阿昔洛韦凝胶中促渗剂的选择

目的研究薄荷醇和氮酮对阿昔洛韦凝胶皮肤渗透性的影响。方法制备包含不同浓度的薄荷醇和氮酮的5%阿昔洛韦凝胶，采用改良的Franz扩散池，用体外小鼠皮肤进行透皮作用研究，紫外分光光度法测定阿昔洛韦累积渗透量及渗透速率。结果不含促渗剂的阿昔洛韦凝胶的渗透速率为0.862 mg·h^-1，含1%，3%，5%薄荷醇的阿昔洛韦凝胶的渗透速率分别目的研究薄荷醇和氮酮对阿昔洛韦凝胶皮肤渗透性的影响。方法制备包含不同浓度的薄荷醇和氮酮的5%阿昔洛韦凝胶，采用改良的Franz扩散池，用体外小鼠皮肤进行透皮作用研究，紫外分光光度法测定阿昔洛韦累积渗透量及渗透速率。结果不含促渗剂的阿昔洛韦凝胶的渗透速率为0.862 mg·h^-1，含1%，3%，5%薄荷醇的阿昔洛韦凝胶的渗透速率分别为0.839，1.973，0.967 mg·h^-1，含1%，3%，5%氮酮的阿昔洛韦凝胶的渗透速率分别为0.693，0.969，0.789 mg·h^-1，含3%薄荷醇和1%，3%，5%氮酮的阿昔洛韦凝胶的渗透速率分别为1.237，0.997，0.928 mg·h^-1。结论3%薄荷醇对阿昔洛韦凝胶有明显的促渗作用。为0.839，1.973，0.967 mg·h^-1，含1%，3%，5%氮酮的阿昔洛韦凝胶的渗透速率分别为0.693，0.969，0.789 mg·h^-1，含3%薄荷醇和1%，3%，5%氮酮的阿昔洛韦凝胶的渗透速率分别为1.237，0.997，0.928 mg·h^-1。结论3%薄荷醇对阿昔洛韦凝胶有明显的促渗作用。     

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...     

不同基质及促渗剂对奥氮平贴剂体外透皮吸收的影响

目的:研究不同基质及促渗剂对奥氮平贴剂体外透皮促渗作用的影响.方法:采用不同基质及促渗剂制备奥氮平贴剂;采用卧式双室扩散池,以离体大鼠皮肤为模型,通过HPLC法测定药物浓度,拟合奥氮平透皮吸收的累积透过量和透过速率.结果:由Duro-Tak 87-4098型压敏胶制备的贴剂具有较好的稳态渗透速率,5%薄荷脑+10%肉豆蔻酸异丙酯合用对奥氮平促渗效果明显,促渗倍率达5.86倍.结论:奥氮平在以5%薄荷脑+10%肉豆蔻酸异丙酯为促渗剂,Duro-Tak 87-4098型压敏胶为基质时具有较好的透皮吸收.     

促渗剂对贴剂中双氯芬酸二乙胺的经皮促渗作用

目的 制备双氯芬酸二乙胺(DDEA)水凝用胶贴剂,研究不同促渗剂对水凝胶贴剂中DDEA体外透皮吸收的影响.方法 以具有良好生物相容性的亲水性高分子材料为基质材料制备DDEA水凝胶贴剂;用离体大鼠腹部皮肤为模型,采用改良Franz扩散池装置进行经皮渗透实验.HPLC法测定不同时间点接收池中DDEA的浓度,计算药物的累积渗透量和经皮渗透动力学参数.结果 不同促渗剂对DDEA的经皮渗透有不同程度的促进作用,其中薄荷脑的促渗作用最为显著.薄荷脑对DDEA的促渗在1%～5%,呈正相关剂量效应关系,薄荷脑用量为5%时,药物的稳态透皮速率可达18.121 μg·cm-2·h-1,与空白对照组相比增渗倍数为5.45.结论 薄荷脑可作为DDEA水凝胶贴剂的促渗剂,并可开发此新型水凝胶贴剂.     

