Current Status and Future Prospects of Transdermal Drug Delivery

Pharmaceutical Research -     

氟对大鼠免疫器官的影响及“抗氟灵”对氟拮抗作用的研究

本文研究了对大鼠免疫器官的影响及“抗氟灵”对氟的拮抗作用。２４只大鼠被随机分成３组,Ａ组为阴性对照组,Ｂ组对染氟组,Ｃ组为氟加“抗氟灵”组,观察与检测了所有动物的胸腺及脾脏的蛋白质含量,脏器重量,脏器系数及形态学变化。结果显示;Ｂ组动物胸腺与脾脏的蛋白含量,脏器重量,脏器系数均明显下降,胸腺皮质明显变薄,淋巴细胞稀疏;Ｃ组动物的这些指标变化不明显。     

lontophoretic Delivery of a Series of Tripeptides Across the Skin in Vitro

The iontophoresis of eight tripeptides, of the general structure alanine–X–alanine, has been measured across hairless mouse skin in vitro. The peptides were blocked (a) at the carboxyl terminus using the mixed anhydride reaction with t-butylamine and (b) at the amino terminus by acetylation with ¹⁴C-acetic anhydride. The nature of the central residue (X) was varied by selecting one of five neutral amino acids, two negatively chargeable moieties (aspartic and glutamic acids), and a positively chargeable species (histidine). Constant current iontophoresis at 0.36 mA/cm², using Ag/AgCl electrodes, was performed for 24 hr in diffusion cells, which allowed both anode and cathode to be situated on the same (epidermal) side of a single piece of skin. Due to a combination of osmotic and electroosmotic forces, the anodal iontophoretic flux of neutral peptides was significantly greater than passive transport. Steady-state fluxes were not achieved, however, suggesting that time-dependent changes in the properties of the skin barrier may be occurring. Limited, further experiments confirmed that, on a 24-hr time scale, these changes were not fully reversible. The cathodal delivery of anionic permeants was well controlled at a steady and highly enhanced rate by the current flow. This behavior closely paralleled earlier work using simple negatively charged amino acids and N-acetylated amino acid derivatives. It appears that the normalized iontophoretic flux of these anionic species is independent of lipophilicity but may be inversely related to molecular weight. The positively charged peptide, Ac–Ala–His–Ala–NH(Bu^t), showed greater anodal iontophoretic enhancement when delivered from a donor solution at pH 4.0 than from a solution at pH 7.4. This was consistent with (a) the corresponding behavior of histidine alone and (b) the existence of a pK _a for these compounds at 6. Steady-state delivery was not achieved, although the levels of enhancement, especially at pH 4, were the largest observed. A preliminary investigation of tripeptide stability to either (i) electrolysis in the donor compartment or (ii) cutaneous metabolism revealed very little degradation under the conditions of the experiment. Overall, this research supports the principle of enhanced peptide delivery across the skin by iontophoresis and indicates a number of areas (e.g., mechanism and extent of current-induced changes in skin barrier function, molecular size dependence, pathways of current flow) on which further work should be focused.     

Sensory Excitatory Postsynaptic Potentials Mediated by NMDA and non-NMDA Receptors in the Thalamus in vivo

Excitatory amino acid neurotransmitters, such as l-glutamate, act at several receptors in the brain, which are sometimes referred to as N-methyl-d-aspartate (NMDA) and non-NMDA receptors. Extensive in vitro work indicates that both NMDA receptors and non-NMDA receptors contribute to excitatory postsynaptic potentials (epsps). The contribution of NMDA receptors to epsps in vivo under physiological conditions is, however, almost unknown. The receptors that mediate the epsps evoked in thalamic relay cells by natural stimulation of sensory afferents have been investigated in anaesthetized rats, and we report the first pharmacological characterization of an excitatory amino acid receptor-mediated epsp in vivo involving both non-NMDA receptors and, in particular, NMDA receptors.     

