ES2594303T3 - Formulaciones de insulina - Google Patents
Formulaciones de insulina Download PDFInfo
- Publication number
- ES2594303T3 ES2594303T3 ES13714303.8T ES13714303T ES2594303T3 ES 2594303 T3 ES2594303 T3 ES 2594303T3 ES 13714303 T ES13714303 T ES 13714303T ES 2594303 T3 ES2594303 T3 ES 2594303T3
- Authority
- ES
- Spain
- Prior art keywords
- insulin
- nacl
- glycerol
- ins
- measured
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 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 abstract description 192
- 102000004877 Insulin Human genes 0.000 title description 102
- 108090001061 Insulin Proteins 0.000 title description 102
- 229940125396 insulin Drugs 0.000 title description 94
- 239000000203 mixture Substances 0.000 title description 36
- 238000009472 formulation Methods 0.000 title description 35
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 abstract description 243
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 abstract description 216
- 239000011780 sodium chloride Substances 0.000 abstract description 108
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 abstract description 32
- 101000976075 Homo sapiens Insulin Proteins 0.000 abstract description 9
- 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 abstract description 9
- 239000004026 insulin derivative Substances 0.000 abstract description 9
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 abstract description 3
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 2
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 abstract 1
- 239000011701 zinc Substances 0.000 description 93
- JADVWWSKYZXRGX-UHFFFAOYSA-M thioflavine T Chemical compound [Cl-].C1=CC(N(C)C)=CC=C1C1=[N+](C)C2=CC=C(C)C=C2S1 JADVWWSKYZXRGX-UHFFFAOYSA-M 0.000 description 42
- 230000015572 biosynthetic process Effects 0.000 description 41
- 238000003860 storage Methods 0.000 description 22
- 239000012535 impurity Substances 0.000 description 20
- 238000000034 method Methods 0.000 description 20
- 239000000523 sample Substances 0.000 description 19
- 238000012360 testing method Methods 0.000 description 19
- QTWJRLJHJPIABL-UHFFFAOYSA-N 2-methylphenol;3-methylphenol;4-methylphenol Chemical compound CC1=CC=C(O)C=C1.CC1=CC=CC(O)=C1.CC1=CC=CC=C1O QTWJRLJHJPIABL-UHFFFAOYSA-N 0.000 description 18
- 229930003836 cresol Natural products 0.000 description 18
- 239000000178 monomer Substances 0.000 description 18
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 17
- 206010061592 cardiac fibrillation Diseases 0.000 description 17
- 230000006240 deamidation Effects 0.000 description 17
- 230000002600 fibrillogenic effect Effects 0.000 description 17
- 239000000126 substance Substances 0.000 description 17
- 229910052725 zinc Inorganic materials 0.000 description 17
- WEDIKSVWBUKTRA-WTKGVUNUSA-N CC[C@H](C)[C@H](NC(=O)CN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H]1CSSC[C@@H]2NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CSSC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc3c[nH]cn3)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)Cc3ccccc3)C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](Cc3c[nH]cn3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc3ccc(O)cc3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](Cc3ccc(O)cc3)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc3ccc(O)cc3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC2=O)C(=O)N[C@@H](CC(N)=O)C(O)=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](Cc2ccccc2)C(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)NC1=O)[C@@H](C)O)[C@@H](C)CC Chemical compound CC[C@H](C)[C@H](NC(=O)CN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H]1CSSC[C@@H]2NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CSSC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc3c[nH]cn3)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)Cc3ccccc3)C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](Cc3c[nH]cn3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc3ccc(O)cc3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](Cc3ccc(O)cc3)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc3ccc(O)cc3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC2=O)C(=O)N[C@@H](CC(N)=O)C(O)=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](Cc2ccccc2)C(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)NC1=O)[C@@H](C)O)[C@@H](C)CC WEDIKSVWBUKTRA-WTKGVUNUSA-N 0.000 description 16
- 108010073961 Insulin Aspart Proteins 0.000 description 16
- 238000005259 measurement Methods 0.000 description 13
