异烟肼介入凝胶体外抗结核作用及安全性评价

目的：观察异烟肼凝胶体外抗结核活性和支气管介入的安全性。方法：手工法，仪器法分别测定异烟肼、异烟肼凝胶的最小抑菌浓度和最小杀菌浓度及家兔经支气管介入的安全性。结果：异烟肼凝胶对H37RV标准株，牛型结核分枝杆菌MIC值均为1mg.L^-1，对草分枝杆菌MIC值为8mg.L^-1，对H37RV标准株，牛型结核分枝杆菌MBC值均为4mg.L^-1，对草分枝杆菌MBC值为16mg.L^-1，异烟肼凝胶与异烟肼单体MIC、MBC值差异无显著性；动物安全性试验阴性，结论：异烟肼凝胶具有与异烟肼单体相同的抗结核菌药效，卡波姆基质不影响异烟肼的抗菌活性；卡波姆基质异烟肼凝胶应用安全。     

吡嗪酰胺介入凝胶体外抗结核活性及安全性评价

目的 :观察吡嗪酰胺凝胶体外抗结核作用和支气管介入的安全性。方法 :手工法、仪器法分别测定吡嗪酰胺单体、吡嗪酰胺凝胶的最小抑菌浓度 (MIC)和最小杀菌浓度 (MBC)及家兔经支气管介入的安全性试验。结果 :吡嗪酰胺凝胶对人型结核分枝杆菌标准株、牛型结核分枝杆菌、草分枝杆菌MIC值分别为1mg/L、1mg/L、10mg/L ,MBC值分别为10mg/L、10mg/L、40mg/L ;吡嗪酰胺凝胶与吡嗪酰胺单体MIC、MBC值无显著性差异 ;动物安全性试验阴性。结论 :吡嗪酰胺凝胶具有与吡嗪酰胺单体相同的抗结核菌药效 ,卡波姆基质不影响吡嗪酰胺的抗菌活性 ;卡波姆基质吡嗪酰胺凝胶应用安全     

帕司烟肼的不良反应

1　过敏反应患者 ,男 ,56岁 ,因肺结核给予帕司烟肼治疗 ,5ｄ后发现腹部、背部密布斑片状红色斑丘疹且瘙痒 ,1周后全身皮肤又出现红色小疹 ,随后出现大小不等的水疱最大者 9ｃｍ ,以大腿内侧足跟、脚踝明显。背部、肘部、臀部、骶尾部等皮肤受压部位出现糜烂破溃 ,双下肢水肿加重。停药后经对症治疗 ,1周后皮肤开始脱屑 ,破溃处逐渐愈合 ,双下肢水肿逐渐消退[1 ] 。2　过敏性休克患者 ,男 ,62岁 ,因肺结核首次服用帕司烟肼 0 .5ｇ,1ｈ后出现发热、寒战、胸闷、气短 ,Ｒ 36次·ｍｉｎ 1 ,Ｐ 1 4 0次·ｍｉｎ 1 ,ＢＰ60 0ｍｍＨｇ,呼吸急促 ,…     

吡嗪酰胺介入凝胶体外抗结核活性及临床应用

目的观察吡嗪酰胺凝胶体外抗结核作用和支气管介入的安全性。方法手工法、仪器法分别测定吡嗪酰胺单体、吡嗪酰胺凝胶的最小抑菌浓度(MIC)和最小杀菌浓度(MBC)及家兔经支气管介入的安全性试验。结果吡嗪酰胺凝胶对人型结核分枝杆菌标准株、牛型结核分枝杆菌、草分枝杆菌MIC值分别为1.0、1.0、10mg/L,MBC值分别为10、10、40mg/L;吡嗪酰胺凝胶与吡嗪酰胺单体MIC、MBC值无显著性差异;动物安全性试验阴性。结论吡嗪酰胺凝胶具有与吡嗪酰胺单体相同的抗结核菌药效,卡波姆基质不影响吡嗪酰胺的抗菌活性;卡波姆基质吡嗪酰胺凝胶应用安全。     

