HRP20000427A2 - Insoluble compositions for controlling blood glucose - Google Patents
Insoluble compositions for controlling blood glucose Download PDFInfo
- Publication number
- HRP20000427A2 HRP20000427A2 HR20000427A HRP20000427A HRP20000427A2 HR P20000427 A2 HRP20000427 A2 HR P20000427A2 HR 20000427 A HR20000427 A HR 20000427A HR P20000427 A HRP20000427 A HR P20000427A HR P20000427 A2 HRP20000427 A2 HR P20000427A2
- Authority
- HR
- Croatia
- Prior art keywords
- insulin
- protein
- derivatized
- human insulin
- mixture according
- Prior art date
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- 239000000203 mixture Substances 0.000 title claims description 183
- 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 title claims description 34
- 239000008103 glucose Substances 0.000 title claims description 33
- 210000004369 blood Anatomy 0.000 title claims description 32
- 239000008280 blood Substances 0.000 title claims description 32
- 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 claims description 501
- 101000976075 Homo sapiens Insulin Proteins 0.000 claims description 479
- 102000004169 proteins and genes Human genes 0.000 claims description 457
- 108090000623 proteins and genes Proteins 0.000 claims description 457
- 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 description 337
- 238000002360 preparation method Methods 0.000 claims description 243
- 102000004877 Insulin Human genes 0.000 claims description 225
- 108090001061 Insulin Proteins 0.000 claims description 225
- 229940125396 insulin Drugs 0.000 claims description 191
- 239000000126 substance Substances 0.000 claims description 140
- 108010007568 Protamines Proteins 0.000 claims description 136
- 102000007327 Protamines Human genes 0.000 claims description 136
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 107
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 106
- 239000000194 fatty acid Substances 0.000 claims description 106
- 229930195729 fatty acid Natural products 0.000 claims description 106
- 238000000034 method Methods 0.000 claims description 105
- 229940048914 protamine Drugs 0.000 claims description 100
- 239000002244 precipitate Substances 0.000 claims description 97
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 95
- 150000004665 fatty acids Chemical class 0.000 claims description 92
- 239000011701 zinc Substances 0.000 claims description 89
- 229910052725 zinc Inorganic materials 0.000 claims description 88
- 239000013081 microcrystal Substances 0.000 claims description 84
- 230000015572 biosynthetic process Effects 0.000 claims description 64
- 239000000725 suspension Substances 0.000 claims description 57
- 230000000536 complexating effect Effects 0.000 claims description 55
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 55
- 108010076181 Proinsulin Proteins 0.000 claims description 53
- 150000001875 compounds Chemical class 0.000 claims description 53
- 239000012736 aqueous medium Substances 0.000 claims description 52
- 239000004026 insulin derivative Substances 0.000 claims description 51
- 239000002904 solvent Substances 0.000 claims description 43
- 150000001768 cations Chemical class 0.000 claims description 42
- 230000000087 stabilizing effect Effects 0.000 claims description 42
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 claims description 39
- 108091005647 acylated proteins Proteins 0.000 claims description 37
- 229910052751 metal Inorganic materials 0.000 claims description 37
- 239000002184 metal Substances 0.000 claims description 37
- 239000003755 preservative agent Substances 0.000 claims description 35
- 230000008569 process Effects 0.000 claims description 35
- 125000004432 carbon atom Chemical group C* 0.000 claims description 34
- -1 fatty acid acylated insulin Chemical class 0.000 claims description 29
- 150000004671 saturated fatty acids Chemical group 0.000 claims description 28
- 206010012601 diabetes mellitus Diseases 0.000 claims description 22
- 238000001556 precipitation Methods 0.000 claims description 22
