BR112015025805A2 - compostos de ligação de nh3 e métodos para inibir o transporte de fosfato - Google Patents

compostos de ligação de nh3 e métodos para inibir o transporte de fosfato

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Publication number
BR112015025805A2
BR112015025805A2 BR112015025805A BR112015025805A BR112015025805A2 BR 112015025805 A2 BR112015025805 A2 BR 112015025805A2 BR 112015025805 A BR112015025805 A BR 112015025805A BR 112015025805 A BR112015025805 A BR 112015025805A BR 112015025805 A2 BR112015025805 A2 BR 112015025805A2
Authority
BR
Brazil
Prior art keywords
methods
nhe3
phosphate
phosphate transport
kidneys
Prior art date
Application number
BR112015025805A
Other languages
English (en)
Inventor
Carreras Christopher
Charmot Dominique
Labonte Eric
g lewis Jason
W Jacobs Jeffrey
Original Assignee
Ardelyx Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ardelyx Inc filed Critical Ardelyx Inc
Publication of BR112015025805A2 publication Critical patent/BR112015025805A2/pt

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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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/545—Heterocyclic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/547—Chelates, e.g. Gd-DOTA or Zinc-amino acid chelates; Chelate-forming compounds, e.g. DOTA or ethylenediamine being covalently linked or complexed to the pharmacologically- or therapeutically-active agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/55—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/18—Drugs for disorders of the endocrine system of the parathyroid hormones
    • A61P5/20—Drugs for disorders of the endocrine system of the parathyroid hormones for decreasing, blocking or antagonising the activity of PTH
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Urology & Nephrology (AREA)
  • Pulmonology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Endocrinology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

abstract title: nhe3-binding compounds and methods for inhibiting phosphate transport provided are nhe3-binding and/or nhe3-modulating agents having activity as phosphate transport inhibitors, including inhibitors of phosphate transport in the gastrointestinal tract and the kidneys, and methods for their use as therapeutic or prophylactic agent.. embodiments of the present invention include methods for inhibiting phosphate uptake in the gastrointestinal tract or kidneys of a patient in need of phosphate lowering, comprising administering to the patient a compound that binds to nhe3 and is substantially active in the gastrointestinal tract or kidneys to inhibit transport of phosphate ions (pi) therein upon administration to the patient in need thereof. tradução do resumo resumo patente de invenção: "compostos de ligação de nh3 e métodos para inibir o transporte de fosfato". são fornecidos agentes de modulação de nhe3 e/ou de ligação de nhe3 tendo atividade como inibidores de transporte de fosfato, incluindo inibidores de transporte de fosfato no trato gastrointestinal e nos rins, e métodos para seu uso como agente terapêutico ou profilático.
BR112015025805A 2013-04-12 2014-04-10 compostos de ligação de nh3 e métodos para inibir o transporte de fosfato BR112015025805A2 (pt)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201361811613P 2013-04-12 2013-04-12
US201361888879P 2013-10-09 2013-10-09
PCT/US2014/033603 WO2014169094A2 (en) 2013-04-12 2014-04-10 Nhe3-binding compounds and methods for inhibiting phosphate transport

Publications (1)

Publication Number Publication Date
BR112015025805A2 true BR112015025805A2 (pt) 2017-07-25

Family

ID=51690123

Family Applications (1)

Application Number Title Priority Date Filing Date
BR112015025805A BR112015025805A2 (pt) 2013-04-12 2014-04-10 compostos de ligação de nh3 e métodos para inibir o transporte de fosfato

Country Status (27)

