HRP20030202A2 - A method of analgesia - Google Patents
A method of analgesiaInfo
- Publication number
- HRP20030202A2 HRP20030202A2 HR20030202A HRP20030202A HRP20030202A2 HR P20030202 A2 HRP20030202 A2 HR P20030202A2 HR 20030202 A HR20030202 A HR 20030202A HR P20030202 A HRP20030202 A HR P20030202A HR P20030202 A2 HRP20030202 A2 HR P20030202A2
- Authority
- HR
- Croatia
- Prior art keywords
- pain
- tetrodotoxin
- ttx
- cancer
- sodium channel
- Prior art date
Links
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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Landscapes
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- Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)
- Laser Surgery Devices (AREA)
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB001245171A CN1284536C (zh) | 2000-09-18 | 2000-09-18 | 河豚毒素或蛤蚌毒素及其类似物在制备用于全身镇痛的镇痛药中的应用 |
| PCT/CN2001/001391 WO2002022129A1 (en) | 2000-09-18 | 2001-09-11 | A method of analgesia |
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| HRP20030202A2 true HRP20030202A2 (en) | 2005-02-28 |
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| HR20030202A HRP20030202A2 (en) | 2000-09-18 | 2003-03-17 | A method of analgesia |
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| EP (3) | EP2298306B1 (ru) |
| JP (1) | JP2004508404A (ru) |
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| CN (1) | CN1284536C (ru) |
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| BR (1) | BR0113961A (ru) |
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| EE (1) | EE200300106A (ru) |
| ES (1) | ES2435463T3 (ru) |
| HR (1) | HRP20030202A2 (ru) |
| HU (1) | HUP0302677A3 (ru) |
| IL (1) | IL154342A0 (ru) |
| IS (1) | IS6719A (ru) |
| MX (1) | MXPA03002389A (ru) |
| NO (1) | NO323960B1 (ru) |
| PL (1) | PL360616A1 (ru) |
| SK (1) | SK3732003A3 (ru) |
| UA (1) | UA76960C2 (ru) |
| WO (1) | WO2002022129A1 (ru) |
| YU (1) | YU17103A (ru) |
| ZA (1) | ZA200301852B (ru) |
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| JP2001526648A (ja) | 1997-04-22 | 2001-12-18 | コセンシス・インコーポレイテッド | 炭素環及びヘテロ環で置換されたセミカルバゾン及びチオセミカルバゾン、及びその使用 |
| CN1236773C (zh) | 2000-11-22 | 2006-01-18 | 南宁枫叶药业有限公司 | 用于镇痛、麻醉或治疗药物依赖性的制剂 |
| US7119062B1 (en) | 2001-02-23 | 2006-10-10 | Neucoll, Inc. | Methods and compositions for improved articular surgery using collagen |
| CN1269482C (zh) * | 2001-05-18 | 2006-08-16 | 威克斯医药有限公司 | 钠离子通道阻断剂和阿片类镇痛剂在制备用于对哺乳动物进行协同镇痛的药物中的应用 |
| CN1203860C (zh) * | 2001-06-22 | 2005-06-01 | 威克斯医药有限公司 | 钠离子通道阻断剂和阿司匹林在制备用于对哺乳动物进行协同镇痛的药物中的应用 |
| US20030100574A1 (en) | 2001-11-15 | 2003-05-29 | Wilson Nestor Antonio Lagos | Use and application of a pharmaceutical composition containing a mixture of natural-origin heterocyclical guanidine, for cosmetology, wound healing, focal dystonia and muscular spasm-related clinical pathologies |
| WO2004013637A1 (en) * | 2002-08-01 | 2004-02-12 | Bayer Healthcare Ag | Diagnostics and therapeutics for diseases associated with g-protein coupled receptor 37 (gpr37) |
