可乐定透皮贴剂体外透皮性能研究

目的:研究可乐定透皮贴剂体外透皮性能.方法:用离体豚鼠皮肤为透皮屏障,采用改进Franz扩散池,比较康倍得公司研制的可乐定透皮贴剂(C-TTS)、美国的可乐定透皮贴剂(Catapres-TTS)和国内的可乐定透皮贴剂(N-TTS)的体外透皮性能.检测方法为高效液相色谱法.结果:C-TTS与Catapres-TTS两种贴剂体外经皮渗透曲线符合零级方程(Q=kt),两者透皮速率无显著性差异(P>0.05);N-TTS体外经皮渗透曲线符合Ritger-peppas方程(Q=ktm),其透皮速率与C-TTS比较有显著性差异(P<0.01).3种样品试验结束揭去贴片后,皮肤中有一定的药物残留量,并且残留量与贴片面积呈线性关系.结论:C-TTS可以维持7d的恒定经皮渗透,与Catapres-TTS体外透皮行为相似.     

酮洛芬不同透皮制剂的体外透皮性和释放性

分别制备含1%、3%、5%酮洛芬的混合型巴布剂、交联型巴布剂、透皮贴剂,以同浓度的酮洛芬凝胶剂作为对照组,采用改良Franz透皮扩散池,以离体小鼠皮肤为透皮屏障,考察酮洛芬在不同制剂中的体外透皮和释放性能.结果表明,同浓度酮洛芬在不同受试制剂的透皮速率依序为交联型巴布剂＞混合型巴布剂＞凝胶剂＞透皮贴剂;3%酮洛芬在不同贴膏剂中的释放速率依序为混合型巴布剂＞交联型巴布剂＞透皮贴剂.     

非洛地平-美托洛尔复方贴剂的透皮吸收促进剂优化

目的：优化复合透皮吸收促进剂，制备非洛地平-美托洛尔复方贴剂，并对其外观、物理特性、体外药物释放和经皮渗透性能进行综合评价。方法：以药物体外释放速率和稳态透皮速率为指标，通过正交设计试验考察桉叶油醇、月桂氮[艹卓]酮和丙二醇体系对贴剂质量的影响，优选最佳复合透皮吸收促进剂构成。结果：优选的透皮吸收促进剂最佳含量分别为桉叶油醇5％、月桂氮[艹卓]酮3％和丙二醇12%，以该促透体系制备的贴剂药物体外释放速率和稳态透皮速率高，外观和理化特性较佳，物理黏性适宜，各指标均达到预期设计要求。结论：桉叶油醇-月桂氮[艹卓]酮-丙二醇（5：3：12）复合体系对非洛地平和关托洛尔的协同促透作用显著，且稳定可靠，是非洛地平关托洛尔复方贴剂的优良透皮吸收促进剂。     

氟比洛芬透皮贴剂的质量控制及体外透皮试验

目的:建立氟比洛芬贴剂的质量控制方法,并考察其体外透皮效果.方法:以HPLC法测定氟比洛芬的含量,并测定黏附性能、含量均匀度等指标;同时对其小鼠离体皮肤透皮特性进行了测试.结果:建立的HPLC法可用来测定氟比洛芬的含量,在0.1～100 mg·L-1范围内线性关系良好,该贴剂具有良好的黏附性能,24 h内累积渗透量为979.9 μg.结论:建立的方法可用于氟比洛芬贴剂的质量控制,其体外透皮效果良好.     

盐酸川芎嗪透皮贴剂体外透皮速率测定和体外释放研究

目的研究盐酸川芎嗪透皮贴剂的经皮吸收的可行性。方法采用高效液相色谱法测定透皮接受液和释放接受液中盐酸川芎嗪的浓度。结果体外透皮实验和体外释放实验结果表明：盐酸川芎嗪在24h内以一定的速率（0．1014mg／cm^2h^1恒速渗透,其释放符合Higuchi方程。此外,该贴剂的体外释放速率为0．1332mg／cm^2h^1/2。结论盐酸川芎嗪透皮贴剂为皮肤限速型的骨架控释透皮给药系统。     

不同促渗剂对马钱子碱贴剂体外透皮吸收的影响

目的:研究不同促渗剂对马钱子碱贴剂体外透皮促渗作用的影响.方法:采用不同浓度、不同种类促渗剂制备马钱子碱贴剂;采用改良Franz扩散池,以离体雄性大鼠皮肤为模型,通过高效液相色谱法测定药物浓度,拟合马钱子碱透皮吸收的累积透过量和透过速率.结果:以3%氮酮制备的马钱子碱贴剂具有较好的体外透过速率及累积透过量;促渗剂合用时...     