- 230000002335 preservative effect Effects 0.000 claims description 21
- 239000000872 buffer Substances 0.000 claims description 17
- 241001465754 Metazoa Species 0.000 claims description 16
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 claims description 16
- 238000002156 mixing Methods 0.000 claims description 15
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims description 12
- 239000000178 monomer Substances 0.000 claims description 12
- 201000001421 hyperglycemia Diseases 0.000 claims description 11
- 238000004090 dissolution Methods 0.000 claims description 10
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 claims description 10
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 claims description 10
- FBUKVWPVBMHYJY-UHFFFAOYSA-N nonanoic acid Chemical compound CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 9
- CFKMVGJGLGKFKI-UHFFFAOYSA-N 4-chloro-m-cresol Chemical compound CC1=CC(O)=CC=C1Cl CFKMVGJGLGKFKI-UHFFFAOYSA-N 0.000 claims description 8
- IWDCLRJOBJJRNH-UHFFFAOYSA-N p-cresol Chemical compound CC1=CC=C(O)C=C1 IWDCLRJOBJJRNH-UHFFFAOYSA-N 0.000 claims description 8
- QWVGKYWNOKOFNN-UHFFFAOYSA-N o-cresol Chemical compound CC1=CC=CC=C1O QWVGKYWNOKOFNN-UHFFFAOYSA-N 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 238000012217 deletion Methods 0.000 claims description 6
- 230000037430 deletion Effects 0.000 claims description 6
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 claims description 6
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 claims description 6
- TUNFSRHWOTWDNC-UHFFFAOYSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 claims description 6
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 claims description 5
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 claims description 5
- 229960002216 methylparaben Drugs 0.000 claims description 5
- 230000006641 stabilisation Effects 0.000 claims description 5
- 238000011105 stabilization Methods 0.000 claims description 5
- 229960002242 chlorocresol Drugs 0.000 claims description 4
- 230000001788 irregular Effects 0.000 claims description 4
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 claims 12
- 230000003381 solubilizing effect Effects 0.000 claims 1
- 235000018102 proteins Nutrition 0.000 description 378
- 239000000243 solution Substances 0.000 description 283
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 129
- 239000013078 crystal Substances 0.000 description 113
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 69
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 45
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 45
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 43
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 42
- 238000002425 crystallisation Methods 0.000 description 40
- 230000008025 crystallization Effects 0.000 description 40
- 239000012071 phase Substances 0.000 description 38
- 229950008679 protamine sulfate Drugs 0.000 description 37
- 108010081368 Isophane Insulin Proteins 0.000 description 33
- 102000005237 Isophane Insulin Human genes 0.000 description 32
- 230000009471 action Effects 0.000 description 32
- 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 description 32
- LEMUFSYUPGXXCM-JNEQYSBXSA-N caninsulin Chemical compound [Zn].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](CC3N=CN=C3)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(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)C1C=NC=N1 LEMUFSYUPGXXCM-JNEQYSBXSA-N 0.000 description 32
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- 238000002474 experimental method Methods 0.000 description 22
- 150000003839 salts Chemical class 0.000 description 22
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- 125000003277 amino group Chemical group 0.000 description 16
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- 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
- A61K38/28—Insulins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
-
