HUP0104111A2 - Stabil, koncentrált inzulinkészítmény pulmonáris bejuttatáshoz - Google Patents
Stabil, koncentrált inzulinkészítmény pulmonáris bejuttatáshoz Download PDFInfo
- Publication number
- HUP0104111A2 HUP0104111A2 HU0104111A HUP0104111A HUP0104111A2 HU P0104111 A2 HUP0104111 A2 HU P0104111A2 HU 0104111 A HU0104111 A HU 0104111A HU P0104111 A HUP0104111 A HU P0104111A HU P0104111 A2 HUP0104111 A2 HU P0104111A2
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- HU
- Hungary
- Prior art keywords
- insulin
- human insulin
- human
- des
- lys
- Prior art date
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- 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 title claims abstract description 284
- 102000004877 Insulin Human genes 0.000 title claims abstract description 136
- 108090001061 Insulin Proteins 0.000 title claims abstract description 136
- 229940125396 insulin Drugs 0.000 title claims abstract description 134
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- 230000002685 pulmonary effect Effects 0.000 title abstract description 8
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 claims abstract description 61
- 101000976075 Homo sapiens Insulin Proteins 0.000 claims abstract description 54
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims abstract description 48
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims abstract description 10
- 150000001450 anions Chemical class 0.000 claims abstract description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims abstract description 3
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- 239000000203 mixture Substances 0.000 claims description 42
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 22
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- 229910019142 PO4 Inorganic materials 0.000 claims description 4
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Classifications
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- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
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Abstract
A tal lm ny olyan vizes inzulinkészítményre vonatkozik, amely 6-15 mMhum n inzulint, vagy analógot, vagy sz rmazékot, a klorid-iontól ésacet tiontól eltérő b rmilyen anionból legfeljebb 10 mM mennyiséget,hat inzulin molekul nként 2-5 Zn2-iont, és hat inzulin molekul nkéntlegal bb 3 fenolos molekul t tartalmaz. A tal lm ny szerintikészítmény alkalmas diabeteses betegek pulmon ris úton t"rténőbeadagol sra. Ó
Claims (20)
- SZABADALMI IGÉNYPONTOK1. Egy vizes inzulin készítmény azzal jellemezve, hogy 6-15 mM humán inzulint, vagy analógot, vagy származékot, a kloridiontól és acetátiontól eltérő bármilyen anionból kevesebb, mint 10 mM mennyiséget, hat inzulin molekulánként 2-5 Zn2+iont és hat inzulin molekulánként legalább 3 fenolos molekulát tartalmaz.
- 2. Az 1. igénypont szerinti inzulin készítmény azzal jellemezve, hogy körülbelül 6 mM, körülbelül 9 mM, körülbelül 12 mM vagy körülbelül 15 mM humán inzulint, vagy inzulin analógot, vagy származékot tartalmaz.
- 3. Az 1. vagy a 2. igénypont szerinti inzulin készítmény azzal jellemezve, hogy 50 mM mennyiségig terjedő fenolos molekulát, előnyösen hat inzulin molekulánként 3-12 fenolos molekulát, még előnyösebben hat inzulin molekulánként 3 - 9 fenolos molekulát tartalmaz.
- 4. Egy az 1-3. igénypontok bármelyike szerinti inzulin készítmény azzal jellemezve, hogy 40 mM-nál kevesebb, előnyösen 30 mM-nál kevesebb kloridiont, még előnyösebben 5-20 mM kloridiont tartalmaz.
- 5. Egy aa 1-4. igénypontok bármelyike szerinti inzulin készítmény azzal jellemezve, hogy 5 mM mennyiségű foszfátot tartalmaz.
- 6. Egy az 1-5. igénypontok bármelyike szerinti inzulin készítmény azzal jellemezve, hogy hat inzulin molekulánként 2-4 Zn2+-iont, előnyösen 2,2 - 3,2 Zn2+-iont tartalmaz.
- 7. Egy az 1-6. igénypontok bármelyike szerinti inzulin készítmény azzal jellemezve, hogy még 5-150 mM zwitterionos amint, előnyösen glicil-glicint vagy glicint tartalmaz.
- 8. Egy az 1-7. igénypontok bármelyike szerinti inzulin készítmény azzal jellemezve, hogy a továbbiakban 5 - 50 mM tris-hidroxi-metil-aminometánt tartalmaz.
