2.Drug Supply and Formulation (1)Prior to entering clinical trials,adequate drug supplies of pharmaceutical-grade material must be available. (2)Bulk chemical synthesis protocols, natural product isolation, adequate amounts of raw materials for drug or its synthetic precursors. 2019/8/28 Institute of clinical pharmacology,AHMU 16
2.Drug Supply and Formulation (1) Prior to entering clinical trials, adequate drug supplies of pharmaceutical-grade material must be available. (2) Bulk chemical synthesis protocols, natural product isolation, adequate amounts of raw materials for drug or its synthetic 2019/8/28 Institute of clinical pharmacology, AHMU 16 precursors
Pay attention to: Manufacturing of pharmaceutical products must be conducted under current Good Manufacturing Practice (cGMP) guidelines,which was defined by FDA. NMho心ts Aasocintion Good Manufacturing Practices Certification Ayyind fe Sirio Pharma Co.,Ltd. " Ag420.内29日 年444卡 ( 6刊d Good Manufacturing Practice workshop for biological agents 2019/8/28 Institute of clinical pharmacology,AHMU 17
Pay attention to: Manufacturing of pharmaceutical products must be conducted under current Good Manufacturing Practice (cGMP) guidelines, which was defined by FDA . 2019/8/28 Institute of clinical pharmacology, AHMU 17 Good Manufacturing Practice workshop for biological agents
3.In Vivo Studies-Preclinical Pharmacodynamic in Animal Models (1)The adequacy of any specific animal model depends on its validity, selectivity,predictability,and reproducibility. (2)Mouse and rat model systems have several advantages over the use of higher mammals for investigating mammalian biology and disease states. 1 BCG YACCINE (FREEZE-DRIED Bacillus Calmette Guerin (BCG)vaccine CIA mice model Rat with AA 2019/8/28 Institute of clinical pharmacology,AHMU 18
3.In Vivo Studies —Preclinical Pharmacodynamic in Animal Models (1) The adequacy of any specific animal model depends on its validity, selectivity, predictability, and reproducibility. (2) Mouse and rat model systems have several advantages over the use of higher mammals for investigating mammalian biology and disease states. 2019/8/28 Institute of clinical pharmacology, AHMU 18 CIA mice model Rat with AA Bacillus Calmette Guerin (BCG) vaccine
TNF-alpha L.1 Pae hyperplastic synovium, AI pannus, cartilage CIA erosion PGE 2 Paws swelling inhibit Pae significantly suppressed inflammatory response and pro-inflammatory mediator (IL-1, TNF-alpha and PGE2)production by synoviocytes in collagen induced arthritis(CIA )rats. 2019/8/28 Institute of clinical pharmacology,AHMU 19
TNF- alpha hyperplastic synovium, pannus, cartilage CIA erosion AI Pae IL-1 2019/8/28 Institute of clinical pharmacology, AHMU 19 Paws swelling PGE 2 Pae significantly suppressed inflammatory response and pro-inflammatory mediator (IL-1, TNF- alpha and PGE2) production by synoviocytes in collagen induced arthritis (CIA )rats. inhibit
Ras↑ Gi Pae Raf FLS of CIA p-MEK1/2 cAMP PKA p-ERK1/2 Phosphorylated active 4… inhibit Pae regulates G proteins-AC-cAMP signaling and Ras-MAPKs signaling: FLS,fibroblast like synoviocytes 2019/8/28 Institute of clinical pharmacology,AHMU
Ras p- MEK1/2 Raf FLS of CIA Gi Pae cAMP AC 2019/8/28 Institute of clinical pharmacology, AHMU 20 p- ERK1/2 inhibit active Pae regulates G proteins- AC -cAMP signaling and Ras-MAPKs signaling； FLS, fibroblast like synoviocytes PKA Phosphorylated