薄荷醇衍生物对荜茇提取物贴剂中胡椒碱体外经皮通透性的影响

目的研究薄荷醇衍生物对荜茇提取物贴剂中胡椒碱体外经皮通透性的影响,探讨将荜茇提取物制成贴剂的可行性。方法采用卧式双室扩散池,以离体大鼠皮肤作为通透屏障进行体外透皮实验,用HPLC法测定接收池中胡椒碱的浓度。结果戊酸薄荷醇酯、己酸薄荷醇酯、丁酸薄荷醇酯和乳酸薄荷醇酯对胡椒碱经皮吸收有明显的促透效果,其中以戊酸薄荷醇酯的促透效果最好;庚酸薄荷醇酯、十四酸薄荷醇酯和油酸薄荷醇酯的促透作用不明显;薄荷醇对胡椒碱的经皮吸收有抑制作用。结论在含有化学促进剂的贴剂中,胡椒碱的累积透过量及稳态通透速率均显著增加,说明将荜茇提取物制成贴剂是可行的。     

渗透促进剂对止泻凝胶膏中胡椒碱透皮的影响

制备含不同渗透促进剂的止泻凝胶膏,采用Franz扩散池考察各处方的体外透皮行为.采用HPLC法测定制品中胡椒碱含量.结果表明,当促渗剂以4％的浓度单用时,N-甲基吡咯烷酮(NMP)的促渗效果最好,月桂氮时酮和1,2-丙二醇的效果相近.促进剂组合使用时促进胡椒碱透皮的作用更强,其中4％月桂氮艰酮+4％丙二醇+8％ NMP为本复方的渗透促进剂时效果较好.     

荜茇提取物中5个生物碱的含量测定与对垂体后叶素所致大鼠实验性心肌缺血的影响

目的 建立荜茇提取物中5个生物碱含量测定方法,并评估该提取物对垂体后叶素所致大鼠实验性心肌缺血的影响。方法 采用HPLC法同时测定5个生物碱的含量;采用经舌下静脉注射垂体后叶素造成急性心肌缺血模型,以造模前后T波变化绝对值、心率及其变化百分率为观测指标,评估荜茇提取物大、中、小三个剂量组对大鼠实验性心肌缺血的影响。结果 3批荜茇提取物中胡椒碱平均含量为56.1%、49.7%、51.6%;N-异丁基-2E,4E-十八烷二烯酰胺平均含量为4.48%、4.21%、4.28%;几内亚胡椒碱平均含量为0.461%、0.378%、0.396%;荜茇明碱平均含量为1.73%、1.67%、1.70%;胡椒酰胺平均含量为0.554%、0.461%、0.493%。荜茇提取物大、中、小剂量组均有降低T波变化绝对值的作用;除大剂量组在个别时间点有降低心率的作用之外,其它各实验组在各时间点对心率变化率无显著影响。结论 所建立的生物碱含量测定分析方法可准确测定荜茇提取物中5个生物碱的含量;药效试验证明荜茇提取物具有较好的抗心肌缺血活性。     

荜茇提取物对地鼠脂质代谢紊乱的影响

目的研究荜茇提取物对高血脂症地鼠血脂的影响。方法给予高脂饲料建立金黄地鼠高血脂模型,将动物随机分为正常对照组、模型组、辛伐他汀组、荜茇提取物组、去胡椒碱荜茇提取物组,除正常对照组外其余各组均给予高脂饲料喂养2或4周,每周测量体质量,分别在第2周末和第4周末用全自动生化分析仪检测血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、肝脏指数、肝脂质TC和TG。结果与正常对照组比较,模型组TC,TG和LDL显著增加(P<0.01),HDL显著降低;与模型组比较,荜茇提取物组在第2周和第4周均能显著降低TC,TG和LDL,显著升高HDL(P<0.05或P<0.01);去胡椒碱荜茇提取物组在第2周能显著降低LDL,升高HDL,在第4周有降低TC,TG,LDL的趋势,但差异无统计学意义,能显著升高HDL(P<0.05);各受试物组动物在前两周体质量显著低于模型组,而后2周差异无统计学意义;4周时荜茇提取物组能显著降低肝脂质TC,TG;各受试物组均能显著降低肝指数。结论荜茇提取物可显著改善高血脂症地鼠血脂水平,其中胡椒碱为其主要有效成分,且与其他各成分有协同降血脂作用。     

