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1 Proteomic analysis of pathogenic alteration (Sho, 証 ) diagnosed by Kampo medicine and establishment of tailor-made treatment Institute of Natural Medicine, University of Toyama, and The 21 st Century COE Program Ikuo SAIKI, Director & Professor
2 西 洋 医 学 的 病 態 分 類 Pathogenic recognition by western/modern medicine 証 診 断 病 名 診 断 Disease diagnosis 東 洋 医 学 的 病 態 分 類 Pathogenic recognition by Kampo medicine Sho diagnosis 気 虚 (Ki-kyo) 瘀 血 (Oketsu) 水 滞 (Suitai) 糖 尿 病 性 網 膜 症 (Diabetic retinopathy) (Rheumatoid arthritis) 関 節 リ ウ マ チ (Atopic dermatitis) ア ト ピ ー 性 皮 膚 炎 (Menopausal syndrome) 更 年 期 障 害 Pathogenic recognition in Kampo medicine ( 漢 方 医 学 ), is based on the diagnosis of individual pathogenic alteration, so called Sho ( 証 ), consisting of symptom and constitution (responder/non-responder) of patients with different disease states. 2
3 Disease diagnosis Sho diagnosis Western medicine Proteomic pattern analysis by Protein Chip Array System (SELDI-TOF/MS) Eastern medicine (Kampo) Kampo medical doctors have specialized knowledge and experiences for Sho 証 diagnosis, and then determine appropriate Kampo formulations. However, it is difficult for western medical doctors to perform Sho diagnosis and to determine Kampo formulations. If holistic patterns of Sho 証, which are associated with determination of Kampo formulations, are investigated by proteomic analysis using plasma of patients with different disease states, general medical doctors can easily understand and use Kampo medicines for patients. 3
4 Proteomic analysis of Sho of rheumatoid arthritis patients with or without oketsu (blood stagnant) according to diagnosis by Western medicine and Kampo medicine Diagnosis by Western medicine: Rheumatoid arthritis (ACR core set) by Kampo medicine: Oketsu, i.e. blood stagnant syndrome (Oketsu score) Kampo medicine: keishibukuryogan (pills) Toyama Prefectural Central Hospital weeks Keishibukuryogan 桂 枝 茯 苓 丸 16 RA patients Oketsu score Proteomic analysis Oketsu score Proteomic analysis Oketsu score Proteomic analysis Respondesr/non-responder (ACR20) multiple biomarkers Data Mining Databse phenomic fingerprints 4
5 陰 イオン 交 換 陽 イオン 交 換 金 属 イオン 順 相 疎 水 性 Biomek 2000 Protein chip system SELDI-TOF/MS 5
6 桂 枝 茯 苓 丸 Keishibukuryogan (KBG) Cinnamomi Cortex 桂 枝 Paeoniae radix 芍 薬 Persicae semen 桃 仁 Hoelen 茯 苓 Moutan cortex 牡 丹 皮 Keisibukuryogan 桂 枝 茯 苓 丸 体 力 中 等 度 もしくはそれ 以 上 の 人 で の ぼせて 赤 ら 顔 のことが 多 く 下 腹 部 に 抵 抗 圧 痛 を 訴 える 場 合 に 用 いる お 血 に 伴 う 諸 症 状 に 用 いる 3D-HPLC profile 6
7 Hierarchical cluster analysis of ProteinChip Array results for the expression profiles of plasma proteins in rheumatoid arthritis patients with or without Oketsu ( 瘀 血 ) Oketsu vs Non-Oketsu ( 瘀 血 vs 非 瘀 血 ) (266 peaks) Clustering of plasma samples Oketsu ( 瘀 血 ) score 20~30 30 < Clustering of significant peak intensity 1 0 Average 7
8 Classification of rheumatoid arthritis patients with or without Oketsu ( 瘀 血 ) treated with Keishi-bukuryo-gan ( 桂 枝 茯 苓 丸 ), by expression of peak A, B or C obtained from Protein Chip Array System A B C 関 節 リウマチ Peak_A Oketsu/Non-oketsu Cassification Peak_B Peak_C Oketsu 瘀 血 Non-oketsu 非 瘀 血 Oketsu 瘀 血 Non-oketsu 非 瘀 血 Oketsu 瘀 血 Non-oketsu 非 瘀 血 8
9 Classification of rheumatoid arthritis patients with or without Oketsu ( 瘀 血 ) by expression of peak A, B and C obtained from Protein Chip Array System Oketsu-improving Kampo medicine: Keishi-bukuryo-gan Peak_C C 於 血 非 瘀 血 Oketsu Non-oketsu Peak_A A Peak_B B 9
