JP2007514771A - 糖尿病を治療するための組成物および方法 - Google Patents
糖尿病を治療するための組成物および方法 Download PDFInfo
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- JP2007514771A JP2007514771A JP2006545568A JP2006545568A JP2007514771A JP 2007514771 A JP2007514771 A JP 2007514771A JP 2006545568 A JP2006545568 A JP 2006545568A JP 2006545568 A JP2006545568 A JP 2006545568A JP 2007514771 A JP2007514771 A JP 2007514771A
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- cysteamine
- diabetes
- additional therapeutic
- compound
- insulin
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Abstract
Description
本出願は、2003年12月19日に出願された米国特許仮出願第60/531,119号、および2004年7月27日に出願された米国特許仮出願第60/591,709号の恩典を主張する。
糖尿病は、治癒されない慢性疾患である。現在、約1820万人、または米国において人口の6.3%が糖尿病を有している。およそ1300万人は診断されている一方、520万人は、疾患を有していることに気づいていないと推定される。2000年の疾患による死亡の6番目の主要原因として、糖尿病は、米国の医療機関に毎年推定1320億ト゛ルの費用を課している。National Diabetes Information Clearinghouse, NIH出版 No. 04-3892, November 2003。糖尿病に関連した経済的費用より深刻であるのは、糖尿病に関連した生活の質の低下、健康に関わる重篤な合併症/予後、および死亡である。
本発明は、糖尿病を治療するために用いられる通常の物質にしばしば関連する多くの望ましくない副作用を改善しながら糖尿病を治療するための組成物および方法を提供する。好ましい態様において、本発明は、糖尿病および糖尿病に関連する症状を治療および/または予防のためのみならず、糖尿病関連合併症、病態、または疾患の発症を予防または遅らせるための独自の組成物および方法を提供する。
本発明は、糖尿病と診断された患者を治療するための方法を提供する。本発明は、糖尿病を治療するために、システアミン化合物と少なくとも一つの付加的治療物質との有益な治療的併用を初めて提供する。好ましい態様において、本発明は、システアミン化合物およびメトホルミンの同時投与による、糖尿病の発症と共に糖尿病に関連した合併症を治療および/または予防するための組成物および方法を提供する。
体重300±20gのオスのGoto-Kakizakiウィスターラット(GKラット)19匹を1ケージに3〜4匹ずつ、スチール製ケージ内で飼育した。ケージを2日毎に交換した。室内温度および相対湿度を、それぞれ23±3℃および65±1%に維持した。飼料および飲料水を与えた。GKラットを1ヶ月間順化させた。すべてのGKラットが糖尿病の症状(すなわち、多食、多飲、頻尿、ならびに高い血漿グルコース値およびインスリン抵抗性)を示した時、それらを無作為に3群に分けた:対照群にラット7匹、処置I群および処置II群にラット各6匹。
実験の1日前の17時00分に、全群から飲料水以外のすべての飼料を取り除いた。2日目の9時30分に、すべてのGKラットの空腹時血漿グルコースを測定した。10時00分に、グルコース負荷試験(2g/kg BW)を実施し、同様に、すべてのGKラットの血漿グルコースレベルを測定した。3日目に、対照群のGKラットに生理食塩水溶液(2ml/ラット)を経口投与し、処置I群およびII群のGKラットにメトホルミン溶液を経口投与した(17mg/kg体重(BW)、1日1回9時30分に2ml)。この治療プログラムをその後の数日間実施した。9日目に、空腹時血漿グルコースを測定し、全群の全GKラットに対して経口グルコース負荷試験を再度実施した。
10日目に、処置II群のGKラットに対する治療プログラムを変更し、その後の6日間は、システアミン塩酸塩とともにメトホルミンを経口投与した(メトホルミン17mg/kg BW、システアミン塩酸塩15mg/kg BW)。一方、対照群および処置I群に対する治療プログラムは未変更のままとした。この治療プログラムを6日間実施した。
治療プログラム変更後6日間に、空腹時血漿グルコースを測定し、かつグルコース負荷試験を実施し、ならびに全群の全GKラットの血液および組織試料(肝臓、十二指腸、膵臓腺、脂肪、および筋肉)を採取した。血液試料を4℃で3時間保存し、3500rpmで10分間遠心分離した。次いで、血清を回収し、-20℃で保存した。組織試料は、採取後に液体窒素中に入れ、次いで、-80℃で保存した。
約13週齢かつ体重321〜323gのGoto-Kakizakiウィスター(GK)ラット36匹(Shanghai Slaccas Laboratory Animal Centerから購入)を個別のケージに2週間入れて動物施設に順化させた。飼料および水を適宜与えた。
小規模の非盲検無作為化試験を中国のnational reference center for diabetesで実施した。II型糖尿病と診断された両方の性別の60名の患者(年齢30〜75歳)を採用した。全被験者は説明を受け、参加することに同意した。糖尿病は、1999年に設けられたWHOの基準に基づいて診断した。さらに、選択された患者は、以下の基準を満たした:(1)糖尿病歴5年未満、(2)空腹時血漿グルコースレベルが7〜14mmol/L、(3)血清トリグリセリドレベルが2.5mmol/L以上、(4)尿タンパク排出が30mg/日以上、および(5)過去1ヶ月内に抗脂質薬およびおよびACE阻害剤を摂取していないこと。以下の状態を有する患者は調査から除外した:(1)心臓、肝臓および/または腎臓の機能障害、(2)過去3ヶ月間に、急性の糖尿病合併症および/もしくは任意の急性の心血管合併症、または他の慢性疾患を罹患、ならびに(4)妊娠または授乳中。