- 238000002296 dynamic light scattering Methods 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 10
- 101001012217 Conus geographus Con-Ins G3 Proteins 0.000 description 9
- 101710186643 Insulin-2 Proteins 0.000 description 9
- 102000004169 proteins and genes Human genes 0.000 description 9
- 108090000623 proteins and genes Proteins 0.000 description 9
- 101001012221 Conus tulipa Con-Ins T3 Proteins 0.000 description 8
- 239000002245 particle Substances 0.000 description 8
- 241000894007 species Species 0.000 description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 238000002523 gelfiltration Methods 0.000 description 6
- 238000011534 incubation Methods 0.000 description 6
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 6
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 239000004246 zinc acetate Substances 0.000 description 6
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000013020 final formulation Substances 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 239000001632 sodium acetate Substances 0.000 description 4
- 235000017281 sodium acetate Nutrition 0.000 description 4
- FYZPCMFQCNBYCY-WIWKJPBBSA-N Insulin degludec Chemical compound CC[C@H](C)[C@H](NC(=O)CN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H]1CSSC[C@@H]2NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CSSC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc3c[nH]cn3)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)Cc3ccccc3)C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](Cc3c[nH]cn3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc3ccc(O)cc3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](Cc3ccc(O)cc3)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc3ccc(O)cc3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC2=O)C(=O)N[C@@H](CC(N)=O)C(O)=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](Cc2ccccc2)C(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H]([C@@H](C)O)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCC(O)=O)C(O)=O)C(O)=O)NC1=O)[C@@H](C)O)[C@@H](C)CC FYZPCMFQCNBYCY-WIWKJPBBSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 238000009792 diffusion process Methods 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 108010050259 insulin degludec Proteins 0.000 description 3
- 239000013067 intermediate product Substances 0.000 description 3
- 238000000386 microscopy Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 238000006384 oligomerization reaction Methods 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 239000007983 Tris buffer Substances 0.000 description 2
- -1 [2- (2- {2- [2- (2-Aminoethoxy) ethoxy] acetylamino} ethoxy) ethoxy] acetyl Chemical group 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 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 2
- 238000010828 elution Methods 0.000 description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 238000011179 visual inspection Methods 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- 101100179824 Caenorhabditis elegans ins-17 gene Proteins 0.000 description 1
- 101150089655 Ins2 gene Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000003941 amyloidogenesis Effects 0.000 description 1
- 238000005311 autocorrelation function Methods 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 238000002144 chemical decomposition reaction Methods 0.000 description 1
- 238000013523 data management Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- MNNHAPBLZZVQHP-UHFFFAOYSA-N diammonium hydrogen phosphate Chemical compound [NH4+].[NH4+].OP([O-])([O-])=O MNNHAPBLZZVQHP-UHFFFAOYSA-N 0.000 description 1
- 229910000388 diammonium phosphate Inorganic materials 0.000 description 1
- 235000019838 diammonium phosphate Nutrition 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229960004717 insulin aspart Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- JBQYATWDVHIOAR-UHFFFAOYSA-N tellanylidenegermanium Chemical compound [Te]=[Ge] JBQYATWDVHIOAR-UHFFFAOYSA-N 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/62—Insulins
-
- 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
- A61K47/02—Inorganic compounds
-
- 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
- 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
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Organic Chemistry (AREA)
- Endocrinology (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Toxicology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Dermatology (AREA)
- Immunology (AREA)
- Inorganic Chemistry (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP12163730 | 2012-04-11 | ||
