1992 Fiscal Year Final Research Report Summary
Studies on the Physiological Activities of Novel Vitamin D_3 Derivatives
| Project/Area Number |
02671024
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | Kobe Women's College of Pharmacy |
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Principal Investigator |
KOBAYASHI T Kobe Women's College of Pharmacy Professor, 薬学部, 教授 (40068325)
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| 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)
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| Project Period (FY) |
1990 – 1992
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| Keywords | Active Vitamin D_3 / Calcium / Osteporosis / Vitamin D Binding Protein / Differentiation / Immune Regulating Activity / Parathyroid / Receptor |
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| 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.
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