环酯红霉素片

<正> [药品名称]通用名:环酯红霉素片;商品名:达发新(Davercin);英文名:Erythromycin Cyclic 11,12-Carbonate Tablets;汉语拼音:Huanzhi Hongmeisupian;本品主要成分及其化学名称为:红霉素环11,12-碳酸酯;其结构式为:     

红霉素环11,12-碳酸酯的体外抗菌活性研究

目的评 价红霉素环11，12-碳酸酯的体外抗菌活性。方法 采用琼脂平皿二倍稀释法测定国产和进口红霉素环11，12-碳酸酯对临床分离致病菌的体外抗菌作用，并与红霉素、罗红霉素、克拉霉素、地红霉素、阿奇霉素和乙酰螺旋霉素进行了比较。结果 国产和进口红霉素环11，12-碳酸酯对579株临床分离菌的抗菌活性相近，对革兰氏阳性菌和厌氧菌的抗菌活性比红霉素强2～8倍，优于罗红霉素、克拉霉素、地红霉索、阿奇霉素、乙酰螺旋霉素，但对革兰氏阴性菌的抗菌活性稍弱于阿奇霉素。红霉索环11，12-碳酸酯对金葡菌显示抑菌作用，对化脓链球菌在2～4倍MIC浓度时显示杀菌作用；红霉素环11，12-碳酸酯抗金葡菌和化脓链球菌的活性随着pH的增加而增强，接种量和血清浓度对国产红霉素环11，12-碳酸酯抗金葡菌和化脓链球菌的活性无明显影响。结论 红霉素环11，12-碳酸酯具有较强的体外抗菌活性，国产红霉素环11，12-碳酸酯抗菌活性与进口相近，优于红霉素、罗红霉素、克拉霉素、地红霉素、阿奇霉素和乙酰螺旋霉素。     

托吡酯治疗婴儿痉挛27例

目的观察托吡酯单一和联合用药治疗婴儿痉挛的疗效。方法36 例痉挛患儿随机分为4组，A组10例，单用托吡酯；B组9例，给予托吡酯加氯硝西泮；C组8例，给予托吡酯加促皮质素；D组9例，给予氯硝西泮加促皮质素。托吡酯片口服开始剂量1 mg·kg^-1·d^-1，每周增加1 mg·kg^-1，目标剂量9～16 mg·kg^-1·d^-1；促皮质素12.5～20.0 U·d^-1肌内注射，4周后改为口服泼尼松，1 mg·kg^-1·d^-1，3个月后停药；氯硝西泮片口服开始时0.01～0.03 mg·kg^-1·d^-1，逐渐加量到0.1～0.2 mg·kg^-1·d^-1。0.5 a后进行疗效评定。结果0.5 a后，A、B、C、D 4组的有效率分别为100.0%，89.0%，89.0%和78.0%，使用托吡酯组的疗效明显高于不使用托吡酯组。结论托吡酯治疗婴儿痉挛疗效好于促皮质素和氯硝西泮，且单用疗效好于联合用药，不良反应相对较少。但该实验例数较少，具体疗效尚需进一步观察。     

环扁桃酯的新合成路线的研究

目的 设计周围血管扩张药环扁桃酯的新合成路线。方法 以苯为原料,与草酰氯单乙酯反应制备苯乙酮酸乙酯（2）, 2 与顺式 3,3,5-三甲基环己醇通过酯交换合成顺式 3,3,5-三甲基环己醇苯乙酮酸酯（3）, 3 在锌粉和甲酸铵条件下发生还原得到环扁桃酯。结果与结论 合成目标化合物的总收率为59.6%,目标化合物的结构经¹H-NMR、¹³C-NMR、IR 谱确证。新合成路线具有原料廉价易得、操作简便、收率高的特点。     

