N4-(4-羧基丁基)-ara- c与乙二胺引入的葡聚糖的缀合物。药物释放谱及其抗肿瘤作用的进一步体内研究。

Drug design and delivery Pub Date : 1991-04-01
H Onishi, Y Seno, P Pithayanukul, T Nagai
{"title":"N4-(4-羧基丁基)-ara- c与乙二胺引入的葡聚糖的缀合物。药物释放谱及其抗肿瘤作用的进一步体内研究。","authors":"H Onishi,&nbsp;Y Seno,&nbsp;P Pithayanukul,&nbsp;T Nagai","doi":"","DOIUrl":null,"url":null,"abstract":"<p><p>In vitro and further in vivo work with a conjugate formed from the cytotoxic drug 1-beta-arabinofuranosylcytosine (ara-C) and dextran 2000 are described. In the preparation of this conjugate, functionalisation of ara-C was via N4-(4-carboxybutyryl)-ara-C (glu-ara-C), permitting conjugation with amino groups introduced by prior reaction of the oxidised dextran with ethylenediamine; by varying the proportions of the reaction components, 5.4 to 7.7% w/w loadings of ara-C were obtained. At physiological pH, in vitro, drug release from a 5.4% loaded conjugate was gradual and was dominantly ara-C; at lysosomal pH (pH 5) the release rate was much slower and more ara-U was formed. Antitumour effects were evaluated in L1210 leukaemic mice following single (1 day after inoculation) or double (2 and 6 days after inoculation) intraperitoneal injection of ara-C, glu-ara-C, or a 7.7% loaded conjugate at three dose levels. In all cases, the increase in lifespan was greatest following use of the conjugate, but the differences in the effects of ara-C and the conjugate were only significant at the lowest dose level. Glu-ara-C was virtually inactive under all conditions.</p>","PeriodicalId":11271,"journal":{"name":"Drug design and delivery","volume":"7 2","pages":"139-45"},"PeriodicalIF":0.0000,"publicationDate":"1991-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Conjugate of N4-(4-carboxybutyryl)-ara-C and ethylenediamine-introduced dextran. Drug release profiles and further in vivo study of its antitumor effects.\",\"authors\":\"H Onishi,&nbsp;Y Seno,&nbsp;P Pithayanukul,&nbsp;T Nagai\",\"doi\":\"\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>In vitro and further in vivo work with a conjugate formed from the cytotoxic drug 1-beta-arabinofuranosylcytosine (ara-C) and dextran 2000 are described. In the preparation of this conjugate, functionalisation of ara-C was via N4-(4-carboxybutyryl)-ara-C (glu-ara-C), permitting conjugation with amino groups introduced by prior reaction of the oxidised dextran with ethylenediamine; by varying the proportions of the reaction components, 5.4 to 7.7% w/w loadings of ara-C were obtained. At physiological pH, in vitro, drug release from a 5.4% loaded conjugate was gradual and was dominantly ara-C; at lysosomal pH (pH 5) the release rate was much slower and more ara-U was formed. Antitumour effects were evaluated in L1210 leukaemic mice following single (1 day after inoculation) or double (2 and 6 days after inoculation) intraperitoneal injection of ara-C, glu-ara-C, or a 7.7% loaded conjugate at three dose levels. In all cases, the increase in lifespan was greatest following use of the conjugate, but the differences in the effects of ara-C and the conjugate were only significant at the lowest dose level. Glu-ara-C was virtually inactive under all conditions.</p>\",\"PeriodicalId\":11271,\"journal\":{\"name\":\"Drug design and delivery\",\"volume\":\"7 2\",\"pages\":\"139-45\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"1991-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Drug design and delivery\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug design and delivery","FirstCategoryId":"1085","ListUrlMain":"","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

摘要

本文描述了细胞毒性药物1- β -阿拉伯糖醛基胞嘧啶(ara-C)和葡聚糖2000形成的缀合物在体外和体内的进一步工作。在该缀合物的制备中,ara-C的功能化是通过N4-(4-羧基丁基)-ara-C(葡萄糖-ara-C)进行的,允许与氧化右旋糖酐与乙二胺预先反应引入的氨基结合;通过改变反应组分的比例,可以获得5.4 ~ 7.7% w/w的ara-C负荷。在生理pH下,5.4%负载的缀合物的体外药物释放是渐进的,主要是ara-C;在溶酶体pH (pH 5)时,释放速度较慢,形成更多的ara-U。在L1210白血病小鼠中,单次(接种后1天)或两次(接种后2天和6天)腹腔注射ara-C、glu-ara-C或负载7.7%的缀合物,以三个剂量水平评估其抗肿瘤作用。在所有情况下,使用缀合物后寿命的增加最大,但ara-C和缀合物的效果差异仅在最低剂量水平下显着。在所有条件下,Glu-ara-C几乎都没有活性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Conjugate of N4-(4-carboxybutyryl)-ara-C and ethylenediamine-introduced dextran. Drug release profiles and further in vivo study of its antitumor effects.

In vitro and further in vivo work with a conjugate formed from the cytotoxic drug 1-beta-arabinofuranosylcytosine (ara-C) and dextran 2000 are described. In the preparation of this conjugate, functionalisation of ara-C was via N4-(4-carboxybutyryl)-ara-C (glu-ara-C), permitting conjugation with amino groups introduced by prior reaction of the oxidised dextran with ethylenediamine; by varying the proportions of the reaction components, 5.4 to 7.7% w/w loadings of ara-C were obtained. At physiological pH, in vitro, drug release from a 5.4% loaded conjugate was gradual and was dominantly ara-C; at lysosomal pH (pH 5) the release rate was much slower and more ara-U was formed. Antitumour effects were evaluated in L1210 leukaemic mice following single (1 day after inoculation) or double (2 and 6 days after inoculation) intraperitoneal injection of ara-C, glu-ara-C, or a 7.7% loaded conjugate at three dose levels. In all cases, the increase in lifespan was greatest following use of the conjugate, but the differences in the effects of ara-C and the conjugate were only significant at the lowest dose level. Glu-ara-C was virtually inactive under all conditions.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
期刊最新文献
In-silico drug design: An approach which revolutionarised the drug discovery process Insoluble drug delivery technologies: review of health benefits and business potentials Microscopy characterisation of micro- and nanosystems for pharmaceutical use Synthesis and anticonvulsant activity of 3-(3'-trifluoromethylphenoxy)-pyridines and -dihydropyridines. Synthesis of the diastereomers of 5-(2,2-dichlorocyclopropyl)- and 5-(2-chlorocyclopropyl)-2'-deoxyuridine, and the antiviral and cytotoxic activity of these and bromo analogues.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1