中药离子导入治疗慢性前列腺炎36例临床观察

目的 :观察中药离子导入治疗慢性前列腺炎的疗效 ,并评价它的安全性和可靠性。方法 :用自我专利技术“前列腺病离子治疗器直肠插入管”进行中药离子导入治疗已确定诊断的慢性前列腺炎患者共 3 6例 ,用主观症状改善率及前列腺液常规检查结果对比评估疗效。结果 :治疗组总有效率为 10 0 % ,痊愈率为 5 2 .8% ,副作用发生率为 13 .9% ,主观症状改善率与客观指标检测分析差别有显著性意义 (P <0 .0 0 1)。结论 :用自我专利技术“前列腺病离子治疗器直肠插入管”中药离子导入是治疗慢性前列腺炎的一种安全、有效的方法     

Iontophoretic transdermal delivery of buspirone hydrochloride in hairless mouse skin

The transdermal delivery of buspirone hydrochloride across hairless mouse skin and the combined effect of iontophoresis and terpene enhancers were evaluated in vitro using Franz diffusion cells. Iontophoretic delivery was optimized by evaluating the effect of drug concentration, current density, and pH of the vehicle solution. Increasing the current density from 0.05 to 0.1 mA/cm² resulted in doubling of the iontophoretic flux of buspirone hydrochloride, while increasing drug concentration from 1% to 2% had no effect on flux. Using phosphate buffer to adjust the pH of the drug solution decreased the buspirone hydrochloride iontophoretic flux relative to water solutions. Incorporating buspirone hydrochloride into ethanol:water (50:50 vol/vol) based gel formulations using carboxymethylcellulose and hydroxypropylmethylcellulose had no effect on iontophoretic delivery. Incorporation of three terpene enhancers (menthol, cineole, and terpineol) into the gel and when combined with iontophoresis it was possible to deliver 10 mg/cm²/day of buspirone hydrochloride.     

Magnesium and Fluoride Distribution in Human Cementum with Age

Sixty-two human teeth, obtained from subjects aged 11 to 80 years, were used to determine the magnesium and fluoride concentration and distribution with age in human cementum. Transverse sections were prepared from the root region of teeth. Samples, each 30 μm thick, were abraded in sequence from the cementum surface and the cemento-dentine junction by an abrasive micro-sampling technique. Magnesium concentrations were lower in the cementum surface, and increased towards the cemento-dentine junction (CDJ), while fluoride concentrations were higher in cementum surfaces and tended to decrease towards CDJ. Fluoride distribution patterns were similar to that reported earlier while average fluoride concentration increased with age, however, either no change or decreasing tendencies were observed with magnesium. Received: 5 January 1998 / Accepted: 20 July 2000 / Online publication: 2 November 2000     

电超导中药经皮外治药物性白细胞减少症162例疗效观察

目的:探讨电超导中药经皮外治药物性白细胞减少症的疗效。方法:将212例患者分为2组,治疗组162例,对照组50例。治疗组用中药外治法,对照组用口服西药升白细胞治疗,10天为1疗程。2组患者均在治疗后3、7、10天进行疗效观察。结果:治疗3、7、10天后,2组疗效比较,经统计学处理,差异有非常显著性意义(P<0.01)。结论:中药外治法可作为药物性白细胞减少症的一种治疗途径应用于临床。     

多肽蛋白质类药物离子导入经皮给药的研究进展

论述了多肽蛋白质类药物离子导入经皮给药的特点及主要影响因素,重点介绍了近年来国际上对胰岛素、降血钙素、促黄体(生成)激素释放激素、精氨酸抗利尿激素(加压素)等多肽蛋白质类药物离子导入经皮给药的研究进展.     

氟对铝作业工人的健康影响

目的　探讨氟对铝作业工人的健康影响。方法　采用作业环境空气中氟化物测定和职业健康检查等方法进行调查研究。结果　接触组神经衰弱、咳嗽、胸闷、四肢疼痛、关节痛及四肢麻木明显高于对照组 (P <0 0 1)。接触组确诊的 2例Ⅰ期氟病患者和 10 8例氟观察对象、5 4例氟斑牙主要表现与对照组相比差异具有高度显著性 (P <0 0 1)。铝电解工心律不齐和心电图异常项次之合计的检出率明显增高 ,与对照组比较 ,差异均有高度显著性 (P <0 0 1)。结论　氟对铝作业工人的健康影响比较严重 ,应引起有关部门的重视