抗真菌中药的作用机理研究进展

综述了 90年代以来在研究抗真菌中药作用机理方面取得的进展、存在的问题并对中药的抗真菌研究前景进行了展望。     

海洋细菌Bacillus coagulans spp.heishijiaosis 发酵液抗真菌活性及其机制研究

目的对凝结芽胞杆菌黑石礁新亚种LU-B02产生的抗白色念珠菌活性物质的作用靶位及抑菌谱进行了研究。方法采用山梨醇保护形态变异法结合扫描电镜超微结构观察研究了活性物质的作用靶位,最小抑菌浓度(MIC)法比较了该菌发酵液对不同真菌的抑菌活性。结果该活性物质抑制白色念珠菌细胞壁中的主要组分——葡聚糖的合成从而造成其细胞壁残缺。该活性物质具有抗真菌专一性,对革兰氏阳性代表菌金黄色葡萄球菌和革兰氏阴性代表菌大肠杆菌等细菌均无抑制效果,而对人体病原真菌抑菌效果较为明显,尤其是对白色念珠菌的抑制效果较好。MIC测定表明白色念珠菌对LU-B02活性物质高度敏感,相当于斯皮仁诺8~16μg,抑菌效价每毫升相当于3 500 U制霉菌素或洁尔阴活性的4倍。发酵液在酸性条件下加入0.2%冰片时,室温下存放6个月仍可保持良好的抗白色念珠菌活性。结论凝结芽孢杆菌黑石礁新亚种(Bacillus coagulans spp.heishijiaosis)产生的活性物质在控制以白色念珠菌为主的真菌感染方面具有良好应用前景。     

Halogenated benzoate derivatives of altholactone with improved anti-fungal activity

Altholactone exhibited the anti-fungal activity with a high MIC value of 128 μg ml^?1 against Cryptococcus neoformans and Saccharomyces cerevisiae. Fifteen ester derivatives of altholactone 1–15 were modified by esterification and their structures were confirmed by spectroscopic methods. Most of the ester derivatives exhibited stronger anti-fungal activities than that of the precursor altholactone. 3-Bromo- and 2,4-dichlorobenzoates (7 and 15) exhibited the lowest minimal inhibitory concentration (MIC) values against C. neoformans at 16 μg ml^?1_, while the 4-bromo-, 4-iodo-, and 1-bromo-3-chlorobenzoates (11–13) displayed potent activity against S. cerevisiae with MIC values of 1 μg ml^?1. In conclusion, this analysis indicates that the anti-fungal activity of altholactone is enhanced by addition of halogenated benzoyl group to the 3-OH group.     

高良姜中的抗白念珠菌化学成分

目的 研究高良姜抗白念珠菌的活性成分。方法 以生物活性追踪结合色谱分离，用纸片扩散法检测抑菌作用，以各种色谱柱层析，包括制备高效液相色谱，得到单体化学成分，用波谱技术鉴定各化合物的结构，测定各化合物的抗菌效价。结果 高良姜三氯甲烷提取物的抑菌活性最强。从三氯甲烷提取物中分离得到6个有抑菌活性的化合物，分别鉴定为2个黄酮类化合物：高良姜素（galangin）和芹菜素（apigenin）；3个二芳基庚烷类化合物：7-（4-羟苯基）-1-苯基-4-烯-3-庚酮、5-羟基-1-（4-羟苯基）-7-苯基-3-庚酮，和1-（4-羟基-3-甲氧基苯基）-7-（4-羟苯基）-3，5-庚醇；1个半日花型二萜类化合物：16-醛-8（17），12-半日花二烯-15酸。结论 抗白念珠菌实验表明，这6个化合物对白念珠菌均有一定的抑菌活性。     

苔色酸酯的合成及抗真菌作用的研究

目的合成出一系列苔色酸酯,并测试其抗真菌作用.方法以石花为原料,经丙酮提取得到红粉苔酸,用半合成方法,制备苔色酸酯.以试管内药液稀释法,考察苔色酸酯的抗真菌作用.结果合成出了7个苔色酸酯,其结构经元素分析、IR和ESI-MS等表征;其中5个对常见的浅层致病真菌如絮状表皮癣菌等的最低抑菌浓度范围在20～150 μg·mL-1,4个对深层真菌如申克孢子丝菌等的最低抑菌浓度在40～300 μg·mL-1.结论苔色酸酯对9种致病真菌抑菌作用显著,且效果均优于3,5-二羟基甲苯.     

