异佛尔酮二异氰酸酯溶液扩链合成聚乳酸类药物缓释剂

以外消旋乳酸(D,L-LA)直接熔融聚合得到的低相对分子质量聚外消旋乳酸(PDLLA)为原料,通过二异氰酸酯扩链合成了聚乳酸类药物缓释材料。当采用异佛尔酮二异氰酸酯(IPD I)为扩链剂,反应在四氢呋喃溶液中进行时,扩链反应工艺条件为:扩链剂用量n(NCO)∶n(OH)=2∶1时,66℃下回流反应2 h,相对分子质量增加近2.92倍。与2,4-甲苯二异氰酸酯(TD I)扩链法相比,IPD I溶液扩链法不仅提高产物相对分子质量的效果非常接近,具有反应温和、条件易调控等优点,而且使所得聚乳酸类药物缓释材料具有较高的生理安全性。

Synthesis of Poly(lactic acid) Drug Delivery Material through the Chain Extension of Isophorone Diisocyanate in Solution State

Starting from lower molecular weight poly(D,L-lactic acid)(PDLLA) produced by direct melt polycondensation of D,L-lactic acid(D,L-LA),poly(lactic acid) drug delivery material was synthesized through diisocyanate chain extension.Using isophorone diisocyanate(IPDI) as chain extender and tetrahydrofuran(THF) as solvent,the conditions for the chain extension synthesis were studied.Under the reaction conditions including NCO/OH molar ratio 2.0,reflux temperature 66 ℃ and reaction time 2 h,viscosity-average molecular weight(Mη) of chain extension product could be about 3 times higher than before.Compared with the chain extension of 2,4-tolylene diisocyanate(TDI) in solution state,the IPDI solution method had similar effect in increasing Mη under the mild conditions.More importantly,the novel IPDI chain extension method was advantageous to make the poly(lactic acid) drug delivery material with better physiological security than that by TDI chain extension method.