粒细胞集落刺激因子雾化吸入治疗放射性口腔黏膜炎的临床观察

放射治疗是头颈部肿瘤治疗的主要方法之一,急性放射性口腔炎是头颈部肿瘤放疗中常见的并发症。急性放射性口腔黏膜炎可造成咽喉疼痛,进食困难,营养状态变差,生活质量下降,甚至导致病原体通过破损的黏膜屏障向全身扩散,给患者造成严重的危害。严重的口腔黏膜炎可造成放疗中断．进而影响肿瘤治疗的效果。因此,防治黏膜放射损伤是临床上迫切需要解决的问题。     

粒细胞集落刺激因子治疗化疗后口腔黏膜炎的临床观察

目的观察粒细胞集落刺激因子治疗化疗后口腔黏膜炎的疗效。方法93例患者随机分为两组。对照组用0.09％生理盐水漱口。治疗组在0.09％生理盐水漱口后加用含粒细胞集落刺激因子的自配液涂抹。结果对照组申21例显效。23例好转。治疗组中34例显效,10例好转。2组间差异有统计学意义。结论粒细胞集落刺激因子对化疗后口腔黏膜炎有显著疗效．可减轻化疗所致的口腔黏膜炎患者的痛苦．值得推广使用。     

重组人粒细胞刺激因子漱口治疗肺癌化疗并发口腔黏膜炎的效果

目的观察重组人粒细胞刺激因子(rh G-CSF)漱口治疗肺癌化疗并发口腔黏膜炎的效果。方法选取2018年1月-12月湖北省红安县人民医院收治的肺癌化疗并发口腔黏膜炎患者100例,按照随机数字表法分为观察组和对照组,每组50例,观察组采用重组人粒细胞刺激因子、羧甲基纤维素钠、甲硝唑加入注射用水漱口,对照组采用羧甲基纤维素钠、甲硝唑加入注射用水漱口。比较2组患者临床疗效和治疗前后临床症状积分。结果观察组患者总有效率为90. 00%高于对照组的72. 00%(χ2=10. 526,P <0. 05)。治疗后2组表皮溃烂、表皮脱落及疼痛积分均低于治疗前(P <0. 05),且观察组低于对照组(P <0. 05)。结论重组人粒细胞刺激因子漱口治疗肺癌化疗并发口腔黏膜炎效果好,值得临床推广应用。     

重组人粒细胞集落刺激因子的临床应用

本文回顾近年来相关文献,概述rhG-CSF的临床应用状况.该药可刺激骨髓细胞增加ANC、单核细胞、T淋巴细胞数量,增强ANC的吞噬作用,用于改善肿瘤、白血病患者放化疗后的ANC减少以及因粒细胞缺乏所合并的感染、骨髓移植后的造血恢复、外周血干细胞动员疗效确切.但有些肿瘤细胞能合成G-CSF,G-CSF也能促进某些肿瘤细胞的生长和转移.临床可根据个体情况选择恰当的用药时机、疗程、剂量,并进行药效监控,以达到合理用药.     

自制漱口液联合粒细胞集落刺激因子治疗放射性口腔黏膜炎

目的:观察自制漱口液漱口联合粒细胞集落刺激因子(G-CSF)喷涂治疗放射性口腔黏膜炎的疗效.方法:60例头颈部肿瘤放疗后发生口腔黏膜炎的患者随机分为治疗组和对照组各30例,治疗组使用自制漱口液漱口后,将稀释后的G-CSF喷涂于口腔溃疡创面,对照组使用复方替硝唑漱口液漱口,qid,分别于三餐后和睡前使用,两周后观察两组治疗效果.结果:治疗组总有效率90.0%,明显优于对照组的50.0%,差异有统计学意义(P<0.05).结论:自制漱口液漱口联合G-CSF喷涂治疗放射性口腔黏膜炎的效果好,且配制简单,值得推广.     