中药抗真菌的研究进展

概括阐述了上个世纪90年代以来抗真菌中药的研究进展,归纳出中药可通过对真菌细胞结构、功能及大分子生成等多方面、多途径的影响而发挥其抗真菌作用,并对中药抗真菌研究目前所存在的问题加以分析并提出展望。     

The In-vitro Antifungal Spectrum of Itraconazole

Summary: The activity of itraconazole on 6113 fungal strains belonging to 252 species was evaluated in fluid media. The test medium was brain heart infusion broth for all fungi, except for Pityrosporum ovale, for which it was Dixon broth. Most of the human and animal pathogens and a large number of saprophytes were highly sensitive: dermatophytes, Candida, Cryptococcus, Torulopsk, Pityrosporum, Aspergillus, Penicillium, Sporothrix, dimorphic fungi, phaeohyphomycetes, agents of eufungal mycetoma, Entomophtorales and various others. The majority of Fusarizm species and the Zygomycetes were poorly sensitive. Itraconazoie was not only fungistatic at low concentrations, but also fungicidal for the tested organisms, such as Microsporum canis, Trichophyton mentagrophytes, Candida albicans, C. tropicalis, Aspergillus fumigatus, P. ovale and Cryptococcus neofor-mans with or without replenishment. Itraconazole was able to block the morpho-genetic transformation of C. albicam from the yeast phase into the (pseudo)-mycelium phase.     

Pharmacodynamic studies of voriconazole: informing the clinical management of invasive fungal infections

Introduction: Voriconazole is a broad-spectrum antifungal agent commonly used to treat invasive fungal infections (IFI), including aspergillosis, candidiasis, Scedosporium infection, and Fusarium infection. IFI often occur in immunocompromised patients, leading to increased morbidity and mortality.

Areas covered: The objective of this review is to summarize the pharmacodynamic properties of voriconazole and to provide considerations for potential optimal dosing strategies. Studies have demonstrated superior clinical response when an AUC/MIC >25 or C_min/MIC >1 is attained in adult patients, correlating to a trough concentration range as narrow as 2–4.5 mg/L; however, these targets are poorly established in the pediatric population. Topics in this discussion include voriconazole use in multiple age groups, predisposing patient factors for IFI, and considerations for clinicians managing IFI.

Expert commentary: The relationship between voriconazole dosing and exposure is not well defined due to the large inter- and intra-subject variability. Development of comprehensive decision support tools for individualizing dosing, particularly in children who require higher dosing, will help to increase the probability of achieving therapeutic efficacy and decrease sub-therapeutic dosing and adverse events.     

Comparison of Dermatopharmacokinetic vs. Clinicial Efficacy Methods for Bioequivalence Assessment of Miconazole Nitrate Vaginal Cream, 2% in Humans

Purpose. To compare the dermatopharmacokinetic vs. clinical trial methods for bioequivalence assessment of two miconazole nitrate vaginal cream, 2% products. Methods. The dermatopharmacokinetic method determined the bioequivalence of two products simultaneously in 24 healthy subjects, as a function of C_max and AUC_{0- t} parameters using miconazole nitrate content in harvested volar forearm stratum corneum. The clinical trial method determined bioequivalence as a function of clinical, mycological culture and therapeutic cure(s) after 7 days of product use and 30 days after therapy cessation in 106 female subjects with positive signs and symptoms of vaginitis, KOH vaginal smears and Candida cultures, randomly assigned to test or reference product. Results. The dermatopharmacokinetic method demonstrated that the two products were not bioequivalent, while the clinical trial method concluded bioequivalence. Conclusion. The dermatopharmacokinetic method allowed simultaneous evaluation of both products in the same subject, within the same study period, and was more sensitive and discriminating in the assessment of bioequivalence between the two miconazole nitrate vaginal cream, 2% products than the clinical trial method.