TWI353250B - Glp-1 pharmaceutical compositions - Google Patents
Glp-1 pharmaceutical compositions Download PDFInfo
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- TWI353250B TWI353250B TW093139220A TW93139220A TWI353250B TW I353250 B TWI353250 B TW I353250B TW 093139220 A TW093139220 A TW 093139220A TW 93139220 A TW93139220 A TW 93139220A TW I353250 B TWI353250 B TW I353250B
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- 239000008194 pharmaceutical composition Substances 0.000 title claims description 9
- 101100337060 Caenorhabditis elegans glp-1 gene Proteins 0.000 title description 7
- 239000000203 mixture Substances 0.000 claims description 119
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 48
- -1 erythroglucose Chemical compound 0.000 claims description 23
- 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 22
- 150000003839 salts Chemical class 0.000 claims description 21
- 239000011701 zinc Substances 0.000 claims description 21
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 20
- 229910052725 zinc Inorganic materials 0.000 claims description 20
- 239000002253 acid Substances 0.000 claims description 18
- 239000008103 glucose Substances 0.000 claims description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 16
- 239000007864 aqueous solution Substances 0.000 claims description 16
- 239000000872 buffer Substances 0.000 claims description 12
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 11
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 11
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 239000003755 preservative agent Substances 0.000 claims description 9
- 230000002335 preservative effect Effects 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 6
- 150000001412 amines Chemical class 0.000 claims description 6
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- 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 5
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- 239000003381 stabilizer Substances 0.000 claims description 5
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical group OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 5
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 5
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims description 4
- 239000005695 Ammonium acetate Substances 0.000 claims description 4
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- 206010018404 Glucagonoma Diseases 0.000 claims description 4
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- 102000007327 Protamines Human genes 0.000 claims description 4
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- 235000019257 ammonium acetate Nutrition 0.000 claims description 4
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- ATHGHQPFGPMSJY-UHFFFAOYSA-N spermidine Chemical compound NCCCCNCCCN ATHGHQPFGPMSJY-UHFFFAOYSA-N 0.000 claims description 4
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 claims description 3
- 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 3
- 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 3
- 229930091371 Fructose Natural products 0.000 claims description 3
- 239000005715 Fructose Substances 0.000 claims description 3
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 claims description 3
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 claims description 3
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- 102000006947 Histones Human genes 0.000 claims description 3
- 108010033040 Histones Proteins 0.000 claims description 3
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 claims description 3
- 229930195725 Mannitol Natural products 0.000 claims description 3
- 108010039918 Polylysine Proteins 0.000 claims description 3
- 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 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 3
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 claims description 3
- 235000003704 aspartic acid Nutrition 0.000 claims description 3
- 235000019445 benzyl alcohol Nutrition 0.000 claims description 3
- 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 3
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 3
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 claims description 3
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 claims description 3