本発明の新規な組成物は、1〜95重量%のシステアミン化合物と包接化合物ホスト物質のような担体を1〜80重量%含む。ある態様において、本発明の組成物はさらに、システアミン化合物と同時に投与した場合、治療的成果を確実にする用量の付加的治療物質を含む。
Claims (48)
- 少なくとも一つの付加的治療物質と共にシステアミン化合物の有効量を患者に同時投与する段階を含む、糖尿病を治療する方法。
- 付加的治療物質が、遺伝子に基づく薬学的化合物、インスリン;スルホニル尿素;インスリン分泌促進物質;α-グルコシダーゼ阻害剤;ビグアナイド;メグリチニド;チアゾリジンジオン;D-フェニルアラニン;身体運動;食事の摂取の改善;および体重減少からなる群より選択される、請求項1記載の方法。
- 患者に投与されるシステアミン化合物の有効量が、約400 mg/kg体重または等モル量未満である、請求項1記載の方法。
- 患者に投与されるシステアミン化合物の有効量が、約30 mg/kg体重または等モル量である、請求項3記載の方法。
- システアミン化合物が、システアミン、システアミン塩、システアミンのプロドラッグ、システアミンの類似体、システアミンの誘導体、システアミンの結合体、およびシステアミンの代謝物からなる群より選択される、請求項1記載の方法。
- システアミン化合物が、システアミン塩酸塩、リン酸システアミン、パントテン酸、またはシステアミンである、請求項5記載の方法。
- システアミン化合物および付加的治療物質が経口、非経口、静脈内、筋肉内、経皮、口腔内経路、皮下、または坐剤によって摂取される、請求項1記載の方法。
- 付加的治療物質がビグアナイドである、請求項1記載の方法。
- 付加的治療物質がメトホルミンである、請求項8記載の方法。
- メトホルミンの有効量が約40 mg/kg体重/日未満である、請求項9記載の方法。
- 付加的治療物質がインスリンおよび血糖降下化合物である、請求項1記載の方法。
- 少なくとも一つの付加的治療物質と共にシステアミン化合物の有効量を患者に同時投与する段階を含み、システアミン化合物の有効量が400 mg/kg体重未満である、糖尿病に関連した合併症の重症度、強度、または持続を減少させる方法。
- 患者に投与されるシステアミンの有効量が約30 mg/kg体重、または等モル量である、請求項12記載の方法。
- 付加的治療物質が、遺伝子に基づく薬学的化合物、インスリン;スルホニル尿素;インスリン分泌促進物質;α-グルコシダーゼ阻害剤;ビグアナイド;メグリチニド;チアゾリジンジオン;D-フェニルアラニン;身体運動;食事の摂取の改善;および体重減少からなる群より選択される、請求項12記載の方法。
- システアミン化合物が、システアミン、システアミン塩、システアミンのプロドラッグ、システアミンの類似体、システアミンの誘導体、システアミンの結合体、およびシステアミンの代謝物からなる群より選択される、請求項12記載の方法。
- システアミン化合物が、システアミン塩酸塩、リン酸システアミン、パントテン酸、またはシステアミンである、請求項15記載の方法。
- システアミン化合物および付加的治療物質が経口、非経口、静脈内、筋肉内、経皮、口腔内経路、皮下、または坐剤によって摂取される、請求項12記載の方法。
- 付加的治療物質がビグアナイドである、請求項12記載の方法。
- 付加的治療物質がメトホルミンである、請求項18記載の方法。
- メトホルミンの有効量が約40 mg/kg体重/日未満である、請求項19記載の方法。
- 付加的治療物質がインスリンおよび血糖降下化合物である、請求項12記載の方法。
- 糖尿病に関連した合併症が、皮膚疾患、細菌感染症、真菌感染症、糖尿病性皮膚障害、リポイド類壊死、糖尿病性疾患、発疹状黄色腫症、アレルギー性皮膚反応、指端硬化症、播種性環状肉芽腫、黒色表皮症、歯肉疾患、眼障害、緑内障、白内障、網膜症、腎疾患、ニューロパシー、全身性ニューロパシー、末梢性全身性多発ニューロパシー、中枢性ニューロパシー、大腿ニューロパシー、神経障害性関節炎、頭蓋ニューロパシー、自律神経ニューロパシー、圧迫性ニューロパシー、糖尿病性筋萎縮、痛風、心血管疾患/障害、高血圧症、心疾患、心臓発作、および卒中からなる群より選択される、請求項12記載の方法。
- 少なくとも一つの付加的治療物質と共にシステアミン化合物の有効量を患者に同時投与する段階を含み、システアミン化合物の有効量が400 mg/kg体重未満である、糖尿病または糖尿病に関連した合併症の発症を予防する方法。
- 患者に投与されるシステアミン化合物の有効量が、約30 mg/kg体重または等モル量である、請求項23記載の方法。
- 付加的治療物質が、遺伝子に基づく薬学的化合物、インスリン;スルホニル尿素;インスリン分泌促進物質;α-グルコシダーゼ阻害剤;ビグアナイド;メグリチニド;チアゾリジンジオン;D-フェニルアラニン;身体運動;食事の摂取の改善;および体重減少からなる群より選択される、請求項23記載の方法。
- システアミン化合物が、システアミン、システアミン塩、システアミンのプロドラッグ、システアミンの類似体、システアミンの誘導体、システアミンの結合体、およびシステアミンの代謝物からなる群より選択される、請求項23記載の方法。
- システアミン化合物が、システアミン塩酸塩、リン酸システアミン、パントテン酸またはシステアミンである、請求項26記載の方法。
- システアミン化合物および付加的治療物質が、経口、非経口、静脈内、筋肉内、経皮、口腔内経路、皮下、または坐剤によって摂取される、請求項23記載の方法。
- 付加的治療物質がビグアナイドである、請求項23記載の方法。
- 付加的治療物質がメトホルミンである、請求項29記載の方法。
- メトホルミンの有効量が約40 mg/kg体重/日未満である、請求項30記載の方法。
