製薬企業の新薬開発のなかでのIITの位置づけ、期待する事
|
|
|
- つかさ いちぞの
- 6 years ago
- Views:
Transcription
1 第 2 部 First in human(fih) 試験をめぐる諸問題 企業での FIH 試験導入の考え方 : 日本での規制面 実施施設での問題点 ( 外資の立場から ) ヤンセンファーマ株式会社 坂本倫次 1
2 Disclaimer 本発表は演者の個人的見解を示すものであり 所属する組織の正式な見解ではないことをご留意ください The following comments are my personal opinions only and should not be construed as representing the policies or opinions of Janssen Pharma KK. 2
3 本日の内容 1. 製薬企業の新薬開発の中での FIH 試験の位置付け 2. 日本国内での FIH 試験実施に際して考慮すべき点 ( 外資の立場から ) 3. 日本において FIH 試験を実施するために外資系製薬企業の日本法人がなすべきこと 3
4 4
5 新薬開発の中での FIH POC の位置づけ Oncology 早期臨床開発における日本の 2 つの課題 1. First-in-Human (FIH) 試験の日本脱出 2. Proof-of-Concept (POC) 試験の日本脱出 FIH 試験 POC 試験が日本を脱出するとどうなるか? 1. ドラッグラグ問題 : 最初が遅れれば全てが遅れる 2. デスバレー ( 死の谷 ) 問題 : ベースは日本人研究者が発見したが 5
6 日本国内での FIH 試験実施に際して 考慮すべき点 ( 外資の立場から ) 1. 規制面 FIH 試験実施にあたり非臨床試験データが必要十分として受け入れられること 2. 施設面 施設のインフラ ( 人的支援体制とネットワークを含む ) が FIH 試験実施に対応していること 3. 企業判断面 外資系製薬企業が日本国内において FIH 試験を実施する合理的理由があること 海外本社から 開発リスクを共有する ( 共有できる ) パートナー として認識されていること 6
7 1. 規制面 依然 いくつかの問題は存在するが プロトコール変更 試験デザイン変更が困難 Phase 2 への移行に時間を要する ICH S9 に沿って 抗悪性腫瘍薬の非臨床試験に関するガイドラインについて ( 平成 22 年 6 月 ) 通知 本ガイドラインに沿って非臨床試験を実施することにより 日本での FIH 試験実施に際し 特に大きな障害は無い 7
8 2. 施設面 依然 いくつかの問題は存在するが 日本語の資材 資料が必要 試験デザインに対応した flexibility (PK sampling 体制等 ) IRB 審査 契約に時間を要する 早期 探索的臨床試験拠点整備事業 早期 探索的臨床研究中核病院を中心に FIH 試験実施に必要な基盤インフラが整備されつつある これらの施設の体制確立により 施設面での大きな障害は無くなる ( と期待 ) 今後 日本での FIH 試験実施の原動力として大いに期待される 8
9 3. 企業判断面 外資系製薬企業による日本での FIH 試験実施には 日本企業以上の高いハードルが存在 国内の研究所で創出された化合物や抗体を持つ日本企業さえ 海外でFIH 試験を実施 外資系製薬企業の多くは日本で創薬研究を行っていない 海外本社に対し 日本国内において FIH 試験を実施する合理的理由 をいかに示せるか 開発リスクを共有する ( 共有できる ) パートナー であることをいかに認識させるか 9
10 日本国内での FIH 試験実施に際して考慮 すべき点 ( 外資の立場からのまとめ ) 1. 規制面 ICH S9 ガイドラインにより 特に大きな障害は無い 2. 施設面 施設の基盤インフラ ( 人的支援体制とネットワークを含む ) が整備されつつあり 特に大きな障害は無い 3. 企業判断面 外資系製薬企業の日本法人が日本国内において FIH 試験を実施するに際し 現状 最も高いハードル 日本国内においてFIH 試験を実施する合理的理由 開発リスクを共有する ( 共有できる ) パートナー 10
11 日本において FIH 試験を実施するために 外資系製薬企業の日本法人がなすべきこと (1) 1. Oncology 早期開発 (FIH, POC) に対応した人的 組織的能力の獲得及び向上 開発リスクを共有する ( 共有できる ) パートナー 2. 基礎研究やビジネスの戦略について 海外本社との日常的な情報交換により日本への投資を促す 規制面 施設面でFIH 実施に大きな障害が無い 日本市場が継続的に魅力的なマーケットであり 事業開発投資の価値が他の諸国に比しても高い 具体的なターゲット領域を提示して それに必要なパイプライン誘致または候補開発品を提案 11
12 日本において FIH 試験を実施するために 外資系製薬企業の日本法人がなすべきこと (2) 3. 日本国内において FIH 試験を実施する合理的理由を説明 日本の得意領域 強み 欧米より高い疾患頻度のがん 治療成績が欧米よりも良好ながん 圧倒的多数の基礎研究成果を持つがん バイオマーカーによる POC 獲得 質 付加価値の高さ等 人種差 民族差早期確認の必要性 PK Safety 12
