊联合奥拉西坦注射液治疗轻中度血管性痴呆的疗效。方法 选取濮阳市人民医院2012年1月—2015年3月收治的轻中度血管性痴呆患者90例,采用随机数字表法分为治疗组(45例)和对照组(45例)。所有患者均给予常规降血脂、抗血小板聚集治疗,对照组给予静脉滴注奥拉西坦注射液4 g,加入到0.9%生理盐水500 mL,1次/d。治疗组在对照组基础上口服灯盏生脉胶囊,2粒/次,1次/d。两组均连续治疗12周。治疗前后采用简易智能精神状态量表(MMSE)和蒙特利尔认知评估量表(MoCA)评价患者认知功能;采用日常生活能力量表(ADL)评价患者日常生活自理能力;比较两组患者血管内中膜厚度(IMT)。结果 治疗后2、4、12周,两组MMSE、MoCA评分均显著上升(P< 0.05),且治疗组MMSE、MoCA评分显著高于对照组(P< 0.05);治疗后2、4、12周,两组ADL评分均显著升高(P< 0.05),且治疗组ADL评分显著高于对照组(P< 0.05)。治疗后两组IMT均显著降低(P< 0.05),且治疗组IMT显著低于对照组(P< 0.05)。结论 灯盏生脉胶囊联合奥拉西坦注射液治疗轻中度血管性痴呆疗效确切,可显著改善患者的认知功能和日常生活行为,具有一定的临床推广应用价值。     

注射用益气复脉(冻干)味的测定

目的 建立一种用于测定注射用益气复脉（冻干）滋味的方法,以保证不同生产批次间的质量稳定。方法 采用Alpha MOS公司电子舌（Astree）测定注射用益气复脉（冻干）6批样品,以0.01 mol/L盐酸为校准溶液,以蒸馏水为稀释溶剂,样品采集时间为60 s,每次分析时间120 s,每个样品重复测9次,利用Alpha Soft V14.2软件进行数据分析。结果 注射用益气复脉（冻干）的酸、甜、苦3个滋味表现较明显,且批间差异不大;利用主成分分析能很好地区分不同批次样品在味道上的差异;不同样品间味道的相对强度存在差异;利用独立建模分析对其他批次样品进行鉴定,识别率为100%。结论 所建立的方法具有样品处理方法简单、操作简单、快速、检测成本低、污染小等特点,可用于注射用益气复脉（冻干）滋味的测定。     

生脉注射液3种成分在心肌缺血模型Beagle犬体内的药动学研究

目的 研究生脉注射液活性成分人参皂苷Rg₁、人参皂苷Re、五味子醇甲在正常和心肌缺血状态下Beagle犬体内的药动学变化。方法 选用Agilent ZORBAX SB-C₁₈色谱柱,流动相为乙腈-水,梯度洗脱,质谱采用选择反应监测（SIM）方式进行正离子检测3种活性成分。用WinNonlin 6.3软件和SPSS 19.0软件计算各给药组药动学参数,并进行统计分析。结果 造模后,人参皂苷Rg₁半衰期缩短;人参皂苷Re表观分布容积增大,肾清除率减慢;模型组五味子醇甲半衰期延长,体内平均滞留时间延长,表观分布容积增大,肾清除率减慢。结论 Beagle犬滴注生脉注射液后,人参皂苷Rg₁、人参皂苷Re、五味子醇甲在心肌缺血模型犬体内的药动学特征,与正常犬的药动学特征存在很大差异。     

Antioxidative and anti-inflammatory effects of phenolic compounds from the roots of <Emphasis Type="Italic">Ulmus macrocarpa</Emphasis>

The roots of Ulmus macrocarpa Hance (Ulmaceae) have been used as an oriental traditional medicine for the treatment of inflammation, ulcers, cancers, and parasites. Activity guided isolation from the roots of U. macrocarpa yielded three flavonoids [catechin 7-O-β-D-apiofuranoside (1), (+)-catechin (2), taxifolin 6-C-glucopyranoside (3)], and one coumarin [fraxin (4)]. To investigate the antioxidative and anti-inflammatory effects of these compounds, DPPH radical scavenging activity and inhibitory activity against nitric oxide (NO) production in LPS-stimulated RAW 264.7 cells were examined and the expression of inducible NO synthase (iNOS) and cyclooxidase-2 (COX-2) were measured by RT-PCR and Western Blotting in HaCaT cells. Compounds 1, 2, and 3 showed moderate antioxidative activities compared with L-ascorbic acid as a positive control. NO production was reduced and the expressions of iNOS and COX-2 and their mRNA were inhibited by the addition of samples (1–4). These results suggest that the phenolic compounds from the roots of U. macrocarpa might be developed as antioxidant and anti-inflammatory agents.     