- 付加的治療物質がインスリンおよび血糖降下化合物である、請求項31記載の方法。
- システアミン化合物の有効量および少なくとも一つの付加的治療物質の有効量を含む組成物。
- 付加的治療物質が、遺伝子に基づく薬学的化合物、インスリン;スルホニル尿素;インスリン分泌促進物質;α-グルコシダーゼ阻害剤;ビグアナイド;メグリチニド;チアゾリジンジオン;およびD-フェニルアラニンからなる群より選択される、請求項33記載の組成物。
- 包接化合物ホスト物質をさらに含む、請求項33記載の組成物。
- 包接ホスト物質がシクロデキストリン;M-β-CD;HP-β-CD;HE-β-CD;ポリシクロデキストリン、E-β-CD、および分枝シクロデキストリンからなる群より選択される、請求項35記載の組成物。
- システアミン化合物の有効量が400 mg/kg体重未満である、請求項33記載の組成物。
- 患者に投与されるシステアミン化合物の有効量が、約30 mg/kg体重または等モル量である、請求項37記載の組成物。
- 付加的治療物質がビグアナイドである、請求項33記載の組成物。
- 付加的治療物質がメトホルミンである、請求項39記載の組成物。
- 付加的治療物質の有効量が、約40 mg/kg体重/日未満である、請求項40記載の組成物。
- 生物学的要因がインスリン増殖因子1、C-ペプチド、遊離の脂肪酸、血中尿酸、アディポネクチン、グルコース輸送体、トリグリセリド、低密度リポタンパク質、および高密度リポタンパク質からなる群より選択される、少なくとも一つの付加的治療物質と共にシステアミン化合物の有効量を同時投与する段階を含む、糖尿病と診断された患者における少なくとも一つの生物学的要因を調節する方法。
- 生物学的要因がインスリン感受性に影響を及ぼす、請求項42記載の方法。
- インスリン感受性に影響を及ぼす生物学的要因がグルコース輸送体である、請求項43記載の方法。
- 生物学的要因が、患者における糖尿病関連合併症または病態の発症または診断における要因であって、システアミン化合物および付加的治療物質の同時投与が、患者における糖尿病関連合併症または病態を治療する、請求項42記載の方法。
- 生物学的要因が、患者における糖尿病の発症または診断における要因であって、システアミン化合物および付加的治療物質の同時投与が、患者における糖尿病を治療する、請求項42記載の方法。
- 以下の段階を含む、無症候性の患者における糖尿病または糖尿病に関連した合併症の発症を予防する方法:
糖尿病の臨床発現に先立つマーカーの存在に関して患者を評価する段階;および
システアミン化合物および少なくとも一つの付加的治療物質を患者に同時投与する段階。 - マーカーが、インスリンに対する自己抗体(IAA)、島細胞に対する自己抗体(ICA)、グルタミン酸デカルボキシラーゼ(GAD)からなる群より選択される、請求項47記載の方法。
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007536244A (ja) * | 2004-05-03 | 2007-12-13 | オメガ バイオ‐ファーマ(アイ.ピー.3)リミテッド | 代謝を調節するための材料および方法 |
JP2013529292A (ja) * | 2010-04-13 | 2013-07-18 | エム−ラブ・アクチェンゲゼルシャフト | 緑内障の診断方法 |
JP2018528254A (ja) * | 2015-09-22 | 2018-09-27 | バイキング セラピューティクス,インコーポレーテッド | グルコース産生阻害物質との併用療法 |
JP2020505359A (ja) * | 2017-01-25 | 2020-02-20 | アデア ファーマシューティカルズ,インコーポレイテッド | システアミンプロドラッグ |
Families Citing this family (42)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7785627B2 (en) | 2002-09-20 | 2010-08-31 | Watson Pharmaceuticals, Inc. | Pharmaceutical formulation containing a biguanide and a thiazolidinedione derivative |
US9060941B2 (en) | 2002-09-20 | 2015-06-23 | Actavis, Inc. | Pharmaceutical formulation containing a biguanide and a thiazolidinedione derivative |
US8084058B2 (en) | 2002-09-20 | 2011-12-27 | Watson Pharmaceuticals, Inc. | Pharmaceutical formulation containing a biguanide and a thiazolidinedione derivative |
US7959946B2 (en) | 2002-09-20 | 2011-06-14 | Watson Pharmaceuticals, Inc. | Pharmaceutical formulation containing a biguanide and a thiazolidinedione derivative |
CN100391448C (zh) * | 2003-11-19 | 2008-06-04 | 奥加生物药业(I.P.1)有限公司 | 提高乙醇代谢和减轻宿醉效应的物质和方法 |
EP1696897B1 (en) * | 2003-12-19 | 2011-07-06 | Omega Bio-Pharma (I.P.3) Limited | Compositions for treating diabetes |
US20050143473A1 (en) * | 2003-12-19 | 2005-06-30 | Wong Gary K.P. | Methods for treating allergy |
