莫匹罗星软膏的质量评价

目的评价国内不同企业生产的莫匹罗星软膏的质量。方法按照现行质量标准检验结合探索性研究,包括对产品的有关物质、聚乙二醇含量、黏度、粒度、酸碱度、透皮吸收等的考察,综合评价产品质量及现行质量标准对产品质量的可控性。结果抽取的127批样品,按国家标准检验合格率为100.0%。探索性研究结果表明,酸碱度测定结果均近中性;6个生产企业样品杂质种类和水平相近;但黏度、粒度、透皮吸收等存在差异。结论目前莫匹罗星软膏总体质量较好;现行标准需进一步完善,建议增/修订有关物质检测方法;建议企业对莫匹罗星软膏剂的处方、工艺进行再评价。     

A study on flow properties of semisolid dosage forms

There are a wide variety of semi-solid ointments used for healing the skin diseases, whose therapeutic and skin penetration abilities may greatly differ from one another depending on the compositions of ointment vehicles. A computer optimization technique was applied to obtain the optimum formula of o/w type ointment giving the in vitro maximum absorption rate through hairless rat skin membrane. Some of the formulations were selected to find out a relationship between skin penetration of ointment and its rheological characteristics. The experimental value of absorption rate obtained from the ointment by optimum formula agreed well with the theoretical value obtained from a polynomial regression analysis. Three kinds of ointments selected among 15 formulations were obtained with a concentric cylinder type rheometer (Model; Rheolab SM-HM Physica, Germany) at 20, 30, 40 and 50°C for rheograms of rhelolgical properties of o/w type ointments. As the temperature was raised, all products showed a decrease in both shear stress and yield values. The higher skin penetration, the lower shear stress showed.     

黄连痔疮膏处方的筛选及含量测定

目的优选黄连痔疮膏的制剂处方以及含量测定。方法用正交设计法对黄连痔疮膏的制剂处方进行筛选,以耐热,耐寒实验,涂展性,稳定性,释药速度的综合评分为指标。并用高效液相法对筛选出来的最佳软膏剂测定含量。结果黄连痔疮膏的最佳制剂处方为浸膏∶基质=1∶3,硬脂酸：（液体石蜡＋三乙醇胺）=2∶1,液体石蜡：三乙醇胺=2∶1,且其含量测定指标成分盐酸小檗碱在0.252~2.252μg范围内呈良好线性,R2=0.9998;平均回收率为99.55%,RSD=0.4%。结论该处方设计合理,制剂工艺可行,且含量测定结果准确,重现性好。     

2006-2008年我院麻醉性镇痛药调查分析

目的调查分析该院临床使用麻醉性镇痛药品的情况,为临床合理使用提供更好的依据。方法统计分析2006-2008年麻醉药品处方,利用限定日剂量（DDD）值和用药频度（DDDs）值评价药物利用指数（DUI）。结果除硫酸吗啡控释片、盐酸吗啡注射液和枸橼酸芬太尼透皮贴剂的处方构成比例逐年增加外,其他变化不大。盐酸哌替啶注射液、盐酸吗啡注射液、磷酸可待因片（30mg）、枸橼酸芬太尼透皮贴剂的DUI〈1,硫酸吗啡控释片的DUI〉1但〈1.2,枸橼酸芬太尼注射液（0.1mg）DUI〉1.5而枸橼酸芬太尼注射液（0.5mg）的DUI〉2。结论该院硫酸吗啡控释片和枸橼酸芬太尼透皮贴剂已作为癌痛治疗的首选药,麻醉性镇痛药品使用较合理。     

Viscosity of pharmacopeial multimolecular ointment vehicles and pharmaceutical availability of a model therapeutic agent

Viscosity was tested of basic ointment vehicles such as: white petrolatum, yellow petrolatum, anhydrous lanolin and eucerin produced by different manufacturers. Ointment vehicles of definite type differ significantly in rheological parameters. In the same group of products, the experimentally determined viscosity value of some vehicles is two-fold (petrolatum, anhydrous lanolin) or even three-fold (eucerin) higher than that of others. On the basis of rheological tests, using Einstein-Smoluchowski equation (D = kT/ 6pireta), theoretical coefficient was calculated of a model therapeutic agent--salicylic acid diffusion (-log chi2(i) = 1,22) from the tested vehicles to the external compartment. The obtained results were related to the performed in vitro measurements of the rate of salicylic acid release from the above mentioned ointment vehicles to model acceptor fluid. High correlation was observed between theoretical values of diffusion coefficients calculated on the basis of viscosity measurements and tested experimentally pharmaceutical availability of salicylic acid. It was confirmed by describing this dependence with regression equations of high correlation coefficients (r > or = 0,9667). Marked disproportions between rheological parameters of the vehicles of definite type produced by individual manufacturers are the cause of differences in pharmaceutical availability of therapeutic agents contained in these vehicles.     

