酮洛芬二元醇质体凝胶抗炎镇痛作用考察

摘 要 目的: 考察酮洛芬（KP）二元醇质体（KPBE）凝胶的抗炎镇痛作用及皮肤刺激性。方法: KPBE凝胶的镇痛效果采用小鼠热板法及醋酸扭体法进行观察,抗炎作用采用大鼠佐剂性关节炎模型研究其对足肿胀及滑膜关节组织的影响,并观察家兔经皮应用时的皮肤刺激反应。结果与相同浓度的KP一元醇质体（KPE）凝胶及市售KP凝胶进行比较。结果:与KPE凝胶及市售KP凝胶相比,KPBE凝胶可显著提高小鼠的热痛阈值(P<0.05) ,并能显著减少醋酸致小鼠扭体次数(P<0.05),对佐剂引起的大鼠足肿胀关节炎有明显的抑制作用(P<0.05),同时KPBE凝胶对豚鼠皮肤无明显刺激性。结论:KPBE凝胶具有抗炎镇痛、皮肤刺激性小的特点,值得进一步研发。     

麝香祛痛气雾剂的抗炎镇痛作用与毒理学考察

目的:研究麝香祛痛气雾剂局部给药的抗炎镇痛作用及毒性反应。方法:用二甲苯致小鼠耳肿胀和角叉菜胶致大鼠足跖肿胀,考察麝香祛痛气雾剂的抗炎作用;用小鼠醋酸扭体法和热板法,观察麝香祛痛气雾剂的镇痛作用。观察家兔一次性局部给药的急性毒性和皮肤刺激性,观察豚鼠给药的皮肤致敏性。结果:麝香祛痛气雾剂局部皮肤给药,可明显减轻小鼠耳肿胀度,降低角叉菜胶致大鼠足跖肿胀;对小鼠醋酸扭体和热板反应均呈剂量相关性镇痛作用;对家兔和豚鼠无明显急性毒性反应、刺激性和致敏作用。结论:麝香祛痛气雾剂局部给药,具有明显的抗炎镇痛作用,无明显毒性、刺激性和致敏性。     

CDG的镇痛、抗炎作用研究

目的观察CDG抗炎、镇痛和抗佐剂性关节炎的作用。方法采用醋酸扭体法、小鼠腹腔毛细血管通透性试验、二甲苯致小鼠耳肿胀试验和弗氏完全佐剂致大鼠佐剂性关节炎试验。结果CDG 0.04、0.08g.kg-1可明显减少冰醋酸所致小鼠的扭体反应次数和减轻佐剂致原发性大鼠右后足跖肿胀(P<0.05、0.01);CDG 0.08g.kg-1能显著抑制冰醛酸致小鼠毛细血管通透性增加(P<0.05)和明显减轻小鼠耳廓肿胀度(P<0.01)。结论CDG具有较好的镇痛、抗急性炎症和抗佐剂性关节炎的作用。     

半边莲不同提取物镇痛抗炎作用

目的研究半边莲不同溶剂提取物的镇痛抗炎作用。方法制备半边莲水提取物和75%乙醇提取物,采用醋酸扭体实验和热板实验测定半边莲提取物镇痛作用,二甲苯致小鼠耳廓肿胀实验和10%蛋清致小鼠足跖肿胀实验测定半边莲提取物抗炎作用。结果半边莲水提取物可明显抑制醋酸所致小鼠扭体反应（P＜0.01）;给予半边莲水提取物和醇提取物1,2 h,小鼠热板痛阈值明显提高（P＜0.05或P＜0.01）;半边莲提取物能抑制二甲苯所致小鼠耳廓肿胀（P＜0.05或P＜0.01）;半边莲提取物在致炎后0.5,1,2,4 h能显著抑制10%蛋清所致小鼠足跖肿胀（P＜0.05或P＜0.01）。结论半边莲提取物有明显的镇痛和抗炎作用。     

