不同浓度氮酮、薄荷醇对盐酸特比萘芬体外经皮渗透作用的影响

为选择促进盐酸特比萘芬(TBF)透皮扩散作用的促渗剂,选用立式Franz扩散池,以犬离体皮肤为透皮屏障,通过计算含不同浓度氮酮(AZ)、薄荷醇(MT)组盐酸特比萘芬透皮试验的累积渗透量Q、稳态流速Jss、渗透系数Kp和增渗比ER等参数来比较促渗效果.结果显示试验中所有组别促渗剂都具有促渗作用,作用由强至弱依次为1%AZ**>5%MT**>3%AZ**>3%MT**>1%MT*>5%AZ*,其中薄荷醇组促渗效果与浓度呈线性正相关,而氮酮组则呈线性负相关.虽然各组促渗剂均起促进作用,但薄荷醇组的效果优于氮酮组,加之薄荷醇属天然物质,毒副作用低,所以更适合作为药物外用制剂的促渗剂.     

氮酮对中药透皮软膏体外透皮作用的影响

为了研究氮酮对中药透皮软膏的促透作用,试验采用高效液相色谱(HPLC)法测定了含不同含量氮酮的中药透皮软膏中咖啡酸的透皮量。结果表明:含0.5%、1%、2%、4%和6%氮酮的中药透皮软膏中咖啡酸4h累计透皮量分别为9.0979,15.1596,36.2538,37.5216,32.3093μg;咖啡酸渗透量不与氮酮含量呈正相关;通过最小二乘法拟合,中药透皮软膏中氮酮含量为4%时咖啡酸渗透效果最好。     

冰片、薄荷醇及氮酮对乳炎清凉巴布剂透皮吸收的影响

目的:考察冰片、薄荷醇、氮酮3种促渗剂联合应用对乳炎清凉巴布剂体外透皮吸收的影响,确定其最优组合。方法:利用ZTY-型透皮扩散仪,以乳牛皮肤为材料,采用三因素三水平正交试验设计,以HPLC法检测乳炎清凉巴布剂主要成分绿原酸在不同时间的透皮含量,计算各组透皮吸收速率、累积渗透量等。结果:9个试验组均有绿原酸透皮吸收,组间有显著性差异,其中A1B1C2(冰片∶薄荷醇∶氮酮为1%∶1%∶3%)为最优组合。结论:冰片、薄荷醇、氮酮3种促渗剂按1%、1%、3%联合应用能显著促进乳炎清凉巴布剂中绿原酸的透皮吸收。     

不同浓度促透剂对绿原酸体外透皮吸收的影响

目的:通过小鼠体外透皮实验,探讨不同促透剂对绿原酸巴布剂药贴体外透皮吸收的影响,确定最佳促透剂及其浓度,为研制绿原酸透皮吸收制剂奠定良好的基础。方法:采用改良Franz扩散池法,以离体小鼠皮肤为透皮屏障,加入不同浓度促透剂制备绿原酸巴布剂药贴,以HPLC法考察绿原酸不同时间透过量,以绿原酸为定量指标进行体外透皮吸收检测。结果:单一促透剂中以1%氮酮效果最佳,5%油酸效果次之。结论:常用促透剂氮酮、油酸均可以使巴布剂中的绿原酸透过皮肤,且以1%氮酮促透效果最佳。     

薄荷醇和氮酮对甲硝唑在犬中体外透皮吸收的影响

研究不同的溶液载体（PBS,5％薄荷醇和5％氮酮）和不同部位的皮肤对甲硝唑在犬中体外透皮吸收和皮内摄取的影响。取下北京犬颈部、胸部以及腹部皮肤,-20℃保存。使用时,皮肤解冻固定在改良Franz透皮扩散仪上,保持恒速（200±1）r／min,恒温（35±0．5）℃。在扩散池中的皮肤角质层上加入2mL溶液载体（含甲硝唑58．4μmol）,以20％乙醇为溶剂溶解薄荷醇和氮酮,在预定时间点取样1mL,采用HPLC方法测定各接受液中的药物量和皮肤中摄取的药物量。结果显示,与PBS相比,薄荷醇和氮酮能增加所有部位甲硝唑的透皮吸收量和皮内摄取量（P〈0．05）。同一溶液载体在不同部位的渗透性存在差异,腹部〉颈部〉胸部,不同部位的皮内摄取量也存在差异,颈部〉胸部〉腹部。说明甲硝唑在不同溶液载体和不同部位皮肤的渗透性存在差异。     

