细胞色素C注射液不充氮气新工艺技术总结

<正> 细胞色素C(Cytochrome C)是一以铁卟啉为辅基的结合蛋白质,它以还原型和氧化型两种状态存在。溶于水。氧化型溶解度较还原型为大。氧化型其水溶液呈深棕红色,还原型其水溶液呈橙红色。目前我国药典规定细胞色素C注射液中的细胞色素C应为还原型,色泽为橙红色。为了得到稳定的还原型制剂,目前国内在制备其注射液时、除了添加双甘胺肽增溶、稳定外,在加入固体抗氧剂亚硫酸钠、亚硫酸氢钠的同时,还在保存、制剂时充以氮气,以减少空气中氧对细胞色素C的作用。但是充填氮气需要严格、繁杂的处理和操做、稍有不当就会使药液污染。为此,在分析了细胞色素C的理化特征和制剂特点的基础上设计了不充氮气新工艺。     

细胞色素C注射液不充氮气新工艺

还原型细胞色素C溶液在配制注射液时,容易氧化变色成为氧化型细胞色素C,为了避免这一点,配制注射液时除了加入抗氧剂亚硫酸氢钠(或亚硫酸钠),还充入惰性气体——氮气,逐出安瓿内残余氧,从而有效地保证细胞色素C注射液的稳定。但是,我们在充填氮气过程中发现,由于手工操作,充氮后不能即时熔封,火焰喷射速度强弱不等,造成安瓿内熔封后,空气残余量有多有少,这样贮存一定时间后,即发生变色不一的不     

关于细胞色素C注射液不充氮气的探讨

还原型细胞色素C溶液在配制注射剂时,容易氧化变色成为氧化型细胞色素C,为了避免这一点配制注射剂时除了加入抗氧剂,亚硫酸氧钠(亚硫酸钠),而外还充入隋性气体——氮气,逐出安瓶内残余氧,从而有效地保证细胞色素C注射液的稀定。但是,我们在充填氮气过程中发现,由于手工操作,充氮后不能即时熔封,火焰喷射速度强弱不等,造成安瓶内熔封后,空气残余量有多有少,这样贮存一定时间后,即发生变色不一的不     

注意附加剂在注射液配伍中的影响

临床医生经常把细胞色素丙注射液与维生素C注射液配伍在一起使用。104种《注射液物理化学配伍禁忌表》表示这两药配伍时无可见的配伍禁忌,但是维生素C 注射液在制备时都加入0.05%的     

细胞色素C粗品质量标准探讨

以本质量标准为依据，收购细胞色素C粗品为原料，生产的细胞色素C注射液，一次合格率可达99．5％。     

对解决细胞色素C注射液澄明度的探讨

细胞色素C注射液的澄明度不合格是常遇到的问题,我厂在开始生产的过程中因澄明度不合格使试验工作几次遇到仃顿,拖延了一年之久没有报批上去。今年四月中旬,我们又重新进行细胞色素C注射液的生产 ,经多方面摸索终于攻克了细胞色素C注射液澄明度不合格的难关。细胞色素C注射液澄明度不合格,主要是药液分装到安瓿中后,放置一段时间(约10天左右)药液中会出现一些白块和其     

细胞色素C注射液细菌内毒素检测法研究

目的: 建立细胞色素C注射液的细菌内毒素检查方法.方法: 用两个生产厂的鲎试剂对细胞色素C注射液进行干扰试验研究.结果: 细胞色素C注射液对细菌内毒素检查无干扰作用.结论: 可以用细菌内毒素检查法(凝胶法)代替家兔热原检查法控制其热原.     

陶土吸附法在细胞色素C注射液生产中的应用

在细胞色素C生产中,采用陶土吸附法,既能提高注射液的澄明度,又能除去致敏物质。生产实践表明,本工艺能很好地解决细胞色素C注射液的澄明度和致敏问题,产品各项质量指标均能达到中国药典一九九○版的标准.     

细胞色素C注射液细菌内毒素检查方法的建立

目的建立细胞色素C注射液细菌内毒素检查方法.方法按中国药典2000年版二部方法和指导原则进行实验.结果干扰实验表明供试品稀释10倍可消除干扰.结论细胞色素C注射液细菌内毒素检查法可代替家兔法热原检查.     