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US (4) US10272079B2 (pt)
EP (3) EP2983667B1 (pt)
JP (5) JP6377132B2 (pt)
KR (3) KR102287207B1 (pt)
CN (2) CN109966293A (pt)
AU (2) AU2014250956B2 (pt)
BR (1) BR112015025805A2 (pt)
CA (1) CA2909169A1 (pt)
CY (1) CY1121929T1 (pt)
DK (1) DK2983667T3 (pt)
ES (1) ES2735992T3 (pt)
HK (1) HK1221400A1 (pt)
HR (1) HRP20191000T1 (pt)
HU (1) HUE044550T2 (pt)
IL (3) IL284624B2 (pt)
LT (1) LT2983667T (pt)
MX (2) MX2015014351A (pt)
NZ (1) NZ752535A (pt)
PL (1) PL2983667T3 (pt)
PT (1) PT2983667T (pt)
RS (1) RS58969B1 (pt)
RU (1) RU2675364C2 (pt)
SI (1) SI2983667T1 (pt)
TW (3) TW202123938A (pt)
UY (1) UY35532A (pt)
WO (1) WO2014169094A2 (pt)
ZA (1) ZA201508006B (pt)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10543207B2 (en) 2008-12-31 2020-01-28 Ardelyx, Inc. Compounds and methods for inhibiting NHE-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders
CA2909169A1 (en) * 2013-04-12 2014-10-16 Ardelyx, Inc. Nhe3-binding compounds and methods for inhibiting phosphate transport
IL280864B2 (en) * 2013-08-09 2024-03-01 Ardelyx Inc Compounds and methods for inhibiting phosphate transport
TWI666206B (zh) 2014-07-25 2019-07-21 日商大正製藥股份有限公司 以雜芳基取代之苯基四氫異喹啉化合物
JP6903923B2 (ja) * 2016-01-22 2021-07-14 大正製薬株式会社 ヘテロアリールで置換されたフェニルテトラヒドロイソキノリン化合物を有効成分として含有する医薬
JP7292207B2 (ja) * 2017-01-09 2023-06-16 アルデリックス， インコーポレイテッド 消化管障害を処置するために有用な化合物
KR20190128626A (ko) * 2017-01-09 2019-11-18 알데릭스, 인코포레이티드 Nhe-매개 역수송의 저해제
WO2020051014A1 (en) 2018-09-04 2020-03-12 Teva Pharmaceuticals International Gmbh Processes for the preparation of tenapanor and intermediates thereof
KR20210091185A (ko) * 2018-10-25 2021-07-21 에어젠 파마 엘티디. 혼합 금속 화합물을 이용한 치료 방법
WO2020181555A1 (zh) 2019-03-14 2020-09-17 深圳仁泰医药科技有限公司 Nhe3抑制剂的晶型a及其制备方法和应用
MA54900A (fr) * 2019-05-16 2022-03-23 Lilly Co Eli Composés inhibiteurs de l'échangeur sodium-hydrogène 3
EP3972599A1 (en) 2019-05-21 2022-03-30 Ardelyx, Inc. Combination for lowering serum phosphate in a patient
CN112679427B (zh) * 2019-10-17 2023-05-12 江苏恒瑞医药股份有限公司 四氢异喹啉类衍生物、其制备方法及其在医药上的应用

