HRP20170155T1 - Vodeni pripravci koji sadrže metionin - Google Patents
Vodeni pripravci koji sadrže metionin Download PDFInfo
- Publication number
- HRP20170155T1 HRP20170155T1 HRP20170155TT HRP20170155T HRP20170155T1 HR P20170155 T1 HRP20170155 T1 HR P20170155T1 HR P20170155T T HRP20170155T T HR P20170155TT HR P20170155 T HRP20170155 T HR P20170155T HR P20170155 T1 HRP20170155 T1 HR P20170155T1
- Authority
- HR
- Croatia
- Prior art keywords
- arg
- glu
- human insulin
- gly
- lys
- Prior art date
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- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 title claims 3
- 229930182817 methionine Natural products 0.000 title claims 3
- 238000002360 preparation method Methods 0.000 title 1
- 101000976075 Homo sapiens Insulin Proteins 0.000 claims 85
- 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 83
- JUFFVKRROAPVBI-PVOYSMBESA-N chembl1210015 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)N[C@H]1[C@@H]([C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO[C@]3(O[C@@H](C[C@H](O)[C@H](O)CO)[C@H](NC(C)=O)[C@@H](O)C3)C(O)=O)O2)O)[C@@H](CO)O1)NC(C)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)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)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 JUFFVKRROAPVBI-PVOYSMBESA-N 0.000 claims 69
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 claims 68
- 108010011459 Exenatide Proteins 0.000 claims 37
- 229960001519 exenatide Drugs 0.000 claims 36
- QEFRNWWLZKMPFJ-YGVKFDHGSA-N L-methionine S-oxide Chemical compound CS(=O)CC[C@H](N)C(O)=O QEFRNWWLZKMPFJ-YGVKFDHGSA-N 0.000 claims 18
- 239000008194 pharmaceutical composition Substances 0.000 claims 13
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical class 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 11
- 239000004026 insulin derivative Substances 0.000 claims 10
- 239000000126 substance Chemical group 0.000 claims 10
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims 6
- 150000003839 salts Chemical class 0.000 claims 5
- 125000003277 amino group Chemical group 0.000 claims 4
- 238000009472 formulation Methods 0.000 claims 4
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 claims 4
- 239000000203 mixture Substances 0.000 claims 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims 2
- 125000000539 amino acid group Chemical group 0.000 claims 2
- 150000001413 amino acids Chemical class 0.000 claims 2
- 206010012601 diabetes mellitus Diseases 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- SSAAJZQUEUTACT-MDBKHZGBSA-N exendin 2 Chemical compound C([C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(N)=O)C1=CN=CN1 SSAAJZQUEUTACT-MDBKHZGBSA-N 0.000 claims 2
- 108010028997 heliodermin Proteins 0.000 claims 2
- 239000003755 preservative agent Substances 0.000 claims 2
- 230000002335 preservative effect Effects 0.000 claims 2
- 239000011701 zinc Substances 0.000 claims 2
- 229910052725 zinc Inorganic materials 0.000 claims 2
- 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 1
- WADQOGCINABPRT-UHFFFAOYSA-N 3-chloro-2-methylphenol Chemical compound CC1=C(O)C=CC=C1Cl WADQOGCINABPRT-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- OBMZMSLWNNWEJA-XNCRXQDQSA-N C1=CC=2C(C[C@@H]3NC(=O)[C@@H](NC(=O)[C@H](NC(=O)N(CC#CCN(CCCC[C@H](NC(=O)[C@@H](CC4=CC=CC=C4)NC3=O)C(=O)N)CC=C)NC(=O)[C@@H](N)C)CC3=CNC4=C3C=CC=C4)C)=CNC=2C=C1 Chemical compound C1=CC=2C(C[C@@H]3NC(=O)[C@@H](NC(=O)[C@H](NC(=O)N(CC#CCN(CCCC[C@H](NC(=O)[C@@H](CC4=CC=CC=C4)NC3=O)C(=O)N)CC=C)NC(=O)[C@@H](N)C)CC3=CNC4=C3C=CC=C4)C)=CNC=2C=C1 OBMZMSLWNNWEJA-XNCRXQDQSA-N 0.000 claims 1
