NO322571B1 - Kondenserte azepiner som vasopressinagonister - Google Patents
Kondenserte azepiner som vasopressinagonister Download PDFInfo
- Publication number
- NO322571B1 NO322571B1 NO20023137A NO20023137A NO322571B1 NO 322571 B1 NO322571 B1 NO 322571B1 NO 20023137 A NO20023137 A NO 20023137A NO 20023137 A NO20023137 A NO 20023137A NO 322571 B1 NO322571 B1 NO 322571B1
- Authority
- NO
- Norway
- Prior art keywords
- pharmaceutically acceptable
- acceptable salt
- compound according
- proline
- methyl
- Prior art date
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- 150000001538 azepines Chemical class 0.000 title claims description 4
- 229940083335 Vasopressin agonist Drugs 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 61
- 150000003839 salts Chemical class 0.000 claims description 28
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 16
- 229910052717 sulfur Inorganic materials 0.000 claims description 16
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- 238000000034 method Methods 0.000 claims description 14
- 238000002360 preparation method Methods 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 229910052801 chlorine Inorganic materials 0.000 claims description 11
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- 208000003450 Neurogenic Diabetes Insipidus Diseases 0.000 claims description 8
- 201000010064 diabetes insipidus Diseases 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- 201000005119 neurohypophyseal diabetes insipidus Diseases 0.000 claims description 8
- -1 OBn Chemical group 0.000 claims description 7
- 229910052794 bromium Inorganic materials 0.000 claims description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 7
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- 208000034158 bleeding Diseases 0.000 claims description 5
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- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
-
- 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
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- 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
- A61P5/10—Drugs for disorders of the endocrine system of the posterior pituitary hormones, e.g. oxytocin, ADH
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- 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
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- 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
- A61P7/12—Antidiuretics, e.g. drugs for diabetes insipidus
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Cephalosporin Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0000079.4A GB0000079D0 (en) | 2000-01-05 | 2000-01-05 | Novel antidiuretic agents |
| PCT/GB2001/000023 WO2001049682A1 (en) | 2000-01-05 | 2001-01-04 | Condensed azepines as vasopressin agonists |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20023137D0 NO20023137D0 (no) | 2002-06-27 |
| NO20023137L NO20023137L (no) | 2002-06-27 |
| NO322571B1 true NO322571B1 (no) | 2006-10-30 |
Family
ID=9883168
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20023137A NO322571B1 (no) | 2000-01-05 | 2002-06-27 | Kondenserte azepiner som vasopressinagonister |
Country Status (34)
| Country | Link |
|---|---|
| US (3) | US7074781B2 (de) |
| EP (1) | EP1248784B1 (de) |
| JP (2) | JP3869723B2 (de) |
| KR (1) | KR100605466B1 (de) |
| CN (1) | CN1183129C (de) |
| AR (1) | AR035327A1 (de) |
| AT (1) | ATE366730T1 (de) |
| AU (1) | AU777538B2 (de) |
| BR (1) | BR0107414B1 (de) |
| CA (1) | CA2396277C (de) |
| CY (1) | CY1108034T1 (de) |
| CZ (1) | CZ303444B6 (de) |
| DE (1) | DE60129298T2 (de) |
| DK (1) | DK1248784T3 (de) |
