DE102004045720A1 - Stabile Dosierungsform von Phenylalanin-Derivaten - Google Patents
Stabile Dosierungsform von Phenylalanin-Derivaten Download PDFInfo
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- DE102004045720A1 DE102004045720A1 DE102004045720A DE102004045720A DE102004045720A1 DE 102004045720 A1 DE102004045720 A1 DE 102004045720A1 DE 102004045720 A DE102004045720 A DE 102004045720A DE 102004045720 A DE102004045720 A DE 102004045720A DE 102004045720 A1 DE102004045720 A1 DE 102004045720A1
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- Prior art keywords
- pharmaceutical formulation
- buffer
- oder
- active ingredient
- alkyl
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- 150000002993 phenylalanine derivatives Chemical class 0.000 title abstract description 5
- 239000002552 dosage form Substances 0.000 title 1
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 29
- 206010027476 Metastases Diseases 0.000 claims abstract description 11
- 238000011282 treatment Methods 0.000 claims abstract description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 106
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 83
- -1 amidino, hydroxyamidino, guanidino Chemical group 0.000 claims description 81
- 239000000203 mixture Substances 0.000 claims description 71
- 238000009472 formulation Methods 0.000 claims description 56
- 239000000243 solution Substances 0.000 claims description 52
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 claims description 28
- 239000004480 active ingredient Substances 0.000 claims description 24
- 239000000872 buffer Substances 0.000 claims description 24
- 150000001875 compounds Chemical class 0.000 claims description 24
- 206010028980 Neoplasm Diseases 0.000 claims description 22
- 229920005862 polyol Polymers 0.000 claims description 20
- 150000003077 polyols Chemical class 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 18
- 239000012141 concentrate Substances 0.000 claims description 16
- 239000003795 chemical substances by application Substances 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 13
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 11
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 11
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 8
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 8
- 235000010355 mannitol Nutrition 0.000 claims description 8
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- KIPIDQBXOKPNDP-QMMMGPOBSA-N (2s)-2-[(diaminomethylideneamino)-hydroxyamino]-3-phenylpropanoic acid Chemical class NC(N)=NN(O)[C@H](C(O)=O)CC1=CC=CC=C1 KIPIDQBXOKPNDP-QMMMGPOBSA-N 0.000 claims description 3
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- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 claims description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 2
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- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 claims description 2
- 206010061218 Inflammation Diseases 0.000 claims description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 2
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- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 claims description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 2
- 229930006000 Sucrose Natural products 0.000 claims description 2
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 claims description 2
- 206010064930 age-related macular degeneration Diseases 0.000 claims description 2
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 claims description 2
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- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 claims description 2
- 230000004054 inflammatory process Effects 0.000 claims description 2
- 239000008101 lactose Substances 0.000 claims description 2
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- 150000003467 sulfuric acid derivatives Chemical class 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
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- 239000002797 plasminogen activator inhibitor Substances 0.000 abstract description 9
- 230000001173 tumoral effect Effects 0.000 abstract 1
- ISJSHQTWOHGCMM-NDEPHWFRSA-N ethyl 4-[(2s)-3-(3-carbamimidoylphenyl)-2-[[2,4,6-tri(propan-2-yl)phenyl]sulfonylamino]propanoyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1C(=O)[C@@H](NS(=O)(=O)C=1C(=CC(=CC=1C(C)C)C(C)C)C(C)C)CC1=CC=CC(C(N)=N)=C1 ISJSHQTWOHGCMM-NDEPHWFRSA-N 0.000 description 85
