实验室微搅拌器

帕洛诺司琼贴片的体外透过性能及在大鼠体内的药动学

制备了帕洛诺司琼透皮贴片并考察其体外释放和透过行为，以及在大鼠体内的药动学特征。分别采用 3 种不同类 型的含羟基丙烯酸压敏胶 (PSA-1、PSA-2 和 PSA-3) 制备出 F1、F2、F3 贴片，通过影响因素试验、体外释放和体外透 皮试验进行评价，筛选出优化贴片进行大鼠药动学试验。结果表明，处方 F2 中帕洛诺司琼的有关物质含量明显低于处 方 F1 和 F3，且帕洛诺司琼具有较快的释放速率及较高的体外透过能力，48 h 累积透过率达到 (78.8±11.6)％。F2 贴片的 大鼠药动学试验结果表明，贴片组比市售注射组有更长的消除半衰期 [ (26.4±6.8) h vs.(16.4±5.9) h]，绝对生物利用度为 (33.1±13.2)％。因此，PSA-2 制备的帕洛诺司琼透皮贴片经皮给药的可行性较高。

Pharmacokinetics and pharmacodynamics of glycyrrhetinic acid with Paeoniflorin after transdermal administration in dysmenorrhea model mice

Background: Glycyrrhetinic acid (GA) and paeoniflorin (PF) are the main active ingredients in Chinese peony- Liquorice Decoction, a widely used Traditional Chinese Medicine. Hypothesis/Purpose: The aim of this work was to investigate the combinatory analgesic effect of GA and PF after percutaneous administration and to define their pharmacokinetic/pharmacodynamic (PK/PD) characteristics. Study design and Methods: GA and PF were produced to transdermal patches based on previous research, and the permeation parameters of GA and PF in the patches were investigated with in vitro experiments. Dysmenorrhea model mice were then produced to compare the analgesic effects of the patches with different proportions of GA-PF. In the in vivo assessment, the number of writhes exhibited by the dysmenorrhea mice was recorded at designated time points, and skin, muscle under skin and plasma samples were collected, for assessments of drug distribution, pharmacokinetics parameters and PK/PD characteristics. Results and conclusion: In dysmenorrhea mice, GA-PF and meloxicam (the positive control drug) could relieve pain to equal degrees. Specifically, a single dose of the optimized patches (10%GA-10%PF, wt) exerted a steady analgesic effect for 48 h in dysmenorrhea mice, but this effect lagged behind the changes in the plasma concentration. Evaluation with the Bliss Independence criterion revealed that the two ingredients displayed a synergistic effect. Then the PK/PD relationship of GA in this compound preparation was defined with this synergistic effect. The preparation might be suitable for topical spasmolysis and anti-inflammatory therapy

Fabrication of pH sensitive amphiphilic hot-melt pressure sensitive adhesives for transdermal drug delivery system

Based on the blend of styrene-isoprene-styrene (SIS) thermoplastic elastomer and acrylic resin Eudragits EPO, amphiphilic hot-melt pressure sensitive adhesives (HMPSAs) were fabricated. Compatibility and micromorphology of SIS/EPO blends (SEBs) were analyzed with differential scanning calorimetry (DSC), atomic force microscopy (AFM) and scanning electron microscopy (SEM). The results showed that when the mass ratio of SIS to EPO was 1:1
1:2, bicontinuous structure was formed. Following the addition of an appropriate amount of polyethylene glycol (PEG), mineral oil and C5 resin, the amphiphilic HMPSAs were prepared. Because of the compatibility between SIS and EPO, as well as the hydrogen bond interaction between EPO and PEG, amphiphilic HMPSAs showed good thermostability. The adhesive performance of HMPSAs was measured with 1801 peeling strength and holding power. Geniposide and oleanolic acid were used as model drugs to investigate drug release behavior. When the mass ratio of PEG to SEB was 13:30
16:30, the HMPSAs could maintain good adhesion performance and achieve continual release of both hydrophilic and lipophilic drugs. In weakly acidic conditions, the HMPSAs exhibited good hygroscopicity and release profile, it was shown that pH sensitive amphiphilic HMPSAs were more suitable for transdermal drug delivery system (TDDS).

