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Studies on the Physiological Activities of Novel Vitamin D_3 Derivatives

Research Project

Project/Area Number 02671024
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionKobe Women's College of Pharmacy

Principal Investigator

KOBAYASHI T  Kobe Women's College of Pharmacy Professor, 薬学部, 教授 (40068325)

Co-Investigator(Kenkyū-buntansha) TAKEUCHI A  Kobe Women's College of Assistant, 薬学部, 講師 (80154970)
MASUDA S  Kobe Women's College of Assistant Professor, 薬学部, 講師 (90157206)
OKANO T  Kobe Women's College of Associate Professor, 薬学部, 助教授 (20131542)
TSUGAWA N  Kobe Women's College of Assistant (30207352)
Project Period (FY) 1990 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1992: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1991: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1990: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsActive Vitamin D_3 / Calcium / Osteporosis / Vitamin D Binding Protein / Differentiation / Immune Regulating Activity / Parathyroid / Receptor / 活性型ビタミンD_3 / ビタミンD_3 / 活性型ビタミンD_3誘導体 / レセプタ- / ビタミンD結果蛋白質
Research Abstract

We have synthesized the two novel vitamin D_3 derivatives, 22-oxa-1,25-dihydroxyvitamin D_3 (oxacalcitriol : OCT) and 2beta-hydroxypropoxy-1,25-dihydroxy-vitamin D_3 (Hydroxypropoxycalcitriol : HCT), and studied their physiological activities. The results are summarized in the following ;
.Although OCT behaved similar to 1,25-dihydroxyvitamin D_3 (1,25-D_3) in the in vitro bone resorption, it did not give response in the in vivo calcemic activities which were different from 1,25-D_3. Since OCT shows similar activity to 1,25-D_3 in inducing differentiation of leukemia cells to normal macrophage cells, it is a promising candidate for treatment of leukemia and other calcinogenic diseases without causing hypercalcemia.
2.We have established a method for the determination of HCT in plasma and found that the half-life of HCT in blood is longer than that of 1,25-D_3 because of stronger vinding to plasma vitamin D binding protein than 1,25-D_3. We have also studied the preventive and therapeutic effects on bone mineral loss in ovariectomized rats and showed that HCT improved bone mineral density and mechanical bone strength in the pre-osteoporosis and osteoprosis model rats made by ovariectomy more effectively than 1,25-D_3. The results suggest that HCT is a promising candidate for treatment of osteoporosis.

Report

(4 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • 1990 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] 岡野 登志夫: "Regulatory activity of 2β-(hydroxypropoxy)-1α,25-dihydroxyvitamin D3, a novel synthetic vitamin D3 derivative, on calcium metabolism" Biochem.Biophys.Res.Commun.163. 1444-1449 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 岡野 登志夫: "Protein-binding properties of 22-oxa-1α,25-di-hydroxyvitamin D3, a synthetic analogue of 1α,25-dihydroxyvitamin D3" J.Nutr.Sci.Vitaminol.35. 529-533 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 岡野 登志夫: "A novel synthetic vitamin D3 Analogue,2-beta-(3-hydroxypropoxy)-calcitriol:Its biological activities and pharmacological effects on calcium metabolism" Contribution to Nephrology. 91. 116-122 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 小林 正: "Metabolism and transporting system of 22-oxacalci-triol" Contribution to Nephrology. 91. 129-133 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 西井 易穂: "Characteristic of two novel analogues;22-oxa-1α,25-dihydroxyvitamin D3 (OCT) and 2β-(hydroxypropoxy)-1α,25-dihydroxyvitamin D3 (ED-71)" Vitamin D Gene Reguration, Structure-Function Analysis and Clinical Application. 289-297 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 小林 正: "2β-(3-Hydroxypropoxy)-1α,25-dihydroxyvitamin D3 (ED-71), preventive and therapeutic effects on bone mineral loss in ovariectomized rats" Bioorganic and Medical Chemistry Letters.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Toshio Okano: "Regulatory activities of 2beta- (3-hydroxypropoxy)-1 ,25-di-hydroxyvitamin D_3 derivative, on calcium metabolism" Biochem.Biophys.Res. Commun. Vol.163. 1444-1449 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Toshio Okano: "Protein-binding Properties of 22-oxa-1alpha, 25-dihydroxyvitamin D_3, a synthetic analogue of 1alpha, 25- dihydroxyvitamin D_3" J.Nutr.Sci.Vitaminol. Vol.35. 529-533 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Toshio Okano: "A novel synthetic vitamin D_3 analogue, 2-beta-(3-hydroxy-propoxy)-calcitriol (ED-71) : Its biological activities and pharmacological effects on calcium meta bolism" Contribution to Nephrology. Vol.91. 116-122 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Tadashi Kobayashi: "Metabolism and transporting system of 22-oxacalcitriol" Contribution to Nephrology. Vol.91. 129-133 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yasuho Nishii: "Characteristic of two novel vitamin D_3 analogues ; 22-oxa- 1alpha, 25-dihydroxyvitamin D_3 (OCT) and 2beta-(3-hydroxypropoxy)-1 , 25-dihydroxyvitamin D_3 (ED-71)" Vitamin D Gene Regulation, Structure-Function Analysis and Clinical Application. 289-297 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 岡野 登志夫: "A novel synthetic vitamin D_3 Analogue,2-beta-(3-hydroxypropoxy)-calcitriol(ED-71):Its biological activitiess and pharmacolkogical effects on calcium metabolism" Contribution to Nephrology. 91. 116-122 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] 小林 正: "Metabolism and transporting system of 22-oxacalcitriol" Contribution to Nephrology. 91. 129-133 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] 津川 尚子: "Metabolism of orally administered ergosterol and 7-dehydro-cholesterol in rats and lack of evidence for their vitamin D biological activity" J.Nutr.Sci.Vitaminol.38. 15-25 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 増田 園子: "A method for the simultaneous determination of vitamin D_2,D_3 and thier metabolitess in plassma and its application to plasma sampless obtained from normal subjects and patients" Food Chemistry. 45. 215-225 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 小林 正: "2β-(3-Hydroxypropoxy)-1α,25-dihydroxyvitamin D_3(ED-71),preventive and therapeutic effects on bone mineral loss in ovariectomized rats" Bioorganic and Medical Chemistry Letters.