- 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 1
- 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 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims 1
- 101800004266 Glucagon-like peptide 1(7-37) Proteins 0.000 claims 1
- 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 1
- -1 His (A8) Chemical compound 0.000 claims 1
- 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 1
- YSDQQAXHVYUZIW-QCIJIYAXSA-N Liraglutide Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCC)C(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)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](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)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=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 YSDQQAXHVYUZIW-QCIJIYAXSA-N 0.000 claims 1
- 108010019598 Liraglutide Proteins 0.000 claims 1
- 229930195725 Mannitol Natural products 0.000 claims 1
- 101710176384 Peptide 1 Proteins 0.000 claims 1
- 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 1
- 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 1
- 239000007864 aqueous solution Substances 0.000 claims 1
- 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 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 239000008121 dextrose Substances 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 108010015174 exendin 3 Proteins 0.000 claims 1
- LMHMJYMCGJNXRS-IOPUOMRJSA-N exendin-3 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)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](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@H](C)O)[C@H](C)O)C(C)C)C1=CC=CC=C1 LMHMJYMCGJNXRS-IOPUOMRJSA-N 0.000 claims 1
- 125000002642 gamma-glutamyl group Chemical group 0.000 claims 1
- 239000007951 isotonicity adjuster Substances 0.000 claims 1
- 239000008101 lactose Substances 0.000 claims 1
- 229960002701 liraglutide Drugs 0.000 claims 1
- 239000000594 mannitol Substances 0.000 claims 1
- 235000010355 mannitol Nutrition 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 238000010979 pH adjustment Methods 0.000 claims 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 claims 1
- GCYXWQUSHADNBF-AAEALURTSA-N preproglucagon 78-108 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(=O)NCC(O)=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 GCYXWQUSHADNBF-AAEALURTSA-N 0.000 claims 1
- 108090000765 processed proteins & peptides Proteins 0.000 claims 1
- 239000011780 sodium chloride Substances 0.000 claims 1
- 239000000600 sorbitol Substances 0.000 claims 1
Classifications
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- 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
- A61K38/26—Glucagons
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
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Claims (16)
1. Vodena farmaceutska formulacija koja sadrži analog inzulina ili derivat inzulina, ili njihovu farmakološki podnošljivu sol, i metionin, a pH formulacije je 4.5 ili manje, i
(I) analog inzulina je odabran iz skupine koju čine Gly(A21), Arg(B31), Arg(B32) ljudski inzulin, Lys(B3), Glu(B29) ljudski inzulin, Asp(B28) ljudski inzulin, Lys(B28) Pro(B29) ljudski inzulin, Des(B30) ljudski inzulin i analog inzulina s formulom I
