氨苄青霉素,羧苄青霉素中寡聚物的分离分析

在葡聚糖凝胶ＳｅｐｈａｄｅｘＧ－１０（４０～１２０μｍ）凝胶色谱系统中，用１ｍｏｌ／Ｌ的硫酸胺溶液（ｐＨ７．２）作流动相，实现了对氨苄青霉素、羧苄青霉素高聚物、寡聚物和药物本身的分离，利用ＦＡＢ－ＭＳ、ＨＰＬＣ等分析手段证明，氨苄青霉素、羧苄青霉素中的寡聚物主要为混合二聚体：在氨苄青霉素中主要含开环和闭环二种不同结构的聚合物，在羧苄青霉素中为其Ｄ型和Ｌ型旋光异构体形成的同聚和异聚聚合物。     

氨苄青霉素聚合物的研究——Ⅱ.氨苄青霉素中聚合物的含量测定

采用以乙腈或甲醇磷酸盐缓冲液为移动相,在C18反相色谱柱上进行线性梯度洗脱的高效液相色谱方法可以把氨苄青霉素和它的各个聚合物完全分开,同时可以计算出各个聚合物相对于氨苄青霉素的百分含量。用此方法测定了国内外样品39批,结果表明各批间氨苄青霉素二聚物的含量差异很大,在0.1～13.6％之间。     

氨苄青霉素中致敏性杂质的比较分析及产品致敏性评价方法的建立

溶媒结晶工艺和喷雾干燥工艺生产的氨苄青霉素中致敏性杂质的种类不同。前者主要为非聚合物类杂质,后者含有聚合物类杂质和非聚合物类杂质。豚鼠PCA试验证明两类杂质引发过敏反应的能力和与其作用的氨苄青霉素抗体的匹配程度有关。用凝胶过滤法,对54批国产和进口的氨苄青霉素样品进行了考察。结果表明,各批样品间非聚合物类杂质的含量差异很大。以聚合物类杂质含量和非聚合物类杂质含量二个指标来评价氨苄青霉素的致敏性,在广泛考察样品的基础上,用模式识别(Pattern recognition)法建立了评价商品氨苄青霉素致敏性的数学模型,可以方便地对不同样品的致敏性进行评价、比较。     

氨苄青霉素钠生产中的质量控制

喷干法生产氨苄青霉素钠具有工艺简单,生产量大等特点,但对质量控制的要求比较严格,影响质量的因素很多,抓住几项操作中的控制点,对提高氨苄青霉素钠的质量起着关键作用。1 开环开环指标直接关系到氨苄青霉素钠的药效,影响开环有以下几个因素。1.1 加碱量的控制:加碱终点的控制十分关     

氨苄青霉素聚合物的研究——Ⅰ.氨苄青霉素聚合物的分离分析

本文采用DEAE-葡聚糖凝胶A-25离子交换柱层析法从氨苄青霉素钠的水溶液中分离到它的各种聚合物,通过快原子轰击质谱和红外吸收光谱确证它们分别是氨苄青霉素的二聚、三聚、四聚和五聚物。这些聚合物在兔抗青霉噻唑蛋白(BPO_(16)-HSA)血清致敏豚鼠被动皮肤过敏反应(PCA)中皆呈阳性反应,因此它们是氨苄青霉素过敏反应的主要过敏原之一。     

分光光度法测定制剂中的羟氨苄青霉素和克拉维酸

羟氨苄青霉素常与克拉维酸配伍,该制剂用于常见的细菌感染症,包括对单用羟氨苄青霉素耐药的多种感染。英国药典法测定羟氨苄青霉素原料和胶囊,将待测样品与咪唑汞试剂反应后,在325nm处测定吸光度。其它还有碘量法,荧光分光光度法和极谱法,也有报道用高效液相色谱法的。本文报道用一阶导数分光光度法同时测定羟氨苄青霉素和克拉维酸。结果准确,重现性好。     

氨苄青霉素聚合物分析的进展

综述氨苄青霉素聚合物的聚合机理，目前常用的聚合物及氨苄青霉素的分析方法，并对其进行比较，并探讨聚合物分析的新进展。     

氨苄青霉素钠溶媒结晶工艺的研究

我厂制备注射用氨苄青霉素钠,以往一直采用在氨苄青霉素悬浮液中,滴加氢氧化钠成盐,而后喷雾干燥的工艺。这一工艺的优点是操作简便,热原、澄明度控制把握性大。缺点是成品含量低、开环物高。为了提高氨苄青霉素钠质量我们从1978年5月开始,对溶媒结晶工     

