动态显色法检测注射用重组人粒细胞巨噬细胞刺激因子中内毒素的含量

目的建立定量检测注射用重组人粒细胞巨噬细胞集落刺激因子（rhGM—CSF）中内毒素的质控方法。方法采用动态显色法,通过标准曲线的可靠性验证和干扰试验,建立检测rhGM—CSF中内毒素的定量方法。结果标准曲线可靠性验证中,曲线的R2均〉0．98,标准曲线成立;干扰试验显示,供试品复溶后稀释5倍后加入0．5EU／ml的标准内毒素作为供试品回收液,经检测其内毒素回收率均接近100％,该稀释倍数下,供试品浓度对内毒素实验的干扰作用较小;另外,日常检测2批供试品的内毒素含量均小于限值,与凝胶法检测结果一致。结论该动态显色法方法可用于rhGM—CSF中内毒素的定量检测。     

重组人粒细胞巨噬细胞刺激因子致过敏性休克1例

1病例资料患者,女,62岁,左侧颈部无痛性包块2周。于2012年4月12日收住院。既往身体健康,无药物、食物过敏史。体检：T 36.2℃,P 90次/min,R 22次/min,BP 110/80 mmHg。发育正常,检查合作,神志清楚,全身皮肤及巩膜无黄染,全身浅表淋巴结无肿大,无突眼,左侧甲状腺可触及,可随吞咽上下移动。     

重组人粒细胞巨噬细胞集落刺激因子比色测定中最适波长的研究

目的：研究重组人粒细胞巨噬细胞集落刺激因子比色测定中的最适波长。方法：采用UV－2001紫外分光光度计在0－700nm波长处测定其吸收度，绘制标准曲线。结果：该法测定样品在595nm处有最大吸收度，在695处无吸收。结论：重组人粒细胞巨噬细胞集落刺激因子比色测定中的最适波长为595nm。     

重组人粒细胞-巨噬细胞集落刺激因子治疗胃溃疡

哈药集团技术中心 1 前言 重组人粒细胞-巨噬细胞集落刺激因子(英文名称:Recombinant human granulocyte-macrophage colony stimulating factor,简称rhGM-CSF)作为九十年代以来高新技术生物工程产品,具有促进骨髓粒系造血的恢复,升高外周血白细胞数的作用,现已广泛应用于白血病及肿瘤病人的大剂量放化疗,严重感染等白细胞减少性疾病的治疗.     

外用重组人粒细胞巨噬细胞刺激因子凝胶治疗浅Ⅱ度烫伤的药效学考察

目的：考察外用重组人粒细胞巨噬细胞刺激因子（rhGM-CSF）凝胶与磺胺嘧啶锌霜剂对大鼠浅Ⅱ度烫伤的药效学差异。方法：30只SD大鼠随机分为空白组、磺胺嘧啶锌霜剂组、外用rhGM-CSF凝胶组,每组10只。采用将大鼠脱毛区置于85℃恒温水浴中15 s的方法制成10%体表面积浅Ⅱ度烫伤模型,观察用药前后的心率、痛阈以及创面愈合时间、愈合率等是否具有统计学差异。结果：与磺胺嘧啶锌霜剂相比,外用rhGM-CSF凝胶对大鼠心脏影响较小;创面愈合的平均时间明显缩短,为（17±1.08）天;在烫伤用药后第20天痊愈率为100%。结论：外用rhGM-CSF凝胶对大鼠浅Ⅱ度烫伤具有较好的治疗效果。     

大肠杆菌表达重组人粒细胞—巨噬细胞集落刺激因子的中试纯化

重组人粒细胞 -巨噬细胞集落刺激因子 (rHuGM -CSF)表达产物在大肠杆菌中以包涵体的形式存在。方法　包涵体高压匀浆破菌抽提后 ,经凝胶过滤层析、复性、离子交换层析及凝胶过滤层析等纯化步骤。结果终产物纯度达 97% ,比活性达 1 2× 10 7U/mg蛋白 ,测定N端 2 0个氨基酸系列与其DNA系列推导的氨基酸系列完全一致。     

重组人粒细胞巨噬细胞刺激因子药物利用评价标准的建立与应用

目的 建立注射用重组人粒细胞巨噬细胞刺激因子(Recombinant Human Granulocyte/Macrophage Colony-stimulating Factor for Injection, rhGM-CSF)药物利用评价标准,为临床合理应用rhGM-CSF提供参考。方法 以rhGM-CSF药品说明书为基础,参考相关指南和文献,并通过与临床专家讨论建立药物利用评价标准,采用回顾性调查方法,对漳州市某医院2019年6月～2022年6月使用rhGM-CSF的住院患者病历进行评价。结果 共纳入157份病历,用药合理率为66.24%,不合理用药情况主要为给药剂量不适宜(13.38%)、给药时机不适宜(10.83%)、超说明书用药(7.01%)等方面。结论 建立的rhGM-CSF药物利用评价标准有较强的科学性、实用性和可行性,在给药剂量、给药时机等管理方面可进一步优化。     

重组人粒细胞刺激因子的纯化方法

目的:建立G-CsF的纯化方法.方法:对包涵体进行有效洗涤,采用疏水层析进行纯化.结果:包涵体纯度大于70%,产品反向纯度大于95%,电泳纯度大T98%.结论:所建立的G-CSF的纯化方法简便可行,适用于工业化生产.     

