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Oral absorption enhancement of cromo...

Ding, Xuan.

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Oral absorption enhancement of cromolyn sodium through non-covalent complexation.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Oral absorption enhancement of cromolyn sodium through non-covalent complexation./
作者:	Ding, Xuan.
面頁冊數:	153 p.
附註:	Source: Dissertation Abstracts International, Volume: 65-08, Section: B, page: 3967.
Contained By:	Dissertation Abstracts International65-08B.
標題:	Health Sciences, Pharmacy. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3143031
ISBN:	9780496009800

Oral absorption enhancement of cromolyn sodium through non-covalent complexation.
Ding, Xuan.

Oral absorption enhancement of cromolyn sodium through non-covalent complexation. - 153 p.

Source: Dissertation Abstracts International, Volume: 65-08, Section: B, page: 3967.

Thesis (Ph.D.)--The University of Wisconsin - Madison, 2004.

Cromolyn sodium has been successfully used topically in the prophylactic treatment of allergic diseases. Due to its extreme hydrophilicity, the oral bioavailability of cromolyn is minimal. An oral dosage form of cromolyn is desired to improve patient compliance and to provide a supplementary treatment of systemic inflammation. Sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAG) belongs to a family of low molecular weight delivery agents synthesized by Emisphere Technologies, Inc. When co-administered with certain polar drugs, such as human growth hormone, insulin, calcitonin, heparin, and cromolyn, they can markedly enhance their oral absorption.

ISBN: 9780496009800Subjects--Topical Terms:

1017737
Health Sciences, Pharmacy.

Oral absorption enhancement of cromolyn sodium through non-covalent complexation.
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500 $a Source: Dissertation Abstracts International, Volume: 65-08, Section: B, page: 3967.
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502 $a Thesis (Ph.D.)--The University of Wisconsin - Madison, 2004.
520 $a Cromolyn sodium has been successfully used topically in the prophylactic treatment of allergic diseases. Due to its extreme hydrophilicity, the oral bioavailability of cromolyn is minimal. An oral dosage form of cromolyn is desired to improve patient compliance and to provide a supplementary treatment of systemic inflammation. Sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAG) belongs to a family of low molecular weight delivery agents synthesized by Emisphere Technologies, Inc. When co-administered with certain polar drugs, such as human growth hormone, insulin, calcitonin, heparin, and cromolyn, they can markedly enhance their oral absorption.
520 $a Based on several in-depth mechanistic studies at cellular and subcellular levels, it has been concluded that unlike classical absorption enhancers, SNAC does not compromise absorption barriers to cause the enhancement. Neither does it mobilize any identified intrinsic transport systems or chemically modify these drugs. It has been suggested that SNAC noncovalently interacts with these drugs to improve their physicochemical properties, mainly hydrophobicity for absorption. This study has been launched in order to distinguish oral absorption enhancement by SNAC from the enhancement by classical absorption enhancers, and more important, to provide solid evidence to support the hypothesized non-covalent cromolyn-SNAC complexation and its relevance to oral absorption enhancement of cromolyn.
520 $a From Caco-2 cell monolayers permeability studies, we observe intestinal transport of cromolyn is significantly increased with the assistance of SNAC. Similar to previous studies, no cytotoxicity is observed, implied by no dramatic LDH leakage and no significant flux of passive transcellular and paracellular diffusion markers. Cromolyn and SNAC are found to weakly interact with each other. The predominant driving force is ring-stacking effect, involving the twin aromatic rings of cromolyn and the hydroxybenzamide moiety of SNAC. One interaction mode is that SNAC inserts this moiety between the cromolyn rings. Other complexes comprising different ring stacking modes with various stoichiometries co-exist in solution. Such non-covalent complexation can alter the hydration of cromolyn and thus optimize its hydrophobicity for oral absorption.
520 $a All these findings suggest that SNAC improves oral absorption of cromolyn sodium by non-covalently interacting with the drug to optimize its hydrophobicity.
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