- 9. Egy az 1-8. igénypontok bármelyike szerinti inzulin készítmény azzal jellemezve, hogy kationként nátriumionokat, káliumionokat vagy ezek keverékét tartalmazza.
- 10. Egy az 1-9. igénypontok bármelyike szerinti inzulin készítmény azzal jellemezve, hogy 0,001 tömeg% - 1 tömeg% nem-ionos felületaktív anyagot, előnyösen tween 20-at vagy Polox 188-at is tartalmaz.
- 11. Egy az 1-10. igénypontok bármelyike szerinti inzulin készítmény azzal jellemezve, hogy 1 mM - 10 mM anionos felületaktív anyagot, előnyösen nátrium-taurokolátot tartalmaz.
- 12. Egy az 1-11. igénypontok bármelyike szerinti inzulin készítmény azzal jellemezve, hogy humán inzulint tartalmaz.
- 13. Egy az 1-12. igénypontok bármelyike szerinti inzulin készítmény azzal jellemezve, hogy egy humán inzulin analógot tartalmaz, ahol a B28 pozícióban Asp, Lys, Leu, Val vagy Alá és a B29 pozícióban Lys vagy Pro szerepel, vagy des(B28-B30), des(B27) vagy des(B30) humán inzulint jelent.
- 14. A 13. igénypont szerinti inzulin készítmény azzal jellemezve, hogy egy humán inzulin analógot tartalmaz, ahol a B28 pozíció Asp-t, vagy Lys-t, és a B29 pozíció Lys-t vagy Pro-t jelent, előnyösen AspB28 humán inzulint vagy LysB28ProB29 humán inzulint jelent.
- 15. Az 1 - 11. igénypontok bármelyike szerinti inzulin készítmény azzal jellemezve, hogy olyan humán inzulin származékot jelent, ami egy vagy több lipofil szubsztituenst tartalmaz, előnyösen acilált inzulint jelent.
- 16. A 15. igénypont szerinti inzulin készítmény azzal jellemezve, hogy az inzulin származék B29-NE-mirisztoil-des(B30) humán inzulint, B29-NE-palmitoil-des(B30) humán inzulint, B29-NE-mirisztoil-humán inzulint, B29-NE-palmitoil-humán inzulint, B28-NE-mirisztoil-LysB28ProB29 humán inzulint, B28-NE-palmitoil-LysB28ProB29 humán inzulint, B30-NEmirisztoil-ThrB29LysB3° humán inzulint, B30-NE-palmitoil-ThrB29LysB3° humán inzulint, B29-NE-(N-palmitoil-y-glutamil)-des(B30) humán inzulint, B29-NE-(N-litokolil-y-glutamil)-des(B30) humán inzulint, B29-NE-(o-karboxiheptadekanoil)-des(B30) humán inzulint, és B29-NE-(o-karboxiheptadekanoil)-humán inzulint jelent.
- 17. A 16. igénypont szerinti inzulin készítmény azzal jellemezve, hogy az inzulin származék B29-NE-mirisztoil-des(B30) humán inzulint vagy B29-NE-(N-litokolil-y-glutamil)-des(B30) humán inzulint jelent.
- 18. Egy az 1-17. igénypontok bármelyike szerinti inzulin készítmény azzal jellemezve, hogy egy inzulin analógot vagy humán inzulint, valamint egy inzulin származékot tartalmaz.
- 19. Egy az 1-18. igénypontok bármelyike szerinti inzulin készítmény azzal jellemezve, hogy a fenolos molekulák fenolt, m-krezolt, klór-krezolt, timolt vagy ezek keverékét jelentenek.