13 1st ステップ : 日本 海外同時並行 FIH 試験の事例 New approach for assessment of potential ethnic differences in parallel phase l/ll studies in the United States and Asia. T. Doi, D. Oh, Y. Bang, S. Y. Rha, H. C. Chung, N. Sakamoto, K. Schlienger, D. A. Bergstrom, W. J. Grossman, A. Ohtsu Background:... Two parallel phase I studies were conducted in Korea/Japan (K/J) and the United States. K/J study has started 3 months after U.S. study. Methods: The phase I designs were essentially identical between the K/J and U.S. studies.... to determine... (MTD) and evaluate safety, efficacy, PK profile, and pharmacodynamics (PD).... K/J study also included a phase II portion in which MTD was tested in an enriched population of gastric carcinoma patients..... On average, enrollment for each dose level cohort was achieved within 2 weeks under effective collaboration and frequent communication with investigators in K/J. Conclusions: Performing an interstudy PK comparison of parallel phase I studies in Asia and the United States may be one option to evaluate the potential for ethnic differences in oncology drug development since PK profile and the other parameters can be compared at each dose level. J Clin Oncol 28:15s, 2010 (suppl; abstr 2549) ASCO 2010 General Poster Session (#2549 ) 13
14 2nd ステップ : 日本での True FIH 試験の事例 A first in human phase I dose escalation study first in class orally available novel, in patients with advanced solid tumors. T. Doi, H. Murakami, K. Wan, M. Miki, H. Kotani, N. Sakamoto, N. Yamamoto, A. Ohtsu Methods: Sequential cohorts of 3 to 6 patients (pts) with progressive advanced or metastatic solid tumors... following a toxicity guided dose escalation design. A total of 17 pts were treated at doses from 20 to 120 mg. Results: Reversible hematotoxicity was the main side effect constituting DLTs observed at 100 mg and 120 mg. Two confirmed PRs were observed in pts with parotid gland carcinoma at 80 mg and small cell lung cancer at 120 mg. Conclusions: Preliminary results from this first in human trial confirm the favorable PK and safety profiles of the potentially first in class Encouraging antitumor efficacy has been observed supporting as a therapeutic target and further clinical development of this compound. J Clin Oncol 29: 2011 (suppl; abstr 3012) ASCO 2011 Poster Discussion Session (#3012) 14
15 外資系日本法人での FIH 試験導入の考え方 Phase I Phase 2 Phase 3 現状 日本人での安全性 忍容性確認 Global Ph 3 とのブリッジング Global Ph 3 への参加 将来像 日本人での安全性 忍容性確認 Global Ph 3 とのブリッジング Global Ph 3 への参加 FIH POC 国際共同治験を主導 Oncology Business in Japan 15
16 Positive Cycle ( 正のスパイラル ) for Oncology Development/Business in the 2 nd largest market in the world 1. 日本市場の魅力度 ポテンシャルをアピール 2. 具体的なターゲット領域を提示しパイプライン誘致または候補開発品を提案 Oncology 早期開発 (FIH, POC) 1. 基礎研究について日常的な情報交換 2. 開発リスクを共有できるパートナーとしての Commitment & Presence Oncology Business in Japan First/Best in Class Oncology 後期開発 ( 国際共同治験を日本が主導 ) 16
