rhGH和IFN-γ对肝硬化大鼠肝组织中蛋白合成代谢的影响

目的 了解重组生长激素(rhGH)及γ-干扰素(IFN-γ)对肝硬化蛋白合成代谢的影响.方法 采用Proctor改良法,建立CCl4致大鼠肝硬化模型,合格模型随机分为空白对照组(NS,1 mL·d-1,sc)、阳性对照组(马洛替酯100 mg· kg-1·d-1,ig)、rhGH组(rhGH 0.8 IU· kg-1·...     

ELISA法研究聚乙二醇重组人生长激素注射液单次给药人体药代动力学

目的 建立ELISA方法研究聚乙二醇重组人生长激素(PEG-rhGH)注射液单次给药人体药代动力学.方法 将30名健康受试者随机分成4组(其中两组为自身对照),分别单次皮下注射PEG-rhGH注射液(0.1 mg·kg-1、0.2 mg·kg-1、0.4 mg·kg-1)、注射用重组人生长激素(rhGH)(0.067mg· kg-1).ELISA法测定不同时间点PEG-rhGH、rhGH的血药浓度,并计算药代动力学参数.结果 PEG-rhGH、rhGH血药浓度分别在0.312 5～40.0000 ng·ml-1、0.312 5～10.0000 ng· ml-1范围内线性关系良好,最低检测性均为0.312 5ng· ml-1,批间、批内RSD均＜15％. PEG-rhGH(0.1、0.2、0.4 mg·kg-1)、rhGH(0.067mg· kg-1)的t1/2分别为:(31.70±4.70)h、(32.19±4.58)h、(30.39±5.93)h、(1.95±0.44)h,Tmax为:(22.20±9.82)h、(29.40±10.75)h、(40.80±8.39)h、(3.20±1.10)h,Cmax:(105.24±45.37)ng·ml-1、(379.09±109.61)ng·m1-1、(920.69±293.21)ng·ml-1、(30.17±3.20)ng·m1-1,CL/F:(26.97±13.86) ml· kg-1· h-1、(9.21±4.05) ml· kg-1· h-1、(6.29±2.87) ml· kg-1· h-1、(284.26±43.47)ml· kg-1· h-1,AUC0→∞:(4657.70±2337.30) ng· m1-1·h、(25279.58±9407.63) ng· ml-1·h、(74438.89±29 007.81) ng·ml-1·h、(240.97±39.40) ng·ml-1·h.结论 PEG-rhGH体内过程符合线性动力学特征,与rhGH相比,明显推迟达峰时间、延长半衰期、减慢清除率,具有长效特征.     

重组人生长激素对大鼠肠道屏障功能的影响

目的 探讨重组人生长激素(rhGH)对大鼠肠道屏障功能的影响.方法 45只SD大鼠随机均分为3组:A组不予处理;B组肌注生理盐水;C组用肌注rhGH 1.25 U· kg-1·d-1治疗.1周后测量各组大鼠小肠绒毛高度、肠腺隐窝深度、黏膜厚度以及绒毛表面积和小肠黏膜CD3+、CD4+、CD8+和IgA+细胞数.结果 C组的小肠绒毛高度、肠腺隐窝深度、黏膜厚度以及绒毛表面积等形态学相关参数明显好于A组和B组(P＜0.05);C组小肠黏膜CD3+、CD4+、CD8+和IgA+细胞数高于A组和B组(P＜0.05);A组与B组上述指标的差异无统计学意义.结论 rhGH可以增强小肠黏膜屏障功能及免疫屏障功能.     

聚乙二醇化人重组生长激素对去垂体幼鼠脏器功能的影响

目的 探讨聚乙二醇化重组人生长激素(PEG-rh GH)对去垂体幼鼠主要脏器的影响。方法 SD雄性幼鼠随机取88只进行去垂体手术造模,另18只假手术组为对照组。术后2周,选成模幼鼠54只,分为模型组、重组人生长激素(rh GH)组、PEG-rh GH组。每晚sc生理盐水0.25 mg/kg,并且rh GH组每晚sc注射用重组人生长激素0.25 mg/kg,PEG-rh GH组每周第1天晚上sc注射用重组人生长激素1.40 mg/kg。治疗4周后,检测肝功能ALT、AST、TBIL、DBIL水平,肾功能BUN、CREA水平,心肌酶谱CK、CKMB及肝脏、心脏、肾脏的病理组织和肝脏的转录生长因子β1(TGF-β1)和肾脏C-fos蛋白表达。结果 肝功能中AST、TBIL水平下降;肾功能中CREA水平升高;肝脏、肾脏、心脏病理未见明显异常;肝脏TGF-β1、肾脏C-fos蛋白表达组间无差异。结论 PEG-rh GH对肝脏、肾脏、心脏的组织形态和功能无明显不良影响。     