重组人粒细胞集落刺激因子致急性肾衰竭

1名54岁男性失代偿期肝硬化患者,皮下注射重组人粒细胞集落刺激因子(rhG-CSF)200μg,1次/d。用药后第2天患者出现尿色变深,第4天出现眼睑水肿,肉眼血尿、少尿等症状。BUN由4.8mmol/L升至7.9mmol/L(最高13.9mmol/L),Cr由113μmol/L升至154μmol/L(最高308μmol/L)。停用rhG-CSF,给予还原型谷胱甘肽、硫普罗宁、呋塞米等对症支持治疗。2周后肾功能恢复正常。     

国产重组人粒细胞集落刺激因子Ⅱ期临床试验

目的观察国产重组人粒细胞集落刺激因子（rhG-CSF）防治实体瘤化疗所致白细胞（WBC）和中性粒细胞（ANC）减少的临床疗效和不良反应。方法采用多中心、随机自身交叉对照方法将69例入组的肿瘤化疗患者随机分成AB组和BA组。AB组第1周期为治疗周期（A周期）,采用化疗加rhG-CSF,第2周期为对照周期（B周期）,单纯化疗。BA组第1周期单纯化疗,第2周期化疗加G-CSF。比较2周期WBC和ANC变化并观察不良反应。结果60例可供疗效分析及评价不良反应。A周期WBC下降及ANC下降持续的天数明显少于B周期（P<0.01）;A周期WBC,ANC最低值显著高于B周期（P<0.01）;化疗21d时因WBC<4.0×109     

长效化重组人粒细胞集落刺激因子的研究进展

重组人粒细胞集落刺激因子(rhG-CSF)在临床上主要用于辅助治疗癌症患者因放/化疗引起的中性粒细胞减少症,但存在体内稳定性差、半衰期短等问题,需要反复多次给药,容易使患者产生药物耐受性及免疫排斥等不良反应,因此有必要开发长效化rhG-CSF来提高其临床药效。本文综述了近年来利用聚乙二醇(PEG)修饰、融合蛋白以及新剂型等技术开发长效化rhG-CSF的研究进展,展望了其未来发展趋势。     

rhGM-CSF漱口液治疗放射性口腔黏膜炎的疗效观察

目的观察rhGM-CSF漱口液治疗放射性口腔黏膜炎的疗效。方法 40例接受放射治疗后发生放射性口腔黏膜炎的鼻咽癌患者,随机分为两组。治疗组20例,使用rhGM-CSF漱口液含漱。对照组20例,使用生理盐水漱口。两组均为10~20mL/次,4次/d,疗程均为14d。根据急性黏膜反应分级标准RTOG2.0进行疗效评价。结果治疗组有效率为85%,对照组55%,两组对比,P。结论 rhGM-CSF漱口液局部应用治疗放射性口腔黏膜炎疗效好。     

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。     

重组人粒细胞-巨噬细胞集落刺激因子治疗早期糖尿病足溃疡疗效观察

目的:观察局部皮下注射重组人粒细胞-巨噬细胞集落刺激因子(rhGM-CSF)治疗糖尿病足溃疡患者的疗效。方法:36例糖尿病足溃疡1～3级患者均用胰岛素强化控制血糖在理想范围内,溃疡面先用强力碘清洁消毒处理,再用生理盐水冲洗,清除坏死组织,第2次用生理盐水冲洗,然后随机分为2组。治疗组:直接将rhGM-CSF注射剂按5μg.kg-1.d-1沿创面周围皮下注射,每日1次;对照组:常规消毒清洁创面后,用无菌凡士林纱布覆盖溃疡面,每天换药1次,2组均治疗30d。结果:治疗组与对照组的总有效率分别为100.0%、83.3%(P<0.05);平均住院时间分别为21、32d(P<0.05)。结论:rhGM-CSF局部皮下注射较常规换药可提高糖尿病足溃疡1～3级患者的总有效率,促进糖尿病足慢性创面的愈合。     

重组人粒细胞集落刺激因子rhG—CSF的纯化工艺探讨

粒细胞集落刺激因子(granulocyte colony stimulating factor G-CSF)主要来源于巨嗜细胞,内皮细胞及纤维母细胞。能高度特异性的刺激中性白细胞系的功能活化因子。在这里我们对rhG-CSF的纯化工艺进行探讨。通常对rhG-CSF的纯化采用S-200和DE柱进行纯化,在这里我们采用另外一种方法,即采用Q柱和CM柱进行纯化。并对其比较讨论。     

重组人粒细胞集落刺激因子rhG-CSF稳定性研究

粒细胞集落刺激因子（granulocyte colony stimulating factor G-CFS)主要来源于巨嗜细胞,内皮细胞及纤维母细胞。能高度特异性的刺激中性白细胞系的功能活化因子。为了探索重组人粒细胞集落刺激因子rhG-CSF稳定性,我们在4摄氏度的条件下,不同PH值,不同添加剂的条件下,对其活性的影响。     

