ES2869884T3 - Composiciones de galacto-ramnogalacturonato para el tratamiento de la esteatohepatitis no alcohólica y la enfermedad de hígado graso no alcohólico - Google Patents
Composiciones de galacto-ramnogalacturonato para el tratamiento de la esteatohepatitis no alcohólica y la enfermedad de hígado graso no alcohólico Download PDFInfo
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- ES2869884T3 ES2869884T3 ES12831657T ES12831657T ES2869884T3 ES 2869884 T3 ES2869884 T3 ES 2869884T3 ES 12831657 T ES12831657 T ES 12831657T ES 12831657 T ES12831657 T ES 12831657T ES 2869884 T3 ES2869884 T3 ES 2869884T3
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- rhamnogalacturonate
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Classifications
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- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
- C08B37/0045—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid alpha-D-Galacturonans, e.g. methyl ester of (alpha-1,4)-linked D-galacturonic acid units, i.e. pectin, or hydrolysis product of methyl ester of alpha-1,4-linked D-galacturonic acid units, i.e. pectinic acid; Derivatives thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/736—Glucomannans or galactomannans, e.g. locust bean gum, guar gum
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/732—Pectin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
- C08B37/0087—Glucomannans or galactomannans; Tara or tara gum, i.e. D-mannose and D-galactose units, e.g. from Cesalpinia spinosa; Tamarind gum, i.e. D-galactose, D-glucose and D-xylose units, e.g. from Tamarindus indica; Gum Arabic, i.e. L-arabinose, L-rhamnose, D-galactose and D-glucuronic acid units, e.g. from Acacia Senegal or Acacia Seyal; Derivatives thereof
Landscapes
- Health & Medical Sciences (AREA)
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- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
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- Engineering & Computer Science (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- Emergency Medicine (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
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| US201261656288P | 2012-06-06 | 2012-06-06 | |
| PCT/US2012/055360 WO2013040324A1 (en) | 2011-09-16 | 2012-09-14 | Galacto-rhamnogalacturonate compositions for the treatment of non-alcoholic steatohepatitis and non-alcoholic fatty liver disease |
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| ES2869884T3 true ES2869884T3 (es) | 2021-10-26 |
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| MX (1) | MX360979B (cg-RX-API-DMAC7.html) |
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| WO2008011216A2 (en) * | 2006-05-16 | 2008-01-24 | Pro-Pharmaceuticals, Inc. | Galactose-pronged polysaccharides in a formulation for antifibrotic therapies |
| MX363923B (es) | 2011-12-28 | 2019-04-08 | Galectin Therapeutics Inc | Composicion de farmaco de carbohidrato novedoso para el tratamiento de enfermedades humanas. |
| AU2013271585B2 (en) | 2012-06-06 | 2018-02-01 | Galectin Therapeutics, Inc. | Galacto-rhamnogalacturonate compositions for the treatment of diseases associated with elevated inducible nitric oxide synthase |
| WO2014043708A1 (en) * | 2012-09-17 | 2014-03-20 | Traber Peter G | Method for enhancing specific immunotherapies in cancer treatment |
| CA2924597A1 (en) | 2013-09-19 | 2015-03-26 | The Research Foundation For The State University Of New York | Methods and materials for treating diabetes or liver steatosis |
| TW201618794A (zh) * | 2014-03-10 | 2016-06-01 | 拉荷亞製藥公司 | 用於治療腎臟疾病之組成物及方法 |
| JP2017525702A (ja) * | 2014-08-18 | 2017-09-07 | ファーマジェネシス， インコーポレイテッド | ポリガラクツロナンラムノガラクツロナン（ｐｇｒｇ１）組成物 |
| MA41120A (fr) * | 2014-12-02 | 2017-10-10 | Afimmune Ltd | Compositions comprenant le 15-hepe et méthodes de traitement ou de prévention de la fibrose à l'aide de celles-ci |
