环吡酮胺乳膏含量的分光光度法测定

<正> 环吡酮胺乳膏(Ciclopirox Olamine Cream)为-抗真菌药。该药的含量测定,美国药典XXI版采用比色法,操作比较繁琐,查阅有关资料,尚未见到其他方法。笔者参考文献给出的环吡酮胺E_(1cm)~(1%)值,采用紫外分光光度法测定环吡酮胺乳膏的含量,操作简便,结果准确,现予报道。实验部分仪器、试剂与药品紫外分光光度计(岛津UV-200、岛津UV-250、国产751);无水乙醇(分析试剂);环吡酮胺精制品(湖北省医药工业研究所提供);环吡酮胺乳膏(湖北省医药工     

不同透皮促进剂对环吡酮胺和水杨酸体外经皮渗透性的影响

目的：以环吡酮胺和水杨酸为模型药物。研究透皮促进剂对外用抗真菌药的促透特性。方法：在离体透皮实验装置上进行透皮吸收试验和贮库效应的研究。结果：1%氮酮和1%薄荷醇联用对环吡酮胺经皮渗透的促进作用明显高于其它组，1%的薄荷醇对水杨酸促透效果最佳。而由1%氮酮。2.5%丙二酮，2.5%油酸，1%薄荷醇合用对环吡酮胺的体外经皮渗透虽具有明显的促进作用和时滞明显缩短。但是与二联使用透皮促进剂比较并无明显优点。结论：薄荷醇和氮酮对环吡酮胺和水杨酸体外经皮吸收具有显的促进作用。两联用对脂溶性化合物环吡酮胺的促透作用更明显。     

HPLC法测定复方环吡酮胺溶液中有效成分的含量

目的建立HPLC法同时测定复方环吡酮胺溶液中苯佐卡因和环吡酮胺两组分的含量。方法采用美国Agilent ZORBAX SB-C18色谱柱,以甲醇-乙腈-水-冰醋酸（15∶35∶50∶0.3）为流动相。检测波长为300nm,流速为1mL.min-1。结果苯佐卡因和环吡酮胺在15min内完全分离,两者在10～120mg.L-1范围内线性关系良好,平均回收率分别为101.15%和100.70%,相对标准偏差（RSD）均小于2%（n=9）;日内精密度和日间精密度（RSD）均小于2%（n=5）。结论本法准确、可靠、重复性好,可有效控制环吡酮胺溶液的质量。     

环吡酮胺涂膜剂的制备及体外透皮试验

目的：制备环吡酮胺涂膜剂,研究其透皮吸收性能。方法：用加速试验法研究环吡酮胺涂膜剂的热稳定性动力学,以双室渗透扩散装置进行环吡酮胺体外渗透试验。结果：试验结果表明,环吡酮胺涂膜剂降解反应为一级动力学过程,预测其有效期为２年,其体外透皮释药方程为Ｑ＝６３．１５４１ｔ－６０．７２９９（ｒ＝０．９９４０）,８ｈ累积渗透量为５０５．２３ｕｇ．ｃｍ＾－２。结论：环吡酮胺涂膜剂为一种新颖的控释型外用制剂。涂膜     

HPLC法测定环吡酮胺搽剂的含量及其有关物质

目的:建立HPLC测定环吡酮胺搽剂中环吡酮胺的含量.方法:采用Agilent ZORBAX SB-C18色谱柱(250 mm×4.6 mm,5μm),以甲醇∶乙腈∶水相(含25 mmol·L-1枸缘酸和2.5 mmol·L-1 EDTA,20％ NaOH调pH 7.0)(32∶ 18∶ 50)为流动相,检测波长为307 nm,流速为l ml·min-1,柱温30℃,进样量20μl.结果:有关物质含量为0.58％,环吡酮胺在20 ～ 200mg·L-1范围内线性关系良好(r=0.999 6),平均回收率为101.23％(RSD=1.88％,n=9).结论:本法准确、可靠、重复性好,可用于控制环吡酮胺搽剂的质量和有关物质的测定.     

