伊曲康唑醇质体的制备及体外经皮渗透研究

目的考察醇质体凝胶作为伊曲康唑透皮给药载体的可行性。方法采用注入法制备伊曲康唑醇质体进而用卡波姆制备成凝胶,采用透皮扩散试验仪对大鼠皮肤进行体外经皮渗透实验;以HPLC测定药物含量求算积累渗透量及稳态透皮速率,并测定药物在皮肤表皮和真皮中的滞留量。结果伊曲康唑醇质体凝胶的经皮渗透率是其水溶液的9.20倍,是体积分数为30%乙醇环糊精溶液的1.97倍。结论醇质体凝胶能提高伊曲康唑的透皮速率,增加药物在皮肤内的滞留量。     

甲磺酸帕珠沙星凝胶制备及经皮吸收研究

目的制备甲磺酸帕珠沙星凝胶,并考察其体外透皮吸收的效果。方法以卡波姆2020为基质,以离体小鼠皮肤作为透皮屏障,用改良Franz扩散池,双波长紫外分光光度法测定含量。结果凝胶为白色半透明细腻胶状,甲磺酸帕珠沙星在3μg/ml～10μg/ml浓度范围内呈良好线性关系（r=0.9993）,平均回收率为100.3%,RSD为1.4%（n=9）。药物8h的累积透过量为130μg/cm2。结论工艺方法简单可行,制剂具有体外透皮吸收效果。     

中药凝胶贴膏与软膏剂的体外透皮特性比较研究

目的研究主药成分及处方量相同的两种不同剂型的中药烫伤制剂透皮吸收效果。方法采用改进的Franz扩散池进行体外透皮试验,取离体大鼠鼠皮作为透皮屏障,采用紫外分光光度法测定接收液中的有效成分含量并作为评价指标,比较两种剂型的透皮吸收能力。结果同一时间段内,凝胶贴膏的累积透皮量和累积透皮率均明显高于软膏剂,而且随着时间的增加,二者差值逐渐增大,尤其在12 h时,凝胶贴膏的累积透皮率约为软膏剂的1.6倍。结论凝胶贴膏在透皮性能上明显优于软膏剂,其透皮吸收迅速、载药量大、使用更方便,可在临床上进一步研究使其用于治疗烧烫伤。     

异丁香酚的离体透皮吸收研究

采用静态渗透室装置,测定异丁香酚皮片涂药后不同时间对小鼠离体皮肤透皮吸收率,异丁香酚采用ＧＣ法测定。结果：异丁香酚经离体小鼠皮肤的渗透率随时间的增加而增加,２４ｈ后,异丁香酚的渗透率为１．００％,结论：异丁香酚通能透皮吸收。     

念珠菌属的分布及其对五种抗真菌药物的耐药性分析

目的检测念珠菌对5种抗真菌药物体外敏感性，了解念珠菌耐药性变化趋势。方法用沙氏培养基进行真菌分离，采用念珠菌显色培养基作菌种鉴定，用ATBFUNGUS3药敏试剂盒测定抗真菌药物对临床分离的念珠菌最低抑菌浓度（MIC）。结果白色念珠菌的耐药率为最低，它除对伊曲康唑耐药率为10．8％外，其余均低于5．4％；而以克柔念珠菌的耐药率最高，它对氟康唑和伊曲康唑的耐药率大于33.3％。结论不同念珠菌对常用抗真菌药物耐药性存在差异，白色念珠菌对抗真菌药物的耐药性要低于非白色念珠菌。因此真菌的培养鉴定和药敏试验对临床合理选择抗真菌药物十分重要。     

平阳霉素和卡铂动物体外透皮试验

目的观察抗癌药平阳霉素、卡铂在不同条件下动物体外透皮速率。方法以小鼠皮为模型膜；以直流电离子导入或加入氮酮促透剂对以上药物做透皮实验，分别以紫外分光光度法或络合分光光度法测定平阳霉素、卡铂透过的药量。结果以直流电导入或加入氮酮促透剂比普通药物透皮速率明显增加。结论此实验为临床透皮用抗癌药提供参考，可适当采用加入氮酮促透剂或直流电导入，提高药物透皮速率。     

