Viscomate NP-800基吲哚美辛水凝胶贴剂的研究

目的:探讨影响ViscomateNP-800基水凝胶强度的处方因素以及氮酮和薄荷脑对吲哚美辛水凝胶贴剂中药物透过小鼠皮肤的促透效果.方法:采用ACM-2LVT型2L-爱工舍混合机制备水凝胶并用SHIMPO数字扭矩仪测定凝胶强度;采用巴布剂涂布装置制备吲哚美辛水凝胶贴剂;采用YB-P6型智能透皮试验仪和紫外分光光度计考察药物透过小鼠皮肤的透过率.结果:按Viseomate NP-800 5%.甘羟铝0.2%.酒石酸0.2%,EDTA 0.3%,水64.3%,甘油30%制备的水凝胶初始凝胶强度较低,随放置时间延长,凝胶强度明显提高;和含有氮酮和薄荷脑的贴剂相比,阴性样品的吲哚美辛皮肤透过率明显较低.结论:以Viscomate NP-800 为高分子骨架的水凝胶基质易于涂布,涂布后有足够的强度,适合用作贴剂的水凝胶基质;含有3%氮酮和0.3%薄荷脑的吲哚美辛水凝胶贴剂中药物透过小鼠皮肤的透过性较好.     

双指数方程在青藤碱脂质体贴剂体外透皮特性拟合中的应用研究

为研究青藤碱脂质体贴剂的体外透皮特性,采用Franz扩散池进行体外透皮扩散,对不同时间点的接收液进行采样1 mL,并随即更换1 mL新鲜的接收液,HPLC法测定接收液浓度,并进行模型拟合。以AIC及相关系数为判断标准,结果表明双指数双相动力学方程为最佳拟合。     

Development and Evaluation of Ethyl Cellulose-Based Transdermal Films of Furosemide for Improved In Vitro Skin Permeation

Transdermal films of the furosemide were developed employing ethyl cellulose and hydroxypropyl methylcellulose as film formers. The effect of binary mixture of polymers and penetration enhancers on physicochemical parameters including thickness, moisture content, moisture uptake, drug content, drug–polymer interaction, and in vitro permeation was evaluated. In vitro permeation study was conducted using human cadaver skin as penetration barrier in modified Keshary–Chein diffusion cell. In vitro skin permeation study showed that binary mixture, ethyl cellulose (EC)/hydroxypropyl methylcellulose (HPMC), at 8.5:1.5 ratio provided highest flux and also penetration enhancers further enhanced the permeation of drug, while propylene glycol showing higher enhancing effect compared to dimethyl sulfoxide and isopropyl myristate. Different kinetic models, used to interpret the release kinetics and mechanism, indicated that release from all formulations followed apparent zero-order kinetics and non-Fickian diffusion transport except formulation without HPMC which followed Fickian diffusion transport. Stability studies conducted as per International Conference on Harmonization guidelines did not show any degradation of drug. Based on the above observations, it can be reasonably concluded that blend of EC–HPMC polymers and propylene glycol are better suited for the development of transdermal delivery system of furosemide.     

Effect of several factors on the mechanical properties of pressure-sensitive adhesives used in transdermal therapeutic systems

The effects of coating thickness, type of adhesive, and type and concentration of enhancer on the mechanical properties of two acrylic pressure-sensitive adhesives (PSAs) were investigated using a 2(4) factorial design and an optimization technique. Sixteen formulations containing 0% or 10% of either caprylic acid or methyl laurate in two different PSAs, namely Duro-Tak 87-2196 and Duro-Tak 87-2097, were prepared. The adhesive properties of these laminates were evaluated by applying the 90 degrees Dynamic Adhesive Strength Peel Test (90 degrees DASPT) and 1800 Release Liner Peel Test (180 degrees RLPT). Coating thickness, concentration of enhancer, and type of adhesive did affect the 90 degrees DASPT. For the 180 degrees RLPT, the most significant factors were coating thickness and concentration of enhancer, with a strong interaction observed between the two. Coating thickness and concentration of enhancer were also used to create mathematical models that correlated these factors with the mechanical properties of the PSAs. For this purpose, the optimization technique 3(2) was applied. It was found that the correlation of the above factors can be adequately described with polynomial equations, which can be used for predicting the mechanical properties of the laminates containing the above PSAs and methyl laurate (0%-10%).     

