2000 Fiscal Year Final Research Report Summary
Studies on Binding Mechanism of Hydrophobic Medicine to Hard Tissues
| Project/Area Number |
11672143
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Physical pharmacy
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| Research Institution | The University of Tokushima |
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Principal Investigator |
SHIMABAYASHI Saburo The University of Tokushima, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (20025703)
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| Project Period (FY) |
1999 – 2000
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| Keywords | hydroxyapatite / hydrophobic medicine / hard tissues / surface complex / hemimicelle / admicelle / intermolecular interaction / apatite particle formation / surface modification |
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| Research Abstract |
1. Hydroxyapatite (HAP) is a main inorganic component of mammalian hard tissues, which are a composite of HAP and organic compounds such as proteins and mucopolysaccharides. During this period, we planned to clarify the binding mechanism of hydrophobic medicine to hard tissues.
2. Bovine serum albumin and Na chondroitin-6-sulfate were cooperatively adsorbed on HAP at a neutral pH.This result is suggesting that surface proteins having hydrophobic groups could bind hydrophobic drugs through a hydrophobic interaction even in the presence of other organic compounds on the surface. This fact also suggests that the hard tissues could bind drugs via surface proteins, of which segments are exposed and protruding from the surface.
3. Alkyl phosphate (AP) was adsorbed on the nuclei when the HAP was formed, resulting in decrease in its crystallinity. It was a crystal poison. The adsorption mechanism was of isomorphous substitution between a terminal phosphate group of AP and orthophosphate ion of t
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he HAP.However, the particle formation was accelerated because the fine particle of AP (acid form) or its micelle (ion form) behaved as crystal seeds after capturing Ca2+ from an aqueous phase (i.e., heterogeneous nucleation).
4. HAP was treated with sodium dodecylsulfate (SDS). It was adsorbed by virtue of isomorphous substitution with phosphate ion on the surface as the same manner as that of AP.TritonX and TritonN soluble in water were adsorbed by HAP after the treatment. Water insoluble dye methyl yellow was also adsorbed in the presence of SDS.These results are showing that hydrophobic interaction after the treatment is important for hydrophobic compounds to be adsorbed and/or to bind to the surface of HAP.
5. As mentioned above, hydrophobic interaction plays an important role in binding hydrophobic drugs irrespective of water-soluble or-insoluble to the surface of hard tissues, where proteins cover the crystal surface of biological HAP.Thus, the surface complex and/or surface modification were stressed. Less
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