氧氟沙星滴耳液的临床疗效及体外抗菌活性

目的：观察氧氟沙星滴耳液的临床疗效及体外抗菌活性。方法：急慢性化脓性中耳炎120例,采用随机单盲法分成2组,治疗组80例,对照组40例。分别用国产0．3％氧氟沙星滴耳液,及进口0．3％氧氟沙星滴耳液（0．3％Tarivid滴耳液）治疗,疗程7天,同时分离临床致病菌13种105株,测定两制剂最低抑菌浓度（MIC）。结果：治疗组总有效率为96％,对照组98％,两组疗效相似（P＞0．05）。两制剂对13种105株革兰阳性和阴性菌均有显著抗菌作用,氧氟沙星滴耳液MIC50平均为0．39μg／ml,Tarivid滴耳液MIC50平均值为0．40μg／ml,两者抗菌活性相似。结论：氧氟沙星滴耳液的临床疗效及体外抗菌活性与进口制剂相似。     

国产盐酸左旋氧氟沙星体外抗菌活性研究

通过体外抗菌试验,检测了国产盐酸左旋氧氟沙星对常见致病菌最小抑菌浓度(MIC)、最小杀菌浓度(MBC)及杀菌曲线,了解其体外抗菌活性。结果表明该药对常见致病菌均显示了较强的体外抗菌效果,氧氟沙星比左旋氧氟沙星的MIC高l～2倍,显示了抗菌药效上的优势,与国外左旋氧氟沙星实验报道基本一致^[1]。     

国产盐酸左旋氧氟沙星体外抗菌活性研究

通过体外抗菌试验,检测了国产盐酸左旋氧氟沙星对常见致病菌最小抑菌浓度(MIC)、最小杀菌浓度(MBC)及杀菌曲线,了解其体外抗菌活性。结果表明该药对常见致病菌均显示了较强的体外抗菌效果,氧氟沙星比左旋氧氟沙星的MIC高1～2倍,显示了抗菌药效上的优势,与国外左旋氧氟沙星实验报道基本一致     

盐酸左氧氟沙星体外抗菌活性的研究

采用试管二倍稀释法测定了盐酸左氧氟沙星对临床分离的279株细菌的最低抑菌浓度（MIC）,并与环丙沙星,氧氟沙星作了比较。结果表明：肺炎杆菌,金黄色葡萄球菌,伤寒杆菌及痢疾杆菌对该药甚为敏感,盐酸左氧氟沙星对上述细菌MIC的范围,MIC50,MIC90分别为0．03－128ug/ml,0.03mu/ml,4ug/ml,0.03-128ug/ml,0.06ug/ml,16ug/ml,0.03-64ug/ml,0.03ug/ml,0.125ug/ml;0.03-2ug/ml,0.03ug/ml,2ug/ml,较氧氟沙星抗菌作用强。     

左旋氧氟沙星类似物的合成及其抗菌抗肿瘤活性研究

目的：设计合成有抗菌抗肿瘤活性的喹诺酮药物。方法和结果：根据推理药物设计原理,设计并合成了16个新型抗菌抗肿瘤喹诺酮类化合物,并研究其构效关系。结论：用9株细菌及4株肿瘤细胞评价了它们的体外抗菌活性(MIC值)及抗肿瘤活性(抑瘤率%)。其中,化合物16～20有较好的抗肿瘤及抗菌活性。     

枝原体和尿原体对左氧氟沙星衍生物(YH7)的体外敏感性研究

采用微量稀释法测定了(S)-9氟-2，3-二氢-3-甲基-10-（4-（2-嘧啶）-1-哌嗪基）-7-氧代-7H-吡啶并[1,2,3-de][1,4]苯并恶嗪-6-羧酸（YH7）等氟喹诺酮及大环内酯类、四环素类抗生素对人型支原体（Mh）、口腔枝原体（M.ora）、唾液枝原体（M.sal）、解脲枝原体（Uu）的体外敏感性。结果显示：YH7对Mh、M、ora、M、sal、Uu的最低抑制浓度（MIC）分别为0.5、0.25、0.125、0.125mg/L。它的抑菌活性是氧氟沙星2-16倍，与红霉素、柱晶白霉素相当。Mh、Uu对YH7及交沙霉素不易产生诱导耐药性，而对红霉素和四环素易产生诱导耐药性。而对红霉素升四环素产生耐药的Mh和Uu菌株对红霉素和四环素交叉耐药而对YH7和交沙霉素无交叉耐药。     

