微柱离心-HPLC测定马来酸噻吗洛尔醇质体包封率

目的 建立马来酸噻吗洛尔醇质体包封率测定方法.方法 采用pH梯度法制备马来酸噻吗洛尔醇质体,微柱离心法分离醇质体和游离药物,HPLC检测醇质体中药物的含量.结果 马来酸噻吗洛尔在浓度范围2.0~10μg·m L-1与峰面积呈线性关系,r=0.99999,回收率≥99.84%;,微柱离心法能将醇质体和游离药物完全分离,醇质体的平均包封率为62.67%.结论 方法准确可靠,简便,可用于马来酸噻吗洛尔醇质体质量控制.     

Testosterone ethosomes for enhanced transdermal delivery

Physiological decrease in testosterone levels in men with age causes various changes with clinical significance. Recent testosterone replacement therapy is based mainly on transdermal nonpatch delivery systems. These products have the drawback of application on extremely large areas to achieve required hormone blood levels. The objective of the present study was to design and test a testosterone nonpatch formulation using ethosomes for enhanced transdermal absorption. The ethosomal formulation was characterized by transmission electron microscopy and dynamic light scattering for structure and size distribution and by ultracentrifugation for entrapment capacity. To evaluate the feasibility of this delivery system to enhance testosterone permeation through the skin, first the systemic absorption in rats was compared with a currently used gel (AndroGel®). Further, theoretical estimation of testosterone blood concentration following ethosomal application in men was made. For this purpose, in vitro permeation experiments through human skin were performed to establish testosterone skin permeation values. In the design of these experiments, testosterone solubility in various solutions was measured and the effect of the receiver medium on the skin barrier function was assessed by confocal laser scanning microscopy. Theoretical estimation shows that testosterone human plasma concentration value in the upper part of the physiological range could be achieved by application of the ethosomal formulation on an area of 40 cm². This area is about 10 times smaller than required with current nonpatch formulations. Our work shows that the ethosomal formulation could enhance testosterone systemic absorption and also be used for designing new products that could solve the weaknesses of the current testosterone replacement therapies.     

尼美舒利醇质体抗炎镇痛作用与皮肤刺激性研究

目的考察尼美舒利醇质体经皮给药的镇痛抗炎作用及皮肤刺激性。方法采用小鼠热板法和醋酸扭体法观察尼美舒利醇质体的止痛作用;建立大鼠佐剂性关节炎模型,观察尼美舒利醇质体对大鼠足肿胀及滑膜关节组织的影响;利用健康豚鼠观察尼美舒利醇质体皮肤刺激反应。结果与对照组比较,中、高剂量尼美舒利醇质体能明显提高小鼠自身的热痛阈值（P＜0.05）;并能使醋酸致小鼠扭体次数显著减少（P＜0.05）;抗炎实验结果表明,尼美舒利醇质体对佐剂引起的大鼠足肿胀关节炎有明显的抑制作用（P＜0.05）;尼美舒利醇质体对豚鼠无皮肤刺激作用。结论尼美舒利醇质体具有明显的抗炎、镇痛作用,且皮肤刺激性较小,是一种有效的经皮给药制剂。     

醋酸泼尼松龙醇质体的制备及其药剂学性质考察

目的:制备醋酸泼尼松龙醇质体并考察其药剂学性质。方法:采用乙醇注入法制备醇质体。以包封率为指标,以处方中药物与大豆磷脂质量比(A)、胆固醇与大豆磷脂质量比(B)、无水乙醇占处方总量的百分比(C)为考察因素进行正交设计优化处方;考察优化后处方所制醇质体的形态、粒径、Zeta电位、包封率、稳定性等,差示量热分析法考察其热力学特性。结果:最佳处方为平均A包1:封20率,B为1(:766、.C793±0%0.2;9以)%此,处贮方藏制30备d的稳醇定质性体较外好形。圆差整示光量滑热,分平析均法粒结径果为(表2明78,.醋5±酸4泼6.7尼)松nm龙,Z以et无a电定位形为状(态-包31封.6于±醇0.0质4)体m中V,。结论:醋酸泼尼松龙醇质体制备工艺简单,优化处方所制制剂药剂学性质符合要求。     

