摘要
目的考察国内市售低分子肝素产品间的差异,研究其结构特征、相对分子质量及其分布与生物活性的关系。方法采用分光光度法测定产品的特征组份的含量,生物显色法测定抗凝血的生物活性,凝胶渗透色谱法测定相对分子质量及其分布。将这些参数进行统计学分析。结果6种低分子肝素产品间分子的特能组成,相对分子质量及其分布和生物活性上均显示极显著性差异。相关性研究表明,分子中葡萄糖醛酸和葡萄糖胺的含量与低分子肝素相对分子质量、抗-Xa活性、抗-Ⅱa活性呈负相关;低分子肝素相对分子质量与抗-Ⅹa活性、抗-Ⅱa活性呈正相关;而硫酸基含量与低分子肝素相对分子质量、抗-Ⅹa活性、抗-Ⅱa活性呈正相关。结论每一个低分子肝素产品间都存在着明显的差异,具有不同的特点,临床使用中应按指征个体化给药。
Abstract
OBJECTIVE To investigate the difference between lowmolecule-weight-heparin products in market,and to study the relationship among their special structure,molecular weight and bioactivity.METHODS The contents of special structure were determined by spectrophotometry;the bioactivity of anticoagulation was obtained by bio-coloration;the molecular weight and its distribution were measured using gel permeation chromatography;these parameters were statistically analyzed.RESULTS There is exactly significant difference among special structure,molecular weight and bioactivity of the six low molecule heparin products in market.There is negative correlation between the content of glycuronic acid,aminoglucose and molecular weight,anti-Ⅹa activity,anti-Ⅱa activity.There is positive correlation between molecular weight and anti-Ⅹa activity,anti-Ⅱa activity.While there is positive correlation between the quantity of sulphuric group and anti-Ⅹa activity,anti-Ⅱa activity.CONCLUSION Every low molecule heparin product has its own feature,and they should be used individualized in clinic.
关键词
低分子肝素 /
葡萄糖醛酸 /
葡萄糖胺 /
硫酸基 /
抗-Ⅹa活性 /
抗-Ⅱa活性 /
相对分子质量
{{custom_keyword}} /
Key words
low-molecule-weight-heparin /
glycuronic acid /
aminoglucose /
sulphuric group /
anti-Ⅹa activity /
anti-Ⅱa activity /
molecular weight
{{custom_keyword}} /
顾健;杨军;张春燕;张海英;李玉珍.
6种市售低分子肝素的分子特性及生物活性的比较[J]. 中国药学杂志, 2007, 42(06): 461-465
GU Jin;YNG Jun;ZHNG Chun-yn;ZHNG Hi-ying;LI Yu-zhen.
Compare of Molecule Characteristics and Bioactivity of Low-Molecular-Weight-Heparin Products in Market [J]. Chinese Pharmaceutical Journal, 2007, 42(06): 461-465
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] CAO P， ZHANG L S. Study on anticoagulant effects and antithrombotic effects of low molecule weight heparin (LMWH) [J] .Chin J Hosp Pharm (中国医院药学杂志)，2001，21（5）：289-291.
[2] YANG X H， LING P X， WANG F S，et al.Application of heparin in Autoimmune disease[J] .Chin Biochem J(中国生物化学杂志)，1995，15 ：281-283.
[3] RACINE E.Differentiation of the low-molecular-weight heparins[J] .Pharmacotherapy， 2001， 21： 62-70.
[4] WANG F S，LING P X.Study on Biochemical Pharmaceutics(生化药物研究)[M] .Beijing：People health press，1997：110-225.
[5] XIE J Q， WANG F S， CUI H F，et al. Optimization on the opera tion procedure of chondroitin sulfate content determination[J] . Chin J Biochem Pharm (中国生化药物杂志)， 2000， 21： 243-244.
[6] BITTER T， MUIR H M.Amodified Uronic acid carbazole reaction[J] .Anal Biochem，1962，4：330-334.
[7] TERHO T T，HARTIAL A K. Method for determination of the sulfate content of glycosaminoglycans[J] .Anal Biochem，1971，41：471-476.
[8] British Pharmacopoeia(2003) [S] .2003：920.
[9] FAREED J， JESKE W， HOPPENSTEADT D，et al.Are the available low-molecular weighe heparin preparations the same[J] . Semin Thromb Hemost，1996，22 (suppl 1)： 77-91.
[10] LOU Z， ZHANG T M. Relationship between molecular weight and antithrombus effectof low-molecular-weight heparins from low- anticoagulatedheparins[J] .Chin Pharm J(中国药学杂志)，1991，26：552-554.
[11] SHI F， JI S L， CHI Y Q，et al.Preparation of LMWH and the relationship between its structure and bioactivity[J] .Chin J Biochem Pharm (中国生化药物杂志)， 2003， 24： 101-104.
[12] GAO H， ZHANG T M， ZHANG Z G. Physico-chemical property and bioactivity of heparin from different source[J] .Acta Acad Med Shandong(山东医科大学学报)，1987，25（2）：41-46.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