Family Cites Families (123)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3926891A (en) 1974-03-13 1975-12-16 Dow Chemical Co Method for making a crosslinkable aqueous solution which is useful to form soft, water-swellable polyacrylate articles
US3997484A (en) 1974-04-03 1976-12-14 The United States Of America As Represented By The Secretary Of Agriculture Highly-absorbent starch-containing polymeric compositions
US3935099A (en) 1974-04-03 1976-01-27 The United States Of America As Represented By The Secretary Of Agriculture Method of reducing water content of emulsions, suspensions, and dispersions with highly absorbent starch-containing polymeric compositions
US4090013A (en) 1975-03-07 1978-05-16 National Starch And Chemical Corp. Absorbent composition of matter
JPS51125468A (en) 1975-03-27 1976-11-01 Sanyo Chem Ind Ltd Method of preparing resins of high water absorbency
JPS5346389A (en) 1976-10-07 1978-04-25 Kao Corp Preparation of self-crosslinking polymer of acrylic alkali metal salt
US4190562A (en) 1977-04-04 1980-02-26 The B. F. Goodrich Company Improved water absorbent copolymers of copolymerizable carboxylic acids and acrylic or methacrylic esters
US4470975A (en) 1977-10-21 1984-09-11 The Johns Hopkins University Method and composition for the elimination of water from an animal body
US4286082A (en) 1979-04-06 1981-08-25 Nippon Shokubai Kagaku Kogyo & Co., Ltd. Absorbent resin composition and process for producing same
JPS6025045B2 (ja) 1980-03-19 1985-06-15 製鉄化学工業株式会社 塩水吸収能のすぐれたアクリル酸重合体の製造方法
JPS57158209A (en) 1981-03-25 1982-09-30 Kao Corp Production of bead-form highly water-absorbing polymer
JPS5832607A (ja) 1981-08-20 1983-02-25 Kao Corp 吸水性に優れた吸水材料の製造法
US4985518A (en) 1981-10-26 1991-01-15 American Colloid Company Process for preparing water-absorbing resins
JPS6187702A (ja) 1984-10-05 1986-05-06 Seitetsu Kagaku Co Ltd 吸水性樹脂の製造方法
US4708997A (en) 1985-07-22 1987-11-24 The Dow Chemical Company Suspending agent for the suspension polymerization of water-soluble monomers
US4806532A (en) 1985-10-08 1989-02-21 Mayo Foundation For Medical Education And Research Inhibition of epithelial phosphate transport
DE3544770A1 (de) 1985-12-18 1987-06-19 Stockhausen Chem Fab Gmbh Verfahren und vorrichtung zum kontinuierlichen herstellen von polymerisaten und copolymerisaten der acrylsaeure und/oder methacrylsaeure
US4766004A (en) 1986-12-19 1988-08-23 Warner-Lambert Company Crunchy, highly palatable, bulk-increasing, dietary fiber supplement composition
IT1217123B (it) 1987-02-05 1990-03-14 Rotta Research Lab Derivati otticamente attivi dell acido 5 pentilammino 5 oxo pentanoico r ad attivita antagonista della colecistochinina e procedimento per la loro preparazione
US4999200A (en) 1987-12-09 1991-03-12 Marion Laboratories Psyllium tablet composition, method of manufacture and method of use
US5149541A (en) 1988-10-03 1992-09-22 The Procter & Gamble Company Psyllium-containing produces with a distribution of particle size
US5145906A (en) 1989-09-28 1992-09-08 Hoechst Celanese Corporation Super-absorbent polymer having improved absorbency properties
US5126150A (en) 1990-10-01 1992-06-30 The Procter & Gamble Company Compositions containing psyllium
HUT64023A (en) 1991-03-22 1993-11-29 Sandoz Ag Process for producing aminoguanidine derivatives and pharmaceutical compositions comprising such compounds
