| Project/Area Number |
10672165
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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 |
応用薬理学・医療系薬学
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| Research Institution | Setsunan University |
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Principal Investigator |
YAMASHITA Shinji Setsunan University, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (00158156)
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| Co-Investigator(Kenkyū-buntansha) |
SAKANE Toshiyasu Setsunan University, Faculty of Pharmaceutical Sciences, Assistant Professor, 薬学部, 講師 (50215638)
KOHNO Takeyuki Setsunan University, Faculty of Pharmaceutical Sciences, Assistant Professor, 薬学部, 講師 (50178224)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Systemic Immune Response / Oral Tolerance / Protein Drugs / IgG Antibody / Drug Disposition / 経口免疫寛溶 |
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| Research Abstract |
In this study, we have proposed a new strategy to solve the immunological problems of protein drugs by induction of oral tolerance. By using ovalbumin (OVA) as a model protein drug, it was clearly demonstrated that, after repeating intraveneous administration, systemic immune response profoundly affects the pharmacokinetic aspects of proteins. Oral pre-ingestion of OVA perfectly suppressed the immune response of OVA by inducing oral tolerance, suggesting the possibility to overcome the immunological problems of protein drugs. The potency of oral tolerance to suppress the systemic immune response was compared with that of cyclosporin A (CsA), immune suppressive drug. Both oral tolerance and CsA effectively suppressed the immune response where the plasma concentration pattern of OVA was almost the same with those in control experiments, although anti-OVA IgG levels in CsA treated rats were apparently elevated. Further studies were carried out with the bioactive proteins such as insulin. Again, the pharmacological effect of insulin declined after the repeated administration of it. The induction of oral tolerance by oral preingestion of insulin significantly improved the pharmacological effect of it. In conclusion, we have demonstrated the usefulness of our strategy to overcome the immunological problems of protein drugs. This strategy is expected to be used in the clinical stage for the efficient and safe therapy with the protein drugs.
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