WO2005067899A2 (en) * | 2004-01-13 | 2005-07-28 | Omega Bio-Pharma (I.P.2) Limited | Methods for treating stress and affecting biological immune systems using a cysteamine compound |
BRPI0512923A (pt) * | 2004-06-30 | 2008-04-15 | Omega Bio Pharma I P 1 Ltd | materiais e métodos para melhorar a saúde, imunidade e crescimento de mariscos |
US20070172514A1 (en) * | 2006-01-20 | 2007-07-26 | Francis Chi | Materials and methods for improving livestock productivity |
MX2008009647A (es) | 2006-01-27 | 2008-09-25 | Univ California | Cisteamina recubierta entéricamente, cistamina y derivados de ella. |
AU2013267044B2 (en) * | 2006-01-27 | 2016-07-07 | The Regents Of The University Of California | Enterically coated cysteamine, cystamine and derivatives thereof |
US8138227B2 (en) * | 2006-07-06 | 2012-03-20 | Trustees Of Dartmouth College | Method for inhibiting or reversing non-enzymatic glycation |
US7993687B2 (en) | 2006-07-12 | 2011-08-09 | Julianne Marie Kawa | Compositions and methods for management of diabetes |
ES2603879T3 (es) | 2007-07-19 | 2017-03-01 | Takeda Pharmaceutical Company Limited | Preparación sólida que comprende alogliptina e hidrocloruro de metformina |
KR20100091219A (ko) | 2007-11-30 | 2010-08-18 | 더 리전트 오브 더 유니버시티 오브 캘리포니아 | 시스테아민 산물을 이용한 비-알코올성 지방성간염(nash) 치료 방법 |
WO2011130719A2 (en) | 2010-04-15 | 2011-10-20 | The Regents Of The University Of Michigan | A biosynthetic pathway for heterologous expression of a nonribosomal peptide synthetase drug and analogs |
GB201021186D0 (en) | 2010-12-14 | 2011-01-26 | Novabiotics Ltd | Composition |
SI2661266T1 (sl) | 2011-01-07 | 2021-01-29 | Anji Pharma (Us) Llc | Terapije, na osnovi kemosenzoričnih receptorskih ligandov |
US11759441B2 (en) | 2011-01-07 | 2023-09-19 | Anji Pharmaceuticals Inc. | Biguanide compositions and methods of treating metabolic disorders |
US9572784B2 (en) | 2011-01-07 | 2017-02-21 | Elcelyx Therapeutics, Inc. | Compositions comprising statins, biguanides and further agents for reducing cardiometabolic risk |
US9480663B2 (en) * | 2011-01-07 | 2016-11-01 | Elcelyx Therapeutics, Inc. | Biguanide compositions and methods of treating metabolic disorders |
US9211263B2 (en) | 2012-01-06 | 2015-12-15 | Elcelyx Therapeutics, Inc. | Compositions and methods of treating metabolic disorders |
US8796338B2 (en) | 2011-01-07 | 2014-08-05 | Elcelyx Therapeutics, Inc | Biguanide compositions and methods of treating metabolic disorders |
US11974971B2 (en) | 2011-01-07 | 2024-05-07 | Anji Pharmaceuticals Inc. | Compositions and methods for treating metabolic disorders |