| EE (1) | EE200200367A (de) |
| ES (1) | ES2288923T3 (de) |
| GB (1) | GB0000079D0 (de) |
| HK (1) | HK1046910B (de) |
| HR (1) | HRP20020481B1 (de) |
| HU (1) | HU229937B1 (de) |
| IL (1) | IL149528A0 (de) |
| MX (1) | MXPA02006546A (de) |
| MY (1) | MY140467A (de) |
| NO (1) | NO322571B1 (de) |
| NZ (1) | NZ518803A (de) |
| PL (1) | PL211341B1 (de) |
| PT (1) | PT1248784E (de) |
| RU (1) | RU2259367C2 (de) |
| SI (1) | SI1248784T1 (de) |
| SK (1) | SK287005B6 (de) |
| UA (1) | UA73152C2 (de) |
| UY (1) | UY26521A1 (de) |
| WO (1) | WO2001049682A1 (de) |
| ZA (1) | ZA200205180B (de) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7138393B2 (en) | 1998-07-24 | 2006-11-21 | Wyeth | Biologically active vasopressin agonist metabolites |
| GB0000079D0 (en) | 2000-01-05 | 2000-02-23 | Ferring Bv | Novel antidiuretic agents |
| MXPA02009382A (es) * | 2000-03-27 | 2003-01-28 | Applied Research Systems | Derivados de pirrolidina farmaceuticamente activos. |
| WO2001074769A1 (en) * | 2000-03-27 | 2001-10-11 | Applied Research Systems Ars Holding N.V. | Pharmaceutically active pyrrolidine derivatives as bax inhibitors |
| GB0015601D0 (en) * | 2000-06-26 | 2000-08-16 | Ferring Bv | Novel antidiuretic agents |
| GB0115515D0 (en) * | 2001-06-25 | 2001-08-15 | Ferring Bv | Oxytocin agonisys |
| GB0210397D0 (en) | 2002-05-07 | 2002-06-12 | Ferring Bv | Pharmaceutical formulations |
| RU2326868C2 (ru) * | 2003-04-28 | 2008-06-20 | Астеллас Фарма Инк. | Производное 4,4-дифтор-1,2,2,4-тетрагидро-5н-1-бензазепина или его соль |
| DE60305043T2 (de) * | 2003-11-13 | 2006-11-30 | Ferring B.V. | Blisterverpackung und feste Dosierungsform enthaltend Desmopressin |
| WO2006054560A1 (ja) * | 2004-11-17 | 2006-05-26 | Kissei Pharmaceutical Co., Ltd. | 芳香族アミド誘導体、それを含有する医薬組成物およびそれらの医薬用途 |
| CA2602351A1 (en) * | 2005-03-25 | 2006-10-05 | Kissei Pharmaceutical Co., Ltd. | Urea derivative, medicinal composition containing the same, and medicinal use of these |
| WO2007052517A1 (ja) * | 2005-10-31 | 2007-05-10 | Sumitomo Chemical Company, Limited | ヒドロキシ－２－ピロリジンカルボキシアミド化合物の製法 |
| JP5220611B2 (ja) * | 2006-09-25 | 2013-06-26 | キッセイ薬品工業株式会社 | １，４−ベンゾジアゼピン誘導体、それを含有する医薬組成物およびそれらの医薬用途 |
| WO2008141081A1 (en) * | 2007-05-10 | 2008-11-20 | Amr Technology, Inc. | Aryl- and heteroaryl-substituted tetrahydrobenzo-1,4-diazepines and use thereof to block reuptake of norepinephrine, dopamine, and serotonin |
| CA2988753A1 (en) | 2007-08-06 | 2009-02-12 | Serenity Pharmaceuticals, Llc | Methods and devices for desmopressin drug delivery |
| US11963995B2 (en) | 2008-05-21 | 2024-04-23 | Ferring B.V. | Methods comprising desmopressin |
| ES2462465T5 (es) * | 2008-05-21 | 2018-02-28 | Ferring B.V. | Desmopresina bucodispersable para aumentar el periodo inicial del sueño no alterado por nocturia |
| US20100286045A1 (en) | 2008-05-21 | 2010-11-11 | Bjarke Mirner Klein | Methods comprising desmopressin |
| GB201005623D0 (en) | 2010-04-01 | 2010-05-19 | Vantia Ltd | New polymorph |
| GB201105537D0 (en) * | 2011-03-31 | 2011-05-18 | Vantia Ltd | New process |
| WO2020154581A1 (en) | 2019-01-24 | 2020-07-30 | Assia Chemical Industries Ltd | Solid state forms of fedovapagon-salicyclic acid co-crystal |
Family Cites Families (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3960886A (en) | 1968-07-03 | 1976-06-01 | Sterling Drug Inc. | Substituted N-arylanilines |
| CH599752A5 (de) | 1973-04-18 | 1978-05-31 | Ciba Geigy Ag | |
| CA1047490A (en) | 1973-04-18 | 1979-01-30 | Friedrich Karrer | Ethers |
| DE2355454A1 (de) | 1973-11-07 | 1976-10-07 | Paul Geisslinger | Lochmaschine |
