琥乙红霉素颗粒微生物限度检查方法验证研究

目的建立琥乙红霉素颗粒的微生物限度检查方法。方法《中国药典》2005年版二部附录XIJ微生物限度检查法。结果采用培养基稀释法时琥乙红霉素颗粒仍含有较强的抑菌作用,但改用薄膜过滤法,能完全消除抑菌作用。结论琥乙红霉素颗粒微生物限度检查可采用薄膜过滤法,冲洗量为500ml。     

阿咖酚散微生物限度检查方法的验证

目的:建立阿咖酚散的微生物限度检查法,并对该法进行方法学验证。方法:采用2005年版《中国药典》附录微生物限度检查法中的3种方法对阿咖酚散进行研究,通过比较回收率来确定适宜的检查方法。结果:平皿法的5种试验菌的回收率均低于70%;薄膜过滤法回收率达85%以上;控制菌采用培养基稀释法可检出试验菌。结论:本品中细菌、霉菌和酵母菌检查宜采用薄膜过滤法,控制菌检查宜采用培养基稀释法。     

白花油微生物限度检查法的验证

目的 建立白花油微生物限度检查法。方法 采用（中国药典）2005年版一部附录微生物限度检查法项下的相关方法进行验证。结果 薄膜过滤法可有效去除白花油中的抑菌成分。结论 薄膜过滤法可作为白花油微生物限度检查的方法。     

无菌检查法中不容忽视的几个问题

20 0 0年版《中华人民共和国药典》(简称《中国药典》)中无菌检查法有了较大的改进 ,为确保检查的准确性 ,现简述几个不容忽视的问题。1　实验室人员及设备要求无菌检查应由具有微生物学专业知识 ,较高水平无菌操作熟练人员或相应资格经过正式微生物培训合格的人员 ,取得主管单位授予的合格证后 ,方可进行无菌检查。无菌实验区域内必须经过高效微粒空气过滤器过滤处理的层流空气 ,尽可能除去微生物污染。 2 0 0 0年版《中国药典》收载的薄膜过滤法对大容量供试品采用全封闭过滤系统 ,所以凡生产大容量灭菌制剂(≥ 50ｍＬ)的药厂与医院均需用购置符合《中国药典》要求的全封闭过滤系统。2　培养基及其灵敏度试验2 .1　培养基测试　无菌检查用培养基 ,无论是市售脱水培养基或配制的培养基 ,灭菌后就澄清无沉淀 ,还须进行无菌试验 ,硫乙醇酸盐流体培养基置 30～ 35℃培养 48ｈ,真菌培养基置 2 0～2 5℃培养 3ｄ均应无菌生长 ,如有菌生长需重新配制。2 .2　灵敏度试验　 2 0 0 0年版《中国药典》要求培养基质量应通过灵敏度检查。许多制药单位忽略了此项检查 ,导致检查结果的不可靠。2 .3　培养基临用前检查　硫乙...     

薄膜过滤法在药品检验中的应用

《中华人民共和国药典》中将微孔滤膜作为细菌、微生物限度检查法中的重要检查方法之一,薄膜过滤法的运用越来越广泛.薄膜过滤法操作简单、 检测数据准确的特点使其在药品检验中的运用频率越来越大.本文主要探讨薄膜过滤法在药品检验中制药、微生物原菌及药物验证环节的运用方法及原理,以期为药品检验过程提供理论依据.     

3种医院软膏剂微生物限度检查方法学研究

目的建立氯达软膏、利唑软膏、硫磺软膏医院软膏剂微生物限度检查方法。方法按《中国药典》2010年版二部微生物限度检查法中对细菌、霉菌及酵母菌计数方法和控制菌检查法进行验证。结果氯达软膏和利唑软膏细菌、霉菌及酵母菌计数检查采用薄膜过滤法,控制菌检查均采用薄膜过滤法;硫磺软膏细菌、霉菌及酵母菌计数检查采用培养基稀释法,控制菌金黄色葡萄球菌检查采用培养基稀释法,铜绿假单胞菌检查采用常规法。结论医院软膏制剂必须通过方法验证试验建立合理的检验方法,以保证检验结果的准确性。     