5-氟尿嘧啶脂质体凝胶剂在兔耳增生性瘢痕中的透皮吸收研究

目的探讨脂质体包裹的5-氟尿嘧啶对兔耳增生性瘢痕组织的透皮吸收能力。方法在兔耳增生性瘢痕模型上进行透皮扩散,比较5-氟尿嘧啶脂质体及其普通凝胶剂对瘢痕皮肤的渗透能力。结果在体瘢痕透皮试验12h后,脂质体组瘢痕组织中的5-氟尿嘧啶单位面积透皮药量显著高于普通凝胶剂组（234.57±56.25）μg.cm-2和（45.24±9.38）μg.cm-2,P〈0.01。结论在体瘢痕组织透皮试验中,脂质体剂型优于普通凝胶剂型促进5-氟尿嘧啶透皮的能力。     

卡泊芬净经验性治疗白血病并发真菌感染的临床疗效分析与评价

目的 评估卡泊芬净经验性治疗白血病并发真菌感染的疗效分析及不良反应.方法 选择2009年1月-2011年10月医院白血病并发真菌感染的50例患者,分为卡泊芬净及伊曲康唑两组,每组25例,卡泊芬净组给予卡泊芬净经验性治疗,伊曲康唑组给予伊曲康唑抗真菌治疗,两组治疗时间均持续至体温恢复正常后5d或疗程达14 d或连续痰涂片阴性后3d;对两种药物的疗效和不良反应进行观察和评价.结果 卡泊芬净和伊曲康唑在治疗白血病并发真菌感染中,总有效率分别为88.0％和64.0％,差异有统计学意义(P＜0.05),两组比较后发现,卡泊芬净较伊曲康唑不良反应少,耐受性好.结论 在白血病并发真菌感染的治疗中,卡泊芬净较伊曲康唑疗效更好,不良反应更少,患者耐受性更好,是治疗白血病并发真菌感染安全有效的药物.     

伊曲康唑联合2％酮康唑洗剂治疗念珠菌性龟头炎46例疗效观察

伊曲康唑（斯皮仁诺）和酮康唑分别属于三唑类及咪唑类抗真菌药物，它们均具有抗菌谱广，疗效高，耐受性好和副作用低的特点。近年来我科采用伊曲康唑联合2％酮康唑洗剂（采乐）治疗念珠菌性龟头炎，取得较好疗效。现报道如下。     

伊曲康唑治疗深部真菌感染的疗效观察

伊曲康唑是一种广谱的三唑类抗真菌药,已广泛用于治疗各种真菌感染,目前国内外对伊曲康唑注射液在重症监护室中治疗危重病患者深部真菌感染的研究报道极少.本研究通过回顾分析ICU中应用伊曲康唑注射液治疗深部真菌感染患者的临床资料,评价伊曲康唑注射液在治疗深部真菌感染的疗效和安全性.     

In vitro test of nicotine's permeability through human skin. Risk evaluation and safety aspects.

Permeability tests with Franz' diffusion cells and an in vitro test model were made to evaluate the importance of dermal absorption of nicotine as a pathway for intoxication. Studies were carried out to ensure that safety procedures, when spilling nicotine on skin, are sufficient to prevent poisoning. Pure nicotine and nicotine in various concentrations in water or ethanol were applied on human skin or gloves in Franz' cells. Washing was simulated by removing nicotine from skin after 3 or 5 min. Permeation rate (flux) and lag time were calculated and estimated for human skin. Different glove materials were tested for their nicotine breakthrough time. Flux depended on concentration in a non-linear way when nicotine-water solutions were tested. Highest flux was found in 50% w/w nicotine dissolved in water. Solutions with low concentration of nicotine (1% w/w) dissolved in water had a similar permeation rate to 100% nicotine. Flux was found to be low when using ethanol as a vehicle; flux was also pH-dependent. The nicotine-water solution containing acetic acid had the lowest flux. The tests where nicotine was washed away revealed that skin served as a possible nicotine depot, because nicotine concentration in the receptor compartment continued to increase after removing the nicotine from the surface. The length of contact time affected the amount of substance passing the skin, resulting in great difference between 3 and 5 min contact time, 5 min giving higher nicotine concentration and 3 min lower. This emphasizes the importance of washing away nicotine spilled on skin rapidly. Two glove types were tested and they were found to be appropriate in their use with nicotine if changed regularly.     