几种代谢促进剂简介

一、细胞色素C(Cytochrome C)细胞色素C是细胞色素体系中的一个成份。细胞色素体系是机体生物氧化中极重要的电子传递体系。它们是一类不耐热的含铁结合蛋白质,其辅基是铁卟啉的衍生物。1886年Macmunn氏首先在肌肉中发现这类物质,称为肌血素。其后1925年Keilin在     

Solution structure of iron(III)-anthracycline complexes.

The interaction of Fe(3+) with the anthracycline anticancer drug idarubicin (Ida) was studied by absorption, CD, M?ssbauer, and EPR spectroscopy. The formation of two major Fe(3+)-Ida complexes, labeled I and II, was observed. In complex I, Fe(3+) ion was bound to anthracycline at the {C(12)=O; C(11)-O(-)} coordination site. In complex II, two Fe(3+) ions were bound at sites {C(5)=O; C(6)-O(-)} and {C(12)=O; C(11)-O(-)}, respectively. Complex I was an equimolar monomeric species with a 1:1 Fe(3+):Ida stoichiometry (beta(1) = 4.8 x 10(11) M(-1)), whereas in complex II the anthracycline ligand was bridging two metal ions, alternatively bound to both anthracycline ring chelating sites with the assumption that the ratio of Fe(3+):Ida in complex II was 2:1 (beta(2) = 5.3 x 10(24) M(-2)). Alternatively, complex II may be oligomeric with Fe(3+):Ida = 1:1 and with each Fe(3+) bridging two Ida molecules. Our findings could be important in understanding the biological effects of the anthracycline-ferric complexes. Thus, providing information about the nature of the Fe(3+)-Ida system, we suggest that the formal 1:3 Fe(3+):anthracycline complexes, reported in the previous literature, could be a mixture of species I, II, and free ligand.     

吲达帕胺在释放介质中的稳定性及影响因素

目的：考察吲达帕胺在不同pH介质中的稳定性情况及影响其稳定性的主要因素。方法：采用高效液相色谱法（HPLC），考察不同温度、pH及Fe3+浓度条件下溶液稳定性情况，并考察加入不同稳定剂对于吲达帕胺降解的影响。结果：吲达帕胺在pH 1.0~3.0介质中的降解与t1/2呈线性关系，pH的降低、温度的升高及金属离子（Fe3+）的增加会加速吲达帕胺的降解。依地酸二钠或维生素C能有效减少其在酸性溶液下的降解。结论：吲达帕胺溶液在pH 1.0~3.0介质中不稳定，影响其降解的主要因素包括pH、温度和金属离子（Fe3+）；在pH 4.5、pH 6.8及水介质中稳定。依地酸二钠或维生素C是有效的稳定剂。     

A strong protective action of guttiferone-A, a naturally occurring prenylated benzophenone, against iron-induced neuronal cell damage

Guttiferone-A (GA) is a natural occurring polyisoprenylated benzophenone with several reported pharmacological actions. We have assessed the protective action of GA on iron-induced neuronal cell damage by employing the PC12 cell line and primary culture of rat cortical neurons (PCRCN). A strong protection by GA, assessed by the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carbox-anilide (XTT) assay, was revealed, with IC(50) values <1 μM. GA also inhibited Fe(3+)-ascorbate reduction, iron-induced oxidative degradation of 2-deoxiribose, and iron-induced lipid peroxidation in rat brain homogenate, as well as stimulated oxygen consumption by Fe(2+) autoxidation. Absorption spectra and cyclic voltammograms of GA-Fe(2+)/Fe(3+) complexes suggest the formation of a transient charge transfer complex between Fe(2+) and GA, accelerating Fe(2+) oxidation. The more stable Fe(3+) complex with GA would be unable to participate in Fenton-Haber Weiss-type reactions and the propagation phase of lipid peroxidation. The results show a potential of GA against neuronal diseases associated with iron-induced oxidative stress.     

Differential inhibitory mechanism of Fe2+ and Fe3+ on contraction of ileal longitudinal smooth muscle.