红花油微生物限度检查法的验证

目的建立红花油的微生物限度检查法。方法采用2005年版《中国药典（一部）》附录中微生物限度检查法项下的相关方法进行验证。结果薄膜过滤法可有效去除红花油中的抑菌成分。结论薄膜过滤法可作为红花油的微生物限度检查方法。     

盐酸阿扑吗啡鼻喷剂微生物限度检查方法的验证

目的建立盐酸阿扑吗啡鼻喷剂微生物限度检查方法,所检测的样品及检验程序不得对可能存在的各类微生物产生抑制作用。方法《中国药典））2010年版二部附录收载的微生物限度检查法中的薄膜过滤法进行实验。结果薄膜过滤法试验中稀释剂对照组的菌回收率和试验组的菌回收率均大于70％,微生物没有抑制作用。结论微生物限度检查方法可以采用薄膜过滤法。     

复方白及液微生物限度检查方法适用性研究

目的:对复方白及液微生物限度检查方法适用性进行研究,建立该产品的微生物限度检查方法.方法:按照《中国药典》2020年版要求,分别采用培养基倾注法、薄膜过滤法,进行微生物计数方法适用性试验.采用常规法、薄膜过滤法、培养基稀释法进行控制菌检查方法适用性试验.结果:微生物计数方面,培养基倾注法不能满足要求,采用薄膜过滤法,需...     

曲咪新乳膏微生物限度检查法的验证

目的建立曲咪新乳膏微生物限度检查法。方法采用《中国药典》2005年版二部附录微生物限度检查法项下的相关方法进行验证。结果薄膜过滤法可有效去除曲咪新乳膏中的抑菌成分。结论薄膜过滤法可作为曲咪新乳膏微生物限度检查的方法。     

HPLC法测定抗妇炎胶囊中木兰花碱、黄柏碱、药根碱、巴马汀、小檗碱、槐果碱、苦参碱、氧化槐果碱、槐定碱和氧化苦参碱

目的 采用高效液相色谱（HPLC）法同时测定抗妇炎胶囊中木兰花碱、黄柏碱、药根碱、巴马汀、小檗碱、槐果碱、苦参碱、氧化槐果碱、槐定碱和氧化苦参碱10种活性成分。方法 采用InerSustain AQ-C₁₈色谱柱（250 mm×4.6 mm,5 μm）,流动相A：乙腈–无水乙醇（80∶20）,流动相B：0.1%磷酸溶液,梯度洗脱,检测波长220 nm,体积流量1.0 mL/min,柱温30℃,进样量10 μL。结果 木兰花碱、黄柏碱、药根碱、巴马汀、小檗碱、槐果碱、苦参碱、氧化槐果碱、槐定碱和氧化苦参碱分别在2.69～134.50、1.95～97.50、0.63～31.50、0.86～43.00、11.95～597.50、0.59～29.50、6.08～304.00、4.85～242.50、1.66～83.00、19.79～989.50 μg/mL线性关系良好（r≥0.999 3）;平均回收率分别为99.11%、98.23%、96.95%、97.78%、100.02%、97.21%、99.66%、99.52%、98.81%、100.08%,RSD值分别为1.04%、1.23%、1.37%、1.65%、0.70%、1.28%、0.65%、0.81%、1.11%、0.63%。结论 建立的HPLC法可用于抗妇炎胶囊中10种活性成分的测定,作为抗妇炎胶囊质量控制方法。     

Susceptibility to erythromycin of anaerobes of the genera Bacteroides, Fusobacterium, Sphaerophorus, Veillonella, Clostridium, Corynebacterium, Peptococcus, Peptostreptococcus

The minimal inhibitory concentrations (MIC) of erythromycin were determined by broth dilution tests for 313 anaerobic strains, most of which were clinical isolates. All the gram-positive anaerobes tested (84 Peptococcaceae, including 21 Peptostreptococcus anaerobius and 15 Peptococcus variabilis; 65 Corynebacterium acnes and 29 Clostridium strains, including 13 C. perfringens) were sensitive (MIC values 0.012 through 3.12 microgram erythromycin/ml); so were 111 cultures of gram-negative anaerobes (52 Bacteroides fragilis, 12 B. thetaiotaomicron, 7 B. vulgatus, 13 B. oralis, 4 B. melaninogenicus, 10 Sphaerophorus necrophorus, 2 Veillonella sp., 11 members of other species). Erythromycin at concentrations of 6.25 through 200.0 microgram/ml was active against 24 strains (1 B. fragilis, 4 Fusobacterium fusiforme, 9 Sph. freundi, 10 Sph. varius). The present results are compared to the limited number of reports existing with regard to the susceptibility of anaerobes to erythromycin.     

