造血干细胞动员剂硫酸葡聚糖的临床前及人体试用研究

EXPERIMENTAL STUDY AND NORMAL INDIVIDUAL TRIAL USE OF HEMOPOIETIC STEM CELL MOBILIZER DS

为了阐明临床应用造血干细胞动员剂硫酸葡聚糖(DS)的可能性,用不同动物进行了动员效果、LD_(50)过敏实验和正常人体试用研究。结果表明,给狗静脉注射分子量为10kDa的DS后,血中MNC和CFU-GM呈时相性变化,1h开始增加,5h达到高峰值;LD_(50)为1128.6mg/kg(雄性小鼠)和1369.4mg/kg(雌性小鼠),两者之间无显著差异;分子量为10kDa的DS过敏反应为阴性结果,15kDa的DS为阳性结果;34例正常人体试用,DS可使血中CFU-GM、BFU-E和CFU-GEMM,分别增加到给药前的8倍、10.5倍和12倍,有效、安全剂量约为15～20mg/kg。分子量为10kDa的DS人体试用研究属国内外首次报道。

In order to determine the possibility of the clinical application of the mobilizer DS, studies on its mobilizing effect, LD_(50), anaphylactic reaction and normal individual trial use were carried out. The results showed that the numbers of MNC and CFU-GM in peripheral blood began to increase and reached peak values 5 hours after intravenous injection of DS with molecular weight of 10kDa; LD_(50) of DS in male and female mice were 1128.6 mg/kg and 1369.4 mg/kg respectively. The difference is insignificant. DS with MW of 10kDa had a negative anaphylactic reaction while that of 15kDa gave a positive one. In the trial use of DS, the numbers of CFU-GM, BFU-E and CFU-GEMM in peripheral blood increased by 8, 10.5 and 12 fold respectively, in 34 volunteers. The safe and effective dose of DS was about 15-20 mg/kg. The normal individual trial use of DS with MW of 10kDa has not been reported yet in literature.