单克隆抗体—表阿霉素免疫偶合物的制备和体外活性

用双功能试剂己二酰肼制备腙键连接的聚谷氨酸—表阿霉素,通过控制交联条件,所得产物克服了大分子自身交联的缺点,交联率较高。聚谷氨酸的载药量与分子量呈正比,平均每8～11个谷氨酸单体连接1分子表阿霉素。分子量为14300的聚谷氨酸做载体其载药量为1:11,与单抗交联所得的偶合物McAb:PGA:PAR为1:2:22。偶合物较好地保留了抗体活性,体外细胞毒性较游离药物略有下降,但表现出单抗介导的靶细胞选择性杀伤作用。本研究用腙键交联法成功地制备了药/抗比高且体外有效的免疫偶合物,为进一步制备细胞靶向的肿瘤化疗制剂奠定了基础。     

从青霉素G生产7-氨基脱乙酰氧基头孢烷酸

综述了以青霉素Ｇ钾为原料经氧化,酯化,扩环,水解,脱苯乙酰基等反应制备了７－氨基脱乙酰氧基头孢烷酸的合成工艺。     

丹红注射液中迷迭香酸、紫草酸、丹酚酸B在大鼠血浆中的浓度测定

目的:建立测定大鼠血浆中丹红注射液中迷迭香酸、紫草酸、丹酚酸B浓度的方法。方法:采用HPLC法,色谱柱为Diamonsil C18柱(250 mm×4.6 mm5,μm);流动相为乙腈-0.4%的磷酸水,梯度洗脱;流速为1.0 mL.min-1;检测波长为288 nm。结果:迷迭香酸在4.0～100.0μg.mL-1浓度范围内线性关系良好(r=0.9925);回收率在85.0%～101.4%之间,日内、日间RSD<8%;紫草酸在4.0～100.0μg.mL-1浓度范围内线性关系良好(r=0.991 1);回收率在84.4%～93.9%之间,日内、日间RSD<9%;丹酚酸B在2.0～200.0μg.mL-1浓度范围内线性关系良好(r=0.998 6);回收率在80.0%～97.4%之间,日内、日间RSD<5%。结论:本文所建立的方法灵敏度好、准确率高,可用于丹红注射液中迷迭香酸、紫草酸、丹酚酸B的药代动力学研究。     

S-腺苷蛋氨酸联合熊去氧胆酸治疗妊娠期肝内胆汁淤积症的临床疗效及对肝功能、炎症因子的影响

目的 探讨S-腺苷蛋氨酸联合熊去氧胆酸治疗妊娠期肝内胆汁淤积症（ICP）的临床疗效及对肝功能、炎症因子的影响。方法 将100例ICP患者随机分为2组各50例,对照组仅予熊去氧胆酸单药治疗,观察组在对照组的基础上联用S-腺苷蛋氨酸治疗。比较两组治疗前后的瘙痒评分、肝功能指标、血清白介素-12（IL-12）和IL-18水平变化及妊娠结局。结果 治疗后观察组瘙痒评分明显低于对照组,差异有统计学意义（P<0.05）。观察组血清总胆红素（TBIL）、总胆汁酸（TBA）、丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）水平明显低于对照组,差异有统计学意义（P<0.05）;白细胞介素（IL）-12、IL-18水平明显低于对照组,差异有统计学意义（P<0.05）。观察组早产、羊水污染Ⅱ度、新生儿Apgar评分≤ 7分的发生率明显低于对照组,差异有统计学意义（P<0.05）。结论 S-腺苷蛋氨酸联合熊去氧胆酸治疗ICP疗效优越,可显著改善患者的肝功能及血清炎症因子水平,改善妊娠结局。     

RP-HPLC法测定中药茯苓皮中茯苓酸A和3-表去氢土莫酸的含量

目的：建立一种可用于评价茯苓皮药材质量的含量测定方法。方法：采用Dikma Dimonsal C18色谱柱（250mm×4.6mm,5μm）,以0.1％甲酸水溶液和乙腈为流动相,流速：1.0mL·min^-1,检测波长：243nm,柱温：25℃,用梯度洗脱法同时测定茯苓皮药材中茯苓酸A和3-表去氢土莫酸的含量。结果：测得茯苓酸A和3.表去氢土莫酸的线性范围分别为0.073-0.292g·L^-1（r=0.9997）和0.027—0.135g·L^-1（r=0.9999）;加样回收率分别为102.63％和98.88％。结论：该法能快速、准确地测定茯苓皮中两个活性成分的含量,为茯苓皮的质量控制提供了一个较好的检测方法。     

银杏叶提取物中银杏酸的HPLC测定

建立了HPLC法检测银杏叶提取物中银杏酸含量的方法。银杏叶提取物以氯仿萃取，无水硫酸钠干燥后浓缩，残留物溶于甲醇后进行HPLC分析。采用Hypersil C18柱，柱温为30℃，流动相为甲醇—水—冰醋酸(85：14．5：0．5)，检测波长为311nm。银杏酸在2—32μg／m1浓度范围内线性关系良好(r＝0．9999)，平均回收率为99．4％，RSD为1．2％，检测限为5ng。     

卤虫卵油脂肪酸组成分析及α-亚麻酸含量测定

目的采用毛细管气相色谱法分析卤虫卵油的脂肪酸主要组成并建立测定卤虫卵油中α-亚麻酸含量的方法。方法采用DB-WAX毛细管柱;程序升温:起始温度150℃,升温速率3℃.min-1,结束温度240℃,保持10 min;氢焰离子化检测器温度250℃。结果卤虫卵油中不饱和脂肪酸占总脂肪酸质量分数超过70%,其中油酸、α-亚麻酸质量分数分别为26.9%、27.7%。α-亚麻酸甲酯质量在0.719～3.60μg内线性关系良好(r=0.999 8,n=5),平均回收率为101.6%,RSD=2.3%。结论毛细管气相色谱法可作为卤虫卵油α-亚麻酸的含量测定方法。     