肠腑康胶囊B的质量标准研究

目的建立肠腑康胶囊B(北败酱、厚朴、荜茇等)的质量控制方法。方法采用薄层色谱对本制剂中北败酱、厚朴、荜茇进行定性鉴别;以高效液相色谱法对荜茇中主要成分胡椒碱进行含量测定。结果薄层色谱可鉴别出北败酱、厚朴、荜茇的特征性斑点;制剂中胡椒碱的平均含量为6.76mg·g-1。结论方法简便,专属性强,重现性好,可用于其质量控制。     

高效液相色谱法测定六味木香散中荜茇的含量

六味木香散系蒙古族验方 ,由木香、荜茇、栀子等六味药组成。荜茇具有温中散寒、下气止痛功效 ,为六味木香散主药。胡椒碱是荜茇药材所含主要有效活性成分 ,含量较高 ,为控制六味木香散质量 ,将胡椒碱作为其内控指标。薄层扫描法测定六味木香散中荜茇的含量[1] ,操作方法比较繁琐、费时 ,且误差较大。本文采用高效液相色谱法测定[2 ] ,操作简单、省时 ,结果准确、可信 ,精密度、重现性较好。1　仪器与试药ＦＲＡＮＫ - 2 0 0 0Ｐ型高效液相色谱仪 (配有色谱工作站 ) ;ＴＰ - 30 0超声波振荡器 ;甲醇为色谱纯 ;其他试药均为优级纯 ;胡椒碱对…     

HPLC测定荜茇三味散中胡椒碱的含量

目的:建立荜茇(荜茇、诃子、山楂)三味散中胡椒碱的含量测定的方法。方法:采用高效液相色谱法测定,色谱柱为Kromasil(C18,5um,250mm×4.6mm)色谱柱,流动相为甲醇-水(77:23),检测波长为343nm。结果:胡椒碱在进样量6.96ug~1.99ug范围内与峰面积呈良好的线性关系,r=0.9999,平均回收率为102.9%,RSD为1.4%。结论:HPLC法简单准确,精密度高,分离度良好,可用于荜茇三味散的质量控制。     

荜茇及其有效成分胡椒碱的研究进展

目的:对荜茇及其有效成分胡椒碱药理作用的研究进展进行阐述,为其进一步研究及合理利用提供参考.方法:通过查阅国内外近15年有关荜茇及其有效成分胡椒碱的相关文献,并对其进行整理与归纳.结果:荜茇及其有效成分胡椒碱具有抗癌、抗氧化、抗炎、抗菌、免疫调节、保肝、神经保护等多种药理活性及安全性.结论:通过对荜茇及其有效成分胡椒碱...     

透皮促进剂对酮基布洛芬体外经皮渗透的影响

酮基布洛芬(KP)体外经皮渗透性实验研究表明,KP经皮渗透是一个零级速率过程。利用离体鼠皮为渗透屏障考察KP在月桂氮艹卓酮(AZ)、油酸(OA)、1-甲基-2-吡咯烷酮(2P)、N,N-二甲基甲酰胺(DMF)、月桂醇(LA)、丙二醇(PG)6种透皮促进剂作用下的透皮效果,发现这些透皮促进剂对KP透皮速率的影响有明显差别。其中油酸、月桂氮艹卓酮、1-甲基-2-吡咯烷酮和丙二醇可促进KP吸收透皮,促进强度依次为OA>AZ>2P>PG,并且两种透皮促进剂OA与AZ或2P合用有较好的协同作用,而DMF、月桂醇和高浓度丙二醇则阻滞KP经皮渗透。     

HPLC法测定荜茇根中胡椒碱的含量

目的:建立测定荜茇根中胡椒碱含量的方法。方法:采用高效液相色谱法。色谱柱为Inertsil ODS-3(250 mm×4.6 mm,5μm),流动相为甲醇-水(77∶23,V/V),检测波长为343 nm,流速为1.0 ml/min,柱温为30℃。结果:胡椒碱的质量浓度在0.000 8⁰.024 0 mg/ml范围内与其峰面积积分值呈良好的线性关系(r=0.999 9);精密度、稳定性、重复性试验的RSD<2%;平均加样回收率为100.85%,RSD=0.82%(n=6)。结论:该方法简便、快速、准确、重复性好,可用于荜茇药材的质量控制。     

6种促进剂对西替利嗪体外经皮渗透的影响

目的 :研究 6种不同的促进剂对西替利嗪体外经皮渗透的促进作用。方法 :用Valia Chien水平扩散池 ,选择了丙二醇、月桂氮芯卓 酮 (azone)、柠烯 (dipentene)、水杨酸甲酯、含 10 %薄荷脑的丙二醇、含 10 %樟脑的丙二醇作为促进剂 ,采用离体SD大鼠腹部皮肤用促渗剂预处理的方式 ,建立以去氯羟嗪为内标的反相离子对高效液相色谱法 ,测定接收液中西替利嗪的含量。结果 :除丙二醇和水杨酸外其余几种促进剂对西替利嗪体外经皮渗透都有显著的促进作用 (P <0 .0 1)。以含 10 %薄荷脑的丙二醇的促渗效果最好。结论 :月桂氮芯卓 酮、柠烯、薄荷脑、樟脑可以作为促渗剂用于西替利嗪经皮吸收制剂     