Safety assessment of poloxamers 101, 105, 108, 122, 123, 124, 181, 182, 183, 184, 185, 188, 212, 215, 217, 231, 234, 235, 237, 238, 282, 284, 288, 331, 333, 334, 335, 338, 401, 402, 403, and 407, poloxamer 105 benzoate, and poloxamer 182 dibenzoate as used in cosmetics

Poloxamers are polyoxyethlyene, polyoxypropylene block polymers. The impurities of commercial grade Poloxamer 188, as an example, include low-molecular-weight substances (aldehydes and both formic and acetic acids), as well as 1,4-dioxane and residual ethylene oxide and propylene oxide. Most Poloxamers function in cosmetics as surfactants, emulsifying agents, cleansing agents, and/or solubilizing agents, and are used in 141 cosmetic products at concentrations from 0.005% to 20%. Poloxamers injected intravenously in animals are rapidly excreted in the urine, with some accumulation in lung, liver, brain, and kidney tissue. In humans, the plasma concentration of Poloxamer 188 (given intravenously) reached a maximum at 1 h, then reached a steady state. Poloxamers generally were ineffective in wound healing, but were effective in reducing postsurgical adhesions in several test systems. Poloxamers can cause hypercholesterolemia and hypertriglyceridemia in animals, but overall, they are relatively nontoxic to animals, with LD(50) values reported from 5 to 34.6 g/kg. Short-term intravenous doses up to 4 g/kg of Poloxamer 108 produced no change in body weights, but did result in diffuse hepatocellular vacuolization, renal tubular dilation in kidneys, and dose-dependent vacuolization of epithelial cells in the proximal convoluted tubules. A short-term inhalation toxicity study of Poloxamer 101 at 97 mg/m(3) identified slight alveolitis after 2 weeks of exposure, which subsided in the 2-week postexposure observation period. A short-term dermal toxicity study of Poloxamer 184 in rabbits at doses up to 1000 mg/kg produced slight erythema and slight intradermal inflammatory response on histological examination, but no dose-dependent body weight, hematology, blood chemistry, or organ weight changes. A 6-month feeding study in rats and dogs of Poloxamer 188 at exposures up to 5% in the diet produced no adverse effects. Likewise, Poloxamer 331 (tested up to 0.5 g/kg day(-1)), Poloxamer 235 (tested up to 1.0 g/kg day(-1)), and Poloxamer 338 (at 0.2 or 1.0 g/kg day(-1)) produced no adverse effects in dogs. Poloxamer 338 (at 5.0 g/kg day(-1)) produced slight transient diarrhea in dogs. Poloxamer 188 at levels up to 7.5% in diet given to rats in a 2-year feeding study produced diarrhea at 5% and 7.5% levels, a small decrease in growth at the 7.5% level, but no change in survival. Doses up to 0.5 mg/kg day(-1) for 2 years using rats produced yellow discoloration of the serum, high serum alkaline phosphatase activity, and elevated serum glutamicpyruvic transaminase and glutamic-oxalacetic transaminase activities. Poloxamers are minimal ocular irritants, but are not dermal irritants or sensitizers in animals. Data on reproductive and developmental toxicity of Poloxamers were not found. An Ames test did not identify any mutagenic activity of Poloxamer 407, with or without metabolic activation. Several studies have suggested anticarcinogenic effects of Poloxamers. Poloxamers appear to increase the sensitivity to anticancer drugs of multidrug-resistant cancer cells. In clinical testing, Poloxamer 188 increased the hydration of feces when used in combination with a bulk laxative treatment. Compared to controls, one study of angioplasty patients receiving Poloxamer 188 found a reduced myocardial infarct size and a reduced incidence of reinfarction, with no evidence of toxicity, but two other studies found no effect. Poloxamer 188 given to patients suffering from sickle cell disease had decreased pain and decreased hospitilization, compared to controls. Clinical tests of dermal irritation and sensitization were uniformly negative. The Cosmetic Ingredient Review (CIR) Expert Panel stressed that the cosmetic industry should continue to use the necessary purification procedures to keep the levels below established limits for ethylene oxide, propylene oxide, and 1,4-dioxane. The Panel did note the absence of reproductive and developmental toxicity data, but, based on molecular weight and solubility, there should be little skin penetration and any penetration of the skin should be slow. Also, the available data demonstrate that Poloxamers that are introduced into the body via routes other than dermal exposure have a rapid clearance from the body, suggesting that there would be no risk of reproductive and/or developmental toxicity. Overall, the available data do not suggest any concern about carcinogenesis. Although there are gaps in knowledge about product use, the overall information available on the types of products in which these ingredients are used, and at what concentration, indicates a pattern of use. Based on these safety test data and the information that the manufacturing process can be controlled to limit unwanted impurities, the Panel concluded that these Poloxamers are safe as used.     

