1986 Fiscal Year Final Research Report Summary
Pharmaceutical Study on Human Serum Albumin as Solubilizer and Stabilizer of Drugs
| Project/Area Number |
59870075
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| Research Category |
Grant-in-Aid for Developmental Scientific Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Physical pharmacy
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| Research Institution | NAGOYA CITY UNIVERSITY |
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Principal Investigator |
IKEDA Ken Nagoya City University, 薬学部, 教授 (50080164)
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| Co-Investigator(Kenkyū-buntansha) |
NAOKO Ohta Nagoya City University, 薬学部, 助手 (50117818)
YUKIHISA Kurono Nagoya City University, 薬学部, 助手 (50080205)
TOSHIHISA Yotsuyanagi Nagoya City University, 薬学部, 助教授 (40080189)
稲葉 光治 小野薬品工業(株), 中央研究所, 製剤研究部門長
INABA Kohji Ono Pharmaceutical Co.
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| Project Period (FY) |
1984 – 1986
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| Keywords | Human Serum Albumin / Solubilizer of Drugs / 薬物の安定化剤 |
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| Research Abstract |
The results of this pharmaceutical studies on human serum albumin (HSA), were published in scientific jounal articles as follows.
(1) Basic studies on esterase-like activity of HSA.
(a) Effects of R-type drug bindings on the reaction of di-p-nitrophenyl adi-pate with HSA : R-type drugs enhance this reaction which proceed by 2 steps presumably with tyrosine residue. (b) Hydrolysis of 2,4-dinitrophenyl diethyl phosphate by HSA : More than two hystidine residue near R-site may be involved, which was assumed from DFP modification. (c) Subdivison of R-type drugs ingibiting the activity towards p-nitrophenyl acetate : Two subdivisions are discriminated by the effect on the gydrolysis of 3,5-di-nitroaspirin and florescence quenching.
(2) Effect of HSA on chemical stability of various drugs.
(a) Hydrolysis of gabexate mesilate by HSA : By kinetic analysis histidine residue was found to be involved as active group. (b) Interaction of thromboxane <A_2> synthetase inhibiters (ONO-1580 and OKY-046) with HSA : Binding sites and para meters of these drugs were determined. (c) pH-Dependent degradation and stabilization of meclofenoxate hydrochloride by HSA : Chemical kinetic scheme was estasblished on the accelration and inhibition of the hydrolysis rate. (d) Photo-stabilization and solubilizastion of aldose reductase inbihitor, ONO-2235, by HSA : HSA solubilizes this drug several ten times and protects photo-instability.
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