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 30
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- 229910052736 halogen Inorganic materials 0.000 description 28
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 24
- 102100031358 Urokinase-type plasminogen activator Human genes 0.000 description 23
- 125000004093 cyano group Chemical group *C#N 0.000 description 23
- 150000002367 halogens Chemical class 0.000 description 23
- 125000000449 nitro group Chemical class [O-][N+](*)=O 0.000 description 23
- 125000004043 oxo group Chemical group O=* 0.000 description 23
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 23
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 18
- 210000004027 cell Anatomy 0.000 description 16
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 12
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 12
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- 125000003118 aryl group Chemical group 0.000 description 10
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- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 description 9
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 9
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- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
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- 125000003710 aryl alkyl group Chemical group 0.000 description 6
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 6
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
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- MJIDYLIDXWGFRN-QMMMGPOBSA-N (2s)-2-[2-(diaminomethylidene)hydrazinyl]-3-phenylpropanoic acid Chemical class NC(=N)NN[C@H](C(O)=O)CC1=CC=CC=C1 MJIDYLIDXWGFRN-QMMMGPOBSA-N 0.000 description 4
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- 229940024606 amino acid Drugs 0.000 description 4
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Priority Applications (15)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102004045720A DE102004045720A1 (de) | 2004-09-21 | 2004-09-21 | Stabile Dosierungsform von Phenylalanin-Derivaten |
| US11/631,891 US9089532B2 (en) | 2004-09-21 | 2005-09-20 | Stable dosage form of phenylalanine derivatives |
| MX2007000399A MX2007000399A (es) | 2004-09-21 | 2005-09-20 | Forma de dosis estable para derivados de fenilalanina. |
| KR1020077005447A KR101228385B1 (ko) | 2004-09-21 | 2005-09-20 | 페닐알라닌 유도체의 안정한 제형 |
| JP2007532821A JP5054529B2 (ja) | 2004-09-21 | 2005-09-20 | フェニルアラニン誘導体の安定な投与形 |
| BRPI0515533A BRPI0515533B8 (pt) | 2004-09-21 | 2005-09-20 | formulação farmacêutica estável para inibir urocinase |
| DE502005010237T DE502005010237D1 (de) | 2004-09-21 | 2005-09-20 | Stabile dosierungsform von phenylalanin-derivaten |
| ES05786251T ES2347670T3 (es) | 2004-09-21 | 2005-09-20 | Forma de dosificacion estable de derivados de fenilalanina. |
| PCT/EP2005/010143 WO2006032461A1 (de) | 2004-09-21 | 2005-09-20 | Stabile dosierungsform von phenylalanin-derivaten |
| CA2580639A CA2580639C (en) | 2004-09-21 | 2005-09-20 | Stable dosing form of phenylalanine derivatives |
| AT05786251T ATE480260T1 (de) | 2004-09-21 | 2005-09-20 | Stabile dosierungsform von phenylalanin-derivaten |
| EP05786251A EP1799265B1 (de) | 2004-09-21 | 2005-09-20 | Stabile dosierungsform von phenylalanin-derivaten |
| AU2005287582A AU2005287582B2 (en) | 2004-09-21 | 2005-09-20 | Stable dosing form of phenylalanine derivatives |
| RU2007115064/15A RU2358736C2 (ru) | 2004-09-21 | 2005-09-20 | Стойкая лекарственная форма из производных фенилаланина |
| CN2005800256252A CN1993144B (zh) | 2004-09-21 | 2005-09-20 | 苯丙氨酸衍生物的稳定剂型 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102004045720A DE102004045720A1 (de) | 2004-09-21 | 2004-09-21 | Stabile Dosierungsform von Phenylalanin-Derivaten |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE102004045720A1 true DE102004045720A1 (de) | 2006-03-23 |
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Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE102004045720A Withdrawn DE102004045720A1 (de) | 2004-09-21 | 2004-09-21 | Stabile Dosierungsform von Phenylalanin-Derivaten |
| DE502005010237T Expired - Lifetime DE502005010237D1 (de) | 2004-09-21 | 2005-09-20 | Stabile dosierungsform von phenylalanin-derivaten |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE502005010237T Expired - Lifetime DE502005010237D1 (de) | 2004-09-21 | 2005-09-20 | Stabile dosierungsform von phenylalanin-derivaten |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US9089532B2 (https=) |
