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)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Organic Chemistry (AREA)
- Endocrinology (AREA)
- Engineering & Computer Science (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Toxicology (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- Dermatology (AREA)
- Oil, Petroleum & Natural Gas (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 (https=) |
| EP (1) | EP2836508B1 (https=) |
| JP (1) | JP6199956B2 (https=) |
| KR (1) | KR20150002777A (https=) |
| CN (1) | CN104364260B (https=) |
| AU (1) | AU2013247047A1 (https=) |
| BR (1) | BR112014025132A2 (https=) |
| CA (1) | CA2870313A1 (https=) |
| ES (1) | ES2594303T3 (https=) |
| MX (1) | MX2014012096A (https=) |
| WO (1) | WO2013153000A2 (https=) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2371361T3 (es) | 2005-12-28 | 2011-12-30 | Novo Nordisk A/S | Composiciones que comprenden una insulina acilada y zinc y método de producción de dichas composiciones. |
| HUE032284T2 (en) | 2008-03-18 | 2017-09-28 | Novo Nordisk As | Protease-stabilized, acylated insulin analogues |
| DK2632478T3 (da) | 2010-10-27 | 2019-10-07 | Novo Nordisk As | Behandling af diabetes melitus under anvendelse af insulinindsprøjtninger indgivet med varierende indsprøjtningsintervaller |
| EP2991672A1 (en) | 2013-04-30 | 2016-03-09 | Novo Nordisk A/S | Novel administration regime |
| JP6499184B2 (ja) | 2013-10-07 | 2019-04-10 | ノヴォ ノルディスク アー／エス | インスリン類似体の新規な誘導体 |
| PE20210857A1 (es) * | 2016-12-16 | 2021-05-18 | Novo Nordisk As | Composiciones farmaceuticas que contienen insulina |
| GB201707189D0 (en) * | 2017-05-05 | 2017-06-21 | Arecor Ltd | Novel formulations |
| JP2020534939A (ja) * | 2017-09-27 | 2020-12-03 | ベクトン・ディキンソン・アンド・カンパニーＢｅｃｔｏｎ， Ｄｉｃｋｉｎｓｏｎ Ａｎｄ Ｃｏｍｐａｎｙ | 漏出検出機能付きの流体供給装置 |
| US10335464B1 (en) | 2018-06-26 | 2019-07-02 | Novo Nordisk A/S | Device for titrating basal insulin |
| US12343383B2 (en) | 2019-07-12 | 2025-07-01 | Novo Nordisk A/S | High concentration insulin formulation |
| CN118754967A (zh) | 2019-12-30 | 2024-10-11 | 甘李药业股份有限公司 | 胰岛素衍生物 |
| AU2022300061A1 (en) * | 2021-06-25 | 2024-02-01 | Gan & Lee Pharmaceuticals Co., Ltd. | Acylated insulin-containing pharmaceutical composition |
| US20250340610A1 (en) * | 2022-01-28 | 2025-11-06 | Gan & Lee Pharmaceuticals Co., Ltd. | Acylated insulin |
| 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 |
| US3950517A (en) | 1970-05-08 | 1976-04-13 | National Research Development Corporation | Insulin derivatives |
| 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 |
| 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 |
| EP0112861B1 (de) | 1982-07-02 | 1988-01-27 | Jugo-Import-Export-Anstalt | Innenschalung für rotationssymmetrische Bauten |
| 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 |
| JPH03506023A (ja) | 1988-07-20 | 1991-12-26 | ノボ ノルデイスク アクツイエセルスカプ | ポリペプチド |
| 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 |
| KR930001305B1 (ko) | 1989-10-19 | 1993-02-25 | 니뽕 유우시 가부시끼가이샤 | 당 응답형 고분자 복합체(Polymer Complexes of Sugar Response Type) |
| US5179189A (en) | 1990-01-19 | 1993-01-12 | Nova Pharmaceutical Corporation | Fatty acid terminated polyanhydrides |