- 20. Egy az 1-19. igénypontok bármelyike szerinti inzulin készítmény azzal jellemezve, hogy a pH érték 7 - 8,5, előnyösen 7,4 - 7,9 értékek között mozog.A meghatalmazott ^-BQROS ISjy
Applications Claiming Priority (2)
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|---|---|---|---|
| DKPA199801327 | 1998-10-16 | ||
| PCT/DK1999/000556 WO2000023098A1 (en) | 1998-10-16 | 1999-10-15 | Stable concentrated insulin preparations for pulmonary delivery |
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| Publication Number | Publication Date |
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| HUP0104111A2 true HUP0104111A2 (hu) | 2002-04-29 |
| HUP0104111A3 HUP0104111A3 (en) | 2002-05-28 |
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| HU0104111A HUP0104111A3 (en) | 1998-10-16 | 1999-10-15 | Stable concentrated insulin preparations for pulmonary delivery |
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| EP (2) | EP1172114B1 (hu) |
| JP (1) | JP4212240B2 (hu) |
| KR (1) | KR100617286B1 (hu) |
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| ES (2) | ES2177323T3 (hu) |
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| US5783556A (en) * | 1996-08-13 | 1998-07-21 | Genentech, Inc. | Formulated insulin-containing composition |
| DE10114178A1 (de) | 2001-03-23 | 2002-10-10 | Aventis Pharma Gmbh | Zinkfreie und zinkarme Insulinzubereitungen mit verbesserter Stabilität |
| NZ519403A (en) * | 2001-06-21 | 2005-03-24 | Pfizer Prod Inc | Use of insulin in a medicament to reduce weight gain in a diabetic patient who is using exogenous insulin to control blood sugar levels |
| WO2003094956A1 (en) | 2002-05-07 | 2003-11-20 | Novo Nordisk A/S | Soluble formulations comprising monomeric insulin and acylated insulin |
| DE10227232A1 (de) | 2002-06-18 | 2004-01-15 | Aventis Pharma Deutschland Gmbh | Saure Insulinzubereitungen mit verbesserter Stabilität |
| CA2517310C (en) * | 2003-02-28 | 2015-11-24 | Chugai Seiyaku Kabushiki Kaisha | Stabilized protein-containing formulations comprising a poloxamer |
| JP2007523842A (ja) * | 2003-03-11 | 2007-08-23 | ノボ ノルディスク アクティーゼルスカブ | 酸安定化されたインスリンを含有する薬学的製剤 |
| EP2107069B1 (en) | 2003-08-05 | 2013-01-16 | Novo Nordisk A/S | Novel insulin derivatives |
| US20090074882A1 (en) | 2005-12-28 | 2009-03-19 | Novo Nordisk A/S | Insulin compositions and method of making a composition |
| JP5550338B2 (ja) | 2006-07-31 | 2014-07-16 | ノボ・ノルデイスク・エー／エス | ペグ化持続型インスリン |
| HUE029512T2 (hu) | 2006-09-22 | 2017-03-28 | Novo Nordisk As | Proteázrezisztens inzulinanalógok |
| EP2152243A2 (en) * | 2007-04-30 | 2010-02-17 | Novo Nordisk A/S | Highly concentrated insulin solutions and compositions |
| JP5496082B2 (ja) | 2007-04-30 | 2014-05-21 | ノボ・ノルデイスク・エー／エス | タンパク質組成物を乾燥させる方法、乾燥タンパク質組成物、及び乾燥タンパク質を含有する薬学的組成物 |
| JP5552046B2 (ja) * | 2007-06-13 | 2014-07-16 | ノボ・ノルデイスク・エー／エス | インスリン誘導体を含有する薬学的製剤 |
| JP5762001B2 (ja) | 2008-03-14 | 2015-08-12 | ノボ・ノルデイスク・エー／エス | プロテアーゼ安定化インスリンアナログ |
| WO2009115469A1 (en) | 2008-03-18 | 2009-09-24 | Novo Nordisk A/S | Protease stabilized, acylated insulin analogues |
| AU2011235959C1 (en) * | 2008-06-13 | 2013-10-10 | Eli Lilly And Company | PEGylated insulin lispro compounds |
| TWI451876B (zh) * | 2008-06-13 | 2014-09-11 | Lilly Co Eli | 聚乙二醇化之離脯胰島素化合物 |
| PT3228320T (pt) | 2008-10-17 | 2020-03-26 | Sanofi Aventis Deutschland | Combinação de uma insulina e de um agonista do glp-1 |
| KR20110085985A (ko) | 2008-10-30 | 2011-07-27 | 노보 노르디스크 에이/에스 | 하루 한번 주사 빈도보다 적은 인슐린 주사를 사용한 진성 당뇨병의 치료 |