    • Related Report
      1992 Annual Research Report
  • [Publications] 小林 正: "Transporting systems and tissue distribution of 22-oxa-1α,25-dihydroxyvitamin D_3,a noncalcemic analogue of 1α,25-dihydroxyvitamin D_3,in rats" European J. Biochemistry.

    • Related Report
      1992 Annual Research Report
  • [Publications] 岡野 登志夫: "Regulatory Activities of 2βー(3ーHydroxypropoxy)ー1α,25ーdihydroxyvitamin D_3,a Novel Synthetic Vitamin D Derivative,on Calcium Metabolism" Biochem.Biophys.Res.Commun.163. 1444-1449 (1989)

    • Related Report
      1991 Annual Research Report
  • [Publications] 岡野 登志夫: "Plansma Binding Properties of 22ーOxaー1α,25ーdihydroxyーvitamin D_3,a Sythetic Analogue of 1α,25ーDihydroxyーvitamin D_3" J.Nutr.Sci.Vitaminol.35. 529-533 (1989)

    • Related Report
      1991 Annual Research Report
  • [Publications] 岡野 登志夫: "A Novel Synthetic Vitamin D_3 Analogue,2ーBetaー(3ーHydroxypropoxy)ーCalcitriol(EDー71):Its Biological Activities and Pharmacological Effects on Calcium Metabolism" Contributions to Nephrology.Calcium Regulating Hormones II.Calcium Transport,Bone Metabolism and New Drugs(Karger,Basel). 91. 116-122 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 小林 正: "Metabolism and Transporting System of 22ーOxacalcitriol" Contribution to Nephrology.Calcium Regulating Hormones II.Calcium Transport,Bone Metabolism and New Drugs(Karger,Basel). 91. 129-133 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 津川 尚子: "A Novel Vitamin D_3 Analogue,22ーOxacalcitriol(OCT):Its Differnt Behaviours from Calcitriol in Plasma Transport System" Vitamin D,Gene Regulation,StructureーFunction Analysis and Clinical Application(Proceedings of the 8th Workshop on Vitamin D,Paris,1991). 312-313 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 小林 正: "Transporting System and Tissue Distribution of 22ーOxaー1,25ーdihydroxyvitamin D_3,a Noncalcemic Analogue of 1,25ーDihydroxyvitamin D_3,in Rats" Eur.J.Biochem.

    • Related Report
      1991 Annual Research Report
  • [Publications] 岡野 登志夫: "Regulatory activities of 2βー(3ーhydroxypropoxy)ー1α,25ーdihydroxyvitamin D_3,a novel synthetic vitamin D derivative,on calcium metabolism." Biochem.Biophys.Res.Commun.163. 1444-1449 (1989)

    • Related Report
      1990 Annual Research Report
  • [Publications] 岡野 登志夫: "Plasma binding properties of 22ーoxaー1α,25ーdihydroxyーvitamin D_3,a synthetic analogue of 1α,25ーdihydroxyーvitamin D_3." J.Nutr.Sci.Vitaminol.35. 529-533 (1989)

    • Related Report
      1990 Annual Research Report
  • [Publications] 岡野 登志夫: "Transporting system in blood and tissue distribution of 22ーoxaー1α,25ーdihydroxyvitamin D_3,a noncalcemic analogue of 1α,25ーdihydroxyvitamin D_3,in rats." Endocrinology.

    • Related Report
      1990 Annual Research Report
  • [Publications] 岡野 登志夫: "A novel vitamin D analog [2βー(3ーhydroxypropoxy)ー1α,25ーdihydroxyvitamin D_3],Calcium regulatory activity,protein binding capacity and half life in plasma." J.Nutr.Sci.Vitaminol.

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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