依托咪酯与丙泊酚联合用于高龄患者胆囊切除胆总管探查手术的麻醉

目的 研究依托咪酯与丙泊酚联合用于高龄患者胆囊切除胆总管探查手术麻醉的应用价值. 方法 30例择期行开腹胆囊切除、胆道探查术患者,随机分为依托咪酯＋丙泊酚组（A组）和依托咪酯组（B组）. A组经静脉给予咪达唑仑0.03 mg&#8226;kg^-1,依托咪酯0.2 mg&#8226;kg^-1,丙泊酚0.5 mg&#8226;kg-1,芬太尼3～4 μg&#8226;kg^-1复合维库溴铵0.15 mg&#8226;kg-1诱导. B组经静脉给予咪达唑仑0.03 mg&#8226;kg^-1,依托咪酯0.3 mg&#8226;kg^-1,芬太尼3～4 μg&#8226;kg^-1复合维库溴铵0.15 mg&#8226;kg^-1诱导. 采用惠普多功能监护仪记录患者麻醉前、麻醉诱导后、插管即刻、插管后1 min及手术全程血压、心率,并记录患者肌震颤及术后24 h恶心呕吐等不良反应发生率. 结果 A组3例、B组2例于麻醉诱导后出现血压轻度下降,A组1例、B组2例于气管插管后血压上升、心率增快,但两组间比较差异无显著性（P＞0.05）. A组有1例术后第1天出现恶心,B组有6例术后第1天出现恶心、5例呕吐,与A组比较,差异有显著性（P＜0.05）. 结论 依托咪酯与丙泊酚联合用于高龄患者胆囊切除胆总管探查手术麻醉中,对血流动力学影响轻微,同时降低术后恶心呕吐的发生率.     

地红霉素肠溶微丸颗粒生物等效性研究

目的 建立测定人血浆中红霉素胺浓度的液相色谱 质谱联用(LC-MS)方法,研究地红霉素肠溶微丸颗粒在健康志愿者中的生物利用度,评价试验制剂和对照制剂的生物等效性.方法采用两制剂双周期自身对照交叉试验设计,20名健康志愿者,单剂量口服地红霉素试验制剂和参比制剂各500 mg,用LC-MS法测定血浆代谢物红霉素胺的浓度.用DAS 软件处理血药浓度数据和计算参数,并进行统计学分析.药物浓度 时间曲线下面积(AUC)及峰浓度(Cmax)经对数转换后作多因数方差分析和双单侧t检验并计算90%可信区间;达峰时间(tmax)进行非参数检验,对两种制剂作出生物等效性评价.结果建立血浆红霉素胺浓度的HPLC-MS测定法.红霉素胺的浓度与吸收峰面积比值在浓度5～1 000 ng.mL^-1范围内呈线性关系,线性回归方程为A＝68.87C+1.47(r＝0.999 7),最低检测浓度为5 ng.mL^-1.低、中、高浓度的方法回收率为98.32%,99.16%,97.87%,平均提取回收率为72.42%,71.63%,73.38%,日内、日间RSD均小于9%.单剂量口服500 mg的地红霉素试验制剂和参比制剂的主要药动学参数AUC0→96分别为(3 537.39±576.32)和(3 065.47±558.63) ng.mL^-1.h,AUC_0→∞分别为(4 059.27±737.25)和(3 831.76±687.51) ng.mL^-1.h;C_max分别为(415.84±81.24)和(420.36±63.21) ng.mL^-1;t_max为(3.25±0.28)和(3.47±0.35)h.受试制剂的相对生物利用度为(105.72±17.83)%.结论LC-MS测定法适用于测定人血浆中红霉素胺的浓度.统计分析结果表明,两种制剂的主要药动学参数之间无明显差异,两种制剂具有生物等效性.     

新型大环内酯类抗生素塞红霉素关键中间体的合成

目的:合成新型大环内酯类抗生素ABT-773(cethromycin,塞红霉素)关键中间体并进行工艺改进.方法:3-(3-喹啉)-2(E)-丙烯-1-醇叔丁基碳酸酯以3-溴喹啉为原料经3步合成侧链,然后从红霉素A肟开始,经酯化、烃基化、去保护得到目标化合物.结果:经质谱、核磁共振氢谱确证,合成了ABT-773侧链和关键中间体,总收率达46%.结论:本工艺简单,成本低,收率高.     

