绿原酸致敏性的综合研究与评价

Comprehensive research and evaluation of chlorogenic acid allergy

目的：通过不同纯度绿原酸的致敏试验结果，结合对文献的综合分析，揭示绿原酸的非致敏原性。方法：设定了不同纯度绿原酸提取物组（绿原酸20％～99％）、注射用绿原酸组、不同纯度绿原酸提取物和注射用绿原酸的透析内液组和外液组、过期和降解后的注射用绿原酸组作为受试药物，以豚鼠和大鼠为受试动物，分别采用全身主动过敏试验和皮肤被动过敏试验进行致敏性验证；采用LC．MS法鉴定了透析内液中大分子残留物的相对分子质量范围。结果：质量分数高于92％的绿原酸提取物、注射用绿原酸及其降解物和含小分子的透析外液均未发生过敏反应；质量分数低于40％的绿原酸提取物及其透析内液均被LC—MS鉴定出大分子化合物并且发生明显的过敏反应。结论：根据试验结果和国内外相关文献，均证明了绿原酸没有致敏原性，而低纯度提取物中存在的大分子物质才与致敏反应密切相关。

Objective：The non-allergy of chlorogenic acid was demonstrated by the study result of allergy with different purity of ehlorogenic acid and comprehensive analysis of literature. Method ： The allergies of different samples, which contained the different purity of chlorogenic acid extracts, chlorogenic acid for injection, interior solution of dialysis, external solution of dialysis, post-term chlorogenic acid for injection and chlorogenie acid for injection with degradation, were validated with active systemic anaphylaxis and passive cutaneous anaphylaxis on rats and guinea pigs respectively. The range of molecular weight of maeromolecular remains after dialysis were identified by LC-MS. Result： Allergic reactions were happened in dialysis isolated maeromolecular substances, which were identified by LC-MS, and lower purity extracts（ purity of chlorogenic acid ≤40% ）, while the reactions were not happened in isolated micromolecular substances and high purity samples （purity of chlorogenic acid ≥ 92% ）. Conclusion： Macromoleeules in lower purity of chlorogenic acid extracts were relative closely to the allergen causing anaphylaxis, but not the ehlorogenie acid, which was demonstrated according to the study result and analysis of literatures home and abroad.