微针用于生物大分子及纳米药物透皮给药的尝试与挑战

生物大分子及纳米药物,比如,亚单位疫苗、DNA疫苗、以及针对真皮层的治疗药物,作为近年来新兴的治疗药物,在有些治疗领域有着透皮给药的需求。由于具有靶向性高,疗效显著等特点,生物大分子及纳米药物逐渐成为新的研究热点。微针作为一种新型的给药技术,不仅具有无痛、给药方便等优点,而且运用物理手段可大幅提高大分子甚至纳米药物的透皮吸收及皮层靶向,能够避过胃肠道消化作用以及肝脏首过效用。将微针技术与生物大分子药物相结合,能够同时发挥两者的优势,实现高靶向生物药物的无痛给药。本文简述微针透皮给药技术、以及生物大分子给药的研究进展,对微针技术用于生物大分子及纳米药物透皮给药的尝试研究做了介绍和总结,对存在的技术挑战进行了分析和展望。     

Transdermal Delivery of Insulin by Amidated Pectin Hydrogel Matrix Patch in Streptozotocin-Induced Diabetic Rats: Effects on Some Selected Metabolic Parameters

Purpose

Studies in our laboratory are concerned with developing optional insulin delivery routes based on amidated pectin hydrogel matrix gel. We therefore investigated whether the application of pectin insulin (PI)-containing dermal patches of different insulin concentrations sustain controlled release of insulin into the bloodstream of streptozotocin (STZ)-induced diabetic rats with concomitant alleviation of diabetic symptoms in target tissues, most importantly, muscle and liver.

Methods

Oral glucose test (OGT) responses to PI dermal matrix patches (2.47, 3.99, 9.57, 16.80 µg/kg) prepared by dissolving pectin/insulin in deionised water and solidified with CaCl₂ were monitored in diabetic rats given a glucose load after an 18-h fast. Short-term (5 weeks) metabolic effects were assessed in animals treated thrice daily with PI patches 8 hours apart. Animals treated with drug-free pectin and insulin (175 µg/kg, sc) acted as untreated and treated positive controls, respectively. Blood, muscle and liver samples were collected for measurements of selected biochemical parameters.

Results

After 5 weeks, untreated diabetic rats exhibited hyperglycaemia and depleted hepatic and muscle glycogen concentrations. Compared to untreated STZ-induced diabetic animals, OGT responses of diabetic rats transdermally applied PI patches exhibited lower blood glucose levels whilst short-term treatments restored hepatic and muscle glycogen concentrations. Plasma insulin concentrations of untreated diabetic rats were low compared with control non-diabetic rats. All PI treatments elevated plasma insulin concentrations of diabetic rats although the levels induced by high doses (9.57 and 16.80 µg/kg) were greater than those caused by low doses (2.47 and 3.99 µg/kg) but comparable to those in sc insulin treated animals.

Conclusions

The data suggest that the PI hydrogel matrix patch can deliver physiologically relevant amounts of pharmacologically active insulin.

Novelty of the Work

A new method to administer insulin into the bloodstream via a skin patch which could have potential future applications in diabetes management is reported.     

芬太尼透皮贴剂对吗啡不耐受晚期癌痛患者疼痛介质水平及生存质量的影响

目的:探讨芬太尼透皮贴剂对吗啡不耐受晚期癌痛患者疼痛介质水平及生存质量的影响。方法:回顾性分析我院2016年12月~2017年12月收治的102例吗啡不耐受晚期癌痛患者为研究对象,按治疗方式不同分为对照组和研究组,每组51例。对照组予以氨酚羟考酮片治疗,研究组予以芬太尼透皮贴剂治疗。比较两组的镇痛疗效,治疗前后血清疼痛介质、视觉模拟评分(VAS)、生活质量水平的变化和不良反应的发生情况。结果:治疗后,研究组镇痛总有效率显著高于对照组(86.27%vs. 68.23%,P0.05)。治疗后,两组血清P物质(SP)、前列腺素E2(PGE2)及VAS评分均较治疗前显著下降,且研究组以上指标均明显低于对照组,两组血清β-内啡肽(β-EP)均较治疗前明显上升,且研究组显著高于对照组(P0.05)。两组治疗后精神状况、心理状况、功能状况、生理状况及社会功能评分均较治疗前显著上升,且研究组以上指标均显著高于对照组(P0.05)。治疗后,研究组恶心呕吐、便秘、头晕嗜睡发生率低于对照组(P0.05)。结论:芬太尼透皮贴剂对吗啡不耐受晚期癌痛患者的镇痛效果确切,能够调节疼痛介质表达,提高患者的生存质量,是治疗晚期癌痛有效、安全的阿片类药物。     

