rhG-CSF对大鼠局灶性脑缺血保护作用研究

目的 观察重组人粒细胞集落刺激刺激因子对大鼠局灶性脑缺血保护作用.方法 采用光化学法制作大鼠局灶性脑缺血模型,测定脑组织超氧化物歧化酶活性及丙二醛含量,测量脑梗死体积.结果 脑缺血后SOD活性降低,rhG-CSF能提高SOD活性,随rhG-CSF浓度增高,SOD活性有增高趋势.脑缺血后MDA含量升高,rhG-CSF能降低MDA含量,随rhG-CSF浓度增高,MDA含量有降低趋势.脑缺血后形成局灶脑梗死,rhG-CSF能降低脑缺血后形成局灶脑梗死范围,随rhG-CSF浓度越高,局灶脑梗死范围有缩小趋势.结论 重组人粒细胞集落刺激刺激因子对大鼠局灶性脑缺血后神经元有保护作用.     

酶联免疫吸附试验法研究PEG-rhG-CSF与rHSA-hG-CSF在小鼠体内的药代动力学

研究重组人粒细胞集落刺激因子(rhG-CSF)、聚乙二醇修饰的重组人粒细胞集落刺激因子(PEG-rhG-CSF)与重组人血清白蛋白-粒细胞集落刺激因子融合蛋白(rHSA-hG-CSF)在小鼠体内的药代动力学，验证两种方法对rhG-CSF半衰期(T_1/2)的影响。小鼠分别皮下给药rhG-CSF，PEG-rhG-CSF与rHSA-hG-CSF后，在不同时间点采血并分离血清，采用双抗体夹心酶联免疫吸附试验法测定血清中rhG-CSF的浓度，用3P87药动学软件进行曲线拟合并计算参数。结果显示，rhG-CSF，PEG-rhG-CSF与rHSA-hG-CSF的半衰期(T_1/2)分别为2.1，14.2和10.6 h，后两者半衰期分别为rhG-CSF的7倍、5倍；PEG-rhG-CSF和rHSA-hG-CSF的达峰时间T_peak分别为rhG-CSF的15倍、13倍。通过ELISA法检测比较rhG-CSF，PEG-rhG-CSF与rHSA-hG-CSF在小鼠体内的药代动力学，表明PEG修饰与白蛋白融合技术可以延长rhG-CSF的半衰期。     

预防性应用rhG-CSF的随机对照研究

重组人粒细胞集落刺激因子(rhG-CSF)由于能促进中性粒细胞前驱细胞的分化增殖,并促使骨髓中成熟的中性粒细胞释放到外周血循环中,因而对于化疗引起的WBC减少有特效治疗作用。我们于2000年10月至2001年12月对接受化疗的肿瘤患者采用随机自身交叉对照的方法,探讨预防性应用和随症应用rhG-CSF有无差异。     

rhG-CSF对大鼠局灶性脑缺血认知功能的保护作用

目的 观察重组人粒细胞集落刺激刺激因子(rhG-CSF)对大鼠局灶性脑缺血后空间记忆的脑保护作用.方法 采用光化学法制作大鼠局灶性脑缺血模型,用Morris水迷宫检测大鼠空间记忆能力.结果 大鼠局灶性脑缺血后大鼠空间记忆能力降低,rhG-CSF能提高大鼠局灶性脑缺血后大鼠空间记忆能力,rhG-CSF对大鼠局灶性脑缺血后神经元有保护作用.结论 大鼠局灶性脑缺血损害大鼠空间记忆能力,rhG-CSF对大鼠局灶性脑缺血后空间记忆能力有保护作用.     

人重组粒细胞集落刺激因子对大鼠缺血性脑梗死预后的影响

目的：探讨人重组粒细胞集落刺激因子（rhG-CSF）对大鼠缺血性脑梗死预后的影响。方法：采用线栓法制作大鼠缺血性脑梗死模型,比较给药组与对照组在神经功能评分（Nss评分）和Morris水迷宫方面的不同预后。结果：大鼠缺血性脑梗死使大鼠的神经功能和空间记忆能力降低,注射rhG-CSF的大鼠有助于恢复神经功能,提高空间记忆能力。结论：rhG-CSF对于大鼠缺血性脑梗死的预后具有积极作用。     