促进剂预处理皮肤对环吡酮胺经皮渗透的影响

目的：考察透皮促进剂对环吡酮胺经皮渗透的影响,方法：用透皮促进剂预处理离体小鼠皮肤,以改良的Franz扩散装置进行体外渗透实验,结果：环吡酮胺经皮渗透符合零级动力学过程,几种透皮促进剂的促渗作用大小依次为月桂氮zhuo酮－丙二醇（1：1）＞二甲基亚砜＞月桂氮zhuo＞水溶性月桂氮zhuo酮＞N－甲基吡咯烷酮＞薄荷油,结论：体外实验证明,透皮促进剂可增加环吡酮胺的透皮吸收。     

HPLC法测定环吡酮胺软膏中环吡酮胺的含量

目的用HPLC法测定环吡酮胺软膏中环吡酮胺的含量。方法采用美国phenom enex Luna C18柱(250×4.6mm,5μm),以流动相A(甲醇)∶流动相B(乙腈)∶流动相C(含25mm o l.L-1枸橼酸、2.5mm o l.L-1乙二胺四乙酸二钠,用20%氢氧化钠溶液调pH 7.0)(45∶25∶30)的混合溶液作为流动相,流速为每分钟1.0mL,检测波长为304nm。结果环吡酮胺在30~240μg.mL-1范围内浓度与峰面积的线性关系良好(r=0.9999),低(80%)、中(100%)、高(120%)3种不同浓度环吡酮胺的平均回收率范围为99.8%~100.1%,RSD为0.17%~0.35%,空白基质对环吡酮胺的含量测定没有干扰。结论本方法简便,快速,结果准确,可靠,重现性好,比《中国药典》2000年版的分光光度法更能准确地测定环吡酮胺的含量,可供本品质量控制用。     

环吡酮胺软膏治疗体股癣及花斑癣临床观察

目的：探讨环吡酮胺软膏对体癣、股癣及花斑癣的临床治疗效果。方法：应用1％环吡酮软膏治疗体癣31例，股癣40例，花斑癣41例，与2％硝酸咪康唑霜进行对比。结果：环吡酮胺组中体癣、股癣及花斑癣的治愈率分别是87．1％，82．5％和85．4％；硝酸咪康唑组的治愈率分别为73．3％，58．8％和53．1％。疗效差异显著。结论：环吡酮胺软膏治疗体癣、股癣和花斑癣的疗效明显优于硝酸咪康唑霜。     

环吡酮胺阴道栓微生物限度检查方法学验证

目的建立环吡酮胺阴道栓微生物限度检查方法。方法按《中国药典》2010年版二部要求进行方法学验证。结果采用培养基稀释法(每皿0.2mL)有较强的抑菌性;改用薄膜过滤法(冲洗量每膜500mL),经菌落计数方法的验证,试验组与稀释剂对照组5种菌株的回收率均达到70%以上;控制菌验证也符合药典要求。结论该法可消除环吡酮胺阴道栓的抑菌作用,适用于该制剂的微生物限度检查。     

环吡酮胺涂膜剂的制备及含量测定

目的:制备环吡酮胺涂膜荆,采用高效液相色谱法测定含量。方法:采用Hypersil ODS C_(18)(250mm×4.6mm,5μm)色谱柱,以0.02mol·L~(-1)磷酸二氢钠溶液-甲醇(40:60)为流动相,流速:1.0ml·min~(-1),检测波长为304nm,柱温:30℃。结果:环吡酮胺及有关物质能得到完全分离,环吡酮胺在32～192μg·ml~(-1)浓度范围内呈良好的线性关系,r=0.999 6。平均回收率为100.5%,RSD=0.9%(n=9)。结论:制备工艺简单,含量测定方法准确、可靠。     

浙新霉素对皮肤癣菌的体外抗真菌活性研究

目的：评价浙新霉素体外抗真菌活性。方法：采用CLSI推荐的M-38A方案测定浙新霉素对7种皮肤癣菌最小抑菌浓度（MIC）及最小杀菌浓度（MFC）。结果：浙新霉素对7种皮肤癣菌的MIC范围为0.125-2.000μg·ml^-1,MFC范围为0.250-4.000μg·ml^-1。结论：浙新霉素具有较强的抗真菌活性,能抑制和杀灭絮状表皮癣菌、红色毛癣菌、紫色毛癣菌、犬小孢子菌、须癣毛癣菌、断发毛癣菌、石膏样小孢子菌等多种皮肤癣菌。     

硫色满酮并氮杂环衍生物体外抗真菌活性及构效关系研究

对硫色满酮并氮杂环衍生物进行体外抗真菌实验,筛选具有抗真菌活性的化合物并探讨其构效关系。方法：利用微量稀释法,以氟康唑和两性霉素B为阳性对照药,测定硫色满酮类并氮杂环衍生物对白色念珠菌、新生隐球菌、断发毛癣茵、红色毛癣菌、申克孢子丝菌（菌丝相）、石膏样小孢子菌、卡氏枝孢霉、黑曲霉、絮状毛癣菌的体外抑菌活性。结果：Bb,Da,Db,I,K对絮状表皮癣菌抑制作用显著,尤其Db的MIC低于两性霉素B;K对石膏样小孢子丝菌的MIC与两性霉素B相当。二甲氨基和甲氧基取代后,抗真菌比其他取代基化合物抗真菌活性高。结论：硫色满酮并氮杂环衍生物对常见致病真菌有一定的体外抑菌活性,值得深入研究。     