| DK45590D0 (https=) | 1990-02-21 | 1990-02-21 | Novo Nordisk As | |
| DK155690D0 (da) | 1990-06-28 | 1990-06-28 | Novo Nordisk As | Nye peptider |
| AU8091091A (en) | 1990-07-26 | 1992-02-18 | University Of Iowa Research Foundation, The | Novel drug delivery systems for proteins and peptides using albumin as a carrier molecule |
| AU8546591A (en) | 1990-09-13 | 1992-04-15 | 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 |
| CA2114141A1 (en) | 1991-07-26 | 1993-02-18 | Panayiotis Pericleous Constantinides | W/o microemulsions |
| US5206219A (en) | 1991-11-25 | 1993-04-27 | Applied Analytical Industries, Inc. | Oral compositions of proteinaceous medicaments |
| NZ245170A (en) | 1991-11-26 | 1994-07-26 | Lilly Co Eli | Insulin and proinsulin analogues with arg at b31, b32 and ao and pharmaceutical compositions |
| ES2099193T3 (es) | 1991-12-18 | 1997-05-16 | Hoechst Ag | Procedimiento para la obtencion de soluciones con contenido en insulina. |
| AU5171293A (en) | 1992-10-14 | 1994-05-09 | Regents Of The University Of Colorado, The | Ion-pairing of drugs for improved efficacy and delivery |
| EP0666752A4 (en) | 1992-10-16 | 1996-09-11 | Smithkline Beecham Corp | THERAPEUTIC MICROEMULSIONS. |
| JPH08502490A (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 | 組成物 |
| EP0684833A4 (en) | 1993-02-17 | 1996-09-11 | Smithkline Beecham Corp | MICRO-EMULSIONS COMPRISING THERAPEUTIC PEPTIDES. |
| EP0684834A4 (en) | 1993-02-17 | 1996-09-25 | Smithkline Beecham Corp | MICROEMULSIONS CONTAINING THERAPEUTIC PEPTIDES. |
| AU685784B2 (en) | 1993-02-23 | 1998-01-29 | Genentech Inc. | Excipient stabilization of polypeptides treated with organic solvents |
| 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 |
| EP1132404A3 (en) | 1993-09-17 | 2002-03-27 | Novo Nordisk A/S | Acylated insulin |
| US6869930B1 (en) | 1993-09-17 | 2005-03-22 | Novo Nordisk A/S | Acylated insulin |
| GB9323588D0 (en) | 1993-11-16 | 1994-01-05 | Cortecs Ltd | Hydrophobic preparation |
| ATE416755T1 (de) | 1994-03-07 | 2008-12-15 | Nektar Therapeutics | Verfahren und zusammensetzung für die pulmonale darreichung von insulin |
| 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 |
| CZ289343B6 (cs) | 1995-03-17 | 2002-01-16 | Novo Nordisk A/S | Inzulinový derivát a farmaceutický prostředek pro léčení diabetes |
| 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 |
| AU3255397A (en) | 1996-07-05 | 1998-02-02 | Novo Nordisk A/S | Method for the production of precursors of insulin, precursors of insulin analogues, and insulin like peptides |
| ATE278711T1 (de) | 1996-07-11 | 2004-10-15 | Novo Nordisk As | Verfahren zur selektiven acetylierung |
| US5981489A (en) | 1996-07-18 | 1999-11-09 | Alza Corporation | Non-aqueous protic peptide formulations |
| PT821006E (pt) | 1996-07-26 | 2004-09-30 | Aventis Pharma Gmbh | Derivados de insulina com ligacao a zinco aumentada |
| IL119029A0 (en) | 1996-08-07 | 1996-11-14 | Yeda Res & Dev | Long-acting drugs and pharamaceutical compositions comprising them |
| SK285019B6 (sk) | 1997-01-30 | 2006-04-06 | Novartis Ag | Tvrdá želatínová tobolka |
| US5898067A (en) | 1997-02-07 | 1999-04-27 | Novo Nordisk A/S | Crystallization of proteins |