国产尼美舒利的药效学研究

本文研究了国产尼美舒利在小鼠、大鼠及家兔体内的抗炎、镇痛和解热作用.结果表明.尼美舒利抑制巴豆油致小鼠耳廓肿胀(ED_(50)为49.2mg·kg~(-1));抑制角叉菜胶致大鼠足肿(ED_(50)为2.75mg·kg(-1));0.6mg·kg~(-1)剂量对大鼠佐剂关节炎有显著预防和治疗作用。100mg·kg~(-1)对小鼠醋酸扭体法的抑制率为68％;对热板法致痛的痛阈提高率为55％。ip给药对蛋白胨致家兔发热的解热作用.其最小有效剂量为2mg·kg~(-1);5mg·kg~(-1)ig可显著降低啤酒酵母致大鼠升高的体温.证实国产尼美舒利具有很强的抗炎、镇痛和解热作用。     

金苓痛风舒微丸抗炎镇痛作用的实验研究

目的探讨金苓痛风舒微丸的抗炎、镇痛作用。方法采用二甲苯致小鼠耳廓肿胀实验、角叉菜胶致大鼠足跖肿胀实验观察其抗炎作用;采用冰醋酸致痛小鼠扭体实验、小鼠尾根部加压致痛实验观察其镇痛作用。结果金苓痛风舒微丸可明显抑制二甲苯所致的小鼠耳廓的炎症肿胀（P〈0.05）;有效抑制角叉菜胶致大鼠足跖肿胀程度（P〈0.05）;对醋酸致小鼠扭体反应有明显对抗作用（P〈0.05）;显著升高小鼠痛阈值。结论金苓痛风舒微丸具有显著的抗炎、镇痛作用。     

白术醇提物的抗炎镇痛活性研究

目的 探讨白术醇提物的抗炎镇痛活性,为进一步研究白术抗炎镇痛的作用机制提供基础。方法 采用热板法测定白术不同剂量组小鼠的痛阈值,腹腔注射0.6%醋酸刺激致痛模型(扭体法)观察白术3个不同剂量的镇痛作用;采用二甲苯致小鼠耳廓肿胀实验和角叉菜胶致大鼠足肿胀实验观察白术3个不同剂量的抗炎作用。结果 高、中剂量的白术醇提物可显著增加小鼠的热板痛域值(P<0.01,P<0.01),减少腹腔注射醋酸引起的小鼠扭体反应次数(P<0.01,P<0.01),而白术低剂量组不能有效的提高小鼠的痛阈值(P>0.05)和减少扭体反应次数(P>0.05)。在抗炎试验中,高、中剂量的白术醇提取可显著抑制小鼠耳廓肿胀度(P＜0.01,P＜0.01),而低剂量组对小鼠耳廓肿胀抑制效果不明显(P＞0.05);高剂量组在2h后能显著抑制大鼠足跖肿胀,中剂量组(除6h时间点)与白术低剂量组(除3h时间点)在药后0.5-6h之间与模型组比较均无显著性差异(P＞0.05)。结论 白术醇提物具有较好的抗炎、镇痛作用,并且随着剂量的增大,抗炎镇痛活性增强。     

尼美舒利醇质体的体外经皮渗透特性及皮肤刺激性

目的:考察醇质体作为尼美舒利经皮给药载体的体外渗透性及刺激性。方法:采用注入法制备尼美舒利醇质体,采用Franz扩散池和鼠皮进行体外渗透实验,HPLC测定药物浓度并计算药物稳态透皮速率、12 h累积释放量及皮内滞留量;采用小鼠皮肤红斑平均积分考察尼美舒利醇质体刺激性。结果:测得尼美舒利醇质体的稳态经皮渗透速率和12 h累积释放量分别是(16.28±1.68)μg.(cm2.h)-1,(195.38±19.89)μg/cm2,与脂质体相比提高了1.9倍(P<0.05);而醇质体的皮内滞留量为(318.67±38.57)μg/cm2,仅是脂质体的1.07倍(P>0.05)。皮肤刺激性实验显示,NIM醇质体的红斑指数与生理盐水的差异并不明显(P>0.05)。结论:尼美舒利醇质体的经皮渗透性和皮肤刺激性都优于脂质体,是一种有效的经皮给药制剂。     