AU2012213435B2 (en) * | 2011-02-02 | 2017-03-30 | Sanofi-Aventis Deutschland Gmbh | Prevention of hypoglycaemia in diabetes mellitus type 2 patients |
KR20140097132A (ko) * | 2011-11-22 | 2014-08-06 | 더 리젠츠 오브 더 유니버시티 오브 캘리포니아 | 허혈성 손상을 치료하기 위한 시스테아민 및/또는 시스타민 |
MX2014008190A (es) | 2012-01-06 | 2015-02-04 | Elcelyx Therapeutics Inc | Composiciones de biguanida y métodos para tratar transtornos metabólicos. |
MX2014008189A (es) | 2012-01-06 | 2015-02-12 | Elcelyx Therapeutics Inc | Composiciones y metodos para tratar trastornos metabolicos. |
US20140314841A1 (en) | 2013-04-19 | 2014-10-23 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Serv | Use of Cysteamine and Derivatives Thereof to Suppress Tumor Metastases |
TWI649100B (zh) | 2013-06-17 | 2019-02-01 | 地平線罕見醫學製藥有限責任公司 | 延遲釋放型半胱胺珠粒調配物,以及其製備及使用方法 |
WO2015015403A2 (en) * | 2013-08-01 | 2015-02-05 | Mahesh Kandula | Compositions and methods for the treatment of diabetes and pre-diabetes |
EP3628640B1 (en) * | 2014-09-02 | 2023-08-09 | Hub Therapeutics | Methods of making a deuterated or a non-deuterated molecule and pharmaceutical formulations for treatment |
GB201416716D0 (en) * | 2014-09-22 | 2014-11-05 | Novabiotics Ltd | Use |
RU2766579C2 (ru) | 2015-07-02 | 2022-03-15 | ХОРАЙЗОН ОРФАН ЭлЭлСи | Цистеаминдиоксигеназа-резистентные аналоги цистеамина и их применение |
WO2017062363A1 (en) * | 2015-10-05 | 2017-04-13 | Joslin Diabetes Center | Methods of use of betatrophin |
CN106620715B (zh) * | 2015-11-04 | 2021-04-06 | 江苏恒瑞医药股份有限公司 | 一种治疗糖尿病的药物组合物及其制备方法 |
US10537528B2 (en) | 2015-11-16 | 2020-01-21 | The Regents Of The University Of California | Methods of treating non-alcoholic steatohepatitis (NASH) using cysteamine compounds |
US10143665B2 (en) | 2015-11-17 | 2018-12-04 | Horizon Orphan Llc | Methods for storing cysteamine formulations and related methods of treatment |
US10155948B2 (en) | 2016-05-12 | 2018-12-18 | Kangwon National University University-Industry Cooperation Foundation and | Pharmaceutical composition for preventing or treating diabetic complications and screening method for preventive or therapeutic agent for diabetic complications |
KR101881662B1 (ko) * | 2016-05-12 | 2018-07-26 | 강원대학교산학협력단 | 당뇨성 합병증 예방 및 치료용 약제학적 조성물 및 당뇨성 합병증 예방 또는 치료제 스크리닝 방법 |
CN109439553B (zh) * | 2018-12-26 | 2020-08-21 | 华熙生物科技股份有限公司 | 产麦角硫因的菌株及其筛选方法 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003519621A (ja) * | 1999-11-03 | 2003-06-24 | ブリストル−マイヤーズ スクイブ カンパニー | 糖尿病の治療方法 |
Family Cites Families (26)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4062950A (en) * | 1973-09-22 | 1977-12-13 | Bayer Aktiengesellschaft | Amino sugar derivatives |