| BR112017018882A2 (pt) * | 2015-03-03 | 2018-04-17 | Kohjin Life Sciences Co Ltd | composição para aperfeiçoamento ou prevenção de uma doença de fígado gorduroso não alcoólico |
| US10639322B2 (en) | 2015-03-27 | 2020-05-05 | The Research Foundation For The State University Of New York | Methods and materials for reducing amyloid beta levels within a mammal |
| CN113896628A (zh) | 2015-05-13 | 2022-01-07 | Ds生物制药有限公司 | 包含15-氧代-epa或15-氧代-dgla的组合物及其制备和使用方法 |
| AU2016288699B2 (en) * | 2015-06-30 | 2020-11-26 | Eiger Group International, Inc. | Use of chloroquine and clemizole compounds for treatment of inflammatory and cancerous conditions |
| US20190000923A1 (en) * | 2015-12-22 | 2019-01-03 | Novartis Ag | Methods of treating or ameliorating metabolic disorders using growth differentiation factor 15 (gdf-15) |
| KR102346913B1 (ko) * | 2016-03-04 | 2022-01-04 | 갈랙틴 사이언시즈, 엘엘씨 | 갈렉틴과 관련된 질환의 예방 및 치료를 위한 셀레노갈락토시드 화합물 및 이의 용도 |
| FR3050112B1 (fr) | 2016-04-15 | 2020-09-04 | Soc Civ Immobiliere Gecinq | Utilisation de l'acide fenofibrique dans le traitement des maladies hepatiques |
| AU2017274521B2 (en) * | 2016-06-03 | 2021-08-19 | Chemocentryx, Inc. | Method of treating liver fibrosis |
| US10342785B2 (en) | 2016-11-04 | 2019-07-09 | Askat Inc. | Use of EP4 receptor antagonists for the treatment of NASH-associated liver cancer |
| JP7677755B2 (ja) | 2017-04-14 | 2025-05-15 | ジェレシス，エルエルシー | 腸透過性関連障害を治療又は予防するための組成物及び方法 |
| JP7204676B2 (ja) | 2017-05-12 | 2023-01-16 | ガレクティン・サイエンシーズ・リミテッド・ライアビリティ・カンパニー | 疾患の予防および治療用の化合物およびその使用 |
| US20200163897A1 (en) * | 2017-07-04 | 2020-05-28 | The Regents Of The University Of California | Methods of treating liver diseases associated with portal tract or periportal inflammation |
| ES2902226T3 (es) * | 2017-07-19 | 2022-03-25 | Bio Rad Europe Gmbh | Combinaciones de biomarcadores para evaluar la esteatohepatitis no alcohólica y/o el estatus de la fibrosis hepática |
| GB201804922D0 (en) | 2018-03-27 | 2018-05-09 | Ucl Business Plc | Traatment |
| CN112672765A (zh) | 2018-06-29 | 2021-04-16 | 格莱科斯生物医药公司 | 结合物 |
| US20230038373A1 (en) | 2019-12-18 | 2023-02-09 | Glykos Biomedical Oy | Stabile conjugate |
| EP4153164A4 (en) * | 2020-05-22 | 2024-06-26 | Durect Corporation | Treatment of non-alcoholic steatohepatitis (nash) |
Family Cites Families (34)
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| DE4011285A1 (de) * | 1990-04-06 | 1991-10-10 | Steigerwald Arzneimittelwerk | Arzneimittel zur behandlung von hyperlipidaemie und/oder atherosklerose |
| US6297229B1 (en) | 1994-11-14 | 2001-10-02 | Mayo Foundation For Medical Education And Research | Use of ursodeoxycholic acid to treat nonalcoholic steatohepatitis |
| US5760010A (en) | 1995-01-01 | 1998-06-02 | Klein; Ira | Method of treating liver disorders with a macrolide antibiotic |
| US6180139B1 (en) | 1998-12-04 | 2001-01-30 | Viva America Marketing, Inc. | Composition and method for treating nonalcoholic steatohepatitis |
| AU4055000A (en) * | 1999-04-13 | 2000-11-14 | Daniel K. Hsu | Galectin expression is induced in cirrhotic liver and hepatocellular carcinoma |
| AU777254B2 (en) | 1999-04-20 | 2004-10-07 | Board Of Trustees Of Southern Illinois University, The | Methods of treating clinical diseases with isoflavones |
| CN1142272C (zh) * | 2000-02-02 | 2004-03-17 | 中国人民解放军军事医学科学院百环生物医学研究中心 | 携带人肝细胞生长因子基因的重组腺病毒的用途 |
| AU3668501A (en) * | 2000-02-04 | 2001-08-14 | Seo Hong Yoo | Preparation of aqueous clear solution dosage forms with bile acids |
| US6596762B2 (en) | 2001-05-17 | 2003-07-22 | The Regents Of The University Of Colorado | Antioxidant compositions and use for treatment of hepatic steatosis and steatohepatitis |
| HUP0401156A2 (hu) * | 2001-07-20 | 2004-12-28 | Intermune, Inc. | Májfibrózis kezelésére szolgáló módszerek |
| US7312208B2 (en) | 2002-08-28 | 2007-12-25 | Asahi Kasei Pharma Corporation | Quaternary ammonium compounds |