Disposition of fluvastatin, an inhibitor of HMG-COA reductase, in mouse, rat, dog, and monkey

The physiological disposition of fluvastatin, a potent inhibitor of hydroxymethylglutaryl-CoA reductase and thus cholesterol synthesis, has been studied in the mouse, rat, dog, and monkey using 14C- or 3H-labeled drug. Oral doses of fluvastatin were absorbed at a moderate to rapid rate. The extent of absorption was dose-independent and was essentially complete in all four species studied. However, the drug was subject to extensive presystemic hepatic extraction followed by direct excretion via the bile, thus minimizing the systemic burden and yielding high liver/peripheral tissue concentration gradients for fluvastatin and its metabolites. Only at high doses far exceeding the intended human daily dose of ca 0.6 mg kg-1 did fluvastatin bioavailability approach unity, apparently due to saturation of the first-pass effect. Dose-normalized blood levels of fluvastatin and total radioactivity were higher in the dog than in the other species, suggesting a smaller distribution volume in the former. Fluvastatin was partially metabolized before excretion, the extent of metabolism being smallest in the dog and greatest in the mouse. The half-life of intact fluvastatin ranged from 1-2h in the monkey to 4-7h in the dog. Regardless of the dose or dose route, the administered radioactivity was recovered predominantly in feces, with the renal route accounting for less than 8 per cent of the dose. No tissue retention of radioactivity was observed, and material balance was essentially achieved within 96h after dosing.     

Simultaneous measurement of bupivacaine, etidocaine, lidocaine, meperidine, mepivacaine, and methadone

A gas-liquid chromatographic method for the simultaneous measurement of bupivacaine, etidocaine, lidocaine, meperidine, mepivacaine, and methadone in serum is described. The drugs and the internal standard, prilocaine, are extracted from 1 ml of serum. The procedure involves a two-step extraction and injection of the extract into a gas chromatograph equipped with a 10-ft OV-11 glass column and a nitrogen-phosphorus detector. The temperature gradient program results in a run time of 16 min and retention times for meperidine, prilocaine (internal standard), lidocaine, etidocaine, mepivacaine, methadone, and bupivacaine of 3.8, 5.4, 6.0, 8.7, 11.0, 11.7, and 14.8 min, respectively. Standard curves for all drugs were linear over the 80 to 2,000-ng/ml range and recovery of all components averaged 97 +/- 2% with the lowest detection limit of 10 ng/ml for all drugs except meperidine and methadone, which were 20 ng/ml. The within-day coefficients of variation ranged from 12 to 8% at 500 ng/ml. The day-to-day coefficients of variation of the slope and intercept values ranged from 2 to 0% and 130 to 3%, respectively. Response factors of the nitrogen-specific collector varied with the drug analyzed and resulted in peak area variation at constant offset and attenuation of 30%. This method is intended and adequate for therapeutic monitoring of chronically treated pain patients who are being given various combinations of local anesthetic and/or narcotic agents.     