舒利通颗粒的镇痛抗炎作用研究

目的:研究舒利通颗粒的镇痛抗炎作用。方法:采用醋酸建立小鼠疼痛扭体模型;采用二甲苯致小鼠耳廓肿胀和大鼠棉球肉芽肿形成模型;分别观察舒利通颗粒的镇痛及抗炎作用。结果:舒利通颗粒可显著降低小鼠扭体反应次数(P<0.01);减轻小鼠耳廓肿胀(P<0.05);减少大鼠肉芽肿形成(P<0.01)。结论:舒利通颗粒对疼痛和炎症具有明显的镇痛和抗炎作用。     

地黄双花颗粒抗炎止痒镇痛作用的药效学

目的：研究地黄双花颗粒（DG）抗炎、止痒、镇痛作用。方法：用小鼠耳肿法及大鼠足肿胀法观察其抗炎作用；小鼠扭体法；组胺所致豚鼠瘙痒法。结果：DG能减少醋酸致小鼠扭体反应次数；明显减轻二甲苯致小鼠耳部的炎症肿胀；有效抑制角叉菜胶致大鼠足跖的急性炎症；提高豚鼠对磷酸组织胺的致痒阈。结论：DG对实验动物模型具有明显的抗炎、止瘁和镇痛作用。     

Evaluation of Skin Viability Effect on Ethosome and Liposome-Mediated Psoralen Delivery via Cell Uptake

This study investigated the effect of skin viability on its permeability to psoralen delivered by ethosomes, as compared with liposomes. With decreasing skin viability, the amount of liposome-delivered psoralen that penetrated through the skin increased, whereas skin deposition of psoralen from both ethosomes and liposomes reduced. Psoralen delivery to human-immortalized epidermal cells was more effective using liposomes, whereas delivery to human embryonic skin fibroblast cells was more effective when ethosomes were used. These findings agreed with those of in vivo studies showing that skin psoralen deposition from ethosomes and liposomes first increased and then plateaued overtime, which may indicate gradual saturation of intracellular drug delivery. It also suggested that the reduced deposition of ethosome- or liposome-delivered psoralen in skin with reduced viability may relate to reduced cellular uptake. This work indicated that the effects of skin viability should be taken into account when evaluating nanocarrier-mediated drug skin permeation. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3120–3126, 2014     

乙醇脂质体对多奈哌齐经皮转运的促进作用

目的：制备多奈哌齐乙醇脂质体,从而进一步有效优化药物的经皮转运。方法：采用注入法制备多奈哌齐乙醇脂质体;通过形态,粒径分布和包封率对乙醇脂质体进行了初步表征,运用Franz 扩散池和共聚焦激光扫描电镜考察了乙醇脂质体的经皮转运情况。结果：多奈哌齐乙醇脂质体（乙醇含量45%）包封率明显高于多奈哌齐脂质体;多奈哌齐乙醇脂质体透皮量分别为脂质体及乙醇溶液的4.32倍和1.89倍。结论：乙醇脂质体可有效携带药物进入皮肤深层。     

Ethosomes,binary ethosomes and transfersomes of terbinafine hydrochloride: A comparative study

The aim of this study was to compare the skin permeation of ethosomes, binary ethosomes and transfersomes of Terbinafine Hydrochloride (TH) under non-occlusive conditions. These lipid vesicles were prepared and characterized for shape, size, zeta-potential and entrapment efficiency. Franz diffusion cells and confocal laser scanning microscopy (CLSM) were used for the percutaneous absorption studies. The quantity of drug in the skin from ethosomes, binary ethosomes (the weight ratio of ethanol to propylene glycol 7:3, ethanol-PG = 7:3, w/w), and transfersomes was 1.26, 1.51 (p <0.05), 1.56 (p <0.01) times higher than that of TH from traditional liposomes (control). The skin deposition of the applied dose (DD%) of TH from ethosomes, binary ethosomes, and transfersomes was 3.34 (p < 0.05), 9.88 (p < 0.01), 2.52 times higher than that of TH from control. The results of CLSM experiments showed that penetration depth and fluorescence intensity of Rhodamine B from binary ethosomes was much greater than that from ethosomes and transfersomes. These results indicated the binary ethosomes (ethanol-PG = 7:3, w/w) most effectively permitted drug penetration through skin; transfersomes made drug easiest to accumulate in the skin. Ethosomes improved drug delivery with greater improvement in skin permeation than improvement in skin deposition.     

