Solubilization and Stabilization of an Anti-HIV Thiocarbamate,NSC 629243, for Parenteral Delivery,Using Extemporaneous Emulsions

The O-alkyl-N-aryl thiocarbamate, I, (2-chloro-5-[[(l-methyl-ethoxy)thioxomethyl]amino]benzoic acid, 1-methylethylester, NSC 629243, also known as Uniroyal Jr.) is an experimental anti-HIV drug with very low water solubility (1.5 µg/mL). Early clinical studies required an injectable solution at 15 mg/mL, representing a solubility increase of 10⁴-fold. Adequate solubilization of this hydrophobic drug was achieved in 20% lipid emulsions. Extemporaneous emulsions were prepared by adding a concentrated drug solution to a commercially available parenteral emulsion. Various methods of preparation to minimize drug precipitation during its addition and enhance redissolution of precipitated drug were evaluated. The stability and mechanism(s) of decomposition of NSC 629243 in both 20% lipid emulsions and in natural oil vehicles were examined. In lipid emulsions, the shelf life at 25°C varied from 1 to >10 weeks, depending on the extent to which air was excluded from the preparation. The shelf life of 50 mg/mL solutions in natural oils at 25°C varied from <1 to >100 days depending on the oil and its supplier. A qualitative correlation was found between the initial rate of oxidation and the peroxide concentration in the oil. The primary degradation product in both systems was shown to be a disulfide dimer, II, formed via oxidation. Oxidation was inhibited by vacuum-sealing of emulsion formulations or incorporation of an oil-soluble thiol, thioglycolic acid (TGA), into oil formulations. TGA may inhibit oxidation by consuming free radicals or peroxide initiators or by reacting with the disulfide, II, to regenerate the starting drug.     

中药地榆的性状及显微鉴定

研究国内来源于地榆属8个不同种、变种与变型的地榆及2种混淆品的生药性状、组织构造及其粉末的鉴别特征,并分别列出生药性状、组织构造及粉末特征的检索表。     

甲状腺素在抗甲状腺药物治疗格雷夫斯病复发中的作用

目的：探讨格雷夫斯病（Graves,diseaes)经抗甲状腺药物（ATD）治疗后用甲状腺素减少复发的效果。方法：对新确立诊断的60例Graves病患者,在他巴唑治疗0．5年后,随机分为3组：A组：给予小剂量他巴唑加左旋甲状腺素（L－T4）50μg/d;B组：单纯小剂量他巴唑治疗;C组：同A组。治疗24个月后,A组停他巴唑,单用L－T4 50μg/d;B组继续以他巴唑维持量,C组他巴唑维持量加L－T4 50μg/d,半年后停药随访。结果A、C组TSAb;B组继续以他巴唑维持量,C组他巴唑维持量加L－T450μg/d,半年后停药随访。结果A、C组TSAb滴度较B组低,但3组停药1年内复发率差异无显著意义,分别为4／20,20％、5．20,25％和4／20,20％,结论他巴唑加用甲状腺素以及延长甲腺素的治疗,较单用巴唑治疗Graves病并不能更好地降低复发率,促甲状腺素受体抗体水平尚不足Graves病复发的惟一因素。     

环丙沙星与氧氟沙星联用抗结核药物肝毒性比较

目的　研究环丙沙星或氧氟沙星联用抗结核药的肝毒性并探讨其机制。方法　分别测定异烟肼和利福平联合用药 (IR)组及其分别联用氧氟沙星 (IRO)或环丙沙星 (IRC)组小鼠的血清谷氨酸氨基转移酶 (ALT)、肝指数、肝匀浆丙二醛 (MDA)含量、肝微粒体细胞色素P45 0和线粒体Ca2 ATP酶活性 ,及肝病理检查 ,结果与对照组以及实验组之间进行比较。结果　与正常对照组比较 ,IR组及IRO组的血清ALT、肝细胞匀浆MDA明显增高 (P <0 .0 5 ) ,而IRC组变化不大 (P >0 .0 5 ) ;同时发现IR组和IRO组的肝微粒体细胞色素P45 0含量较高和线粒体Ca2 ATP酶活性较低 ,而IRC组则相反 ;病理检查IRO和IRC组肝细胞坏死程度稍轻但与IR组比较无明显差异。结论　氧氟沙星、环丙沙星不增加异烟肼和利福平联用肝毒性 ,且环丙沙星有一定的拮抗作用。     

女性输卵管结扎术后腰痛病机及医疗体育疗法

对女性输卵管结扎术后腰痛进行调查和病理分析 ,以中药配合医疗体育康复治疗术后腰痛 ,取得较好疗效 ,并提出预防措施。     

脂肝清对高胆固醇血症家兔模型脂质代谢影响的实验研究

目的: 明确中药脂肝清对高脂血症防治作用,探讨其作用机制。方法: 以饲喂高脂饲料复制高胆固醇血症家兔模型,观察血清和肝脂质代谢,并且采用脂肝清进行预防实验,同时与一类降脂药洛伐他汀 (Lovastatine)作对照。结果: 1)中药明显降低血清TC、LDL C、TC/HDL C比值 (P<0.01或P<0.05),降低血清氨基转移酶活力 (P<0.01).2)中药明显降低肝TC、TG及LDL C含量。结论: 脂肝清具有调整血清脂质代谢,促进肝组织中脂质的排泄及保护肝功能等作用。     

脾虚证与益气健脾治疗对T、B淋巴细胞活性影响的实验观察

为探讨脾虚证机体特异性免疫应答的变化及益气健脾中药的影响,采用利血平注射法复制脾虚证模型,观察分别代表细胞与体液免疫功能的T、B淋巴细胞活性变化、血清IgG,IgM的水平及益气健脾基本方剂四君子汤对它们的影响,结果脾虚证模型大鼠T细胞转化率及B细胞分泌的IgM水平显著降低,通过灌服四君子汤可明显预防两者的降低,因而认为脾虚证细胞与体液免疫均降低,而以细胞免疫的降低为主,益气健脾中药具有明显防治作用。     

蒙药广枣总黄酮对大鼠离体心脏功能的影响

目的：探讨广枣总黄酮(TFC)对心功能的影响。方法：采用Langendorff灌流法．用多导生理记录仪测定大鼠离体心脏的心率、心肌收缩力及心电图的变化。结果：TFC使正常灌流的大鼠离体心脏心电图的P—R问期延长．心率减慢．心肌收缩力增强;对缺氧灌流所导致的心率减慢和心脏收缩力减弱均呈明显的对抗作用。结论：TFC可改善心功能。     

临床常用药物对人体酸碱平衡的影响

目的：探讨临床常用药物对人体酸碱平衡的影响,指导临床工作。方法：用酸度计测定九种药品ｐＨ值,计算氢离子浓度。结果：偏碱性的药物有５０ｇ／Ｌ碳酸氢钠,谷氨酸钠、谷氨酸钾注射液;偏酸性的药物有盐酸精氨酸、维生素Ｃ、各种浓度葡萄糖注射液、氯化钠注射液。结论：临床上一些常用药品会影响人体的酸碱平衡,尤其在机体酸碱平衡调节发生障碍的情况下,更应谨慎。     

朱丹溪善用风药治疗血证谈

复习朱丹溪有关医学文献 ,阐发其应用风药治疗血证的机制 ,主要有 :风药直接止血 ;风药升阴散火止血 ;风药散火解毒、凉血止血 ;风药炒黑止血 ;风药振脾益气止血 ;祛除致病因素 ;其它。