JP4499363B2 - 血清グルコースの減少方法 - Google Patents
血清グルコースの減少方法 Download PDFInfo
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- JP4499363B2 JP4499363B2 JP2002582950A JP2002582950A JP4499363B2 JP 4499363 B2 JP4499363 B2 JP 4499363B2 JP 2002582950 A JP2002582950 A JP 2002582950A JP 2002582950 A JP2002582950 A JP 2002582950A JP 4499363 B2 JP4499363 B2 JP 4499363B2
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Classifications
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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
- A61K31/74—Synthetic polymeric materials
- A61K31/785—Polymers containing nitrogen
- A61K31/787—Polymers containing nitrogen containing heterocyclic rings having nitrogen as a ring hetero atom
-
- 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
- A61K31/74—Synthetic polymeric materials
- A61K31/785—Polymers containing nitrogen
-
- 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
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Landscapes
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Obesity (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Applications Claiming Priority (3)
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|---|---|---|---|
| US28444501P | 2001-04-18 | 2001-04-18 | |
| US30556401P | 2001-07-13 | 2001-07-13 | |
| PCT/US2002/011493 WO2002085377A1 (en) | 2001-04-18 | 2002-04-10 | Method for lowering serum glucose |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010009197A Division JP2010090172A (ja) | 2001-04-18 | 2010-01-19 | 血清グルコースの減少方法 |
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| Publication Number | Publication Date |
|---|---|
| JP2004535384A JP2004535384A (ja) | 2004-11-25 |
| JP2004535384A5 JP2004535384A5 (enExample) | 2005-12-22 |
| JP4499363B2 true JP4499363B2 (ja) | 2010-07-07 |
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| JP2002582950A Expired - Lifetime JP4499363B2 (ja) | 2001-04-18 | 2002-04-10 | 血清グルコースの減少方法 |
| JP2010009197A Pending JP2010090172A (ja) | 2001-04-18 | 2010-01-19 | 血清グルコースの減少方法 |
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Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6733780B1 (en) | 1999-10-19 | 2004-05-11 | Genzyme Corporation | Direct compression polymer tablet core |
| ES2637020T3 (es) * | 2001-04-18 | 2017-10-10 | Genzyme Corporation | Uso de polímero de amina para reducir la glucosa sérica |
| AU2003282867A1 (en) * | 2002-10-22 | 2004-05-13 | Genzyme Corporation | Amine polymers for promoting bone formation |
| US7608674B2 (en) * | 2003-11-03 | 2009-10-27 | Ilypsa, Inc. | Pharmaceutical compositions comprising cross-linked small molecule amine polymers |
| US7449605B2 (en) * | 2003-11-03 | 2008-11-11 | Ilypsa, Inc. | Crosslinked amine polymers |
| US7767768B2 (en) * | 2003-11-03 | 2010-08-03 | Ilypsa, Inc. | Crosslinked amine polymers |
| US7335795B2 (en) * | 2004-03-22 | 2008-02-26 | Ilypsa, Inc. | Crosslinked amine polymers |
| US7385012B2 (en) * | 2003-11-03 | 2008-06-10 | Ilypsa, Inc. | Polyamine polymers |
| US7459502B2 (en) * | 2003-11-03 | 2008-12-02 | Ilypsa, Inc. | Pharmaceutical compositions comprising crosslinked polyamine polymers |
| ES2397159T3 (es) * | 2004-03-26 | 2013-03-05 | Mitsubishi Tanabe Pharma Corporation | Agente mejorador de la resistencia a insulina |
| US7985418B2 (en) | 2004-11-01 | 2011-07-26 | Genzyme Corporation | Aliphatic amine polymer salts for tableting |
| WO2006072054A1 (en) * | 2004-12-30 | 2006-07-06 | Genzyme Corporation | Zinc-containing treatments for hyperphosphatemia |
| JP2009507019A (ja) * | 2005-09-02 | 2009-02-19 | ジェンザイム・コーポレーション | リン酸塩を除去する方法およびそれに使用される重合体 |
| KR101547925B1 (ko) | 2005-09-15 | 2015-08-27 | 젠자임 코포레이션 | 아민 중합체에 대한 샤셋 제형 |
| WO2007056405A2 (en) * | 2005-11-08 | 2007-05-18 | Genzyme Corporation | Magnesium-containing polymers for the treatment of hyperphosphatemia |
| EP2043627A2 (en) * | 2006-07-05 | 2009-04-08 | Genzyme Corporation | Iron(ii)-containing treatments for hyperphosphatemia |
| US7964182B2 (en) * | 2006-09-01 | 2011-06-21 | USV, Ltd | Pharmaceutical compositions comprising phosphate-binding polymer |