重组人粒细胞巨噬细胞集落刺激因子凝胶剂治疗溃疡药效学研究

目的观察重组人粒细胞巨噬细胞集落刺激因子(gm-csf)凝胶剂治疗溃疡的药效。方法在豚鼠背部造溃疡模型,将凝胶剂外涂于豚鼠背部的溃疡处,不同时间内考察gm-csf凝胶剂对溃疡的药效。结果gm-csf凝胶剂组及gm-csf原液组同盐水组、基质组比较,溃疡面积明显缩小,有显著差异。结论gm-csf凝胶剂对溃疡有明显的治疗作用。     

Absorption of Recombinant Human Granulocyte Colony-Stimulating Factor (rhG-CSF) from Rat Nasal Mucosa

Nasal absorption of recombinant human granulocyte colony-stimulating factor (rhG-CSF) was examined in the rat. The relative bioavailability of rhG-CSF for subcutaneous administration was 2%, as evaluated from the immunologically active rhG-CSF concentration in rat plasma and the area under the curve (AUC) of the plasma rhG-CSF concentration versus time for 8 hr. Pharmacological availability relative to subcutaneous administration was determined from the increase in total blood leukocyte numbers. The pharmacological availability was 5–10%, determined from the AUC for the increased ratio of total leukocyte numbers versus time for 48 hr; it was slightly dependent on the pH and the osmotic pressure of the dosing solution. Accordingly, the plasma concentration of rhG-CSF did not always reflect its pharmacological effects. Relative bioavailability and pharmacological availability were increased about 23 times and 3 times, respectively, by polyoxyethylene 9-lauryl ether (Laureth-9), but no increase in availability occurred with sodium glycocholate. The increase in total leukocyte numbers was maintained during multiple rhG-CSF dosing, and the addition of Laureth-9 further increased the pharmacological effects of this agent. This study indicates that nasal administration of rhG-CSF is an effective parenteral administration route.     

Renal Clearance of a Recombinant Granulocyte Colony-Stimulating Factor,Nartograstim, in Rats

Purpose. To clarify the role of the kidney in the elimination of a recombinant human granulocyte colony-stimulating factor, nartograstim, we have investigated its pharmacokinetics in rats with renal failure. Methods. The steady-state clearance (CL_ss) were determined by the intravenous infusion for 4 hr to unilateral renally-ligated and cisplatin-treated rats, whose renal functions were about 50 and 10 % of controls, respectively. Results. CL_ss of nartograstim (27 ml/hr/kg) in the renally-ligated rats at a high infusion rate was significantly lower (25%) than in control rats (p<0.05). CL_ss in these rats, at a low infusion rate was 95 ml/hr/kg, 14 % lower than in control rats. The saturable CL_ss in these rats, 68 ml/hr/kg, was not significantly different from control rats (75 ml/hr/kg, p>0.05). Also, CL_ss in cisplatin-treated rats with extensive renal failure, at a high infusion rate, decreased to 57 % of controls. Furthermore, the total body clearances (CL_tot) of nartograstim after bolus intravenous administration to renally-ligated and cisplatin-treated rats were reduced to 33–49 % of controls. Conclusions. These results suggest that the kidney may be responsible for 40– 50 % of the nonsaturable clearance of nartograstim. Thus, the kidney should make a major contribution to the elimination of nartograstim when rats are given a high dose of nartograstim, which saturates the receptor-mediated clearance.     

注射用盐酸柔红霉素中细菌内毒素的动态显色基质法定量测定

建立了动态显色基质法定量测定注射用盐酸柔红霉素中细菌内毒素含量。对样品添加定量的标准内毒素进行干扰预试验,当柔红霉素浓度为25μg/ml时可排除干扰,6批样品细菌内毒素的含量均小于4.3EU/mg。     

Exposure-Based Safety Evaluation of Recombinant Human Macrophage Colony-Stimulating Factor (M-CSF) in Cynomolgus Monkeys

