Aim To develop pluronic F127 （PF127） based formulations of penciclovir （PCV） aimed at enhancing its ocular bioavailability. Methods Thermosensitive in situ gels of penciclovir were prepared through combination of ...Aim To develop pluronic F127 （PF127） based formulations of penciclovir （PCV） aimed at enhancing its ocular bioavailability. Methods Thermosensitive in situ gels of penciclovir were prepared through combination of HPMC K4M or carbopol 934P and pluronic F127. Optimized formulations were examined through measuring gelation temperature, rheology speciality, drug release behavior, pharmacokinetics and ocular irritation. Results The gelation temperature was reduced by adding HPMC K4M or carbopol 934P, and the viscosity was enhanced slightly. Either HPMC K4M or carbopol 934P delayed the release of PCV from in situ gel. PCV was released by non-Fickian diffusion. The study of ocular irritation for different PCV formulations did not show any irritation or damage for the cornea. PCV bioavailability from combination of carbopol 934P and pluronic F127 gels was higher than that obtained from any other gels. Conclusion Pluronic F127 formulations of PCV can be used as liquid for administration by instilling into the eye. Facilitated by the appropriate eye temperature, the formulations were transformed to gel phase. On the basis of in vitro and in vivo results, PCV formulations containing HPMC K4M or carbopol 934P and low concentration of pluronic F127 （12%） showed potential for use as a drug delivery system with improved ocular bioavailability.展开更多
Solubility of 2-amino-6-chloropurine in Mitsunobu solvents could be significantly improved after its exocyclic amino group is protected via N-tert-butoxycarbonylation.The bis-Boc protected 2-amino-6-chloropurine also ...Solubility of 2-amino-6-chloropurine in Mitsunobu solvents could be significantly improved after its exocyclic amino group is protected via N-tert-butoxycarbonylation.The bis-Boc protected 2-amino-6-chloropurine also shows excellent activity and N9 selectivity in the coupling with various alcohols by a Mitsunobu reaction.Then,a new practical and efficient method is established for the synthesis of penciclovir(PCV) from bis-Boc-2-amino-6-chloropurine 9 and the side chain of 5-(2-hydroxyethyl)-2,2-dimethyl-1,3-dioxane 5—the latter being a more easily prepared cyclic precursor of the diacetate side chain used in the conventional process.The coupling of 9 with 5 proceeded regioselectively at a N9 position of purine derivative for a good yield under Mitsunobu conditions.展开更多