Chitosan hydrogel as a base for transdermal delivery of berberine and its evaluation in rat skin.

Berberine is the main ingredient of Coptis spp. This study selected berberine as a model drug to design a transdermal delivery system for the treatment of cutaneous leishmaniasis. Berberine was incorporated into chitosan hydrogel to prepare ointments. The physicochemical properties of the ointments and the release profile of berberine were investigated. The results indicated that the viscosity of chitosan hydrogel increased with an increasing amount of lactic acid or EDTA. The effect of EDTA on the viscosity was greater than that of lactic acid. By differential scanning calorimetry (DSC) measurement, no interaction was found to occur between chitosan and the soluble berberine. The release rate of berberine was inversely proportional to ointment viscosity. In in vitro skin perfusion studies, only trace amounts of berberine permeated through the rat skin due to its low oil-water partition coefficient. Surfactants were used as penetration enhancers to increase the percutaneous absorption of berberine. Among the enhancers, benzalkonium chloride was found to be the most efficient. Additionally, Tween 80 could increase the loading amount of berberine in the skin.     

肝素类化合物透皮吸收制剂的研究前景

综述了肝素类化合物用于局部治疗的软膏剂的研究情况，探讨了该类化合物用于全身治疗的透皮吸收制剂的制备方法和研制低分子肝素透皮治疗系统的可行性。     

黄连膏体外透皮吸收及抗炎活性研究

目的：采用改良的Franz透皮扩散池考察黄连膏中主要活性成分的体外透皮吸收情况,同时对黄连膏的抗炎活性进行初步研究。方法：选用改良Franz透皮扩散池,接收液为30%乙醇生理盐水,以小鼠背部皮肤为透皮材料,采用紫外分光光度法及高效液相色谱法测定透皮接收液中盐酸小檗碱、芝麻酚、芝麻素及总生物碱的含量,计算透皮吸收动力学参数,考察黄连膏中抗炎活性成分的累计透过量及吸收规律;取30只SPF级小鼠,随机分为5组,即模型组、醋酸地塞米松乳膏组（100 mg·kg^-1）、黄连膏高剂量组0.075 g·g^-1（生药/膏）、黄连膏中剂量组0.15 g ·g^-1（生药/膏）、黄连膏低剂量组0.3g ·g^-1（生药/膏）,每组6只。阳性对照组为醋酸地塞米松乳膏组,进行2,4-二硝基氯苯（DNCB）致小鼠耳肿胀实验,观察黄连膏对炎症的抑制作用。结果：黄连膏中芝麻酚、盐酸小檗碱、芝麻素及总生物碱在24 h内的累积透过量分别为2.82,4.10,0.78,16.54 μg·cm^-2;稳态透皮速率（J_s）分别为0.125 2,0.181 4,0.034 2,0.745 7 μg·cm^-2·h^-1;与阳性对照组比较,黄连膏高剂量组显著抑制DNCB所致小鼠耳肿胀。结论：黄连膏具有良好的体外透皮性能及抗炎活性,24 h内单位面积累积透过量随药物中主要有效成分含量升高而增加,经皮渗透行为符合零级动力学方程。     

Biopharmaceutics: Effect of Ointment Bases on Topical and Transdermal Delivery of Salicylic Acid in Rats: Evaluation by Skin Microdialysis