Synergistic penetration of ethosomes and lipophilic prodrug on the transdermal delivery of acyclovir

The aim of this study was to investigate the lipophilic prodrug as a means of promoting acyclovir (ACV) that exhibited biphasic insolubility into the ethosomes for optimum skin delivery. Acyclovir Palmitate (ACV-C₁₆) was synthesized as the lipophilic prodrug of ACV. The ethosomal system and the liposomal system bearing ACV or ACV-C₁₆ were prepared, respectively. The systems were characterized for shape, zeta potential value, particle size, and entrapment efficiency. Franz diffusion cells and confocal laser scanning microscopy were used for the percutaneous absorption studies. The results showed that the entrapment efficiency of ACV-C₁₆ ethosomes (87.75%) were much higher than that of ACV ethosomes (39.13%). The quantity of drug in the skin from ACV-C₁₆ ethosomes at the end of the 24 h transdermal experiment (622.89 μg/cm²) was 5.30 and 3.43 times higher than that from ACV-C₁₆ hydroalcoholic solution and ACV ethosomes, respectively. This study indicated that the binary combination of the lipophilic prodrug ACV-C₁₆ and the ethosomes synergistically enhanced ACV absorption into the skin.     

Microwave-aided skin drug penetration and retention of 5-fluorouracil-loaded ethosomes

ABSTRACT

Objectives: Skin drug retention is required in local treatment of skin cancer. This study investigated the interplay effects of ethosomes and microwave in transdermal drug delivery. Skin pre-treatment by microwave and applied with liquified medicine is deemed to ‘cement’ the skin thereby raising skin drug deposition.

Methods: 5-fluorouracil-loaded ethosomes were prepared and subjected to size, zeta potential, morphology, drug content, drug release and skin permeation tests. The molecular characteristics of untreated, microwave and/or ethosome-treated skins were examined by Fourier transform infrared and raman spectroscopy, thermal and electron microscopy techniques.

Results: The skin drug retention was promoted using larger ethosomes with negative zeta potentials that repelled anionic lipids of skin and hindered vesicle permeation into deep layers. These ethosomes had low ethanol content. They were less able to fluidize the lipid and defluidize the protein domains at epidermis to enlarge aqueous pores for drug permeation. Pre-treatment of skin by 2450 MHz microwave for 2.5 min further increased skin drug penetration and retention of low ethanol ethosomes and provided lower drug permeation than cases treated for 1.15 min and 5 min. A 2.5 min treatment might be accompanied by specific dermal protein fluidization via C=O moiety which translated to macromolecular swelling, narrowing of intercellular spaces at lower skin layers, increased drug retention and reduced drug permeation.

Conclusion: Ethosomes and microwave synergized to promote skin drug retention.     

Analgesic efficacy and pharmacokinetics of topical nimesulide gel in healthy human volunteers: double-blind comparison with piroxicam, diclofenac and placebo

Objective: The present study was conducted to compare the analgesic efficacy of a new topical gel formulation of nimesulide (10 mg of pure drug) with that of placebo, diclofenac and piroxicam gels (10 mg of pure drug) in three parallel groups in a double-blinded, randomized fashion with vehicle placebo. The analgesic activity of nimesulide was subsequently correlated with its pharmacokinetic profile. Methods: The drugs were applied on a fixed marked area on the skin of the right forearm. Pain stimulus was administered using a modification of the Hollander method, before and at 15, 30, 60, 120 min and 240 min post-treatment. The pain experienced by the subjects was ranked separately on the visual analogue scale (VAS) and the ten-point category scale. Antinociception induced by the treatments was evaluated through the placebo-related ratings (PRR) and total pain relief (TOTPAR) analysis. The plasma concentration of nimesulide was estimated using high-performance liquid chromatography (HPLC). Results: Nimesulide exhibited better efficacy than diclofenac, piroxicam and placebo. It demonstrated faster onset of action in concordance with earlier studies. Peak analgesic effect was observed at 120 min post-treatment, which correlated with the pharmacokinetic profile of the drug in gel formulation. In this study, diclofenac was found to be superior to piroxicam though both drugs exhibited peak analgesic effect at 60 min post-treatment. In the modified Hollander method, a good correlation was found between the ten point category scale and the VAS, indicating that it may serve as a sensitive and reliable method for the screening of analgesic drugs. Conclusion: The superior analgesic activity of nimesulide (as gel formulation), correlating with its pharmacokinetic profile, indicates that the topical route of administration may be a safe and effective alternative to the presently used oral and rectal routes. Received: 20 October 1997 / Accepted in revised form: 22 April 1998     

