表面活性剂泊洛沙姆188临界胶束浓度的模拟计算

建立了一种介观模拟计算表面活性剂临界胶束浓度(CMC)的方法。以非离子表面活性剂泊洛沙姆188为研究对象,计算了其在298K下的临界胶束浓度(CMC),分析了泊洛沙姆188在水中相行为和有序参数的变化,为表面活性剂增溶作用的研究提供了基础。     

表面活性剂泊洛沙姆188临界胶束浓度的模拟计算

建立了一种介观模拟计算表面活性剂临界胶柬浓度（CMC）的方法。以非离子表面活性剂泊洛沙姆188为研究对象，计算了其在298K下的临界胶束浓度（CMC），分析了泊洛沙姆188在水中相行为和有序参数的变化，为表面活性剂增溶作用的研究提供了基础。     

Improved solubility and in vitro dissolution of Ibuprofen from poloxamer gel using eutectic mixture with menthol

To improve the solubility and in vitro dissolution of poorly water-soluble ibuprofen with poloxamer and menthol, the effects of menthol and poloxamer 188 on the aqueous solubility of ibuprofen were investigated. The dissolution study of ibuprofen delivered by poloxamer gels composed of poloxamer 188 and menthol were performed. In the absence of poloxamer, the solubility of ibuprofen increased until the ratio of menthol to ibuprofen increased from 0:10 to 4:6, followed by an abrupt decrease in solubility above the ratio of 4:6, indicating that 4 parts of ibuprofen formed eutectic mixture with 6 parts of menthol. In the presence of poloxamer 188, the solutions with the same ratio of menthol to ibuprofen showed abrupt increase in the solubility of ibuprofen. Furthermore, the solution with ratio of 4:6 showed more than 2.5- and 6-fold increase in the solubility of ibuprofen compared with that without poloxamer and that without menthol, respectively. The poloxamer gel with menthol/ibuprofen ratio of 1:9 and higher than 15% poloxamer 188 showed the maximum solubility of ibuprofen, 1.2 mg/ml. Menthol improved the dissolution rates of ibuprofen from poloxamer gels. Dissolution mechanism showed that the dissolution rate of ibuprofen from the poloxamer gels without menthol was independent of the time, but the drug might be dissolved from the poloxamer gels with menthol by Fickian diffusion. Thus, the poloxamer gels developed using eutectic mixture with menthol, which gave the improved solubility and dissolution of drug, are potential candidates for ibuprofen-loaded transdermal and rectal delivery system.     

巴洛沙星眼用原位凝胶的制备及质量控制

目的：建立巴洛沙星眼用原位凝胶剂的制备及质量控制方法。方法：以泊洛沙姆407为基质,卡波姆940为增稠剂,尼泊金乙酯为抑茵荆,氯化钠为渗透压调节剂,制备巴洛沙星眼用原位凝胶剂;采用HPLC法测定含量。结果：巴洛沙星浓度在5．0～50．0μg·ml^-1范围内线性关系良好（r=0．9996）,平均回收率为100．6％（RSD=1．41％）;家免眼刺激性实验表明本制剂无刺激性,符合《中国药典》对眼用制剂的质量要求。结论：该制剂处方设计合理,制备方法简便,含量测定方法适用于本品质量控制。     

温度敏感型盐酸小檗碱眼用原位凝胶的制备研究

目的 制备温度敏感型盐酸小檗碱眼用原位凝胶.方法 以泊洛沙姆407和188为温敏材料,采用搅拌子法测定溶液-凝胶相转变温度优化处方;采用高效液相色谱法测定盐酸小檗碱.结果 温度敏感型原位凝胶的胶凝温度随泊洛沙姆407浓度增大而降低,随泊洛沙姆188浓度增加先升高后降低,模拟泪液的稀释可使胶凝温度升高,建立了泪液稀释后相变温度与泊洛沙姆浓度的拟合方程,经Design-Expert软件优化盐酸小檗碱温敏型眼用原位凝胶的处方为25%泊洛沙姆407和4.19%泊洛沙姆188;优化处方在29.7℃为自由流动的液体,泪液稀释后在34.5℃能够发生相变形成凝胶.结论 该眼用温度敏感凝胶符合眼部应用要求,体现出良好的眼部应用前景.     

新型药用辅料—泊洛沙姆407急性毒性初步研究

目的：了解泊洛沙姆407的急性毒性作用。方法：泊洛沙姆407凝胶昆明小鼠腹腔注射（ip），观察小鼠死亡率及血丙氨酸转移酶（ALT）、尿素氦（BUN）、总胆固醇（CH）及甘油三酯（TG）含量变化。结果：中、小剂量泊洛沙姆407小鼠ip对ALT、BUN无明显影响，但可致血脂一过性增高；小鼠ip25％泊洛沙姆407凝胶5．0g／kg，死亡率为50％。结论：泊洛沙姆407是一个毒性较低的药用辅料。     

Modification of the Copolymers Poloxamer 407 and Poloxamine 908 can Affect the Physical and Biological Properties of Surface Modified Nanospheres