Microdialysis has been used to determine the concentration of salicylic acid in skin tissue and plasma periodically for 4 h to evaluate the effect of ointment bases on topical and transdermal delivery of salicylic acid. The ointment bases examined were solbase (water-soluble), poloid and white petrolatum (oleaginous), hydrophilic poloid (water in oil (w/o) type emulsion lacking water) and absorptive ointment (w/o-type emulsion containing water). The ointments (0.1 g) containing 25 μmol salicylic acid were applied for 2 h to the surface of rat skin (1 cm²) with (intact) or without the stratum corneum. For intact skin, the extent of topical delivery from different ointments, evaluated by the area under the concentration-time curve (AUC) of salicylic acid in the skin tissue (AUCskin), increased in the order solbase. white petrolatum, poloid, hydrophilic poloid. absorptive ointment. The ratio of AUC_skin (topical delivery) to the AUC of salicylic acid in plasma (AUC_plasma, transdermal delivery) varied remarkably among the different bases, the greatest ratio being observed for absorptive ointment. When the ointments were applied to skin surface without stratum corneum, AUC_skin for solbase was much higher (about 45 times that for intact skin), whereas only a small (two-fold) increase was observed for poloid and hydrophilic poloid and the increase was negligible for white petrolatum and absorptive ointment. For skin without the stratum corneum, the ratio AUC_skin/AUC_plasma for the different ointments was comparable, although the magnitudes of AUC_skin and AUC_plasma still varied substantially. The variance of AUC values arises as a result of the different rates of release of salicylic acid from the bases. These results indicate that: the topical and transdermal delivery of salicylic acid in intact skin varies substantially among different ointment bases, and the greatest topical delivery is observed for absorptive ointment; use of absorptive ointment increases the retention of salicylic acid in the stratum corneum; and the stratum corneum functions strongly as a penetration barrier for solbase, moderately for poloid and hydrophilic poloid, and less for absorptive ointment and white petrolatum.     

In vitro release,rheological, and stability studies of mefenamic acid coprecipitates in topical formulations

A suitable topical formulation of mefenamic acid was developed in order to eliminate the gastrointestinal disorders associated with its oral administration. Drug coprecipitates prepared with different polymers at various drug-to-polymer ratios improved drug solubility and dissolution compared to pure drug and physical mixtures. PVP polymers (ratio 1:4) produced the best results. Aqueous ionic cream, ointments of absorption and water soluble bases and gels of methylcellulose, carboxymethylcellulose sodium, HPMC, Carbopol^® 934 and 940, and Pluronic^® F127 bases containing 1–10% drug as coprecipitates of PVP polymers (1:4) were prepared. The highest drug release was achieved at 1% drug concentration from water soluble base and methylcellulose among cream/ointment and gel bases, respectively. Gels, in general yielded better release than creams/ointments. All tested medicated creams/ointments exhibited plastic flow while all gels conformed to pseudoplasticity. Most of them showed thixotropy, a desired property of topical preparations. Stability studies revealed that HPMC and methylcellulose had the smallest changes in drug content, viscosity, and pH among the formulations. Considering drug release, rheological properties, and stability, methylcellulose gel containing 1% drug as coprecipitates of PVP K90 was the best among the studied formulations, was promising for improving bioavailability of mefenamic acid and can be used in future studies.     

盐酸地尔硫芯卓软膏基质处方筛选

目的： 优选盐酸地尔硫芯卓软膏的基质及处方组成。方法： 采用析因分析法筛选出最优的基质处方,以外观性状、离心稳定性、耐寒耐热稳定性以及膏体延展性为考察指标对盐酸地尔硫芯卓的基质处方进行筛选,最后对优选出的处方进行质量控制。结果： 最优化的处方为2%盐酸地尔硫芯卓,PEG400/4000比例为1.5：1,10%甘油,10%丙二醇,7%乙醇及2%月桂氮芯卓酮。结论： 盐酸地尔硫芯卓乳膏制备方法简单,稠度与延展性适宜,性状稳定,质量可控。     

Determination of prednisolone in ointments

A method for the quantitative determination of prednisolone in ointment preparations is described. It uses TLC and UV spectrophotometry in combination. Solutions and ointments are chromatographed using silica gel GF 254 and various solvent systems, the layers containing the active ingredient are eluted and the substance determined at 240 nm.     

Extraction of components from hydrocortisone mixtures using high pressure thin layer chromatography

Chromatographic conditions for the separation of five pairs of active compounds occuring in four ointment preparations and an aerosol one were elaborated. The ways of extraction of hydrocortisone esters (acetate and butyrate), chlorquinaldol, oxytetracycline base and oxytetracycline hydrochloride from the ointments as well as purification of the extracts prior to the HPLC analysis were described. The proposed analytical methods are for more specific and precise from those used until now in the home-made preparations quality control.     