- 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
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Diabetes (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Endocrinology (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US6860197P | 1997-12-23 | 1997-12-23 | |
| US8885998P | 1998-06-11 | 1998-06-11 | |
| US10994098P | 1998-11-25 | 1998-11-25 | |
| PCT/US1998/027299 WO1999032116A1 (en) | 1997-12-23 | 1998-12-22 | Insoluble compositions for controlling blood glucose |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20000427A2 true HRP20000427A2 (en) | 2001-06-30 |
Family
ID=27371371
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20000427A HRP20000427A2 (en) | 1997-12-23 | 2000-06-23 | Insoluble compositions for controlling blood glucose |
Country Status (24)
| Country | Link |
|---|---|
| US (2) | US6531448B1 (es) |
| EP (1) | EP0925792B1 (es) |
| JP (1) | JP2001526225A (es) |
| KR (1) | KR20010024799A (es) |
| CN (1) | CN1284876A (es) |
| AR (1) | AR019807A1 (es) |
| AT (1) | ATE264690T1 (es) |
| AU (1) | AU2008899A (es) |
| BR (1) | BR9814471A (es) |
| CA (1) | CA2315300A1 (es) |
| CO (1) | CO4970787A1 (es) |
| DE (1) | DE69823319D1 (es) |
| DZ (1) | DZ2691A1 (es) |
| EA (1) | EA003394B1 (es) |
| HR (1) | HRP20000427A2 (es) |
| HU (1) | HUP0100243A3 (es) |
| ID (1) | ID25476A (es) |
| IL (1) | IL136724A0 (es) |
| NO (1) | NO20003269L (es) |
| NZ (1) | NZ505091A (es) |
| PE (1) | PE20000106A1 (es) |
| PL (1) | PL341300A1 (es) |
| TR (1) | TR200001935T2 (es) |
| WO (1) | WO1999032116A1 (es) |
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| EP1432430A4 (en) | 2001-08-28 | 2006-05-10 | Lilly Co Eli | PREMIXTURES OF GLP-1 AND BASALINSULIN |
| EP1448222A4 (en) | 2001-10-19 | 2006-05-17 | Lilly Co Eli | BIPHASIC MIXTURES OF GLP-1 AND INSULIN |
| WO2003053460A1 (en) * | 2001-12-19 | 2003-07-03 | Eli Lilly And Company | Crystalline compositions for controlling blood glucose |
| JP2005539208A (ja) * | 2001-12-21 | 2005-12-22 | スミスクライン ビーチャム コーポレーション | グルコース産生を変化させるための組成物および方法 |
| AU2003236201A1 (en) | 2002-05-07 | 2003-11-11 | Novo Nordisk A/S | Soluble formulations comprising monomeric insulin and acylated insulin |
| DK1581251T3 (da) | 2002-12-31 | 2016-06-27 | Althea Tech Inc | Krystaller af humant væksthormon og fremgangsmåder til fremstilling deraf |
| JP2006519791A (ja) * | 2003-03-13 | 2006-08-31 | ノボ ノルディスク アクティーゼルスカブ | 新規なｎｐｈインスリン製剤 |
| EP1620465A2 (en) * | 2003-04-29 | 2006-02-01 | Eli Lilly And Company | Insulin analogs having protracted time action |
| US20050054818A1 (en) * | 2003-07-02 | 2005-03-10 | Brader Mark Laurence | Crystalline compositions for controlling blood glucose |
| EP1660531A2 (en) * | 2003-08-05 | 2006-05-31 | Novo Nordisk A/S | Novel insulin derivatives |
| BRPI0513508B1 (pt) * | 2004-07-19 | 2021-06-01 | Biocon Limited | Conjugados de insulina-oligômero, formulações e usos desses |
| AU2014200247B2 (en) * | 2004-07-19 | 2015-05-14 | Biocon Limited | Insulin-oligomer conjugates, formulations and uses thereof |
| PL373543A1 (pl) * | 2005-03-10 | 2006-09-18 | Instytut Biotechnologii i Antybiotyków | Kompozycja farmaceutyczna zawierająca biosyntetyczny analog insuliny ludzkiej, oraz jej zastosowanie w terapii cukrzycy |
| CA2915270C (en) * | 2005-08-05 | 2017-07-11 | Amgen Inc. | Stable aqueous protein or antibody pharmaceutical formulations and their preparation |
| WO2007026474A1 (ja) * | 2005-08-29 | 2007-03-08 | Ajinomoto Co., Inc. | 栄養組成物 |
| EP1969004B1 (en) * | 2005-12-28 | 2011-08-10 | Novo Nordisk A/S | Compositions comprising an acylated insulin and zinc and method of making the said compositions |
| WO2007081824A2 (en) * | 2006-01-06 | 2007-07-19 | Case Western Reserve University | Fibrillation resistant proteins |
| WO2007121318A2 (en) * | 2006-04-12 | 2007-10-25 | Emisphere Technologies, Inc. | Formulations for delivering insulin |
| 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 |
| CA2663074A1 (en) | 2006-09-22 | 2008-03-27 | Novo Nordisk A/S | Protease resistant insulin analogues |