17 まとめ 日本において FIH 試験を実施するために外資系製薬企業の日本法人がなすべきこと ( 企業判断面から ) 1. Oncology 早期開発 (FIH, POC) に対応した人的 組織的能力の獲得及び向上 2. 基礎研究やビジネスの戦略について 海外本社との日常的な情報交換による日本への投資促進 3. 日本国内においてFIH 試験を実施する合理的理由を説明 今回 外資の立場から 企業判断面 を中心に取り上げましたが 以下の点も認識しております 規制面 プロトコール変更 試験デザイン変更が困難 Phase 2 への移行に時間を要する 施設面 日本語の資材 資料が必要 試験デザインに対応したflexibility (PK sampling 体制等 ) IRB 審査 契約に時間を要する 17
18 御清聴ありがとうございました 18
1) University Group Diabetes Program: A study of hypoglycemic agents on vascular complica- in patients with adult-onset tions diabetes. I. Design, methods and baseline results. Diabetes 19 (suppl. 2):
A comparison of abdominal versus vaginal hysterectomy for leiomyoma and adenomyosis Kenji ARAHORI, Hisasi KATAYAMA, Suminori NIOKA Department of Obstetrics and Gnecology, National Maizuru Hospital,Kyoto,
大学論集第42号本文.indb
42 2010 2011 3 279 295 COSO 281 COSO 1990 1 internal control 1 19962007, Internal Control Integrated Framework COSO COSO 282 42 2 2) the Committee of Sponsoring Organizations of the Treadway committee
Title 泌尿器科領域に於ける17-Ketosteroidの研究 17-Ketosteroidの臨床的研究 第 III 篇 : 尿 Author(s) 卜部, 敏入 Citation 泌尿器科紀要 (1958), 4(1): 3-31 Issue Date URL
Title 泌尿器科領域に於ける17-Ketosteroidの研究 17-Ketosteroidの臨床的研究 第 III 篇 : 尿 Author(s) 卜部, 敏入 Citation 泌尿器科紀要 (1958), 4(1): 3-31 Issue Date 1958-01 URL http://hdl.handle.net/2433/111559 Right Type Departmental Bulletin
_念3）医療2009_夏.indd
Evaluation of the Social Benefits of the Regional Medical System Based on Land Price Information -A Hedonic Valuation of the Sense of Relief Provided by Health Care Facilities- Takuma Sugahara Ph.D. Abstract
CHEMOTHERAPY JUNE 1993 Table 1. Background of patients in pharmacokinetic study
CHEMOTHERAPY JUNE 1993 Table 1. Background of patients in pharmacokinetic study VOL. 41 S 1 Table 2. Levels (Đg/ml or Đg/g) of S-1006 in serum, bile, and tissue (gallbladder) after oral administration
[001-018]永井(責).indd
![[001-018]永井(責).indd](/thumbs/40/20562853.jpg "[001-018]永井(責).indd")
Beyond the Illusion of The Burmese Harp: A Viewpoint with regard to The Last Frontier in Asia NAGAI Hiroshi Since the end of WWII, the image of Burma Myanmar in Japan has changed several times.- the country
Title 社 会 化 教 育 における 公 民 的 資 質 : 法 教 育 における 憲 法 的 価 値 原 理 ( fulltext ) Author(s) 中 平, 一 義 Citation 学 校 教 育 学 研 究 論 集 (21): 113-126 Issue Date 2010-03 URL http://hdl.handle.net/2309/107543 Publisher 東 京
ABSTRACT The movement to increase the adult literacy rate in Nepal has been growing since democratization in 1990. In recent years, about 300,000 peop
Case Study Adult Literacy Education as an Entry Point for Community Empowerment The Evolution of Self-Help Group Activities in Rural Nepal Chizu SATO Masamine JIMBA, MD, PhD, MPH Izumi MURAKAMI, MPH Massachusetts