HPLC法测定帕司烟肼中间氨基酚的含量

目的：建立帕司烟肼中间氨基酚检查方法,有效控制帕司烟肼产品中间氨基酚含量。方法：色谱柱：十八烷基硅烷键合硅胶柱,流动相：甲醇-10%四丁基氢氧化铵溶液-0.05mol/L磷酸氢二钠-0.05mol/L磷酸二氢钠（100∶21∶450∶450）,检测波长280nm。结果：方法在1.06～3.18μg/mL范围内线性关系好,相关系数r=0.9999（n=5）;加样回收率为99.7%,RSD=0.7%;仪器精密度高,多次进样RSD=0.7%（n=6）。结论：方法专属性强,分离度好,准确度高,能有效控制帕司烟肼中间氨基酚含量。     

帕司烟肼片中间氨基酚和游离肼的检测

目的: 建立帕司烟肼片中间氨基酚和游离肼的 HPLC 测定方法。方法: 间氨基酚色谱柱: Agilent ZORBAX SB-Aq( 4. 6 mm × 250 mm,5 μm) ; 流动相: 甲醇-10% 四丁基氢氧化铵溶液-0. 05 mol·L^{- 1}磷酸二氢钠( 100∶ 2∶ 900) ; 检测波长为220 nm;游离肼色谱柱: Diamonsil Plus C₁₈( 4. 6 mm × 150 mm,5 μm) ; 流动相: 0. 1% 乙二胺四乙酸二钠-乙腈( 31∶ 69) ; 检测波长为310 nm。结果: 间氨基酚和游离肼的线性范围分别为 0. 101 0 ～ 20. 19 μg·m L^{- 1}和 0. 259 0 ～ 51. 80 μg·m L^{- 1}( r≥0. 999 9) ,检测限分别为0. 1 ng、0. 04 ng,平均回收率分别为 99. 39% 、99. 16% ( RSD≤1. 0% ,n = 8) 。结论: 该方法专属性好、操作简便、快速准确,可用于帕司烟肼片中间氨...     

帕司烟肼缓释片的制备与评价

目的制备帕司烟肼缓释片并对其进行质量评价。方法以体外释放度试验为手段,通过单因素试验考察帕司烟肼缓释片的处方及工艺,采用相似因子法和综合评分法进行评价,采用数学模型拟合研究药物的释放机制。结果帕司烟肼缓释片的处方和制备工艺为:帕司烟肼300mg,羟丙基甲基纤维素(HPMC K4M)100mg,片剂硬度为6kgf;缓释片中对氨基水杨酸和异烟肼的释放机制符合non-Fickian扩散机制。结论此处方工艺制备的帕司烟肼缓释片释药行为稳定,简便可行,易于工业化生产。     

乳酸左氧氟沙星与帕司烟肼联合应用治疗难治性结核病24 …

研究难治性肺内、肺外结核的治疗，对肝功能异常者和不能耐受一线抗痨方案者及耐多药结核患者提出有效的治疗方案。采用乳酸左氧氟沙星，每晨５～６ｍｇ／ｋｇ１次顿服；帕司烟肼，每日１５～２０ｍｇ／ｋｇ分２～３次口服。根据病人具体情况加选下列药品中的１～２种：卡那霉素，阿米卡星，乙胺丁醇，大蒜素，黄莲素，优福宁。对２４例患者采用以上方案治疗１年以上，每阶段均做详细观察并记录。结果２４例患者有效１９例，显效４例     