1-{2-[(4-取代苯基)甲氧基]-2-(取代苯基)乙基}-1H-氮唑类化合物的合成及抗真菌活性

根据氮唑类抗真菌化合物的构效关系和作用机理,设计合成了29个1-{2-[(4-取代苯基)甲氧基]-2-(取代苯基)乙基}-1H-氮唑类化合物,其中九个为首次报道。初步体外抑菌试验结果表明,大多数目标化合物对八种试验菌株都有不同程度的抗真菌活性。化合物14对白念珠菌的活性与克霉唑及益康唑相当,对其它七种试验菌株的活性明显强于克霉唑及益康唑。化合物4,12对白念珠菌活性差,对其它七种试验菌株的活性也强于克霉唑和益康唑。化合物5,6和23除对白念珠菌外,对其它七种试验菌株,也有较强活性。     

Design, synthesis and antifungal activity of some new imidazole and triazole derivatives

Triazole and imidazole are incorporated into the structures of many antifungal compounds. In this study a novel series of 1,2,4-triazole, imidazole, benzoimidazole, and benzotriazole derivatives was designed as inhibitors of cytochrome P450 14α-demethylase (14DM). These structures were docked into the active site of MT-CYP51, using Autodock program. Sixteen compounds with the best binding energy were synthesized. The chemical structures of the new compounds were confirmed by elemental and spectral ((1) H-NMR and Mass) analyses. All compounds were investigated for antifungal activity against Candida albicans, Candida tropicalis, Candida glabrata, Candida parapeilosis, Candida kruzei, Candida dubliniensis, Aspergillus fomigatus, Aspergillus flavus, Microsporum canis, Microsporum gypseum, Trichophyton mentagrophyte, Epidermophyton floccosum. Some compounds showed excellent in-vitro antifungal activity against most of the tested fungi. Compounds 2, 9, and 10 had antifungal activity against several resistant fungi against fluconazole and itraconazole.     

1-{2-[(4-取代苯基)甲氧基]-2-(取代苯基)乙基}-1H-氮唑类化合物的合成及抗真菌活性

根据氮唑类抗真菌化合物的构效关系和作用机理,设计合成了29个1-{2-[(4-取代苯基)甲氧基]-2-(取代苯基)乙基}-1H-氮唑类化合物,其中九个为首次报道。初步体外抑菌试验结果表明,大多数目标化合物对八种试验菌株都有不同程度的抗真菌活性。化合物14对白念珠菌的活性与克霉唑及益康唑相当,对其它七种试验菌株的活性明显强于克霉唑及益康唑。化合物4,12对白念珠菌活性差,对其它七种试验菌株的活性也强于克霉唑和益康唑。化合物5,6和23除对白念珠菌外,对其它七种试验菌株,也有较强活性。     

环匹罗司氨乙醇对癣的疗效与药敏试验

环匹罗司氨乙醇是一种广谱抗真菌新药。对常见皮肤癣菌的体外最低抑菌浓度(MIC)介于3.9-7.8μg/ml。经对173例体股癣的治疗观察,总有效率为58％。无不良反应。     

1-[2-(N-甲基-N-取代苄基)氨基-2-(2,4-二氟苯基)乙基]-1H-1,2,4-三唑类化合物的合成及抗真菌活性

目的:1-[2-(N-甲基-N-取代苄基)氨基-2-(2,4-二氟苯基) 乙基]-1H-1,2 ,4-三唑类化合物的合成及抗真菌活性研究。方法:通过付-克反应、三唑烷基化、酮亚胺还原和Leuckart 反应,得到关键中间体,然后通过N-烷基化反应制得目标化合物,并用二倍稀释法测定了体外抑菌活性。结果:合成了23 个1-[2-(N-甲基-N-取代苄基) 氨基-2-(2,4-二氟苯基)乙基]-1H-1 ,2,4-三唑类化合物,均为首次报道。所有目标化合物对8 种致病真菌均有不同程度的抗真菌活性。大部分化合物对Candida.albicans 和Candida.parapsilosis 的抗菌活性明显高于布替萘芬,其中1 ,2 ,6 ,13,14 ,19 对Candida.albicans 的抗菌活性是益康唑的8～32 倍,2,13 对Cryptococcu.neoformans 的抗菌活性是布替萘芬的4～8 倍,是益康唑64 ～128 倍。所有化合物对Microsporum .canis 的抗菌活性均高于或相当于益康唑。结论:其中一些化合物显示了较强抗真菌的活性,值得进一步研究。     