52-2.indb
Jpn. J. Health Phys., 52 (2) 55 60 (2017) DOI: 10.5453/jhps.52.55 * 1 * 2 * 2 * 3 * 3 2016 10 28 2017 3 8 Enhancement of Knowledge on Radiation Risk Yukihiko KASAI,* 1 Hiromi KUDO,* 2 Masahiro HOSODA,*
29 28 39 1936 Acquiring technique and forming character in physical education after 1936 Analysis of articles of Kenji Shinozaki FUJIKAWA Kazutoshi The United Graduate School of Education Tokyo Gakugei
Title < 論文 > 公立学校における在日韓国 朝鮮人教育の位置に関する社会学的考察 : 大阪と京都における 民族学級 の事例から Author(s) 金, 兌恩 Citation 京都社会学年報 : KJS = Kyoto journal of so 14: 21-41 Issue Date 2006-12-25 URL http://hdl.handle.net/2433/192679 Right
Jan THE JAPANESE JOURNAL OF ANTIBIOTICS XL-1 Table 1. Outline of administering doses, routes and sampling times *: 4 ml/hr/kg Bacillus subtilis
THE JAPANESE JOURNAL OF ANTIBIOTICS XL-1 Jan. 1987 Jan. 1987 THE JAPANESE JOURNAL OF ANTIBIOTICS XL-1 Table 1. Outline of administering doses, routes and sampling times *: 4 ml/hr/kg Bacillus subtilis
„h‹¤.05.07
Japanese Civilian Control in the Cold War Era Takeo MIYAMOTO In European and American democratic countries, the predominance of politics over military, i.e. civilian control, has been assumed as an axiom.
CHEMOTHERAPY FEB Table 1 Background of volunteers
CHEMOTHERAPY FEB. 1985 Table 1 Background of volunteers Table 3 Reproducibility of saisomicln In the EIA and the RIA Fig.1 Comparison of the EIA with the RIA or bioassay of sisomicin Table 4 Blood levels
中表紙
3 企業での FIH 試験導入の考え方 日本での規制面 実施施設での問題点 November 18, 2011 Shiro Akinaga, Ph.D. Development Division / Kyowa Hakko Kirin Co., Ltd. 1 Hallmarks of Cancer : Next Generation (Cell 144: 646 2011) Imatinib, Gefitinib,
840 Geographical Review of Japan 73A-12 835-854 2000 The Mechanism of Household Reproduction in the Fishing Community on Oro Island Masakazu YAMAUCHI (Graduate Student, Tokyo University) This
Visual Evaluation of Polka-dot Patterns Yoojin LEE and Nobuko NARUSE * Granduate School of Bunka Women's University, and * Faculty of Fashion Science,
Visual Evaluation of Polka-dot Patterns Yoojin LEE and Nobuko NARUSE * Granduate School of Bunka Women's University, and * Faculty of Fashion Science, Bunka Women's University, Shibuya-ku, Tokyo 151-8523
VOL.39 S-3
VOL.39 S-3 CHEMOTHERAPY SEPT.1991 Table 1. Background of characteristics and allocation of 5 healthy male volunteers in a multiple-dose study on panipenem/betamipron Day 1 Fig. 1. Schedule of multiple-dose
Key words : 7432-S, Oral cephem, Urinary tract infection Fig. 1. Chemical structure of 7432-S.