[image]
[image]
[image]
gdje
A0 je Lys ili Arg;
A5 je Asp, Gln ili Glu;
A15 je Asp, Glu ili Gln;
A18 je Asp, Glu ili Asn;
B-1 je Asp, Glu ili amino skupina;
B0 je Asp, Glu ili kemijska veza;
B1 je Asp, Glu ili Phe;
B2 je Asp, Glu ili Val;
B3 je Asp, Glu ili Asn;
B4 je Asp, Glu ili Gln;
B29 je Lys ili kemijska veza;
B30 je Thr ili kemijska veza;
B31 je Arg, Lys ili kemijska veza;
B32 je Arg-amid, Lys-amid ili amino skupina,
dva amino kiselinska ostatka iz skupine koju čine A5, A15, A18, B-1, B0, B1, B2, B3, i B4, istovremeno i međusobno neovisno, su Asp ili Glu, a analog inzulina je naročito odabran iz skupine koju čine:
Arg (A0), His (A8), Glu (A5), Asp (A18), Gly (A21), Arg (B31), Arg (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Glu (A5), Asp (A18), Gly (A21), Arg (B31), Lys (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Glu (A15), Asp (A18), Gly (A21), Arg (B31), Arg (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Glu (A15), Asp (A18), Gly (A21), Arg (B31), Lys (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Glu(A5), Glu (A15), Gly (A21), Arg (B31), Arg (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Glu (A5), Glu (A15), Gly (A21), Arg (B31), Lys (B32) - NH2 ljudski inzulin,
Arg (A0), His(A8), Glu (A5), Gly (A21), Asp (B3), Arg (B31), Arg (B32) - NH2 ljudski inzulin,
Arg (A0), His(A8), Glu (A5), Gly (A21), Asp (B3), Arg (B31), Lys (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Glu (A15), Gly (A21), Asp (B3), Arg (B31), Arg (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Glu (A15), Gly (A21), Asp (B3), Arg (B31), Lys (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Asp (A18), Gly (A21), Asp (B3), Arg (B31), Arg (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Asp (A18), Gly (A21), Asp (B3), Arg (B31), Lys (B32) - NH2 ljudski inzulin,
Arg (A0), His(A8), Gly (A21), Asp (B3), Glu (B4), Arg (B31), Arg (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Gly (A21), Asp (B3), Glu (B4), Arg (B31), Lys (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Glu (A5), Gly (A21), Glu (B4), Arg (B31), Arg (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Glu (A5), Gly (A21), Glu (B4), Arg (B31), Lys (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Glu (A15), Gly (A21), Glu (B4), Arg (B31), Arg (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Glu (A15), Gly (A21), Glu (B4), Arg (B31), Lys (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Asp (A18), Gly (A21), Glu (B4), Arg (B31), Arg (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Asp (A18), Gly (A21), Glu (B4), Arg (B31), Lys (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Glu (A5), Gly (A21), Glu (B0), Arg (B31), Arg (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Glu (A5), Gly (A21), Glu (B0), Arg (B31), Lys (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Glu (A15), Gly (A21), Glu (B0), Arg (B31), Arg (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Glu (A15), Gly (A21), Glu (B0), Arg (B31), Lys (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Asp (A18), Gly (A21), Glu (B0), Arg (B31), Arg (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Asp (A18), Gly (A21), Glu (B0), Arg (B31), Lys (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Glu (A5), Gly (A21), Asp (B1), Arg (B31), Arg (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Glu (A5), Gly (A21), Asp (B1), Arg (B31), Lys (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Glu (A15), Gly (A21), Asp (B1), Arg (B31), Arg(B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Glu (A15), Gly (A21), Asp (B1), Arg (B31), Lys (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Asp (A18), Gly (A21), Asp (B1), Arg (B31), Arg (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Asp (A18), Gly (A21), Asp (B1), Arg (B31), Lys (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Gly (A21), Glu (B0), Asp (B1), Arg (B31), Arg (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Gly (A21), Glu (B0), Asp (B1), Arg (B31), Lys (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Asp (A18), Gly (A21), Asp (B3), Arg (B30), Arg (B31) - NH2 ljudski inzulin,
Arg (A0), His (A8), Asp (A18), Gly (A21), Asp (B3), Arg (B30), Lys (B31) - NH2 ljudski inzulin,
(II) analog inzulina se bira iz skupine koju čine analozi inzulina s formulom II
[image]
[image]
[image]
gdje
A-1 je Lys, Arg ili amino skupina;
A0 je Lys, Arg ili kemijska veza;
A1 je Arg ili Gly;
A5 je Asp, Glu ili Gln;
A15 je Asp, Glu ili Gln;
A18 je Asp, Glu ili Asn;
A21 je Ala, Ser, Thr ili Gly;
B-1 je Asp, Glu ili amino skupina;
B0 je Asp, Glu ili kemijska veza;
B1 je Asp, Glu, Phe ili kemijska veza;
B3 je Asp, Glu ili Asn;
B4 je Asp, Glu ili Gln;
B29 je Arg, Lys ili neka aminokiselina odabrana iz skupine koju čine aminokiseline Phe, Ala, Thr, Ser, Val, Leu, Glu ili Asp, ili kemijska veza;
B30 je Thr ili kemijska veza;
B31 je Arg, Lys ili kemijska veza;
B32 je Arg-amid ili Lys-amid,
gdje ne više od amino kiselinskih ostataka iz skupine koju čine A5, A15, A18, B-1, B0, B1, B2, B3 i B4, istovremeno i međusobno neovisno, su Asp ili Glu, a analog inzulina je odabran naročito iz skupine koju čine:
Arg (A-1), Arg (A0), Glu (A5), His (A8), Gly (A21), Arg (B30) - NH2 ljudski inzulin,
Arg (A-1), Arg (A0), Glu (A5), His (A8), Gly (A21), Lys (B30) - NH2 ljudski inzulin,
Arg (A-1), Arg (A0), Glu (A15), His (A8), Gly (A21), Arg (B30) - NH2 ljudski inzulin,
Arg (A-1), Arg (A0), Glu (A15), His (A8), Gly (A21), Lys (B30) - NH2 ljudski inzulin,
Arg (A-1), Arg (A0), Asp (A18), His (A8), Gly (A21), Arg (B30) - NH2 ljudski inzulin,
Arg (A-1), Arg (A0), His (A8), Gly (A21), Glu (B0), Arg (B30) - NH2 ljudski inzulin,
Arg (A-1), Arg (A0), His (A8), Gly (A21), Glu (B0), Lys (B30) - NH2 ljudski inzulin,
Arg (A-1), Arg (A0), His (A8), Gly (A21), Asp (B3), Arg (B30) - NH2 ljudski inzulin,
Arg (A-1), Arg (A0), His (A8), Gly (A21), Asp (B3), Lys (B30) - NH2 ljudski inzulin,
Arg (A-1), Arg (A0), His (A8), Gly (A21), Glu (B4), Arg (B30) - NH2 ljudski inzulin,
Arg (A-1), Arg (A0), His (A8), Gly (A21), Glu (B4), Lys (B30) - NH2 ljudski inzulin,
Arg (A0), His (A8), Gly (A21), Arg (B31), Arg (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Gly (A21), Arg (B31), Lys (B32) - NH2 ljudski inzulin,
Arg (A0), Glu (A5), His (A8), Gly (A21), Arg (B31), Arg (B32) - NH2 ljudski inzulin,
Arg (A0), Glu (A5), His (A8), Gly (A21), Arg (B31), Lys (B32) - NH2 ljudski inzulin,
Arg (A0), Asp (A18), His (A8), Gly (A21), Arg (B31), Arg (B32) - NH2 ljudski inzulin,
Arg (A0), Asp (A18), His (A8), Gly (A21), Arg (B31), Lys (B32) - NH2 ljudski inzulin,