参仙升脉口服液联合尼非卡兰治疗室性心律失常的临床研究

目的 探讨参仙升脉口服液联合盐酸尼非卡兰治疗室性心律失常的临床疗效.方法 回顾性分析2018年12月—2020年12月在平顶山市第一人民医院进行治疗的52例室性心律失常患者为研究对象,根据用药差别将所有患者分为治疗组和对照组,每组各26例.对照组给予注射用盐酸尼非卡兰,0.3 mg/kg,溶入0.9％氯化钠注射液20 ...     

Establishment of an anti-inflammation-based bioassay for the quality control of the 13-component TCM formula (Lianhua Qingwen)

ContextOwing to the complexity of chemical ingredients in traditional Chinese medicine (TCM), it is difficult to maintain quality and efficacy by relying only on chemical markers.ObjectiveLianhua Qingwen capsule (LHQW) was selected as an example to discuss the feasibility of a bioassay for quality control.Materials and methodsNetwork pharmacology was used to screen potential targets in LHQW with respect to its anti-inflammatory effects. An in vitro cell model was used to validate the prediction. An anti-inflammatory bioassay was established for the quality evaluation of LHQW in 40 batches of marketed products and three batches of destructed samples.ResultsThe tumor necrosis factor/interleukin-6 (TNF/IL-6) pathway via macrophage was selected as the potential target of LHQW. The IC₅₀ value of LHQW on RAW 264.7 was 799.8 μg/mL. LHQW had significant inhibitory effects on the expression of IL-6 in a dose-dependent manner (p < 0.05). The anti-inflammatory biopotency of LHQW was calculated based on the inhibitory bioactivity on IL-6. The biopotency of 40 marketed samples ranged from 404 U/μg to 2171 U/μg, with a coefficient of variation (CV) of 37.91%. By contrast, the contents of forsythin indicated lower CV (28.05%) than the value of biopotency. Moreover, the biopotencies of destructed samples declined approximate 50%, while the contents of forsythin did not change. This newly established bioassay revealed a better ability to discriminate the quality variations of LHQW as compared to the routine chemical determination.ConclusionsA well-established bioassay may have promising ability to reveal the variance in quality of TCM.     

扶正化瘀片联合替诺福韦酯治疗慢性乙型肝炎的临床研究

目的 探讨化橘红防治新型冠状病毒肺炎（COVID-19）的前景,为化橘红的临床应用提供依据。方法 通过文献查阅,对化橘红及其主要化学成分在祛痰、抗急性肺损伤、抗炎、抗肺纤维化、镇咳、抗氧化、抗肝损伤和抗肾损伤等方面的药理作用进行分析,并通过中药系统药理学平台（TCMSP）和查阅文献检索化橘红的化学成分,将各化学成分与血管紧张素转化酶II（ACE2）、3CL水解酶（Mpro）、木瓜样蛋白酶（PLP）和树突状细胞特异性细胞间黏附分子-3结合非整合素因子（DC-SIGN）进行分子对接,预测其在抑制新型冠状病毒（SARS-CoV-2）病毒感染和复制方面的潜在活性。结果 文献分析结果表明,化橘红及其主要化学成分具有祛痰、抗急性肺损伤、抗炎、抗肺纤维化、镇咳、抗氧化、抗肝损伤和抗肾损伤等多方面药理活性;分子对接结果表明,柚皮苷（naringin）、新橙皮苷（neohesperdin）、野漆树苷（rhoifolin）、枸橘苷（poncirin）和西托糖苷（sitogluside）与ACE2、MPro、PLP和DC-SIGN均具有较强的结合力,具有抑制SARS-CoV-2病毒感染宿主细胞和自我复制的潜在活性。结论 化橘红既具有通过多种药理活性改善COVID-19病程进程的潜力,又可能通过作用于ACE2、MPro、PLP和DC-SIGN发挥抑制病毒感染宿主细胞及自我复制的作用。提示化橘红可能对COVID-19的防治具有积极作用。     