New antiretroviral drugs: a review of the efficacy,safety, pharmacokinetics,and resistance profile of tipranavir,darunavir, etravirine,rilpivirine, maraviroc,and raltegravir

Background: The introduction and approval of new antiretroviral agents in the US and Canada bring new opportunities and new challenges. Arguably, for the first time ever, clinicians have the drugs necessary to achieve the goal of suppressing HIV RNA to levels less than 50 copies/mL in even the most treatment-experienced patients and in those with extensive drug-limiting resistance mutations. However, the use of these new agents is complicated by many drug–drug interactions and – to some extent – pre-existing mutations. To derive maximum durability from the use of these newer drugs, a thorough understanding of their indications and limitations is critical. Objective: To thoroughly review the six most recently approved or soon-to-be-approved antiretroviral drugs in the US and Canada: tipranavir, darunavir, etravirine, rilpivirine, maraviroc, and raltegravir. Methods: Discussion of the indications for, and pharmacokinetics, resistance profile, activity, toxicity, and clinical trials results of, the six new agents. Results/conclusions: These six new agents have resulted in marked progress towards the goal of being able to provide HIV-infected individuals with the drugs necessary to achieve decades of durable suppression of HIV without substantial toxicity.     

马蹄金中铁、钙、镁、铜、锌、锰、镍的形态分析

目的：研究马蹄金全草中微量元素的存在形态。方法：采用超声波提取。电感耦合等离子发射光谱法（ICP—AES）对马蹄金不同形态中Fe、Ca、Mg、Cu、Zn、Ma、Ni等元素进行分析。结果：Fe元素在马蹄金中含量最高，而Cu元素含量最低；Ca的提取率最高，Fe的提取率最低；Ca、Mg、Cu、Zn、Mn、Ni6种元素的可溶态均大于悬浮态；且渣中的微量元素含量较高。结论：马蹄金中的微量元素是以无机态为主，多种形态共存的复杂体系。     

Effects of amendments of N, P, Fe on phytoextraction of Cd, Pb, Cu, and Zn in soil of Zhangshi by mustard, cabbage, and sugar beet

Soil contaminated with Cd, Pb, Cu, and Zn in the Zhangshi irrigation area is very hard to be remediated. Phytoextraction is considered as an efficient method to remove these toxic metals from soil. In the present study, three vegetables including sugar beet (Beta vulgaris), mustard (Brassica juncea L.), and cabbage (Brassica oleracea L. var. capitata Linn.) were used to bioaccumulate heavy metals in soil through pots experiment for 90 days; and nutrient elements were applied to stimulate the phytoextraction of metals. Results of bioconcentration factors (BCF) and translocation factors (TF) from this study showed that these plants could phytoextract heavy metals, but the accumulation and translocation of metals differed with species of plants, categories of heavy metals, and some environmental conditions (e.g. nutrients). Meanwhile, the addition of nutrient elements, such as N, P, and Fe, could affect the phytoremediation of heavy metals via promoting the normal metabolism of vegetables or changing forms of metals. Results of this study could provide some available information for in-site bioremediation of soil from Zhangshi irrigation area.     

Strength of drug habits: For heroin,morphine, methadone,alcohol, barbiturates,pentobarbital, benzedrine,cocaine, and marijuana

The drug habits for 78 confirmed opiate addicts were studied on eight scales from the Process Association Test of Addiction (PATA) for many drug names. Through cluster analysis eight stages of addiction were defined: “to be clean”, “to learn about drugs”, “to hustle”, “to chip” (also “to be high”), to be psychologically dependent or “to need a shot”, “to be hooked”, “to kick a habit” and “to be in treatment”. Associations stimulated by the words heroin and morphine were very similar over the eight stages of addiction in opiate addicts. The subjects were especially inclined to associate morphine and heroin with the most severe level of addiction, “to be hooked”. Associations to both methadone and cocaine were elevated at the “hooked” stage, but in other respects associations to these drugs were opposite. Thus, associations to cocaine were focused on the stage of psychological dependence and the lower intermediate stage of addiction, “to chip” and “to be high”, whereas associations to methadone suggested a turning away from addiction as indicated by avoidance associations (“to come down” and “to kick a habit”) as well as associations to “treatment” and “to be clean”. Marijuana, Benzedrine, “goofball” (barbiturates) and alcohol habits were prominent at an intermediate stage of addiction (“to chip” and “to be high”). Avoidance associations were common for Benzedrine and “goofballs” (also pentobarbital) but not for marijuana or alcohol. “Hustling” associations were frequent for marijuana but not for alcohol.