左氧氟沙星治疗伤寒临床疗效和体外抗菌活性研究

评价左氧氟沙星治疗伤寒的临床疗效和体外抗菌活性，方法：以国产和进口左氧氟沙星片剂做随机对照试验治疗急性伤寒共３０例，用药量均为２００ｍｇ，每日２次，疗程７ｄ，结果：两种药物均获得了良好的临床疗效，临床治愈率和细菌清除率均为１００％，国产和进口左氧氟沙星在临床疗效和细菌学疗效方面均无差异，两种药对伤寒杆菌的ＭＩＣ９０均为０．１２５ｍｇ／Ｌ。全部病例未见明显不良反应发生。．     

复方左氧氟沙星喷雾剂的体外抑菌实验

目的:考察复方左氧氟沙星喷雾剂体外抑菌能力。方法:采用琼脂稀释法测定复方左氧氟沙星喷雾剂对常见菌株的最低抑菌浓度(MIC)。结果:复方左氧氟沙星喷雾剂对5种标准菌株(大肠埃希菌ATCC35218、大肠埃希菌ATCC25922、金黄色葡萄球菌ATCC25923、粪肠球菌ATCC29212、铜绿假单胞ATCC27853),临床分离株(淋球菌L20、表皮葡萄球菌U457)的MIC分别为:0.02,0.1,0.1,0.2,0.1,0.1,1.0mg.L-1。结论:复方左氧氟沙星喷雾剂体外有较好的抑菌能力。     

加替沙星体外抗菌活性研究

采用琼脂二倍稀释法测定加替沙星对651株临床分离致病菌的体外抗菌活性，并与左氧氟沙星、司帕沙星、环丙沙星、诺氟沙星、头孢唑林、头孢呋辛、头孢噻肟、头孢他啶、万古霉素、阿米卡星、阿莫西林、哌拉西林/三唑巴坦比较。结果表明，加替沙星具有强而广谱的体外抗菌活性。对甲氧西林敏感的金葡球菌（MSSA）、表葡球菌（MSSE）、肠球菌的MIC90分别为0.125、1、16mg/L，抗菌活性为左氧氟沙星的1-2倍、环丙沙星的2-4倍，逊于第三代头孢菌素类。对肺炎克雷伯氏菌、伤寒沙门氏菌、痢疾杆菌、奇异变形菌、粘质沙雷氏菌，MIC90分别为4、0.25、0.5、4.32mg/L，抗菌活性为左氧氟沙星、司帕沙星、环丙沙星的1-2倍，与第三代头孢菌素类相当。对聚团肠杆菌、阴沟肠杆菌、乙酸钙不动杆菌、铜绿假单胞菌的MIC90分别为32、32、16.4mg/L。加替沙星对革兰氏阳性、阴性菌均具强大抗菌作用。     

清肺消炎丸体外抗菌活性研究

目的观察清肺消炎丸对9种肺炎常见病原菌的体外抗菌作用。方法采用琼脂稀释法,测定清肺消炎丸对9种药敏质控菌株的最低抑菌浓度(MIC)及最低杀菌浓度(MBC)。结果清肺消炎丸对肺炎链球菌、化脓性链球菌、金黄色葡萄球菌、流感嗜血杆菌的MIC分别为6.25、25、25、50mg/mL,相应的MBC分别为12.5、25、50、50mg/mL;对大肠杆菌、铜绿假单胞菌、肺炎克雷伯菌、变形杆菌及白色念珠菌均无明显体外抑菌活性。结论清肺消炎丸对肺炎链球菌、化脓性链球菌、金黄色葡萄球菌、流感嗜血杆菌具有体外抗菌作用,其中对链球菌的抗菌活性较高。     

Effect of food on the pharmacokinetics of YH439 and its metabolites in rats

The pharmacokinetics of YH439 and its metabolites were investigated after oral administration of YH439 to rats to investigate the food effect. After oral administration of YH439, its metabolites, M4 and M5 were detected in plasma. YH439 was not detected in the plasma for both fasted and fed rats for all doses studied. The pharmacokinetic parameters of the metabolites were not affected by food at all doses studied. The results of this study indicated that there are no significant food effects on the pharmacokinetics of YH439 and its metabolites in rats.     