不同浓度中药对枯草芽孢杆菌体外生长的影响

枯草芽孢杆菌为大多数动物肠道中的过路菌群,被世界各国列为允许在畜禽体内使用的益生素生产菌种。其作为饲料添加剂的作用主要有以下几方面:其一,枯草芽孢杆菌以其内生孢子进入动物消化道内虽然不能增殖,但能迅速生长发育并分泌活性很强的胞外酶-蛋白酶、脂肪酶、淀粉酶、糖苷酶等多种酶类,同时还产生降解植物饲料中非淀粉多糖的酶-果胶酶、纤维素酶、葡聚糖酶,这些活性酶直接作用动物消化道的“酶池”,降解饲料中相应的营养成分,提高饲料中营养成分的消化,从而提高蛋白质和能量的利用率,降低料肉比。间接作用是这些活性酶刺激机体本身酶的…     

不同pH和离子浓度对尿酸体外溶解度的影响

在含有不同离子浓度及不同pH的鸡血清中加入饱和量的固体尿酸,放置于42℃水浴并在不同的时间点测定其中的尿酸浓度。结果表明:在低pH的鸡血清中,钙含量的升高(浓度在正常的1.75倍及以下)有促进尿酸溶解的趋势,而在升高pH的鸡血清中,这种作用更明显,随着时间的延长,由于尿酸以尿酸盐的形式析出,尿酸浓度反而下降,pH与离子浓度升高时更明显,即有利于尿酸盐的析出。作者依此认为,高钙高蛋白日粮引起的代谢性碱中毒与电解质紊乱可能是产生禽痛风的重要机理之一。     

白僵蚕不同浓度乙醇提取物的体外抗氧化作用研究

以对DPPH自由基和羟基自由基的清除活性以及还原力为指标,测定白僵蚕不同浓度乙醇提取物的体外抗氧化作用.结果显示,白僵蚕65％、80％、95％乙醇提取物均具有较强的还原力以及对DPPH自由基和羟基自由基的清除作用,其中以白僵蚕80％乙醇提取物的体外抗氧化作用更强.结果表明,白僵蚕80％乙醇提取物富集了白僵蚕的主要抗氧化作用药效成分,可用于白僵蚕的抗氧化资源深度开发.     

Effect of solute lipophilicity on penetration through canine skin

OBJECTIVE: To investigate the effect of lipophilicity on the percutaneous penetration of a homologous series of alcohols through canine skin. DESIGN: Skin harvested from Greyhound thorax was placed in Franz-type diffusion cells and the in vitro passage of radiolabelled (14C) alcohols (ethanol, butanol, hexanol and octanol (Log P 0.19-3.0)) through separate skin sections was measured in replicates of five. Permeability coefficient (kP, cm/h), maximum flux (Jmax, mol/cm2/h) and residue remaining within the skin were determined. RESULTS: The kP increased with increasing lipophilicity (6.2 x 10(-4) +/- 1.6 x 10(-4) cm/h for ethanol to 1.8 x 10(-2) +/- 3.6 x 10(-3) cm/h for octanol). Alcohol residues remaining within each skin sample followed a similar pattern. An exponential decrease in Jmax with increasing lipophilicity was observed. CONCLUSION: Changes in canine skin permeability occur with increasing alcohol lipophilicity. This finding has practical consequences for the design of topical formulations and optimisation of drug delivery through animal skin.     

The effects of skin disease on the penetration kinetics of hydrocortisone through canine skin in vitro

This study investigated the effects of allergic skin disease on the penetration kinetics of hydrocortisone through canine skin in vitro. Full-thickness lesional and nonlesional (normal) skin was removed from the dorsal lumbosacral and dorsocaudal thoracic regions, respectively, of five canine cadavers. The dogs were suspected of having flea allergy dermatitis based on their distribution and types of skin lesions. Nonlesional skin was confirmed to be histologically normal, and the histopathology of the lesional skin was consistent with allergic dermatitis. Excised skin was clipped, mounted in Franz-type diffusion cells, and the transdermal penetration of a saturated, radiolabelled hydrocortisone solution was measured over 30 h. When the penetration data for all five dogs were pooled, a restricted (or residual) maximal likelihood mixed model predicted that the permeability coefficient and pseudosteady-state flux of hydrocortisone was more than twice as great (95% confidence interval 1.55-2.71 times as great; P < 0.0001) through lesional compared with nonlesional skin. There was no significant difference in the lag time for hydrocortisone penetration through lesional compared with nonlesional skin of the dogs. This study has confirmed that the transdermal penetration of hydrocortisone may be altered, typically increased twofold, but could be as high as 10-fold, through lesional compared with nonlesional skin of dogs with suspected flea allergy dermatitis. This is likely to be affected by variables such as disease severity, concurrent infections and interindividual differences in skin characteristics.     

氮酮、二甲基亚砜对中药软膏促透效果的比较研究

由金银花、蒲公英、连翘、紫花地丁、丹参五味中药组成复方,以水提工艺获得提取物,制成复方中药软膏剂.以绿原酸的透皮量作为考核指标,用紫外分光光度法作为检测手段,考查二甲基亚砜、氮酮两种透皮促进剂的促透效果.试验结果表明:氮酮的促透效果显著优于二甲基亚砜,其中以含有5%氮酮的中药软膏透皮效果最好.     