红霉素环11,12-碳酸酯于小鼠体内的抗菌活性研究

目的 评价红霉素环11，12-碳酸酯的体内抗菌活性。方法 采用小鼠腹腔感染模型，观察红霉素环11，12-碳酸酯口服对临床分离的金葡菌、化脓链球菌、肺炎链球菌感染小鼠的体内疗效，并与罗红霉素、红霉素进行比较。结果 红霉素环11，12-碳酸酯口服对金葡菌15、金葡菌91—29、化脓链球菌94—3、化脓链球菌556、肺炎链球菌9—9、肺炎链球菌9—5感染小鼠的ED50值分别为38．84、37．08、8．62、9．15、12．76、31，42mg／kg，抗菌活性比红霉素强2～8倍，与罗红霉素相近。结论 红霉素环11，12-碳酸酯对金葡菌、化脓链球菌和肺炎链球菌感染小鼠均有较强的保护作用，抗菌活性明显优于红霉素，与罗红霉素相近。     

红霉素环11，12—碳酸酯的合成研究

以红霉素A为原料,与环状碳酸酯一步反应得到了红霉素环11,12－碳酸酯,其体内外抗菌活性均强于母体抗体素－红霉素。由于分子内氢键的存在,使之以9R构型的半缩酮异构体形式存在。     

复方单硝酸异山梨酯缓释片人体血药浓度测定的方法学研究

目的 建立复方单硝酸异山梨酯缓释片的人体血药浓度测定方法。方法 应用GC和HPLC分别测定血浆中5-单硝酸异山梨酯和水杨酸的浓度。结果 本实验建立的血药浓度测定方法,血浆中内源性物质不干扰测定,线性范围5-单硝酸异山梨酯为2.72~696.50 ng·mL^-1,水杨酸为0.2~20 mg·mL^-1,日内和日间精密度均小于15%。结论 建立的测定方法适用于复方单硝酸异山梨酯缓释片在人体的血药浓度测定及药代动力学研究。     

L-aspartate of erythromycin A cyclic 11,12-carbonate, a new semisynthetic erythromycin derivative.

Erythromycin A cyclic 11,12-carbonate, a compound with high antibacterial activity, forms with L-aspartic acid a salt possessing valuable properties as a potential chemotherapeutic agent. The L-aspartate of erythromycin A cyclic 11,12-carbonate exhibits strong anti-bacterial activity, especially against Gram-positive bacteria and shows low toxicity. The serum and the lung tissue levels of the discussed salt after a single dose administration to a rat were measured in comparison with those of erythromycin, its L-aspartate, erythromycin cyclic 11,12-carbonate and its L-glutamate. The new erythromycin derivative showed definitely superior characteristics to those of the other substances tested. The activity of the L-aspartate of erythromycin A cyclic 11,12-carbonate in chemotherapy of experimental staphylococcal infection and experimental pneumococcal bronchopneumonia in mice is superior to that of the parent carbonate and erythromycin itself.     

环酯红霉素干混悬剂、胶囊与片剂的生物等效性研究

目的:评价环酯红霉素干混悬剂、胶囊与片剂的生物等效性。方法:18名健康志愿者采用开放、随机、三周期交叉的单中心试验。采用HPLC-MS法测定口服给药后不同时间环酯红霉素的血药浓度。利用DAS 2．0计算药动学参数和进行统计分析。结果:受试者口服750 mg参比制剂环酯红霉素片,受试制剂环酯红霉素干混悬剂和胶囊的C_(max)分别为(1375±s 261)Ixg·L~(-1),(1303土356)μg·L~(-1)和(1307±305)μg·L~(-1);t_(max)分别是(2．4±0．8)h,(2．4±1．0)h和(2．9±0．9)h;4UC_(0～48)分别是(13302±4 369)μg·h·L~(-1),(13596±5519)μg·h·L~(-1)和(13564±4 825)μg·h·L~(-1)。受试制剂的相对生物利用度分别为(102±17)％,(102±15)％。结论:环酯红霉素干混悬剂和胶囊与剂量相同的环酯红霉素片参比制剂具有生物等效性。     

Effect of the treatment period with erythromycin on cytochrome P450 3A activity in humans