应用一些π-接受体以分光光度法测定几种青霉素

本文介绍两种简单、灵敏的测定青霉素类药物的方法。原理是青霉素作为π-电子给予体,2,3-二氯-5,6-二氰对苯醌(DDQ)或7,7,8,8-四氰对醌二甲烷(TCNQ)为π-接受体,两者相互反应定量生成深色阴离子基,用分光光度法测定。用这两种方法分别测定了苄青霉素、无水氨苄青霉素、氨苄青霉素钠、苯唑青霉素、羟氨苄青霉素和甲氧苯青霉素等6种药品的纯品和制剂型药品。DDQ和TCNQ法给出标示量的平均标准偏差分别为99.12%±1.59%～100.65%±1.72%和98.92%±1.09%～101.30%±0.85%。这两种方法比法定法简单、省时和灵敏。DDQ法还可用于当青霉素裂解产物和硫酸链霉素存在时青霉素的常规测定。     

羟氨苄青霉素钠中的聚合杂质

有多种因素可引起青霉素类与头孢菌素类的药物过敏反应,近来普遍认为聚合物杂质占十分重要的地位。用豚鼠皮肤被动致敏试验(PCA)证明,氨苄青霉素(Ampicillin)中分离出的聚合物杂质具强烈的致敏性,在浓水溶液中,氨苄青霉素易于聚合,冷冻干燥品中聚合杂质十分明显。本文报道羟氨苄青霉素(Amoxicillin)钠亦有类似情况,值得注意。     

In-use stability modeling

Experimental design and modeling of in-use stability testing are presented in this paper. In-use open container degradation is considered in terms of time open container or/and the number of instances that the same container is used. Degradation is estimated based on two models, the fixed and the general model. The fixed model estimates in-use degradation for those fixed time points of closed container where the in-used experimental data is collected. The general model estimates in-use degradation for any time point of closed container using the estimated relationship between closed container time and the degradation rate of open container. Data for in-use open container stability does not have to be collected at a closed container time of interest to estimate in-use degradation at this time point as long as this point is within the range of the experiment. Stability of the product in terms of drift from the initial time to the time of interest is calculated as the sum of closed and in-use open containers drifts.     

开放性骨折术后伤口感染113例伤口分泌物细菌培养及耐药性分析

目的:分析开放性骨折术后伤口感染患者伤口分泌物细菌培养及耐药性分析.方法:选取2018年6月至2020年7月安阳市第三人民医院开放性骨折术后伤口感染患者113例,均采集伤口分泌物标本,行细菌培养和药敏试验,分析细菌分布情况和耐药性.结果:113份分泌物标本中共分离出151株致病菌株,30份分泌物标本分离出2株及以上致病...     

盐酸头孢甲肟原料及制剂的聚合物杂质分析

目的:建立盐酸头孢甲肟原料及制剂聚合物杂质的分析方法。方法:采用高浓度溶液降解法制备盐酸头孢甲肟降解溶液;采用高效凝胶色谱法(TSK G2000 SWxl)和柱切换-LC/MSn法对盐酸头孢甲肟降解溶液的聚合物杂质进行分离和结构鉴定,并评估高效凝胶色谱法分离聚合物杂质的专属性;采用Kromasil100-5 C₁₈型色谱柱,以水-乙腈-冰醋酸为流动相进行梯度洗脱,建立盐酸头孢甲肟聚合物的RP-HPLC分析方法,采用二维色谱法和柱切换-LC/MSn法对该方法的专属性进行分析,并对实际供试品进行分析。结果:在盐酸头孢甲肟降解物中鉴定出盐酸头孢甲肟脱3位侧链二聚体及二聚体开环水解物,未发现三聚体及四聚体杂质;高效凝胶色谱法分离盐酸头孢甲肟聚合物杂质时,易受到小分子杂质的干扰,方法专属性与定量准确性差;RP-HPLC法分析盐酸头孢甲肟聚合物杂质时,能够检出盐酸头孢甲肟二聚体及其异构体,专属性良好。结论:高效凝胶色谱法不能对盐酸头孢甲肟的聚合物杂质进行有效质控,建立的反相色谱法分析盐酸头孢甲肟聚合物杂质的专属性良好,可将盐酸头孢甲肟降解溶液可作为聚合物杂质系统适用性溶液。     

采用杂质归属分区域计算法测定氨苄西林丙磺舒胶囊中的有关物质

目的建立氨苄西林丙磺舒胶囊中有关物质的分析方法。方法针对复方制剂的特点,对现行标准进行修订,改变了梯度洗脱程序,建立了HPLC梯度洗脱法,并利用杂质归属分区域计算法计算氨苄西林丙磺舒胶囊中有关物质的含量。结果增加了氨苄西林闭环二聚体的限度,按拟定标准对38批次胶囊进行检验,28批次合格,10批次不合格。结论本法分离度好,灵敏度强,适用于氨苄西林丙磺舒胶囊中有关物质的测定,可为复方制剂的质量控制与安全性评估提供数据参考。     