Interactions of skin thickness and physicochemical properties of test compounds in percutaneous penetration studies

Objectives: To determine the effect of skin thickness on the percutaneous penetration and distribution of test compounds with varying physicochemical properties using in vitro systems. Studies were carried out in accordance with OECD guidelines on skin absorption tests. Methods: Percutaneous penetration of caffeine (log P −0.01), testosterone (log P 3.32), propoxur (log P 1.52) (finite dose in ethanol to water vehicle ratio) and butoxyethanol (log P 0.83) (undiluted finite dose or as an infinite dose 50% [v/v] aqueous solution) through skin of varying thicknesses under occluded conditions was measured using flow through cells for 8–24 h. Saline (adjusted to pH 7.4) was used as receptor fluid, with BSA added for studies with testosterone and propoxur. Following exposure, the remaining surface dose was removed by swabbing and the skin digested prior to scintillation counting. Results: The maximum flux of caffeine was increased with decreasing skin thickness, although these differences were found to be non-significant. The presence of caffeine in the skin membrane was not altered by skin thickness. Maximum flux and cumulative dose absorbed of testosterone and butoxyethanol (in both finite and infinite doses) were markedly reduced with full thickness (about 1 mm thick) skin compared with split thickness skin (about 0.5 mm). Maximum flux of propoxur (dissolved in 60% ethanol) was clearly higher through skin of 0.71 mm than through skin of 1.36 mm, but no difference was found between 0.56 and 0.71 mm. The proportion of propoxur present in the membrane after 24 h increased significantly over the complete range of thicknesses tested (0.56–1.36 mm). Conclusions: A complex relationship exists between skin thickness, lipophilicity and percutaneous penetration and distribution. This has implications for risk assessment studies and for the validation of models with data from different sources.     

双氯芬酸钠透皮控释制剂的研究

目的：探讨不同双氯芬酸钠透皮控释制剂对药物的影响。方法：采用正交设计实验,考察双氯芬酸钠制备过程中乙醇含量、磷脂浓度、柔性辅料的用量及超声处理时间等对包封率的影响;采用正交设计实验,考察丙烯酸树脂为主要成分、琥珀酸为交联剂、柠檬酸三乙酯为增塑剂制对体外透皮率和体外释药性的影响;采用健康大鼠进行药动学实验,研究双氯芬酸钠醇质体在大鼠体内的药动学特征和生物利用度。结果：乙醇含量(A)、磷脂浓度(B)、柔性辅料(D)的用量及超声处理时间(C)四个影响因素对透皮控释贴剂包封率的综合影响效果为B＞A＞C＞D,根据评分,得最佳处方为：A3B2C2D1;得出的最优处方组成为：双氯芬酸钠醇脂质体溶液含量10%、丙烯酸树脂Ⅳ号0.4g,柠檬酸三乙酯0.25g,琥珀酸0.052g,氮酮含量5%;计算得出双氯芬酸钠透皮控释贴剂的相对生物利用度为167.20%,说明采用本研究优化后工艺制备的双氯芬酸钠透皮控释贴剂具有较高的生物利用度。结论：双氯芬酸钠应用醇质体制成透皮控释制剂,透皮吸收的效果好,控释作用显著,相对生物利用度高。     

伊曲康唑口服联合碘伏阴道擦洗治疗复发的性念珠菌性阴道炎的疗效观察

目的探讨伊曲康唑口服联合碘伏阴道擦洗治疗复发性念珠菌性阴道炎的临床疗效。方法 94例复发性念珠菌性阴道炎患者被随机分为两组,对照组行达克宁栓阴道栓塞治疗,;实验组口服伊曲康唑,并用碘伏行阴道擦洗;比较两组治疗效果。结果实验组中治愈16例,显效14例,进步11例,总有效率为87.2%;对照组中治愈9例,显效12例,进步10例,总有效率为66.0%;实验组的治疗有效率明显高于对照组,差异具有统计学意义(P<0.05);实验组分别在第1周,第4周时检查的真菌清除率也明显高于对照组,差异明显(P>0.05)。结论伊曲康唑口服联合碘伏阴道擦洗治疗复发性念珠菌性阴道炎疗效肯定,值得推广应用。     

Oral chronic ethanol administration to rodents by agar gel diet

BACKGROUND: Chronic ethanol administration to rodents requires specially designed equipment and is labor intensive. Here we report a new procedure. METHOD: A commercial liquid diet preparation was made into a gel by addition of 0.5% agar. The gel, containing 5.3% ethanol, was offered in Falcon tubes equipped with a feeding opening. RESULTS: The gel consumption by C57/Bl mice resulted in high blood ethanol levels (average 43 mM). After 6 weeks, marked liver steatosis and significantly increased serum alanine aminotransferase levels had developed. CONCLUSIONS: Administration of ethanol in a nutritionally adequate gel provides a simple method for studies on chronic ethanol effects in rodents.     