| RU2218349C2 (ru) | 1997-10-24 | 2003-12-10 | Ново Нордиск А/С | Агрегаты производных инсулина человека |
| JP2001521006A (ja) | 1997-10-24 | 2001-11-06 | イーライ・リリー・アンド・カンパニー | 不溶性インシュリン組成物 |
| ZA989744B (en) | 1997-10-31 | 2000-04-26 | Lilly Co Eli | Method for administering acylated insulin. |
| ES2230727T3 (es) | 1997-11-12 | 2005-05-01 | Alza Corporation | Procedimiento de administracion dermal de polipeptidos. |
| US6531448B1 (en) | 1997-12-23 | 2003-03-11 | Eli Lilly And Company | Insoluble compositions for controlling blood glucose |
| AU8029798A (en) | 1998-06-12 | 2000-01-05 | Deutsches Wollforschungsinstitut | Insulin analogue |
| GB9814172D0 (en) | 1998-06-30 | 1998-08-26 | Andaris Ltd | Formulation for inhalation |
| CA2341624C (en) | 1998-08-25 | 2008-12-02 | 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 |
| UA65636C2 (uk) | 1998-10-16 | 2004-04-15 | Ново Нордіск А/С | Стабільні концентровані препарати інсуліну для доставки через легені |
| 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 |
| WO2000043034A2 (en) | 1999-01-26 | 2000-07-27 | Eli Lilly And Company | Monodisperse hexameric acylated insulin analog formulations |
| WO2000047203A1 (en) | 1999-02-12 | 2000-08-17 | Mqs, Inc. | 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 |
| CN1409640A (zh) | 1999-12-16 | 2003-04-09 | 伊莱利利公司 | 稳定性改善的多肽组合物 |
| 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 |
| CZ20033182A3 (cs) | 2001-05-21 | 2004-09-15 | Nektar Therapeutics | Inzulínový prostředek a způsob podávání inzulínu |
| 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 WITH EXTENDED CIRCULAR HALF TIME |
| UY27439A1 (es) | 2001-09-07 | 2003-04-30 | Nobex Corp | Procedimiento para sintetizar un conjunto de oligomero-polipeptido insulina, conjugado oligomero-polipeptido de proinsulina, composicion de conjugado oligomero-insulina, procedimiento para sintetizar un conjugado oligomero-polipeptido c-peptido, conj |
| US7030082B2 (en) | 2001-09-07 | 2006-04-18 | Nobex Corporation | Pharmaceutical compositions of drug-oligomer conjugates and methods of treating disease therewith |
| US6770625B2 (en) | 2001-09-07 | 2004-08-03 | Nobex Corporation | Pharmaceutical compositions of calcitonin drug-oligomer conjugates and methods of treating diseases therewith |
| EP1453860A2 (en) | 2001-12-02 | 2004-09-08 | Novo Nordisk A/S | Novel glucose-dependant insulins |
| AU2002362039B2 (en) | 2001-12-03 | 2007-07-26 | Soligenix, Inc | Stabilized reverse micelle compositions and uses thereof |
| AU2002314790A1 (en) | 2001-12-05 | 2003-06-23 | Dow Global Technologies Inc. | Method for immobilizing a biologic in a polyurethane-hydrogel composition, a composition prepared from the method, and biomedical applications |
| CZ2004710A3 (cs) | 2001-12-20 | 2005-02-16 | Eli Lilly And Company | Inzulínová sloučenina s protrahovaným účinkem |
| UA46669C2 (uk) | 2001-12-29 | 2005-12-15 | Товариство З Обмеженою Відповідальністю "Мако" | Спосіб приготування готової лікарської форми інсуліну пролонгованої дії |
| WO2003094951A1 (en) | 2002-05-07 | 2003-11-20 | Novo Nordisk A/S | Soluble formulations comprising insulin aspart and insulin detemir |
| JP5599543B2 (ja) | 2002-05-07 | 2014-10-01 | ノヴォ ノルディスク アー／エス | 単量体インスリン及びアシル化インスリンを含む可溶性製剤 |