Purpose. To investigate the effects of the modification of the copolymers poloxamer 407 and poloxamine 908 on the physical and biological properties surface modified polystyrene nanospheres. Methods. A method to modify poloxamer 407 and poloxamine 908, introducing a terminal amine group to each PEO chain has been developed. The aminated copolymers can be subsequently radiolabelled with lodinated (I¹²⁵) Bolton-Hunter reagent. The aminated copolymers were used to surface modify polystyrene nanospheres. The physical and biological properties of the coated nanospheres were studied using particle size, zeta potential, in vitro non-parenchymal cell uptake and in vivo biodistribution experiments. Results. The presence of protonated amine groups in the modified copolymers significantly affected the physical and biological properties of the resulting nanospheres, although the effects were copolymer specific. The protonated surface amine groups in both copolymers reduced the negative zeta potential of the nanospheres. Acetylation of the copolymer's free amine groups resulted in the production of nanospheres with comparable physical properties to control unmodified copolymer coated nanospheres. In vivo, the protonated amine groups in the copolymers increased the removal of the nanospheres by the liver and spleen, although these effects were more pronounced with the modified poloxamer 407 coated nanospheres. Acetylation of the amine groups improved the blood circulation time of the nanospheres providing modified poloxamine 908 coated nanospheres with comparable biological properties to control poloxamine 908 coated nanospheres. Similarly, modified poloxamer 407 coated nanospheres had only slightly reduced circulation times in comparison to control nanospheres. Conclusions. The experiments have demonstrated the importance of copolymer structure on the biological properties of surface modified nanospheres. Modified copolymers, which possess comparable properties to their unmodified forms, could be used in nanosphere systems where antibody fragments can be attached to the copolymers, thereby producing nanospheres which target to specific body sites.     

Poloxamer 188对关节软骨加压负重后软骨细胞损伤的干预

目的 通过给正常人离体膝关节软骨体外加压负重,同时应用细胞表面活性剂Poloxamer 188的体外实验,探讨Poloxamer 188对钝性损伤时膝关节软骨的保护作用. 方法 将正常人离体膝关节软骨块样本分为正常对照组(n=6),非加压负重;非治疗组(n=12),加压负重;治疗组(n=12),加压负重后加Poloxamer 188.非治疗组和治疗组的样本加压负重570 N(20 MPa)的载荷.关节软骨加压负重后,各组中一半的标本在加压负重后1 h通过荧光染色观察,应用图像分析软件计算浅层软骨细胞(软骨全层的20%)的生存率.各组中剩下的一半标本用DMEM缓冲液依次漂洗3次,继续培养至加压负重后24 h.24 h后同样通过荧光染色观察,应用图像分析软件计算浅层软骨细胞(软骨全层的20%)的生存率. 结果 加压负重后软骨块中软骨细胞的存活率急剧下降.加压负重后软骨块中软骨细胞的坏死在浅层十分明显.非治疗组浅层软骨细胞存活率在第1小时和第24小时分别为55%和38%.与非治疗组相比,钝性损伤后治疗组的浅层细胞生存率在第1小时和第24小时显著增长为76%和57%(P<0.05). 结论 Poloxamer 188对浅层软骨细胞有一定的保护作用.利用Poloxamer 188早期干预软骨细胞的损伤,可能对延缓创伤后继发性关节炎的发病有一定的意义.     

新目安眼用即型凝胶与普通凝胶兔眼内药动学特性比较研究

目的 探索新目安眼用即型凝胶相变过程对兔眼内房水中药物药动学特性的影响，并与普通凝胶比较，评价该即型凝胶的剂型特征。方法 以新西兰家兔为试验对象，采用眼部给予新目安眼用即型凝胶（存在相变过程）和普通凝胶后，按时间点取房水，测定更昔洛韦含量，建立药物在房水中的药动学方程，计算体内药动学参数，比较两者的差别。结果 新目安眼用即型凝胶房水中更昔洛韦药动学方程为C=18.94×e^{-0.015 4 t}-18.94×e^{-0.079 85 t}，普通凝胶房水中更昔洛韦药动学方程为C=15.42×e^{-0.015 3 t}-15.42×e^{-0.048 8 t}，说明两者在兔眼内的药动学机制相同。从各药动学参数比较分析，新目安眼用即型凝胶由于相变过程使达峰时间仅为25.51 min，达峰浓度高达10.31 μg·mL^-1，吸收半衰期缩短为8.679 min，AUC提高到992.4 μg·mL^-1·min，而普通凝胶达峰时间为34.63 min，达峰浓度仅为6.232 μg·mL^-1，吸收半衰期为14.20 min，AUC仅为691.4 μg·mL^-1·min。结论 即型凝胶相转变过程能将相变潜能（△H）转变成药物角膜渗透的动能，可最大限度发挥药效。     

温敏凝胶中尼美舒利含量测定及稳定性研究

目的：建立温敏凝胶中尼美舒利的含量测定方法并考察其各种条件下的稳定性。方法：采用HPLC法,色谱柱为岛津Shim-Pack C18-ODS柱（150 mm×4.6 mm,5μm）,甲醇-水-冰醋酸（65∶35∶0.8）为流动相,流速为1.0 ml·min^-1;检测波长：299 nm;柱温：30℃,进样量为10μl。结果：凝胶中尼美舒利与各杂质及降解产物分离良好,在2.43-24.37μg·ml^-1范围内线性关系良好（r=0.999 8）,平均回收率为100.02%（RSD=1.12%,n=5）。最低检测限为0.098μg·ml^-1,最低定量限为0.25μg·ml^-1。强光照射试验、破坏性试验及长期稳定性试验结果表明,尼美舒利温敏凝胶长期稳定性良好,但在高温碱性、高温酸性、高温强氧化溶液和强光照条件下不稳定。结论：该方法可用于温敏凝胶中尼美舒利含量测定及稳定性研究,方法准确、可靠。制剂对热和光照的稳定性较差,宜阴凉避光保存。