| EP12163730 | 2012-04-11 | ||
| US201261624463P | 2012-04-16 | 2012-04-16 | |
| US201261624463P | 2012-04-16 | ||
| EP13157748 | 2013-03-05 | ||
| EP13157748 | 2013-03-05 | ||
| US201361778554P | 2013-03-13 | 2013-03-13 | |
| US201361778554P | 2013-03-13 | ||
| PCT/EP2013/057196 WO2013153000A2 (en) | 2012-04-11 | 2013-04-05 | Insulin formulations |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2594303T3 true ES2594303T3 (es) | 2016-12-19 |
Family
ID=49328249
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES13714303.8T Active ES2594303T3 (es) | 2012-04-11 | 2013-04-05 | Formulaciones de insulina |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US9481721B2 (enExample) |
| EP (1) | EP2836508B1 (enExample) |
| JP (1) | JP6199956B2 (enExample) |
| KR (1) | KR20150002777A (enExample) |
| CN (1) | CN104364260B (enExample) |
| AU (1) | AU2013247047A1 (enExample) |
| BR (1) | BR112014025132A2 (enExample) |
| CA (1) | CA2870313A1 (enExample) |
| ES (1) | ES2594303T3 (enExample) |
| MX (1) | MX2014012096A (enExample) |
| WO (1) | WO2013153000A2 (enExample) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL1969004T3 (pl) | 2005-12-28 | 2012-01-31 | Novo Nordisk As | Kompozycje zawierające acylowaną insulinę i cynk oraz sposób wytwarzania tych kompozycji |
| DK2254906T3 (en) | 2008-03-18 | 2017-01-23 | Novo Nordisk As | Protease-stabilized acylated insulin analogues |
| RU2013123515A (ru) | 2010-10-27 | 2014-12-10 | Ново Нордиск А/С | Лечение сахарного диабета с помощью инъекций инсулина, вводимых с различными интервалами |
| WO2014177623A1 (en) | 2013-04-30 | 2014-11-06 | Novo Nordisk A/S | Novel administration regime |
| AU2014333979B2 (en) | 2013-10-07 | 2018-02-15 | Novo Nordisk A/S | Novel derivative of an insulin analogue |
| HUE060149T2 (hu) * | 2016-12-16 | 2023-02-28 | Novo Nordisk As | Inzulint tartalmazó gyógyászati készítmények |
| GB201707189D0 (en) * | 2017-05-05 | 2017-06-21 | Arecor Ltd | Novel formulations |
| EP3687602A4 (en) * | 2017-09-27 | 2021-06-23 | Becton, Dickinson and Company | LIQUID DISPENSER WITH LEAK DETECTION |
| US10335464B1 (en) | 2018-06-26 | 2019-07-02 | Novo Nordisk A/S | Device for titrating basal insulin |
| JP7518149B2 (ja) | 2019-07-12 | 2024-07-17 | ノヴォ ノルディスク アー／エス | 高濃度インスリン製剤 |
| WO2022268208A1 (zh) * | 2021-06-25 | 2022-12-29 | 甘李药业股份有限公司 | 含酰化胰岛素的药物组合物 |
| CN116284433B (zh) * | 2022-07-04 | 2023-09-12 | 北京惠之衡生物科技有限公司 | 一种胰岛素和glp-1的缀合物及其应用 |
| CN118063589A (zh) * | 2024-02-04 | 2024-05-24 | 乐普健糖药业(重庆)有限公司 | 一种超长效胰岛素类似物及其制备方法和用途 |
Family Cites Families (166)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2832685A (en) | 1952-05-24 | 1958-04-29 | Crest Foods Co Inc | Solubilization of milk proteins |
| GB894095A (en) | 1960-02-08 | 1962-04-18 | Tanaka Shoichi | A therapeutic device for personal wear |
| US3528960A (en) | 1968-10-07 | 1970-09-15 | Lilly Co Eli | N-carboxyaroyl insulins |
| US3719655A (en) | 1969-12-05 | 1973-03-06 | Lilly Co Eli | Process for the crystallization of the ammonium and alkali metal salts in insulin |
| US3869437A (en) | 1970-05-08 | 1975-03-04 | Nat Res Dev | Mono-, di, and N{HD A1{B , N{HU B1{B , N{HU B29{B -tri-acylated insulin |
| US3950517A (en) | 1970-05-08 | 1976-04-13 | National Research Development Corporation | Insulin derivatives |
| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| US4033941A (en) | 1975-12-17 | 1977-07-05 | Eli Lilly And Company | Process for purifying glucagon |
| GB1492997A (en) | 1976-07-21 | 1977-11-23 | Nat Res Dev | Insulin derivatives |
| JPS6030650B2 (ja) | 1979-10-26 | 1985-07-17 | 日本油脂株式会社 | 座薬基剤組成物 |
| JPS5767548A (en) | 1980-10-14 | 1982-04-24 | Shionogi & Co Ltd | Insulin analog and its preparation |
| HU186826B (en) | 1982-06-18 | 1985-09-30 | Richter Gedeon Vegyeszet | Method and apparatus for analysing of solution samples with high series number |
| DE3375496D1 (en) | 1982-07-02 | 1988-03-03 | Jugo Import Export Anstalt | Formwork for rotationally symmetric structures |
| US4839341A (en) | 1984-05-29 | 1989-06-13 | Eli Lilly And Company | Stabilized insulin formulations |
| DK347086D0 (da) | 1986-07-21 | 1986-07-21 | Novo Industri As | Novel peptides |
| PH25772A (en) | 1985-08-30 | 1991-10-18 | Novo Industri As | Insulin analogues, process for their preparation |
| US4849227A (en) | 1986-03-21 | 1989-07-18 | Eurasiam Laboratories, Inc. | Pharmaceutical compositions |
| PH23446A (en) | 1986-10-20 | 1989-08-07 | Novo Industri As | Peptide preparations |
| US5266310A (en) | 1987-09-17 | 1993-11-30 | Boehringer Ingelheim International Gmbh | Stabilization of therapeutically active proteins in pharmaceutical preparations |