促渗剂促进氨氯地平凝胶剂透皮作用的研究

目的 :研究促渗剂对氨氯地平凝胶剂透皮作用的影响。方法 :采取简单小室法 ,用离体小鼠皮肤进行体外透皮扩散试验 ,计算含不同促渗剂的 2 %氨氯地平凝胶的累积渗透量Q及渗透速率k。结果 :1%～ 5 %薄荷脑、1%～ 5 %氮酮对 2 %氨氯地平凝胶的累积渗透量Q及渗透速率k均显著地提高 (P <0 0 1) ;10 %～ 30 %丙二醇显著地降低 2 %氨氯地平凝胶的Q与k值 (P <0 0 1) ,并明显抑制薄荷脑、氮酮的促渗作用 ;薄荷脑与氮酮的联用则无联合增效作用。结论 :提示薄荷脑、氮酮可作为促渗剂在氨氯地平凝胶剂中单独使用     

透皮促渗剂对醋酸地塞米松壳聚糖凝胶透皮特性的影响

目的观察透皮促渗剂对醋酸地塞米松壳聚糖凝胶透皮特性的影响。方法实验分为无促渗剂组和促渗剂组。无促渗剂组为0.75%药物5%壳聚糖凝胶剂;促渗剂组根据含促渗剂不同又分为月桂氮酮+丙二醇、月桂氮酮、丙二醇+二甲亚砜、二甲亚砜+月桂氮酮组。以无毛大鼠皮肤为渗透屏障,进行体外渗透实验,分析该凝胶稳态透皮速率（Js）和Js提高率。结果无促渗剂组①Js为（3.75±0.56） μg&#8226;（cm2） 1&#8226;h 1。促渗剂组效果明显,其中二甲亚砜+月桂氮酮组②Js为（8.12±0.58） μg&#8226;（cm2） 1&#8226;h 1,月桂氮酮+丙二醇组③Js为（5.41±0.74） μg&#8226;（cm2） 1&#8226;h 1,丙二醇+二甲亚砜组④Js为（4.31±0.42） μg&#8226;（cm2） 1&#8226;h 1,月桂氮酮组⑤Js为（4.35±0.36） μg&#8226;（cm2） 1&#8226;h 1。与①比较,②的Js提高率为2.17%（P＜0.01）,与③④⑤比较,②的Js分别为1.51,1.89,1.87倍（P＜0.05或P＜0.01）。结论混合促渗剂具有比单一促渗剂更好的促渗效果。     

促渗剂对酮洛芬凝胶透皮作用的影响

采取简单小室法,用离体小鼠皮肤进行体外透皮扩散试验,计算含不同促渗剂的２％酮洛芬凝胶的累积渗透量Ｑ及渗透速率ｋ。比较其结果,１￣５％薄荷脑、１￣５％氮酮对２％酮洛芬凝胶的累积渗透量Ｑ及渗透速率ｋ均显著地提高,１０￣３０％丙二醇显著地降低２％酮洛芬凝胶的Ｑ与ｋ,并明显抑制薄菏脑、氮酮的促渗作用;薄荷脑与氮酮的联用并无联合增效作用。提示薄荷脑、氮酮可作为促渗剂在酮芬胶剂中单独全盘和。     

醋酸烯诺孕酮透皮贴剂的制备及不同促渗剂对其促渗作用考察

目的：制备醋酸烯诺孕酮透皮贴剂,并考察5种促渗剂单用和联用对贴剂的促渗作用。方法：采用正交试验,以初黏力和累积渗透量（Q）为指标,优化Druo-tak87-2287压敏胶、聚维酮（PVP）K30、乙酰丙酮铝的用量,考察250h内的平均Q;比较质量分数均为5%的氮酮（Azone）、油酸（OA）、肉豆蔻酸异丙酯（IPM）、桉叶油（OE）和丙二醇（PG）及1%、3%、5%、7%OE和3%OE＋1%Azone、3%OE＋3%Azone、3%OE＋5%Azone的贴剂250h内的Q、透皮速率常数（Jss）及增渗倍数。结果：压敏胶、PVPK30、乙酰丙酮铝的用量分别为15、2、0.03g,250h的平均Q为60.83μg/cm2;5%OE单用时250h内的Q最大,为118.12μg/cm2,Jss为0.71μg/（cm2·h）,增渗倍数为2.2;3%OE＋5%Azone联用时250h内的Q最大,为175.96μg/cm2,Jss为1.102μg（/cm2·h）,增渗倍数为3.22。结论：所制备的贴剂初黏力符合要求,3%OE＋5%Azone对醋酸烯诺孕酮透皮贴剂有明显促渗作用。     

