炎痛喜康控释片在人体内的药动学研究

本文应用高效液相色谱法测定了8名健康受试者自身交叉服用炎痛喜康普通片与控释片(分别服用单剂量20mg)后的血药浓度。用非线性最小二乘模型嵌合的计算机程序对数据进行处理,表明该药在体内为一室模型,并求得各项参数如下:普通片,k_a=1.568h~(-1),k=0.0191h~(-1),V=7.9201,t_(max)=4.4h,C_(max)=2.502μg/ml,AUC=150.04h·μg/ml;控释片,ka=0.185h~(-1),k=0.0223h~(-1),V=7.3561,t_(max)=15.3h,C_(max)=2.048μg/ml,AUC=129.63h·μg/ml.     

Olopatadine hydrochloride suppresses the rebound phenomenon after discontinuation of treatment with a topical steroid in mice with chronic contact hypersensitivity

BACKGROUND: Olopatadine hydrochloride (olopatadine; Allelock) is one of the second-generation antihistamines that are treated for allergic disorders such as rhinitis, urticaria and eczema dermatitis. Olopatadine has recently been shown to have inhibitory effects on the chronic contact hypersensitivity induced by repeated application of oxazolone in mice. Although topical steroids have widely been prescribed for atopic dermatitis, a relapse often occurs within several days after discontinuation of their prolonged use. OBJECTIVES: We investigated the possible efficacy of olopatadine against the relapse after discontinuation of prolonged use of topical prednisolone in the Balb/c mice with oxazolone-induced chronic contact hypersensitivity. METHODS: Mice with the chronic contact hypersensitivity induced by repeated application of oxazolone were treated with olopatadine as a sequential therapeutic agent. The effects of olopatadine were quantified by measurements of ear-swelling, and levels of cytokines and histamine in the lesioned ear. Results Topical prednisolone (0.05 mg/ear/day) significantly inhibited the increases in ear swelling and production of IL-1beta, IL-4, IL-18, granulocyte-macrophage colony-stimulating factor (GM-CSF) and histamine. However, after discontinuation of the treatment with topical prednisolone, the inflammation relapsed and the IL-4 level exceeded the control one. The sequential treatment with olopatadine (10 mg/kg/day) after discontinuation of the treatment with topical prednisolone alone, or topical prednisolone with olopatadine, significantly inhibited the increases in ear swelling and levels of IL-1beta, IL-4, IL-18, GM-CSF, nerve growth factor and histamine. CONCLUSIONS: These results indicate that olopatadine is an antihistamine agent having inhibitory activities against the rebound phenomenon following the discontinuation of topical steroid therapy. Olopatadine is thus expected to be a sequential therapeutic agent after discontinuation of the chronic treatment with a topical steroid.     

盐酸丁卡因滴眼液的稳定性研究

目的 :考察 1 %盐酸丁卡因滴眼液的稳定性 ,确定其有效贮存期。方法 :采用经典恒温法预测其有效期。结果 :经典恒温法[1 ] 预测室温贮存期约为 2 0d ,冰箱贮存期约为 1 1 0d。结论 :该制剂对热不稳定 ,应冷藏。     

Sevelamer hydrochloride with or without alphacalcidol or higher dialysate calcium vs calcium carbonate in dialysis patients: an open-label, randomized study.

BACKGROUND: Sevelamer hydrochloride was recently proposed as a phosphate binder to prevent hypercalcaemia in place of calcium alkaline salts in dialysis patients. So far, it has been evaluated only in patients receiving calcitriol, without comparison with CaCO(3) alone, although the latter was found to be as effective as the combination of calcitriol and Al(OH)(3) in suppressing parathyroid hormone (PTH) without inducing hypercalcaemia and to have a better lowering effect on serum phosphate. Moreover, this bile salt binder may decrease serum 25-OH vitamin D. Therefore, we compared for 5 months two strategies for controlling moderate hyperparathyroidism: CaCO(3) alone vs sevelamer in conjunction with measures to increase calcium balance. METHODS: Forty-two patients were randomized: 21 continued their treatment with 4.8 g/day CaCO(3) and 21 were switched to sevelamer (initial dose: 2.4 g/day, increased to 4.4 g/day). Each month, when serum-corrected calcium decreased below 2.30 mmol/l, dialysate calcium was increased or alphacalcidol was given at each dialysis session, according to serum PO(4) levels. The following parameters were monitored: serum Ca, PO(4), bicarbonate and protein, weekly; and serum PTH, 25-OH vitamin D and total, LDL and HDL cholesterol monthly. RESULTS: Except for higher serum phosphate at month 1, lower serum bicarbonate at month 2 and lower LDL cholesterol at month 5 in the sevelamer group, no difference was found between the two groups. Compared with baseline levels, PTH increased and 25-OH vitamin D decreased significantly in both groups, these two parameters being inversely correlated. CONCLUSIONS: Given comparable control of plasma calcium, phosphate and 25-OH vitamin D, PTH control is comparable in both strategies. Sevelamer does not induce greater vitamin D depletion than CaCO(3). The transient decrease of serum bicarbonate after discontinuation of CaCO(3) in the sevelamer group suggests a less optimal prevention of acidosis. The sevelamer-induced decrease in LDL cholesterol gives this drug a potential advantage in cardiovascular prevention.     