Arg (A0), Glu (A15), His (A8), Gly (A21), Arg (B31), Arg (B32) - NH2 ljudski inzulin,
Arg (A0), Glu (A15), His (A8), Gly (A21), Arg (B31), Lys (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Gly (A21), Asp (B3), Arg (B31), Arg (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Gly (A21), Asp (B3), Arg (B31), Lys (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Gly (A21), Glu (B4), Arg (B31), Arg (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Gly (A21), Glu (B4), Arg (B31), Lys (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Gly (A21), Glu (B0), Arg (B31), Arg (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Gly (A21), Glu (B0), Arg (B31), Lys (B32) - NH2 ljudski inzulin,
Arg (A0), His (A8), Gly (A21), Arg (B30) - NH2 ljudski inzulin,
Arg (A0), His (A8), Gly (A21), Lys (B30) - NH2 ljudski inzulin,
Arg (A-1), Arg (A0), His (A8), Gly (A21), Arg (B30) - NH2 ljudski inzulin,
Arg (A-1), Arg (A0), His (A8), Gly (A21), Lys (B30) - NH2 ljudski inzulin,
Arg (A0), Arg (A1), His (A8), Gly (A21), Arg (B30) - NH2 ljudski inzulin,
Arg (A0), Arg (A1), His (A8), Gly (A21), Lys (B30) - NH2 ljudski inzulin,
His (A8), Gly (A21), Arg (B31), Arg (B32) - NH2 ljudski inzulin, ili
(III) derivat inzulina koji se bira iz skupine koju čine B29-N-miristoil-des(B30) ljudski inzulin, B29-N-palmitoil-des(B30) ljudski inzulin, B29-N-miristoil ljudski inzulin, B29-N-palmitoil ljudski inzulin, B28-N-miristoil LysB28ProB29 ljudski inzulin, B28-N-palmitoil-LysB28ProB29 ljudski inzulin, B30-N-miristoil-ThrB29LysB30 ljudski inzulin, B30-N-palmitoil- ThrB29LysB30 ljudski inzulin, B29-N-(N-palmitoil-Υ-glutamil)-des(B39) ljudski inzulin, B29-N-(N-litokolil-Υ-glutamil)-des(B30) ljudski inzulin, B29-N-(ω-karboksiheptadekanoil)-des(B30) ljudski inzulin, i B29-N-(ω-karboksiheptadekanoil) ljudski inzulin.
2. Farmaceutska formulacija prema zahtjevu 1, naznačena time da sadrži
0.001 do 0.2 mg/ml cinka,
0.1 do 5.0 mg/ml konzervansa, i
5.0 do 100 mg/ml sredstva za izotoničnost.
3. Farmaceutska formulacija prema zahtjevu 1 ili 2, naznačena time da sadrži konzervans odabran iz skupine koja sadrži fenol, m-krezol, klorkrezol, benzil alkohol, te parabene i/ili sredstvo za izotoničnost odabrano iz skupine koja sadrži manitol, sorbitol, laktozu, dekstrozu, trehalozu, natrijev klorid, i glicerol.
4. Farmaceutska formulacija prema jednom ili više zahtjeva od 1 do 3, naznačena time da ima pH u rasponu od pH 2.5 - 4.5, poželjno u rasponu od pH 3.0 - 4.0, te poželjnije u području pH 3.75.
5. Farmaceutska formulacija prema jednom ili više zahtjeva od 1 do 4, naznačena time da su analog inzulina i/ili derivat inzulina prisutni u koncentraciji od 240 - 3000 nmol/ml.
6. Farmaceutska formulacija prema jednom ili više zahtjeva od 1 do 5, naznačena time da sadrži glicerol u koncentraciji od 20 do 30 mg/ml, poželjno u koncentraciji od 25 mg/ml.
7. Farmaceutska formulacija prema jednom ili više zahtjeva od 1 do 6, naznačena time da sadrži m-krezol u koncentraciji od 1 do 3 mg/ml, poželjno u koncentraciji od 2 mg/ml.
8. Farmaceutska formulacija prema jednom ili više zahtjeva od 1 do 7, naznačena time da sadrži cink u koncentraciji od 0.01 ili 0.03 ili 0.08 mg/ml.
9. Farmaceutska formulacija prema jednom ili više zahtjeva od 1 do 8, naznačena time da dodatno sadrži gukagonu sličan peptid-1 (GLP1) ili njegov analog ili derivat, ili eksendin-3 i/ili -4 ili njegov analog ili derivat.