芬太尼透皮贴剂不良反应观察

目的 :了解住院患者应用芬太尼透皮贴剂 (多瑞吉)的疗效及不良反应 ,促进临床合理用药。方法 :观察我院肿瘤科37例住院患者应用芬太尼透皮贴剂的情况 ,评价其止痛效果及不良反应发生率、程度和转归。结果 :芬太尼透皮贴剂止痛效果确切 ,癌痛缓解率达100% ;发生不良反应的有4例 ,发生率为10 8%。结论 :芬太尼透皮贴剂应用于癌痛治疗的效果确切 ,但要注意监测药物不良反应 ,避免不合理用药     

氢溴酸加兰他敏贴剂的制备及体外释放和透皮特性研究

目的：制备氢溴酸加兰他敏贴剂,并对其体外释放度和体外透皮特性进行考察。方法：采用丙烯酸酯乳液型压敏胶为基质制备氢溴酸加兰他敏贴剂,按《中华人民共和国药典》规定方法进行贴剂的体外释放度测定;采用改良Franz扩散池,以离体小鼠皮肤为屏障进行氢溴酸加兰他敏贴剂的体外透皮特性研究。结果：氢溴酸加兰他敏贴剂的体外释放符合Higu-chi方程,24 h累积释药量占总药量的41.81%;体外透皮符合零级方程,24 h累积渗透量占总药量的19.99%。结论：采用丙烯酸酯乳液型压敏胶为基质制备的氢溴酸加兰他敏贴剂具有较好的体外释放和透皮特性。     

奥昔布宁透皮贴剂的制备及其体外透皮性研究

目的：制备奥昔布宁透皮贴剂,并对其体外透皮性进行研究。方法：以奥昔布宁为主药,聚丙烯酸树脂E100为辅料,制备奥昔布宁透皮贴剂。采用高效液相色谱法,比较不同渗透促进剂（3％、5％氮酮,5％、10％、15％三醋酸甘油酯,5％、10％肉豆蔻酸异丙酯）对奥昔布宁透皮贴剂的稳态透皮速率（z）的影响,选出最佳渗透促进剂;采用正交试验法,以上和初黏力、持黏力为指标．考察增塑剂癸二酸二丁酯、交联剂丁二酸用量和载药量对贴剂透皮性的影响,优化最佳处方。结果：最佳渗透促进剂为15％三醋酸甘油酯;最优处方为增塑剂25％、交联剂6％、载药量25％;制备的奥昔布宁透皮贴剂的体外为6．24gg／（cm2·h）,初黏力为22号钢珠,持黏力为81min。结论：制备的奥昔布宁透皮贴剂具有良好的透皮性。     

岩藻黄质水凝胶透皮贴剂体外释放度及透皮率的测定

目的研究不同吸收促进剂对岩藻黄质水凝胶透皮贴剂体外释放度及透皮率的影响。方法采用HPLC法测定岩藻黄,Ultimate色谱柱(250mm×4.6mm,5μm),流动相为乙腈-水(70%~100%、100%~100%、100%~70%),检测波长为449nm,流速为1.0mL/min,进样量20μL。采用Franz透皮扩散池,以离体小鼠腹部皮肤为透皮屏障,3%薄荷醇、3%氮酮、1%,3%,5%油酸为吸收促进剂,测定岩藻黄质透皮贴剂透皮率,考察各类促渗剂对岩藻黄质经皮吸收的影响。采用《中国药典》释放度测定法第三法测定岩藻黄质水凝胶透皮贴剂体外释放度,释放介质为60%乙醇–生理盐水。结果各类吸收促进剂对岩藻黄质水凝胶透皮贴剂的经皮渗透均有一定的促进作用,以5%油酸最为显著。岩藻黄质水凝胶透皮贴剂的体外释放行为比较符合零级方程,J=11.785μg·cm-2·h-1。结论以亲水性高分子材料为基质,5%油酸为吸收促进剂,制成岩藻黄质水凝胶贴剂,为其药代动力学和临床研究研究提供依据。     

The role of hair follicles in the percutaneous absorption of caffeine

Aims

The skin and its appendages are our protective shield against the environment and are necessary for the maintenance of homeostasis. Hypotheses concerning the penetration of substances into the skin have assumed diffusion through the lipid domains of the stratum corneum. It is believed that while hair follicles represent a weakness in the shield, they play a subordinate role in the percutaneous penetration processes. Previous investigation of follicular penetration has mostly addressed methodical and technical problems. Our study utilized a selective closure technique of hair follicle orifices in vivo, for the comparison of interfollicular and follicular absorption rates of caffeine in humans.

