司丙红霉素的急性毒性研究

目的:观察司丙红霉素对小鼠的急性毒性反应和死亡情况。方法:采用三种不同给药途径对昆明小鼠进行了急性毒性研究。结果:灌胃给药的LD50为2134.6(1761.8~2586.4)m g/kg,腹腔注射给药LD50为305.5(272.2~341.9)m g/kg,静脉注射给药LD50为121.2(115.3~127.3)m g/kg。结论:司丙红霉素用于临床是较安全的。     

司丙红霉素对大鼠的长期毒性

目的:考察连续给予司丙红霉素(EPAC)对大鼠的毒性反应.方法:健康SD大鼠分别按体重随机分为低、中、高剂量组和蒸馏水组.低、中、高剂量组给药量分别为75,150和300 mg·kg-1,连续灌胃给药90 d.结果:司丙红霉素300 mg·kg-1剂量组大鼠进食量减少,体重减轻,并伴有呕吐;150和300 mg·kg-1剂量组大鼠血清总胆红素(T-Bil)及天冬氨酸转氨酶(AST)升高;300mg·kg-1剂量组血清丙氨酸转氨酶(ALT)升高.1个月恢复期后,150和300mg·kg-1剂量组各项指标均恢复正常.75 mg·kg-1剂量组大鼠各项指标无明显影响.结论:司丙红霉素可引起可逆性毒性反应,大鼠口服司丙红霉素90 d的安全剂量为75 mg·kg-1.     

司丙红霉素安全性药理学研究

目的:观察司丙红霉素对大鼠心血管、呼吸系统和小鼠中枢神经系统的影响。方法:健康SD大鼠分别按体重随机分为低、中、高3个剂量组和溶媒对照组。给药组分别从十二脂肠给予司丙红霉素75,150,300 mg·kg~(-1),对血压、心电图(ECG)、呼吸频率及呼吸幅度进行观察。小鼠实验分低、中、高3个剂量组及溶媒对照共4个组,分别灌胃给予司丙红霉素75,150,300 mg·kg~(-1),对动物一般活动和睡眠时间进行观察。结果:司丙红霉素300 mg·kg~(-1)剂量组使大鼠心率下降,对舒张压、收缩压、ECG之QRS时间、ST段、T波、QT间期、呼吸频率及呼吸幅度无明显的影响;对小鼠一般活动和睡眠时间无明显影响。75,150 mg·kg~(-1)剂量组对大鼠、小鼠各项指标无明显影响。结论:司丙红霉素300 mg·kg~(-1)对心血管系统有一定影响,可使大鼠心率下降。     

地红霉素的合成研究

目的研究地红霉素的合成工艺。方法以红霉素为原料，经与水合肼缩合，硼氢化钠还原，再与2-（2-甲氧基乙氧基）乙缩醛缩合得到地红霉素。结果该合成路线不仅收率高，产品纯，而且无需过柱分离。结论该工艺路线适合工业化生产。     

地红霉素的合成

以红霉素A为原料,经红霉素腙路线合成红霉素胺,与2－（2－甲氧基乙氧基）乙缩醛一步缩合得到地红霉素,总收率为38．2％。本研究对红霉素腙的合成方法及缩合反应的反应条件进行了改进。     

司帕沙星与红霉素随机对照治疗支原体肺炎53例

目的评价国产司帕沙星治疗支原体肺炎的有效性和安全性.方法采用随机对照方法,以红霉素为对照.共治疗患者53例,司帕沙星组28例,口服,200 mg,每日1次;红霉素组25例,口服,250 mg,每日4次.疗程10～14日.结果司帕沙星组与红霉素组有效率分别为96.4%和96.0%,治愈率分别为82.1%和84.0%,病原菌清除率分别为96.4%和96.0%,无显著性差异(P＞0.05).不良反应发生率分别为3.6%和32.0%,有显著性差异(P＜0.05).结论采用司帕沙星治疗支原体肺炎安全有效.     

恶丙嗪合成工艺研究

以安息香为起始原料，从几条睡线中选择最适用的工艺路线，对恶丙嗪加以合成。     

影响琥乙红霉素合成的主要因素

揭示国内琥乙红霉素合成的两个主要环节,缩合反应和结晶过程。进一步揭示影响两个环节的主要因素,并总结绘制出坐标图。     

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。     

克拉霉素的合成

红霉素碱经肟化、保护再经甲基化、脱保护得到克拉霉素 ,总收率达 40 %以上。     

一种大孔吸附树脂的合成及在红霉素提取中的应用

以高含量工业级二乙烯苯悬浮聚合 ,合成了一系列大孔吸附树脂 ,从中筛选到一种树脂PT4 ,其对红霉素的吸附性能接近对红霉素吸附性能好的市售进口树脂AmberliteXAD 16。同时研究了用大孔吸附树脂提取红霉素的方法 ,包括吸附树脂和洗脱剂的筛选 ,吸附条件和解吸条件的考察。确定了使用PT4 树脂在pH9.2 ,流速 4BV/h的条件下对红霉素滤液的动态吸附量为 12 .2× 10 4 μ/g湿树脂 ,采用乙酸丁酯洗脱 ,洗脱液流速为 0 .5BV/h、2 .5BV洗脱液情况下洗脱率为 92 %。     

紫外分光光度法测定红霉素明胶微球的含量

目的采用紫外分光光度法测定红霉素明胶微球的含量。方法紫外分光光度法。结果红霉素溶液在0.0191~0.0522mg.mL-1浓度范围内,吸收度与浓度之间呈良好的线性关系C=0.0663A-0.0008mg.mL-1,r=0.9999:总平均回收率99.91%,RSD=0.28%(n=9)。结论该方法操作简便,结果准确可靠,适用于该制剂的质量评价。     

Synthesis of two and antibacterial activity of one novel oxime ether derivatives of erythromycin A

The synthesis of novel erythromycin A 9-O-(2-ethenesulfony-ethyl)-oxime and erythromycin A 9-O-(3-oxo-butyl)-oxime from erythromycin A (EA) by the Michael reaction is described and to describe the effects of transformation of ketone in position 9 of EA to an oxime ether. This transformation occurred in a single step without protecting of any functional moiety of erythromycin oxime and zero waste manner in good yield. The antibacterial screen of EA 9-O-(2-ethenesulfony-ethyl)-oxime is also reported.     