Key words : 7432-S, Oral cephem, Urinary tract infection Fig. 1. Chemical structure of 7432-S. Table 1. Clinical summary of acute uncomplicated cystitis patients treated with 7432-S UTI : Criteria by the
Comparative Study of Media Use Capacity for 8th Grade Students Yoshiro Kawakami Hirohisa Suzuki The world is experiencing a variety of changes resulting from the widespread diffusion of information technology.
VOL. 34 S-2 CHEMOTH8RAPY 913
VOL. 34 S-2 CHEMOTH8RAPY 913 914 CHEMOTHERAPY APR. 1986 Fig. 1 Chemical structure of T-2588 and T-2525 T- 2588 pivaloyloxymethyl (+ )- (6 R, 7 R)-7-[(Z)-2- (2-amino- 4-thiazolyl)-2-methox yiminoacetamido]-3-[(
220 INTERRELATIONSHIPS AMONG TYPE OF REINFORCEMENT, ANXIETY, GSR, AND VERBAL CONDITIONING Koji Tamase Department of Psychology, Nara University of Education, Nara, Japan This investigation examined the
SpecimenOTKozGo indd
TM The Kozuka Gothic TM typeface family is composed of six weights that cover various uses ranging from body text composition to headline compositions. This typeface family is now available in OpenType
〈企業特集：検査機器・試薬・技術の新たな展開〉新規マイコプラズマ抗原検査キット—プロラスト®Myco
New immunochromatographic assay kit for Mycoplasma pneumoniae infection 'PRORAST Myco' Shohei Ohshima, Yasushi Shimada, Atsuko Minagawa, Kazuyuki Sugiyama and Yumiko Hirayama Mycoplasma pneumoniae infection
Kyushu Communication Studies 第２号
Kyushu Communication Studies. 2004. 2:1-11 2004 How College Students Use and Perceive Pictographs in Cell Phone E-mail Messages IGARASHI Noriko (Niigata University of Health and Welfare) ITOI Emi (Bunkyo
No.3 14
Mar.2003 13 1950m 53 (1998 1961 86.5 80 90 30% (1997 ),2001),2001) 1 2 3 4 5 6 No.3 14 Mar.2003 15 No.3 16 Mar.2003 17 No.3 18 Mar.2003 19 20 No.3 Mar.2003 21 -------------------------------------------------------------------------------------------------------------------------
The Journal of the Japan Academy of Nursing Administration and Policies Vol 7, No 2, pp 19 _ 30, 2004 Survey on Counseling Services Performed by Nursi
The Journal of the Japan Academy of Nursing Administration and Policies Vol 7, No 2, pp 19 _ 30, 2004 Survey on Counseling Services Performed by Nursing Professionals for Diabetic Outpatients Not Using
DISTRIBUTION OF NEUROPEPTIDES IN THE INFERIOR NASAL TURBINATE MUCOSA OF PATIENTS WITH ALLERGIC RHINITIS KAZUHIRO YAMAMOTO. M.D. Department of Otolaryngology, School of Medicine, Kitasato University, Sagamihara
46
The Journal of the Japan Academy of Nursing Administration and Policies Vol. 16, No. 1, PP 45-56, 2012 Factors Related to Career Continuation among Nurses Raising Children Mayumi Iwashita 1) Masayo Takada
untitled
1988 2000 2002 2004 2006 2008 IFN Lamivudine Adefovir Entecavir 1 Total number 560 Sex (male/female) 424/136 Age (years)* 38 (15-68) Duration of treatment (weeks)* 26 (1-592) Follow-up time (years) 75(05-21
産業構造におけるスポーツ産業の範囲に関する研究Ⅰ
Abstract This study is emphasizes that the sports industry holds big weight with the economy of our country but tends to be disregarded The study sees it us a peculiar industry which has ports of both
2) Dolphin, A., Jenner, P., Marsden, C,D., Pycock, C. and Tarsy, D. : Pharmacological evidence for cerebral dopamine receptor blockade by metoclopramide in rodents, Psychopharmacologia, 41 : 133, 1975.