| JPH01254699A (ja) | 1988-04-05 | 1989-10-11 | Kodama Kk | インスリン誘導体及びその用途 |
| AU616205B2 (en) | 1988-07-20 | 1991-10-24 | Novo Nordisk A/S | Human insulin analogs and preparations containing them |
| KR0148748B1 (ko) | 1988-09-16 | 1998-08-17 | 장 크라메르, 한스 루돌프 하우스 | 사이클로스포린을 함유하는 약학조성물 |
| DE3844211A1 (de) | 1988-12-29 | 1990-07-05 | Hoechst Ag | Neue insulinderivate, verfahren zu deren herstellung, ihre verwendung und eine sie enthaltende pharmazeutische zubereitung |
| US5514646A (en) | 1989-02-09 | 1996-05-07 | Chance; Ronald E. | Insulin analogs modified at position 29 of the B chain |
| AU6417790A (en) | 1989-09-22 | 1991-04-18 | Tsi-Madison Research Institute | Method and compositions for one-step cryopreservation of embryos |
| CA2027930C (en) | 1989-10-19 | 1998-06-30 | Tsuyoshi Miyazaki | Polymer complexes of a sugar response type |
| US5179189A (en) | 1990-01-19 | 1993-01-12 | Nova Pharmaceutical Corporation | Fatty acid terminated polyanhydrides |
| DK45590D0 (enExample) | 1990-02-21 | 1990-02-21 | Novo Nordisk As | |
| DK155690D0 (da) | 1990-06-28 | 1990-06-28 | Novo Nordisk As | Nye peptider |
| WO1992001476A1 (en) | 1990-07-26 | 1992-02-06 | University Of Iowa Research Foundation | Novel drug delivery systems for proteins and peptides using albumin as a carrier molecule |
| WO1992004893A1 (en) | 1990-09-13 | 1992-04-02 | Smithkline Beecham Corporation | Non-aqueous liquid oral suspensions |
| DK10191D0 (da) | 1991-01-22 | 1991-01-22 | Novo Nordisk As | Hidtil ukendte peptider |
| US5336782A (en) | 1991-04-24 | 1994-08-09 | Kuraray Co., Ltd. | Long chain carboxylic acid imide ester |
| DK0597007T3 (da) | 1991-07-26 | 1996-11-18 | Smithkline Beecham Corp | V/O mikroemulsioner |
| US5206219A (en) | 1991-11-25 | 1993-04-27 | Applied Analytical Industries, Inc. | Oral compositions of proteinaceous medicaments |
| CZ342492A3 (en) | 1991-11-26 | 1993-06-16 | Lilly Co Eli | Derivatives of tri-arginine insulin, process of their preparation and a pharmaceutical composition in which said derivatives are comprised |
| EP0547544B1 (de) | 1991-12-18 | 1997-03-12 | Hoechst Aktiengesellschaft | Verfahren zur Gewinnung von insulinhaltigen Lösungen |
| WO1994008599A1 (en) | 1992-10-14 | 1994-04-28 | The Regents Of The University Of Colorado | Ion-pairing of drugs for improved efficacy and delivery |
| WO1994008603A1 (en) | 1992-10-16 | 1994-04-28 | Smithkline Beecham Corporation | Compositions |
| JPH08502492A (ja) | 1992-10-16 | 1996-03-19 | スミスクライン・ビーチャム・コーポレイション | 治療用ミクロエマルジョン |
| WO1994019001A1 (en) | 1993-02-17 | 1994-09-01 | Smithkline Beecham Corporation | Microemulsions comprising therapeutic peptides |
| EP0684834A4 (en) | 1993-02-17 | 1996-09-25 | Smithkline Beecham Corp | MICROEMULSIONS CONTAINING THERAPEUTIC PEPTIDES. |
| CZ296649B6 (cs) | 1993-02-23 | 2006-05-17 | Genentech, Inc. | Zpusob výroby stabilizovaného polypeptidového prostredku zahrnující stabilizování polypeptidu protidenaturaci organickými rozpoustedly, jeho príprava a prostredek pro regulované uvolnování polypeptidu |
| US5359030A (en) | 1993-05-10 | 1994-10-25 | Protein Delivery, Inc. | Conjugation-stabilized polypeptide compositions, therapeutic delivery and diagnostic formulations comprising same, and method of making and using the same |
| US5506203C1 (en) | 1993-06-24 | 2001-02-06 | Astra Ab | Systemic administration of a therapeutic preparation |
| US6869930B1 (en) | 1993-09-17 | 2005-03-22 | Novo Nordisk A/S | Acylated insulin |
| DE69428134T2 (de) | 1993-09-17 | 2002-05-02 | Novo Nordisk A/S, Bagsvaerd | Acyliertes insulin |
| GB9323588D0 (en) | 1993-11-16 | 1994-01-05 | Cortecs Ltd | Hydrophobic preparation |
| ATE264096T1 (de) | 1994-03-07 | 2004-04-15 | Nektar Therapeutics | Verfahren und mittel zur verabreichung von insulin über die lunge |
| US6500645B1 (en) | 1994-06-17 | 2002-12-31 | Novo Nordisk A/S | N-terminally extended proteins expressed in yeast |
| US5693609A (en) | 1994-11-17 | 1997-12-02 | Eli Lilly And Company | Acylated insulin analogs |
| US5646242A (en) | 1994-11-17 | 1997-07-08 | Eli Lilly And Company | Selective acylation of epsilon-amino groups |
| US6251856B1 (en) | 1995-03-17 | 2001-06-26 | Novo Nordisk A/S | Insulin derivatives |
| CA2215694A1 (en) | 1995-03-17 | 1996-09-26 | Novo Nordisk A/S | Insulin derivatives |
| US5824638A (en) | 1995-05-22 | 1998-10-20 | Shire Laboratories, Inc. | Oral insulin delivery |
| US20010041786A1 (en) | 1995-06-07 | 2001-11-15 | Mark L. Brader | Stabilized acylated insulin formulations |