| AU2003236521A1 (en) | 2002-06-13 | 2003-12-31 | Nobex Corporation | 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 |
| WO2004026794A2 (en) | 2002-09-17 | 2004-04-01 | Merck & 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 |
| ES2375056T3 (es) | 2003-06-03 | 2012-02-24 | Novo Nordisk A/S | Composiciones pept�?dicas farmacéuticas estabilizadas. |
| PL1633391T3 (pl) | 2003-06-03 | 2012-03-30 | Novo Nordisk As | Stabilizowane farmaceutycznie kompozycje peptydowe |
| PL1633876T3 (pl) | 2003-06-17 | 2009-01-30 | Sembiosys Genetics Inc | Sposoby wytwarzania insuliny w roślinach |
| WO2005005477A2 (en) | 2003-07-11 | 2005-01-20 | Novo Nordisk A/S | Stabilised insulin compositions |
| DK1648933T3 (da) | 2003-07-25 | 2009-09-07 | Conjuchem Biotechnologies Inc | Langvarige insulinderivater og fremgangsm der |
| CA2531988C (en) | 2003-08-05 | 2016-06-28 | Novo Nordisk A/S | Novel insulin derivatives |
| AU2004264958B2 (en) | 2003-08-13 | 2010-04-15 | Biocon, Ltd | 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 |
| DK3300721T4 (da) | 2003-11-20 | 2025-03-03 | Novo Nordisk As | Propylenglycol-holdige peptidformuleringer hvilke er optimale til fremstilling og til anvendelse i injektionsindretninger |
| US7371381B2 (en) | 2003-12-12 | 2008-05-13 | Amgen Inc. | Anti-galanin antibodies 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 |
| EP1734938B1 (en) | 2004-03-26 | 2012-06-20 | Universita' Degli Studi Di Parma | Insulin highly respirable microparticles |
| CA2563533C (en) | 2004-04-15 | 2013-10-01 | Shmuel A. Ben-Sasson | Compositions capable of facilitating penetration across a biological barrier |
| CA2567056A1 (en) | 2004-05-10 | 2005-12-08 | Nastech Pharmaceutical Company Inc. | Compositions and methods for enhanced mucosal delivery of parathyroid hormone |
| RU2527893C2 (ru) | 2004-07-19 | 2014-09-10 | Биокон Лимитед | Инсулин-олигомерные конъюгаты, их препараты и применения |
| WO2006020580A2 (en) | 2004-08-09 | 2006-02-23 | Alios Biopharma Inc. | Synthetic hyperglycosylated, protease-resistant polypeptide variants, oral formulations and methods of using the same |
| KR101644250B1 (ko) | 2004-08-23 | 2016-07-29 | 맨카인드 코포레이션 | 약물 전달용 디케토피페라진염, 디케토모르포린염 또는 디케토디옥산염 |
| EP1802287A2 (en) | 2004-09-27 | 2007-07-04 | Sigmoid Biotechnologies Limited | Minicapsule formulations |
| JP2008528549A (ja) | 2005-01-27 | 2008-07-31 | ノボ ノルディスク アクティーゼルスカブ | 構造的に充分に定義された分岐ポリマーと接合されたインスリン誘導体 |
| US20080171695A1 (en) | 2005-02-02 | 2008-07-17 | Novo Nordisk A/S | Insulin Derivatives |
| EP2256130B1 (en) | 2005-02-02 | 2013-09-25 | Novo Nordisk A/S | Novel insulin derivatives |
| JP2008533100A (ja) | 2005-03-18 | 2008-08-21 | ノボ ノルディスク アクティーゼルスカブ | Ｐｅｇ化された単鎖インスリン |
| 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 |
| US8097584B2 (en) | 2005-05-25 | 2012-01-17 | Novo Nordisk A/S | Stabilized formulations of insulin that comprise 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 |
| ES2371361T3 (es) | 2005-12-28 | 2011-12-30 | Novo Nordisk A/S | Composiciones que comprenden una insulina acilada y zinc y método de producción de dichas composiciones. |
| 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 |
| WO2007104737A1 (en) | 2006-03-13 | 2007-09-20 | Novo Nordisk A/S | Acylated single chain insulin |
