重组人生长激素长效制剂的研究进展

重组人生长激素长效制剂能延长药物在体内的滞留时间,有效增加患者用药的顺应性、降低用药相关的医护成本。本文重点综述微球、生物可降解性凝胶、聚乙二醇化等重组人生长激素长效制剂的制备方法及其研究进展。     

基因重组人生长激素治疗儿童生长激素缺乏症

小儿因垂体前叶分泌的生长激素不足所导致的矮身体称生长激素缺乏症 (ＧＨＤ)。我国儿童发病率约为 1∶85 0 0。其中下丘脑、垂体无明显病灶 ,但生长激素 (ＧＨ)分泌功能不足 ,原因不明者称为特发性生长激素缺乏症。近年来临床上常用ＧＨ替代治疗。最早用于治疗ＧＨＤ的制剂是从人脑垂体中提取的。1985年用基因重组人生长激素 (ｒ ｈＧＨ)取代人垂体生长激素应用于临床以来 ,ＧＨＤ的治疗状况大为改善。目前ｒ ｈＧＨ的替代治疗已成为ＧＨＤ的首选治疗措施 ,广泛用于临床。1　用法研究结果表明 ,每日 1次皮下注射ｒ ｈＧＨ的疗效远较以往隔…     

国产重组人生长激素药效实验方法初探

目前国外对重组人生长激素（recombinanthumangrowthhormone，rhGH）的研究较为广泛，其有促生长发育作用，与机体代谢关系密切，临床上用于小儿生长发育迟缓、手术或创伤恢复期、老人免疫功能降低等’‘－”。对rhGH的动物实验国内尚未见报道。本文研究了国产重组人生长激素可     

国产重组人生长激素治疗儿童生长激素缺乏症临床疗效观察

正确评价国产重组人生长激素对促进生长激素缺乏症儿童身高增长作用的疗效和安全性,观察相关血清生化指标的变化,方法：造反２ＣＨＤ患儿９例,给予国产ｒ－ｈＧＨ０．１ｉｕ／ｋｇ．ｄ;疗程６个月。结论国产ｒ－ｈＧＨ治疗ＧＨＤ近期疗效肯定,而且安全可靠。     

国产重组人生长激素注射液在健康受试者中的生物等效性

目的:评价单一给药后受试制剂(重组人生长激素注射液)和参比制剂(注射用重组人生长激素)的生物等效性及安全性.方法:研究采用单中心、双周期、随机、盲法、自身交叉对照设计.将48例受试者平均分为2组,每组受试者分别在2个周期交叉皮下注射重组人生长激素(r-hGH)受试制剂或参比制剂0.067 mg·kg-1(0.2 IU·...     

重组人生长激素治疗垂体性侏儒症的临床观察

用基因工程重组的人生长激素治疗垂体性侏儒症（GHD）13例6个月，所有患儿身高都有不同程度增加。平均共增高8．3±1．2cm，身高落后值（SDS）由治疗前的-5．51±0．94减少到治疗后的-4．20±0．96。在6个月的用药期，13例患儿身高增长速率明显增加，为16．6±2．4cm·y-1，与治疗前24±0.6cm·y-1相比增加非常明显（P＜0．001）。除少数患者用药初期与注射部位皮肤出现暂时性红斑外，未见其他不良反应。     

重组人生长激素临床应用进展

人生长激素(hGH)是脑垂体分泌的一种蛋白质类激素,是由191个氨基酸组成的单链多肽。1986年已能用基因工程技术合成与天然人的GH结构相同的191肽GH(RhGH)。国产RhGH也已经问世(安徽安科生物高技术有限责任公司生产)。以往RhGH主要用于儿童及成人GH缺乏的替代治疗以及各种原因引起的矮小症,取得了较好效果。鉴于hGH生理作用复杂,目前RhGH的临床应用有一些新的进展,现综述如下。     

重组人生长激素的质量鉴定

用SDS-PAGE、IFE、RP-HPLC、HIC、HPSEC、HPLC-胰肽图谱分析、生物测定、斑点免疫印迹、ELISA和地高辛标记DNA探针等多种手段，对国产r-hGH进行全面质量鉴定并与国外同类产品进行比较。其结果表明，国产r-hGH的质量基本达到国外国类产品的水平。为DNA重组药物的质控积累了重要数据。     

放射免疫法研究乳糖基重组人生长激素和重组人生长激素的药代动力学

目的 :比较研究乳糖基重组人生长激素 (L -rhGH )和重组人生长激素 (rhGH )在小鼠血和肝中的药代动力学。方法 :用注射免疫法测定L -rhGH和rhGH在小鼠血、肝脏中的药物浓度。结果 :静脉注射后 ,两者的药代动力学过程存在显著性差异 ,L -rhGH在肝中的分布量较rhGH增加 ,且T1/2 仅为rhGH的17 9 % ;L -rhGH在血中亦表现为短维持时间、低分布量。结论 :L -rhGH呈现出更符合人体生理的药代动力学特征     