Small molecule allosteric modulators of phosphodiesterase 4

Phosphodiesterase 4 (PDE4) inhibitors have shown benefit in human clinical trials but dosing is limited by tolerability, particularly because of emesis. Novel cocrystal structures of PDE4 catalytic units with their regulatory domains together with bound inhibitors have revealed three different PDE4 conformers that can be exploited in the design of novel therapeutic agents. The first is an open conformer, which has been employed in the traditional approach to the design of competitive PDE4 inhibitors. The second is an asymmetric dimer in which a UCR2 regulatory helix from one monomer is placed in a closed conformation over the opposite active site in the PDE4 dimer (trans-capping). Only one active site can be closed by an inhibitor at a time with the consequence that compounds exploiting this conformer only partially inhibit PDE4 enzymatic activity while retaining potency in cellular and in vivo models. By placing an intrinsic ceiling on the magnitude of PDE4 inhibition, such compounds may better maintain spatial and temporal patterning of signaling in cAMP microdomains with consequent improved tolerability. The third is a symmetric PDE4 conformer in which helices from the C-terminal portion of the catalytic unit cap both active sites (cis-capping). We propose that dual-gating of PDE4 activity may be further fine tuned by accessory proteins that recognize open or closed conformers of PDE4 regulatory helices.     

Ampicillin polymers: identification by gel-filtration chromatography

A method for determining the polymers formed in an aqueous solution of ampicillin is described. It is based mainly on the elucidation of molecular mass that can be assigned to the fractions separated by anion-exchange chromatography. After validation by means of a modification of the imidazole reagent, 6 peaks have been obtained. These peaks corresponds to the monomeric unit and the following 5 even polymers.     

Ligand recognition mechanism of G-CSF receptor and metabotropic glutamate receptor

A three-dimensional view of ligand-receptor recognition at the atomic level is crucial to understand the molecular mechanism of receptor activation. This review describes the structure-function relationships of two receptors important for pharmaceutical science. Granulocyte colony-stimulating factor (G-CSF) is the principal growth factor regulating the maturation, proliferation, and differentiation of the precursor cells of neutrophilic granulocytes. We have determined the crystal structure of G-CSF complexed to the BN-BC domains, the principal ligand binding region of the G-CSF receptor. In a novel oligomerization scheme, the two receptor domains complex in a 2:2 ratio to the ligand, with a noncrystallographic pseudo-two-fold axis through primarily the interdomain region and secondarily the BC domain. This first structural view of a gp130-type receptor-ligand complex presents a new molecular basis for cytokine-receptor recognition. The metabotropic glutamate receptors (mGluRs) are key receptors in the modulation of excitatory synaptic transmission in the central nervous system. Three different crystal structures of the extracellular ligand-binding region (LBR) of mGluR1 have been determined, in a complex with glutamate and in two unliganded forms. They all showed disulfide-linked homo-dimers, of which the "active" and "resting" conformations are modulated through the novel dimeric interface by a packed alpha-helical structure. The bilobed protomer architectures flexibly change their domain arrangements between an "open" or "closed" conformation. Glutamate binding stabilizes both the "active" dimer and "closed" protomer in dynamic equilibrium. Four domain movements within the dimer affect the separation of the transmembrane and intracellular regions and thereby activate the receptor.     

注射用氨苄西林钠舒巴坦钠中有关物质HPLC检测方法的改进

目的建立有效的注射用氨苄西林钠舒巴坦钠有关物质检测方法。方法采用HPLC梯度洗脱法,色谱柱为Phenomenex     

Prevalence of subgingival bacteria resistant to aminopenicillins and metronidazole in dental patients from Yemen and Norway

The purpose of this study was to assess the prevalence of resistance to aminopenicillins and metronidazole among selected subgingival species in dental patients from Yemen and Norway. Three subgingival samples were collected by paper points from each of 34 Yemeni and 21 Norwegian adult volunteers and then pooled. Each of the 55 pooled samples was plated on fastidious anaerobic blood agar containing 2 microg/mL ampicillin or metronidazole, or no antimicrobial. Species identification of growth was done using DNA-DNA checkerboard hybridisation. The overall proportion of ampicillin resistance among the 18 identified species was 28.9% and 7.9% in the Yemeni and Norwegian samples, respectively, whereas for metronidazole it was 60.3% and 11.3%. The number of species resistant to ampicillin and metronidazole was significantly higher (P < 0.016 and P = 0.0000, respectively) in the Yemeni than in the Norwegian samples.