| BRPI0717008A2 (pt) * | 2006-09-01 | 2014-01-21 | Usv Ltd | Processo para o preparo de cloridrato de sevelamer e formulação do mesmo |
| WO2008042222A2 (en) | 2006-09-29 | 2008-04-10 | Genzyme Corporation | Amide dendrimer compositions |
| WO2008076242A1 (en) | 2006-12-14 | 2008-06-26 | Genzyme Corporation | Amido-amine polymer compositions |
| EP2361171A4 (en) * | 2008-09-15 | 2014-11-05 | Shasun Chemicals And Drugs Ltd | PROCESS FOR PREPARING NETWORKED POLYMERS IN A NON-AQUEOUS SOLUTION |
| AU2010209293A1 (en) * | 2009-01-22 | 2011-09-08 | Usv Limited | Pharmaceutical compositions comprising phosphate-binding polymer |
| US9566299B2 (en) | 2013-02-08 | 2017-02-14 | Wockhardt Limited | Oral pharmaceutical composition of aliphatic amine polymer or salts thereof |
| CA2906501A1 (en) * | 2013-03-15 | 2014-09-25 | Genzyme Corporation | Sequestrants of advanced glycation end product (age) precursors |
| EP3164155B1 (en) | 2014-06-13 | 2022-02-09 | United Therapeutics Corporation | Treprostinil formulations |
| MA41202A (fr) * | 2014-12-18 | 2017-10-24 | Genzyme Corp | Copolymères polydiallymine réticulé pour le traitement du diabète de type 2 |
| WO2018124264A1 (ja) | 2016-12-28 | 2018-07-05 | 富士フイルム株式会社 | 窒素原子含有ポリマー又はその塩の乳化液、その製造方法、及び粒子の製造方法 |
| JP6992084B2 (ja) | 2017-10-16 | 2022-01-13 | 富士フイルム株式会社 | 高リン血症治療剤 |
| CN116018146A (zh) * | 2021-08-24 | 2023-04-25 | 中美华世通生物医药科技(武汉)股份有限公司 | 用于治疗高尿酸血症的聚合物、组合物和方法 |
| ES2980624T3 (es) * | 2021-08-24 | 2024-10-02 | Waterstone Pharmaceuticals Wuhan Co Ltd | Polímeros, composiciones y métodos para tratar hiperuricemia |
Family Cites Families (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4528847A (en) * | 1983-10-04 | 1985-07-16 | D. Halmi And Associates, Inc. | Flow metering device with recessed pressure taps |
| JPS6090243A (ja) | 1983-10-25 | 1985-05-21 | Nitto Boseki Co Ltd | 小球状モノアリルアミン橋かけ重合体の製造方法 |
| US4528347A (en) | 1983-11-10 | 1985-07-09 | 501 Nitto Boseki, Co. Ltd | Process for producing polymers of monoallylamine |
| US5468727A (en) * | 1990-12-13 | 1995-11-21 | Board Of Regents, The University Of Texas System | Methods of normalizing metabolic parameters in diabetics |
| JP3507523B2 (ja) | 1993-05-12 | 2004-03-15 | 積水化学工業株式会社 | 糖質吸収抑制剤 |
| US5487888A (en) | 1993-05-20 | 1996-01-30 | Geltex, Inc. | Iron-binding polymers for oral administration |
| US5607669A (en) | 1994-06-10 | 1997-03-04 | Geltex Pharmaceuticals, Inc. | Amine polymer sequestrant and method of cholesterol depletion |
| US5624963A (en) | 1993-06-02 | 1997-04-29 | Geltex Pharmaceuticals, Inc. | Process for removing bile salts from a patient and compositions therefor |
| US5900475A (en) | 1994-06-10 | 1999-05-04 | Geltex Pharmaceuticals, Inc. | Hydrophobic sequestrant for cholesterol depletion |
| US5618530A (en) | 1994-06-10 | 1997-04-08 | Geltex Pharmaceuticals, Inc. | Hydrophobic amine polymer sequestrant and method of cholesterol depletion |
| US5703188A (en) | 1993-06-02 | 1997-12-30 | Geltex Pharmaceuticals, Inc. | Process for removing bile salts from a patient and compositions therefor |
| US5667775A (en) | 1993-08-11 | 1997-09-16 | Geltex Pharmaceuticals, Inc. | Phosphate-binding polymers for oral administration |
| US5496545A (en) * | 1993-08-11 | 1996-03-05 | Geltex Pharmaceuticals, Inc. | Phosphate-binding polymers for oral administration |
| TW474813B (en) | 1994-06-10 | 2002-02-01 | Geltex Pharma Inc | Alkylated composition for removing bile salts from a patient |
| JP4156684B2 (ja) * | 1996-03-05 | 2008-09-24 | 三菱化学株式会社 | 高リン血症予防および／または治療剤 |
| US6203785B1 (en) | 1996-12-30 | 2001-03-20 | Geltex Pharmaceuticals, Inc. | Poly(diallylamine)-based bile acid sequestrants |
| US5925379A (en) | 1997-03-27 | 1999-07-20 | Geltex Pharmaceuticals, Inc. | Interpenetrating polymer networks for sequestration of bile acids |
| TW592727B (en) | 1997-04-04 | 2004-06-21 | Chugai Pharmaceutical Co Ltd | Phosphate-binding polymer preparations |