FR2674849B1 (fr) 1991-04-02 1994-12-23 Logeais Labor Jacques Nouveaux derives de n-cyclohexyl benzamides ou thiobenzamides, leurs preparations et leurs applications en therapeutique.
US5140102A (en) 1991-09-23 1992-08-18 Monsanto Company Pentadecapeptide, guanylin, which stimulates intestinal guanylate cyclase
US5824645A (en) 1991-12-30 1998-10-20 Neurex Corporation Method of treating inflammation
ATE165977T1 (de) 1991-12-30 1998-05-15 Neurex Corp Methoden zur erzeugung von analgesie und zur verstärkung von opiat-analgesie
US5969097A (en) 1992-06-23 1999-10-19 G. D. Searle & Co. Human guanylin
DK0612723T3 (da) 1993-02-20 1998-03-30 Hoechst Ag Substituerede benzoylguanidiner, fremgangsmåde til fremstilling, deres anvendelse som lægemiddel, som inhibitor af den cellulære Na+/H+-udbytning eller som diagnostikum samt lægemiddel med indhold deraf
US5629377A (en) 1993-03-10 1997-05-13 The Dow Chemical Company Water absorbent resin particles of crosslinked carboxyl containing polymers and method of preparation
IL109570A0 (en) 1993-05-17 1994-08-26 Fujisawa Pharmaceutical Co Guanidine derivatives, pharmaceutical compositions containing the same and processes for the preparation thereof
US5489670A (en) 1993-10-29 1996-02-06 G. D. Searle & Co. Human uroguanylin
US7357946B2 (en) 1994-04-15 2008-04-15 Adamoli Jr James R Uses for cellulose-containing aggregates
US5610145A (en) 1994-04-15 1997-03-11 Warner-Lambert Company Tachykinin antagonists
US5650222A (en) 1995-01-10 1997-07-22 The Procter & Gamble Company Absorbent foam materials for aqueous fluids made from high internal phase emulsions having very high water-to-oil ratios
DE19518796A1 (de) 1995-05-22 1996-11-28 Hoechst Ag Fluorphenylsubstituierte Alkenylcarbonsäure-guanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament
US5795864A (en) 1995-06-27 1998-08-18 Neurex Corporation Stable omega conopetide formulations
DK1336409T3 (da) 1995-06-27 2007-08-13 Eisai R&D Man Co Ltd Sammensætninger af formuleringer til fremstilling af analgesimidler og til hæmning af fremadskridende neuropatiske smertelidelser
US6054429A (en) 1996-03-08 2000-04-25 Elan Pharmaceuticals, Inc. Epidural method of producing analgesia
US5550167A (en) 1995-08-30 1996-08-27 The Procter & Gamble Company Absorbent foams made from high internal phase emulsions useful for acquiring aqueous fluids
TR199800924T2 (xx) 1995-11-24 1998-08-21 Smithkline Beecham S.P.A. Quinoline t�revleri.
GB9524104D0 (en) 1995-11-24 1996-01-24 Smithkline Beecham Spa Novel compounds
DE19548812A1 (de) 1995-12-27 1997-07-03 Hoechst Ag Verwendung von Inhibitoren des zellulären Na·+·/H·+·-Exchangers (NHE) zur Herstellung eines Medikaments zur Atemstimulation
EP0837055A1 (en) 1996-07-30 1998-04-22 Hoechst Aktiengesellschaft Substituted Indanylidineacetylguanidines, process for their preparation, their use as medicaments or diagnostic and medicaments containing them
DE19633966A1 (de) 1996-08-22 1998-02-26 Hoechst Ag Phenylsubstituierte Alkenylcarbonsäure-guanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament
AU4176997A (en) 1996-09-16 1998-04-02 Warner-Lambert Company 3-alkyl-3-phenyl-piperidines
ATE386531T1 (de) 1997-02-28 2008-03-15 Nycomed Gmbh Synergistische kombination von pde-hemmern und adenylatcyclase-agonisten bzw. guanylcyclyse- agonisten
NZ329807A (en) 1997-04-23 2000-07-28 Pfizer NK-1 receptor antagonists and P receptor antagonists 2-Diarylmethyl-3-amino-1-azabicyclo[2.2.2]octane derivatives and amino substituted N-containing rings as agents for treating irritable bowel syndrome