不同基质及促渗剂对姜黄素脂质体凝胶经皮渗透的影响

考察了凝胶基质种类及浓度和促渗剂对姜黄素脂质体凝胶经小鼠离体皮肤的累积渗透量及皮肤滞留量的影响.所得优化处方为:以1％卡波姆为凝胶基质,加入2％月桂氮草酮和2％薄荷醇为复合促渗剂.所得制品的24h累积渗透量、稳态渗透速率及皮肤滞留量均显著高于姜黄素脂质体.     

噻吗洛尔贴剂经皮渗透促渗剂的筛选

目的：通过以噻吗洛尔贴剂的多种新型促渗剂进行筛选来得到促渗效果最好的新型促渗剂。方法：利用大鼠皮肤渗透模型和紫外分光光度法。结果：选用桉叶油与1，2-丙二醇（1：1）为贴剂促渗剂。结论：噻吗洛尔经皮吸收贴剂，具有使用方便、可持续按一定速率给药、毒副作用小等优点。     

促进剂对酮洛芬巴布剂体外透皮性的影响探讨

目的:通过几种常用促进剂对酮洛芬巴布剂体外促渗作用研究,筛选出适合用于酮洛芬巴布剂的透皮促进剂。方法:分别制备单独含2%或4%的桉叶油、油酸、薄荷脑、聚乙二醇400、月桂氮芯卓酮、聚山梨醇酯-80的酮洛芬巴布剂贴片,以及4%的桉叶油分别与2%的油酸、薄荷脑、聚乙二醇400合用的酮洛芬巴布剂贴片,采用改良Franz透皮扩散池,以离体小鼠背部皮肤为透皮屏障,贴敷12h,以渗透速率及12h累积渗透量为指标,探讨促进剂对酮洛芬体外透皮性的影响。结果:与空白组对照,2%聚山梨醇酯-80、2%月桂氮卓芯酮单独使用不能明显提高酮洛芬的渗透速率(P>0.05),4%聚山梨醇酯-80、4%月桂氮卓芯酮和其他的促进剂都能明显的提高酮洛芬的经皮渗透(P<0.01),对酮洛芬透皮速率提高大小顺序为油酸≥桉叶油>薄荷脑>聚乙二醇400>月桂氮卓芯酮>聚山梨醇酯-80。结论:油酸、桉叶油、薄荷脑、聚乙二醇400均可作为酮洛芬巴布剂透皮促进剂。     

Structure Activity Relationships in Alkylammonium C12-Gemini Surfactants Used as Dermal Permeation Enhancers

The purpose of this study was to determine the ability and the safety of a series of alkylammonium C12-gemini surfactants to act as permeation enhancers for three model drugs, namely lidocaine HCl, caffeine, and ketoprofen. In vitro permeation studies across dermatomed porcine skin were performed over 24 h, after pretreating the skin for 1 h with an enhancer solution 0.16 M dissolved in propylene glycol. The highest enhancement ratio (enhancement ratio (ER) = 5.1) was obtained using G12-6-12, resulting in a cumulative amount of permeated lidocaine HCl of 156.5 μg cm⁻². The studies with caffeine and ketoprofen revealed that the most effective gemini surfactant was the one with the shorter spacer, G12-2-12. The use of the latter resulted in an ER of 2.4 and 2.2 in the passive permeation of caffeine and ketoprofen, respectively. However, Azone was found to be the most effective permeation enhancer for ketoprofen, attaining a total of 138.4 μg cm⁻² permeated, 2.7-fold over controls. This work demonstrates that gemini surfactants are effective in terms of increasing the permeation of drugs, especially in the case of hydrophilic ionized compounds, that do not easily cross the stratum corneum. Skin integrity evaluation studies did not indicate the existence of relevant changes in the skin structure after the use of the permeation enhancers, while the cytotoxicity studies allowed establishing a relative cytotoxicity profile including this class of compounds, single chain surfactants, and Azone. A dependence of the toxicity to HEK and to HDF cell lines on the spacer length of the various gemini molecules was found.     

