CN101199856B - 一种携氧抗休克药物 - Google Patents
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Abstract
一种携氧抗休克药物，其特征在于它的基础配方为：在浓度为3～10％、分子量为20～200kD的羟乙基淀粉溶液中加入纳米级载氧物质和防止不良反应的成分。其优越性在于：既有良好的血浆扩容作用，又能给缺氧组织供氧，保证人体各器官能迅速缓解或纠正缺氧状态，逐渐恢复正常生理功能，达到救治目的；与此同时，由于缺血而引发的血管内皮水肿、炎性反应等不良现象，可在携氧药物溶液中加入一定浓度的防止副反应的成分，达到有效防治的目的。
Description
(一)技术领域：
本发明涉及一种药物，尤其是一种携氧抗休克药物。
(二)背景技术：
人工胶体溶液如明胶、右旋糖酐和羟乙基淀粉等氯化钠注射液均是用于低血容量和休克患者治疗的常用有效药物。但是，当失血量过大或其他原因引起的深度休克时，人体组织特别是心、脑、肾等组织需要供氧才能挽回生命时，仅靠单纯的胶体溶液来扩充血循环容量和维持正常循环时就难以维持生命。现有的抗休克药物(例如，人工胶体溶液等)均不具有供氧功能，因而在临床实践中迫切需要一种具有携氧功能的抗休克药物。
(三)发明内容：
本发明的发明目的在于设计一种携氧抗休克药物，它既具有良好的血浆扩容作用，又能给缺氧组织供氧，保证人体各器官能迅速缓解或纠正缺氧状态，从而逐渐恢复正常生理功能，达到救治目的；与此同时，由于缺血而引起的血管内皮水肿、炎性反应等不良现象也能得到有效的防治。
本发明的技术方案为：一种携氧抗休克药物，其特征在于它的基础配方为：在浓度为3～10％、分子量为20～200kD的羟乙基淀粉溶液中加入纳米级载氧物质和防止不良反应的成分。
上述所说的羟乙基淀粉HES、纳米载氧物质和防止不良反应成分的质量标准均应符合大剂量静脉注射液要求，即大于500mL静脉注射液。
上述所说的羟乙基淀粉的摩尔替代度Ms为0.4～0.6。
上述所说的纳米载氧物质为聚合血红蛋白Poly-Hb溶液，浓度范围2％～10％，其分子量为32～128kD，粒子半径为5～50nm。
上述所说的防止不良反应成分为糖类、氨基酸和抗氧化剂。
上述所说的糖类为葡萄糖、麦芽糖、甘露醇或木糖醇。
上述所说的羟乙基淀粉溶液中可以加入2.5～7.5％的浓度为0.85～3.90％的氯化钠。
上述所说的聚合血红蛋白为人、牛或猪的血红蛋白。
上述所说的聚合血红蛋白的分子量分布中小于32kD的聚合血红蛋白含量不多于3.0％，32～64kD的聚合血红蛋白含量小于10％。
上述所说的抗氧化剂为肌肽、维生素C、谷胱甘肽或硫代硫酸钠。
本发明的优越性在于：1、在保持良好血浆扩容效果和生理胶体渗透压前提下，加入2～10％适当分子量的载氧物质，而这种载氧物质是采用人胎盘或成人外周血红蛋白经过系列生物和化学技术改造后，其携氧和供氧功能类似于人正常红细胞的同种生理功能；2、由于载氧粒子半径只相当于红细胞半径的1/400或更小，比人红细胞更容易通过毛细血管向组织供氧，甚至红细胞不能通过的狭窄毛细血管，纳米级载氧药物也能大量通过，及时纠正组织特别是心脑组织缺氧状态，达到良好的救治效果；3、所采用的Poly-Hb，平均分子量为96kD～128kD，未聚合的小于30kD分子量的Hb含量＜3％，可保持良好的无肾损害和异常升血压等副作用，又具有血浆扩容效果；4、HES为低分子量(20～40kD)制品，浓度为3～10％，既能满足整体药物扩容效果，又使得保持黏度较低，有利于改善血流动力学，更易于给组织供氧；5、在配方中加入高渗NaCl，可以防止补液过程中易发生的氧自由基损害。
(四)具体实施方式：
实施例：一种携氧抗休克药物，其特征在于它的基础配方为：在浓度为6％、分子量为100kD的羟乙基淀粉溶液中加入纳米级载氧物质和防止不良反应的成分。
上述所说的羟乙基淀粉HES、纳米载氧物质和防止不良反应成分的质量标准均应符合大剂量静脉注射液要求，即大于500mL静脉注射液。
上述所说的羟乙基淀粉的摩尔替代度Ms为0.5。
上述所说的纳米载氧物质为聚合血红蛋白Poly-Hb溶液，浓度范围5％，其分子量为80kD，粒子半径为22nm。
上述所说的防止不良反应成分为糖类、氨基酸和抗氧化剂。
上述所说的糖类为葡萄糖。
上述所说的羟乙基淀粉溶液中可以加入5％的浓度为2％的氯化钠。
上述所说的聚合血红蛋白为人的血红蛋白。
上述所说的聚合血红蛋白的分子量分布中小于32kD的聚合血红蛋白含量不多于3.0％，32～64kD的聚合血红蛋白含量小于10％。
上述所说的抗氧化剂为肌肽。
本发明一种携氧抗休克药物实验效果分析：
采用SD大鼠做携氧抗休克药物动物换血试验，试验分成试剂对照组和样品实验组，每只动物换血量达到全血量的50％，血压降至40mmHg，动物处于深度昏迷状态，然后分别静脉注射试剂(羟乙基淀粉)和6％浓度的上述药物。实验结果表明，试剂组动物存活时间平均为32.86小时，而样品组动物存活时间平均达72.00小时以上。样品组动物存活时间明显高于试剂对照组。
Claims (8)
1.一种携氧抗休克药物，其特征在于它的基础配方为：在浓度为3～10％、分子量为20～200kD的羟乙基淀粉溶液中加入纳米级载氧物质和防止不良反应的成分；所说的载氧物质为聚合血红蛋白溶液，浓度范围2％～10％，其分子量为32～128kD，粒子半径为5～50nm；所说的防止不良反应的成分为糖类、氨基酸和抗氧化剂。
2.根据权利要求1所说的一种携氧抗休克药物，其特征在于所说的羟乙基淀粉、纳米级载氧物质和防止不良反应成分的质量标准均应符合大剂量静脉注射液要求，所说的大剂量静脉注射液为大于500mL静脉注射液。
3.根据权利要求1或2所说的一种携氧抗休克药物，其特征在于所说的羟乙基淀粉的摩尔替代度Ms为0.4～0.6。
4.根据权利要求1所说的一种携氧抗休克药物，其特征在于所说的糖类为葡萄糖、麦芽糖、甘露醇或木糖醇。
5.根据权利要求1所说的一种携氧抗休克药物，其特征在于所说的羟乙基淀粉溶液中加入2.5～7.5％的浓度为0.85～3.90％的氯化钠。
6.根据权利要求1所说的一种携氧抗休克药物，其特征在于所说的聚合血红蛋白为人、牛或猪的血红蛋白。
7.根据权利要求1所说的一种携氧抗休克药物，其特征在于所说的聚合血红蛋白的分子量分布中小于32kD的聚合血红蛋白含量不多于3.0％，32～64kD的聚合血红蛋白含量小于10％。
8.根据权利要求1所说的一种携氧抗休克药物，其特征在于所说的抗氧化剂为肌肽、维生素C、谷胱甘肽或硫代硫酸钠。
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