莫西克汀是一种大环内酯类抗寄生虫药,通过一系列过程阻断神经递质的传递,致使寄生虫长期麻痹而死亡,综述了合成路线及药物应用研究,展望了莫西克汀药物的未来发展趋势.

奥拉替尼(Oclacitinib)是一种新型、高效的非受体络氨酸激酶(JAK)抑制剂,用于控制犬类的过敏性皮肤病引起的瘙痒.综述了近年来奥拉替尼的研究进展,介绍和评述了合成路线及方法、药物应用研究.展望了奥拉替尼药物未来的发展趋势.

异噁唑啉类药物是一种新型杀虫剂,主要用于犬和猫体外寄生虫的预防与治疗.目前已上市的异噁唑啉类药物有:Fluralaner、Sarolaner、Afoxolaner和Lotilaner.对以上四种药物的合成方法进行概述.并总结了这些合成方法的优缺点.为该类药物的工业化生产提供一定的参考依据.

对加米霉素合成工艺进行了优化.(E)-红霉素A肟在氢氧化锂存在下于异丙醇中经异构化得(Z)-红霉素A肟,以THF作溶剂,在冰水浴条件下与对甲苯磺酰氯的丙酮溶液反应,然后经异丙醇重结晶得重排产物9-脱氧-12-脱氧-9,12-亚胺醚-8a,9-二脱氢-8a-氮杂-8a-红霉素A,纯度90％.在甲醇-水中经硼氢化钠还原得9-脱氧-8a-氮杂-8a-同型红霉素A,纯度94％.最后在钯炭催化下与丙醛经还原烃化得目标化合物,纯度99.6％,总收率30.7％.优化后的工艺反应条件温和、操作便捷,且各中间体均采用重结晶精制,质量便于控制,适合工业化生产.

建立了加米霉素对照品的标定方法.采用紫外光谱、红外光谱、核磁共振波谱、质谱和X射线单晶衍射进行结构确认,高效液相色谱法进行纯度检查,质量平衡法进行定量分析,并采用定量核磁技术对赋值结果进行验证.结果显示,加米霉素对照品原料纯度为99.9％;质量平衡法赋值结果为98.8％,定量核磁共振法验证结果为98.3％.加米霉素对照品原料定量赋值结果准确、可靠,能够用于加米霉素原料及制剂的鉴别和含量测定.

[目的]建立用HPLC测定加米霉素含量的方法.[方法]采用高效液相色谱法,色谱柱为XBridge C18柱(250 mm×4.6 mm,5μm),流动相为磷酸盐缓冲液(取0.05 mol/L磷酸氢二钾溶液,用稀磷酸调节pH至8.0)-乙腈(30:70),流速为1.0 mL/min,柱温为30℃;检测波长为205 nm.[结果]加米霉素在0.4984～1.9936 mg/mL(r=0.9999)峰面积与浓度呈良好的线性关系,平均加样回收率为99.2％,RSD=0.6％.[结论]该方法重复性良好,能准确测定加米霉素的含量.

[目的]建立加米霉素原料药中丙醛、丙酮、乙腈、乙酸乙酯、正庚烷和吡啶6种溶剂残留的检测方法.[方法]采用气相色谱法,色谱柱为DB-624(30 m×0.32 mm×1.8μm);采用氢火焰离子化检测器(FID),温度250℃,载气为N2;程序升温,流速为1.2 mL/min.[结果]丙醛、丙酮、乙腈、乙酸乙酯、正庚烷和吡啶在各自浓度范围内线性关系良好,检测限分别为1.7、5.0、4.1、5.0、1.7和2.0 ng,平均加样回收率为99.1％～103.0％.[结论]该方法适用于加米霉素原料中溶剂残留的检测.

为了评价加米霉素的急性毒性及其对6种呼吸系统病原菌的体外抑菌活性,试验采用改良寇氏法测定了加米霉素对小鼠的半数致死量(LD50),采用肉汤微量稀释法评价了加米霉素对多杀性巴氏杆菌CVCC399、猪链球菌CVCC556、金黄色葡萄球菌CVCC26033、副猪嗜血杆菌5型、胸膜肺炎放线杆菌CVCC262、支气管败血波氏杆菌Bb-3的体外抗菌活性.结果 表明:小鼠腹腔注射加米霉素的LD5o为1 086 mg/kg,属于低毒性药物;加米霉素对6株菌的最低抑菌浓度(MIC)值为0.031 25～1μg/mL之间,具有很好抗菌活性.

参照《中华人民共和国兽药典》2015版(后简称兽药典)一部附录200页细菌内毒素检查法的有关规定,对加米霉素注射液内毒素限度及检查方法进行了研究.结果显示,加米霉素注射液在0.075～0.3mg/mL时对鲎试剂无增强或抑制作用,产品内毒素含量均小于限定值125EU/mL,符合规定.通过试验研究,建立了加米霉素注射液的内毒素检查方法,且采用凝胶法对其进行细菌内毒素检查是可行的.

通过对复方磺胺嘧啶混悬液的辅料及分散工艺进行研究,确定了复方磺胺嘧啶混悬液的制备工艺.选择0.4%的羧甲基纤维素钠作为助悬剂;确定了2.5%的柠檬酸钠作为反絮凝剂;确定了高剪切作为分散工艺,最终确定了复方磺胺嘧啶混悬液的制备工艺.将产品按照质量标准进行检测,结果符合规定.

Gamithromycin is a novel semisynthesis macrolide for animals,which has curative effects on prevention and treatment of bovine respir-atory disease,and has wide application and development prospects .In this research,the physic-chemical properties,synthesis conditions and phar-macological activities were reviewed,which aimed at providing reference for clinical veterinary application.

To optimize the mechanochemical assisted extraction of purple lilac glucoside from Manyprickle Acanthopanax, water, ethyl alcohol, methanol heat reflux and mechanochemical assisted extraction were compared and HPLC was used to assay the content of purple lilac glucoside. The result showed that the optimum extraction condition is mechanochemical assisted extraction. Purple lilac glucoside was classified, but also other effectives were separated effectively, thereby minimize the interference of other active ingredients. The product quality is stable, environment-friendly and provide the extraction method of purple lilac glucoside from Manyprickle Acanthopanax.

To study the best extraction process of Qinhuang granules,the obtaining rate of extraction and the ephedrine content were taken as indexes for the water extraction process of ephedrae herb,and the obtaining rate of extraction,the baicalin content and the glycyrrhizic acid content as indexes for the water decoction extraction process of scutellariae radix,glycyrrhizae radix,radix sophorae tonkinensis,platycodon grandiflorum and indigowoad root.The extraction process of Qinhuang granules was optimized by orthogonal design. The optimal conditions for the water extraction of Ephedrae Herba was 8- fold amount of water,reflux 6 h( ≤ 70 ℃). The optimal conditions of Scutellariae Radix,glycyrrhizae radix,radix sophorae tonkinensis,platycodon grandiflorum and indigowoad root was10- fold amount of water,reflux 4 h( 70 ℃). The extracting method is reasonable,stable,and suitable for industrialized production.