A comparison of sodium fusidate ointment and mupirocin ointment in superficial skin sepsis

Sodium fusidate ointment and mupirocin ointment were compared in 354 patients with superficial skin sepsis. The ointments were applied 3-times daily, or once daily when covered by a dressing, and the response assessed after 6 to 8 days. Both preparations proved effective clinically with 86% of patients responding. There was no difference between the two preparations in cases of primary infection (85% to both ointments), including a sub-group with impetigo (sodium fusidate 88% and mupirocin 84%), or secondary infection (sodium fusidate 81% and mupirocin 89%). Sodium fusidate ointment (98%) was significantly better (p less than 0.05) than mupirocin (82%) in patients with other superficial infections. Both ointments were equally effective in cases where Gram-positive, Gram-negative or mixed Gram-positive/Gram-negative bacteria were isolated. Adverse effects were reported in 1.0% of patients using sodium fusidate ointment and in 7.4% of patients using mupirocin ointment. The majority of complaints concerned the greasiness of mupirocin ointment.     

Transdermal absorption of propofol in rats

Propofol (PF), a highly lipophilic anesthetic, has several desirable properties, such as the rapid onset and cessation of its effects upon intravenous infusion. In this study, the transdermal absorption of PF was investigated with the aim of the development of an alternative route of administration. PF solutions containing isopropyl myristate (IPM), ethanol or propylene glycol (PG) at various concentrations were prepared and applied to the abdominal skin of rats. Petrolatum and fatty alcohol propylene glycol (FAPG) ointments containing PF were also prepared and applied to the dorsal skin. Eyelid opening was measured and the ratio of the measured value to the initial value was calculated to evaluate the level of the pharmacological effect of the preparation. The PG solution containing 80% PF achieved higher plasma PF concentrations than the 100% PF solution. The PF-FAPG ointment produced a higher plasma PF concentration than the PF-petrolatum ointment. Furthermore, a drowsy state was confirmed after transdermal administration of 42% PF-FAPG ointment. These results indicate that the combination of PF and PG was appropriate for the transdermal absorption of PF, and PF was absorbed through the rat skin to an extent sufficient to cause a continuous sedative effect.     

The percutaneous action of a heparin-allantoin-dexpanthenol combination in a specific ointment base. Thrombolytic action on the rabbit ear

Experimentally induced thrombi of ear veins in albino rabbits have been treated locally with heparin-containing ointments in presence or absence of allantoin and dexpanthenol, the heparin concentration varying. While the ointments, containing heparin only, induce no or only minor thrombolytic activity, the combination ointments Hepathrombin Adenylchemie containing heparin, allantoin and dexpanthenol show significant thrombolytic activity. This effect is dependent upon the heparin concentration, yet, heparin doses above 50 000 IU per 100 g of ointment do not enhance the thrombolysis furthermore. Further, the studies show that the effective components of Hepathrombin do penetrate into and through the skin, allantoin and dexpanthenol being important components of the ointment probably supporting the transdermal penetration of heparin. The studies also demonstrate the only local thrombolytic effect of the Hepathrombin ointments because the thrombus of the right ear, always treated with ointment base only, did not show any change in length as contrasted to that of the left ear of the same animal treated with the Hepathrombin ointments. Mechanisms of the locally by Hepathrombin/heparin induced thrombolysis will be discussed.     

高效液相色谱法对四种双氯灭痛软膏剂透皮效果的研究

目的：本实验采用高效液相色谱法,以离体小白鼠腹部皮肤为透皮屏障,比较了四种双氯灭痛软膏剂的透皮效果,方法：实验用法国Gilson公司的HPLC仪,以C18为固定相,甲醇－水（含HAc 0.36%)=80:20为流动相,紫外检测波长280nm。平均回收率为99．59％,RSD＜3．28％,检测限为1．0ug/ml。结果：1号样品透皮率最高,3号与1号相比较透皮吸收无显著性差异（P＞0．05）,2号或4号分别与1号相比,其透皮吸收均有显著性差异（P＜0．05）,结论：1号品值得进一步开发。