Percutaneous Penetration of Acyclovir Through Excised Hairless Mouse and Rat Skin: Effect of Vehicle and Percutaneous Penetration Enhancer

The effects of vehicle and percutaneous penetration enhancer on the penetration of acyclovir through excised hairless mouse and rat skin were investigated. Four solvents, propylene glycol (PG), ethanol (ET), isopropanol (IPA), and isopropyl myristate (IPM), were employed as vehicles, in combination with four enhancers, l-farnesylazacycloheptan-2-one (7FU), l-geranylazacycloheptan-2-one (7GU), l-geranylazacyclopentan-2-one (5GU), and l-dodecylazacycloheptan-2-one (Azone). Acyclovir was suspended in vehicles to avoid the effect of the thermodynamic activity of acyclovir in the vehicle. The penetration of acyclovir through hairless mouse skin from IPA was enhanced by 7GU, whereas that from IPM was not affected. All combinations of vehicle and penetration enhancer were examined using rat skin. No effect of the enhancers was observed in the IPM vehicle. The estimated solubility parameters of vehicles and enhancers indicated that the polarities of IPM and the enhancers are similar, which prevents effective penetration of the enhancers from IPM. However, the penetration of acyclovir from the other vehicles was increased by the enhancers. The combination of hydrophilic vehicle and hydrophobic enhancer resulted in a large enhancing effect. The disappearance of the enhancers from the vehicle correlated with their enhancing activity, but other factors also seemed to affect the penetration enhancement of acyclovir.     

Effects of Enantiomer and Isomer Permeation Enhancers on Transdermal Delivery of Ligustrazine Hydrochloride

Enantiomers and isomers, such as D-limonene, L-limonene, and α-terpinene, were selected as enhancers. The effects and mechanisms of penetration enhancers on in vitro transdermal delivery of ligustrazine hydrochloride (LH) across hairless porcine dorsal skin were investigated. Transdermal fluxes of LH through porcine skin were determined in vitro by Franz-type diffusion cells. D-limonene, L-limonene, and α-terpinene could significantly promote the transdermal fluxes of LH, but no statistical difference (p > 0.05) between them was found. The lag time of L-limonene and α-terpinene were 2.55 and 2.20 times compared with that of D-limonene. Fourier transform-infrared (FTIR) was carried out to analyze the effects of enhancers on the biophysical natures of the stratum corneum (SC) and the permeation enhancement mechanism. FTIR spectra revealed that the changes of peak shift and peak area due to C-H stretching vibrations in the SC lipids were associated with the selected enhancers. All of them could perturb and extract the SC lipids to different extent and L-limonene showed obvious changes. Morphological changes of the skin treated with enhancers were monitored by a scanning electron microscope (SEM). The extraction of the SC lipids by the enhancers led to the disruption of SC and the desquamated SC flake. Apparent density (AD) was newly proposed to estimate the desquamated extent of SC flake. The results showed that the enantiomers and isomers enhanced the permeation of LH by pleiotropic mechanisms.     

