CN114286670B - 含有地夸磷索或其盐、及聚乙烯吡咯烷酮的水性眼科用组合物 - Google Patents
含有地夸磷索或其盐、及聚乙烯吡咯烷酮的水性眼科用组合物 Download PDFInfo
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- CN114286670B CN114286670B CN202080059970.2A CN202080059970A CN114286670B CN 114286670 B CN114286670 B CN 114286670B CN 202080059970 A CN202080059970 A CN 202080059970A CN 114286670 B CN114286670 B CN 114286670B
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- eye
- drops
- sodium
- ophthalmic composition
- polyvinylpyrrolidone
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- 239000000203 mixture Substances 0.000 title claims abstract description 259
- 229950003529 diquafosol Drugs 0.000 title claims abstract description 110
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- 239000001267 polyvinylpyrrolidone Substances 0.000 title claims abstract description 82
- NMLMACJWHPHKGR-NCOIDOBVSA-N P(1),P(4)-bis(uridin-5'-yl) tetraphosphate Chemical compound N1([C@@H]2O[C@@H]([C@H]([C@H]2O)O)COP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@H]([C@@H](O2)N2C(NC(=O)C=C2)=O)O)O)C=CC(=O)NC1=O NMLMACJWHPHKGR-NCOIDOBVSA-N 0.000 title claims abstract description 36
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- OWTGMPPCCUSXIP-FNXFGIETSA-J tetrasodium;[[(2r,3s,4r,5r)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl] [[[(2r,3s,4r,5r)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl]oxy-oxidophosphoryl] phosphate Chemical compound [Na+].[Na+].[Na+].[Na+].N1([C@@H]2O[C@@H]([C@H]([C@H]2O)O)COP([O-])(=O)OP([O-])(=O)OP([O-])(=O)OP([O-])(=O)OC[C@@H]2[C@H]([C@H]([C@@H](O2)N2C(NC(=O)C=C2)=O)O)O)C=CC(=O)NC1=O OWTGMPPCCUSXIP-FNXFGIETSA-J 0.000 description 97
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- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
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- A61K9/0012—Galenical forms characterised by the site of application
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Landscapes
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CN114646705A (zh) * | 2022-03-22 | 2022-06-21 | 武汉绿合医药科技有限公司 | 一种地夸磷索钠滴眼液有关物质含量检测方法 |
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Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5591426A (en) * | 1993-07-02 | 1997-01-07 | Bausch & Lomb Incorporated | Ophthalmic solution for artificial tears |
US6274626B1 (en) * | 1998-12-22 | 2001-08-14 | Bausch & Lomb Incorporated | Pheniramine-containing compositions and method for treating allergic responses |
CN1413114A (zh) * | 1999-12-27 | 2003-04-23 | 参天制药株式会社 | 用于稳定泪液层的体系 |
CN103096929A (zh) * | 2010-09-10 | 2013-05-08 | 参天制药株式会社 | 以组合p2y2受体激动剂和透明质酸或其盐为特征的干眼症治疗剂、干眼症的治疗方法、及干眼症治疗剂的应用 |
CN104203254A (zh) * | 2012-03-26 | 2014-12-10 | 参天制药株式会社 | 含有地夸磷索的滴眼液 |
US20160213708A1 (en) * | 2012-01-08 | 2016-07-28 | Medicure Technologies Ltd. | Ophthalmic composition |
WO2016195072A1 (ja) * | 2015-06-05 | 2016-12-08 | 参天製薬株式会社 | ソフトコンタクトレンズが装用されたドライアイ患者の眼に点眼されるように用いられることを特徴とするドライアイ治療剤 |
CN111757742A (zh) * | 2018-02-28 | 2020-10-09 | 参天制药株式会社 | 含有地夸磷索及阳离子性聚合物的眼科用组合物 |
Family Cites Families (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0365270A (ja) | 1989-07-31 | 1991-03-20 | Kanzaki Paper Mfg Co Ltd | 塗布シートの製造方法 |
JPH0365270U (ko) | 1989-10-31 | 1991-06-25 | ||
US5358706A (en) * | 1992-09-30 | 1994-10-25 | Union Carbide Chemicals & Plastics Technology Corporation | Muco-adhesive polymers |