05_藤田先生_責
This report shows innovation of competency of our faculty of social welfare. The aim of evaluation competency is improvement in the Social welfare education effects, by understanding of studentʼs development
ON A FEW INFLUENCES OF THE DENTAL CARIES IN THE ELEMENTARY SCHOOL PUPIL BY Teruko KASAKURA, Naonobu IWAI, Sachio TAKADA Department of Hygiene, Nippon Dental College (Director: Prof. T. Niwa) The relationship
16_.....E...._.I.v2006
55 1 18 Bull. Nara Univ. Educ., Vol. 55, No.1 (Cult. & Soc.), 2006 165 2002 * 18 Collaboration Between a School Athletic Club and a Community Sports Club A Case Study of SOLESTRELLA NARA 2002 Rie TAKAMURA
国土技術政策総合研究所 研究資料
ISSN TECHNICAL NOTE of National Institute for Land and Infrastructure Management No256 September 2005 Experimental Study on Seismic Behavior of Seawalls for Controlled Waste Disposal Shingo KANO, Katsuya
駒田朋子.indd
2 2 44 6 6 6 6 2006 p. 5 2009 p. 6 49 12 2006 p. 6 2009 p. 9 2009 p. 6 2006 pp. 12 20 2005 2005 2 3 2005 An Integrated Approach to Intermediate Japanese 13 12 10 2005 8 p. 23 2005 2 50 p. 157 2 3 1 2010
GPGPU
GPGPU 2013 1008 2015 1 23 Abstract In recent years, with the advance of microscope technology, the alive cells have been able to observe. On the other hand, from the standpoint of image processing, the
Table 1. Antibacterial activitiy of grepafloxacin and other antibiotics against clinical isolates
Table 1. Antibacterial activitiy of grepafloxacin and other antibiotics against clinical isolates Table 2-1. Summary of patients treated with grepafloxacin for respiratory infection 1) Out: outpatient,
\ (1963): Recent Trends of Urban Geography in Japan A, A, A, G, 53 93^ 102 Yamaga S, & Y, Masai (1966) : Japanese Urban Geography-General View Japanese Geography 1966; Spec, Publ, No,1 Ass, Jap, Geogrs,
CHEMOTHERAPY Table 1 Urinary excretion of mezlocillin Fig. 4 Urinary excretion of mezlocillin Fig. 3 Blood levels of mezlocillin
CHEMOTHERAPY Fig. 2 Urinary excretion of mezlocillin Fig. 1 Blood levels of mezlocillin CHEMOTHERAPY Table 1 Urinary excretion of mezlocillin Fig. 4 Urinary excretion of mezlocillin Fig. 3 Blood levels
2 94
32 2008 pp. 93 106 1 Received October 30, 2008 The purpose of this study is to examine the effects of aerobics training class on weight loss for female students in HOKURIKU UNIVERSITY. Seventy four female
Title 生活年令による学級の等質化に関する研究 (1) - 生活年令と学業成績について - Author(s) 与那嶺, 松助 ; 東江, 康治 Citation 研究集録 (5): 33-47 Issue Date 1961-12 URL http://hdl.handle.net/20.500.12000/ Rights 46 STUDIES ON HOMOGENEOUS
06’ÓŠ¹/ŒØŒì
FD. FD FD FD FD FD FD / Plan-Do-See FD FD FD FD FD FD FD FD FD FD FD FD FD FD JABEE FD A. C. A B .. AV .. B Communication Space A FD FD ES FD FD The approach of the lesson improvement in Osaka City University
,, 2024 2024 Web ,, ID ID. ID. ID. ID. must ID. ID. . ... BETWEENNo., - ESPNo. Works Impact of the Recruitment System of New Graduates as Temporary Staff on Transition from College to Work Naoyuki
Corrections of the Results of Airborne Monitoring Surveys by MEXT and Ibaraki Prefecture
August 31, 2011 Corrections of the Results of Airborne Monitoring Surveys by MEXT and Ibaraki Prefecture The results of airborne monitoring survey by MEXT and Ibaraki prefecture released on August 30 contained