| US6423754B1 (en) | 1997-06-18 | 2002-07-23 | Geltex Pharmaceuticals, Inc. | Method for treating hypercholesterolemia with polyallylamine polymers |
| FR2766195A1 (fr) | 1997-07-21 | 1999-01-22 | Transgene Sa | Polymeres cationiques, complexes associant lesdits polymeres cationiques et des substances therapeutiquement actives comprenant au moins une charges negative, notamment des acides nucleiques, et leur utilisation en therapie genique |
| US6083497A (en) | 1997-11-05 | 2000-07-04 | Geltex Pharmaceuticals, Inc. | Method for treating hypercholesterolemia with unsubstituted polydiallylamine polymers |
| US6726905B1 (en) | 1997-11-05 | 2004-04-27 | Genzyme Corporation | Poly (diallylamines)-based phosphate binders |
| US5985938A (en) | 1997-11-05 | 1999-11-16 | Geltex Pharmaceuticals, Inc. | Method for reducing oxalate |
| WO1999040990A1 (en) | 1998-02-17 | 1999-08-19 | University Of Maryland | Anion binding polymers and the use thereof |
| EP1340510A1 (en) * | 1998-12-23 | 2003-09-03 | G.D. Searle LLC. | Combinations of cholesteryl ester transfer protein inhibitors and bile acid sequestering agents for cardiovascular indications |
| AU7856200A (en) * | 1999-10-07 | 2001-05-10 | University Of Maryland | Sugar binding polymers and the use thereof |
| TWI241195B (en) * | 2000-04-10 | 2005-10-11 | Shionogi & Co | Preventive agent for bile acidic diarrhea |
| ES2637020T3 (es) * | 2001-04-18 | 2017-10-10 | Genzyme Corporation | Uso de polímero de amina para reducir la glucosa sérica |
| US20020198202A1 (en) | 2001-06-07 | 2002-12-26 | Wyeth | Combination of a PTPase inhibitor and an antilipemic agent |
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2002
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- 2002-04-10 DK DK02726733T patent/DK1392331T3/da active
- 2002-04-10 NZ NZ528831A patent/NZ528831A/en unknown
- 2002-04-10 AU AU2002257145A patent/AU2002257145B2/en not_active Expired
- 2002-04-10 DE DE60225908T patent/DE60225908T2/de not_active Expired - Lifetime
- 2002-04-10 ES ES02726733T patent/ES2304437T3/es not_active Expired - Lifetime
- 2002-04-10 KR KR10-2003-7013678A patent/KR20040018358A/ko not_active Withdrawn
- 2002-04-10 MX MXPA03009568A patent/MXPA03009568A/es unknown
- 2002-04-10 WO PCT/US2002/011493 patent/WO2002085377A1/en not_active Ceased
- 2002-04-10 DK DK08002418.5T patent/DK1923064T3/en active
- 2002-04-10 CN CNA028099958A patent/CN1511039A/zh active Pending
- 2002-04-10 EP EP02726733A patent/EP1392331B1/en not_active Expired - Lifetime
- 2002-04-10 JP JP2002582950A patent/JP4499363B2/ja not_active Expired - Lifetime
- 2002-04-10 CA CA2444046A patent/CA2444046C/en not_active Expired - Fee Related
- 2002-04-10 PT PT80024185T patent/PT1923064T/pt unknown
- 2002-04-10 AT AT02726733T patent/ATE390927T1/de active
- 2002-04-10 BR BR0209134-8 patent/BRPI0209134B8/pt not_active IP Right Cessation
- 2002-04-17 US US10/125,700 patent/US7229613B2/en not_active Expired - Lifetime
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Also Published As
| Publication number | Publication date |
|---|---|
| CA2444046A1 (en) | 2002-10-31 |
| DE60225908T2 (de) | 2009-05-14 |
| ES2304437T3 (es) | 2008-10-16 |
| WO2002085377A8 (en) | 2002-11-28 |
| ES2637020T3 (es) | 2017-10-10 |
| BRPI0209134B1 (pt) | 2019-08-27 |
| US20020187121A1 (en) | 2002-12-12 |
| KR20040018358A (ko) | 2004-03-03 |
| MXPA03009568A (es) | 2004-02-12 |
| US20070286841A1 (en) | 2007-12-13 |
| PT1923064T (pt) | 2017-08-23 |
| JP2004535384A (ja) | 2004-11-25 |
| CN1511039A (zh) | 2004-07-07 |
| DK1392331T3 (da) | 2008-06-23 |
| US7229613B2 (en) | 2007-06-12 |
| JP2010090172A (ja) | 2010-04-22 |
| WO2002085377A1 (en) | 2002-10-31 |
| BR0209134A (pt) | 2004-06-15 |
| NZ528831A (en) | 2005-07-29 |
| ATE390927T1 (de) | 2008-04-15 |
| BRPI0209134B8 (pt) | 2021-05-25 |
| DE60225908D1 (de) | 2008-05-15 |
| DK1923064T3 (en) | 2017-10-02 |
| EP1392331A1 (en) | 2004-03-03 |
| EP1392331B1 (en) | 2008-04-02 |
| AU2002257145B2 (en) | 2005-06-02 |
| CA2444046C (en) | 2011-06-07 |
| CY1119486T1 (el) | 2018-03-07 |
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