Testosterone Ethosomes for Enhanced Transdermal Delivery

Physiological decrease in testosterone levels in men with age causes various changes with clinical significance. Recent testosterone replacement therapy is based mainly on transdermal nonpatch delivery systems. These products have the drawback of application on extremely large areas to achieve required hormone blood levels. The objective of the present study was to design and test a testosterone nonpatch formulation using ethosomes for enhanced transdermal absorption. The ethosomal formulation was characterized by transmission electron microscopy and dynamic light scattering for structure and size distribution and by ultracentrifugation for entrapment capacity. To evaluate the feasibility of this delivery system to enhance testosterone permeation through the skin, first the systemic absorption in rats was compared with a currently used gel (AndroGel®). Further, theoretical estimation of testosterone blood concentration following ethosomal application in men was made. For this purpose, in vitro permeation experiments through human skin were performed to establish testosterone skin permeation values. In the design of these experiments, testosterone solubility in various solutions was measured and the effect of the receiver medium on the skin barrier function was assessed by confocal laser scanning microscopy. Theoretical estimation shows that testosterone human plasma concentration value in the upper part of the physiological range could be achieved by application of the ethosomal formulation on an area of 40 cm². This area is about 10 times smaller than required with current nonpatch formulations. Our work shows that the ethosomal formulation could enhance testosterone systemic absorption and also be used for designing new products that could solve the weaknesses of the current testosterone replacement therapies.     

睾酮及其酯类醇质体凝胶剂的体内外渗透行为比较

目的:比较睾酮、丙酸睾酮、十一酸睾酮醇质体凝胶剂的体内外渗透行为。方法:制备睾酮、丙酸睾酮、十一酸睾酮醇质体凝胶剂,采用Franz扩散池和高效液相色谱法,以累积透过量和渗透速率为指标,比较3种醇质体凝胶剂经小鼠皮肤的体外渗透行为;以睾酮贴剂为阳性对照,采用电化学法检测3种醇质体凝胶剂涂铺于大鼠背部0、3、6、9、12、24、36、48 h后睾酮的血药浓度,DAS 2.0软件计算药动学参数。结果:睾酮、丙酸睾酮、十一酸睾酮醇质体凝胶剂24 h的累积渗透量分别为(234.31±13.8)、(175.63±41.1)、(72.60±15.3)μg/cm2,渗透速率分别为(10.25±1.9)、(7.64±1.4)、(2.96±0.8)μg/(cm2·h);上述3种醇质体凝胶剂和阳性对照的药动学参数依次为cmax(20.19±2.57)、(17.50±2.91)、(0.23±0.04)、(14.97±2.12)ng/ml,t1/2Ka(2.80±0.45)、(3.36±0.59)、(4.02±0.62)、(4.20±0.71)h,AUC0-48 h(13.85±1.96)、(13.93±2.13)、(0.35±0.07)、(11.76±2.31)ng·h/ml。结论:睾酮和丙酸睾酮醇质体凝胶剂具有较好的体内外渗透行为。     

乙醇脂质体对多奈哌齐经皮转运的促进作用

目的：制备多奈哌齐乙醇脂质体,从而进一步有效优化药物的经皮转运。方法：采用注入法制备多奈哌齐乙醇脂质体;通过形态,粒径分布和包封率对乙醇脂质体进行了初步表征,运用Franz 扩散池和共聚焦激光扫描电镜考察了乙醇脂质体的经皮转运情况。结果：多奈哌齐乙醇脂质体（乙醇含量45%）包封率明显高于多奈哌齐脂质体;多奈哌齐乙醇脂质体透皮量分别为脂质体及乙醇溶液的4.32倍和1.89倍。结论：乙醇脂质体可有效携带药物进入皮肤深层。