| Project/Area Number |
19780102
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Food science
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| Research Institution | University of Hyogo |
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Principal Investigator |
NAKAGAWA Kyuya University of Hyogo, 工学研究科, 助教 (90433325)
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| Project Period (FY) |
2007 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥3,790,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥390,000)
Fiscal Year 2009: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2008: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2007: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | 凍結乾燥 / 凍結 / 結晶多形 / 氷結晶 / マンニトール / 超音波 / 乳酸脱水素酵素(LDH) / 結晶多系 / 水結晶 / 乳酸脱水素酵素LDH |
|---|
| Research Abstract |
This research work on optimization of pharmaceutical freeze-drying process was to investigate solid structural properties that form in the cryo-concentrated phase during freezing. The results from mannitol freeze-drying test concluded that the crystalline structures (polymorphs) were heterogeneously distributed in the dried bulk dependent to its freezing condition. When we add a model protein (enzyme, lactic acid dehydrogenase was employed) in the starting formulation, the enzymatic activity in the freeze-dried bulk was also heterogeneously distributed. It was clearly suggested that the activity variances were due to the structural property variances of the lyoprotectant. We thus had an attempt to stabilize the freeze-dried enzyme activity simply by the process operation, that is, freezing process. It was found that the ultrasound device that can control the ice nucleation event was useful to control thermal history of the solution during freezing, and to control the solid structure of crystalline substances. However, it was not so much effective to control the solid structure in the solution with lyoprotectant. Nevertheless, kinetics of the structural change (such as sol-gel transition) of the lyoprotectant was supposed to be a crucial factor to stabilize protein. A substance that exhibits gelling feature was thus employed as a lyoprotectant. As a matter of fact, we found that the cooling protocol and the sol-gel transition kinetics were strongly correlated to the protein activities. These results indicate that the stability (or activity) of freeze-dried protein pharmaceutics is to be controlled simply by thermal protocols that controls structural characteristics of solid substances during freezing.
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