Studies on the development of new drug adsorption-enhancing systems based on physiological action of nitric oxide (NO)
基于一氧化氮(NO)生理作用的新型药物吸附增强系统开发研究
基本信息
- 批准号:10672092
- 负责人:
- 金额:$ 1.66万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (C)
- 财政年份:1998
- 资助国家:日本
- 起止时间:1998 至 1999
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The objective of this investigation was to evaluate the potential of nitric oxide (NO) donors as a new class of absorption-enhancing agent which may act on epithelial cells of mucosal membrane (intestinal, rectal, nasal and so on) through epithelial actions of a chemical mediator, NO, released from each donor such as S-nitroso-N-acetyl-DL-penicillamine (SNAP). When model drug of poorly absorbed macromolecule such as inslulin and recombinant human granulocyte colony-stimulating factor was administered with SNAP into the rectum or the nasal cavity of rabbits, significant increase of absorption of these macromolecular drugs was observed. The absorption enhancement of macromolecular drug by SNAP was decreased when these two drugs were administered in combination with NO scavenger such as carboxy-PTIO. These results suggest that NO plays an essential role in enhancement of drug absorption. We found that SNAP had very low potential for cytotoxicity, as evaluated by the cell detachment assay, release of lactate dehydrogenase (LDH) from cultured cells and morphological observations of rectal and nasal tissue of rabbits that received SNAP. A NO donor such as SNAP is a promising absorption-enhancing agent for rectal and nasal delivery systems of poorly absorbed drug such as protein drug. However, several research subjects concerning the absorption-enhancing mechanism of NO in detail remain to he done. Further experiments including instrumental analysis should be studied.
本研究的目的是评估一氧化氮(NO)供体作为一类新型吸收促进剂的潜力,它可以通过化学介质NO的上皮作用作用于粘膜(肠、直肠、鼻腔等)的上皮细胞,每个供体释放的化学介质NO如S-亚硝基-N-乙酰基-DL-青霉胺(SNAP)。当胰岛素和重组人粒细胞集落刺激因子等难吸收的大分子药物模型药物与SNAP一起给予家兔直肠或鼻腔时,观察到这些大分子药物的吸收显着增加。当这两种药物与羧基-PTIO等NO清除剂联合给药时,SNAP对大分子药物的吸收增强作用减弱。这些结果表明NO在增强药物吸收方面起着重要作用。我们发现,通过细胞脱离试验、培养细胞中乳酸脱氢酶 (LDH) 的释放以及接受 SNAP 的兔子的直肠和鼻组织的形态学观察来评估,SNAP 的细胞毒性潜力非常低。 NO 供体(例如 SNAP)是一种很有前途的吸收促进剂,适用于吸收不良的药物(例如蛋白质药物)的直肠和鼻腔递送系统。然而,关于NO吸收增强机制的一些详细研究课题仍有待完成。应研究包括仪器分析在内的进一步实验。
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Yoshiteru Watanabe et al.: "Absorption enhancement of a protein drug by nitric oxide donor: Effect on nasal absorption of human granulocyte colony-stimulating factor"Journal of Drug Targeting. (in press). (2000)
Yoshiteru Watanabe 等人:“一氧化氮供体对蛋白质药物的吸收增强:对人粒细胞集落刺激因子鼻吸收的影响”药物靶向杂志。
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- 影响因子:0
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- 通讯作者:
Naoki Utoguchi et al.: "Nitric oxide donors enhance rectal absorption of macromolecules in rabbits"Pharmaceutical Research. 15. 870-876 (1998)
Naoki Utoguchi 等人:“一氧化氮供体增强兔子直肠对大分子的吸收”药物研究。
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- 影响因子:0
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WATANABE Yoshiteru其他文献
WATANABE Yoshiteru的其他文献
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{{ truncateString('WATANABE Yoshiteru', 18)}}的其他基金
Strategic approach based on molecular mechanism for modulation of barrier function of tight junction to enhance delivery of new biopharmaceuticals
基于分子机制调节紧密连接屏障功能以增强新生物药物递送的战略方法
- 批准号:
25460222 - 财政年份:2013
- 资助金额:
$ 1.66万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Studies of barrier function of tight junction in epithelial celllayers and strategic development of novel methods for drug permeation enhancement in cells
上皮细胞层紧密连接屏障功能的研究和细胞内药物渗透增强新方法的战略开发
- 批准号:
21590178 - 财政年份:2009
- 资助金额:
$ 1.66万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
A Novel Strategy for Enhancement of Permeation and Absorption of Drugs by Modulation of Proteins Constructed Barrier Function in Biomembrane
通过调节生物膜中蛋白质构建的屏障功能来增强药物渗透和吸收的新策略
- 批准号:
19590159 - 财政年份:2007
- 资助金额:
$ 1.66万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Studies on Drug Permeation in Placental Barrier by RNA Interference
RNA干扰药物在胎盘屏障渗透的研究
- 批准号:
17590136 - 财政年份:2005
- 资助金额:
$ 1.66万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Development of Gene Transfer Systems into Placental Cells for Studies of Drug Transport Mechanism in Blood-Placenta Barrier
开发胎盘细胞基因转移系统以研究血胎盘屏障中的药物转运机制
- 批准号:
15590139 - 财政年份:2003
- 资助金额:
$ 1.66万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
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