帕司烟肼用于复治涂阳肺结核患者的临床疗效观察

目的观察和评价含帕司烟肼方案在复治涂阳肺结核患者治疗中的效果。方法将120例复治涂阳肺结核患者随机分为治疗组60例和对照组60例,治疗组化疗方案以帕司烟肼为主,联合利福喷汀,吡嗪酰胺,乙胺丁醇,对照组用异烟肼加PAS,联合用药同治疗组。采用全程监督化疗管理,按各自方案实施化疗。结果治疗组经治疗3、6、9、12个月痰结核菌阴转率明显高于对照组,且各时间点差异均有统计学意义(P<0.05)。疗程结束时治疗组和对照组病灶治疗有效(明显吸收+吸收)率分别为88.3%(53/60)和68.3%(41/60),两组比较差异有统计学意义(χ2=7.07,P<0.05)。疗程结束时治疗组和对照组空洞闭合率分别为72.9%(35/48)和50.0%(23/46),空洞治疗有效(闭合+缩小)率分别为85.4%(41/48)和60.9%(28/46),两组空洞闭合率、空洞治疗有效率比较差异有统计学意义(χ2=5.22、7.25,P<0.05)结论用含帕司烟肼方案治疗复治涂阳肺结核患者有助于痰菌阴转病灶吸收和空洞闭合,不良反应发生率低,值得推广应用。     

HPLC法测定帕司烟肼片中对氨基水杨酸和异烟肼的含量

目的：用ＨＰＬＣ法测定帕司烟肼片中对氨基水杨酸和异烟肼的含量。方法：以ＯＤＳ为固定相,流动相为０．０５％十二烷基硫酸钠－甲醇（７：１,含０．２％醋酸钠）,检测波长为２５４ｎｍ,采用外标法。结果：对氨基水杨酸、异烟肼的线性范围分别为０．２１～１．２μｇ和０．１８～１．１μｇ,回收率分别为１００．１％和１００．５％。结论：本法结果准确,重现性好,以此法测定帕司烟肼的含量,更具合理性,能有效地控制质量。     

利复星凝胶对家兔体外抗结核的活性研究

目的研究利复星联合卡波姆凝胶对家兔体外抗结核的安全性。方法采用HPLC法测定血清中利复星浓度,在体外检测MIC、MBC、时间-杀菌及耐药梯度。测定利复星凝胶的最小抑菌、杀菌浓度及家兔经支气管介入的安全性。结果8例肺结核患者血药峰浓度于1.22h达4.52±0.72mg.L-1,分别1次给药24h后,最低血药浓度为0.52±0.26mg.L-1,表观分布容积V/FC为77.48±8.33mg.L-1。该药MIC、MBC值分别为0.5、1.0mg.L-1,耐药梯度范围0.5~48mg.L-1。利复星凝胶对H37RV标准株、牛型结核分枝杆菌、草分枝杆菌的MIC值分别为0.1、0.1、0.4mg.L-1,MBC值分别为0.2、0.21、.6mg.L-1;与利复星单体的MIC、MBC比较无显著差异。结论耐药肺结核患者服用利复星24h,其体内血药浓度维持在最低杀菌浓度MBC之上,介入治疗用药浓度应在48mg.L-1以上。     

Comparative in vitro activity of phenothiazines against multidrug-resistant Mycobacterium tuberculosis

The comparative activity of five phenothiazines against multidrug-resistant strains of Mycobacterium tuberculosis (MDRTB) was studied using the Bactec 460 system. The order of antimycobacterial activity of the phenothiazines was: chlorpromazine = thioridazine > promethazine > promazine = desipramine. However, the levels required for an MIC 50 exceeded 1 mg/l and are beyond those that are clinically achievable. As phenothiazines are concentrated by macrophages that phagocytose and have in situ activity against mycobacteria, these agents may be considered for use as adjuvants for the management of freshly diagnosed tuberculosis in patients from populations with a high prevalence of MDRTB.     