The effects of vehicle and region of application on in vitro penetration of testosterone through canine skin

The effects of the vehicles phosphate-buffered saline (PBS), ethanol (EtOH; 50% in PBS w/w) and propylene glycol (PG; 50% in PBS w/w) and the region of administration on in vitro transdermal penetration of testosterone was investigated in the dog. Skin was harvested from the thorax, neck (dorsal part) and groin regions of greyhounds after euthanasia and stored at -20 degrees C until required. The skin was then de-frosted and placed into Franz-type diffusion cells which were maintained at approximately 32 degrees C by a water-bath. Saturated solutions of testosterone, containing trace amounts of radiolabelled (14C) testosterone, in each vehicle were applied to the outer (stratum corneum) surface of each skin sample and aliquots of receptor fluid were collected at 0, 2, 4, 8, 16, 20, 22 and 24h and analysed for testosterone by scintillation counting. The maximum flux (J(max)) of testosterone was significantly higher for all sites when dissolved in a vehicle containing 50% EtOH or 50% PG, compared to PBS. In contrast, higher residues of testosterone were found remaining within the skin when PBS was used as a vehicle. This study shows that variability in percutaneous penetration of testosterone could be expected with formulation design and site of application.     

The effects of surface preparation on the penetration of hydrocortisone through canine skin

This study investigated the effects of common skin surface preparations on the penetration kinetics of hydrocortisone through canine skin. Thoracic skin from five dogs was clipped of hair, divided between five treatment groups and prepared as follows: shaved (S); tape-stripped with adhesive bandage (TS); cleaned with aqueous chlorhexidine (Aq-C); cleaned with alcoholic chlorhexidine (Al-C); or allocated to the control group and had no further preparation performed (C). The skin samples were mounted in Franz-type diffusion cells and transdermal hydrocortisone penetration was measured over 30h. The pseudo-steady-state flux (J(SS)) of hydrocortisone through S, Al-C, Aq-C and TS skin was, respectively, 2.3 (P=0.021), 2.2 (P=0.037), 2.0 (P=0.070) and 1.5 (P=0.351) times greater than through the control skin, but there were no significant differences in the lag times (t(lag)) for hydrocortisone penetration between the groups. The study has shown that some skin surface preparations can significantly increase the subsequent penetration of hydrocortisone through canine skin in vitro.     

In vitro development and characterization of canine epidermis on a porcine acellular dermal matrix

The aim of this study was to develop and to characterize a canine skin epidermal model able to form a proper epidermis on a porcine acellular dermal matrix (PADM). In addition, the role of fibroblasts in skin barrier formation was studied by incorporating or omitting canine dermal fibroblasts in the PADM. Canine epidermal composites were developed by seeding keratinocytes onto the surface of PADM that were previously seeded or non-seeded with dermal fibroblasts. After 14days of culture under air-exposed conditions and in a special growth medium, skin composites were histologically processed and immunohistochemically characterized to determine the expression of cytokeratins and of vimentin and the presence of basement membrane. In all composites, keratinocytes underwent differentiation to a multilayer epidermis with 5-7 viable cell layers. The stratum basalis, stratum spinosum, stratum granulosum and stratum corneum were identified. The expression of cytokeratins was similar to that described in healthy canine epidermis. Laminin and collagen IV immunostaining revealed a homogeneous layer in the epidermal-dermal junction only when the matrix had been seeded by canine dermal fibroblasts. The model may become a simple, useful and cost-effective tool to investigate the biology and pathology of canine epidermis and could partially replace animal testing in several areas of dermatological research.     

Regional differences in the in vitro penetration of methylsalicylate through equine skin

Commercial formulations of non-steroidal anti-inflammatory drugs (NSAIDs) are developed for human use but the extent to which they will pass through equine skin is unknown. Skin was harvested from five Thoroughbred geldings from the thorax, groin and leg (dorsal metacarpal) regions and frozen (-20 degrees C) until required. Two grams of methylsalicylate (MeSa) gel was applied to defrosted full-thickness samples in diffusion cells and the penetration of MeSa and its active metabolite, salicylate (Sa), through skin samples were measured over 24 h. Significantly higher (P < or = 0.02) total salicylate (AUC; MeSa + Sa) penetrated through skin from the leg region (5491.3 h mg/L), compared to thorax (3710.7 h mg/L) and groin (3571.5 h mg/L). In addition, there was a significantly higher (P0.01) rate of penetration of total Sa through leg skin in the first 6h after application. It was concluded that the commercial formulation of MeSa would achieve therapeutic levels of total salicylate beneath sites of topical application, with a faster and more pronounced response through the leg region, compared to the upper body.