对美涤克灵免水消毒洁手液消毒功效的研究

目的 测试美涤克灵免水消毒洁手液(60％酒精凝胶，简称美涤克灵)在医疗环境中的抗菌效果；评估美涤克灵在反复多次使用后的安全性。方法 对美涤克灵与普通洁手液和杀菌性洁手液的抗菌活性进行了比较；实验的设计和方法是遵照美国医护人员手部消毒标准步骤而完成的；手部皮肤对各种实验液体经25次连续使用后的反应由皮肤病专家进行鉴定。结果 美涤克灵在标准的洗手过程中杀菌效果为最好，其次是杀菌性洁手液，再次是普通洁手液；美涤克灵和实验中使用的其他两种洁手液均未造成对手部皮肤的不良反应。结论 对于医护人员来说，无论是从杀菌效果、使用的便宜性或对手部皮肤的保护性来看，美涤克灵都是最理想的医用消毒洁手液；我们的实验结果显示美涤克灵也应是普通人群在居家、旅游、工作和上学等日常生活中的理想保健用品，因为该产品杀菌效果强、极宜使用，而且反复使用后对皮肤没有副作用。     

Allopurinol gel mitigates radiation-induced mucositis and dermatitis

It has not been verified whether allopurinol application is beneficial in decreasing the severity of radiation-induced oral mucositis and dermatitis. Rats were divided into 4 groups and received 15 Gy irradiation on the left whisker pad. Group 1 received only irradiation. Group 2 was maintained by applying allopurinol/carrageenan-mixed gel (allopurinol gel) continuously from 2 days before to 20 days after irradiation. Group 3 had allopurinol gel applied for 20 days after radiation. Group 4 was maintained by applying carrageenan gel continuously from 2 days before to 20 days after irradiation. The intra oral mucosal and acute skin reactions were assessed daily using mucositis and skin score systems. The escape thresholds for mechanical stimulation to the left whisker pad were measured daily. In addition, the irradiated tissues at the endpoint of this study were compared with na?ve tissue. Escape threshold in group 2 was significantly higher than that in group 1, and mucositis and skin scores were much improved compared with those of group 1. Concerning escape threshold, mucositis and skin scores in group 3 began to improve 10 days after irradiation. Group 4 showed severe symptoms of mucositis and dermatitis to the same extent as that observed in group 1. In the histophathological study, the tissues of group 1 showed severe inflammatory reactions, compared with those of group 2. These results suggest that allopurinol gel application can mitigate inflammation reactions associated with radiation-induced oral mucositis and dermatitis.     

Ethanol signals for apoptosis in cultured skin cells.

Ethanol is commonly used in cosmetic and pharmaceutical preparations. To test whether ethanol may cause apoptosis in skin cells, we treated A431 epidermoid skin cells and neonatal human primary skin cells with different concentrations of ethanol, for different time periods. Ethanol was toxic to cells in both a dose- and time-dependent manner and increased the percentage of cells undergoing apoptosis. Treatment of cells with 40 and 100 mM ethanol increased release of the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) into culture medium and increased its expression in cells. The TNF-alpha was toxic to A431 epidermoid skin cells at concentrations similar to those released by cells on exposure to ethanol. Ethanol-treated cells examined by electron microscopy showed organelle damage, condensed chromatin, and apoptotic bodies. Therefore, even at low concentrations, ethanol may induce apoptosis in skin cells by enhancing the effects of TNF-alpha.     

骨科术前不同备皮法对皮肤细菌数量的影响研究

目的比较三种备皮法对骨科皮肤菌落数影响。方法择期内植入术病人180例分三组,使用不同清洁剂。A组：消毒软皂溶液;B组：消毒软皂溶液和5％PVP—I;C组：75％酒精和5％PVP—I。结果备皮后、手术消毒前组间比较。A组与B组C组之间有统计学意义;C组与B组无统计学意义。结论选择手术室电话通知病房接病人时的备皮时机,用消毒软皂溶液或75％酒精联合5％PVP—I备皮,备皮距手术时间越短,能有效减少皮肤表面细菌数量并保持较长时间的清洁效果,达到骨科备皮的严格要求,值得临床推荐。