人粒细胞集落刺激因子包涵体的提取及其复性研究

研究人粒细胞集落刺激因子（ｒｈＧ－ＣＳＦ）包涵体的复性方法。方法：采用我室发明的包涵体提纯新方法。结果：复性回收率可达９０％以上,生物活性达天然比活的８０％以上。结论：对ｒｈＧ－ＣＳ Ｆ包涵体提纯和复性的研究,建立了ｒｈＧ－ＣＳＦ的复性新方法。     

重组人粒细胞集落刺激因子（rhG-CSF）的安全性与临床评价

目的：评价重组人粒细胞集落刺激因子在临床应用的作用机制、药代动力学、适应证、用法、用量及其禁忌证。方法：采用国内外文献综述方法。结果及结论：rhG-CSF在治疗粒细胞减少症、严重感染等方面有良好的前景,但选择适应证、个体化用药很重要。     

Sustained In Vivo Activity of Recombinant Bovine Granulocyte Colony Stimulating Factor (rbG-CSF) Using HEPES Buffer

The purpose of this study was to develop a long-acting injectable formulation of bG-CSF for veterinary use. However, in order to achieve sustained in vivo activity it was first necessary to stabilize the protein at the injection site. Preformulation studies, as well as literature, suggest that bG-CSF aggregates at neutral pH ranges (i.e., pH 6–8) and at temperatures of ～40°C. Therefore, bG-CSF will not retain its activity for an extended period of time at the injection site. During this study we determined that HEPES buffer has a very significant impact on protein stability as well as on biological performance.

Recombinant bovine granulocyte colony stimulating factor (rbG-CSF) was formulated in 1 M HEPES buffer for subcutaneous injection into cows. bG-CSF formulated in 1 M HEPES buffer resulted in sustained in vivo activity of bG-CSF compared to the “control” formulation (control formulation: 5% mannitol, 10 mM acetate buffer, 0.004% tween-80, pH 4). White blood cell (WBC) count was used as a marker to evaluate in vivo activity of the formulation. WBC numbers remained above a threshold value for only 24–30 h for the control formula. However, when bG-CSF was formulated in 1 M HEPES, the WBC remained above threshold for 3 days or 72 h. Formulating bG-CSF in 1 M HEPES at pH 7.5 also resulted in greater solution stability. This was surprising since bG-CSF is intrinsically not stable at neutral pH. The effect of 1 M HEPES on the T_M (temperature at maximum heat flow on calorimetry scan) of bG-CSF was determined by microcalorimetry. In the absence of 1 M HEPES buffer the T_M was 48°C (onset ～40°C), while bG-CSF formulated in 1 M HEPES buffer has a T_M of 59°C (onset ～50°C). Similar organic buffers, such as MOPS, HEPPS, TES, and tricine, also resulted in improved solution stability as well as in sustained in vivo activity. The dramatic effect of these buffers on stability and biological performance of bG-CSF is not well understood. One hypothesis is that the electrostatic interaction between the zwitterionic form of these buffers and bG-CSF provides stabilization against denaturation.     

Pulmonary Absorption of Recombinant Methionyl Human Granulocyte Colony Stimulating Factor (r-huG-CSF) After Intratracheal Instillation to the Hamster

Recombinant methionyl human granulocyte colony stimulating factor (G-CSF), a molecule of 18.8 kDa, has been shown to induce a systemic response after delivery by aerosol. In this work, rate and extent of absorption as well as the response were determined after bolus administration of solutions by intratracheal instillation (IT). The protein was quantified using a specific ELISA and the biological response was assessed by monitoring the increase in numbers of circulating white blood cells (WBC). A dose–response curve was obtained after IT, subcutaneous injection (SC), and intracardiac injection (IC) of 100 µL of a nominal dose ranging from 1 to 1000 µg/kg G-CSF (n = 5). WBC numbers were determined 24 hr postadministration. Absorption and clearance kinetics were determined after IT and IC of 500 µg/kg protein over a 24-hr time period (n = 5). The response of the lung to G-CSF was monitored by WBC counts and differentials in lung lavage fluid. 73.6 ± 10.5% (n = 7) of the IT dose reached the lung lobes. The response to single doses of G-CSF by IT or SC was similar, with WBC numbers increasing over 4× baseline at the higher doses. Absorption from the lung was rapid and did not follow first-order kinetics. Clearance after the IC dose was described by a biexponential equation ( = 1.41, = 0.24 hr^–1). Peak serum levels were obtained 1–2 hr after IT. The bioavailability was 45.9% of the administered dose and 62.0% of the dose reaching the lung lobes. These results indicate that G-CSF is rapidly absorbed from the lung. Pulmonary delivery via the airways has promise as an alternative to parenteral injection.