目的:基于二维高效液相色谱-四极杆-飞行时间串联质谱技术(2D-LC-Q TOF/MS),鉴定喷昔洛韦乳膏有关物质的结构。方法:采用ODS(250 mm×4.6 mm, 5μm)色谱柱,以0.15%甲酸10 mmol·L^(-1)甲酸铵缓冲溶液-乙腈为流动相,进行一维梯...目的:基于二维高效液相色谱-四极杆-飞行时间串联质谱技术(2D-LC-Q TOF/MS),鉴定喷昔洛韦乳膏有关物质的结构。方法:采用ODS(250 mm×4.6 mm, 5μm)色谱柱,以0.15%甲酸10 mmol·L^(-1)甲酸铵缓冲溶液-乙腈为流动相,进行一维梯度洗脱,对喷昔洛韦乳膏及其依照ICH原则强制降解样品的有关物质进行分离,并分别富集各有关物质;再采用Phenomenex Luna SCX(250 mm×4.6 mm, 5μm)色谱柱,以0.1%甲酸20 mmol·L^(-1)甲酸铵缓冲溶液-乙腈为流动相,进行二维梯度洗脱,实现各有关物质与喷昔洛韦乳膏基质的良好分离。利用电喷雾正离子化-四极杆-飞行时间串联质谱高分辨测定各有关物质母离子及其子离子的准确质量和元素组成,并解析鉴定其结构。结果:在所建立的2D-LC-Q TOF/MS分析条件下,喷昔洛韦与其有关物质分离良好,检测出喷昔洛韦乳膏及其强制降解样品中21个主要有关物质。根据其色谱保留行为、光谱特征、质谱特征及与其他核苷类药物已知有关物质的差异,结合合成和制剂工艺路线分析,可鉴定出它们的结构,它们均为首次被鉴定出的有关物质。结论:研究结果为喷昔洛韦乳膏的质量控制提供了参考依据。展开更多
目的:探究喷昔洛韦联合阿昔洛韦软膏治疗带状疱疹的疗效及患者疼痛、血清IL-2、IL-6水平变化情况。方法:选取2016年9月至2020年10月间本院收治的142例带状疱疹患者为研究对象,采用简单随机分组法分为观察组和对照组,71例/组。对照组采...目的:探究喷昔洛韦联合阿昔洛韦软膏治疗带状疱疹的疗效及患者疼痛、血清IL-2、IL-6水平变化情况。方法:选取2016年9月至2020年10月间本院收治的142例带状疱疹患者为研究对象,采用简单随机分组法分为观察组和对照组,71例/组。对照组采用常规软膏涂抹治疗,观察组在此基础上给予喷昔洛韦治疗。比较两组疗效、临床症状改善时间(带状疱疹结痂、水疱停止发展、疼痛消失时间);比较治疗前后两组患者神经痛评分(VAS);比较治疗前后两组血清炎症因子[白细胞介素-2(IL-2)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)]变化;比较治疗前后T细胞亚群[T淋巴细胞(T lymphocyte,CD3^(+))、辅助性T细胞(Helper T cells,CD4^(+))、细胞毒性T细胞(Cytotoxic T cells,CD8^(+))、CD4^(+)/CD8^(+)]变化;记录治疗期间不良反应发生率。结果:治疗7d后,观察组治疗有效率高于对照组(P<0.05);观察组临床症状改善时间均短于对照组(P<0.05);治疗后两组VAS评分均降低且观察组低于对照组(P<0.05);治疗后,两组IL-2、IL-10水平和CD3^(+)、CD4^(+)及CD4^(+)/CD8^(+)均升高,且观察组高于对照组(P<0.05);两组IL-6水平均下降,且观察组低于对照组(P<0.05)。治疗期间两组不良反应发生率无明显差异(P>0.05)。结论:喷昔洛韦联合阿昔洛韦软膏治疗带状疱疹的疗效显著,能缓解神经疼痛,缩短症状消退时间,调节炎症因子,提高免疫功能,且安全性高。展开更多
文摘Aim To develop pluronic F127 （PF127） based formulations of penciclovir （PCV） aimed at enhancing its ocular bioavailability. Methods Thermosensitive in situ gels of penciclovir were prepared through combination of HPMC K4M or carbopol 934P and pluronic F127. Optimized formulations were examined through measuring gelation temperature, rheology speciality, drug release behavior, pharmacokinetics and ocular irritation. Results The gelation temperature was reduced by adding HPMC K4M or carbopol 934P, and the viscosity was enhanced slightly. Either HPMC K4M or carbopol 934P delayed the release of PCV from in situ gel. PCV was released by non-Fickian diffusion. The study of ocular irritation for different PCV formulations did not show any irritation or damage for the cornea. PCV bioavailability from combination of carbopol 934P and pluronic F127 gels was higher than that obtained from any other gels. Conclusion Pluronic F127 formulations of PCV can be used as liquid for administration by instilling into the eye. Facilitated by the appropriate eye temperature, the formulations were transformed to gel phase. On the basis of in vitro and in vivo results, PCV formulations containing HPMC K4M or carbopol 934P and low concentration of pluronic F127 （12%） showed potential for use as a drug delivery system with improved ocular bioavailability.