| US20030104981A1 (en) | 1995-11-03 | 2003-06-05 | Jelena Mandic | Human insulin analogues |
| US6451970B1 (en) | 1996-02-21 | 2002-09-17 | Novo Nordisk A/S | Peptide derivatives |
| WO1998001473A1 (en) | 1996-07-05 | 1998-01-15 | Novo Nordisk A/S | Method for the production of precursors of insulin, precursors of insulin analogues, and insulin like peptides |
| EP0938502B1 (en) | 1996-07-11 | 2004-10-06 | Novo Nordisk A/S | Selective acylation method |
| US5981489A (en) | 1996-07-18 | 1999-11-09 | Alza Corporation | Non-aqueous protic peptide formulations |
| EP0821006B1 (de) | 1996-07-26 | 2004-04-21 | Aventis Pharma Deutschland GmbH | Insulinderivate mit erhöhter Zinkbindung |
| IL119029A0 (en) | 1996-08-07 | 1996-11-14 | Yeda Res & Dev | Long-acting drugs and pharamaceutical compositions comprising them |
| ATE275963T1 (de) | 1997-01-30 | 2004-10-15 | Novartis Pharma Gmbh | Ölfreie pharmazeutische zusammensetzung welche cyclosporin enthält |
| US5898067A (en) | 1997-02-07 | 1999-04-27 | Novo Nordisk A/S | Crystallization of proteins |
| JP2003525846A (ja) | 1997-10-24 | 2003-09-02 | ノボ ノルディスク アクティーゼルスカブ | ヒトインスリン誘導体の集合体 |
| TR200001050T2 (tr) | 1997-10-24 | 2000-08-21 | Eli Lilly And Company | Çözünmez insülin bileşimleri |
| ZA989744B (en) | 1997-10-31 | 2000-04-26 | Lilly Co Eli | Method for administering acylated insulin. |
| AU1375199A (en) | 1997-11-12 | 1999-05-31 | Alza Corporation | Method for decreasing self-association of polypeptides |
| CO4970787A1 (es) | 1997-12-23 | 2000-11-07 | Lilly Co Eli | Composiciones insolubles de insulina y derivados de insulina que controlan la glucosa sanguinea |
| CA2334859A1 (en) | 1998-06-12 | 1999-12-23 | Kings College London | Insulin analogue |
| GB9814172D0 (en) | 1998-06-30 | 1998-08-26 | Andaris Ltd | Formulation for inhalation |
| EP1107743B1 (en) | 1998-08-25 | 2007-06-27 | Advanced Inhalation Research, Inc. | Stable spray-dried protein formulations |
| TW570805B (en) | 1998-09-01 | 2004-01-11 | Hoffmann La Roche | Water-soluble pharmaceutical composition in an ionic complex |
| US7030083B2 (en) | 1998-09-09 | 2006-04-18 | University Of Washington | Treatment of eclampsia and preeclampsia |
| PL197504B1 (pl) | 1998-10-16 | 2008-04-30 | Novo Nordisk As | Trwałe stężone preparaty insulinowe do podawania do płuc |
| US6660715B2 (en) | 1998-11-19 | 2003-12-09 | Massachusetts Institute Of Technology | Nonaqueous solutions and suspensions of macromolecules for pulmonary delivery |
| US7425541B2 (en) | 1998-12-11 | 2008-09-16 | Medarex, Inc. | Enzyme-cleavable prodrug compounds |
| ATE220917T1 (de) | 1999-01-26 | 2002-08-15 | Lilly Co Eli | Monodisperse formulierungen, die hexamere acylierte insulinanaloge enthalten |
| AU2879100A (en) | 1999-02-12 | 2000-08-29 | Miles A. Libbey Iii | Formulation and system for intra-oral delivery of pharmaceutical agents |
| US6267985B1 (en) | 1999-06-30 | 2001-07-31 | Lipocine Inc. | Clear oil-containing pharmaceutical compositions |
| WO2000061178A1 (en) | 1999-04-13 | 2000-10-19 | Inhale Therapeutics Systems, Inc. | Pulmonary administration of dry powder formulations for treating infertility |
| JP2002543092A (ja) | 1999-04-27 | 2002-12-17 | イーライ・リリー・アンド・カンパニー | 肺投与用インスリン結晶 |
| US6309633B1 (en) | 1999-06-19 | 2001-10-30 | Nobex Corporation | Amphiphilic drug-oligomer conjugates with hydroyzable lipophile components and methods for making and using the same |
| PT1242121E (pt) | 1999-12-16 | 2005-05-31 | Lilly Co Eli | Composicoes polipeptidicas com estabilidade melhorada |
| CN1141974C (zh) | 2000-06-07 | 2004-03-17 | 张昊 | 结肠定位释放的口服生物制剂 |
| KR100508695B1 (ko) | 2001-02-13 | 2005-08-17 | 한국과학기술연구원 | 인슐린의 경구투여용 제형과 그의 제조방법 |
| US7060675B2 (en) | 2001-02-15 | 2006-06-13 | Nobex Corporation | Methods of treating diabetes mellitus |
| US6867183B2 (en) | 2001-02-15 | 2005-03-15 | Nobex Corporation | Pharmaceutical compositions of insulin drug-oligomer conjugates and methods of treating diseases therewith |
| WO2002067969A2 (en) * | 2001-02-21 | 2002-09-06 | Medtronic Minimed, Inc. | Stabilized insulin formulations |
| CN1160122C (zh) | 2001-04-20 | 2004-08-04 | 清华大学 | 一种制备口服胰岛素油相制剂的方法 |
| MY137181A (en) | 2001-05-21 | 2009-01-30 | Nektar Therapeutics | Pulmonary administration of chemically modified insulin |
| US6858580B2 (en) | 2001-06-04 | 2005-02-22 | Nobex Corporation | Mixtures of drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same |
| US6828297B2 (en) | 2001-06-04 | 2004-12-07 | Nobex Corporation | Mixtures of insulin drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same |