Sport and the Media: The Close Relationship between Sport and Broadcasting SUDO, Haruo1) Abstract This report tries to demonstrate the relationship be
Sport and the Media: The Close Relationship between Sport and Broadcasting SUDO, Haruo1) Abstract This report tries to demonstrate the relationship between broadcasting and sport (major sport and professional
988 CHEMOTHERAPY NOV. 1971
988 CHEMOTHERAPY NOV. 1971 VOL. 19 NO. 8 CHEMOTHERAPY 989 Effect of medium-ph and inoculum size on activity of SB-PC heart infusion agar, mcg/ml Sensitivity distribution of Staphylococci to SB-PC in surgical
HP HP ELF 7 52
58 2017pp. 51103 J-POSTL t KH Coder KH CoderJ-POSTL 2016 4 2018312 51 58 2016 1 5 2017 112 2017 3 56 4 4 11 2 3 HP 2017 2 5 17 5 18 20 3 5 18 5 19 5 20 5 7 HP 4 3 222 25 116 12 2 ELF 7 52 2017 12 2 12
ユーザーズマニュアル
1 2 3 4 This product (including software) is designed under Japanese domestic specifications and does not conform to overseas standards. NEC *1 will not be held responsible for any consequences resulting
浜松医科大学紀要
On the Statistical Bias Found in the Horse Racing Data (1) Akio NODA Mathematics Abstract: The purpose of the present paper is to report what type of statistical bias the author has found in the horse
11モーゲージカンパニー研究論文.PDF
2003 Outline of the Study 1. Purpose Housing finance in Japan is now at a turning point because the Government Housing Loan Corporation (the HLC) is scheduled to become an independent administrative
NP-DB NP-DB10 0570-011874 This appliance was designed for use in Japan only where the local voltage supply is AC100V and should not be used in other countries where the voltage and frequency
07_伊藤由香_様.indd
A 1 A A 4 1 85 14 A 2 2006 A B 2 A 3 4 86 3 4 2 1 87 14 1 1 A 2010 2010 3 5 2 1 15 1 15 20 2010 88 2 3 5 2 1 2010 14 2011 15 4 1 3 1 3 15 3 16 3 1 6 COP10 89 14 4 1 7 1 2 3 4 5 1 2 3 3 5 90 4 1 3 300 5
CHEMOTHERAPY Fig. 1 Chemical structure of CXM-AX
Fig. 1 Chemical structure of CXM-AX NOV. 1986 Fig. 2 Sensitivity distribution of clinical isolates organisms (106 cells/ml) a Smurcus 27 strains d) P.m irabilis 15 strains b Ecol i 27 strains 111.morganii
, PDD ASD p.,.,..,..,.,..,.,..,.,.,.,, 146
Study on the System of the Chinese Autistic in Japan Xiaotong Ro abstract This study note is mainly introduced the research of China s autistic child treatment in Japan. There is not very much research
Web Stamps 96 KJ Stamps Web Vol 8, No 1, 2004
The Journal of the Japan Academy of Nursing Administration and Policies Vol 8, No 1, pp 43 _ 57, 2004 The Literature Review of the Japanese Nurses Job Satisfaction Research Which the Stamps-Ozaki Scale
109 Summary The purpose of this paper is to make clear two points. The first one is the history of understandings of the environmental benefits from agriculture in Japan. In 1971 the first comment on the
2 The Bulletin of Meiji University of Integrative Medicine 3, Yamashita 10 11
1-122013 1 2 1 2 20 2,000 2009 12 1 2 1,362 68.1 2009 1 1 9.5 1 2.2 3.6 0.82.9 1.0 0.2 2 4 3 1 2 4 3 Key words acupuncture and moxibustion Treatment with acupuncture, moxibustion and Anma-Massage-Shiatsu