10. Farmaceutska formulacija prema zahtjevu 9, naznačena time da sadrži:
(i) eksendin-4,
(ii) analog eksendina-4 odabran iz skupine koja sadrži
H-desPro36-eksendin-4-Lys6-NH2,
H-des(Pro36,37)-eksendin-4-Lys4-NH2 i
H-des(Pro36,37)-eksendin-4-Lys5-NH2,
ili njihovu farmakološki podnošljivu sol, ili
(iii) analog eksendina-4 odabran iz skupine koja sadrži
desPro36 [Asp28]eksendin-4 (1-39),
desPro36 [IsoAsp28]eksendin-4 (1-39),
desPro36 [Met(O)14, Asp28]eksendin-4 (1-39),
desPro36 [Met(O)14, IsoAsp28]eksendin-4 (1-39),
desPro36 [Trp(O2)25, Asp28]eksendin-2 (1-39),
desPro36 [Trp(O2)25 IsoAsp28]eksendin-2 (1-39),
desPro36 [Met(O)14Trp(O2)25, Asp28]eksendin-4 (1-39) i
desPro36 [Met(O)14Trp(O2)25, IsoAsp28]eksendin-4 (1-39),
ili njihovu farmakološki podnošljivu sol, peptid Lys6-NH2 je proizvoljno vezan na C-krajeve analoga eksendina-4.
11. Farmaceutska formulacija prema zahtjevu 9, naznačena time da sadrži analog eksendina-4 koji je odabran iz skupine koju čine
H-(Lys)6- des Pro36 [Asp28]eksendin-4(1-39)-Lys6-NH2
des Asp28Pro36, Pro37, Pro38 eksendin-4(1-39) -NH2,
H-(Lys)6- des Pro36, Pro37, Pro38 [Asp28]eksendin-4(1-39) -NH2,
H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Asp28]eksendin-4(1-39) -NH2,
des Pro36, Pro37, Pro38 [Asp28]eksendin-4(1-39)-(Lys)6-NH2,
H-(Lys)6- des Pro36, Pro37, Pro38 [Asp28]eksendin-4(1-39)-(Lys)6-NH2,
H-Asn-(Glu)5- des Pro36, Pro37, Pro38 [Asp28]eksendin-4(1-39)-(Lys)6-NH2,
H-(Lys)6- des Pro36 [Trp(O2)25, Asp28]eksendin-4(1-39)-Lys6-NH2,
H- des Asp28 Pro36, Pro37, Pro38 [Trp(O2)25]eksendin-4(1-39) -NH2,
H-(Lys)6- des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]eksendin-4(1-39) -NH2,
H-Asn-(Glu)5- des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]eksendin-4(1-39) -NH2,
des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]eksendin-4(1-39)-(Lys)6-NH2,
H-(Lys)6- des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]eksendin-4(1-39)-(Lys)6-NH2,
H-Asn-(Glu)5- des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]eksendin-4(1-39)-(Lys)6-NH2,
H-(Lys)6- des Pro36 [Met(O)14, Asp28]eksendin-4(1-39)-Lys6-NH2,
des Met(O)14 Asp28 Pro36, Pro37, Pro38 eksendin-4(1-39) -NH2,
H-(Lys)6- des Pro36, Pro37, Pro38 [Met(O)14, Asp28]eksendin-4(1-39) -NH2,
H-Asn-(Glu)5- des Pro36, Pro37, Pro38 [Met(O)14, Asp28] eksendin-4(1-39) -NH2,
des Pro36, Pro37, Pro38 [Met(O)14, Asp28]eksendin-4(1-39)-(Lys)6-NH2,
H-(Lys)6- des Pro36, Pro37, Pro38 [Met(O)14, Asp28]eksendin-4(1-39)-Lys6-NH2,
H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Met(O)14, Asp28] eksendin-4(1-39)-(Lys)6-NH2,
H-(Lys)6- des Pro36 [Met(O)14, Trp(O2)25, Asp28]eksendin-4(1-39)-Lys6-NH2,
des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25]eksendin-4(1-39) -NH2,
H-(Lys)6- des Pro36, Pro17, Pro38 [Met(O)14, Trp(O2)25, Asp28]eksendin-4(1-39) -NH2,
H-Asn-(Glu)5- des Pro36, Pro37, Pro38 [Met(O)14, Asp28] eksendin-4(1-39) -NH2,
des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]eksendin-4(1-39)-(Lys)6-NH2,
H-(Lys)6- des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]eksendin-4(1-39)-(Lys)6-NH2,
H-Asn-(Glu)5- des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] eksendin-4(1-39)-(Lys)6-NH2,
ili njihova farmakološki podnošljiva sol.