| EP1423136A4 (en) | 2001-08-10 | 2007-07-25 | Epix Pharm Inc | POLYPEPTIDE CONJUGATES HAVING INCREASED CIRCULATION HALF-VIES |
| US7030082B2 (en) | 2001-09-07 | 2006-04-18 | Nobex Corporation | Pharmaceutical compositions of drug-oligomer conjugates and methods of treating disease therewith |
| PT1430082E (pt) | 2001-09-07 | 2010-01-15 | Biocon Ltd | Métodos de síntese de conjugados de polipéptido de insulina-oligómero, e conjugados de polipéptido de pró-insulina-oligómero e método de síntese dos mesmos |
| US6770625B2 (en) | 2001-09-07 | 2004-08-03 | Nobex Corporation | Pharmaceutical compositions of calcitonin drug-oligomer conjugates and methods of treating diseases therewith |
| WO2003048195A2 (en) | 2001-12-02 | 2003-06-12 | Novo Nordisk A/S | Glucose dependant release of insulin from glucose sensing insulin derivatives |
| US8535650B2 (en) | 2001-12-03 | 2013-09-17 | Soligenix, Inc. | Stabilized reverse micelle compositions and uses thereof |
| EP1456371A1 (en) | 2001-12-05 | 2004-09-15 | Dow Global Technologies Inc. | Method for immobilizing a biologic in a polyurethane-hydrogel composition, a composition prepared from the method, and biomedical applications |
| EP1545460A4 (en) | 2001-12-20 | 2005-11-16 | Lilly Co Eli | INSULIN MOLECULE WITH TEMPORARY EFFECT |
| UA46669C2 (uk) | 2001-12-29 | 2005-12-15 | Товариство З Обмеженою Відповідальністю "Мако" | Спосіб приготування готової лікарської форми інсуліну пролонгованої дії |
| EP1506003A1 (en) | 2002-05-07 | 2005-02-16 | Novo Nordisk A/S | Soluble formulations comprising insulin aspart and insulin detemir |
| ATE496064T1 (de) | 2002-05-07 | 2011-02-15 | Novo Nordisk As | Lösliche formulierungen, die monomeres insulin und acyliertes insulin enthalten |
| US7601688B2 (en) | 2002-06-13 | 2009-10-13 | Biocon Limited | Methods of reducing hypoglycemic episodes in the treatment of diabetes mellitus |
| CN1165549C (zh) | 2002-06-15 | 2004-09-08 | 江苏万邦生化医药股份有限公司 | 胰岛素的纯化方法 |
| AU2003272347A1 (en) | 2002-09-17 | 2004-04-08 | Merck And Co., Inc. | Removal of aldehyde impurity by reactive polystyrene resin |
| US20040185068A1 (en) | 2003-03-18 | 2004-09-23 | Zhi-Jian Yu | Self-emulsifying compositions, methods of use and preparation |
| PL1633391T3 (pl) | 2003-06-03 | 2012-03-30 | Novo Nordisk As | Stabilizowane farmaceutycznie kompozycje peptydowe |
| CN1812808B (zh) | 2003-06-03 | 2012-07-04 | 诺沃挪第克公司 | 稳定化的药物肽组合物 |
| DE602004015980D1 (de) | 2003-06-17 | 2008-10-02 | Sembiosys Genetics Inc | Verfahren zur insulinproduktion in pflanzen |
| EP1644411A2 (en) | 2003-07-11 | 2006-04-12 | Novo Nordisk A/S | Stabilised insulin compositions |
| AU2004261319B2 (en) | 2003-07-25 | 2010-12-23 | Conjuchem Biotechnologies Inc. | Long lasting insulin derivatives and methods thereof |
| BRPI0413276B8 (pt) | 2003-08-05 | 2021-05-25 | Novo Nordisk As | derivado de insulina, complexo de zinco do mesmo, e, composição farmacêutica |
| WO2005016312A1 (en) | 2003-08-13 | 2005-02-24 | Nobex Corporation | Micro-particle fatty acid salt solid dosage formulations for therapeutic agents |
| EP1687428A1 (en) | 2003-11-14 | 2006-08-09 | Novo Nordisk A/S | Processes for making acylated insulin |
| US20050118206A1 (en) | 2003-11-14 | 2005-06-02 | Luk Andrew S. | Surfactant-based gel as an injectable, sustained drug delivery vehicle |
| CN104826116A (zh) | 2003-11-20 | 2015-08-12 | 诺沃挪第克公司 | 对于生产和用于注射装置中是最佳的含有丙二醇的肽制剂 |
| WO2005058961A2 (en) | 2003-12-12 | 2005-06-30 | Amgen Inc. | Antibodies specific for human galanin, and uses thereof |
| DE10358387A1 (de) | 2003-12-13 | 2005-07-07 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Pulver enthaltend niedermolekulares Dextran und Verfahren zu deren Herstellung |
| JP4792457B2 (ja) | 2004-03-26 | 2011-10-12 | ユニヴァーシタ’デグリ ステュディ ディ パルマ | 高度に呼吸に適したインスリンのマイクロ粒子 |
| US20050232981A1 (en) | 2004-04-15 | 2005-10-20 | Ben-Sasson Shmuel A | Compositions capable of facilitating penetration across a biological barrier |
| MXPA06012980A (es) | 2004-05-10 | 2007-06-12 | Nastech Pharm Co | Composiciones y metodos para el suministro mucosal mejorado de la hormona paratiroidea. |
| WO2006014673A2 (en) | 2004-07-19 | 2006-02-09 | Nobex Corporation | Insulin-oligomer conjugates, formulations and uses thereof |
| EP1789074A4 (en) | 2004-08-09 | 2009-08-12 | Alios Biopharma Inc | PROTEASE-RESISTANT HYPERGLYCOSYL SYNTHETIC POLYPEPTIDE VARIANTS, ORAL FORMULATIONS AND METHODS OF USING THE SAME |
| EP2314298B1 (en) | 2004-08-23 | 2015-05-27 | MannKind Corporation | Microparticles comprising diketopiperazine salts for drug delivery |