文摘Solubility of 2-amino-6-chloropurine in Mitsunobu solvents could be significantly improved after its exocyclic amino group is protected via N-tert-butoxycarbonylation.The bis-Boc protected 2-amino-6-chloropurine also shows excellent activity and N9 selectivity in the coupling with various alcohols by a Mitsunobu reaction.Then,a new practical and efficient method is established for the synthesis of penciclovir(PCV) from bis-Boc-2-amino-6-chloropurine 9 and the side chain of 5-(2-hydroxyethyl)-2,2-dimethyl-1,3-dioxane 5—the latter being a more easily prepared cyclic precursor of the diacetate side chain used in the conventional process.The coupling of 9 with 5 proceeded regioselectively at a N9 position of purine derivative for a good yield under Mitsunobu conditions.
文摘目的:基于二维高效液相色谱-四极杆-飞行时间串联质谱技术(2D-LC-Q TOF/MS),鉴定喷昔洛韦乳膏有关物质的结构。方法:采用ODS(250 mm×4.6 mm, 5μm)色谱柱,以0.15%甲酸10 mmol·L^(-1)甲酸铵缓冲溶液-乙腈为流动相,进行一维梯度洗脱,对喷昔洛韦乳膏及其依照ICH原则强制降解样品的有关物质进行分离,并分别富集各有关物质;再采用Phenomenex Luna SCX(250 mm×4.6 mm, 5μm)色谱柱,以0.1%甲酸20 mmol·L^(-1)甲酸铵缓冲溶液-乙腈为流动相,进行二维梯度洗脱,实现各有关物质与喷昔洛韦乳膏基质的良好分离。利用电喷雾正离子化-四极杆-飞行时间串联质谱高分辨测定各有关物质母离子及其子离子的准确质量和元素组成,并解析鉴定其结构。结果:在所建立的2D-LC-Q TOF/MS分析条件下,喷昔洛韦与其有关物质分离良好,检测出喷昔洛韦乳膏及其强制降解样品中21个主要有关物质。根据其色谱保留行为、光谱特征、质谱特征及与其他核苷类药物已知有关物质的差异,结合合成和制剂工艺路线分析,可鉴定出它们的结构,它们均为首次被鉴定出的有关物质。结论:研究结果为喷昔洛韦乳膏的质量控制提供了参考依据。
文摘目的:探究喷昔洛韦联合阿昔洛韦软膏治疗带状疱疹的疗效及患者疼痛、血清IL-2、IL-6水平变化情况。方法:选取2016年9月至2020年10月间本院收治的142例带状疱疹患者为研究对象,采用简单随机分组法分为观察组和对照组,71例/组。对照组采用常规软膏涂抹治疗,观察组在此基础上给予喷昔洛韦治疗。比较两组疗效、临床症状改善时间(带状疱疹结痂、水疱停止发展、疼痛消失时间);比较治疗前后两组患者神经痛评分(VAS);比较治疗前后两组血清炎症因子[白细胞介素-2(IL-2)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)]变化;比较治疗前后T细胞亚群[T淋巴细胞(T lymphocyte,CD3^(+))、辅助性T细胞(Helper T cells,CD4^(+))、细胞毒性T细胞(Cytotoxic T cells,CD8^(+))、CD4^(+)/CD8^(+)]变化;记录治疗期间不良反应发生率。结果:治疗7d后,观察组治疗有效率高于对照组(P<0.05);观察组临床症状改善时间均短于对照组(P<0.05);治疗后两组VAS评分均降低且观察组低于对照组(P<0.05);治疗后,两组IL-2、IL-10水平和CD3^(+)、CD4^(+)及CD4^(+)/CD8^(+)均升高,且观察组高于对照组(P<0.05);两组IL-6水平均下降,且观察组低于对照组(P<0.05)。治疗期间两组不良反应发生率无明显差异(P>0.05)。结论:喷昔洛韦联合阿昔洛韦软膏治疗带状疱疹的疗效显著,能缓解神经疼痛,缩短症状消退时间,调节炎症因子,提高免疫功能,且安全性高。