The mechanism of the inhibition of K(+)-induced contraction caused by ferrous (Fe(2+)) and ferric (Fe(3+)) ions were analysed in guinea-pig ileal longitudinal muscle and taenia coli. Fe(2+)increased the threshold for Ca(2+)-induced contraction in Ca(2+)-free, K(+)-depolarized taenia coli. However, Fe(3+)reduced the size of the maximal response to Ca(2+)without shifting the dose-response curves in taenia coli. Both 10 mM Fe(2+)and 2 mM Fe(3+)caused significant decreases in Ca uptake, as determined by the La method, during K(+)-induced ileal contraction. After treatment with 10 mM Fe(2+)in a state of cell membrane depolarization with K(+)for 30 min, the ileal K(+)-induced tonic contraction was completely restored by washing with medium containing EDTA, a chelator of divalent cations, and Fe(2+)remaining in muscle was almost eliminated by washing. In contrast, after treatment with 2 mM Fe(3+)in K(+)medium, K(+)-induced contraction was reversed only to a slight degree by washing with medium containing deferoxamine, a chelator of trivalent cations, and Fe(3+)in muscle largely remained despite the washing. These results suggest that Fe(2+)binds to the ileal surface membrane and reduces the contraction in response to K(+)mainly by inhibiting Ca(2+)influx. Fe(3+)may exert an inhibitory action on intracellular sites, in addition to the interference of Ca(2+)influx at the cell membrane.     

Antioxidant properties of carnosine re-evaluated with oxidizing systems involving iron and copper ions

Carnosine has antioxidant properties and is efficient in the treatment of chemically-induced inflammatory lesions in animals. However, some studies question its biological significance as antioxidant and show lack of protection and even pro-oxidant effect of carnosine in systems containing nickel and iron ions. The ability of carnosine to: (1) reduce Fe(3+) into Fe(2+) ions; (2) protect deoxyribose from oxidation by Fe(2+)-, Fe(3+)-, and Cu(2+)-H(2)O(2)-EDTA systems; (3) protect DNA from damage caused by Cu(2+)-, and Fe(2+)-H(2)O(2)-ascorbate systems; (4) inhibit HClO- and H(2)O(2)-peroxidase-induced luminol dependent chemiluminescence was tested in vitro. At concentration 10 mM carnosine reduced 16.6+/-0.5 nmoles of Fe(3+) into Fe(2+) ions during 20 min. incubation and added to plasma significantly increased its ferric reducing ability. Inhibition of deoxyribose oxidation by 10 mM carnosine reached 56+/-5, 40+/-11 and 30+/-11% for systems containing Fe(2+), Fe(3+) and Cu(2+) ions, respectively. The damage to DNA was decreased by 84+/-9 and 61+/-14% when Cu(2+)-, and Fe(2+)-H(2)O(2)-ascorbate systems were applied. Combination of 10 mM histidine with alanine or histidine alone (but not alanine) enhanced 1.3 and 2.3 times (P<0.05) the DNA damage induced by Fe(2+)-H(2)O(2)-ascorbate. These amino acids added to 10 mM carnosine decreased 3.1-fold (P<0.05) its protective effect on DNA. Carnosine at 10 and 20 mM decreased by more than 90% light emission from both chemiluminescent systems. It is concluded that carnosine has significant antioxidant activity especially in the presence of transition metal ions. However, hydrolysis of carnosine with subsequent histidine release may be responsible for some pro-oxidant effects.     

Antioxidant effect of flavonoids after ascorbate/Fe(2+)-induced oxidative stress in cultured retinal cells

In this study, we investigated the structure-activity relationship of four flavonoids, i.e. eriodictyol, luteolin, quercetin, and taxifolin, in cultured retinal cells after ascorbate/Fe(2+)-induced oxidative stress. The relative order of antioxidant efficacy, determined by the thiobarbituric acid method, was the following: eriodictyol > quercetin > luteolin > taxifolin. Upon preincubation, the flavonoids were also effective in reducing the extent of lipid peroxidation. Oxidative stress, determined by the changes in fluorescence of 2',7'-dichlorodihydrofluorescein, was also decreased in the presence of the flavonoids, showing the following order of antioxidant efficacy: eriodictyol > taxifolin approximately quercetin > luteolin. Ascorbate/Fe(2+)-induced oxidative stress or incubation in the presence of the flavonoids did not significantly affect the viability of retinal cells. We also evaluated the degree of membrane partition of the flavonoids. In this system, the results strongly suggest that the higher antioxidant activity of the flavonoids is not correlated with the presence of a double bond at C(2)-C(3) and/or a hydroxyl group at C(3) on the C ring, but rather may depend on the capacity to inhibit the production of reactive oxygen species to interact hydrophobically with membranes. Eriodictyol was shown to be the most efficient antioxidant in protecting against oxidative stress induced by ascorbate/Fe(2+) in the retinal cells.     