| DE602005010899D1 (de) | 2004-09-27 | 2008-12-18 | Sigmoid Pharma Ltd | Mikrokapseln mit einem methylxanthin und einem kortikosteroid |
| WO2006079641A2 (en) | 2005-01-27 | 2006-08-03 | Novo Nordisk A/S | Insulin derivatives conjugated with structurally well defined branched polymers |
| EP2292653B1 (en) | 2005-02-02 | 2014-05-21 | Novo Nordisk A/S | Novel insulin derivatives |
| JP4933455B2 (ja) | 2005-02-02 | 2012-05-16 | ノヴォ ノルディスク アー／エス | 新規のインスリン誘導体 |
| WO2006097521A1 (en) | 2005-03-18 | 2006-09-21 | Novo Nordisk A/S | Pegylated single-chain insulin |
| WO2006103657A2 (en) | 2005-03-31 | 2006-10-05 | Dexcel Pharma Technologies Ltd. | A solid composition for intra-oral delivery of insulin |
| US20080200383A1 (en) | 2005-04-08 | 2008-08-21 | Amylin Pharmaceuticals, Inc. | Pharmaceutical Formulations Comprising Incretin Peptide and Aprotic Polar Solvent |
| EP1888118B1 (en) | 2005-05-25 | 2016-08-17 | Novo Nordisk A/S | Polypeptide formulations stabilized with ethylenediamine |
| WO2007006320A1 (en) | 2005-07-12 | 2007-01-18 | Sherine Hassan Abbas Helmy | Drinkable oral insulin liquid and capsules |
| WO2007041481A1 (en) | 2005-09-29 | 2007-04-12 | Biodel, Inc. | Rapid acting and prolonged acting insulin preparations |
| JP2009512709A (ja) | 2005-10-20 | 2009-03-26 | エムディーアールエヌエー，インコーポレイテッド | 速効型インスリンの経鼻投与 |
| PL1969004T3 (pl) | 2005-12-28 | 2012-01-31 | Novo Nordisk As | Kompozycje zawierające acylowaną insulinę i cynk oraz sposób wytwarzania tych kompozycji |
| WO2007081824A2 (en) | 2006-01-06 | 2007-07-19 | Case Western Reserve University | Fibrillation resistant proteins |
| US20090069216A1 (en) | 2006-02-21 | 2009-03-12 | Novo Nordisk A/S | Single-Chain Insulin Analogues and Pharmaceutical Formulations Thereof |
| DE602007009496D1 (de) | 2006-02-27 | 2010-11-11 | Novo Nordisk As | Insulinderivate |
| JP2009530242A (ja) | 2006-03-13 | 2009-08-27 | ノボ・ノルデイスク・エー／エス | アシル化単鎖インスリン |
| EP2024390B1 (en) | 2006-05-09 | 2015-08-19 | Novo Nordisk A/S | Insulin derivative |
| EP2386572B1 (en) | 2006-05-09 | 2015-07-08 | Novo Nordisk A/S | Insulin derivative |
| WO2008015099A2 (en) | 2006-07-31 | 2008-02-07 | Novo Nordisk A/S | Pegylated, extended insulins |
| ES2601839T3 (es) | 2006-09-22 | 2017-02-16 | Novo Nordisk A/S | Análogos de insulina resistentes a proteasas |
| EP2152243A2 (en) | 2007-04-30 | 2010-02-17 | Novo Nordisk A/S | Highly concentrated insulin solutions and compositions |
| EP2497462A1 (en) | 2007-06-01 | 2012-09-12 | Novo Nordisk A/S | Stable non-aqueous pharmaceutical compositions |
| EP2514406A1 (en) | 2007-06-01 | 2012-10-24 | Novo Nordisk A/S | Spontaneously dispersible preconcentrates including a peptide drug in a solid or semisolid carrier |
| WO2009010428A1 (en) | 2007-07-16 | 2009-01-22 | Novo Nordisk A/S | Protease stabilized, pegylated insulin analogues |
| US8962794B2 (en) | 2007-08-15 | 2015-02-24 | Novo Nordisk A/S | Insulins with an acyl moiety comprising repeating units of alkylene glycol containing amino acids |
| AU2008288413B2 (en) | 2007-08-15 | 2013-09-26 | Novo Nordisk A/S | Insulin analogues with an acyl and aklylene glycol moiety |
| US20090087484A1 (en) | 2007-09-28 | 2009-04-02 | Alza Corporation | Formulation and dosage form for increasing oral bioavailability of hydrophilic macromolecules |
| WO2009060071A1 (en) * | 2007-11-08 | 2009-05-14 | Novo Nordisk A/S | Insulin derivative |
| EP2254905B1 (en) | 2008-03-14 | 2016-12-14 | Novo Nordisk A/S | Protease-stabilized insulin analogues |
| DK2254906T3 (en) | 2008-03-18 | 2017-01-23 | Novo Nordisk As | Protease-stabilized acylated insulin analogues |
| WO2010049488A1 (en) | 2008-10-30 | 2010-05-06 | Novo Nordisk A/S | Treating diabetes melitus using insulin injections with less than daily injection frequency |
| EP2370059A1 (en) | 2008-11-28 | 2011-10-05 | Novo Nordisk A/S | Pharmaceutical compositions suitable for oral administration of derivatized insulin peptides |
| US20110294729A1 (en) | 2008-12-09 | 2011-12-01 | Novo Nordisk A/S | Novel Insulin Analogues |
| WO2011033019A1 (en) | 2009-09-16 | 2011-03-24 | Novo Nordisk A/S | Stable non-aqueous liquid pharmaceutical compositions comprising an insulin |
| CN102665676B (zh) | 2009-11-02 | 2015-04-01 | 诺沃-诺迪斯克有限公司 | 非共价结合的白蛋白和酰化胰岛素的药物溶液 |
| CA2786953A1 (en) | 2010-01-12 | 2011-07-21 | Florian Anders Foeger | Pharmaceutical compositions for oral administration of insulin peptides |
| AU2011269000C1 (en) | 2010-06-23 | 2015-10-08 | Novo Nordisk A/S | Insulin derivatives containing additional disulfide bonds |
| US20140315797A1 (en) | 2010-10-15 | 2014-10-23 | Peter Madsen | Novel N-Terminally Modified Insulin Derivatives |