KR100219918B1 (ko) 1997-07-03 1999-09-01 김윤 대장선택적 약물전달용 조성물
US20010006972A1 (en) 1998-04-21 2001-07-05 Stephen A. Williams Nk-1 receptor antagonists for the treatment of symptoms of irritable bowel syndrome
KR20000011247A (ko) 1998-07-23 2000-02-25 김윤 다당류를이용한대장선택성약물전달조성물및약학제제
DE19849722A1 (de) 1998-10-28 2000-05-04 Aventis Pharma Gmbh Substituierte Phenyl-alkenoylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament
CA2371910A1 (en) 1999-01-21 2000-07-27 Brian E. Peerce Inhibitors of intestinal apical membrane na/phosphate co-transportation
FR2789493B1 (fr) 1999-02-09 2001-03-09 Gemplus Card Int Procede de detection d'objets portables et systeme de mise en oeuvre
US6624150B2 (en) 1999-02-26 2003-09-23 Inspire Pharmaceuticals, Inc. Method of treating gastrointestinal tract disease with purinergic receptor agonists
US6287609B1 (en) 1999-06-09 2001-09-11 Wisconsin Alumni Research Foundation Unfermented gel fraction from psyllium seed husks
ES2304352T3 (es) 1999-07-19 2008-10-16 University Of North Carolina At Chapel Hill Compuestos farmacologicamente activos con dos principios activos unidos covalentemente (bloqueante de los canales de sodio/agonista del receptor p2y2) para el tratamiento de superficies mucosas.
AR030911A1 (es) 1999-07-20 2003-09-03 Smithkline Beecham Corp Uso de n-aril-2-sulfonamidobenzamidas para la manufactura de un medicamento para el tratamiento de la insuficiencia renal cronica y composiciones farmaceuticas
US6107356A (en) 1999-08-23 2000-08-22 The Procter & Gamble Company High suction polymeric foam materials
DE19941764A1 (de) 1999-09-02 2001-03-15 Aventis Pharma Gmbh Substituierte Acylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikamente oder Diagnostika sowie sie enthaltende Medikamente
SE9903291D0 (sv) 1999-09-15 1999-09-15 Astra Ab New process
DE19945302A1 (de) 1999-09-22 2001-03-29 Merck Patent Gmbh Biphenylderivate als NHE-3-Inhibitoren
US6887870B1 (en) 1999-10-12 2005-05-03 Bristol-Myers Squibb Company Heterocyclic sodium/proton exchange inhibitors and method
ES2226933T3 (es) 1999-11-01 2005-04-01 John Rhodes Composicion para tratar el estreñimiento y el sindrome del intestino irritable.
AUPQ514600A0 (en) 2000-01-18 2000-02-10 James Cook University Brain injury treatment
WO2001064212A1 (en) 2000-03-01 2001-09-07 University College London Modulators of the endocannabinoid uptake and of the vallinoid receptors
DE10015248A1 (de) 2000-03-28 2001-10-04 Merck Patent Gmbh Bisamidino-Verbindungen als NHE-3 Inhibitoren
DE10019062A1 (de) 2000-04-18 2001-10-25 Merck Patent Gmbh 2-Guanidino-4-aryl-chinazoline als NHE-3 Inhibitoren
AU2001259354A1 (en) 2000-05-02 2001-11-12 Smith Kline Beecham Corporation Phosphate transport inhibitors
AU2001261471A1 (en) * 2000-05-12 2001-11-26 Smithkline Beecham Corporation Phosphate transport inhibitors
US6414016B1 (en) 2000-09-05 2002-07-02 Sucampo, A.G. Anti-constipation composition
DE10043667A1 (de) 2000-09-05 2002-03-14 Merck Patent Gmbh 2-Guanidino-4-aryl-chinazoline
DE10046993A1 (de) 2000-09-22 2002-04-11 Aventis Pharma Gmbh Substituierte Zimtsäureguanidide, Verfahren zur ihrer Herstellung, ihre Verwendung als Medikament sowie sie enthaltendes Medikament
AU2002213048A1 (en) 2000-10-05 2002-04-15 Smith Kline Beecham Corporation Phosphate transport inhibitors
