• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

1998 Fiscal Year Final Research Report Summary

Colon-Specific Drug Delivery System Based on Cyclodextrin Conjugate

Research Project

Project/Area Number 09672331
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 応用薬理学・医療系薬学
Research InstitutionKumamoto University

Principal Investigator

UEKAMA Kaneto  Kumamoto University・Faculty of Pharm.Sci., Professor, 薬学部, 教授 (90040328)

Co-Investigator(Kenkyū-buntansha) HIRAYAMA Fumitoshi  Kumamoto University・Faculty of Pharm.Sci., Associate Professor, 薬学部, 助教授 (90094036)
Project Period (FY) 1997 – 1998
KeywordsCyclodextrin / Colon-specific Drug Delivery / Prodrug / Biodegradation / Intestinal Microflora / Biphenylyl Acetic Acid / Antiinflammatory Effect
Research Abstract

An antiinflammatory 4-biphenylylacetic acid (BPAA), as a model drug, was selectively conjugated onto one of the primary hydroxyl groups of alpha-, beta- and gamma-cyclodextrins (alpha-, beta- and gamma-CyDs) though an ester or amide linkage, (BPAA/alpha-, beta- and gamma-CyD conjugates). and their in-vitro and in- vivo drug release, oral absorption behavior, and antiinflammatory effect in rat model were investigate to evaluate them as a colon-specific drug delivery system. The results obtained were summarized as follows :
1) The NMR and mass spectroscopic results indicate that the BPAA moiety was introduced selectively onto one of the primary hydroxyl groups of CyDs. The aqueous solubilities of the alpha- and beta-CyD conjugates were about 100 and 10 times respectively, that of BPAA, whereas that. of the beta-CyD conjugate decreased to about one-tenth. The ester conjugates released BPAA selectively in rat cecal and colonic contents, whereas they were stable in other biological fluids of rats.
2) The serum levels of BPAA increased about 3 hours after oral administration of the alpha-and -gamma-CyD ester conjugates to rats, accompanying a marked increase in the serum levels, whereas the beta-CyD and the amide conjugates resulted in little increase of the serum levels.
3) The antiinflammatory effect of the gamma-CyD ester conjugate was evaluated, in comparison with that of the beta-CyD complex, using the model of carageenan-induced acute edema in rat paw. In the case of the beta-CyD complex a rapid antiinflammatory response was observed, because of the fast dissolution of the complex. In sharp contrast, the gamma-CyD conjugate needed a fairly long lag time to exhibit, the drug delivery, because BPAA was produced after it had reached the cecum and colon.
The present conjugate approach provides a versatile means for construction of not only colon-specific delivery system but also delay-release system of certain drugs.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] F.Hirayama: "In-vitro Evaluation of Biphenylyl Acetic Acid-β-Cyclodextrin Conjugates as Colon-Targeting Prodrug : Drug Release Behaviour in Rat Biological Media" J.Pharm.Pharmacol.48・1. 27-31 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Uekama: "6 -O-[(4-Biphenylyl)acetyl]-α-,-β-,and -r-cyclodextrins and 6 -deoxy-6-[(4-biphenylyl)acetyl] amino]-α-,-β-,and -r-cyclodextrins : Potential Prodrugs for Colon-Specific Delivery" J.Med.Chem.40・17. 2755-2761 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Irie: "Pharmaceutical Applications of Cyclodextrins.III : Toxicological Issues and Safety Evaluation" J.Pharm,Sci.86・2. 147-162 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Uekama: "Cyclodextrin Drug Carrier Systems" Chem.Rev.98・5. 2045-2076 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Minami: "Colon-specific Drug Delivery Based on a Cyclodextrin Prodrug : Release Behavior of Biphenylylacetic Acid from Its Cyclodextrin Conjugates in Rat Intestinal Tracts after Oral Administration" J.Pharm.Sci.87・6. 715-720 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Miyake: "Solubility and Mass and Nuclear Magnetic Resonance Spectroscopic Studies on Interaction of Cyclosporin A with Dimethyl-α- and β-Cyclodextrins in Aqueous Solution" J.Pharm.Sci.88・1. 39-45 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] F.Hirayama: "In-vitro Evaluation of Biphenylyl Acetic Acid-beta-Cyclodextrin Conjugates as Colon-Targeting Prodrug : Drug Release Behavior in Rat Biological Media" J.Pharm.Pharmacol.48 (1). 27-31 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Uekama: "6-O- [(4-Biphenyly) acetyl] -alpha-, -beta-, and -gamma-cyclodextrins and 6-Deoxy-6- [(4-biphenylyl) - acetyl] -amino-alpha-, -beta-, and -gamma-cyclodextrins : Potential Prodrugs for Colon-Specific Delivery" J.Med.Chem.40 (17). 2755-2761 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Irie: "Pharmaceutical Applications of Cyclodextrins. III : Toxicological Issues and Safety Evaluation" J.Pharm.Sci.86 (2). 147-162 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Uekama: "Cyclodextrins Drug Carrier Systems" Chem.Rev.98 (5). 2045-2076 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Minami: "Colon-Specific Drug Delivery Based on a Cyclo-dextrin Prodrug : Release Behavior of Biphenylylacetic Acid from Its Cyclodextrin Conjugates in Rat Intestinal Tracts after Oral Administration" J.Pharm.Sci.87 (6). 715-720 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Miyake: "Solubility and Mass and Nuclear Magnetic Resonance Spectroscopic Studies on Interaction of Cyclosporin A with Dimethyl-alpha- and -beta-cyclodextrins in Aqueous Solution" J.Pharm.Sci.88 (1). 39-45 (1999)

    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 1999-12-08  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi