Synthesis and antihistamine evaluations of novel loratadine analogues

A series of loratadine analogues containing hydroxyl group and chiral center were synthesized. The effect of the synthesized compounds on the histamine-induced contractions of guinea-pig ileum muscles was studied. In addition, the in vivo asthma-relieving effect of the analogues in the histamine induced asthmatic reaction in guinea-pigs was determined. Most of the compounds exhibited definite H₁ antihistamine activity. The S-enantiomers, compounds 2, 4 and 8, are more potent than the R-enantiomers, compounds 1, 3 and 7. Compound 6 was the most active one among the eight synthesized compounds.     

氯雷他定联合布地奈德鼻喷剂治疗过敏性鼻炎的疗效及对Th1/Th2细胞因子的影响

目的:探究氯雷他定联合布地奈德鼻喷剂治疗过敏性鼻炎的临床疗效及对Th1/Th2细胞因子的影响。方法:选取我院2016年1月至2017年1月收治的过敏性鼻炎患者110例,按随机数字法分为实验组与对照组,两组均为55例。对照组的治疗方法为采用氯雷他定,实验组治疗则在对照组的基础上联合布地奈德鼻喷剂,30 d为一个疗程。对比两组患者治疗30d后的临床疗效、症状缓解时间和不良反应情况,以及治疗前、治疗30 d后Th1/Th2细胞因子白介素-4(IL-4)、γ-干扰素(IFN-γ)的表达水平。结果:治疗30 d后的总有效率,实验组显著高于对照组(P0.05),实验组喷嚏、流涕、鼻痒症状缓解时间显著短于对照组(P0.05),两组疲劳感、肠胃不适、头痛、皮疹发生率比较无统计学差异(P0.05);治疗30d后两组IL-4表达水平显著低于治疗前(P0.05),IFN-γ表达水平显著高于治疗前(P0.05),实验组IL-4表达水平显著低于对照组(P0.05),IFN-γ表达水平显著高于对照组(P0.05)。结论:氯雷他定联合布地奈德鼻喷剂治疗过敏性鼻炎疗效较好,可显著改善患者临床症状,增强患者免疫功能,安全性较好,值得临床推广。     

Mechanical grinding effect on thermodynamics and inclusion efficiency of loratadine-cyclodextrin inclusion complex formation

The interaction of poor water-soluble drug loratadine (LOR) with β-cyclodextrin (β-CD) or hydroxypropyl-β-cyclodextrin (HP-β-CD) in aqueous or solid state was investigated. Mechanical grinding effect on the inclusion steps, thermodynamic kinetics and inclusion efficiency of inclusion complex formation of LOR with β-CD or HP-β-CD was quantitatively investigated by DSC and FT-IR microspectroscopy with curve-fitting analysis. The phase solubility profiles of LOR with β-CD and HP-β-CD were classified as A_L-type phase diagram. The grinding-induced reduction in LOR crystallinity in the presence of β-CD or HP-β-CD was found to be apparent zero-order kinetics. The inclusion efficiency of solid inclusion complex for LOR/β-CD or LOR/HP-β-CD was significantly correlated with the reduction in LOR crystallinity and the grinding time. The mechanism of inclusion complex formation for LOR/β-CD or LOR/HP-β-CD was proposed through the progressive reduction in LOR crystallinity, the promoted LOR amorphization, and molecular inclusion processes in the continuous energy input process of mechanical grinding.