DE3343141A1 (de) * | 1983-11-29 | 1985-06-05 | Hermann P.T. 7400 Tübingen Ammon | Verwendung von cystein-derivaten oder deren salzen, zur steigerung der insulinsekretion der langerhans'schen inseln der bauchspeicheldruese |
CA1322526C (en) | 1987-06-04 | 1993-09-28 | John I. Clark | Chemical prevention or reversal of cataract by phase separation inhibitors |
US5401880A (en) | 1987-06-04 | 1995-03-28 | Oculon Corporation | Chemical prevention or reversal of cataract by phase separation inhibitors |
US5668117A (en) | 1991-02-22 | 1997-09-16 | Shapiro; Howard K. | Methods of treating neurological diseases and etiologically related symptomology using carbonyl trapping agents in combination with previously known medicaments |
US6746678B1 (en) | 1991-02-22 | 2004-06-08 | Howard K. Shapiro | Method of treating neurological diseases and etiologically related symptomology using carbonyl trapping agents in combination with medicaments |
CZ306394A3 (en) | 1993-12-14 | 1995-08-16 | Lilly Co Eli | Aqueous solution of inclusion complex of benzothiophene derivative with water-soluble cyclodextrins, process of its preparation and a pharmaceutical composition containing thereof |
FR2716625B1 (fr) * | 1994-02-25 | 1996-04-26 | Gouchet Franck Arno | Préparation et utilisation de formes pharmaceutiques et cosmétiques contenant des composés d'inclusion avec les cyclodextrines de cystéamine, sels de cystéamine, ou dérivés de la cystéamine, sous forme de sel ou non. |
US5714519A (en) * | 1995-06-07 | 1998-02-03 | Ergo Science Incorporated | Method for regulating glucose metabolism |
KR100245077B1 (ko) * | 1997-04-25 | 2000-02-15 | 김영환 | 반도체 메모리 소자의 딜레이 루프 럭크 회로 |
US6100736A (en) * | 1997-06-05 | 2000-08-08 | Cirrus Logic, Inc | Frequency doubler using digital delay lock loop |
FR2774591B1 (fr) | 1998-02-12 | 2000-05-05 | Lipha | Composition pharmaceutique comprenant l'association metformine et fibrate et son utilisation pour la preparation de medicaments destines a reduire l'hyperglycemie |
US6621496B1 (en) * | 1999-02-26 | 2003-09-16 | Micron Technology, Inc. | Dual mode DDR SDRAM/SGRAM |
US6521266B1 (en) | 1999-09-23 | 2003-02-18 | Morris A. Mann | Composition for growth hormone production and release, appetite suppression, and methods related thereto |
US6630176B2 (en) | 2000-03-07 | 2003-10-07 | Mount Sinai School Of Medicine Of New York University | Herbal remedies for treating allergies and asthma |
WO2001082916A2 (en) * | 2000-05-03 | 2001-11-08 | Tularik Inc. | Combination therapeutic compositions and methods of use |
WO2001095944A2 (en) | 2000-06-12 | 2001-12-20 | Mills Randell L | Photocleavable prodrugs for selective drug delivery |
CN1144585C (zh) | 2000-12-13 | 2004-04-07 | 华扩达动物科学[I.P.2]有限公司 | 含有半胱胺或其盐类的促进动物快速生长的组合物及用途 |