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- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 3
- 230000001939 inductive effect Effects 0.000 claims description 3
- 150000002500 ions Chemical class 0.000 claims description 3
- 239000007951 isotonicity adjuster Substances 0.000 claims description 3
- 239000000594 mannitol Substances 0.000 claims description 3
- 235000010355 mannitol Nutrition 0.000 claims description 3
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 claims description 3
- 229920000724 poly(L-arginine) polymer Polymers 0.000 claims description 3
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- 230000000241 respiratory effect Effects 0.000 claims description 3
- 239000001632 sodium acetate Substances 0.000 claims description 3
- 235000017281 sodium acetate Nutrition 0.000 claims description 3
- 239000004094 surface-active agent Substances 0.000 claims description 3
- 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
- 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
- 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
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 claims description 2
- 229910052921 ammonium sulfate Inorganic materials 0.000 claims description 2
- 235000011130 ammonium sulphate Nutrition 0.000 claims description 2
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 claims description 2
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 claims description 2
- 229940063673 spermidine Drugs 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims 2
- 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 claims 1
- 102400000322 Glucagon-like peptide 1 Human genes 0.000 claims 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
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- 150000001875 compounds Chemical class 0.000 description 96
- 239000000243 solution Substances 0.000 description 61
- 238000000034 method Methods 0.000 description 38
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
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- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 101100335894 Caenorhabditis elegans gly-8 gene Proteins 0.000 description 17
- 238000002347 injection Methods 0.000 description 17
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- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 17
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- 239000011592 zinc chloride Substances 0.000 description 16
- 235000005074 zinc chloride Nutrition 0.000 description 16
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 8
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- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 4
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Landscapes
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- Engineering & Computer Science (AREA)
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
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| US52993203P | 2003-12-16 | 2003-12-16 |
Publications (2)
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| TW093139220A TWI353250B (en) | 2003-12-16 | 2004-12-16 | Glp-1 pharmaceutical compositions |
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| EP (1) | EP1694278A4 (enExample) |
| JP (2) | JP2007514752A (enExample) |
| AR (1) | AR047776A1 (enExample) |
| CA (1) | CA2550695A1 (enExample) |
| TW (1) | TWI353250B (enExample) |
| WO (1) | WO2005058252A2 (enExample) |
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| US20050260259A1 (en) * | 2004-04-23 | 2005-11-24 | Bolotin Elijah M | Compositions for treatment with glucagon-like peptide, and methods of making and using the same |
| US7635463B2 (en) * | 2002-02-27 | 2009-12-22 | Pharmain Corporation | Compositions for delivery of therapeutics and other materials |
| AU2003219922B2 (en) * | 2002-02-27 | 2009-09-10 | Pharmain Corporation | Compositions for delivery of therapeutics and other materials, and methods of making and using the same |
| MX2008001468A (es) * | 2005-06-30 | 2008-04-07 | Sod Conseils Rech Applic | Composiciones farmaceuticas del peptido similar al glucagon-1. |
| PL2347762T3 (pl) | 2005-08-19 | 2019-09-30 | Amylin Pharmaceuticals, Llc | Eksendyna do leczenia cukrzycy i zmniejszania masy ciała |
| KR101529318B1 (ko) | 2005-12-19 | 2015-06-16 | 파마인 코포레이션 | 치료제를 전달하기 위한 소수성 코어 담체 조성물, 이조성물의 제조 방법 및 그 조성물의 이용 방법 |