重组人生长激素治疗严重烧伤患者的研究

目的观察重组人生长激素(rhGH)对重度烧伤后细胞因子水平的影响。方法40例重度烧伤患者,随机分为0.3I U.kg-1.d-1(A组)、0.6I U.kg-1.d-1(B组)及等渗盐水对照组(C组)。于伤后3d开始用药,疗程20d。观察不同时点血清肿瘤坏死因子(TNF-α)、白细胞介素6(IL-6)和白细胞介素8(IL-8)及内毒素水平的变化。结果与对照组相比,rhGH各组TNF-α、IL-6水平下降,B组降低时间出现较早、降幅较大(P<0.01)。同时,患者血清内毒素水平相应下降,呈显著正相关(r=0.9723,P<0.01)。三组之间IL-8水平无明显变化(P>0.05)。结论rhGH能降低重度烧伤患者机体炎症介质的水平,对减轻严重烧伤后全身炎性反应综合征(SIRS)或多器官功能障碍综合征(MODS),提高治愈率有一定帮助。     

重组人生长激素在儿童特重度烧伤中的应用价值探讨

目的 探讨重组人生长激素(rhGH)对特重度烧伤儿童蛋白质、血糖代谢及创面愈合的影响.方法 将40例特重度烧伤儿童随机分为rhGH组和对照组,每组各20例.rhGH组伤后5d开始皮下注射rhGH(0.15～0.2IU·kg-1·d-1),疗程14d,比较两组血浆白蛋白、血红蛋白、血糖浓度及愈合后瘢痕的情况.结果 rhGH组血浆白蛋白、血红蛋白浓度明显升高(P<0.01)、创面愈合时间明显缩短(P<0.01).结论 应用小剂量rhGH治疗儿童特重度烧伤能促进机体蛋白质的合成、缩短创面愈合时间、减少瘢痕的增生,对血糖无影响.     

重组人生长激素治疗青春期前特发性矮小儿童

目的:观察重组人生长激素(rhGH)治疗青春期前特发性矮小的疗效。方法:24例特发性矮小病儿分为2组,治疗组女孩10例,男孩2例,起始治疗年龄为(10.1±s1.9)a,予rhGH0.10～0.13U·kg-1·d-1,治疗时间(0.8±0.3)a。对照组女孩10例,男孩2例,起始观察年龄(9.9±1.7)a,未予rhGH治疗,观察时间(1.1±0.5)a。结果:治疗组治疗后生长的速率为(8.7±1.9)cm·a-1,对照组为(5.0±0.7)cm·a-1,2组差异有非常显著意义(P<0.01)。治疗组对骨龄的身高标准差值(HtSDSBA)增加0.4±0.4,预测成人身高(PHt)增加了(3.1±0.9)cm;对照组HtSDSBA减少0.3±0.5,PHt降低(0.9±1.7)cm,2组比较差异均有非常显著意义(P<0.01)。结论:rhGH对青春期前特发性矮小儿童的生长有促进作用,能改善其PHt。     

重组人生长激素在烧伤病人中疗效观察

目的评价重组人生长激素(rhGH)对烧伤患者的疗效。方法将病人分为rhGH治疗组和对照组,每组各32名患者,根据烧伤情况,又将他们分为手术组(植皮)和非手术组两组,治疗组采用rhGH 0.4 IU.kg-1.d-1肌肉注射,并分析比较两组一般状况,检测患者的体重变化、创面感染情况及供皮区的愈合时间。结果治疗组创面感染率和供皮区愈合时间较对照组短,体重下降减少。结论rhGH对烧伤患者治疗作用明显,并且是安全的。     

绿豆肽调节病毒性肺炎幼鼠T细胞免疫、减轻炎症反应

目的:探讨绿豆肽调节病毒性肺炎幼鼠T细胞免疫、减轻炎症反应机理.方法:对3周龄昆明(KM)幼鼠采用A型流感病毒(H1N1)滴鼻法建立病毒性肺炎模型,将建模成功幼鼠随机分为模型组、利巴韦林组(46 mg·kg-1·d-1)、绿豆肽低、中、高剂量组(50,100,200 mg·kg mb-1·d-1),每组10只;另取10...     