基于加权TOPSIS法的肿瘤患者应用重组人粒细胞集落刺激因子合理性评价

目的建立肿瘤患者应用重组人粒细胞集落刺激因子(rhG-CSF)评价标准,评估rhG-CSF临床使用的合理性。方法以rhG-CSF药品说明书、中国临床肿瘤学会(CSCO)、美国国立综合癌症网络(NCCN)等发布的相关药物指南或专家共识为依据,制定肿瘤患者应用rhG-CSF评价标准,对2018年蚌埠市第三人民医院50例肿瘤患者使用rhG-CSF的归档病历采用加权TOPSIS法进行分析评价。结果rhG-CSF的不合理应用主要集中在给药途径未首选皮下注射、给药剂量不准确和用药疗程不足等。50例病例中相对接近度(Ci)≥80%的有3例(6%), 60%≤Ci<80%的有33例(66%), 40%≤Ci<60%的有14例(28%)。结论基于加权TOPSIS法的rhG-CSF合理性评价发现,该院肿瘤患者应用rhG-CSF基本合理,但仍存在给药途径、给药剂量和用药疗程不合理等方面问题。     

粒细胞集落刺因子在白血病化疗中的临床应用探讨

急性白血病治疗的关键在于早期实施连续强烈化疗,达到完全缓解后实施巩固治疗,是提高白血病长期无病生存率的重要环节。然而急性白血病在争取完全缓解的化疗过程中,往往必需经过一个骨髓抑制阶段,此阶段易感染、出血,是致死原因。在急性白血病化疗过程中如何缩短骨髓抑制期是一个主要问题。重组人粒细胞集落刺激因子(rhG-CSF)对造血有促进作用,我们观察rHG-CSF疗效,现报告如下。1　资料和方法1.1　病例选择:rhG-CSF组与对照组的一般临床资料见附表。两组在年龄、性别、诊断、化疗方案大致相同,对照组采用以前病例,未用rhG-CSF.附表　…     

2例重组人粒细胞集落刺激因子过敏的护理

<正>重组人粒细胞集落刺激因子注射液(rhG-CSF)为利用基因重组技术生产的人粒细胞集落刺激因子,对恶性肿瘤化疗后的中性粒细胞减少症具有明显预防和治疗作用,已广泛应用于临床。rhG-CSF的不良反应主要为骨痛、肌肉酸痛、     

重组人粒细胞集落刺激因子对化疗后中性粒细胞缺乏的有效性和安全性研究

目的：评价重组人粒细胞集落刺激因子（rhG-CSF）对化疗所致中性粒细胞缺乏的恶性血液病患者的临床疗效和安全性。方法：对2012年1~12月我院73例化疗后出现中性粒细胞缺乏的恶性血液病患者进行调查分析,均在粒缺发生后使用rhG-CSF,用SPSS统计软件对信息进行分析。结果：rhG-CSF可以有效缓解化疗后的中性粒细胞缺乏,使白细胞和中性粒细胞数目明显升高,平均恢复时间为（7.77±5.14） d,总有效率为95.9%,研究中根据病人中性粒细胞缺乏发生程度、阶段及持续时间进行个体化给药。结论：rhG-CSF对化疗所致的中性粒细胞缺乏症安全有效。     

重组人粒细胞刺激因子在《中国药典》、《美国药典》和《欧洲药典》中的质量标准对比分析

目的对比重组人粒细胞刺激因子(rhG-CSF,Filgrastim)在《中国药典》(2010年版)、《美国药典》33版初稿和《欧洲药典》(7.0版)中标准的差异,为国内研发机构在rhG-CSF质量标准的提高研究提供参考。方法按三部药典要求,对rhG-CSF产品进行主要关键指标的检测分析。结果《中国药典》在对该产品的标准描述上不如《欧洲药典》(7.0版)和《美国药典》33版初稿,而《美国药典》33版初稿的rhG-CSF标准要求最高。三部药典存在具体内容的区别。结论提高rhG-CSF现行产品质量标准可参照《美国药典》33版初稿。     