微生物法考察威替米星注射液的生物学稳定性

目的:对威替米星注射液的生物学稳定性进行研究。方法:将威替米星注射液置于不同条件下考察其稳定性,采用微生物法和无菌检查法对放置样品的效价稳定性及是否长菌进行检测。结果:本品经高温试验(60.0±s2.0)℃10d,光照试验(4500lx)10d,加速试验[相对湿度(75±5)%,(40.0±2.0)℃]6mo,长期试验[相对湿度(60±5)%,(25.0±2.0)℃]12mo,其效价均未有明显变化,无菌检查亦符合规定。结论:本品在各放置条件下稳定性良好。     

Iron complexing activity of mangiferin, a naturally occurring glucosylxanthone, inhibits mitochondrial lipid peroxidation induced by Fe2+-citrate

Mangiferin, a naturally occurring glucosylxanthone, has been described as having antidiabetic, antiproliferative, immunomodulatory and antioxidant activities. In this study we report for the first time the iron-complexing ability of mangiferin as a primary mechanism for protection of rat liver mitochondria against Fe(2+)-citrate induced lipid peroxidation. Thiobarbituric acid reactive substances and antimycin A-insensitive oxygen consumption were used as quantitative measures of lipid peroxidation. Mangiferin at 10 microM induced near-full protection against 50 microM Fe(2+)-citrate-induced mitochondrial swelling and loss of mitochondrial transmembrane potential (DeltaPsi). The IC(50) value for mangiferin protection against Fe(2+)-citrate-induced mitochondrial thiobarbituric acid reactive substance formation (9.02+/-1.12 microM) was around 10 times lower than that for tert-butylhydroperoxide mitochondrial induction of thiobarbituric acid reactive substance formation. The xanthone derivative also inhibited the iron citrate induction of mitochondrial antimycin A-insensitive oxygen consumption, stimulated oxygen consumption due to Fe(2+) autoxidation and prevented Fe(3+) ascorbate reduction. Absorption spectra of mangiferin-Fe(2+)/Fe(3+) complexes also suggest the formation of a transient charge transfer complex between Fe(2+) and mangiferin, accelerating Fe(2+) oxidation and the formation of a more stable Fe(3+)-mangiferin complex unable to participate in Fenton-type reaction and lipid peroxidation propagation phase. In conclusion, these results show that in vitro antioxidant activity of mangiferin is related to its iron-chelating properties and not merely due to the scavenging activity of free radicals. These results are of pharmacological relevance since mangiferin and its naturally contained extracts could be potential candidates for chelation therapy in diseases related to abnormal intracellular iron distribution or iron overload.     

五味子酚对氧自由基损伤小鼠脾淋巴细胞的保护作用

研究了五味子酚(Sal)对氧自由基损伤小鼠脾淋巴细胞的影响。体外实验结果表明,Sal在5×10^-6mol·L^-1时对Fe²⁺-VitC引起的脾淋巴细胞GSH含量降低有明显的抑制作用,且能阻抑Fe²⁺-Cys引起的MDA生成增加,改善细胞膜的流动性。用扫描电镜观察到Sal在5×10^-4mol·L^-1时可逆转Fe²⁺-VitC引起的脾淋巴细胞表面微绒毛皱折减少、细胞变形等病理改变。体内高氧分压应激损伤小鼠实验表明,igSal20mg·kg^-1×8d可逆转脾淋巴细胞SOD活性代偿性增高,并提高脾淋巴细胞内GSH含量。以上结果提示Sal对氧自由基损伤脾淋巴细胞有保护作用。     

Stability of oxaliplatin in infusion bags containing 5% dextrose injection.

PURPOSE: The stability of oxaliplatin in infusion bags containing 5% dextrose injection was studied. METHODS: Solutions of oxaliplatin 0.7 mg/mL were prepared in polyolefin infusion bags containing 5% dextrose injection and stored at 3-7 degrees C in a lightproof bag, at 20-24 degrees C with continuous exposure to artificial light, and at 20-24 degrees C with continuous exposure to fluorescent light in a lightproof bag. Samples were analyzed at 1, 2, 3, 4, 5, 7, 14, and 30 days and assayed in duplicate. Stability was measured using a stability-indicating high-performance liquid chromatographic method. Samples were also examined for changes in color and pH and for the presence of particulate matter. RESULTS: All samples retained over 90% of their initial concentration over the study period. No color changes or visible precipitation was observed, and the pH of all samples remained stable. Neither temperature nor artificial light had any significant effect on the stability of oxaliplatin. CONCLUSION: Oxaliplatin 0.7 mg/mL in infusion bags containing 5% dextrose injection was chemically stable for at least 30 days at both 3-7 degrees C and 20-24 degrees C without regard to light exposure.