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1992 Fiscal Year Final Research Report Summary

STUDIES ON THE DEVELOPMENT OF VARIOUS TYPES OF DRUG DERIVERY SYSTEM USING CHITIN DERIVATIVES

Research Project

Project/Area Number 02555183
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field 高分子合成
Research InstitutionHokkaido University

Principal Investigator

TOKURA Seiichi  HOKKAIDO UNIV., PROFESSOR, 理学部, 教授 (40000806)

Co-Investigator(Kenkyū-buntansha) SEO Hiroshi  FUJI SPINNING Co.Ltd., RESEARCH DIRECTOR, 商品開発研究所, 主任研究員
MIURA Yoshiaki  HOKKAIDO UNIV., INSTRUCTOR, 理学部, 教務職員 (00240630)
NISHI Norio  HOKKAIDO UNIV., ASSOCIATE PROFESSOR, 理学部, 助教授 (70001857)
SHIGEMASA Yoshihiro  TOTTORI UNIV., PROFESSOR, 工学部, 教授 (00032029)
Project Period (FY) 1990 – 1992
KeywordsCarboxymethyl-chitin / Chitosan beads / Alginate fiber / Sustained release / Drug Derivery System / Bone marrow / Gelation / Polymeric drugs
Research Abstract

The study has been achieved to apply of water-soluble and biodegradable carboxymethyl-chitin(CM-chitin) for the drug derivery system as a drug carrier. The sustained release of drug of prodrug was achieved by the lysozymic hydrolysis of drug carrier in animal body, since CM-chitin tended to adsorb phenyl group drug in the presence of calcium ion and to entrapp the drug or prodrug by the addition of trivalent iron to CM-chitin through the rigid gel formation. A two step hydrolysis was proposed to the controlled release of drug in animal body, when pendant type of polymeric drug was designed by applying peptides as a specific spacer that linkage with drug was able to be hydrolyzed by peptidases. The immunogenicity of each polymeric drug with CM-chitin was also investigated together with metabolic pathway in mice. CM-chitin was found to be accumulated in bone marrow following to the intravenous injection of ^<14>C or FITC labeled CM-chitin derivatives. But accumulations in bone marrow and spleen were found through oral administration. The strong fluorescent was observed both in macrophages and granulocytes, when FITC-labeled CM-chitin was cultured with bone marrow of mouce. Chitosan porous beads were also applied to concentrate the drug and then controlled release of drug was observed through oral administration into rats. A alginate fiber has also been applied to the carrier of peptide drug for oral administration and an effective release of peptide drug was observed.

  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] K.NISHIMURA: "Effect of Chitin Heparinoids on the Activation of Peritoneal Macrophages and on the Production of Monokines in Mice." Mol.Biother.2. 115-120 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.WATANABE: "6-0-carboxymethyl-chitin(CM-chitin)as a drug carrier." Chem.Pharma.Bull.38. 506-509 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J.MURATA: "Inhibition of Tumor Cell Arrest in Lung by Antimetastatic Chitin Heparinoid." Jpn.J.Cancer Res.81. 506-513 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.TOKURA: "Preparation of Alcohol-soluble Chitin Derivatives and Radical Induction by Photo-irradiation." Carbohydr.Polym.13. 363-374 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.SASHIWA: "Lysozyme susceptibility of partially deacetylated chitin." Int.J.Biol.Macromol.12. 295-296 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.TOKURA: "Carboxymethyl-chitin as a drug carrier of sustained release." Carbohydr.Polym.13. 273-281 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] I.SAIKI: "Inhibition by sulphated chitin derivatives of invasion through exta-cellular matrix and enzymatic degradation by metastatic melanoma cells." Cancer Res.50. 3631-3637 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J.MURATA: "Inhibition of Tumor-induced Angiogenesis by sulphated Sulohated Chitin Derivatives." Cancer Res.51. 22-26 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.SASHIWA.: "Distribition of the acetamide group in partially deacetylated chitins." Carbohydr.Res.16. 291-296 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] R.OGAWA: "Preparation of Bacterial Polysacharide of Hybridzed Susceptibility." Sen-i Gakkaishi,. 47. 456-460 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.WATANABE: "Antimetastatic Activity of Neocarzino-statin Incorporated into Controlled Release Gels of CM-chitin." Carbohydr.Polym.17. 29-37 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.TOKURA: "Two-step Hydrolyses of a Polymeric Drug under a Model System." Carbohydr.Polym.19. 185-190 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] R.OGAWA: "Preparation of Bacterial Cellulose Containing N-acetylglucosamine." Carbohydr.Polym.19. 171-178 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Nishimura, S-I.Nishimura, N.Nishi, S.Tokura and I.Azuma: "Effect of Chitin Heparinoids on the Activation of Peritoneal Macrophages and on the Production of Monokines in Mice." Mol. Biother.2. 115-120 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Watanabe, I.Saiki, Y.Uraki, S.Tokura and I.Azuma: "6-O-carboxymethyl-chitin(CM-chitin) as a drug carrier." Chem. Pharma. Bull.38. 506-509 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] J.Murata, I.Saiki, K.Matsuno, S.Tokura and I.Azuma: "Inhibition of Tumor Cell Arrest in Lung by Antimetastatic Chitin Heparinoid." Jpn.J.Cancer Res.81. 506-513 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Tokura, Y.Uraki, K.Ohmiya, A.Tsutsumi and H.Sashiwa: "Preparation of Alcohol-soluble Chitin Derivatives and Radical Induction by Photo-irradiation." Carbohydr. Polym.13. 363-374 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Sashiwa, H.Saimoto, Y.Shigemasa and S.Tokura: "Lysozyme susceptibility of partially deacetylated chitin." Int. J. Biol. Macromol.12. 295-296 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Tokura, S.Baba, Y.Uraki, Y.Miura and O.Hasegawa.: "Carboxymethyl-chitin as a drug carrier of sustained release." Carbohydr. Polym.13. 273-281 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] I.Saiki, J.Murata M.Nakajima, S.Tokura and I.Azuma.: "Inhibition by sulphated chitin derivatives of invasion through extracellular matrix and enzymatic degradation by metastatic melanoma cells." Cancer Res.50. 3631-3637 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] J.Murata, I.Saiki, T.Makabe, Y.Tsuta, S.Tokura and I.Azuma.: "Inhibition of Tumor-induced Angiogenesis by sulphated Sulohated Chitin Derivatives." Cancer Res.51. 22-26 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Sashiwa, H.Saimoto, Y.Shigemasa, R.Ogawa and S.Tokura.: "Distribution of the acetamide group in partially deacetylated chitins." Carbohydr. Res.16. 291-296 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] R.Ogawa, M.Sato Y.Miura, S.Tokura and M.Takai.: "Preparation of Bacterial Polysacharide of Hybridized Susceptibility." Sen-i Gakkaishi. 47. 456-460 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Watanabe, I.Saiki, Y.Matsumoto, I.Azuma, H.Seo: "Antimetastatic Activity of Neocarzinostatin Incorporated into Controlled Release Gels of CM-chitin." Carbohydr. Polym.17. 29-37 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Tokura, Y.Kaneda, Y.Miura and Y.Uraki: "Two-step Hydrolyses of a Polymeric Drug under a Model System." Carbohydr. Polym.19. 185-190 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] R.Ogawa and S.Tokura.: "Preparation of Bacterial Cellulose Containing N-acetylglucosamine." Carbohydr. Polym.19. 171-178 (1992)

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

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Published: 1994-03-24  

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