JP3715529B2 (ja) | 2000-12-19 | 2005-11-09 | 雅嗣 田中 | アルコール代謝促進剤 |
US6746578B2 (en) * | 2001-05-31 | 2004-06-08 | International Business Machines Corporation | Selective shield/material flow mechanism |
JP2006508096A (ja) * | 2002-11-07 | 2006-03-09 | ディーエスエム アイピー アセッツ ビー.ブイ. | 没食子酸エピガロカテキンを含む新規な栄養補助組成物 |
US8017651B2 (en) | 2002-11-22 | 2011-09-13 | Bionexus, Ltd. | Compositions and methods for the treatment of HIV-associated fat maldistribution and hyperlipidemia |
CN100391448C (zh) | 2003-11-19 | 2008-06-04 | 奥加生物药业(I.P.1)有限公司 | 提高乙醇代谢和减轻宿醉效应的物质和方法 |
US20050143473A1 (en) | 2003-12-19 | 2005-06-30 | Wong Gary K.P. | Methods for treating allergy |
EP1696897B1 (en) * | 2003-12-19 | 2011-07-06 | Omega Bio-Pharma (I.P.3) Limited | Compositions for treating diabetes |
BRPI0510613A (pt) * | 2004-05-03 | 2007-10-30 | Omega Bio Pharma Ip3 Ltd | cisteaminas para tratar complicações de hipercolesterolemia e diabete |
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Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003519621A (ja) * | 1999-11-03 | 2003-06-24 | ブリストル−マイヤーズ スクイブ カンパニー | 糖尿病の治療方法 |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007536244A (ja) * | 2004-05-03 | 2007-12-13 | オメガ バイオ‐ファーマ(アイ.ピー.3)リミテッド | 代謝を調節するための材料および方法 |
JP2013529292A (ja) * | 2010-04-13 | 2013-07-18 | エム−ラブ・アクチェンゲゼルシャフト | 緑内障の診断方法 |
JP2016048265A (ja) * | 2010-04-13 | 2016-04-07 | エム−ラブ・アクチェンゲゼルシャフトM−Lab Ag | 緑内障の診断方法 |
JP2018528254A (ja) * | 2015-09-22 | 2018-09-27 | バイキング セラピューティクス,インコーポレーテッド | グルコース産生阻害物質との併用療法 |
JP2020505359A (ja) * | 2017-01-25 | 2020-02-20 | アデア ファーマシューティカルズ,インコーポレイテッド | システアミンプロドラッグ |
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IL176259A (en) | 2016-02-29 |
EP1696897A4 (en) | 2008-12-10 |
AR047779A1 (es) | 2006-02-22 |
ATE515261T1 (de) | 2011-07-15 |
AU2004308934B2 (en) | 2010-04-01 |
EP1696897A1 (en) | 2006-09-06 |
SG149814A1 (en) | 2009-02-27 |
MY143799A (en) | 2011-07-15 |
MXPA06007100A (es) | 2007-01-19 |
RU2367423C2 (ru) | 2009-09-20 |
CA2549717C (en) | 2012-11-13 |
KR101329369B1 (ko) | 2013-11-14 |
WO2005063226A1 (en) | 2005-07-14 |
HK1099507A1 (en) | 2007-08-17 |
KR20070004569A (ko) | 2007-01-09 |
TWI350751B (en) | 2011-10-21 |
US8188151B2 (en) | 2012-05-29 |
US7442720B2 (en) | 2008-10-28 |
JP4845740B2 (ja) | 2011-12-28 |
US20090048154A1 (en) | 2009-02-19 |
TW200524583A (en) | 2005-08-01 |
US20050137125A1 (en) | 2005-06-23 |
EP1696897B1 (en) | 2011-07-06 |
RU2006126062A (ru) | 2008-01-27 |
IL176259A0 (en) | 2006-10-05 |
CA2549717A1 (en) | 2005-07-14 |
CN101897970A (zh) | 2010-12-01 |
AU2004308934A1 (en) | 2005-07-14 |
BRPI0417829A (pt) | 2007-04-10 |
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