12. Farmaceutska formulacija prema zahtjevu 9, naznačena time da dodatno sadrži Arg34, Lys26 (Nε(γ-glutamil(Nα-heksadekanoil))) GLP-1 (7-37) [liraglutid] ili njihovu farmakološki podnošljivu sol.
13. Farmaceutska formulacija prema jednom ili više zahtjeva od 1 do 12, naznačena time da sadrži metionin u koncentraciji od do 10 mg/ml, poželjno od do 3 mg/ml.
14. Postupak za dobivanje formulacije prema jednom ili više zahtjeva od 1 do 13, naznačen time da sadrži
(a) uvođenje komponenata u vodenu otopinu i
(b) podešavanje pH.
15. Uporaba formulacije prema jednom ili više zahtjeva od 1 do 13 naznačena time da je za proizvodnju lijeka za liječenje dijabetes melitusa.
16. Lijek za uporabu za liječenje dijabetes melitusa, naznačen time da je sastavljen od formulacije prema jednom ili više zahtjeva od 1 do 13.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102009031748 | 2009-07-06 | ||
| DE102010013134 | 2010-03-27 | ||
| PCT/EP2010/059436 WO2011003822A2 (de) | 2009-07-06 | 2010-07-02 | Insulinzubereitungen enthaltend methionin |
| EP10730443.8A EP2451437B1 (de) | 2009-07-06 | 2010-07-02 | Wässrige insulinzubereitungen enthaltend methionin |
Publications (1)
| Publication Number | Publication Date |
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| HRP20170155T1 true HRP20170155T1 (hr) | 2017-03-24 |
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| HRP20170155TT HRP20170155T1 (hr) | 2009-07-06 | 2017-01-31 | Vodeni pripravci koji sadrže metionin |
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| US (1) | US20120252724A1 (hr) |
| EP (2) | EP3202394A1 (hr) |
| JP (1) | JP5735960B2 (hr) |
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| CN (4) | CN105535943A (hr) |
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| BR (1) | BR112012000177B1 (hr) |
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| CY (1) | CY1119582T1 (hr) |
| DK (1) | DK2451437T3 (hr) |
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| WO2011003823A1 (de) * | 2009-07-06 | 2011-01-13 | Sanofi-Aventis Deutschland Gmbh | Langsamwirkende insulinzubereitungen |
| AR080669A1 (es) * | 2009-11-13 | 2012-05-02 | Sanofi Aventis Deutschland | Composicion farmaceutica que comprende un agonista de glp-1, una insulina y metionina |
| UY33025A (es) | 2009-11-13 | 2011-06-30 | Sanofi Aventis Deustschland Gmbh | Composicion farmaceutica que comprende un agonista de glp-1 metionina |
| MX339614B (es) | 2010-08-30 | 2016-06-02 | Sanofi - Aventis Deutschland GmbH | Uso de ave0010 para la fabricacion de un medicamento para el tratamiento de la diabetes mellitus tipo 2. |
| 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 |
| KR101874401B1 (ko) * | 2011-06-17 | 2018-07-04 | 할로자임, 아이엔씨 | 히알루로난 분해 효소의 안정한 제형 |
| RU2650616C2 (ru) | 2011-08-29 | 2018-04-16 | Санофи-Авентис Дойчланд Гмбх | Фармацевтическая комбинация для применения при гликемическом контроле у пациентов с сахарным диабетом 2 типа |
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