不同剂量重组人生长激素对非生长激素缺乏性矮小症患儿生长激素-胰岛素样生长因子轴的影响

目的 探讨不同剂量重组人生长激素（rhGH）对非生长激素缺乏性矮小症（NGHDSS）患儿生长激素-胰岛素样生长因子轴的影响。方法 选择2020年6月至2021年9月武汉亚心总医院儿科收治的NGHDSS患儿,按随机数字表法分为对照组和观察组。对照组给予小剂量rhGH[0.10 U/（kg·d）]联合营养治疗,观察组给予大剂量rhGH[0.15 U/（kg·d）]联合营养治疗,均连续治疗12个月。比较两组患儿治疗前后身高变化、身高标准差积分（HtSDS）和生长速度（GV）,分析治疗前后血清生长激素（GH）、胰岛素样生长因子结合蛋白3(IGFBP-3)及胰岛素样生长因子1(IGF-1)水平变化,观察两组不良反应发生情况差异。结果 治疗后,两组患儿HtSDS[对照组（-1.98±0.19）分,观察组（-1.72±0.16）分]、GV[对照组（6.53±0.85）cm/年,观察组（10.36±1.02）cm/年]、身高[对照组（125.06±3.85） cm,观察组（130.89±3.06）cm]及血清IGF-1[对照组（258.76±99.85）μg/L,观察组（301.30±121.26）μ...     

Clinical evaluation of recombinant human growth hormone injection in children with growth hormone deficiency

Recombinant human growth hormone (rhGH) has been widely used in the clinical treatment of growth hormone deficiency. To simplify the injection process and increase drug compliance, application of the GH injection has become a new treatment plan in recent years. The purpose of the current study was to evaluate the efficacy and safety of rhGH injection for the treatment of growth hormone deficiency (GHD) in children in China. In a nationwide, noncomparative, prospective, randomized, open trial, 31 children with confirmed complete GHD received subcutaneous injection of rhGH at 0.25 mg/kg·wk (0.107 IU/kg·d). The injection was given daily and the total weekly amount was separated into 6–7 injections. The patients were followed up at 3-month intervals and the treatment duration was 12 months. The height (HT), annual growth velocity (GV), mean height standard deviation score (HT SDS), blood serum insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGFBP-3), and bone maturity before and after treatment were compared, and the safety of the treatment was analyzed. The mean HT, GV, and HT SDS were increased from 109.0±14 cm, 2.7±0.9 cm/yr, and −4.62 ±1.46 at baseline to 121.8±13.4 cm, 12.9±3.3 cm/yr, and −2.47±1.86 after 12 months of treatment, respectively (P<0.001). At the same time, blood IGF-I and IGFBP- 3 were increased significantly [41.27±64.43 μg/L vs 159.21±167.92 μg/L and 1540.00±1325.11 mg/L vs 3533.93±1413.82 mg/L, respectively (P<0.001)]. The bone age assessments performed 6 and 12 months after the treatment showed that no advanced bone maturation was noted. No serious adverse events occurred during the treatment, and the drug-related adverse events were mainly decreased thyroid function. We conclude that rhGH injection is a safe and effective drug for treatment of growth hormone deficiency in children.     