The safety of M-CSF was assessed in cynomolgus monkeys in anintravenous dosing regimen. Exposure (AUC_0–24) multiples(monkey vs human) were calculated using the no observable adverseeffect level (NOAEL) observed in this study and correlated withknown M-CSF-induced toxicities in a previous continuous intravenousinfusion (civ) study in monkeys. M-CSF was administered by dailyintravenous infusion (2 h) to cynomolgus monkeys (2/sex/ group)at 0.1, 0.3,0.7, and 1.0 mg/kg/day, for 28 consecutive days.Control animals (2/sex) received placebo. The 0.7 mg/kg/daygroup was held for an additional 4-week recovery period. Criteriaevaluated included physical observations, ophthalmoscopy, elec-trocardiography,body weight, food consumption, clinical pathology, antibodyformation, pharmacokinetics, necropsy, organ weights, and histopathology.The only effect previously seen in monkeys after intravenouslyadministered M-CSF occurred in animals in the 0.7 and 1.0 mg/kg/daygroups. They exhibited a slight decrease in platelets betweendays 4 and 12 with subsequent recovery. No effects related toM-CSF administration were evident in macroscopic or microscopicevaluations and there was no evidence of anti-M-CSF antibodyproduction. M-CSF at all dose levels was completely eliminatedwithin each dosing interval with no accumulation. Clearanceof M-CSF was enhanced during the first week of dosing, but returnedto baseline clearance levels by day 27. This dosing regimenwas shown to be remarkably free of toxicities noted in a previousmonkey study where M-CSF was given by civ at similar daily doses.At the high dose, which was considered to be the NOAEL, theAUC_0–24 was 40-fold greater than the AUC_0–24 inclinical trials where 2.0 mg/m² was administered by a daily2-h infusion.     

重组人粒细胞刺激因子用于乳腺癌化疗后辅助治疗专项点评

目的 了解乳腺癌化疗后辅助治疗药物重组人粒细胞刺激因子的使用情况,促进肿瘤化疗患者合理使用此类药物。方法 汇总2016年厦门市妇幼保健院全部乳腺癌化疗病历,抽取150份,建立点评依据,对重组人粒细胞刺激因子用药的适应证、给药时机、用法用量等进行点评。结果 厦门市妇幼保健院重组人粒细胞刺激因子用于乳腺癌化疗后辅助治疗,在预防使用方面主要为给药时机不合理,占总抽查病历的20.22%;而治疗使用方面主要体现为适应证不合理,占总抽查病历的26.23%。结论 临床药师应加强此类药物的监控与评价,寻求、创造更好的循证医学证据,促进临床合理用药。     

重组人粒细胞集落刺激因子注射液的稳定性研究

采用毛细管电泳、反相HPLC、凝胶排阻HPLC、SDS-PAGE非还原电泳、pH值、生物学活性等检测方法对重组人粒细胞集落刺激因子注射液的稳定性进行系统研究,在加速试验、室温留样、贮藏温度留样条件下检测了稳定性。结果样品于2～10°C保存下,外观、pH值、含量、纯度及生物学活性均相当稳定,有效期可暂定为两年。     

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灵活应用1例

化疗是治疗恶性肿瘤的主要手段之一。近年来,新的抗肿瘤药物不断问世,抗肿瘤疗效不断提高[1],在一定范围内,化疗效果常与给药剂量呈正相关,增加化疗药物的剂量经常是提高治疗效果的一个重要因素。但是,随着给药剂量的增加和给药时间的延长,不可避免地会造成骨髓抑制。     

重组人粒细胞集落刺激因子在恶性肿瘤化疗后应用的疗效观察

目的:研究国产重组人粒细胞集落刺激因子(rhG-CSF)在恶性肿瘤化疗后所致白细胞(WBC)和中性粒细胞绝对值(ANC)减少的临床效果及不良反应(ADR)。方法:采用自身交叉方法将62例恶性肿瘤病人随机分为AB和BA2组。AB组A周期为治疗周期,即化疗结束48h开始,用国产rhG-CSF治疗,B周期单用化疗,为对照周期;BA组正好相反。隔日查血常规1次,观察WBC和ANC的变化。结果:国产rhG-CSF可以减轻化疗所致的WBC和ANC下降程度,促进化疗患者WBC和ANC的恢复,缩短WBC和ANC减少的持续时间,有助于化疗按期进行。主要ADR有注射部位疼痛、皮疹、发热、肌肉疼痛、乏力。结论:在恶性肿瘤化疗中应用国产rhG-CSF,能有效减轻WBC和ANC降低,缩短WBC和ANC恢复时间,确保化疗顺利进行。     

重组人粒细胞集落刺激因子肽谱分析方法初探

建立检测重组人粒细胞集落刺激因子肽谱的方法。方法：采用ＲＰ－ＨＰＬＣ法及ＣＺＥ法。结果：检测ｒｈＧ－ＣＳＦ经胰蛋白酶解后的肽段,发现九源公司生产的各批产品的一级结构具有一致性。结论本法适用于基因工程药物的肽谱分析。