| RU2445972C2 (ru) * | 2006-12-29 | 2012-03-27 | Ипсен Фарма С.А.С. | Фармацевтические композиции glp-1 |
| CN101668535B (zh) * | 2006-12-29 | 2017-07-28 | 益普生制药股份有限公司 | Glp‑1药物组合物 |
| US7960336B2 (en) * | 2007-08-03 | 2011-06-14 | Pharmain Corporation | Composition for long-acting peptide analogs |
| US8563527B2 (en) * | 2007-08-20 | 2013-10-22 | Pharmain Corporation | Oligonucleotide core carrier compositions for delivery of nucleic acid-containing therapeutic agents, methods of making and using the same |
| US20100256056A1 (en) * | 2007-09-07 | 2010-10-07 | Zheng Xin Dong | Analogues of exendin-4 and exendin-3 |
| US20090176892A1 (en) | 2008-01-09 | 2009-07-09 | Pharmain Corporation | Soluble Hydrophobic Core Carrier Compositions for Delivery of Therapeutic Agents, Methods of Making and Using the Same |
| WO2009139855A2 (en) * | 2008-05-14 | 2009-11-19 | Ipsen Pharma S.A.S. | Pharmaceutical compositions of somatostatin-dopamine conjugates |
| ES2552646T3 (es) | 2008-05-21 | 2015-12-01 | Amylin Pharmaceuticals, Inc. | Exendinas para disminuir el colesterol y los triglicéridos |
| WO2010016936A1 (en) * | 2008-08-07 | 2010-02-11 | Ipsen Pharma S.A.S. | Pharmaceutical compositions of analogues of glucose-dependent insulinotropic polypeptide |
| JP5486690B2 (ja) | 2009-11-16 | 2014-05-07 | イプセン ファルマ ソシエテ パール アクシオン サンプリフィエ | メラノコルチン受容体リガンドの医薬組成物 |
| BR112012023303A2 (pt) * | 2010-03-15 | 2020-08-25 | Ipsen Pharma S.A.S. | composição farmacêutica de ligantes do receptor do secretagogo do hormônio de crescimento. |
| EP2384733B1 (de) | 2010-05-07 | 2016-07-27 | Ivoclar Vivadent AG | Antimikrobielle Dentalwerkstoffe |
| TWI523863B (zh) | 2012-11-01 | 2016-03-01 | 艾普森藥品公司 | 體抑素－多巴胺嵌合體類似物 |
| JP2016503402A (ja) | 2012-11-01 | 2016-02-04 | イプセン ファルマ ソシエテ パール アクシオン サンプリフィエＩｐｓｅｎ Ｐｈａｒｍａ Ｓ．Ａ．Ｓ． | ソマトスタチン類似体及びそのダイマー |
| BR112020002804A2 (pt) | 2017-08-24 | 2020-07-28 | Novo Nordisk A/S | composição farmacêutica líquida, e, kit |
| IL294521A (en) | 2020-02-18 | 2022-09-01 | Novo Nordisk As | glp-1 compounds and their uses |
Family Cites Families (42)
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| US4783441A (en) * | 1979-04-30 | 1988-11-08 | Hoechst Aktiengesellschaft | Aqueous protein solutions stable to denaturation |
| JP2583257B2 (ja) | 1986-05-05 | 1997-02-19 | ザ・ジェネラル・ホスピタル・コーポレーション | インシュリン向性ホルモン |
| ES2113879T3 (es) * | 1990-01-24 | 1998-05-16 | Douglas I Buckley | Analogos de glp-1 utiles para el tratamiento de diabetes. |
| US5545618A (en) | 1990-01-24 | 1996-08-13 | Buckley; Douglas I. | GLP-1 analogs useful for diabetes treatment |
| US6221958B1 (en) | 1993-01-06 | 2001-04-24 | Societe De Conseils De Recherches Et D'applications Scientifiques, Sas | Ionic molecular conjugates of biodegradable polyesters and bioactive polypeptides |
| US6284727B1 (en) * | 1993-04-07 | 2001-09-04 | Scios, Inc. | Prolonged delivery of peptides |
| NZ250844A (en) | 1993-04-07 | 1996-03-26 | Pfizer | Treatment of non-insulin dependant diabetes with peptides; composition |
| CA2137206A1 (en) | 1993-12-09 | 1995-06-10 | John A. Galloway | Glucagon-like insulinotropic peptides, compositions and methods |
| US5705483A (en) | 1993-12-09 | 1998-01-06 | Eli Lilly And Company | Glucagon-like insulinotropic peptides, compositions and methods |
| US5574008A (en) | 1994-08-30 | 1996-11-12 | Eli Lilly And Company | Biologically active fragments of glucagon-like insulinotropic peptide |
| US5595760A (en) | 1994-09-02 | 1997-01-21 | Delab | Sustained release of peptides from pharmaceutical compositions |
| US5512549A (en) | 1994-10-18 | 1996-04-30 | Eli Lilly And Company | Glucagon-like insulinotropic peptide analogs, compositions, and methods of use |
| US20010006943A1 (en) | 1994-12-23 | 2001-07-05 | Ejvind Jensen | Protracted GLP-1 compositions |
| US5980945A (en) | 1996-01-16 | 1999-11-09 | Societe De Conseils De Recherches Et D'applications Scientifique S.A. | Sustained release drug formulations |
| WO1997029180A1 (en) | 1996-02-06 | 1997-08-14 | Eli Lilly And Company | Diabetes therapy |
| US6264970B1 (en) | 1996-06-26 | 2001-07-24 | Takeda Chemical Industries, Ltd. | Sustained-release preparation |
| DE19629640C1 (de) | 1996-07-23 | 1997-08-28 | Metallgesellschaft Ag | Verfahren zur Herstellung von kristallinem D-Sorbit |
| US6458924B2 (en) | 1996-08-30 | 2002-10-01 | Novo Nordisk A/S | Derivatives of GLP-1 analogs |