| CA1265798A (en) | 1984-12-10 | 1990-02-13 | Motoo Mutsukado | 3(2h)pyridazinone, process for its preparation and anti-allergic agent containing it |
| EP0450097B1 (de) | 1989-10-20 | 1996-04-24 | Otsuka Pharmaceutical Co., Ltd. | Benzoheterozyklische verbindungen |
| US5753677A (en) | 1989-10-20 | 1998-05-19 | Otsuka Pharmaceutical Co., Ltd. | Benzoheterocyclic compounds |
| CA2066104C (en) * | 1991-04-19 | 2003-05-27 | Hidenori Ogawa | Benzazepine derivatives as vasopressin antagonists |
| JPH05320135A (ja) | 1992-05-19 | 1993-12-03 | Yamanouchi Pharmaceut Co Ltd | テトラヒドロベンズアゼピン誘導体 |
| EP0612319A1 (de) | 1992-08-20 | 1994-08-31 | Otsuka Pharmaceutical Co., Ltd. | Benzoheterocyclische verbindungen als oxytocin antagonisten und vasopressinantagonisten. |
| TW270927B (de) * | 1992-10-16 | 1996-02-21 | Otsuka Pharma Co Ltd | |
| AU5533894A (en) | 1992-11-25 | 1994-06-22 | Yamanouchi Pharmaceutical Co., Ltd. | Benzanilide derivative |
| WO1994020473A1 (en) | 1993-03-11 | 1994-09-15 | Yamanouchi Pharmaceutical Co., Ltd. | Compound with vasopressin antagonism |
| GB9307527D0 (en) | 1993-04-13 | 1993-06-02 | Fujisawa Pharmaceutical Co | New venzamide derivatives,processes for the preparation thereof and pharmaceutical composition comprising the same |
| US5843952A (en) | 1993-07-29 | 1998-12-01 | American Cyanamid Company | Tricyclic benzazepine vasopressin antagonists |
| US5968930A (en) | 1993-07-29 | 1999-10-19 | American Cyanamid Company | Tricyclic diazepine vasopressin antagonists and oxytocin antagonists |
| US5760031A (en) | 1993-07-29 | 1998-06-02 | American Cyanamid Company | Tricyclic benzazepine vasopressin antagonists |
| US5516774A (en) | 1993-07-29 | 1996-05-14 | American Cyanamid Company | Tricyclic diazepine vasopressin antagonists and oxytocin antagonists |
| FI1215U1 (fi) * | 1993-12-03 | 1994-02-21 | Valmet Paper Machinery Inc | Anlaeggning i samband med styrningen av en vira |
| WO1995031034A2 (en) * | 1994-05-06 | 1995-11-16 | Philips Electronics N.V. | Microwave transmission system |
| DE69530690T2 (de) | 1994-06-15 | 2004-03-18 | Otsuka Pharmaceutical Co., Ltd. | Benzoheterocyclische derivate verwendbar als vasopressin- oder oxytocin-modulatoren |
| JP2926335B2 (ja) | 1997-06-13 | 1999-07-28 | 大塚製薬株式会社 | 医薬組成物 |
| CN1183134C (zh) * | 1997-07-30 | 2005-01-05 | 惠氏公司 | 三环后叶加压素激动剂 |
| NZ502448A (en) * | 1997-07-30 | 2002-12-20 | Wyeth Corp | Tricyclic vasopressin agonists and medicaments containing these compounds |
| JP2002527438A (ja) | 1998-10-09 | 2002-08-27 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | ４，５−ジヒドロ−イソオキサゾール誘導体及びそれらの製薬学的使用 |
| GB2355454A (en) | 1999-10-20 | 2001-04-25 | Ferring Bv | Antidiuretic agents |
| GB0000079D0 (en) | 2000-01-05 | 2000-02-23 | Ferring Bv | Novel antidiuretic agents |
| GB0015601D0 (en) | 2000-06-26 | 2000-08-16 | Ferring Bv | Novel antidiuretic agents |
| DE10033337A1 (de) | 2000-07-08 | 2002-01-17 | Boehringer Ingelheim Pharma | Biphenylcarbonsäureamide, ihre Herstellung und ihre Verwendung als Arzneimittel |
| GB0120051D0 (en) | 2001-08-16 | 2001-10-10 | Ferring Bv | Oxytocin agonists |
| GB0224557D0 (en) | 2002-10-22 | 2002-11-27 | Glaxo Group Ltd | Novel compounds |
| EP1449844A1 (de) | 2003-02-14 | 2004-08-25 | Ferring B.V. | benzamidderivate als oxytocin-agonisten und vasopressin-antagonisten |
| EP1627876A1 (de) | 2004-08-20 | 2006-02-22 | Ferring B.V. | Kondensierte heterocyclische Verbindungen und ihre Verwendung als antidiuretische Mittel |
| US7341963B2 (en) * | 2005-05-17 | 2008-03-11 | Milliken & Company | Non-woven material with barrier skin |
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2000
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