| US20040223971A1 (en) | 2003-04-07 | 2004-11-11 | Glycogenesys, Inc. | Composition and uses of galectin antagonists |
| US7078064B2 (en) | 2003-12-03 | 2006-07-18 | George Zabrecky | Compositions and methods useful for treating and preventing chronic liver disease, chronic HCV infection and non-alcoholic steatohepatitis |
| WO2005082874A1 (ja) | 2004-02-27 | 2005-09-09 | Asahi Kasei Pharma Corporation | 新規なベンゾチアゼピン及びベンゾチエピン化合物 |
| US8128966B2 (en) * | 2004-03-26 | 2012-03-06 | La Jolla Pharmaceutical Company | Modified pectins, compositions and methods related thereto |
| JP2008105945A (ja) | 2005-02-07 | 2008-05-08 | Ajinomoto Co Inc | アディポネクチンの分泌促進又は誘導作用を有するアシルアミド化合物 |
| WO2006127976A2 (en) | 2005-05-24 | 2006-11-30 | Isis Pharmaceuticals, Inc. | Compositions and their uses directed to ptpru |
| US20090028925A1 (en) | 2005-05-26 | 2009-01-29 | Erion Mark D | Novel Phosphinic Acid-Containing Thyromimetics |
| AU2006262441A1 (en) | 2005-06-20 | 2007-01-04 | Schering Corporation | Piperidine derivatives useful as histamine H3 antagonists |
| US7897591B2 (en) * | 2005-07-28 | 2011-03-01 | Children's Medical Center Corporation | Method of treating fatty liver disease |
| US7906652B2 (en) | 2005-11-28 | 2011-03-15 | Merck Sharp & Dohme Corp. | Heterocycle-substituted 3-alkyl azetidine derivatives |
| WO2008011216A2 (en) * | 2006-05-16 | 2008-01-24 | Pro-Pharmaceuticals, Inc. | Galactose-pronged polysaccharides in a formulation for antifibrotic therapies |
| JP5105297B2 (ja) | 2006-05-25 | 2012-12-26 | 味の素株式会社 | Ｐｐａｒ活性調節剤 |
| CA2654098A1 (en) | 2006-06-13 | 2007-12-21 | Merck Frosst Canada Ltd. | Azacyclopentane derivatives as inhibitors of stearoyl-coenzyme a delta-9 desaturase |
| US20080194575A1 (en) * | 2006-10-04 | 2008-08-14 | Naiara Beraza | Treatment for non-alcoholic-steatohepatitis |
| US7999107B2 (en) | 2007-01-31 | 2011-08-16 | Merck Sharp & Dohme Corp. | Substituted pyrano[2,3-B]pyridine derivatives as cannabinoid-1 receptor modulators |
| EP2636404B1 (en) | 2007-11-30 | 2019-03-20 | The Regents of The University of California | Methods of Treating Non-Alcoholic Steatohepatitis (Nash) Using Cysteamine Products |
| WO2009096455A1 (ja) * | 2008-01-31 | 2009-08-06 | Astellas Pharma Inc. | 脂肪性肝疾患の治療用医薬組成物 |
| WO2009118343A1 (en) * | 2008-03-27 | 2009-10-01 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and kits for determining the occurrence of a liver disease in a subject |
| WO2009151116A1 (ja) | 2008-06-13 | 2009-12-17 | 持田製薬株式会社 | 非アルコール性脂肪肝炎の予防／改善・治療薬 |
| WO2010058295A2 (en) * | 2008-11-18 | 2010-05-27 | Universite D'angers | Non-invasive in vitro method for quantifying liver lesions |
| JP2010229099A (ja) * | 2009-03-27 | 2010-10-14 | Mochida Pharmaceut Co Ltd | 脂質異常症の改善または治療薬 |
| US20110183948A1 (en) * | 2010-01-15 | 2011-07-28 | Infinity Pharmaceuticals, Inc. | Treatment of fibrotic conditions using hedgehog inhibitors |
| MX363923B (es) * | 2011-12-28 | 2019-04-08 | Galectin Therapeutics Inc | Composicion de farmaco de carbohidrato novedoso para el tratamiento de enfermedades humanas. |
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| EP2755480A1 (en) | 2014-07-23 |
| AU2012308491A1 (en) | 2014-04-03 |
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| US20130171151A1 (en) | 2013-07-04 |
| BR112014006220A2 (pt) | 2017-04-11 |
| US20130259870A1 (en) | 2013-10-03 |
| JP2014526513A (ja) | 2014-10-06 |
| WO2013040316A1 (en) | 2013-03-21 |
| US8658787B2 (en) | 2014-02-25 |
| CA2848711A1 (en) | 2013-03-21 |
| CN103945695A (zh) | 2014-07-23 |
| AU2012308491B2 (en) | 2016-01-07 |
| IL231512A0 (en) | 2014-04-30 |
| KR101974675B1 (ko) | 2019-05-02 |
| MX360979B (es) | 2018-11-22 |
| MX2014003213A (es) | 2015-05-15 |
| EP2755480A4 (en) | 2015-04-29 |
| WO2013040324A1 (en) | 2013-03-21 |
| KR20140107180A (ko) | 2014-09-04 |
| CN103945695B (zh) | 2018-04-17 |
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