低分子肝素在内科疾病中的应用

低分子肝素 (ｌｏｗ ｍｏｌｅｃｕｌａｒ ｗｅｉｇｈｔｈｅｐａｒｉｎ ,ＬＭＷＨ)抗凝作用除与抗凝血酶Ⅲ相结合外 ,因分子量小 ,还可以与抗ＦＩＶａ和ＦＸａ相结合 ,催化ＦＩＶａ和ＦＸａ活性。与普通肝素比较 ,ＬＭＷＨ生物利用度高 ,与血浆、血小板亲和力小 ,抗凝作用强 ,出血副作用明显减少 ,故在临床上受到了广泛关注[1 ] 。1　缺血性脑卒中抗血栓治疗对急性缺血性脑卒中患者可以减少深部静脉血栓的发生。有人采用ＬＭＷＨ治疗 34例 ,其中进展型短暂脑缺血发作 3例 ,脑梗死 31例 ;对照组 31例 ,均为脑梗死。两组均应用低分子右旋糖酐 5…     

低抗凝肝素来源低分子肝素口服制剂的研究

以生产肝素的副产品——低抗凝肝素为原料,采用亚硝酸控制解聚法制得了低分子肝素,分子量为5300,抗凝活性为39.2u/mg,测定了理化指标。以对家兔实验性血栓形成的影响为药效学指标,确定低分子肝素口服制剂的处方组成为低分子肝素、油酸、牛胆盐。研究了所制备的低分子肝素胶囊对家兔血液流变学及血栓形成的影响,并试用于部分动脉粥样硬化症志愿者,表明该胶囊可有效地改善家免和动脉粥样硬化症志愿者血液流变性质,抑制血栓形成。     

低相对分子质量肝素钠用于血液透析抗凝的疗效和安全性

目的：观察低相对分子质量肝素（ＬＭＷＨ）钠应用于血液透析的抗凝疗效和安全性。方法：３０例稳定的尿毒症维持性血透患者,随机分为未组分肝素（ＵＦＨ）组和ＬＭＷＨ组。ＵＦＨ首剂４￣６ｍｇ／ｋｇ,追加６￣８ｍｇ／ｈ,透析结束前０．５ｈ停用。ＬＭＷＨ３２００ＩＵ透前一次性ｉｖ。结果：ＬＭＷＨ组秀析器内纤维血栓形成显著较少;用药２和４ｈ血浆ａＸａ活性显著较高,且４与２ｈ比较仅轻度下降;用药后２ｈ血浆部分活化凝     

首批低分子肝素国家标准品的建立

低分子肝素 (ＬＭＷＨ )比普通肝素抗血栓作用强 ,出血副作用小 ,有较高生物利用度和较长的生物半衰期[1] ,其抗血栓作用与其抗活化Ⅹ因子(抗ＦⅩａ)活性相关 ,抗凝作用与其抗活化Ⅱ因子(抗ＦⅡａ即抗凝血酶 )活性相关[2 ,3] ,英国药典ＢＰ1998已收载该品种 ,我国已有多家单位研究生产并申报新药 ,ＬＭＷＨ质量标准拟上中国药典2 0 0 0年版增补版 ,而质量标准实施中必须要有标准品。ＷＨＯ已于 1987年制备并发行ＬＭＷＨ第一次国际标准品 ,批号 85/60 0 [4 ] ,以及 1993年发行用于测定分子量分布的ＬＭＷＨ第一次国际参考品(ＩＲＲ) ,批号 9…     

低抗凝肝素来源低分子肝素口服制剂的研究

以生产肝素的副产品——低抗凝肝素(LAAH)为原料,采用亚硝酸控制解聚和乙醇沉淀技术制备了低分子肝素(LMWH),其平均分子量为5300d,抗凝效价为39.2U/mg。以对家兔实验性血栓形成的影响为药效学指标,确定了口服制剂的配方组成为LMWH、油酸、牛胆盐。用同样配方制备了LMWH胶囊(1)和等抗凝效价的肝素胶囊(2)。     

用分光光度法测定低分子肝素的效价

低分子肝素（ＬｏｗＭｏｌｅｃｕｌａｒＷｅｉｇｈｔＨｅｐａｒｉｎ,ＬＭＷＨ）比普通肝素有较强的抗活化Ⅹ因子（ＦⅩａ）作用和较弱的抗凝血酶（即活化Ⅱ因子,ＦⅡａ）的作用,抗ＦⅩａ与抗ＦⅡａ的活性比率大［１～５］,故抗血栓作用强,出血副作用小,且生物利用度...     