考察尿素含量对重组人粒细胞刺激因子质量的影响

目的考察尿素含量对重组人粒细胞刺激因子(rhG-CSF)质量的影响。方法将含量分别为98%,99.5%的尿素用于rhG-CSF的变复性工艺,并对制成的原液、半成品和成品,按照2005年版《中国药典》分别进行各项质量检测。结果用含量为98%和99.5%的尿素原材料所生产的3批产品的原液和成品,均符合2005年版《中国药典》rhG-CSF注射液的各项要求。结论尿素原材料中尿素含量只要达到≥98.0%的标准就可用于生产,不仅工艺稳定,而且还能降低成本。     

rhG-CSF对小鼠化疗后外周血白细胞减少的治疗作用

目的研究小鼠PC方案化疗后不同时机运用重组人粒细胞集落刺激因子（rhG-CSF）对外周血白细胞减少的治疗作用。方法将小鼠随机分为早期治疗（A）、晚期治疗（B）、预防用药（C）、阴性对照（D）四组,然后按PC方案给予小鼠腹腔注射。继以在外周血中白细胞（WBC）低于正常低值（A组）、外周血WBC降至正常低值一半（B组）及化疗后48h外周血WBC仍在正常范围时（C组）分别连续给予皮下注射rhG-CSF,对照组（D组）给予生理盐水皮下注射代替。观察各组外周血白细胞计数变化。结果①化疗后预防组外周血白细胞值未降至正常范围以下,A组较B组低于正常值的持续时间短、rhG-CSF连续用药后至正常水平恢复时间快。②与治疗组相比,预防用药组化疗后外周血WBC下降的最低值和用rhG-CSF后上升的最高值均高于治疗组,A组又较B组疗效好。③rhG-CSF用药前后相应时间点预防组的WBC值高于治疗组,其中A组高于B组。结论化疗后应用rhG-CSF可有效升高小鼠外周血白细胞数,预防用药较治疗用药、早期用药较晚期用药更能够恢复小鼠化疗后造血功能。     

Pharmacokinetic/pharmacodynamic analysis of neutrophil proliferation induced by rhG-CSF in patients receiving antineoplastic drugs

In the present study, we analyzed the effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on neutrophil counts in cancer patients undergoing chemotherapy using a previously developed pharmacokinetic/pharmacodynamic model.(7)) The time profiles of neutrophil counts in blood after repeated administration of rhG-CSF to lung cancer patients undergoing chemotherapy could be analyzed by this model by considering the inhibition of neutrophil production by antineoplastic drugs. Although deviation was observed between the predicted and observed neutrophil counts in ovarian cancer patients, it may be possible to use this model for determining a rational dosage regimen of rhG-CSF for patients undergoing chemotherapy.     

重组人粒细胞集落刺激因子热稳定性研究

采用凝胶排阻HPLC、SDS-PAGE非还原电泳、生物学活性、蛋白含量等检测方法对两种保护缓冲体系中的重组人粒细胞集落刺激因子(rhG-CSF)稳定性进行研究。在40℃(加速试验)、25℃(室温留样)、2～8℃(贮藏温度)、冻溶一次条件下检测了两种保护缓冲体系中rhG-CSF稳定性。结果rhG-CSF原液于2～8℃保存下,外观、含量、纯度及生物学活性较为稳定,有效期可暂定为三个月,40℃、25℃存放产品不稳定;rhG-CSF保存原液于2～8℃保存下,外观、含量、纯度及生物学活性相当稳定,有效期可暂定为十八个月,40℃存放产品不稳定。RhG-CSF原液及rhG-CSF保存原液均不可冻融。保存原液中的甘露醇(5%)、吐温-80(0.004%)对rhG-CSF具有显著的保护作用。     

The influence of recombinant human granulocyte colony-stimulating factor on granulopoiesis in mice recovering from cyclophosphamide treatment

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was evaluated for its effects on granulopoiesis recovery in mice pretreated with cyclophosphamide. The cytotoxic agent was administered on days 0 and 7. rhG-CSF therapy (injected from days 8 to 28) accelerated the recovery and maintained an increased level of peripheral blood neutrophils. Marrow granuloid precursors depression, due the second dose of cyclophosphamide, was prevented by rhG-CSF, but this hemopoietic growth factor was unable to increase these cells in a similar way to that observed in normal mice. This suggests a decreased granuloid marrow proliferation capacity in cyclophosphamide treated mice. In contrast, in the spleen, rhG-CSF highly increased granuloid precursors. However, the contribution of spleen to granuloid recovery was scarce. Mice receiving rhG-CSF after cyclophosphamide demonstrated a biphasic recovery pattern in bone marrow GM-CFU population. A first rebound of GM-CFUs was followed by a nadir and then a second recovery where GM-CFU progenitor cells were significantly increased was observed. On the other hand, rhG-CSF therapy highly increased the spleen GM-CFU numbers at days 24 to 28. Although rhG-CSF increased splenic granulopoiesis, this result shows that the bulk of granulopoiesis recovery due to rhG-CSF therapy in cyclophosphamide pretreated mice occurred in the marrow.     