Effects of Dimethylformamide and L-Menthol Permeation Enhancers on Transdermal Delivery of Quercetin

In this work a feasibility study of transdermal delivery system for quercertin (Q) in carbopol gel through abdominal hairless pig skin in vitro was performed. Dimethylformamide (DMF) and L-menthol (M) were selected as enhancers. Permeation experiences were carried out by using Franz-type diffusion cells. Phosphate saline buffer (pH 7.4) was used in the receptor compartments. All the system was maintained at 32 ± 0.5°C with a circulating water jacket and magnetic stirring (180 rpm). Samples were analysed by UV-VIS spectrophotometer at 255 nm. Flux (J_m) values, permeation (P) and diffusion (D) coefficients were obtained. Results of Q in CG permeation experiences with different percentages of DMF and M showed that 16.7% DMF and 1.95% L-menthol enhancers were the best quantities for the system tested. Enhancer effect can be attributed to direct action on membrane structure by promoting its distension. Therefore, enhancer substitutes for water in pores, improving active principal permeation through pig skin. M significantly increases Q permeation about 17 times higher than control. The results of permeation experiments with M and DMF using the same enhancer concentration (1.42%) conclude that M action is 9 times higher than DMF, approximately, indicating that M is an effective enhancer for a transdermal therapeutic system of Q in CG as vehicle.     

增渗剂和离子导入对尼莫地平体外经皮渗透性的影响

研究了增渗剂和离子导入技术对尼莫地平（ＮＭ）体外经皮渗透性的作用,渗透促进剂如３％和５％月桂氮卓酮及１０％油酸的２０％丙二醇溶液能增加药物的渗透性（Ｐ＜００５）,其增渗比分别为４６６、４３９及１２６４．离子导入技术能够显著增加药物的渗透性（Ｐ＜００１）,渗透比为８０３．同时表明１０％油酸和３％的月桂氮卓酮丙二醇溶液与离子导入并用,渗透比为１５、８５、８９２．     

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.     

Dimethylamino Acid Esters as Biodegradable and Reversible Transdermal Permeation Enhancers: Effects of Linking Chain Length,Chirality and Polyfluorination

Purpose  Series of N,N-dimethylamino acid esters was synthesized to study their transdermal permeation-enhancing potency, biodegradability and reversibility of action. Effects of chirality, linking chain length and polyfluorination were investigated. Materials and Methods   In vitro activities were evaluated using porcine skin and four model drugs—theophylline, hydrocortisone, adefovir and indomethacin. Biodegradability was determined using porcine esterase, reversibility was measured using electrical resistance. Results  No differences in activity were found between (R), (S) and racemic dodecyl 2-(dimethylamino)propanoate (DDAIP). Substitution of hydrocarbon tail by fluorocarbon one resulted in loss of activity. Replacement of branched linking chain between nitrogen and ester of DDAIP by linear one markedly improved penetration-enhancing activity with optimum in 4–6C acid derivatives. Dodecyl 6-(dimethylamino)hexanoate (DDAK) was more potent than clinically used skin absorption enhancer DDAIP for theophylline (enhancement ratio of DDAK and DDAIP was 17.3 and 5.9, respectively), hydrocortisone (43.2 and 11.5) and adefovir (13.6 and 2.8), while DDAIP was better enhancer for indomethacin (8.7 and 22.8). DDAK was rapidly metabolized by porcine esterase, and displayed low acute toxicity. Electrical resistance of DDAK-treated skin barrier promptly recovered to control values. Conclusion  DDAK, highly effective, broad-spectrum, biodegradable and reversible transdermal permeation enhancer, is promising candidate for future research.     

促渗剂对司来吉兰贴片透皮性能的影响

目的:考察不同质量分数的氮酮、油酸和肉豆蔻酸异丙酯3种促渗剂对司来吉兰贴片经离体豚鼠皮渗透性的影响。方法:采用Franz扩散池进行体外经皮渗透试验,利用高效液相色谱法为浓度测定方法,以不含促渗剂的司来吉兰贴片为对照计算氮酮、油酸和肉豆蔻酸异丙酯的增渗比及表观扩散系数比较促渗剂渗透效果。结果:与对照组比较,质量分数为3%的3种促渗剂增渗倍数分别为1.53、1.37和1.26,表观扩散系数分别增至2.37、1.65、1.13倍。结论:3种促渗剂均可提高司来吉兰贴片的透皮性能,其中以3%氮酮的促渗效果较好。