司帕沙星衍生物(YH37)体外抗微生物活性研究

采用微量稀释法测定了5-氨基-1-环丙基-6，8-二氟-1，4-二氢-7-（3-甲基-1-哌嗪基）-4-氧代喹啉-6-羧酸（YH37）对临床分离的人型支原体（Mh）、解脲脲原体（Uu）以及细菌标准菌株的体外敏感性。结果显示，YH37对Mh的抑制活性较强，MIC90为0．25mg／L，是司帕沙星的1／8；对Uu的MIC90为1mg／L，是司帕沙星的1／4。YH37对Mh、Uu的喹诺酮耐药株有一定的抑制活性，其MIC分别为CPLX的1／4～1／16。YH37对被测细菌的抑制活性是左氧氟沙星的1／8～1／16，是司帕沙星的1／2。     

左氧氟沙星对幽门螺杆菌体外抗菌活性的评价

目的 体外试验检测左氧氟沙星对幽门螺杆菌(Helicobacter.pylori)的敏感性，并以克拉霉索和阿莫西林进行对照研究。方法 琼脂稀释法检测左氧氟沙星对52株幽门螺杆菌的最低抑菌浓度，同时比较在MH培养基pH为4．0、5．0、7．0条件下的MIC。结果 左氧氟沙星耐药菌株1．9％，阿莫西林耐药菌株11．5％，克拉霉索耐药菌株25％。同时对阿莫西林和克拉霉索耐药的菌株(9．6％)，对左氧氟沙星均敏感。左氧氟沙星耐药率明显低于克拉霉素(P＜0．01)，阿莫西林的耐药率也低于克拉霉素(P＜0．05)，但与左氧氟沙星的耐药率无明显差异(P＞0．05)。左氧氟沙星在酸性环境下抗菌活性降低。结论 本地区幽门螺杆菌耐药菌株多见，左氧氟沙星是一种可供选择的治疗药物。     

Antihypertensive and cardiovascular effects of the new calcium antagonist YH334

Antihypertensive effect of YH334 was examined in various experimental hypertension rat models and the systemic and regional hemodynamic profiles of the compound were investigated in conscious spontaneously hypertensive rats (SHR). The antihypertensive potency of YH334 is found to be more than 10 times stronger than that of nitrendipine in the all hypertensive models. The effective doses to lower the initial blood pressure by 20% (ED₂₀) of YH334 were 1.4 mg/kg in normotensive rats (NR), 0.7 mg/kg in SHR, 0.1 mg/kg in DOCA salt hypertensive rats (DHR) and 0.4 mg/kg in renal hypertensive rats (RHR), and the ED₂₀ values of nitrendipine were 15.8 mg/kg in NR, 7.1 mg/kg in SHR, 1.7 mg/kg in DHR and 4.8 mg/kg in RHR. The primary hemodynamic effect of YH334 was characterized by increasing CI and SVI and reducing TPRI of which hemodynamic profile is similar to that of nitrendipine. Both compounds seem to produce potent antihypertensive effects by lowering peripheral resistance in the skeletal muscles. In the organ bath study using isolated rabbit aorta, YH334 was found to be a potent voltage dependent calcium channels blocker without significant inhibitory effect on the receptor operated calcium channels like the most of other dihydropyridine type calcium antagonists. Furthermore, YH334 showed acute diuretic and natriuretic effects in conscious SHR, which may render the unnecessary restriction of sodium in the diet of those patients on long term hypertension therapy. This effect would provide an additional benefit to its potent antihypertensive activity.     

头孢呋新——有临床前途的头孢菌素

本文报道头孢呋新的体外抗菌活性、对β-内酰胺酶的稳定性和临床疗效。结果表明,头孢呋新对革兰阳性菌及绝大多数革兰阴性菌均有较强的抗菌作用。尤其对耐药菌所产生的β-内酰胺酶高度稳定。肝、肾毒性低,用本品治疗20例尿路、肺部、腹腔和皮肤软组织感染,19例有效,因此本品是一个有临床前途的头孢菌素。     

Antibacterial and antiproliferative activities of vulpinic acids in vitro.

The antimicrobial and antiproliferative activities of vulpinic acids (1 a, b, c) have been assayed in vitro. Activity was demonstrated by vulpinic acids on Gram-positive bacteria only. The MIC values of these compounds were found to be ranging from 3.8-31.5 micrograms/ml. The significance of these results is discussed.     