| WO2014009316A1 (en) | 2012-07-09 | 2014-01-16 | Novo Nordisk A/S | Novel use of insulin derivatives |
-
2013
- 2013-04-05 CA CA2870313A patent/CA2870313A1/en not_active Withdrawn
- 2013-04-05 EP EP13714303.8A patent/EP2836508B1/en active Active
- 2013-04-05 MX MX2014012096A patent/MX2014012096A/es unknown
- 2013-04-05 KR KR1020147031291A patent/KR20150002777A/ko not_active Withdrawn
- 2013-04-05 CN CN201380030897.6A patent/CN104364260B/zh active Active
- 2013-04-05 ES ES13714303.8T patent/ES2594303T3/es active Active
- 2013-04-05 BR BR112014025132A patent/BR112014025132A2/pt not_active IP Right Cessation
- 2013-04-05 JP JP2015504909A patent/JP6199956B2/ja active Active
- 2013-04-05 WO PCT/EP2013/057196 patent/WO2013153000A2/en not_active Ceased
- 2013-04-05 AU AU2013247047A patent/AU2013247047A1/en not_active Withdrawn
- 2013-04-05 US US14/391,510 patent/US9481721B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| EP2836508B1 (en) | 2016-06-29 |
| WO2013153000A2 (en) | 2013-10-17 |
| JP2015514120A (ja) | 2015-05-18 |
| AU2013247047A1 (en) | 2014-10-23 |
| CN104364260B (zh) | 2017-02-22 |
| CA2870313A1 (en) | 2013-10-17 |
| WO2013153000A3 (en) | 2013-12-05 |
| EP2836508A2 (en) | 2015-02-18 |
| BR112014025132A2 (pt) | 2017-07-11 |
| US9481721B2 (en) | 2016-11-01 |
| KR20150002777A (ko) | 2015-01-07 |
| US20150126442A1 (en) | 2015-05-07 |
| MX2014012096A (es) | 2014-11-21 |
| JP6199956B2 (ja) | 2017-09-20 |
| CN104364260A (zh) | 2015-02-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2594303T3 (es) | Formulaciones de insulina | |
| Al-Shabib et al. | Molecular insight into binding behavior of polyphenol (rutin) with beta lactoglobulin: Spectroscopic, molecular docking and MD simulation studies | |
| Wang et al. | Red blood cells for glucose‐responsive insulin delivery | |
| Bhaskar et al. | Profound increase in viscosity and aggregation of pig gastric mucin at low pH | |
| Baudouin et al. | Role of hyperosmolarity in the pathogenesis and management of dry eye disease: proceedings of the OCEAN group meeting | |
| Kumar et al. | Hyaluronic acid co-functionalized gold nanoparticle complex for the targeted delivery of metformin in the treatment of liver cancer (HepG2 cells) | |
| Raut et al. | Opalescence in monoclonal antibody solutions and its correlation with intermolecular interactions in dilute and concentrated solutions | |
| Xu et al. | Multimerization and aggregation of native-state insulin: effect of zinc | |
| ES2930149T3 (es) | Composiciones farmacéuticas que contienen insulina | |
| Marino et al. | Nanodevice-induced conformational and functional changes in a prototypical calcium sensor protein | |
| JP7179112B2 (ja) | 安定なタンパク質組成物 | |
| Dear et al. | Enhancing stability and reducing viscosity of a monoclonal antibody with cosolutes by weakening protein-protein interactions | |
| Vinjamuri et al. | Gelatin solution pH and incubation time influences the size of the nanoparticles engineered by desolvation | |
| Georgiev et al. | Lacritin proteoforms prevent tear film collapse and maintain epithelial homeostasis | |
| Abd-Elal et al. | Full factorial design, optimization, in vitro and ex vivo studies of ocular timolol-loaded microsponges | |
| Simončič et al. | Mechanistic differences in the effects of sucrose and sucralose on the phase stability of lysozyme solutions | |
| Ma et al. | Volumetric and viscometric studies of amino acids in vitamin b6 aqueous solutions at various temperatures | |
| Tsubotani et al. | Taurine suppresses liquid–liquid phase separation of lysozyme protein | |
| Özer et al. | Preparation and in vitro evaluation of in situ gelling system containing lithium carbonate for parenteral administration | |
| Rabbi et al. | Study of interaction between febuxostat and bovine serum albumin by fluorescence spectroscopy | |
| Nayak et al. | Nanosuspension–preparation, in vitro and ex vivo evaluations of felodipine hydrochloride | |
| Messina et al. | Random Heteropolymer Excipients Improve the Colloidal Stability of a Monoclonal Antibody for Subcutaneous Administration | |
| Söptei et al. | Intercalation of Bovine Serum Albumin Coated Gold Clusters between Phospholipid Bilayers: Temperature-Dependent Behavior of Lipid-AuQC@ BSA Assemblies with Red Emission and Superlattice Structure | |
| Li et al. | An ameliorated anti-hTNF-α therapy for arthritis via carrier-free macromolecular nanoparticles consisted of infliximab | |
| Marzouk | Characterizing protein-excipient interactions for improved biopharmaceutical formulation |