| EP2074140B8 (en) | 2006-10-04 | 2015-10-28 | Case Western Reserve University | Fibrillation-resistant insulin and insulin analogues |
| EP2152245B1 (en) | 2007-04-30 | 2015-12-02 | Novo Nordisk A/S | Method for drying a protein composition, a dried protein composition and a pharmaceutical composition comprising the dried protein |
| WO2008152106A1 (en) * | 2007-06-13 | 2008-12-18 | Novo Nordisk A/S | Pharmaceutical formulation comprising an insulin derivative |
| BRPI0818004B8 (pt) * | 2007-10-16 | 2021-05-25 | Biocon Ltd | composição farmacêutica sólida administrável por via oral e o processo da mesma. |
| BRPI0820535B8 (pt) | 2007-11-16 | 2021-05-25 | Novo Nordisk As | composições farmacêuticas contendo insulina e um peptídeo insulinotrópico |
| US9260502B2 (en) | 2008-03-14 | 2016-02-16 | Novo Nordisk A/S | Protease-stabilized insulin analogues |
| HUE032284T2 (en) | 2008-03-18 | 2017-09-28 | Novo Nordisk As | Protease-stabilized, acylated insulin analogues |
| WO2009125423A2 (en) * | 2008-04-07 | 2009-10-15 | National Institute Of Immunology | Compositions useful for the treatment of diabetes and other chronic disorder |
| US8993516B2 (en) * | 2008-04-14 | 2015-03-31 | Case Western Reserve University | Meal-time insulin analogues of enhanced stability |
| CA2722168A1 (en) * | 2008-04-22 | 2009-10-29 | Case Western Reserve University | Isoform-specific insulin analogues |
| KR20120129875A (ko) * | 2008-07-31 | 2012-11-28 | 케이스 웨스턴 리저브 유니버시티 | 염소화 아미노산을 갖는 인슐린 유사체 |
| US9200053B2 (en) | 2008-07-31 | 2015-12-01 | Case Western Reserve University | Insulin analogues containing penta-fluoro-Phenylalanine at position B24 |
| EP2344200A2 (en) * | 2008-09-19 | 2011-07-20 | Nektar Therapeutics | Modified therapeutics peptides, methods of their preparation and use |
| WO2010049488A1 (en) * | 2008-10-30 | 2010-05-06 | Novo Nordisk A/S | Treating diabetes melitus using insulin injections with less than daily injection frequency |
| US8399407B2 (en) * | 2009-09-17 | 2013-03-19 | Case Western Reserve University | Non-standard insulin analogues |
| CN102770152B (zh) | 2009-11-25 | 2016-07-06 | 阿瑞斯根股份有限公司 | 肽类的粘膜递送 |
| RU2012123642A (ru) | 2009-12-11 | 2014-01-20 | Кейз Вестерн Ризев Юнивесити | Аналоги инсулина, содержащие хлорированные аминокислоты |
| RU2013123515A (ru) | 2010-10-27 | 2014-12-10 | Ново Нордиск А/С | Лечение сахарного диабета с помощью инъекций инсулина, вводимых с различными интервалами |
| CN102219851B (zh) * | 2011-05-09 | 2012-05-30 | 甘李药业有限公司 | 甘精胰岛素结晶的制备方法 |
| EP2720711A1 (en) | 2011-06-15 | 2014-04-23 | Novo Nordisk A/S | Multi substituted insulins |
| KR20150002777A (ko) | 2012-04-11 | 2015-01-07 | 노보 노르디스크 에이/에스 | 인슐린 제제 |
| WO2013158277A1 (en) * | 2012-04-18 | 2013-10-24 | Waters Technologies Corporation | Methods for quantifying polypeptides using mass spectrometry |
| AU2013255880B2 (en) * | 2012-05-01 | 2017-07-20 | Novo Nordisk A/S | Pharmaceutical composition |
| US9171343B1 (en) | 2012-09-11 | 2015-10-27 | Aseko, Inc. | Means and method for improved glycemic control for diabetic patients |
| US9897565B1 (en) | 2012-09-11 | 2018-02-20 | Aseko, Inc. | System and method for optimizing insulin dosages for diabetic subjects |
| US10421795B2 (en) | 2012-12-17 | 2019-09-24 | Merck Sharp & Dohme Corp. | Process for purifying insulin and analogues thereof |
| US9707275B2 (en) * | 2012-12-19 | 2017-07-18 | Wockhardt Limited | Stable aqueous composition comprising human insulin or an analogue or derivative thereof |
| WO2014116753A1 (en) * | 2013-01-22 | 2014-07-31 | Case Western Reserve University | N-terminal truncated insulin analogues |
| CN103145829B (zh) * | 2013-03-29 | 2015-06-03 | 江苏诺泰制药有限公司 | 一种地特胰岛素的纯化方法 |
| 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 |
| PL3055325T3 (pl) | 2013-10-07 | 2018-06-29 | Novo Nordisk A/S | Nowa pochodna analogu insuliny |
| US9486580B2 (en) | 2014-01-31 | 2016-11-08 | Aseko, Inc. | Insulin management |
| US9898585B2 (en) | 2014-01-31 | 2018-02-20 | Aseko, Inc. | Method and system for insulin management |