Pharmacokinetics of a new reversible proton pump inhibitor,YH1885, after intravenous and oral administrations to rats and dogs: hepatic first-pass effect in rats

The pharmacokinetics of YH1885 were evaluated after intravenous (iv) and oral administrations of the drug to rats and dogs. The reason for the low extent of bioavailability (F) of YH1885 after oral administration of the drug to rats and the absorption of the drug from various rat gastrointestinal (GI) segments were also investigated. After iv administration of YH1885, 5–20 mg kg⁻¹, to rats, the pharmacokinetic parameters of YH1885 seem to be independent of the drug at the dose ranges studied. After oral administration of YH1885, 50–200 mg kg⁻¹, to rats, the area under the plasma concentration–time curve from time zero to 12 or 24 h (AUC_{0–12 h} or AUC_{0–24 h}) was proportional to the oral dose of the drug, 50–100 mg kg⁻¹, however, the AUC_{0–24 h} value at 200 mg kg⁻¹ increased with less proportion to the dose increase (324, 689, and 815 μg · min mL⁻¹ for 50, 100, and 200 mg kg⁻¹, respectively) due to the poor water solubility of the drug. This was proved by the considerable increase in the percentages of the oral dose remaining in the entire GI tract as unchanged YH1885 at 24 h (11.8, 15.3, and 42.8% for 50, 100, and 200 mg kg⁻¹, respectively). The F value after oral administration of YH1885 to rats was relatively low; the value was approximately 40% at the oral dose of 50 and 100 mg kg⁻¹. The reason for the low F in rats was investigated. The liver showed the highest metabolic activity for YH1885 based on an in vitro rat tissue homogenate study; hence, the liver first-pass effect was estimated. The value of AUC after intraportal administration of the drug, 5 mg kg⁻¹, was approximately 70% (116 versus 163 μg · min mL⁻¹) of that after iv administration of the drug, 5 mg kg⁻¹, to rats; the liver first-pass effect of YH1885 in rats was estimated to be approximately 30%. The total body clearance of YH1885 after iv administration of the drug, 5–20 mg kg⁻¹, to rats were considerably lower than the cardiac output of rats, indicating that the lung and/or heart first-pass effect of YH1885 could be negligible in rats. After oral administration of YH1885, 50 and 100 mg kg⁻¹, to rats, the F value was approximately 40%, and approximately 15% of the oral dose was recovered from the entire GI tract as unchanged YH1885 at 24 h, and 30% of the oral dose disappeared with the liver first-pass effect. Therefore, the remainder, approximately 15% of the oral dose, could have disappeared with the small intestine first-pass effect and/or degradation of the drug in the GI tract. YH1885 was absorbed from ileum, duodenum, and jejunum of rat, however, YH1885 was under the detection limit in plasma when the drug was instilled into the rat stomach and large intestine. After iv administration of YH1885, 5–20 mg kg⁻¹, to dogs, the pharmacokinetic parameters of YH1885 also seemed to be independent of the drug at the dose ranges studied. However, after oral administration of YH1885, 0.5 and 2 g per whole body weight, to dogs, the AUC_{0–10 h} values were not significantly different (96.8 versus 98.2 μg · min mL⁻¹) and this could be due to the poor water-solubility of the drug. YH1885 was not detected in the urine after both iv and oral administration of the drug to both rats and dogs. Copyright © 1998 John Wiley & Sons, Ltd.     

左氧沙星与磷霉素联用对金黄色葡萄球菌的体外杀菌活性研究

目的：评价左氧沙星与磷霉素联用对金黄色葡萄球菌的联合抗菌效应。了解左氧沙星单用及与磷霉素联用的杀菌曲线特点。方法：选取3株MSSAATCC29213、临床分离菌SA99、SARN450（实验室菌株）和1株临床分离的MRS-AB6177,采用菌落计数法对不同浓度的左氧沙星或磷霉素单用及两药联合对3株MSSA和1株MRSA进行体外杀菌实验。结果：左氧沙星的杀菌曲线表现出浓度依赖性,磷霉素的杀菌曲线表现出非浓度依赖性。两药1/4MIC浓度单用时虽然均无法抑制MSSA的生长,而两药亚抑菌浓度联合使用后即表现出协同效应和杀菌效应。两药4MIC、8MIC联合时对MRSA表现出杀菌效应。结论：亚抑菌浓度的左氧沙星与磷霉素联合对MSSA即可出现协同杀菌效应。左氧沙星联合磷霉素对MRSA也表现出显著的杀菌活性。