布洛芬二元醇脂质体的制备与评价

目的:制备布洛芬二元醇脂质体并对其进行体外评价。方法:采用注入法制备布洛芬二元醇脂质体,以包封率为指标优化处方中乙醇与丙二醇比例;采用Franz扩散池进行离体皮肤渗透试验,测定布洛芬在接收液内的累积渗透量及皮内滞留量。结果:乙醇与丙二醇比例为7∶3时制得的布洛芬二元醇脂质体包封率最高(73.6±1.4)%,其透过皮肤进入接收液中的累积渗透量为乙醇脂质体的1.82倍。二元醇脂质体[乙醇-丙二醇(7∶3)]和乙醇脂质体24 h皮肤中药物滞留量分别为43.67±2.11和38.02±1.44。结论:二元醇脂质体可有效提高布洛芬的皮肤渗透量及皮内滞留量。     

乙醇脂质体、二元醇脂质体及传递体对多奈哌齐经皮转运的对比性研究

目的:制备多奈哌齐乙醇脂质体、二元醇脂质体和传递体,并比较皮肤渗透性,从而进一步有效优化药物的经皮转运。方法:通过形态,粒径分布,Zeta电位值和包封率对多奈哌齐乙醇脂质体、二元醇脂质体及传递体进行了初步表征,运用Franz扩散池和共聚焦激光扫描电镜考察了3种囊泡的经皮转运情况。结果:当二元醇脂质体包封率最高(89.1±0.42)%时,乙醇-丙二醇=7∶3,且二元醇脂质体(乙醇-丙二醇为7∶3,W/W)在皮肤中24 h的累积渗透百分数分别是乙醇脂质体和传递体的3.9和5.4倍。结论:二元醇醇脂质体(乙醇-丙二醇为7∶3,W/W)时,有效地改善了药物在醇脂质体中的包封率,且显著增加的药物在皮肤中的累积量。     

Topical delivery of 5-aminolevulinic acid-encapsulated ethosomes in a hyperproliferative skin animal model using the CLSM technique to evaluate the penetration behavior

Psoriasis, an inflammatory skin disease, exhibits recurring itching, soreness, and cracked and bleeding skin. Currently, the topical delivery of 5-aminolevulinic acid-photodynamic therapy (ALA–PDT) is an optional treatment for psoriasis which provides long-term therapeutic effects, is non-toxic and enjoys better compliance with patients. However, the precursor of ALA is hydrophilic, and thus its ability to penetrate the skin is limited. Also, little research has provided a platform to investigate the penetration behavior in disordered skin. We employed a highly potent ethosomal carrier (phosphatidylethanolamine; PE) to investigate the penetration behavior of ALA and the recovery of skin in a hyperproliferative murine model. We found that the application of ethosomes produced a significant increase in cumulative amounts of 5–26-fold in normal and hyperproliferative murine skin samples when compared to an ALA aqueous solution; and the ALA aqueous solution appeared less precise in terms of the penetration mode in hyperproliferative murine skin. After the ethosomes had been applied, the protoporphyrin IX (PpIX) intensity increased about 3.64-fold compared with that of the ALA aqueous solution, and the penetration depth reached 30–80 μm. The results demonstrated that the ethosomal carrier significantly improved the delivery of ALA and the formation of PpIX in both normal and hyperproliferative murine skin samples, and the expression level of tumor necrosis factor (TNF)-α was reduced after the ALA–ethosomes were applied to treat hyperproliferative murine skin. Furthermore, the results of present study encourage more investigations on the mechanism of the interaction with ethosomes and hyperproliferative murine skin.