低分子量肝素的临床应用

1916年Ｍｏｌｅａｎ首先发现肝素的抗凝作用 ,肝素 (ｓｔａｎｄａｒｄｈｅａｐａｒｉｎ ,ＳＨ)广泛应用临床抗凝、抗血栓作用 ,还具有抗炎、抗过敏、抗病毒和降血脂作用。由于ＳＨ分子量大 ( 5 0 0 0～ 3 0 0 0 0ｄ) ,仅 1 3分子质量较低的部分有较强抗凝活性 ,一定程度限制了临床应用。自 80年代开始对低分子量肝素 (ｌｏｗ ｍｏｌｅｃｕｌａｒｗｅｉｇｈｔｈｅｐａｒｉｎｓ ,ＬＭＷＨ)研究 ,ＬＭＷＨ是通过化学或酶解裂后生成的肝素片段 ,其平均分子量为 65 0 0ｄ ;本文就其临床应用综述如下。1　静脉血栓预防及治疗大量临床研究认为ＬＭ…     

低分子肝素在麻醉大鼠胃肠道的吸收

以血浆抗Ｘａ活性及体内抗静脉血栓形成为指标，考察了低分子肝素溶液及乳剂在麻醉大鼠胃肠道的吸收情况。     

低分子量肝素的临床应用进展

普通肝素 (或称非极分化肝素 ,ｕＦＨ)是临床广泛使用的经典抗凝药物 ,临床效果显著 ,但其严重的副作用制约了它的应用。低分子量肝素 (ｌｏｗｍｏｌｅｃｕｌａｒｗｅｉｇｈｔｈｅｐａｒｉｎ ,ＬＭＷＨ)是由ｕＦＨ通过酶学的或化学的解聚而产生的 ,但ＬＭＷＨ的有效性和安全性却远优于ｕＦＨ。近年来 ,国内外ＬＭＷＨ的临床应用日益广泛 ,对ＬＭＷＨ的研究也日益活跃 ,现对其临床应用进展做一简述。1　不稳定性心绞痛的预防和治疗不稳定性心绞痛 (ｕｎｓｔａｂｌｅａｎｇｉｎａｐｅｃｔｏｒｉｓ ,ＵＡＰ)是介于稳定性心绞痛和急性心肌梗死之…     

从低抗凝肝素研制低分子肝素及其药物动力学研究

从生产肝素的副产品——低抗凝肝素(LAAH),采用亚硝酸控制解聚和乙醇沉淀技术制备了低分子肝素(LMWH),其平均分子量为6000道尔顿,抗凝效价为35.0U/mg,抗 FXa 活性为110.6抗 FXaU/mg,抗FXa/     

低抗凝活性肝素来源低分子肝素的抗炎活性

实验证明低抗凝活性肝素来源的低分子肝素对琼脂致大鼠足跖肿胀、棉球致小鼠炎症性内芽肿组织增生都具有显著抑制作用;对巴豆油所致的小鼠耳廓肿胀、醋酸所致的腹腔毛细血管通透性的抑制作用在本实验条件下虽无统计学意义,但也表现了抑制的趋势.     

低抗凝肝素来源的低分子肝素研究

以肝素生产的副产品低抗凝肝素(效价61.17u/mg)为原料,经亚硝酸控制解聚和凝胶层析制备低分子肝素,其平均分子量为5200d,抗凝效价为30.33u/mg,氨基己糖、己糖醛酸和总硫酸基的含量均较低,动物实验证明在体内有较强的抗血栓形成作用。     

相对低分子质量肝素对大鼠的抗凝血作用

目的：观察相对低分子质量肝素（LMWH）的抗凝作用。方法：大鼠予LMWH,sc后,采血进行体外循环试验且取血浆测定凝血指标。结果：2或4mg/kg的LMWH能显著延长纤维蛋白栓形成时间（TFT）,显著减少血栓的干湿重量。1mg/kgLMWH仅能延长TFT和减少血栓长度。对常用凝血指标如全血凝血时间（CT）、复钙时间（RT）、凝血酶原时间（PT）和凝血酶时间（TT）也有显著的延长作用,但对白陶土部分凝血活酶时间（KPTT）作用较弱。普通肝素4mg/kg对以上各指标也有极显著的作用。结论：LMWH能抑制血栓形成,同时有导致出血的倾向。     

Low-molecular weight molluscan glycosaminoglycan from bivalve Katelysia opima (Gmelin)

Heparin, the glycosaminoglycan (GAG), was isolated from mollusk Katelysia opima (bivalve). The crude extract was partially purified by DEAE cellulose fractionation using two different molar concentrations of saline solution. Among the fractions F1, F2, F3 and F4, fraction F3 had highmolecular weight and better activity. F3 was further processed to get low-molecular weight heparin (LMWH) by nitrous acid depolymerization, and the total yield was 1.2 g/kg. The crude unfractionated heparin (UFH), fractionated heparin and depolymerized heparin samples were colorimetrically analyzed for the metachromatic shift using azure-A dye, and all the samples were found to be metachromatically active. Both UFH and LMWH showed an anticoagulant activity of 160 USP U/mg. Fractionated molluscan and LMWH were found to have peaks similar to that of standard heparin when assessed by the FTIR spectrum. Finally, molecular weight was determined by gradient polyacrylamide gel electrophoresis for UFH, fractionated F3 and LMWH, which were found to be 31,000, 30,500 and 6000 Da, respectively.     