| EP2015770B1 (en) | 2006-05-09 | 2012-09-26 | Novo Nordisk A/S | Insulin derivative |
| WO2007128815A1 (en) | 2006-05-09 | 2007-11-15 | Novo Nordisk A/S | Insulin derivative |
| CN101573133B (zh) * | 2006-07-31 | 2014-08-27 | 诺沃-诺迪斯克有限公司 | Peg化延长的胰岛素 |
| RU2524150C2 (ru) | 2006-09-22 | 2014-07-27 | Ново Нордиск А/С | Аналоги инсулина, устойчивые к протеазам |
| JP2010525033A (ja) | 2007-04-30 | 2010-07-22 | ノボ・ノルデイスク・エー／エス | 高濃縮のインスリン溶液及び組成物 |
| CN101677944A (zh) | 2007-06-01 | 2010-03-24 | 诺沃-诺迪斯克有限公司 | 稳定的非含水药物组合物 |
| US20110144010A1 (en) | 2007-06-01 | 2011-06-16 | Novo Nordisk A/S | Spontaneously Dispersible Preconcentrates Including a Peptide Drug in a Solid or Semisolid Carrier |
| JP5688969B2 (ja) | 2007-07-16 | 2015-03-25 | ノボ・ノルデイスク・エー／エス | プロテアーゼに対して安定しているペグ化インスリンアナログ |
| US9150633B2 (en) | 2007-08-15 | 2015-10-06 | Novo Nordisk A/S | Insulin analogues with an acyl and alkylene glycol moiety |
| JP5721432B2 (ja) | 2007-08-15 | 2015-05-20 | ノボ・ノルデイスク・エー／エス | アミノ酸含有アルキレングリコール反復単位を含むアシル部を有するインスリン |
| US20090087484A1 (en) | 2007-09-28 | 2009-04-02 | Alza Corporation | Formulation and dosage form for increasing oral bioavailability of hydrophilic macromolecules |
| EP2217621B1 (en) * | 2007-11-08 | 2015-04-22 | Novo Nordisk A/S | Insulin derivative |
| WO2009112583A2 (en) | 2008-03-14 | 2009-09-17 | Novo Nordisk A/S | Protease-stabilized insulin analogues |
| HUE032284T2 (en) * | 2008-03-18 | 2017-09-28 | Novo Nordisk As | Protease-stabilized, acylated insulin analogues |
| JP4959005B2 (ja) | 2008-10-30 | 2012-06-20 | ノボ・ノルデイスク・エー／エス | 毎日の注射頻度より少ないインスリン注射での真性糖尿病の治療 |
| EP2370059A1 (en) | 2008-11-28 | 2011-10-05 | Novo Nordisk A/S | Pharmaceutical compositions suitable for oral administration of derivatized insulin peptides |
| JP2012511506A (ja) | 2008-12-09 | 2012-05-24 | ノヴォ・ノルディスク・アー／エス | 新規インスリンアナログ |
| EP2477644A1 (en) | 2009-09-16 | 2012-07-25 | Novo Nordisk A/S | Stable non-aqueous liquid pharmaceutical compositions comprising an insulin |
| ES2552401T3 (es) | 2009-11-02 | 2015-11-27 | Novo Nordisk A/S | Solución farmacéutica de albúmina unida no covalentemente e insulina acilada |
| CA2786953A1 (en) | 2010-01-12 | 2011-07-21 | Florian Anders Foeger | Pharmaceutical compositions for oral administration of insulin peptides |
| KR20130036290A (ko) | 2010-06-23 | 2013-04-11 | 노보 노르디스크 에이/에스 | 추가 이황화 결합을 함유하는 인슐린 유도체 |
| WO2012049307A2 (en) | 2010-10-15 | 2012-04-19 | Novo Nordisk A/S | Novel n-terminally modified insulin derivatives |
| US20150111820A1 (en) | 2012-07-09 | 2015-04-23 | Novo Nordisk A/S | Novel use of insulin derivatives |
-
2013
- 2013-04-05 CN CN201380030897.6A patent/CN104364260B/zh not_active Expired - Fee Related
- 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 WO PCT/EP2013/057196 patent/WO2013153000A2/en not_active Ceased
- 2013-04-05 KR KR1020147031291A patent/KR20150002777A/ko not_active Withdrawn
- 2013-04-05 JP JP2015504909A patent/JP6199956B2/ja active Active
- 2013-04-05 BR BR112014025132A patent/BR112014025132A2/pt not_active IP Right Cessation
- 2013-04-05 US US14/391,510 patent/US9481721B2/en active Active
- 2013-04-05 MX MX2014012096A patent/MX2014012096A/es unknown