In vitro activity of four fluoroquinolones against Mycobacterium tuberculosis

The in vitro activity of ciprofloxacin, ofloxacin, levofloxacin and moxifloxacin against strains of Mycobacterium tuberculosis was studied. Moxifloxacin and levofloxacin showed the greatest activity having an MIC(90) of 1 mg/l. The MIC(90) for ofloxacin was 2 mg/l and for ciprofloxacin 4 mg/l. Further studies should be made to determine the role played by these compounds in the treatment of tuberculosis.     

Plants in our combating strategies against Mycobacterium tuberculosis: progress made and obstacles met

Context: Traditionally used plants for treating chest-related problems/tuberculosis (TB) have not been evaluated in detail and hence a thorough study is needed in this regard. This knowledge may find application in developing new anti-TB drugs.

Objective: This article elaborates on studying the activity of medicinal plants against different forms of Mycobacterium tuberculosis (Mtb) using different model strains, in vitro and ex vivo assays for studying the tuberculocidal activity and discusses the results from different studies on the activity against different forms of Mtb and human immunodeficiency virus-tuberculosis (HIV-TB) co-infection.

Methods: Scientific databases such as PubMed, Elsevier, Scopus, Google scholar, were used to retrieve the information from 86 research articles (published from 1994 to 2016) related to the topic of this review.

Results: Twenty-three plant species have been reported to possess active molecules against multi-drug resistant (MDR) isolates of Mtb. Seven plants were found to be active against intracellular Mtb and six against dormant bacilli. Seven plants were synergistically effective when combined with anti-TB drugs. Six studies suggest that the beneficial effects of plant extracts are due to their wide array of immuno-modulatory effects manifested by the higher expression of cytokines. Some studies have also shown the dual activity (anti-HIV and anti-TB) of plants.

Conclusion: We emphasize on identifying plants based on traditional uses and testing their extracts/phytomolecules against MDR strains, intracellular Mtb as well as against dormant Mtb. This will help in future to shorten the current therapeutic regimens for TB and also for treating HIV-TB co-infection.     

In vitro activity of linezolid against multidrug-resistant Mycobacterium tuberculosis isolates

Information in the literature regarding the activity of linezolid against multidrug-resistant (MDR) Mycobacterium tuberculosis strains is scarce. We therefore tested the in vitro activity of this drug against 39 MDR M. tuberculosis strains isolated from clinical specimens using the Bactec 460 TB system. All strains were inhibited by < or = 8 mg/L (minimum inhibitory concentration (MIC); MIC50 = 4 mg/L, MIC90 = 8 mg/L). Although the MIC values are higher than in other studies, based on proposed breakpoints all strains were found to be susceptible to linezolid. Further investigations to prove its usefulness in the treatment of MDR tuberculosis should be carried out.     

Comparative in vitro activities of rifamycin analogues against rifampin-sensitive and rifampin-resistant Mycobacterium tuberculosis

Because of widespread emergence of multidrug resistant Mycobacterium tuberculosis worldwide, there is an urgent need for new bactericidal drugs against this organism. Several new analogues of rifamycin are being developed. Susceptibilities of five of the most potent analogues were determined simultaneously on ten isolates each of rifampin-sensitive and rifampin-resistant M. tuberculosis using the radiometric method (BACTEC) with [C(14)]palmitic acid. Against rifampin-sensitive isolates, all five analogues exhibited inhibitory activity, the most potent being KRM-1648, with MICs varying between 0.003 and 0.02S mug/ml (MICs of rifampin were between 0.05 and 0.4 mug/ml). Similar observations were also obtained for the MBCs of these five analogues-KRM-1648 was most potent, with nine out of ten isolates exhibiting a MBC/MIC ratio of 1.0. Among the rifampin-resistant isolates of M. tuberculosis, the most potent rifampicin analogue was, again, KRM-1648, with seven out of ten isolates exhibiting MBC/MIC ratio of 1.0 and the remaining three exhibiting a ratio of 2.0. These results suggests that KRM-1648 should further be explored in the treatment of tuberculosis patients.