Inhalable Liposomes of Low Molecular Weight Heparin for the Treatment of Venous Thromboembolism

This study tests the feasibility of inhalable pegylated liposomal formulations of low molecular weight heparin (LMWH) for treatment of two clinical manifestations of vascular thromboembolism: deep vein thrombosis (DVT) and pulmonary embolism (PE). Conventional distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) and long-circulating pegylated (DSPE–PEG-2000 and DSPE-PEG-5000) liposomes were prepared by hydration method. Formulations were evaluated for particle size, entrapment efficiency, stability, pulmonary absorption, anticoagulant, and thrombolytic effects in rats. Pulmonary absorption was monitored by measuring plasma antifactor Xa activity; anticoagulant and thrombolytic effects were studied by measuring reduction in thrombus weight and amount of dissolved radioactive clot in the blood, respectively. Pegylated liposomal were smaller and showed greater drug entrapment efficiency than conventional liposomes. All formulations produced an increase in pulmonary absorption and circulation time of LMWH upon first dosing. Three repeated dosings of conventional liposomes resulted in decreased half-life and bioavailability; no changes in these parameters were observed with pegylated liposomes. PEG-2000 liposomes were effective in reducing thrombus weight when administered every 48 h over 8 days. In terms of thrombolytic effects and dosing frequency, PEG-2000 liposomes administered via the pulmonary route at a dose of 100U/kg were as effective as 50 U/kg LMWH administered subcutaneously. This paper suggests that inhalable pegylated liposomes of LMWH could be a potential noninvasive approach for DVT and PE treatment. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci99:4554–4564,     

肝素黄杆菌的固定化及其在低分子肝素制备中的探究

低分子肝素较大分子肝素抗凝血作用小,出血等不良反应发生率低,具有更好的临床应用前景。论文对肝素黄杆菌细胞进行缺壁处理,并考察了温度、pH值、通气量、吐温80用量及溶脂时间等因素对菌体生长和诱导产酶的影响,使用正交实验优化了各个因素,分别确定了菌体培养以及诱导产酶的最佳条件。还初步研究了细胞固定化方法,使用海藻酸钠包埋,得到可重复利用的固定化细胞,其酶活性回收率可达到36.1%。利用固定化细胞裂解大分子肝素,最终电泳观测到相对分子质量为5000左右的目标条带,进一步证明了利用固定化细胞生产低分子质量肝素具有可行性。     

Pharmacokinetics and organ distribution in rats of a low molecular weight heparin

Fluorescein-labelled low molecular weight heparin (OP/LMWH) pharmacokinetics and organ distribution were studied in the rat after intravenous administration at doses of 3 and 15 mg/kg. The pharmacokinetics of labelled OP/LMWH was dose-dependent like heparin, however, the anticoagulant activity such as anti-Xa was more prolonged. The rapidity of the disappearance of the fluorescence was quicker than the biological activity. The fluorescence was observed mainly in the liver and kidney as a diffuse aspect in the short time and as a globular aspect in the long time, mainly in Disse's space of the liver. These results confirm that the liver is important in the regulation of heparin metabolism and activity.     

Dose adjusted heparin treatment of deep venous thrombosis: a comparison of unfractionated and low molecular weight heparin

Summary Two studies have been done to establish recommendations for dosage and dose adjustment in the treatment of deep vein thrombosis (DVT) with low molecular weight heparin (LMWH). In the first, 56 patients were randomized in a double blind study to be treated either with unfractionated heparin (UFH) or LMWH s. c. every 12 h. Initial doses were given according to age and sex, disregarding bodyweight, and the dose was then adjusted when the peak plasma heparin concentration fell outside the desired range of 0.5–0.8 anti-FXa U/ml.There were fewer dose adjustments in the LMWH group. The correlation between injected dose (U/kg bodyweight) and the heparin concentration was higher in the LMWH group (r=0.59) than in the UFH group (r=0.38). The results suggest that, in order to obtain the desired heparin concentration, the initial dose of LMWH should be about 100 U/kg bodyweight every 12 h.In the second, open study, this dosage plan was followed in 15 patients. The peak heparin concentration on Day 2 ranged from 0.40 to 0.75 anti-FXa U/ml and adjustment was only required in 3 patients. Day to day variation in peak heparin activity in the individual patient varied little (CV 11–22%), and there was no accumulation.The results indicate that plasma heparin concentration is more predictable using LMWH than UFH, and they point to definite advantages in the use of LMWH in a bodyweight adjusted dosage.     

低分子肝素的抗凝与抗血栓作用

目的研究低分子肝素的抗凝特点及抗栓作用。方法分别测定其抗Xa因子与抗IIa因子的比率(FXa/FIIa);全凝血时间（CT）、复钙时间（RT）、凝血酶原时间（PT）、凝血酶时间（TT）、活化的部分凝血活酶时间（APTT）;制备体内、体外血栓。结果低分子肝素FXa/FIIa<1,对RT、TT的延长作用明显低于肝素,对CT、PT、ATPP无影响;在两种血栓模型中,低分子肝素组的血栓重均低于肝素组。结论低分子肝素对凝血系统的作用低于肝素;而其抗栓作用大于肝素。