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。     

重组人酸性成纤维细胞生长因子的稳定性研究

目的研究重组人酸性成纤维细胞生长因子(rhaFGF)在不同温度下的存放稳定性。方法rhaFGF冻干粉和溶媒在4,25和37℃分别保存30个月;rhaFGF液体在4℃保存56d,在25和37℃分别保存35d。采用MTT法测定rhaFGF的生物活性,同时进行外观性状、水分含量、pH值的测量和无菌试验。结果4℃时,rhaFGF冻干粉、液体和溶媒的各项性质在观察期内都无变化。25℃时,rhaFGF冻干粉、液体的生物活性分别在存放18个月和35d有下降趋势。37℃时,rhaFGF冻干粉、液体的生物活性分别在存放12个月和35d有下降趋势。结论rhaFGF冻干粉在4℃时可有效保存2年;rhaFGF冻干粉溶解后于4℃时保存28d内使用有效;溶媒在4℃时保存2年质量稳定。     

Clinical applications of recombinant human growth hormone in adults

The main function of growth hormone (GH) is to promote linear growth during childhood; however, GH secretion persists throughout life after cessation of skeletal growth. This hormone has important physiological functions apart from growth stimulation. Many aspects of the physiological and pharmacological actions of GH have been recently clarified. Accordingly, in the last years, especially since the introduction of recombinant human GH (rhGH), GH therapeutical applications have increased. In the last years, the main clinical application of rhGH has been to stimulate growth of growth-retarded GH deficient (GHD) children. More recently, rhGH therapy has been approved for other conditions associated with short stature, including Turner syndrome and end stage renal disease. In adults, the only therapeutic indications approved are the adult GHD syndrome and the AIDS-associated wasting. This review outlines the present knowledge of the physiological effects, clinical applications, therapeutic perspectives, side effects, precautions and contraindications of rhGH therapy in adults.     

生长激素促生长作用的疗效观察

目的 观察国产基因重组生长激素（r-hGH)的促生长作用。方法 对11例矮小症儿童作用r-hGH，对2例真性性早熟患儿联合应用r-hGH和促性腺激素释放激素类似物（GnRHa)，治疗3个月，比较其治疗前后的生长速率（GV）和身高标准差得分（HtSDS)。结果 经治疗，各类矮小症儿童的GV和HtSDS均有显著提高，其中生长激素缺乏症患儿提高最显著；性早熟组儿童联用GnRHa和r-hGH治疗时的GV略高于未用药时自然GV，其中1例联用时GV明显高于单用GnRHa时GV。结论 r-hGH对各类矮小症患儿和性早熟儿童均有促生长作用。     

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.     

Clinical applications of recombinant human growth hormone in adults

The main function of growth hormone (GH) is to promote linear growth during childhood; however, GH secretion persists throughout life after cessation of skeletal growth. This hormone has important physiological functions apart from growth stimulation. Many aspects of the physiological and pharmacological actions of GH have been recently clarified. Accordingly, in the last years, especially since the introduction of recombinant human GH (rhGH), GH therapeutical applications have increased. In the last years, the main clinical application of rhGH has been to stimulate growth of growth-retarded GH deficient (GHD) children. More recently, rhGH therapy has been approved for other conditions associated with short stature, including Turner syndrome and end stage renal disease. In adults, the only therapeutic indications approved are the adult GHD syndrome and the AIDS-associated wasting. This review outlines the present knowledge of the physiological effects, clinical applications, therapeutic perspectives, side effects, precautions and contraindications of rhGH therapy in adults.     

重组人生长激素的临床应用进展

生长激素是由脑垂体前叶嗜酸性细胞分泌的一种蛋白质激素，有促进物质代谢和生长发育的作用。目前重组人生长激素被广泛运用于临床，不仅能促进先天性卵巢发育不全综合征和慢性肾脏病患儿生长，同时还能协助治疗充血性心力衰竭、慢性阻塞性肺病、重症急性胰腺炎、严重烧伤，纠正低蛋白血症以及促进创面愈合。     

Detection of doping with recombinant human growth hormone

Detection of doping with recombinant human growth hormone is one of the challenges for antidoping analysis. This review focuses on the most important relevant publications that provide insight into the laboratory measurement of human growth hormone (hGH), antibodies and standards, the isoform approach and the biomarker approach. The isoform approach monitors the changes of hGH molecular isoform composition in serum and was applied at the Olympic Games in Athens in 2004, Turin in 2006 and Beijing in 2008. The markers approach detects a formula score, which reflects the changes in concentration of IGF-1 and P-III-P. All these methodologies measure the concentrations of growth hormone and its isoforms for isoform approach, or the concentrations of IGF-1 and P-III-P. All factors that affect these measurements should be taken into account for the development of methods to detect doping with recombinant hGH.     

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.