In vitro effects of active components of Polygonum Multiflorum Radix on enzymes involved in the lipid metabolism

Ethnopharmacology relevance

Raw and processed Polygoni Multiflori Radix (PMR and PMRP) are used in the prevention and treatment of non-alcoholic fatty liver disease (NAFLD), hyperlipidemia or related diseases. In our previous research, 2, 3, 5, 4′-tetrahydroxy-stilbene-2-O-β-d-glucoside (TSG) displayed the most important role in the total cholesterol (TC) lowering effect among all the chemical constituents of Polygonum multiflorum. Emodin and physcion displayed more favorable triglyceride (TG) reducing effects than TSG. However, there are few researches focus on the approach and mechanism of how do Polygonum multiflorum exhibit good lipid regulation activity. The targeted sites of active substances of Polygonum multiflorum are still not clearly elucidated. This research pays close attention to how major chemical components of Polygonum multiflorum affect the TC and TG contents in liver cells.

Materials and methods

In this research, a sensitive, accurate and rapid in vitro model, steatosis hepatic L02 cell, was used to explore target sites of active chemical substances of Polygonum multiflorum for 48 h. Steatosis hepatic L02 cell was exposed to emodin, physcion and TSG, respectively. The contents of four key enzymes in the pathway of synthesis and decomposition of TC and TG were investigated after exposure. Meanwhile, the contents of lipid transfer protein were also tested. The diacylgycerol acyltransferase 1 (DGAT1) controlled the biosynthesis of TG from free fatty acids while 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase) limited the biosynthesis of TC. Hepatic triglyceride lipase (HTGL) and cholesterol 7α-hydroxylase (CYP7A) played the key role in the lipolysis procedure of TG and TC.

Results

The synthesis of TC and TG in steatosis L02 cells were apparently increased in the model group compared to the control group. Intracellular contents of HMG-CoA reductase and DGAT1 increased 32.33% and 56.52%, while contents of CYP7A and HTGL decreased 21.61% and 47.37%. Emodin, physcion and TSG all showed down-regulation effects on HMG-CoA reductase, while up-regulation effects on CYP7A. The most remarkable effect on HMG-CoA reductase was found on emodin. Emodin could reduce the DGAT1 content from 438.44±4.51 pg/mL in model group to 192.55±9.85 pg/mL (100 μm). The content of HTGL in 300 μm physcion group was 3.15±0.15 U/mL, which was more significantly effective than the control, lovastatin and fenofibrate group.

Conclusions

TSG could raise the content of CYP7A and then promote the lipolysis of cholesterol. Moreover, TSG also showed the best LDL-reducing effect. Emodin could inhibit HMG-CoA reductase and DGAT1, which were key enzymes in the synthesis of TC and TG. Physcion increased the content of HTGL, and then could boost the lipolysis of triglyceride. At the same time, physcion showed the best VLDL-reducing effect. In view of the above conclusions, we contributed the lipid regulation activity to an overall synergy of TSG, emodin and physcion.     

杨振国教授术柏痛风汤治疗痛风52例

[目的]观察杨振国术柏痛风汤治疗痛风疗效。[方法]将52例痛风使用术柏痛风汤,1剂/d,早晚各1次,水煎服。15d为1疗程。治疗3个疗程进行疗效判定。[结果]临床治愈32例,显效11例,有效5例,无效4例,总有效率为92.31%。[结论]术柏痛风汤治疗痛风疗效满意,值得推广。     

丹参胶囊的系统稳定性考察

目的:制备丹参提取物和丹参胶囊,研究二者在高湿、高温和光照条件下的稳定性,并考察丹参胶囊及相关物料的吸湿特性。方法:采用UPLC测定丹参素、迷迭香酸、紫草酸和丹酚酸B的含量,流动相0. 05%磷酸水溶液(A)-乙腈(B)梯度洗脱(0～2 min,93%～79. 2%A; 2～6 min,79. 2%～75%A; 6～9 min,75%～65%A; 9～10. 5 min,65%～10%A; 10. 5～11 min,10%～93%A),流速0. 4 mL·min~(-1),检测波长280 nm。通过测定丹参胶囊及相关物料的吸湿增重,绘制吸湿等温曲线,测算临界相对湿度(CRH)。结果:丹参提取物和丹参胶囊分别在温度40℃,相对湿度75%和92. 5%,光照强度(4 500±500) Lx条件下放置10 d后,4个酚酸成分含量波动均在±10%以内,无明显变化趋势;高温60℃条件,二者中的丹参素变化率分别为47. 45%和32. 24%,丹酚酸B变化率分别为-6. 39%和-9. 64%。吸湿性考察显示,淀粉基丸CRH=58. 5%,丹参提取物CRH=72. 34%,包衣丸CRH=72. 85%,丹参胶囊CRH=73. 55%。结论:高温环境会影响丹参提取物和丹参胶囊中酚酸类指标成分的稳定性,为确保丹参提取物及丹参胶囊质量稳定,应避免高温环境。为防止丹参胶囊及其相关物料过度吸湿,淀粉基丸、丹参提取物、丹参包衣丸和丹参胶囊的生产、贮存环境中相对湿度应控制在相应CRH以下。