| DE122009000079I2 (de) | 1996-08-30 | 2011-06-16 | Novo Nordisk As Novo Alle | Glp-1 derivate |
| UA65549C2 (uk) | 1996-11-05 | 2004-04-15 | Елі Ліллі Енд Компані | Спосіб регулювання ожиріння шляхом периферійного введення аналогів та похідних glp-1 (варіанти) та фармацевтична композиція |
| US5981488A (en) | 1997-03-31 | 1999-11-09 | Eli Lillly And Company | Glucagon-like peptide-1 analogs |
| US6663899B2 (en) | 1997-06-13 | 2003-12-16 | Genentech, Inc. | Controlled release microencapsulated NGF formulation |
| US6380357B2 (en) | 1997-12-16 | 2002-04-30 | Eli Lilly And Company | Glucagon-like peptide-1 crystals |
| JP2002508162A (ja) | 1998-02-27 | 2002-03-19 | ノボ ノルディスク アクティーゼルスカブ | Ｎ末端を短縮したｇｌｐ−１誘導体 |
| DE69916811T2 (de) | 1998-02-27 | 2005-04-14 | Novo Nordisk A/S | Glp-1 derivate mit einem helix-gehalt über 25 %, die partiell strukturierte mizellenartige aggregate bilden |
| CA2324568A1 (en) | 1998-03-20 | 1999-09-30 | Takeda Chemical Industries, Ltd. | Sustained-release preparation of physiologically active polypeptide and production thereof |
| FR2776520B1 (fr) | 1998-03-25 | 2000-05-05 | Sod Conseils Rech Applic | Nouvelles compositions pharmaceutiques destinees a la liberation prolongee de peptides et leur procede de preparation |
| FR2777283B1 (fr) | 1998-04-10 | 2000-11-24 | Adir | Nouveaux composes peptidiques analogues du glucagon-peptide- 1 (7-37), leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| RU2205188C2 (ru) | 1998-06-30 | 2003-05-27 | Ново Нордиск А/С | Затравочные кристаллы для получения пептидов или протеинов |
| US6720407B1 (en) | 1998-08-28 | 2004-04-13 | Eli Lilly And Company | Method for administering insulinotropic peptides |
| PL208751B1 (pl) * | 1998-12-07 | 2011-06-30 | Sod Conseils Rech Applic | Związki stanowiące analogi GLP-1, kompozycje zawierające takie związki oraz zastosowanie takich związków |
| EP1137667B1 (en) * | 1998-12-07 | 2004-11-17 | Societe De Conseils De Recherches Et D'applications Scientifiques S.A.S. | Analogues of glp-1 |
| RU2242244C2 (ru) * | 1999-01-14 | 2004-12-20 | Амилин Фармасьютикалз, Инк. | Новые композиции агонистов эксендина и способы их введения |
| EP1196189A2 (en) | 1999-06-25 | 2002-04-17 | Medtronic MiniMed, Inc. | Multiple agent diabetes therapy |
| US6541225B1 (en) * | 2000-01-26 | 2003-04-01 | Raven Biotechnologies, Inc. | Methods and compositions for generating human monoclonal antibodies |
| AU2001228327A1 (en) | 2000-01-31 | 2001-08-14 | Novo-Nordisk A/S | Crystallisation of a glp-1 analogue |
| US6844321B2 (en) | 2000-01-31 | 2005-01-18 | Novo Nordisk A/S | Crystallization of a GLP-1 analogue |
| DE60137876D1 (de) | 2000-06-16 | 2009-04-16 | Lilly Co Eli | Analoge des Glucagon-ähnlichen Peptids-1 |
| JP2005506956A (ja) * | 2001-06-01 | 2005-03-10 | イーライ・リリー・アンド・カンパニー | 長時間作用性ｇｌｐ−１製剤 |
| ES2298378T3 (es) * | 2001-06-28 | 2008-05-16 | Novo Nordisk A/S | Formulacion estable de glp-1 modificado. |
| GEP20063908B (en) | 2001-10-18 | 2006-08-25 | Bristol Myers Squibb Co | Human glucagon-like-peptide-1 mimics and their use in the treatment of diabetes and related conditions |
| EP1448222A4 (en) | 2001-10-19 | 2006-05-17 | Lilly Co Eli | BIPHASIC MIXTURES OF GLP-1 AND INSULIN |
-
2004
- 2004-12-16 JP JP2006545462A patent/JP2007514752A/ja not_active Ceased
- 2004-12-16 CA CA002550695A patent/CA2550695A1/en not_active Abandoned
- 2004-12-16 AR ARP040104697A patent/AR047776A1/es not_active Application Discontinuation
- 2004-12-16 US US11/015,615 patent/US7521527B2/en not_active Expired - Fee Related
- 2004-12-16 WO PCT/US2004/042389 patent/WO2005058252A2/en not_active Ceased
- 2004-12-16 TW TW093139220A patent/TWI353250B/zh not_active IP Right Cessation
- 2004-12-16 EP EP04814554A patent/EP1694278A4/en not_active Withdrawn
-
2010
- 2010-10-01 JP JP2010224218A patent/JP2011001381A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JP2007514752A (ja) | 2007-06-07 |
| JP2011001381A (ja) | 2011-01-06 |
| AR047776A1 (es) | 2006-02-22 |
| US20050159356A1 (en) | 2005-07-21 |
| CA2550695A1 (en) | 2005-06-30 |
| EP1694278A2 (en) | 2006-08-30 |
| TW200520770A (en) | 2005-07-01 |
| WO2005058252A3 (en) | 2006-08-31 |
| WO2005058252A2 (en) | 2005-06-30 |
| EP1694278A4 (en) | 2009-08-12 |
| US7521527B2 (en) | 2009-04-21 |
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| MM4A | Annulment or lapse of patent due to non-payment of fees |