pH 敏感型热熔压敏胶的制备及释药性能研究

通过物理共混改性苯乙烯-异戊二烯-苯乙烯( SIS) 型热熔压敏胶，阐明改性热熔压敏胶的黏附性能、释药性能、经 皮渗透性能与材料组成的关系，分析 pH 对于改性热熔压敏胶释药和经皮渗透性能的影响。方法 将苯乙烯-异戊二烯-苯乙 烯与丙烯酸树脂尤特奇 EPO 共混制备两亲性热塑弹性体苯乙烯-异戊二烯-苯乙烯/丙烯酸树脂尤特奇 EPO 共混物( SEB) ，使 用扫描电子显微镜和原子力显微镜观测 EPO 共混物的微观形态; 在 EPO 共混物中加入聚乙二醇( PEG) 、矿物油、C5树脂和抗 氧剂制备改性热熔压敏胶，通过测定 180°剥离强度和持黏力分析黏附性能; 使用熊果苷等 6 种有效成分考察亲水/亲脂性药 物的释放性能以及 pH 对释药性能变化的影响; 考察压敏胶中芍药苷、盐酸青藤碱在皮肤表面弱酸性条件下的经皮渗透性能; 使用1H 核磁共振波谱仪( 1H-NMＲ) 分析 pH 对压敏胶与药物分子间的相互影响。结果 当苯乙烯-异戊二烯-苯乙烯-丙烯酸 树脂尤特奇 EPO = 1∶ 2( w/w) 时，制备的苯乙烯-异戊二烯-苯乙烯/丙烯酸树脂尤特奇 EPO 共混物形成“双连续”结构，在此基 础上制备的改性热熔压敏胶具有较好的黏附性能，实现了亲水/亲脂性药物的共同释放，同时明显改善了亲水性药物的经皮 渗透性能; 改性热熔压敏胶显示出 pH 敏感性，在弱酸性条件下丙烯酸树脂尤特奇 EPO 质子化，导致药物快速释放和经皮渗透 性提高。结论 通过共混改性制备的 pH 敏感性热熔压敏胶适合于在经皮给药系统( TDDS) 中应用。

适用于经皮给药系统的SIS-g-NPEO热熔压敏胶 及其释药性研究

通过原位环氧化反应与开环接枝反应相结合，将亲水性壬基酚聚氧乙烯醚（ ） 支链引入聚苯乙烯-异戊二烯-苯乙烯（ ）三嵌段共聚物，制备功能型 热塑弹性 S I S S I S - g - N P E O 体，并以S I S - g - N P E O为骨架，配以增粘树脂、矿物油、氢化松香树脂、抗氧剂等组分，制备了 面向经皮给药系统的S I S - g - N P E O热熔压敏胶，以栀子苷为亲水性模型药物，研究S I S - g - N P E O热 熔压敏胶中各组分对栀子苷的释放影响。结果显示， 树脂和增塑剂 有利于栀子苷释放；矿 C 5 P E G 物油不利于亲水性成分栀子苷的释放。

New Delivery Route of Gambogic Acid Via Skin for Topical Targeted Therapy of Cutaneous Melanoma and Reduction of Systemic Toxicity

Cutaneous melanoma is the deadliest form of skin cancer, and gambogic acid (GA) exhibits potent antimelanoma activity. However, clinical application of GA via intravenous injection and oral administration is limited by systemic toxicity and rapid metabolism in the blood. Here, we developed a new, topical route of GA delivery for anti-melanoma activity and reduction of systemic toxicity. The results indicated that the barrier of the stratum corneum (SC) and low diffusion of GA in the hydrophilic viable skin (epidermis and dermis) limited the GA penetration through intact skin. The combination of azone (AZ) and propylene glycol (PG) showed obvious synergistic effects on skin penetration by GA via improving the permeability of the SC and greatly increasing the skin accumulation of GA, thereby forming a high drug concentration in the skin and achieving a topical targeted treatment of melanoma. In addition, GA (AZePG) achieved the same anti-melanoma effect via topical delivery as via intravenous injection. Intravenous injection and oral administration of GA induced remarkable pathological changes in various organs in mice, whereas GA was not toxic to various organs or to the skin via topical delivery. These findings indicated that topical administration of GA is an alternative route for melanoma treatment. ? 2021 Published by Elsevier Inc. on behalf of the American Pharmacists Association

汪晴教授科研团队研制的治疗“帕金森病”的长效贴剂创新药获批进入临床试验！

大连理工大学汪晴教授科研团队十年攻关，研发的国家2.2类新药“帕金森病”的长效普拉克索透皮贴剂获得临床研究许可！在临床前药学研究中，该科研团队采用了大连科翔科技研制的搅拌、涂布和渗透等系列实验室仪器和中试设备，以及计算机模拟评价系统，圆满完成各项研究工作，各项实验数据顺利通过了CDE的严格核验。