中性粒细胞对红霉素内在化的特殊意义

为了解红霉素被中性粒细胞(PMN)内在化浓聚的规律及其后续意义。采用体外PMN与红霉素共孵育的方法，检测共孵育过程中及刺激活化后细胞内外红霉素浓度比的时相动力学改变。免疫荧光法检测PMN浓聚红霉素后细胞膜表面炎性表征膜结合弹力酶的基础水平及刺激活化后的改变。检测下呼吸道感染大鼠循环注入浓聚红霉素的PMN后，支气管肺胞灌洗液中红霉素浓度与正常大鼠的差异。结果显示，PMN可迅速浓聚红霉素，60min细胞内／外浓度比达高峰16／1，而此时膜表面弹力酶水平则明显下降。刺激活化浓聚红霉素的PMN，可导致细胞内／外浓度比下降，而此时膜表面弹力酶表达上升，但上升幅度低于正常PMN。接受浓聚红霉素PMN注射的下呼吸道感染大鼠，其气道中红霉素浓度明显高于正常大鼠。研究结果提示红霉素可在PMN中迅速浓聚，这种浓聚可导致PMN基础活化水平的降低以及刺激活化反应的抑制。刺激活化可导致浓聚红霉素的部分释放，此特性有助于浓聚于PMN的红霉素向感染部位的定向释放。     

Effect of dehydration on the disposition kinetics of erythromycin in rabbits.

The effect of water deprivation on the physiologic, biochemical, and disposition parameters of erythromycin was investigated in rabbits. The packed cell volume, plasma glucose, and total lipid concentration increased significantly in dehydration. The pharmacokinetic parameters of erythromycin after intravenous administration also changed, suggesting a need for monitoring toxicity of erythromycin in the water-deprived population.     

Effect of erythromycin on the oro-caecal transit time in man

Summary Erythromycins often cause gastrointestinal side-effects due to an increase in motility or to change in the intestinal bacterial flora. In order to evaluate the effect of erythromycin on gastrointestinal motility, 11 healthy volunteers were given placebo, erythromycin stearate (ES) 1000 mg or a therapeutically equivalent single dose of erythromycin acistrate (EA, 2-acetyl erythromycin stearate) 800 mg in a double-blind trial. The orocaecal transit time was measured using the hydrogen breath test with lactulose as the substrate. The transit time was estimated from the H₂-peak (ppm) in end-expiratory breath by two methods, t₁ representing the front and t₂ the bulk of lactulose reaching the colon.t₁ was 51 min in the placebo group, 38 min in the EA and 31 min in the ES group (p < 0.05, ES vs placebo). t₂ was 74 min, 64 min, and 46 min, respectively (p < 0.05, ES vs placebo). The difference between EA and ES was also significant. Six subjects in the ES group but none in the EA group recorded adverse gastrointestinal effects attributable to medication.It was concluded that erythromycin shortens the orocaecal transit time in man and that EA affects the transit time slightly less than ES.     

Effect of multiple-dose erythromycin on everolimus pharmacokinetics

Objective We sought to quantify the influence of the CYP3A inhibitor erythromycin on the pharmacokinetics of everolimus, a CYP3A substrate.Methods This was a two-period, single-sequence, crossover study in 16 healthy subjects. In period 1, subjects received the reference treatment of a single 2-mg dose of everolimus. In period 2, they received the test treatment of erythromycin 500 mg three times daily for a total of 9 days and a single 2-mg dose of everolimus coadministered on the fifth day of erythromycin therapy. The test/reference ratio and 90% confidence interval (CI) were derived for everolimus C _max and AUC.Results During erythromycin coadministration, everolimus C _max increased 2.0-fold (90% CI, 1.8–2.3) from 20±5 ng/ml to 40±10 ng/ml. Everolimus AUC increased 4.4-fold (90% CI, 3.5–5.4) from 116±37 ng h/ml to 524±225 ng h/ml. Everolimus half-life was prolonged by 39% from 32±6 h to 44±6 h. Erythromycin predose concentrations were not changed after single-dose administration of everolimus. Conclusion Multiple-dose erythromycin increased single-dose everolimus blood levels by an average 4.4-fold (range, 2.0–12.6). During erythromycin treatment, a compensatory everolimus dose reduction should be made guided by everolimus therapeutic drug monitoring.This study was financed by Novartis Pharmaceuticals.     

HPLC法测定无味红霉素含量

建立了离子对高效液相色谱法测定无味红霉素含量。采用C8（5μm，4．0mm×125mm）柱（Lichrospher），以含0．1％（V／V）三乙胺的10mmol／L十二烷基硫酸钠溶液（用磷酸调pH3．4）-乙睛（52：48），检测波长为205nm。线性范围992～4958u／ml，r=0．9998（n=5），回收率100.3％，日内平均RSD为0．6％（n＝18），日间平均RSD为0.8％（n＝9）。