| AU2004207010A1 (en) * | 2003-01-30 | 2004-08-12 | Dynogen Pharmaceuticals, Inc. | Methods of treating lower urinary tract disorders using sodium channel modulators |
| CN1568999A (zh) * | 2003-07-14 | 2005-01-26 | 南宁枫叶药业有限公司 | 稳定的医药用河豚毒素冷冻干燥制剂 |
| JP2005154368A (ja) * | 2003-11-27 | 2005-06-16 | Teikoku Seiyaku Co Ltd | ジソピラミド含有神経因性疼痛の鎮痛剤 |
| CN1997373B (zh) * | 2004-05-07 | 2010-12-22 | 菲特托克斯有限公司 | 藻毒素及其用途 |
| JP2007538010A (ja) * | 2004-05-07 | 2007-12-27 | ファイトトックス リミテッド | フィコトキシンの経皮投与 |
| US20050282836A1 (en) * | 2004-06-22 | 2005-12-22 | Weiyang Lin | Solid orally ingestible formulations of tetrodotoxin |
| US20060034823A1 (en) * | 2004-08-13 | 2006-02-16 | Paul Reid | Method of production and use of crotoxin as an analgesic |
| CN100363006C (zh) * | 2004-08-20 | 2008-01-23 | 厦门朝阳生物工程有限公司 | 一种戒毒制剂及其制备方法 |
| EP1799219A1 (en) * | 2004-09-21 | 2007-06-27 | Laboratorios del Dr. Esteve S.A. | Tetrodotoxin and its derivatives for the treatment of central-nervously derived neuropathic pain |
| US20100075992A1 (en) * | 2004-09-22 | 2010-03-25 | Laboratorios Del Dr. Esteve S.A. | Tetrodotoxin and its derivatives for the treament of peripheral-nervously derived neuropathi pain |
| EP1690541A1 (en) * | 2005-02-11 | 2006-08-16 | Laboratorios Del Dr. Esteve, S.A. | Use of a sodium channel blocker and their analogues for the treatment of nicotine dependency |
| TW200640463A (en) * | 2005-02-11 | 2006-12-01 | Esteve Labor Dr | Use of sodium channel blockers and their analogues for the treatment of nicotine dependency |
| EP1714655A1 (en) * | 2005-04-22 | 2006-10-25 | Laboratorios Del Dr. Esteve, S.A. | Use of sodium channel blockers and their analogues for the treatment of nicotine dependency |
| EP1702627A1 (en) * | 2005-03-18 | 2006-09-20 | Laboratorios Del Dr. Esteve, S.A. | Analgesic combination of sodium channel blockers with opioid antagonists |
| EP1931349A4 (en) * | 2005-08-25 | 2009-08-05 | Wex Pharmaceuticals Inc | USE OF SODIUM CHANNEL BLOCKERS TO TREAT MUSCULO-SKELETAL PAIN |
| EP1928452A4 (en) * | 2005-08-25 | 2010-09-01 | Wex Medical Ltd | USE OF SODIUM CHANNEL BLOCKS FOR THE TREATMENT OF VISCERAL PAIN OR PAIN THROUGH CANCER TREATMENT |
| US20070148159A1 (en) * | 2005-12-22 | 2007-06-28 | Reid Paul F | Use of crotoxin as an analgesic - CIP |
| GB0603008D0 (en) * | 2006-02-14 | 2006-03-29 | Portela & Ca Sa | Method |
| EP1844781A1 (en) | 2006-02-22 | 2007-10-17 | Wex Pharmaceuticals Inc. | Use of sodium channel blockers for the treatment of preterm labor |
| EP2394646B1 (en) | 2006-03-27 | 2018-07-25 | Wex Medical Limited | Use of sodium channel blockers for the treatment of neuropathic pain developing as a consequence of chemotherapy |
| WO2007110220A1 (en) * | 2006-03-27 | 2007-10-04 | Wex Pharmaceuticals Inc. | USE OF 4,9-ANHYDRO-TETRODOTOXIN FOR THE TREATMENT OF DISEASES RELATED TO THE VOLTAGE-GATED SODIUM CHANNEL α SUBUNIT NAV 1.6 |
| EP1844782A1 (en) * | 2006-03-27 | 2007-10-17 | Wex Pharmaceuticals, Inc | Use of 4,9-anhydro-tetrodotoxin for the treatment of diseases related to the voltage-gated sodium channel subunit Nav1.6 |