G-CSF loaded biodegradable PLGA nanoparticles prepared by a single oil-in-water emulsion method

A new formulation method was developed for preparing poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles loaded with recombinant human granulocyte colony-stimulating factor (rhG-CSF). Lyophilized rhG-CSF powder and PLGA polymer were directly co-dissolved in a single organic phase, and the resulting solution was dispersed into an aqueous solution. PLGA nanoparticles encapsulating rhG-CSF were produced by a spontaneous emulsion/solvent diffusion method. In this manner, rhG-CSF was molecularly dissolved in the polymer phase. Release profile of rhG-CSF from PLGA nanoparticles was compared with those from two kinds of PLGA microparticles which were separately prepared by either single oil-in-water (O/W) or double water-in-oil-in-water (W/O/W) emulsion technique. The sizes of rhG-CSF loaded nanoparticles, O/W microparticles, and W/O/W microparticles were about 257 nm, 4.7 microm, and 4.3 microm, respectively. For rhG-CSF nanoparticles, about 90% of encapsulated rhG-CSF was released out in a sustained manner from PLGA nanoparticles over a 1 week period, but for rhG-CSF microparticles, only about 20% of rhG-CSF could be released out during the same period. Reversed phase and size exclusion chromatograms revealed that the structural integrity of released rhG-CSF from nanoparticles was nearly intact, compared to that of native rhG-CSF.     

重组人粒细胞刺激因子在《中国药典》和《欧洲药典》中质量标准不同点的对比分析

目的对比重组人粒细胞刺激因子(rhG-CSF,Filgrastim)在《中国药典》(2005年版)和《欧洲药典》(6.3版)中标准的不同点,为国内研发机构对基因重组蛋白产品的研发及国内企业对该产品的进出口提供参考。方法按两部药典要求,对国产产品实样进行部分关键指标的检测分析。结果两部药典对该产品的标准描述上存在具体内容的区别。结论:在现代药物的研发和生产中,对药品的国际及国内标准要进行综合分析而拟定。     

重组人粒细胞集落刺激因子的高效液相色谱分析

目的：测定重组人粒细胞集落刺激因子（ｒｈＧ－ＣＳＦ）的蛋白浓度、分子量及纯度。方法：反相高效液相色谱（ＲＰ－ＨＰＬＣ）法及高效体积排阻色谱法（ＳＥＣ）。结果：蛋白浓度测定方法可靠,平均回收率为１００．１７％,ＲＳＤ＝０．８％,重现性好,日内ＲＳＤ＝０．７％,日间ＲＳＤ＝１．１％,且与福林－酚法（Ｌｏｗｒｙ法）测得结果无显著差异。样品无需处理,可直接上样,同时可得到样品的纯度数据。ＳＥＣ法测得分子量     

Bioavailability of granulocyte colony-stimulating factor administered enterally to suckling mice

The developing fetal and neonatal gastrointestinal (GI) tract is influenced by many growth factors, including epidermal growth factor (EGF), insulin-like growth factor (IGF), transforming growth factor (TGF), and erythropoietin (Epo). Granulocyte colony-stimulating factor (G-CSF), typically regarded as a hematopoietic growth factor, might also be included because it exists in high concentrations in amniotic fluid, colostrum, and human milk, and because granulocyte CSF receptors (G-CSF-R) are abundantly expressed on the villous enterocytes of the developing intestine. As a first step toward understanding whether the effects of G-CSF on the GI tract were local or systemic, we sought to determine whether recombinant human G-CSF (rhG-CSF) administered enterally to suckling mice, is absorbed into the circulation, and if so, whether the G-CSF-R is essential for this absorption. We enterally administered rhG-CSF to suckling mice, selecting a daily dose based on the amount of G-CSF normally swallowed by the fetus and neonate (3 ng), or in other mice, a dose of G-CSF 100 times larger (300 ng). Pups were tested at either 5-7 days of age, or at 14-16 days of age. C57BL/6 x 129SvJ mice were used. Some mice had a targeted null mutation in the G-CSF-R gene, producing a non-functional G-CSF-R protein. At intervals following the enteral G-CSF dosing, G-CSF concentrations in plasma were measured by specific ELISA. The bioavailability of G-CSF was invariably <1%, regardless of the dose of rhG-CSF given, the age of the pups, or whether they had a functional G-CSF-R. After enteral administration of rhG-CSF to suckling mice, only minimal quantities of G-CSF are absorbed into the circulation, and the G-CSF-R is not essential for this absorption.