乙二醇壳聚糖-二乙烯三胺五乙酸的合成及相对安全性研究

曾峰; 付维林; 李蓉; 李涛; 肖瑶; 张翼; 陈翔宇; 刘明华

doi:10.16016/j.2097-0927.202201123

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乙二醇壳聚糖-二乙烯三胺五乙酸的合成及相对安全性研究

药学 | 更新时间：2026-01-09

- 乙二醇壳聚糖-二乙烯三胺五乙酸的合成及相对安全性研究
- Preparation of ethylene glycol chitosan-diethylenetriamine pentaacetic acid and assessment for its relative safety
- 陆军军医大学学报 2022年44卷第9期页码：967-974
- 作者机构：
  
  1.400038 重庆，陆军军医大学(第三军医大学)第一附属医院：急诊科
  2.400038 重庆，陆军军医大学(第三军医大学)军事预防医学系复合伤研究所，创伤、烧伤与复合伤国家重点实验室
  3.400038 重庆，陆军军医大学(第三军医大学)第一附属医院：关节科
- 作者简介：
  
  [刘明华，E-mail：mhliuswhcq@126.comLIU Minghua, E-mail: mhliuswhcq@126.com
- 基金信息：
  
  军队后勤科研重点项目(BLJ20J005)
- DOI：10.16016/j.2097-0927.202201123
  中图分类号： R818.03; R818.052
- 收稿：2022-01-14，
  
  修回：2022-03-07，
  
  纸质出版：2022-05-15
- 稿件说明：
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曾峰, 付维林, 李蓉, 等. 乙二醇壳聚糖-二乙烯三胺五乙酸的合成及相对安全性研究[J]. 陆军军医大学学报, 2022,44(9):967-974.

Feng ZENG, Weilin FU, Rong LI, et al. Preparation of ethylene glycol chitosan-diethylenetriamine pentaacetic acid and assessment for its relative safety[J]. Journal of Army Medical University, 2022, 44(9): 967-974.
曾峰, 付维林, 李蓉, 等. 乙二醇壳聚糖-二乙烯三胺五乙酸的合成及相对安全性研究[J]. 陆军军医大学学报, 2022,44(9):967-974. DOI： 10.16016/j.2097-0927.202201123.

Feng ZENG, Weilin FU, Rong LI, et al. Preparation of ethylene glycol chitosan-diethylenetriamine pentaacetic acid and assessment for its relative safety[J]. Journal of Army Medical University, 2022, 44(9): 967-974. DOI： 10.16016/j.2097-0927.202201123.

摘要

目的

合成乙二醇壳聚糖-二乙烯三胺五乙酸(glycol chitosan-diethylenetriamine pentaacetic acid，GC-DTPA)并验证其细胞相容性及常规使用剂量范围内全身毒性。

方法

通过有机合成、化学交联方法等将二乙烯三胺五乙酸(diethylenetriamine pentaacetic acid，DTPA)接枝到乙二醇壳聚糖(Glycol Chitosan，GC)上，核磁共振氢谱(proton nuclear magnetic resonance

H NMR)及傅立叶变换红外光谱(Fourier transform infrared，FT-IR)对GC-DTPA进行表征。CCK8法检测不同浓度GC-DTPA对ICE-6细胞增殖的影响。6~8周龄健康SPF级SD大鼠80只，雌雄不拘，体质量180~220 g。随机分为GC-DTPA 60、90、120 mg/kg实验组与对照组(给予同等剂量生理盐水)，每组20只。观察各组大鼠体质量变化及存活率，全自动血液体液分析仪及全自动生化免疫分析仪检测14 d血常规、血生化；HE染色系统显微镜观察各器官病理学变化。

结果

经FT-IR、

H NMR表征，DTPA成功接枝到GC上。不同浓度GC-DTPA组的细胞相对存活率均在90%以上；给药14 d后各剂量组大鼠血常规、血生化等指标差异无临床意义，各器官组织病理未见损伤性改变。

结论

有机合成、化学交联方法合成的GC-DTPA未见明显细胞毒性；口服给药至120 mg/kg时未见明显全身毒性。

Abstract

Objective

To synthesize ethylene glycol chitosan-diethylenetriamine pentaacetic acid (GC-DTPA)

and evaluate its cytocompatibility and systemic toxicity within the dose range of routine use.

Methods

DTPA was grafted onto ethylene glycol chitosan (GC) by organic synthesis and chemical cross-linking method

and was subsequently characterized with proton nuclear magnetic reso

nance (

H NMR) and Fourier transform infrared (FT-IR) spectroscopy. CCK-8 assay was used to detect the effects of different concentrations of GC-DTPA on the proliferation of ICE-6 cells. In addition

80 healthy SPF SD rats (aged 6~8 weeks

body weight 180~220 g) were randomly divided into 4 groups (

=20): control group (given normal saline)

and experimental groups (60

90 and 120 mg/kg GC-DTPA

respectively by intragastric gavage). The change of body weight and survival rate of rats in each group were observed. Blood routine test and blood biochemical examination were performed in the rats on the 14th day after gavage with aid of automatic blood humoral and biochemical immunoassay analyzers respectively. Then

the rats were sacrificed and the pathological changes of organs were observed after HE staining.

Results

FT-IR spectroscopy and 1H-NMR suggested that DTPA was successfully grafted onto GC

and GC-DTPA exhibited excellent cytocompatibility

with cell viability all above 90% after its treatment at different concentrations. In 14 d after administration

no significant differences were seen in the results of blood routine and blood biochemical tests

or in pathological changes of organs and tissues in each group.

Conclusion

The GC-DTPA synthesized by chemical synthesis and cross-linking method shows no obvious cytotoxicity

and no systemic toxicity is seen even after oral administration dose up to 120 mg/kg.

关键词

Keywords

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