Methods

Every single hair follicle within a delimited area of skin was blocked with a microdrop of a special varnish-wax-mixture in vivo. Caffeine in solution was topically applied and transcutaneous absorption into the blood was measured by a new surface ionization mass spectrometry (SI/MS) technique, which enabled a clear distinction to be made between interfollicular and follicular penetration of a topically applied substance.

Results

Caffeine (3.75 ng ml⁻¹) was detected in blood samples, 5 min after topical application, when the follicles remained open. When the follicles were blocked, caffeine was detectable after 20 min (2.45 ng ml⁻¹). Highest values (11.75 ng caffeine ml⁻¹) were found 1 h after application when the follicles were open.

Conclusions

Our findings demonstrate that hair follicles are considerable weak spots in our protective sheath against certain hydrophilic drugs and may allow a fast delivery of topically applied substances.

What is already known about this subject

• In recent years, it has been suggested that hair follicles represent important shunt routes into the skin for drugs and chemicals [1–3].
• In vitro studies have shown the importance of skin appendages for skin penetration by hydrophilic compounds [4]. Investigation of follicular penetration in vivo has been difficult due to the absence of appropriate analytical methods or suitable animal model systems.
• Recently, a new method was described that quantifies follicular penetration in vivo by using selective closure of hair follicles [5].
• Caffeine is frequently used in skin penetration experiments as a model for highly water-soluble compounds. Occlusion [6] and skin thickness [7] seem to have little influence on the penetration of caffeine. However, percutaneous absorption rates for caffeine exhibit regional skin differences in humans in vivo[1].

What this study adds

• The results of the present study demonstrate that a fast drug delivery of caffeine occurs through shunt routes. Therefore, hair follicles are considerable weak spots in our protective sheath against penetration into the body by hydrophilic substances.
• We showed that there is a quantitative distinction between follicular penetration and interfollicular diffusion of caffeine in vivo.
• These findings are of importance for the development and optimization of topically applied drugs and cosmetics. In addition, such properties must be considered in the development of skin protection measures.

     

Environmental and biological monitoring in the estimation of absorbed doses of pesticides

Exposure to pesticides affects most of the population, not only persons occupationally exposed. In a context of high variability of exposure, biological monitoring is important because of the various routes by which exposure can occur and because it assesses both occupational and non-occupational exposure. The main aim of this paper was to critically compare estimates of absorbed dose measured by environmental and biological monitoring in situations in which they could both be applied. The combination of exposure measurements and biological monitoring was found to provide extremely important information on the behaviour of employees, and on the proper use and effectiveness of personal protection equipment.     

Conjunctival Penetration of Insulin and Peptide Drugs in the Albino Rabbit

An in vitro model was used to evaluate the conjunctival penetration of three peptides, [D-ala²]metenkephalinamide (YAGFM, MW 647), substance P (MW 1348), and insulin (MW 5778), in comparison with two nonpeptides, atenolol (MW 266) and timolol (MW 433). All three peptides were hydrolyzed to varying extents during penetration across the conjunctiva. The permeability coefficient for intact YAGFM and insulin was 4.5 ± 0.3 and 4.6 ± 0.7 µm sec^–1, respectively. These values were about two to five times lower than those for atenolol and timolol. No permeability coefficient could be calculated for substance P, since its transconjunctival flux never reached steady state. The conjunctival penetration of YAGFM and insulin was improved by about two and three times, respectively, with the addition of 1% Na glycocholate. Increasing the Na glycocholate concentration was more effective than changing the type of bile salt in improving the conjunctival penetration of insulin. The maximum factor of improvement was 12, as the Na glycocholate concentration was raised to 4%. The way in which Na deoxycholate, glycocholate, and taurocholate affected the conjunctival penetration of atenolol, timolol, and insulin suggests that these three bile salts improved mainly the transcellular penetration of the compounds studied.     

新型经皮渗透促进剂及作用机制的研究进展

角质层(stratumcorneum,SC)是皮肤给药的主要屏障,无论是局部经皮的皮内给药还是经皮吸收进入体循环发挥全身作用都必须克服SC的屏障作用。但绝大部分药物都难以有效地透过SC,在众多克服SC的方法中,化学渗透促进剂(chemical penetration enhancers,CPE)的应用最广泛。除传统的醇类、亚砜类、脂肪酸类、酯类、氮酮、多元醇类等,又发现或合成了许多新型高效的促进剂。文中对近年来国内外关于新型渗透促进剂的文献进行综述,以期为合成和发现更加安全、高效的渗透促进剂提供线索。     