- 2013-04-05 ES ES13714303.8T patent/ES2594303T3/es active Active
- 2013-04-05 AU AU2013247047A patent/AU2013247047A1/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| JP6199956B2 (ja) | 2017-09-20 |
| KR20150002777A (ko) | 2015-01-07 |
| WO2013153000A2 (en) | 2013-10-17 |
| EP2836508B1 (en) | 2016-06-29 |
| CN104364260B (zh) | 2017-02-22 |
| JP2015514120A (ja) | 2015-05-18 |
| US9481721B2 (en) | 2016-11-01 |
| BR112014025132A2 (pt) | 2017-07-11 |
| EP2836508A2 (en) | 2015-02-18 |
| US20150126442A1 (en) | 2015-05-07 |
| CA2870313A1 (en) | 2013-10-17 |
| CN104364260A (zh) | 2015-02-18 |
| WO2013153000A3 (en) | 2013-12-05 |
| MX2014012096A (es) | 2014-11-21 |
| AU2013247047A1 (en) | 2014-10-23 |
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 | |
| Raut et al. | Opalescence in monoclonal antibody solutions and its correlation with intermolecular interactions in dilute and concentrated solutions | |
| Kumar et al. | Hyaluronic acid co-functionalized gold nanoparticle complex for the targeted delivery of metformin in the treatment of liver cancer (HepG2 cells) | |
| Gast et al. | Rapid-Acting and Human Insulins: Hexamer Dissociation Kinetics upon Dilution of the Pharmaceutical Formulation: Gast et al. | |
| Grimes et al. | Carboxyfluorescein: a probe of the blood-ocular barriers with lower membrane permeability than fluorescein | |
| ES2930149T3 (es) | Composiciones farmacéuticas que contienen insulina | |
| JP7179112B2 (ja) | 安定なタンパク質組成物 | |
| Marino et al. | Nanodevice-induced conformational and functional changes in a prototypical calcium sensor protein | |
| Dear et al. | Enhancing stability and reducing viscosity of a monoclonal antibody with cosolutes by weakening protein-protein interactions | |
| RU2663727C2 (ru) | Альтернативные составы для химерных полипептидов tnfr:fc | |
| Vinjamuri et al. | Gelatin solution pH and incubation time influences the size of the nanoparticles engineered by desolvation | |
| Simončič et al. | Mechanistic differences in the effects of sucrose and sucralose on the phase stability of lysozyme solutions | |
| Sozarukova et al. | Serum albumin as a source of and a target for free radicals in pathology | |
| UA129583C2 (uk) | Водний фармацевтичний склад, який містить антитіло проти pd-l1 авелумаб | |
| Sattarahmady et al. | Alginate as an antiglycating agent for human serum albumin | |
| Li et al. | Human islet amyloid polypeptide at the air–aqueous interface: a Langmuir monolayer approach | |
| Biswas et al. | Exploring the role of macromolecular crowding and TNFR1 in cell volume control | |
| Holm et al. | The interrelationship between ligand binding and thermal unfolding of the folate binding protein. The role of self-association and pH | |
| Singh et al. | Investigating the potential of an antidepressant intranasal mucoadhesive microemulsion | |
| Kasahara et al. | Polyphosphate as a novel aggregation suppressor of gamma globulin | |
| Messina et al. | Random heteropolymer excipients improve the colloidal stability of a monoclonal antibody for subcutaneous 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 | |
| Bhavsar et al. | Targeted Lithium Delivery Via Nasal Gel: Improving Efficacy and Safety in Bipolar Disorder Therapy |