| KR101853606B1 (ko) | 2009-07-06 | 2018-05-03 | 사노피-아벤티스 도이칠란트 게엠베하 | 메티오닌을 함유하는 수성 인슐린 제제 |
| DK2498802T3 (en) | 2009-11-13 | 2015-04-13 | Sanofi Aventis Deutschland | Pharmaceutical composition comprising a GLP-1 agonist, insulin and a methionine |
| KR101337322B1 (ko) | 2009-11-13 | 2013-12-06 | 사노피-아벤티스 도이칠란트 게엠베하 | Ｇｌｐ-1 효능제 및 메티오닌을 포함하는 약제학적 조성물 |
| ES2606554T3 (es) | 2010-08-30 | 2017-03-24 | Sanofi-Aventis Deutschland Gmbh | Uso de AVE0010 para la fabricación de un medicamento para el tratamiento de la diabetes mellitus de tipo 2 |
| BR112013010345A2 (pt) | 2010-10-27 | 2017-07-25 | Novo Nordisk As | tratamento de diabetes melitus usando as injeções de insulina administradas com intervalos de variação da injeção |
| US9821032B2 (en) | 2011-05-13 | 2017-11-21 | Sanofi-Aventis Deutschland Gmbh | Pharmaceutical combination for improving glycemic control as add-on therapy to basal insulin |
| PL2750699T3 (pl) | 2011-08-29 | 2015-12-31 | Sanofi Aventis Deutschland | Kombinacja farmaceutyczna do stosowania w kontroli glikemii u pacjentów z cukrzycą typu 2 |
| AR087744A1 (es) | 2011-09-01 | 2014-04-16 | Sanofi Aventis Deutschland | Composicion farmaceutica para uso en el tratamiento de una enfermedad neurodegenerativa |
| CA2870313A1 (en) | 2012-04-11 | 2013-10-17 | Novo Nordisk A/S | Insulin formulations |
| BR112015013223A2 (pt) * | 2012-12-26 | 2017-07-11 | Wockhardt Ltd | composição farmacêutica |
| MX369511B (es) | 2013-04-03 | 2019-11-11 | Sanofi Sa | Tratamiento de la diabetes mellitus mediante formulaciones de insulinas de acción prolongada. |
| JP2016519127A (ja) | 2013-04-30 | 2016-06-30 | ノヴォ ノルディスク アー／エス | 新規投与レジメン |
| AU2014333979B2 (en) | 2013-10-07 | 2018-02-15 | Novo Nordisk A/S | Novel derivative of an insulin analogue |
| AU2015359376B2 (en) | 2014-12-12 | 2021-09-09 | Sanofi-Aventis Deutschland Gmbh | Insulin glargine/lixisenatide fixed ratio formulation |
| TWI748945B (zh) | 2015-03-13 | 2021-12-11 | 德商賽諾菲阿凡提斯德意志有限公司 | 第２型糖尿病病患治療 |
| TW201705975A (zh) | 2015-03-18 | 2017-02-16 | 賽諾菲阿凡提斯德意志有限公司 | 第２型糖尿病病患之治療 |
| GB201607918D0 (en) | 2016-05-06 | 2016-06-22 | Arecor Ltd | Novel formulations |
| ES2886837T3 (es) | 2016-12-16 | 2021-12-21 | Novo Nordisk As | Composiciones farmacéuticas que contienen insulina |
| US10335464B1 (en) | 2018-06-26 | 2019-07-02 | Novo Nordisk A/S | Device for titrating basal insulin |
| US12343383B2 (en) | 2019-07-12 | 2025-07-01 | Novo Nordisk A/S | High concentration insulin formulation |
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| FI78616C (fi) * | 1982-02-05 | 1989-09-11 | Novo Industri As | Foerfarande foer framstaellning av en foer infusionsaendamaol avsedd stabiliserad insulinloesning, som har en foerhoejd zinkhalt. |
| US5506203C1 (en) * | 1993-06-24 | 2001-02-06 | Astra Ab | Systemic administration of a therapeutic preparation |
| US5504188A (en) * | 1994-06-16 | 1996-04-02 | Eli Lilly And Company | Preparation of stable zinc insulin analog crystals |
| US5474978A (en) * | 1994-06-16 | 1995-12-12 | Eli Lilly And Company | Insulin analog formulations |
| ATE369146T1 (de) * | 1996-06-20 | 2007-08-15 | Novo Nordisk As | Insulinpreparation mit mannitol |
| JP2001518915A (ja) * | 1997-03-20 | 2001-10-16 | ノボ ノルディスク アクティーゼルスカブ | インシュリンと吸収増強剤の共沈殿による治療用粉末の調整法 |
| ATE219942T1 (de) * | 1997-03-20 | 2002-07-15 | Novo Nordisk As | Therapeutische pulverformulierung zur pulmonaren anwendung, welche kristallines insulin enthält |
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