Anti-inflammatory effect of novel andrographolide derivatives through inhibition of NO and PGE2 production

Andrographolide (1) is a major diterpene lactone exhibiting anti-inflammatory effects and is found in the plant Andrographis paniculata (Burm. f) Nees, which is widely used in Traditional Chinese Medicine. Synthesis of more effective drugs from andrographolide is very interesting and can prove to be highly useful. In this study, we investigated the anti-inflammatory effects of andrographolide and its derivatives (compounds 2–6) through dimethylbenzene-induced ear edema in mice. Substances under study were administrated intragastrically and the structure–activity relationship was analyzed. Results showed that compounds 5 and 6 significantly inhibited ear edema compared with compound 1 (p < 0.05), indicating that the introduction of p-Chlorobenzylidene to C-15 of compound 2 enhances the anti-inflammatory effect. Moreover, compound 6 exhibited the strongest anti-inflammatory effect against ear edema in mice (79.4%; 1.35 mmol/kg, ig) and paw edema in rats (50.4%; 0.90 mmol/kg, ig). In addition, compound 6 significantly (p < 0.05) inhibited granuloma formation and reduced the increase in vascular permeability induced by peritoneal injection of 0.6% acetic acid solution in mice. Findings indicate that compound 6 exerts its enhanced anti-inflammatory effects by decreasing serum iNOS activity, NO production, and PGE₂ production.     

Anti-inflammatory and anti-osteoarthritis effect of Mollugo pentaphylla extract

Context: Mollugo pentaphylla L. (Molluginaceae) extract (MPE) has been reported to have anti-inflammatory effect on MSU-induced gouty arthritis in a mouse model.

Objective: This study examined the anti-inflammatory activities of an MPE in vitro and anti-osteoarthritis effects on monosodium iodoacetate (MIA)-induced osteoarthritis (OA) in vivo.

Materials and methods: The dried whole plants of M. pentaphylla were extracted with 70% ethanol under reflux. The anti-inflammatory effect of MPE was evaluated in vitro in lipopolysaccharide (LPS)-treated RAW264.7 cells. The anti-osteoarthritic effect of MPE was investigated in a Sprague–Dawley rat model of MIA-induced OA. Each seven male rats were orally administered MPE (75, 150 or 300?mg/kg) or the positive control drug indomethacin (1?mg/kg) 3?days before MIA injection and once daily for 11?days thereafter. After the treatment with MPE, no evidence of systemic adverse effects was observed in any study group.

Results: MPE exhibited anti-inflammatory activity via inhibition of the production of NO (57.8%), PGE2 (97.1%) and IL-6 (93.2%) in LPS-treated RAW264.7 cells at 200?μg/mL. In addition, MPE suppressed IL-1β (60.9%), TNF-α (37.9%) and IL- 6 (40.9%) production and suppressed the synthesis of MMP-2, MMP-9 and COX-2 in the MIA-induced OA rat model.

Conclusions: These results demonstrate that MPE exerts potent anti-inflammatory activities and protects cartilage in an OA rat model. This might be a potential candidate for therapeutic OA treatment.     

生脉注射液联合果糖二磷酸钠治疗小儿病毒性心肌炎疗效观察

目的：探讨生脉注射液联合果糖二磷酸钠治疗小儿病毒性心肌炎的疗效。方法：将76例病毒性心肌炎患儿随机分为三组．对照组给予常规治疗,治疗Ⅰ组常规治疗加果糖二磷酸钠,治疗Ⅱ组常规治疗加生脉注射液和果糖二磷酸钠。结果：对照组有效率68．0％,治疗Ⅰ组有效率76．0％,治疗Ⅱ组有效率96．2％,治疗Ⅱ组与治疗Ⅰ组及对照组比较差异均有统计学意义（P〈0．05）。结论：生脉注射液联用果糖二磷酸钠是小儿病毒性心肌炎较理想的治疗方法。