半乳糖化重组人生长激素和重组人生长激素在小鼠体内的药物动力学

目的：比较半乳糖化重组人生长激素和重组人生长激素在小鼠体内的药物动力学特征。方法：用＾１２５Ｉ标记Ｇａｌ－ｒｈＧＨ和ｒｈＧＨ、通过小鼠尾静脉ｉｖ，测定血和肝中相对放射性随时间的变化，以３Ｐ８７药物动力学程序进行模型拟合和参数求算。结果：＾１２５Ｉ－ｒｈＧＨ－Ｇａｌ在血中的相对放射性呈现双峰，其体内药行动力学特征与＾１２５Ｉ－ｒｈＣＨ明显不同，进一步证实了Ｇａｌ－ｒｈＧＨ的肝靶向性。     

Efficacy of needle-free administration of recombinant human growth hormone in adults with growth hormone deficiency

AIM: Needle-free administration of recombinant human growth hormone (rhGH) is effective in the treatment of growth hormone deficiency (GHD) in children, but has not been studied in adult patients. Therefore, we evaluated the efficacy of needle-free administration of rhGH in adults with GHD. METHODS: Insulin-like growth factor-I (IGF-I) concentrations were compared in newly diagnosed patients with GHD (n = 21) and in patients previously treated by subcutaneous injection of rhGH (switchers, n = 34), at baseline, 12 months and 24 months. RESULTS: In the new patients, IGF-I standard deviation scores (SDS) increased from - 1.82 +/- 0.46 to + 0.75 +/- 0.33 at 12 months and to + 0.65 +/- 0.41 at 24 months (P < or = 0.001 vs. baseline). In switchers, IGF-I SDS remained unchanged with values of + 0.98 +/- 0.32 at baseline, + 0.87 +/- 0.23 at 12 months and + 0.73 +/- 0.29 at 24 months (P = 0.696 vs. baseline). In new patients, the rhGH dose was 0.46 +/- 0.03 mg day(-1) at 12 months and 0.47 +/- 0.03 mg day(-1) at 24 months. In switchers, the rhGH dose was 0.53 +/- 0.04 mg day(-1) at baseline (s.c. injection), 0.52 +/- 0.03 mg day(-1) at 12 months and 0.48 +/- 0.03 mg day(-1) at 24 months (NS between the different time points). There was no difference in the dose of rhGH at 12 and 24 months between the two groups. Side-effects were generally minor and consisted of local tissue reactions. CONCLUSION: Administration of rhGH by needle-free, transdermal injection is effective in maintaining IGF-I concentrations in the normal range for age in adults with GHD, and is as effective as traditional subcutaneous injection of rhGH.     

特发性生长激素缺乏性矮小症在重组人生长激素治疗1年后身体构成的变化

目的:探讨青春期前特发性人生长激素缺乏症(IGHD)用基因重组人生长激素(rhGH)治疗后其身体构成的改变。方法:17例年龄为(14．6±4．5)岁,骨龄(12．1±0．8)岁的IGHD青少年(男14例,女3例),在rhGH治疗前生长速度每年(2．9±0．7)cm,患者每周0．5 u·kg-1,分5次于临睡前皮下注射rhGH,共1年。测定患者治疗前和治疗后1,3,6,9和12个月身高、体重、体内脂肪百分含量(F％)、去脂肪量(FFM)、左右手握力、血胰岛素样生长因子-1(IGF-1)和血胰岛素样生长因子结合蛋白-3(IGFBP-3)水平,并以2002年中国北方177例正常青少年值作为对照。结果:治疗前IGHD患者的身高、体重、FFM及血IGF-1和IGFBP-3水平均显著低于正常青少年(P<0．05),F％明显高于正常青少年(P<0．05),但体重指数(BMI)值无明显差异。用rhGH治疗1个月及随后治疗中,患者F％均显著低于治疗前(P<0．05),与正常青少年无统计学差异。经rhGH治疗6个月,17例IGHD患者的身高、生长速度、FFM及血IGF-1和IGFBP-3水平均明显增加(均P<0．05),其改变值均与F％的下降值相关(P均<0．01)。治疗1年后,所有患者的握力均明显增加。结论:IGHD青少年在使用rhGH后,身高、FFM及握力均显著增加,F％减少,提示患者骨骼和肌内组织的增加及脂肪含量的降低,即身体的构成发生了明显的改变。     

ELISA法研究聚乙二醇化重组人生长激素小鼠体内的药动学

建立了双抗夹心ELISA法检测小鼠血清中聚乙二醇化重组人生长激素（PEG—GH）的浓度。结果表明，PEG-GH和重组人生长激素（rhGH）浓度均在1～150ng/ml范围内呈良好的线性关系。PEG—GH以静脉注射与皮下注射两种途径给药，所得t/2β分别为静注rhGH的34.8倍和39.8倍，清除率明显下降。表明PEG—GH具有长效作用。     