10 Classification of rheumatoid arthritis patients with or without Oketsu ( 瘀 血 ) treated with Keishi-bukuryo-gan ( 桂 枝 茯 苓 丸 ), by expression of peak A and B obtained from Protein Chip Array System A Peak A Improvement of Oketsu ( 瘀 血 改 善 例 ) Oketsu Non-improve Oketsu Improve Non-oketsu Peak B Improvement of Rheumatoid arthritis (リウマチ 有 効 vs 無 効 ) 45 Improve 40 Non-improve B 10
11 Acknowledgements I thank all the members in the projects for the promotion of collaborative works Division of Pathogenic Biochemistry, Institute Natural Medicine, University of Toyama 富 山 大 学 和 漢 医 薬 学 総 合 研 究 所 病 態 生 化 学 分 野 済 木 育 夫 桜 井 宏 明 小 泉 桂 一 木 我 千 鶴 ( 富 山 県 新 世 紀 産 業 派 遣 研 究 員 ) Department of Kampo Diagnostics, Institute Natural Medicine, University of Toyama 富 山 大 学 和 漢 医 薬 学 総 合 研 究 所 漢 方 診 断 学 部 門 柴 原 直 利 酒 井 伸 也 中 川 孝 子 Dept. of Japanese Oriental Medicine, Faculty of Medicine, University of Toyama 富 山 大 学 大 学 院 医 学 薬 学 研 究 部 和 漢 診 療 学 嶋 田 豊 後 藤 博 三 引 網 宏 彰 Dept. of Gynecology, Faculty of Medicine, University of Toyama 富 山 大 学 大 学 院 医 学 薬 学 研 究 部 和 漢 診 療 学 齋 藤 滋 日 高 隆 雄 柳 楽 清 文 Toyama Prefectural Central Hospital 富 山 県 立 中 央 病 院 高 橋 宏 三 Medical Evaluation Laboratory, Research Division, Tsumura and Co. 株 式 会 社 ツムラ 山 本 雅 浩 小 川 和 生 松 本 千 波 小 嶋 徹 子 鈴 木 祥 子 Bioinformatics Division, INTEC Web and Genome Informatics Corporation インテック ウェフ アント ケ ノム インフォマティクス 株 式 会 社 村 元 浩 柴 垣 ゆかり 尾 山 卓 也 亀 谷 聡 Toyama New Industry Organization 富 山 新 世 紀 産 業 機 構 木 我 千 鶴 11
12 Toyama o Toyama Prefecture Toyama Bay Osaka Tokyo Toyama Castle Toyama Bay University of Toyama (Sugitani campus) Tateyama Mountain WAKAN-YAKU Toyama-original Natural Medicine
13 University of Toyama (Two Universities and one college were unified at October 1, 2005) Toyama Medical and Pharmaceutical University Toyama University Takaoka National College Sugitani campus Gofuku campus Takaoka campus Faculty of Medicine University Hospital University of Toyama (Sugitani campus) Faculty of Pharmaceutical Science Institute of Natural Medicine Scientific research of traditional medicines from China and Japan, and other traditional medical treatments from all over the world in cooperation with domestic and international scientists 13
14 Administrative organization In Toyama prefecture, public institutions are making efforts to improve their research and development system. Toyama prefecture has the only prefectural pharmaceutical research institute and prefectural medicinal plants research center in Japan. Institute for Pharmaceutical Research Center for Medical Plants Invited Dr. Kiyoshi TAKATSU as a Director of this institute in April, 2007, who is very famous worldwide in immunology field as the first discoverer of interleukin-5. Grow and disseminate the plants for pharmaceutical materials, establish growing techniques, educate, and expand knowledge of medical plants. 14
15 Characteristics of the Pharmaceutical Industry in Toyama 1 Accumulation of manufacturers of various kinds of medicines About 100 plants for developing new medicines, specialized agents, generics, self-medication products 2 Development of allied and support industry Adequate industry of containers & package printing 3 Leading mfg. techniques & GMP promotion Latest mfg. facilities & high technology Toward building a Major Production Center for Pharmaceutical Industry Investment in plant & equipment (recent 5 yrs.) 600 million $
16 Thank you for your attention! Acknowledgment 16
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