| AR099569A1 (es) | 2014-02-28 | 2016-08-03 | Novo Nordisk As | Derivados de insulina y los usos médicos de estos |
| BR112017004544A2 (pt) | 2014-10-06 | 2018-01-23 | Univ Case Western Reserve | insulina de cadeia simples, composição farmacêutica e método para tratar diabetes mellitus |
| US11081226B2 (en) | 2014-10-27 | 2021-08-03 | Aseko, Inc. | Method and controller for administering recommended insulin dosages to a patient |
| EP3050023B1 (en) | 2014-10-27 | 2021-08-25 | Aseko, Inc. | Subcutaneous outpatient management |
| AU2016308953B2 (en) | 2015-08-20 | 2020-09-10 | Aseko, Inc. | Diabetes management therapy advisor |
| DK3554534T3 (da) | 2016-12-16 | 2021-08-23 | Novo Nordisk As | Farmaceutisk sammensætning omfattende insulin |
| US10335464B1 (en) | 2018-06-26 | 2019-07-02 | Novo Nordisk A/S | Device for titrating basal insulin |
| KR102253318B1 (ko) * | 2020-06-02 | 2021-05-18 | (주)위바이오트리 | 금속 상 변환 화합물 및 이의 제조 방법 |
| CN114306577B (zh) * | 2020-10-10 | 2024-04-09 | 南京汉欣医药科技有限公司 | 一种门冬胰岛素30混悬液的制备方法 |
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-
1998
- 1998-12-21 CO CO98075716A patent/CO4970787A1/es unknown
- 1998-12-21 US US09/217,275 patent/US6531448B1/en not_active Expired - Fee Related
- 1998-12-22 WO PCT/US1998/027299 patent/WO1999032116A1/en not_active Application Discontinuation
- 1998-12-22 AU AU20088/99A patent/AU2008899A/en not_active Abandoned
- 1998-12-22 TR TR2000/01935T patent/TR200001935T2/xx unknown
- 1998-12-22 EA EA200000708A patent/EA003394B1/ru not_active IP Right Cessation
- 1998-12-22 AR ARP980106619A patent/AR019807A1/es unknown
- 1998-12-22 HU HU0100243A patent/HUP0100243A3/hu unknown
- 1998-12-22 CA CA002315300A patent/CA2315300A1/en not_active Abandoned
- 1998-12-22 NZ NZ505091A patent/NZ505091A/xx unknown
- 1998-12-22 PE PE1998001271A patent/PE20000106A1/es not_active Application Discontinuation
- 1998-12-22 JP JP2000525107A patent/JP2001526225A/ja not_active Withdrawn
- 1998-12-22 BR BR9814471-5A patent/BR9814471A/pt not_active IP Right Cessation
- 1998-12-22 KR KR1020007006946A patent/KR20010024799A/ko not_active Application Discontinuation
- 1998-12-22 ID IDW20001227A patent/ID25476A/id unknown
- 1998-12-22 CN CN98813743A patent/CN1284876A/zh active Pending
- 1998-12-22 PL PL98341300A patent/PL341300A1/xx unknown
- 1998-12-22 DZ DZ980301A patent/DZ2691A1/xx active
- 1998-12-22 IL IL13672498A patent/IL136724A0/xx unknown
- 1998-12-23 AT AT98310695T patent/ATE264690T1/de not_active IP Right Cessation
- 1998-12-23 DE DE69823319T patent/DE69823319D1/de not_active Expired - Lifetime
- 1998-12-23 EP EP98310695A patent/EP0925792B1/en not_active Expired - Lifetime
-
2000
- 2000-06-22 NO NO20003269A patent/NO20003269L/no not_active Application Discontinuation
- 2000-06-23 HR HR20000427A patent/HRP20000427A2/hr not_active Application Discontinuation
-
2003
- 2003-01-07 US US10/338,101 patent/US20030144181A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP0925792B1 (en) | 2004-04-21 |
| AR019807A1 (es) | 2002-03-20 |
| US6531448B1 (en) | 2003-03-11 |
| EA003394B1 (ru) | 2003-04-24 |
| KR20010024799A (ko) | 2001-03-26 |
| NZ505091A (en) | 2002-11-26 |
| EP0925792A3 (en) | 2001-09-12 |
| PL341300A1 (en) | 2001-04-09 |
| TR200001935T2 (tr) | 2000-12-21 |
| ATE264690T1 (de) | 2004-05-15 |
| BR9814471A (pt) | 2000-10-10 |
| NO20003269L (no) | 2000-08-23 |
| JP2001526225A (ja) | 2001-12-18 |
| AU2008899A (en) | 1999-07-12 |
| PE20000106A1 (es) | 2000-02-09 |
| NO20003269D0 (no) | 2000-06-22 |
| DZ2691A1 (fr) | 2003-03-29 |
| ID25476A (id) | 2000-10-05 |
| CN1284876A (zh) | 2001-02-21 |
| DE69823319D1 (de) | 2004-05-27 |
| EA200000708A1 (ru) | 2000-12-25 |
| US20030144181A1 (en) | 2003-07-31 |
| CO4970787A1 (es) | 2000-11-07 |
| WO1999032116A1 (en) | 1999-07-01 |
| IL136724A0 (en) | 2001-06-14 |
| CA2315300A1 (en) | 1999-07-01 |
| EP0925792A2 (en) | 1999-06-30 |
| HUP0100243A3 (en) | 2001-09-28 |
| HUP0100243A2 (hu) | 2001-08-28 |
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