盐酸三环哌酯在小鼠体内的药代动力学

目的研究抗胆碱新药盐酸三环哌酯（ＴＣＰＮ）在小鼠体内的药代动力学及组织分布。方法药代动力学采用放射受体分析法研究，组织中的分布用放射同位素分析法研究。结果小鼠ｓｃＴＣＰＮ后，血液中药物浓度的经时过程符合一级吸收二室模型（Ｔ１／２β为２．２８ｈ，Ｔｍａｘ为０．１２５ｈ，Ｃｍａｘ为３．４４μｇ·Ｌ－１，Ｃｌ为２３．０Ｌ·ｋｇ－１·ｈ－１）。小鼠ｓｃ［３Ｈ］－ＴＣＰＮ后，分布高峰放射性依次为肾＞肝＞脑＞颌下腺＞肠１９９８－０４－０３收稿，１９９８－０７－２６修回＊国家自然科学基金资助课题，Ｎｏ３９１３００９０－２作者简介：葛召恒，男，３２岁，硕士，助理研究员；阮金秀，男，６２岁，研究员，博士生导师，中国毒理学会副理事长，中国药理学会药物代谢专业委员会主任委员＞心＞肌肉，唯有脑组织的放射性以较高的水平维持较长的时间。预先给小鼠ｓｃ不同剂量的ＱＮＢ，可不同程度地降低脑中放射性的分布。结论ＴＣＰＮ从血中的消除较快，但在脑组织分布时间长，这与药物与脑中Ｍ受体的特异性结合有关。     

盐酸氯胺酮-β-环糊精包合物的研究

采用正交设计法对饱和水溶液法制备盐酸氯胺酮－β－环糊精包合物的温度、时间及投料比进行选优，显微观察包合物形态，UV和X－射线衍射法测试包合物晶形变化，品尝包合物味觉效果，并测定其稳定性及溶出度。结果表明，按1：2主客克分子比，于25℃电动搅拌3h，制备包合物的包合率和收率较高，包合物已形成一种新物相，具有稳定性高，无苦味及缓释性能。     

川芎嗪诱导大鼠骨髓间质干细胞分化为神经元样细胞的研究

目的用川芎嗪(ligustrazin hydrochloride)在体外定向诱导SD青年鼠骨髓间质干细胞(mesenchymal stem cells，rMSCs)分化为神经元样细胞。方法用低糖DMEM冲洗骨髓腔，收集骨髓细胞悬液，接种在塑料培养瓶中。经体外扩增、纯化，选用第5代后的骨髓间质干细胞进行诱导分化。用10μg／LbFcF预诱导24h，更换成含川芎嗪的无血清培养基DMEM诱导间质干细胞分化为神经元样细胞。用免疫组织化学SABC法鉴定神经丝蛋白(NF—M)、神经元特异性烯醇化酶(NSE)、巢蛋白(nestin)、微管联合蛋白-2(MAP-2)、生长相关蛋白-43(GAP-43)、胶质纤维酸性蛋白(GFAP)的表达。结果第5代间质干细胞形态达到均一，呈梭形。用川芎嗪诱导15min到3h，间质干细胞胞体逐渐增大，并伸出细长突起形似神经元样细胞。免疫组织化学显示NF-M、NSE、nestin、MAP-2和GAP-43表达阳性，而GFAP阴性。对照组上述染色均为阴性。结论川芎嗪可诱导骨髓间质干细胞分化为神经元样细胞。     

盐酸恩丹西酮缓释片的研制及体外释药特性

制备盐酸恩丹西酮缓释片并对影响释药的因素进行考察。以羟丙甲纤维素（HPMC）为骨架材料制备了盐酸恩丹西酮缓释片，通过正交设计试验优选最佳处方和工艺。对影响释药的因素，如HPMC的黏度和用量、填充剂的种类、制片工艺、润湿剂及释放介质pH等进行了考察。盐酸恩丹西酮缓释片体外释药符合Higuchi方程，HPMC的黏度、填充剂的种类及测定释放度的转速对该缓释片的释药几乎无影响，而制片工艺、润湿剂及释放介质pH值对缓释片释药影响较大。盐酸恩丹西酮缓释片在体外12h缓释效果较好。     

高效毛细管电泳法分离多巴胺和5-羟色胺

建立毛细管电泳分离分析多巴胺和 5一羟色胺的方法。采用自由区带电泳法 (CZE) ,4 0mmol/L硼砂缓冲液 2 0PSI气压进样 5s ,定电流 75 μA分离 10min ,二极管阵列PDA检测器检测 ,应用 2 0 0nm检测波长 ,结果显示两种物质完全分离。     

Structural studies on H-2Db and H-2Kd molecules indicate that murine major histocompatibility b and d haplotype alloantigens share structural features

Structural properties of the H-2D^b and H-2K^d murine major histocompatibility complex (MHC) antigens were examined by radiochemical methods. Radiolabelled preparations of the H-2D^b and H-2K^d antigens were obtained by indirect immune precipitation of NP-40 lysates of the lymphoid tumor cell lines EL-4 (H-2^b) and C14 (H-2^d), respectively. After preparation of the 37,000 molecular weight papain fragment the antigens were cleaved with CNBr. The H-2K^d antigen yielded four major CNBr fragments whereas the H-2D^b molecule provided six. These CNBr fragments were subjected to partial NH₂-terminal amino acid sequence analysis and aligned by homology to the H-2K^b glycoprotein. Comparison of the structural properties of the H-2K^d and H-2D^b molecules with previously published data on the other known major transplantation antigens of the b and d haplotypes (H-2K^b, H-2D^d and H-2L^d) reveal a marked structural similarity. First, the data show that certain methionine residues have been highly conserved and that cleavage by CNBr at these positions provides an initial strategy for the study of these molecules. Secondly, disulfide-linked peptides obtained after CNBr cleavage could be aligned and the data suggest the presence of disulfide bridges in homologous positions. Third, after CNBr cleavage both the H-2K^d and H-2D^b molecules yielded two glycopeptides which were homologous to glycopeptides from the H-2K^b molecule. Fourth, overall homology for a limited number of comparable positions is about 81% between the H-2K^b and H-2K^d gene products and 88% between the H-2K^b and H-2D^b gene products.