| EP (1) | EP1799265B1 (https=) |
| JP (1) | JP5054529B2 (https=) |
| KR (1) | KR101228385B1 (https=) |
| CN (1) | CN1993144B (https=) |
| AT (1) | ATE480260T1 (https=) |
| AU (1) | AU2005287582B2 (https=) |
| BR (1) | BRPI0515533B8 (https=) |
| CA (1) | CA2580639C (https=) |
| DE (2) | DE102004045720A1 (https=) |
| ES (1) | ES2347670T3 (https=) |
| MX (1) | MX2007000399A (https=) |
| RU (1) | RU2358736C2 (https=) |
| WO (1) | WO2006032461A1 (https=) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE102004057195A1 (de) * | 2004-11-26 | 2006-06-01 | Wilex Ag | Kristalline Modifikationen von N-Alpha-(2,4,6-Triisopropylphenylsulfonyl)-3-hydroxyamidino-(L)-phenylalanin-4-ethoxycarbonylpiperazid und/oder Salzen davon |
| CN117695284B (zh) | 2020-03-10 | 2025-06-17 | 红山生物医药有限公司 | 冠状病毒感染的治疗 |
| US11471448B2 (en) | 2020-12-15 | 2022-10-18 | Redhill Biopharma Ltd. | Sphingosine kinase 2 inhibitor for treating coronavirus infection in moderately severe patients with pneumonia |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA986594B (en) | 1997-07-25 | 1999-01-27 | Abbott Lab | Urokinase inhibitors |
| US6624169B1 (en) * | 1998-07-20 | 2003-09-23 | Wilex Biotechnology Gmbh | Urokinase inhibitors |
| SI1453852T1 (sl) * | 2001-12-12 | 2007-06-30 | Wilex Ag | Selektivni arilgvanidinpeptidi kot inhibitorji urokinaze |
| AU2003219039A1 (en) * | 2002-03-11 | 2003-09-22 | Curacyte Ag | Urokinase inhibitors, production and use thereof |
| DE10225876A1 (de) * | 2002-06-11 | 2003-12-24 | Wilex Ag | Guanidinophenylalaninverbindungen als Urokinase-Inhibitoren |
| WO2004011449A2 (de) * | 2002-07-25 | 2004-02-05 | Wilex Ag | Verfahren zur herstellung von phenylalanin-derivaten |
| DE10323898A1 (de) * | 2003-05-26 | 2004-12-23 | Wilex Ag | Hydroxyamidin- und Hydroxyguanidin-Verbindungen als Urokinase-Hemmstoffe |
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2004
- 2004-09-21 DE DE102004045720A patent/DE102004045720A1/de not_active Withdrawn
-
2005
- 2005-09-20 BR BRPI0515533A patent/BRPI0515533B8/pt not_active IP Right Cessation
- 2005-09-20 CN CN2005800256252A patent/CN1993144B/zh not_active Expired - Fee Related
- 2005-09-20 EP EP05786251A patent/EP1799265B1/de not_active Expired - Lifetime
- 2005-09-20 WO PCT/EP2005/010143 patent/WO2006032461A1/de not_active Ceased
- 2005-09-20 ES ES05786251T patent/ES2347670T3/es not_active Expired - Lifetime
- 2005-09-20 JP JP2007532821A patent/JP5054529B2/ja not_active Expired - Fee Related
- 2005-09-20 RU RU2007115064/15A patent/RU2358736C2/ru active
- 2005-09-20 US US11/631,891 patent/US9089532B2/en active Active
- 2005-09-20 CA CA2580639A patent/CA2580639C/en not_active Expired - Fee Related
- 2005-09-20 KR KR1020077005447A patent/KR101228385B1/ko not_active Expired - Fee Related
- 2005-09-20 DE DE502005010237T patent/DE502005010237D1/de not_active Expired - Lifetime
- 2005-09-20 AU AU2005287582A patent/AU2005287582B2/en not_active Ceased
- 2005-09-20 MX MX2007000399A patent/MX2007000399A/es active IP Right Grant
- 2005-09-20 AT AT05786251T patent/ATE480260T1/de not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| BRPI0515533B8 (pt) | 2021-05-25 |
| CN1993144B (zh) | 2012-05-30 |
| DE502005010237D1 (de) | 2010-10-21 |
| RU2007115064A (ru) | 2008-10-27 |
| WO2006032461A1 (de) | 2006-03-30 |
| ATE480260T1 (de) | 2010-09-15 |
| KR101228385B1 (ko) | 2013-02-04 |
| ES2347670T3 (es) | 2010-11-03 |
| CA2580639C (en) | 2013-04-23 |
| AU2005287582A1 (en) | 2006-03-30 |
| KR20070054197A (ko) | 2007-05-28 |
| BRPI0515533B1 (pt) | 2020-12-08 |
| US20070244127A1 (en) | 2007-10-18 |
| MX2007000399A (es) | 2008-03-11 |
| BRPI0515533A (pt) | 2008-07-29 |
| JP5054529B2 (ja) | 2012-10-24 |
| AU2005287582B2 (en) | 2010-08-19 |
| US9089532B2 (en) | 2015-07-28 |
| RU2358736C2 (ru) | 2009-06-20 |
| EP1799265A1 (de) | 2007-06-27 |
| CA2580639A1 (en) | 2006-03-30 |
| CN1993144A (zh) | 2007-07-04 |
| EP1799265B1 (de) | 2010-09-08 |
| JP2008513529A (ja) | 2008-05-01 |
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Legal Events
| Date | Code | Title | Description |
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| R005 | Application deemed withdrawn due to failure to request examination |
Effective date: 20110922 |