Effect of penetration enhancers on in vitro percutaneous penetration of nimesulide through rat skin

The influence of several penetration enhancers alone and/or in various combinations on the percutaneous penetration of nimesulide (NM) from Carbopol 934 based gel formulations was investigated. Skin permeation studies were performed using Franz-type diffusion cells and full-thickness abdominal rat skin. Various types of compounds such as ethanol, isopropyl alcohol, propylene glycol, Transcutol, Tween 80 and oleic acid were employed as penetration enhancers. The steady-state flux, the lag time and permeability coefficients of NM for each formulation were calculated. The results showed that the skin permeability of NM from gels tested was significantly increased (P < 0.05) by isopropyl alcohol (40%) and the combination of oleic acid (3%) with Transcutol (30%) when compared with the control formulation. In conclusion, these substances could be considered as penetration enhancers for NM topical formulations.     

Dermal penetration enhancement profile of hexamethylenelauramide and its homologues: in vitro versus in vivo behavior of enhancers in the penetration of hydrocortisone

Several amides of cyclic amines were prepared and tested as penetration enhancers in the diffusion of various drugs through hairless mouse skin in vitro. Hexamethylenelauramide (hexahydro-1-lauroyl-1H-azepine) was selected as a broad spectrum penetration enhancer worthy of further study. Later, the duration of the effect of various enhancers on the penetration barrier in vivo was determined by evaluating the in vitro diffusion of hydrocortisone through skins that had been pretreated in vivo. We found that the longer the pretreatment, the smaller the amount of penetrated hydrocortisone. Furthermore, our results suggested that differences exist in the retention of various enhancers in living mouse skin. The in vitro pretreatment experiments revealed that the penetration through dead skin is slow compared with the penetration through living skin. Neither the nature of the receptor phase, nor the increased temperature of the in vitro experiments, explain the striking differences between the in vivo and the in vitro experiments. Finally, the penetration of hydrocortisone through the stratum corneum in the presence of enhancers, as well as the penetration of 1-dodecylhexahydro-2H-azepin-2-one (laurocapram), hexamethylenelauramide, and oleic acid, were determined using a stratum corneum stripping technique. More hydrocortisone penetrated through the stratum corneum during the first 3 h in the presence of hexamethylenelauramide than in the presence of laurocapram or oleic acid.     

An insight into the role of barrier related skin proteins

It is well-known that intercellular lipids in the stratum corneum (SC) of the skin play an important role in maintaining barrier function, and many types of penetration enhancers affecting lipids are used in topical products to improve transdermal drug permeability. Recently, it was reported that functional proteins in tight junctions of the epidermis are important for barrier function. In this study, the effects of penetration enhancers such as fatty esters, amines/amides, and alcohols on the barrier function of the skin were evaluated in rat skin and normal human-derived epidermal keratinocytes (NHEK). All penetration enhancers decreased the electrical impedance (EI), however, the potencies of some penetration enhancers were not equal between rat skin and NHEK. The differences were clarified by immunohistochemical studies: some fatty esters decreased the immunoreactivity of involucrin and keratin 10 in the upper layer of the epidermis, while alcohols decreased the immunoreactivity of desmoglein-1, claudin-1, and E-cadherin located in the lower layer of the epidermis. From these results, it is suggested that penetration enhancers show new action mechanisms disturbing barrier-related proteins in epidermis, which are classified into two categories depending on their action sites.     

促渗剂对祖师麻总香豆素体外经皮渗透的影响

目的:研究几种常用促渗剂对祖师麻总香豆素体外经皮渗透的影响.方法:采用Tp-5智能扩散仪,离体SD大鼠腹部皮肤为渗透屏障,以累计渗透量为指标,用HPLC法测定有效成分祖师麻甲素的浓度.结果:氮酮、冰片合用丙二醇可作为促渗剂,用于祖师麻总香豆素经皮吸收制剂,且氮酮合用丙二醇效果最好.结论:为研发祖师麻经皮给药制剂提供了实验依据.     