EP2324861A1 (en) 2000-11-20 2011-05-25 Sorbent Therapeutics, Inc. In vivo use of water absorbent polymers
DE10063294A1 (de) 2000-12-19 2002-07-04 Aventis Pharma Gmbh Substituierte Heterocyclo-Norbornylamino-Derivate, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament
DE60233040D1 (de) 2001-03-29 2009-09-03 Synergy Pharmaceuticals Inc Guanylat-cyclase-rezeptor-agonisten zur behandlung von gewebeentzündung und karzinogenese
US6736705B2 (en) 2001-04-27 2004-05-18 Hitachi Global Storage Technologies Polishing process for glass or ceramic disks used in disk drive data storage devices
US20030216449A1 (en) 2001-05-11 2003-11-20 Joseph Weinstock Phosphate transport inhibitors
MY134211A (en) 2001-05-18 2007-11-30 Smithkline Beecham Corp Novel use
JP2007131532A (ja) 2001-09-28 2007-05-31 Kirin Brewery Co Ltd 生体内リン輸送を阻害する化合物およびそれを含んでなる医薬
FR2830451B1 (fr) 2001-10-09 2004-04-30 Inst Nat Sante Rech Med Utilisation de peptides analogues de la thymuline(pat)pour la fabrication de medicaments contre la douleur
JPWO2003048134A1 (ja) 2001-12-05 2005-04-14 日本たばこ産業株式会社 トリアゾール化合物及びその医薬用途
US6911453B2 (en) 2001-12-05 2005-06-28 Aventis Pharma Deutschland Gmbh Substituted 4-phenyltetrahydroisoquinolinium, process for their preparation, their use as a medicament, and medicament containing them
CA2469385A1 (en) 2001-12-05 2003-06-12 Aventis Pharma Deutschland Gmbh Substituted 4-phenyltetrahydroisoquinolines, process for their preparation, their use as medicament, and medicament containing them
DE10161767A1 (de) 2001-12-15 2003-06-26 Merck Patent Gmbh 2-Guanidino-4-heterocyclyl-chinazoline
EP1321142A1 (en) 2001-12-21 2003-06-25 Novartis AG Solid pharmaceutical composition for oral administration of Tegaserod
US6703405B2 (en) 2001-12-22 2004-03-09 Aventis Pharma Deutschland Gmbh Substituted 4-phenyltetrahydroisoquinolinium salts, process for their preparation, their use as a medicament, and medicament containing them
DE10163992A1 (de) 2001-12-24 2003-07-03 Merck Patent Gmbh 4-Aryl-chinazoline
US7119120B2 (en) 2001-12-26 2006-10-10 Genzyme Corporation Phosphate transport inhibitors
US7109184B2 (en) 2002-03-19 2006-09-19 Genzyme Corporation Phosphate transport inhibitors
CN100411618C (zh) 2002-05-17 2008-08-20 迪欧加药品公司 有效的选择性阿片受体调制剂化合物的用途
US7014862B2 (en) 2002-05-20 2006-03-21 The Procter & Gamble Company Chewable compositions containing a gel-forming extract of psyllium
US6923466B2 (en) 2002-12-17 2005-08-02 James Tsai Collapsible handcart capable of extending the area of carrier by operating handle
US7304036B2 (en) 2003-01-28 2007-12-04 Microbia, Inc. Methods and compositions for the treatment of gastrointestinal disorders
US20050054705A1 (en) 2003-02-04 2005-03-10 Aventis Pharma Deutschland Gmbh N-substituted (benzoimidazol-2-yl) phenylamines, process for their preparation, their use as medicament or diagnostic aid, and medicament comprising them
US7026303B2 (en) 2003-02-18 2006-04-11 The Procter & Gamble Company Compositions comprising a polysaccharide component and one or more coating layers
WO2004085448A2 (en) 2003-03-19 2004-10-07 Genzyme Corporation Unsaturated phosphinyl-phosphonate phosphate transport inhibitors
DE10312963A1 (de) * 2003-03-24 2004-10-07 Aventis Pharma Deutschland Gmbh Substituierte 4-Phenyltetrahydroisochinoline, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament, sowie sie enthaltendes Medikament