| EP1844783A1 (en) * | 2006-03-27 | 2007-10-17 | Wex Pharmaceuticals, Inc | Use of 4,9-anhydro-tetrodotoxin for the treatment of diseases related to the voltage-gated sodium channel - subunit Nav1.6 |
| CN100438873C (zh) * | 2006-06-26 | 2008-12-03 | 黄致强 | 将河鲀毒素作为镇痛药的耐受抑制剂在制备复方镇痛制剂中的应用 |
| EP1882692A1 (en) * | 2006-07-28 | 2008-01-30 | Wex Pharmaceuticals Inc. | Dimethano-[1,3]dioxocino[6,5-D]pyrimidine-spiro derivatives of tetrodotoxin, process for their synthesis and uses thereof in the treatment of pain |
| CN101730467A (zh) * | 2007-07-06 | 2010-06-09 | 努恩治疗学股份有限公司 | 神经病性疼痛的治疗 |
| CN101352422B (zh) * | 2008-09-17 | 2011-04-20 | 厦门朝阳生物工程有限公司 | 河豚毒素冻干粉针制剂及其制备方法 |
| US8952152B2 (en) | 2009-03-24 | 2015-02-10 | Proteus S.A. | Methods for purifying phycotoxins, pharmaceutical compositions containing purified phycotoxins, and methods of use thereof |
| US20120034296A1 (en) * | 2009-04-08 | 2012-02-09 | Massachusetts Institute Of Technology | Prolonged duration local anesthesia with minimal toxicity |
| US9107925B2 (en) | 2010-02-10 | 2015-08-18 | Phytotox Limited | Sodium channel blocker for treatment of loss of superficial sensitivity |
| JP2014504184A (ja) | 2010-12-01 | 2014-02-20 | スパイナル・モデュレーション・インコーポレイテッド | 神経構造への薬剤の直接送達 |
| MX2015010749A (es) | 2013-03-14 | 2015-11-30 | Regeneron Pharma | Anticuerpos humanos para nav1.7. |
| CN105142625B (zh) | 2013-03-15 | 2019-09-06 | 儿童医学中心公司 | 用于长效局部麻醉的新蛤蚌毒素组合配制品 |
| US8992927B1 (en) | 2014-07-15 | 2015-03-31 | Kymab Limited | Targeting human NAV1.7 variants for treatment of pain |
| US8986694B1 (en) | 2014-07-15 | 2015-03-24 | Kymab Limited | Targeting human nav1.7 variants for treatment of pain |
| GB201403775D0 (en) | 2014-03-04 | 2014-04-16 | Kymab Ltd | Antibodies, uses & methods |
| WO2018083248A1 (en) | 2016-11-03 | 2018-05-11 | Kymab Limited | Antibodies, combinations comprising antibodies, biomarkers, uses & methods |
| CN107198689A (zh) * | 2017-07-11 | 2017-09-26 | 东新皓特（北京）生化科技有限公司 | 用于治疗疼痛病症的河豚毒素药物组合物及外用药 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4029793A (en) | 1973-06-12 | 1977-06-14 | Astra Pharmaceutical Products, Inc. | Synergistic local anesthetic compositions |
| US4022899A (en) | 1973-06-12 | 1977-05-10 | Astra Pharmaceutical Products, Inc. | Synergistic local anesthetic compositions |
| AU1888195A (en) * | 1994-03-17 | 1995-10-03 | Nanning Maple Leaf Pharmaceutical Co. Ltd. | The use of amino hydrogenated quinazoline compounds and derivatives thereof for abstaining from drug dependence |
| CN1072486C (zh) * | 1996-09-24 | 2001-10-10 | 王维国 | 用于戒毒、镇痛的药剂及其制法 |
| AU6883798A (en) * | 1997-04-02 | 1998-10-22 | Regents Of The University Of California, The | Method of anesthesia |
| US6326020B1 (en) * | 1997-05-16 | 2001-12-04 | Children's Medical Center Corporation | Local anesthetic formulations |
| CN1236773C (zh) * | 2000-11-22 | 2006-01-18 | 南宁枫叶药业有限公司 | 用于镇痛、麻醉或治疗药物依赖性的制剂 |
| CN1269482C (zh) * | 2001-05-18 | 2006-08-16 | 威克斯医药有限公司 | 钠离子通道阻断剂和阿片类镇痛剂在制备用于对哺乳动物进行协同镇痛的药物中的应用 |
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