Effect of natural penetration enhancers on dermal delivery of hydrocortisone acetate

The purpose of the research work was to develop microemulsion (ME) of hydrocortisone acetate (HCA) using natural penetration enhancers and to determine its possibility in effective dermal delivery. Eucalyptus oil, clove oil and lemon grass oil were selected as natural penetration enhancers and pseudo-ternary phase diagrams were plotted using Tween 80 as surfactant and ethanol as cosurfactant. ME of each penetration enhancer was optimized using three factors, three levels Box–Behnken design, with independent variables as penetration enhancer, Tween 80 and ethanol. Formulations were assessed for percentage drug release as dependent variable. Response of these formulations decreased as the concentration of oil ranged from high to low and the response showed positive effect with increase in concentration of Tween 80 and ethanol. The globule size of optimized batches of eucalyptus oil, clove oil and lemon grass oil were found to be 226.1, 129.04 and 818.9 nm respectively. Optimized batches of MEs were then incorporated in carbopol 940 to form ME based gel without affecting their structure. Ex vivo permeation studies showed that amount of drug permeated from ME based gels was less than ME formulation indicating greater retention of HCA into skin layers. Retention of drug in skin layers both dermis and epidermis was higher for all three natural penetration enhancer. Hence natural penetration enhancers can be used for effective delivery of topical corticosteroids to the skin for improved treatment of several skin diseases and can be a better choice over synthetic penetration enhancers in terms of safety.     

Penetration enhancer-containing vesicles (PEVs) as carriers for cutaneous delivery of minoxidil: in vitro evaluation of drug permeation by infrared spectroscopy

Recently, we carried out a research on new liposomal systems prepared by using in their composition a few penetration enhancers which differ for chemical structure and physicochemical properties. The penetration enhancer-containing vesicles (PEVs) were prepared by using soy lecithin and different amounts of three penetration enhancers, 2-(2-ethoxyethoxy) ethanol (Transcutol^®), capryl-caproyl macrogol 8-glyceride (Labrasol^®), and cineole.To study the influence of the PEVs on (trans)dermal delivery of minoxidil, in vitro diffusion experiments were performed through new born pig skin and the results were compared with that obtained applying the vesicular system without enhancer (control) after pretreatment of the skin with the various enhancers. In this study, Fourier transform infrared spectroscopy (FTIR), attenuated total reflectance FTIR (ATR-FTIR) and FTIR imaging were used to evaluate the effective penetration of minoxidil in the skin layers and to discover the influence of the enhancer on the drug topical delivery. These analytical studies allowed us to characterize the drug formulations and to evaluate the vesicle distribution into the skin. Recorded spectra confirmed that the vesicle formulations with penetration enhancers promoted drug deposition into the skin.     

4种透皮吸收促进剂对盐酸苯海拉明透皮性能的影响

目的:研究油酸、1,3-丙二醇、月桂氮酮、丙三醇4种透皮吸收促进剂对盐酸苯海拉明透皮性能的影响。方法:在一定量的盐酸苯海拉明溶液中分别加入4种不同浓度的透皮吸收促进剂,采用改良Franz扩散池进行体外透皮吸收试验,测定不同浓度下不同透皮吸收促进剂的24h累积透过量(Q)。结果:以Q为指标,促透作用油酸>1,3-丙二醇>月桂氮酮>丙三醇,且前三者分别以0.5%、0.5%、0.2%为最佳促透浓度,丙三醇未见有明显的促透作用。结论:4种透皮吸收促进剂在一定浓度下均可增强盐酸苯海拉明局部给药制剂的透皮吸收作用。     

不同透皮促进剂对环孢素A纳米粒丝素蛋白膜剂经皮渗透的影响研究

目的:研究不同透皮促进剂对环孢素A纳米粒丝素蛋白膜剂(简称环孢素A膜剂)经皮渗透的影响,并优选出其最佳透皮促进剂。方法:以不同浓度的氮酮、油酸、月桂醇、丙二醇、尿素单用及氮酮与其他辅料联用作为透皮促进剂,制备环孢素A膜剂;采用药物透皮扩散试验仪,以离体大鼠腹部皮肤为渗透屏障,40%乙醇-生理盐水为接收介质,高效液相色谱法为接收介质中药物含量的测定方法,比较不同透皮促进剂作用下环孢素A累积透皮量(Q)、稳态透皮速率(Js)、增渗倍数(ER)等。结果:氮酮、月桂醇、丙二醇、尿素对环孢素A膜剂均有透皮促进作用,其中以1%氮酮+2%丙二醇的透皮促进效果最好,令24h内Q提高至2.81倍、Js为6.59μg·cm-2·h-1、ER为2.59。结论:1%氮酮+2%丙二醇更适合作为环孢素A膜剂的透皮促进剂。