Antimycobacterial and antifungal isosters of salicylamides

A set of 40 derivatives of 3-hydroxypicolinic acid and 2-sulfanylbenzoic acid, isosteric to salicylanilides was synthesized. The compounds were evaluated for in vitro activity against Mycobacterium tuberculosis, Mycobacterium kansasii and Mycobacterium avium, Candida albicans, Candida tropicalis, Candida krusei, Candida glabrata, Trichosporon beigelii, Aspergillus fumigatus, Absidia corymbifera, Trichophyton mentagrophytes and Microsporum gypseum. Structure-activity relationships of antimycobacterial activity and antifungal activity against T. mentagrophytes and M. gypseum were analyzed by the Free-Wilson method. An increase in antimycobacterial activity was observed only for the sulfanylbenzoic acid derivatives, especially those with the benzyl moiety. The antifungal activity was not significant.     

Ciclopirox: recent nonclinical and clinical data relevant to its use as a topical antimycotic agent

Ciclopirox is a topical antimycotic agent belonging to the chemical class of hydroxypyridones and not related to azoles or any other class of antifungal agents. Its antimicrobial profile includes nearly all of the clinically relevant dermatophytes, yeasts and moulds, and is therefore broader than that of most other antimycotics. It is also active against certain frequently azole-resistant Candida species and against some bacteria. The mechanism of action of ciclopirox is different from that of other topical antifungal drugs, which generally act through ergosterol inhibition. The high affinity of ciclopirox for trivalent metal cations, resulting in inhibition of the metal-dependent enzymes that are responsible for the degradation of peroxides within the fungal cell, appears to be the major determinant of its antimicrobial activity. This unique and multilevel mechanism of action provides a very low potential for the development of resistance in pathogenic fungi, with cases of resistance rarely reported. Ciclopirox also displays mild anti-inflammatory effects in biochemical and pharmacological models; effects also shown in small clinical studies. Scavenging of reactive oxygen species released from inflammatory cells is a likely contributor to these anti-inflammatory effects. Ciclopirox, and its olamine salt, is available in multiple topical formulations, suitable for administration onto the skin and nails and into the vagina. The pharmaceutical forms most widely investigated are 1% ciclopirox olamine cream and 8% ciclopirox acid nail lacquer, but lotion, spray, shampoo, pessary, solution, gel and douche formulations have also been used. Ciclopirox penetrates into the deep layers of the skin, mucosal membranes and nail keratin, reaching concentrations exceeding the minimal fungicidal concentrations for most medically important fungi. A large number of clinical trials were and are still being performed with ciclopirox, starting in the early 1980s. Ciclopirox was first developed for fungal skin infections and vaginal candidiasis, and is currently well established in these indications. More recently, the drug has been clinically investigated in seborrhoeic dermatitis and onychomycosis, showing good efficacy and excellent tolerability. Emphasis in this review is given to a ciclopirox medicated nail lacquer, which is based on an original technology and has superior properties in terms of its affinity to keratin and nail permeation. It has been found to have superior efficacy and safety to another commercially available formulation in the treatment of onychomycosis. The safety features of ciclopirox are well known. The topical drug is devoid of systemic adverse reactions. Mild local reactions characterized by a burning sensation of the skin, irritation, redness, pain or pruritus, generally in less than 5% of treated patients, can be observed following skin and vaginal application. With nail application, the most common adverse event is the appearance of mild erythema in 5% of the treated population. As a general conclusion, although less effective than some oral antimycotic agents in various indications, ciclopirox compares very well in terms of the benefit/risk ratio due to its excellent tolerability and complete absence of serious adverse effects.     

铁螯合剂在地中海贫血治疗中的研究进展

机体铁过载常见于某些遗传性疾病的患者,如地中海贫血。人体铁含量过高可对各脏器功能产生严重影响,并可催化发生氧化还原反应释放羟自由基,破坏多种生物大分子,因此临床对地中海贫血的治疗都需辅以除铁治疗。铁螯合剂可与体内铁离子有效结合并促进铁排泄,降低体内铁含量及其在各器官的病理性沉积。目前临床使用的铁螯合药物有去铁胺、去铁酮和地拉罗司,且均存在局限性。因此,半个世纪以来医药工作者一直致力于寻找口服吸收好、毒副作用小的新药,而HBED,DFT,PIH类化合物有望成为具有临床价值的新铁螯合剂。