US5422116A (en) * | 1994-02-18 | 1995-06-06 | Ciba-Geigy Corporation | Liquid ophthalmic sustained release delivery system |
KR100549904B1 (ko) * | 1996-03-27 | 2006-05-16 | 더 유니버시티 오브 노쓰 캐롤라이나 엣 채플 힐 | 우리딘트리포스페이트및관련화합물을함유하는섬모운동장해치료용약학조성물 |
US5900407A (en) * | 1997-02-06 | 1999-05-04 | Inspire Pharmaceuticals, Inc. | Method of treating dry eye disease with uridine triphosphates and related compounds |
AU2001260643B9 (en) * | 2000-05-30 | 2006-10-19 | Merck Sharp & Dohme Corp. | Ectocornea extension promoters |
KR101484499B1 (ko) * | 2005-02-14 | 2015-01-20 | 존슨 앤드 존슨 비젼 케어, 인코포레이티드 | 안과용 렌즈의 제조방법, 안과용 장치 및 콘택트 렌즈 |
TW201306844A (zh) * | 2010-12-28 | 2013-02-16 | 參天製藥股份有限公司 | 含有迪夸弗索點眼液及其製造方法、不溶性析出物產生之抑制方法 |
KR20120077080A (ko) | 2010-12-30 | 2012-07-10 | 동우 화인켐 주식회사 | 광학필름 및 이를 이용한 백라이트 유닛 |
JP2015032653A (ja) | 2013-08-01 | 2015-02-16 | 株式会社東芝 | 固体撮像装置 |
JP6267003B2 (ja) | 2014-02-27 | 2018-01-24 | 参天製薬株式会社 | ジクアホソルまたはその塩およびレバミピドまたはその塩を組み合わせたことを特徴とする涙液分泌促進剤 |
MA39767B1 (fr) * | 2014-05-07 | 2019-10-31 | Croma Pharma Ges M B H | Solution aqueuse ophtalmique et méthode de traitement du syndrome de l'œil sec |
BR112017013841A2 (pt) * | 2014-12-25 | 2018-06-19 | Santen Pharmaceutical Co., Ltd. | solução oftálmica aquosa |
-
2020
- 2020-08-25 CN CN202311818685.6A patent/CN117771172A/zh active Pending
- 2020-08-25 JP JP2021521065A patent/JP6966667B2/ja active Active
- 2020-08-25 CN CN202080059970.2A patent/CN114286670B/zh active Active
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- 2020-08-25 WO PCT/JP2020/031917 patent/WO2021039748A1/ja active Application Filing
-
2021
- 2021-10-20 JP JP2021171358A patent/JP2022003099A/ja active Pending
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5591426A (en) * | 1993-07-02 | 1997-01-07 | Bausch & Lomb Incorporated | Ophthalmic solution for artificial tears |
US6274626B1 (en) * | 1998-12-22 | 2001-08-14 | Bausch & Lomb Incorporated | Pheniramine-containing compositions and method for treating allergic responses |
CN1413114A (zh) * | 1999-12-27 | 2003-04-23 | 参天制药株式会社 | 用于稳定泪液层的体系 |
CN103096929A (zh) * | 2010-09-10 | 2013-05-08 | 参天制药株式会社 | 以组合p2y2受体激动剂和透明质酸或其盐为特征的干眼症治疗剂、干眼症的治疗方法、及干眼症治疗剂的应用 |
US20160213708A1 (en) * | 2012-01-08 | 2016-07-28 | Medicure Technologies Ltd. | Ophthalmic composition |
CN104203254A (zh) * | 2012-03-26 | 2014-12-10 | 参天制药株式会社 | 含有地夸磷索的滴眼液 |
WO2016195072A1 (ja) * | 2015-06-05 | 2016-12-08 | 参天製薬株式会社 | ソフトコンタクトレンズが装用されたドライアイ患者の眼に点眼されるように用いられることを特徴とするドライアイ治療剤 |
CN111757742A (zh) * | 2018-02-28 | 2020-10-09 | 参天制药株式会社 | 含有地夸磷索及阳离子性聚合物的眼科用组合物 |
Non-Patent Citations (5)
Title |
---|
Combining Sodium Hyaluronate and Polyvinylpyrrolidone Therapies for the Rabbit Cornea: A New Approach to Relief of the Human Dry Eye Syndrome;Moshe Ehrenberg et al.;《Current Eye Research》;第40卷(第9期);第913-922页 * |
Preservative-free ocular hydrating agents in symptomatic contact lens wearers: saline versus PVP solutio;Malet Florence et al.;《EYE & CONTACT LENS》;20030131;第29卷(第1期);第38-43页 * |
双氯芬酸钠滴眼液刺激性的缓解;孙刚等;《药学研究》;第32卷(第1期);第34-35页 * |
地夸磷索滴眼液在干眼治疗中的应用;陈秀洋等;《中国新药与临床杂志》;第38卷(第7期);第390-394页 * |
段辉等.《眼科临床药物手册》.辽宁科学技术出版社,2017,第2页. * |
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JP2022003099A (ja) | 2022-01-11 |
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TW202122094A (zh) | 2021-06-16 |
CN117771172A (zh) | 2024-03-29 |
KR102656181B1 (ko) | 2024-04-08 |
CN114286670A (zh) | 2022-04-05 |
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