The aim of the present study was to estimate the time course change in cytochrome P450 3A (CYP3A) activity during repeated doses of erythromycin. Twelve healthy male volunteers participated in this randomized, 4 x 4 Latin square design study. The pharmacokinetics of a single oral dose of midazolam, a probe for CYP3A activity, were assessed in 4 conditions: (1) midazolam (5 mg) without erythromycin (EM0), (2) erythromycin 2 days + midazolam (2.5 mg) (EM2), (3) erythromycin 4 days + midazolam (2.5 mg) (EM4), and (4) erythromycin 7 days + midazolam (2.5 mg) (EM7). The dose of erythromycin was 800 mg/d. Erythromycin produced a 2.3-, 3.4-, and 3.4-fold increase in dose-corrected area under the curve of midazolam for EM2, EM4, and EM7, respectively, as compared with EM0 (P <.05/6). A significant prolongation of terminal half-life was observed in EM4 and EM7. The relationship between the duration of erythromycin treatment and total clearance of midazolam indicated that a plateau level of CYP3A inhibition can be achieved by 4 days or more of erythromycin treatment. The repeated treatment with erythromycin yields CYP3A inhibition in a duration-dependent manner. A 4-day course of erythromycin treatment produces 90% or more of the maximal inhibition of CYP3A in humans.     

Synthesis of novel 2-substituted quinoline derivatives: antimicrobial, inotropic, and chronotropic activities

Three novel series of quinoline derivatives have been prepared by cyclization of the intermediate 3-(1,3-dioxolan-2-yl)-2-substituted thiocarbamoyl-hydrazinoquinolines with different alpha-halocarbonyl compounds. These series are: 3-(1,3-dioxolan-2-yl)-2-(3-substituted-4-phenylthiazolin-2-y lidene) hydrazinoquinolines; 3-(1,3-dioxolan-2-yl)-2-(3-substituted-5-ethoxycarbonyl- 4-methylthiazoline-2-ylidene)hydrazinoquinolines and 3-(1,3-dioxolan-2-yl)-2- (3-substituted-4-thiazolidinon-2-yl)hydrazinoquinolines. The active methylene group of the latter series was used for the preparation of their arylidene derivatives. The antimicrobial as well as inotropic and chronotropic activities of the prepared compounds were studied.     

Erythromycin A 11,12-methylene acetal

Erythromycin A 11,12-methylene acetal (5) and the corresponding 9-methoxime, 9-dihydro, and 8-hydroxy derivatives have been prepared and their antibacterial activities compared with those of erythromycin A and its 11,12-cyclic carbonate. The simple methylene acetal 5 showed excellent activity against Gram-positive organisms in vitro.     

Synthesis and Biological Activities of Some Benzimidazolone Derivatives

The reaction of 5-nitrobenzimidazolone with phenoxyethyl bromide in presence of potassium carbonate in dimethyl formamide obtained 6-nitro-1,3-bis(2-phenoxyethyl)-1,3-dihydro-2H-benzimidazol-2-one. It was reduced using stannous chloride to get 6-amino -1,3-bis(2-phenoxyethyl)-1, 3-dihydro-2H-benzimidazol -2-one, which was further treated with aromatic sulphonyl chloride to obtain benzimidazolone derivatives, 6a-k. These compounds were tested for antibacterial, antituberculosis and antifungal activity. Most of them have shown very good activity against some gram positive and gram negative microorganisms and fungal strains. Some of them have shown moderate activity against Mycobacterium tuberculosis.     

Synthesis and antibacterial activity of new 4″-O-carbamates of 11,12-cyclic carbonate erythromycin A 6,9-imino ether

A series of new 4″-O-carbamates of 11,12-cyclic carbonate erythromycin A 6,9-imino ether were synthesized and evaluated for their in vitro antibacterial activity. All the desired compounds demonstrated favorable activity (0.03 μg ml(-1)) against erythromycin-susceptible Streptococcus pneumoniae comparable to the references, exhibiting 133-fold higher activity than precursor 2 or 3. Similarly, all of the analogs exhibited improved activity against the erythromycin-resistant S. pneumoniae encoded by the erm gene and the erm and mef genes, showing 4-32-fold more effectiveness than erythromycin A.