基因重组人生长激素治疗青春期前特发性生长激素缺乏症临床试验

目的:评价基因重组人生长激素(rhGH)治疗青春期前特发性生长激素缺乏症(IGHD)患儿6个月的疗效和安全性。方法:对49例IGHD患儿进行rhGH治疗,每晚睡前皮下注射0．5IU·kg~(-1),每周分5次注射,共26周。评价治疗前后身高、生长速度、身高标准差计数(SDS)等指标。结果:在rhGH治疗期间,46例患儿生长速度由每年(2．5±1．0)cm提高到(11．5±2．5)cm(P＜0．005)。身高SDS由治疗前(-4．2±1．8)增为(-3．7±1．8)。同时患儿13和26周血清胰岛素样生长因子(IGF-1)和IGF结合蛋白(IGFBP,)水平均较治疗前明显升高(P＜0．05)。其体重与骨龄无明显变化。治疗后共有15．7%患儿出现甲状腺功能降低,抗hGH抗体阳性率为21．7%,但所有这些现象均未影响患者体格的线性增长。在治疗期间所有患者肝肾功能、血尿常规和代谢性指标(如血糖和血脂水平)等均保持在正常范围。结论:rhGH是治疗IGHD安全有效的药物。     

重组人生长激素对局灶性脑缺血大鼠神经功能恢复的影响

目的：研究重组人生长激素（recombinanthu-mangrowthhormone,rhGH）对大鼠局部脑缺血损伤后的影响。方法：应用线栓法制作SD大鼠大脑中动脉永久性闭塞模型（middlecerebralarteryocclusion,MCAO）,观察rhGH对大鼠脑缺血后脑梗死面积和神经功能（网屏试验、平衡木试验、触觉刺激试验）恢复的情况。结果：皮下注射rhGH后,药物干预组大鼠脑梗死体积较缺血对照组明显减小（P〈0.05）,神经功能恢复水平高于自然恢复组。结论：rhGH能减轻大鼠脑缺血MCAO后的脑实质和神经功能损伤。     

温度敏感型原位凝胶用于蛋白类药物缓释注射给药系统的初步研究

尝试以温度敏感型原位凝胶（TISG）作为重组人生长激素（rhGH）的载体制备缓释注射给药系统，通过改变泊洛沙姆同系物的配比，得到了具有适宜胶凝温度的TISG，并采用无膜溶出模型研究了TISG的体外释药行为。结果表明，rhGH从TISG中的释放遵循零级动力学过程，且胶凝温度接近体温的TISG维持释放的时间较短。大鼠体内实验进一步证实，TISG可延缓rhGH释放，与溶液制剂相比可获得更平缓且持久的血药浓度曲线。     

Feasibility Study on Spray-Drying Protein Pharmaceuticals: Recombinant Human Growth Hormone and Tissue-Type Plasminogen Activator

The feasibility of spray-drying solutions of recombinant methionyl human growth hormone (hGH) and tissue-type plasminogen activator (t-PA) was investigated. hGH was formulated in a mannitol phosphate buffer and t-PA was used in an arginine phosphate formulation containing 0.004% (w/v) polysorbate 80. Using filtered air (90 – 150°C) as the drying medium, hGH could be dried to a residual moisture content of 4%. However, approximately 25% of the protein was degraded during the processing. Results of atomization studies suggest that surface denaturation at the air–liquid interface of the droplets in the spray plays a major role in the degradation of the protein. The addition of 0.1% (w/v) polysorbate 20 into the hGH formulation reduced the formation of soluble and insoluble aggregates by approximately 90% during atomization. During spray-drying the addition of 0.1% (w/v) polysorbate 20 reduced the formation of soluble and insoluble aggregates by approximately 70 and 85%, respectively. In contrast, t-PA remained intact upon atomization. Depending on the spray-drying conditions, product powders with a residual moisture content between 5 and 8% were obtained. No oxidation, aggregation, or denaturation occurred in the protein under several operation conditions. Overall, this study demonstrates that it is feasible to spray-dry t-PA in the current marketed formulation.