盐酸二氢埃托啡与生物大分子的结合物的合成与药理性质研究

SYNTHESIS AND PHARMACOLOGICAL PROPERTIES OF DIHYDROETORPHINE HYDROCHLORIDE CONJUGATES

目的 :从结构改造上尝试延长盐酸二氢埃托啡的作用时间。方法 :设计合成了盐酸二氢埃托啡与人血清白蛋白 (HSA)和聚赖氨酸 (PLL)的结合物 (HSA与DHE·HCl的比例为 1∶5 ,1∶8,1∶16,1∶17,PLL与DHE·HCl的比例为 1∶3 ) ,并用体外透析实验测定了它们的体外水解情况 ,用药理实验测定了它们在小鼠身上的效价和作用时间。结果 :合成了各种比例的盐酸二氢埃托啡与HSA和PLL的结合物 ,体外透析实验和药理实验表明这类大分子结合物的作用时间与盐酸二氢埃托啡相近 ,而降低了效价。结论 :我们认为效价降低、作用时间相当是由于与生物大分子结合后的结合物比原药分子大得多 ,不利于在体内转运和穿过血脑屏障 。

OBJECTIVE:We tried to enlong the duration of action of dihydroetorphine HCl(DHE)by structure modification.METHODS:DHE conjugates of different HAS(1∶5,1∶8,1∶16, 1∶17)and DHE conjugate of PLL(1∶3)were synthesized and their pharmacological properties in rats and hydrolysis properties in vitro were measured.RESULTS:These newly synthesized DHE conjugates do not have a longer duration of action than that of their parent compound and their potencies were lowered in comparison with their parent compound.CONCLUSION:DHE conjugates with large molecule can not transport in the body and unable to penetrate the blood barrier easily may be the cause of the results mentioned above and only small molecule like the patent compound can step into the central nervious system.