US7241775B2 (en) 2003-03-24 2007-07-10 Sanofi-Aventis Deutschland Gmbh Composition, process of making, and medical use of substituted 4-phenyltetrahydroisoquinolines
JP4926473B2 (ja) 2003-03-27 2012-05-09 協和発酵キリン株式会社 生体内リン輸送を阻害する化合物およびそれを含んでなる医薬
US20050244367A1 (en) 2004-05-03 2005-11-03 Ilypsa, Inc. Phospholipase inhibitors localized in the gastrointestinal lumen
AU2005257832A1 (en) 2004-05-14 2006-01-05 The University Of North Carolina At Chapel Hill Prouroguanylin as therapeutic and diagnostic agents
DE102004046492A1 (de) 2004-09-23 2006-03-30 Sanofi-Aventis Deutschland Gmbh Substituierte 4-Phenyltetrahydroisochinoline, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament, sowie sie enthaltendes Medikament
DE102004054847A1 (de) 2004-11-13 2006-05-24 Sanofi-Aventis Deutschland Gmbh Substituierte Benzoylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament
DE102005001411A1 (de) 2005-01-12 2006-07-27 Sanofi-Aventis Deutschland Gmbh Substituierte 4-Phenyltetrahydroisochinoline, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament, sowie sie enthaltendes Medikament
DE102005044815A1 (de) 2005-09-20 2007-03-22 Sanofi-Aventis Deutschland Gmbh Verwendung von Inhibitoren des Na+/H+ Austauschers, Subtyp 5 (NHE5) zur Gedächtnisverbesserung
DE102005044817A1 (de) 2005-09-20 2007-03-22 Sanofi-Aventis Deutschland Gmbh Substituierte 4-Phenyltetrahydroisochinoline, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament, sowie sie enthaltendes Medikament
CA2626961A1 (en) 2005-11-03 2007-05-18 Ilypsa, Inc. Phospholipase inhibitors, including multi-valent phospholipase inhibitors, and use thereof, including as lumen-localized phospholipase inhibitors
JP2009514893A (ja) 2005-11-03 2009-04-09 イリプサ， インコーポレイテッド 多価インドール化合物およびホスホリパーゼａ２インヒビターとしてのその使用
WO2008002971A2 (en) 2006-06-29 2008-01-03 Microbia, Inc. Methods and compositions for the treatment of gastrointestinal disorders
EP2129683A4 (en) 2007-02-26 2011-01-05 Ironwood Pharmaceuticals Inc METHODS AND COMPOSITIONS FOR TREATMENT OF HEART FAILURE AND OTHER DISORDERS
CA2686414A1 (en) 2007-05-04 2008-11-13 Ironwood Pharmaceuticals, Inc. Compositions and methods for treating disorders associated with salt or fluid retention
MX2011001821A (es) 2008-09-02 2011-03-25 Sanofi Aventis Aminoindanos sustituidos y sus analogos, y el uso farmaceutico de los mismos.
PT2384318T (pt) 2008-12-31 2018-02-07 Ardelyx Inc Compostos e métodos para inibir o antiporte mediado por nhe no tratamento de distúrbios associados com a retenção de fluidos ou sobrecarga de sal e distúrbios do trato gastrointestinal
WO2012054110A2 (en) 2010-07-07 2012-04-26 Ardelyx, Inc. Compounds and methods for inhibiting phosphate transport
WO2012006475A1 (en) 2010-07-07 2012-01-12 Ardelyx, Inc. Compounds and methods for inhibiting phosphate transport
WO2012006477A1 (en) * 2010-07-07 2012-01-12 Ardelyx, Inc. Compounds and methods for inhibiting phosphate transport
JP5827326B2 (ja) 2010-07-07 2015-12-02 アーデリクス，インコーポレーテッド リン酸輸送を阻害する化合物及び方法
KR102138390B1 (ko) * 2012-08-21 2020-07-27 알데릭스, 인코포레이티드 체액 저류 또는 염 과부하와 연관된 장애 및 위장관 장애의 치료에서 ｎｈｅ-매개된 역수송 저해를 위한 화합물 및 방법
AU2013304813B2 (en) * 2012-08-21 2016-08-04 Ardelyx, Inc. Compounds and methods for inhibiting NHE-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders
CA2909169A1 (en) * 2013-04-12 2014-10-16 Ardelyx, Inc. Nhe3-binding compounds and methods for inhibiting phosphate transport

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