Effect of Habitat Patch Characteristics on Abundance and Diversity of Insects in an Agricultural Landscape

The objective of this study was to test for general effects of patch size, patch isolation, disturbance frequency, and patch life span, on density and diversity of organisms. We sampled predominantly herbivorous insects in 31 alfalfa fields that varied in size, isolation, frequency of disturbance by cutting, and age (number of years planted in alfalfa). Effects on insect relative density and diversity were examined at three taxonomic levels: all insects, eight separate orders, and six legume-specialist weevil species. We found that (a) more isolated alfalfa fields had higher overall insect richness, (b) fields with higher disturbance frequency had lower overall insect richness, and (c) fields of intermediate age had highest insect richness. In some cases these patterns were reflected at lower taxonomic levels, but in many cases they were not. These results are important because they indicate that, although we cannot simultaneously tailor a landscape for each of thousands of species, we may be able to produce desired effects at a more general level. Received 8 August 1997; accepted 2 January 1998.     

Transdermal therapeutic system of carvedilol: Effect of hydrophilic and hydrophobic matrix on in vitro and in vivo characteristics

The purpose of this research was to develop a matrix-type transdermal therapeutic system containing carvedilol with different ratios of hydrophilic and hydrophobic polymeric combinations by the solvent evaporation technique. The physicochemical compatibility of the drug and the polymers was studied by infrared spectroscopy and differential scanning calorimetry. The results suggested no physicochemical incompatibility between the drug and the polymers. In vitro permeation studies were performed by using Franz diffusion cells. The results followed Higuchi kinetics (r=0.9953−0.9979), and the mechanism of release was diffusion mediated. Based on physicochemical and in vitro skin permeation studies, patches coded as F3 (ethyl cellulose: polyvinylpyr-rolidone, 7.5∶2.5) and F6 (Eudragit RL:Eudragit RS, 8∶2) were chosen for further in vivo studies. The bioavailability studies in rats indicated that the carvedilol transdermal patches provided steady-state plasma concentrations with minimal fluctuations and improved bioavailability of 71% (for F3) and 62% (for F6) in comparison with oral administration. The antihypertensive activity of the patches in comparison with that of oral carvedilol was studied using methyl prednisolone acetate—induced hypertensive rats. It was observed that both the patches significantly controlled hypertension from the first hour (P<.05). The developed transdermal patches increase the efficacy of carvedilol for the therapy of hypertension. Published; January 19, 2007     

Selection Strategies of Parasitized Hosts in a Generalist Parasitoid Depend on Patch Quality but Also on Host Size

Host rejection, superparasitism, and ovicide are three possible host selection strategies that parasitoid females can adopt when they encounter parasitized hosts. These differ in costs (in terms of time and energy required) and benefits (in terms of number and quality of offspring produced). Their relative payoff should vary with patch quality, (i.e., proportion of parasitized hosts present), and female choice between them should be adapted accordingly. We conducted behavioral observations to test the effect of the ratio of parasitized/unparasitized hosts present in a patch on the host selection strategies of Pachycrepoideus vindemmiae Rondani (Hymenoptera: Pteromalidae). This species being a generalist known to attack hosts of a great range of size, we also tested the impact of host size on female decisions with two host species differing greatly in size (Drosophila melanogaster and Delia radicum). We evaluated the adaptive value of each strategy in relation to host parasitization status and host size by measuring their duration and the potential number of offspring produced.     

聚丙烯补片材料在腹股沟疝修补中的临床应用研究

目的:采用生物材料补片进行修补,加强腹壁薄弱区域实现功能重建,分析该方法治疗腹股沟疝的临床疗效。方法:选择我院收治的无嵌顿性择期腹股沟疝手术患者30例,随机分为传统修补组与生物补片修补组。比较患者的围手术期指标(手术时间、出血量、住院时间、术后下地活动时间、镇痛药物应用例数)、临床疗效,通过随访比较术后1个月、3个月、6个月患者的VAS评分及主观满意度,记录切口感染及其他并发症的发生情况。结果:所有患者均顺利完成手术,并完成半年以上随访。研究组的手术时间、术中失血量、住院时间、术后下地活动时间、镇痛药物应用均明显短于或低于对照组(P0.05)。两组患者术后1个月、3个月、6个月的VAS评分、主观满意度均较术前显著降低(P0.05),但两组之间相比差异无统计学意义(P0.05)。结论:采用生物补片材料修补腹股沟疝的手术创伤较小且患者恢复期短,近期疗效及安全性与传统手术相当。