Postoperative Assessment by Using a Torque Machine (BIODEX) and MRIs in Patients treated for a Recurrent Anterior Dislocation or Subluxation of the Sh
Postoperative Assessment by Using a Torque Machine (BIODEX) and MRIs in Patients treated for a Recurrent Anterior Dislocation or Subluxation of the Shoulder by HATA Yukihiko MURAKAMI Narumichi Department
<95DB8C9288E397C389C88A E696E6462>
2011 Vol.60 No.4 p.332 338 Usefulness of regional education program for dietary salt reduction: Self-monitoring of urinary salt excretion Kenichiro YASUTAKE[1] Kayoko SAWANO[1] Shoko YAMAGUCHI[1] Hiroko
Motivation and Purpose There is no definition about whether seatbelt anchorage should be fixed or not. We tested the same test conditions except for t
Review of Seatbelt Anchorage and Dimensions of Test Bench Seat Cushion JASIC Motivation and Purpose There is no definition about whether seatbelt anchorage should be fixed or not. We tested the same test
II
No. 19 January 19 2013 19 Regionalism at the 19 th National Assembly Elections Focusing on the Yeongnam and Honam Region Yasurou Mori As the biggest issue of contemporary politics at South Korea, there
[142-160]大野
![[142-160]大野](/thumbs/40/20601947.jpg "[142-160]大野")
Eugene O Neill, ~ Long Day s Journey into NightJourney A Moon for the Misbegotten Moon James O Neill Jr. Journey Journey Journey John Henry Raleigh O Neill s Long Day s Journey into Night and New Irish-Catholicism
2002 31 3 4 5 6 10 12 15 1 18 19 20 1
2002 31 3 4 5 6 10 12 15 1 18 19 20 1 2002 31 2 21 NATO 22 NATO 23 1 24 25 26 27 2 Soviet Industrial Location: A Reexamination 28 29 Department of History and Classics, University of Alberta 30 31 2 2002
2 146
28 2004 pp. 145 159 1 Received October 29, 2004 In 1999, North Korea reversed the negative economic growth of the 90s, and displayed a positive trend which, although weak, was maintained at 1.8% in 2003.
VOL.42 S-1
CHEMOTHERAPY APR. 1994 VOL.42 S-1 CHEMOTHERAPY APR. 1994 Table 1. Criteria for evaluation of clinical efficacy by the Japanese Society of Oral and Maxillo-Facial Surgeons Grades of symptoms and numerical
untitled
Ministry of Land, Infrastructure, Transport and Tourism IATA 996 9 96 96 1180 11 11 80 80 27231 27 27231 231 H19.12.5 10 200612 20076 200710 20076 20086 11 20061192008630 12 20088 20045 13 113 20084
日本職業・災害医学会会誌第51巻第1号
内野ら 下腿骨骨折におけるハイブリッド創外固定器の有用性 31 図 2 軟部組織損傷程度と機能成績 Gustilo IIIB 以上の開放骨折では Gustilo IIIA 以下の開放骨折 及び皮下骨折よりも明らかに機能低下が認められた 図 1 年齢と機能成績 60 歳未満の若年者の方が明らかに良好な成績を示した a b c 図 3 a Gustilo Type IIIB b, c AO 分類 Type
Studies of Foot Form for Footwear Design (Part 9) : Characteristics of the Foot Form of Young and Elder Women Based on their Sizes of Ball Joint Girth
Studies of Foot Form for Footwear Design (Part 9) : Characteristics of the Foot Form of Young and Elder Women Based on their Sizes of Ball Joint Girth and Foot Breadth Akiko Yamamoto Fukuoka Women's University,
29 jjencode JavaScript
Kochi University of Technology Aca Title jjencode で難読化された JavaScript の検知 Author(s) 中村, 弘亮 Citation Date of 2018-03 issue URL http://hdl.handle.net/10173/1975 Rights Text version author Kochi, JAPAN http://kutarr.lib.kochi-tech.ac.jp/dspa