白藜芦醇三甲醚乳胶体外经皮渗透研究

目的制备白藜芦醇三甲醚(BTM)乳胶,考察载药量、促渗剂及其组合对BTM经皮渗透性的影响,评价药物透皮给药的可行性。方法以卡波姆940为凝胶基质制备BTM乳胶,选用改良Franz扩散池,以离体乳猪腹部皮肤为屏障进行体外经皮渗透实验,用HPLC-UV法测定各时间点接收室中药物浓度,计算经皮渗透动力学参数。结果载药量由1%增加到2%时,BTM 24 h单位面积渗透量增加1倍,2%与4%乳胶渗透量没有统计学差异(P>0.1)。促渗剂均可显著促进BTM透皮吸收,其透皮速率为:2%香叶醇>2%肉豆蔻酸异丙酯>2%油酸>2%氮酮>2%橙花叔醇>无促渗剂;香叶醇的浓度大小对BTM的透皮吸收无明显影响(P>0.05);与单用2%香叶醇相比,促渗剂联用(2%香叶醇+2%丙二醇、2%香叶醇+2%肉豆蔻酸异丙酯)未显示出显著协同促渗作用(P>0.05),而2%香叶醇+2%异丙醇则显示弱拮抗促渗作用(P<0.05)。结论常用促渗剂均能不同程度促进BTM经皮渗透,载药量为2%、促渗剂为2%香叶醇时,BTM体外透皮可达最大吸收。但BTM体外透皮吸收具有饱和性,该结果为BTM经皮给药研究提供了基础。     

N-三甲基壳聚糖对双氯芬酸钠经皮渗透作用的研究

目的:考察N-三甲基壳聚糖(N-trimethyl chitosan,TMC)作为透皮吸收促进剂的作用。方法:用壳聚糖及碘甲烷为主要原料,合成季铵化程度为60%的TMC,即TMC60,通过1H-NMR确定其季铵化程度。以2%氮酮为阳性对照,以双氯芬酸钠为模型药物,以离体小鼠皮肤为屏障,采用预处理法考察2%TMC60对双氯芬酸钠透过离体皮肤的促渗作用。结果:经~1H- NMR确定合成得到的TMC60季铵化程度为67.2%。体外透皮实验中,累积透过量及稳态透皮速率大小顺序均为:TMC60组>氮酮组>空白组,TMC60的促进作用强度大于同浓度的氮酮(P<0.05)。结论:TMC对双氯芬酸钠具有较好的经皮促渗透作用。     

N-三甲基壳聚糖对环孢素经皮渗透作用的试验研究

OBJECTIVE To study the penetration effect of N-trimethyl chitosan(TMC) on Cyclosporin.METHODS TMC60 was synthesized by a two-step method using chitosan and methyl-iodide.The degree of quaternization(DQ) of TMC was determined by 1H-NMR.The excised mice ski     

N-三甲基壳聚糖对环孢素经皮渗透作用的试验研究

目的考察N-三甲基壳聚糖(N-trim ethyl ch itosan,TMC)作为透皮吸收促进剂的作用大小。方法用壳聚糖及碘甲烷为主要原料,合成季铵化程度为60%的TMC,即TMC60,通过1H-NMR确定其季铵化程度。以2%氮酮为阳性对照,以环孢素为模型药物,以离体小鼠皮肤为屏障,采用预处理法考察2%TMC60对环孢素透过离体皮肤的促进作用。结果经1H-NMR确定合成得到的TMC60季铵化程度为67.2%。体外透皮实验中,累积透过量及稳态透皮速率大小顺序均为:TMC60组>氮酮组>空白组,TMC60的促进作用强度大于同浓度的氮酮(P<0.05)。结论TMC对环孢素具有较好的经皮渗透作用。     

In vitro skin penetration of propranolol enantiomers

Transfer rates of individual enantiomers of propranolol across human skin were determined in vitro. Percutaneous penetration of propranolol from propylene glycol was negligible at the concentration previously reported to show enantioselective transfer in rat skin. Transfer of (R)- and (S)-propranolol from aqueous solutions of both the racemate and the pure enantiomers showed no differences in the rates of penetration demonstrating that the rate of transfer of propranolol across human skin from these solutions was independent of the stereochemistry of the drug. In addition there was no evidence for racemisation during the transfer process.     

氮酮对丙酸氯倍他索乳膏经皮渗透和吸收的影响

目的：考察氮酮对丙酸氯倍他索乳膏经皮渗透的作用,通过比较累积通过量和皮层中量,分析在该制剂中使用氮酮的利弊。方法：采用直立式扩散池,考察氮酮在０．５％、１．０％、２．０％和５．０％浓度下０．０５％丙酸氯倍他索乳膏经皮渗透２、４、６、８、１０、２４ｈ后累积透过量和稳态流量;分别测定了经皮渗透２４ｈ后每克皮肤组织中部他索的量。结果：４个浓度氮酮均极显著促进ＣＢＴ乳膏经皮渗透（Ｐ〈０．０１）,Ｑ２４分别