PT96841A - Processo para a preparacao de composicoes farmaceuticas de insulina contendo novos complexos insulinicos de co(iii) - Google Patents
Processo para a preparacao de composicoes farmaceuticas de insulina contendo novos complexos insulinicos de co(iii) Download PDFInfo
- Publication number
- PT96841A PT96841A PT96841A PT9684191A PT96841A PT 96841 A PT96841 A PT 96841A PT 96841 A PT96841 A PT 96841A PT 9684191 A PT9684191 A PT 9684191A PT 96841 A PT96841 A PT 96841A
- Authority
- PT
- Portugal
- Prior art keywords
- insulin
- iii
- formula
- ins
- preparation
- Prior art date
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 claims description 130
- 229940125396 insulin Drugs 0.000 title claims description 61
- 102000004877 Insulin Human genes 0.000 title claims description 59
- 108090001061 Insulin Proteins 0.000 title claims description 59
- 238000002360 preparation method Methods 0.000 title claims description 14
- 150000001875 compounds Chemical class 0.000 title claims description 12
- 238000000034 method Methods 0.000 title claims description 12
- 239000000203 mixture Substances 0.000 claims description 39
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 claims description 17
- 101000976075 Homo sapiens Insulin Proteins 0.000 claims description 13
- 239000004026 insulin derivative Substances 0.000 claims description 9
- 108010092217 Long-Acting Insulin Proteins 0.000 claims description 8
- 102000016261 Long-Acting Insulin Human genes 0.000 claims description 8
- 229940100066 Long-acting insulin Drugs 0.000 claims description 8
- 239000003446 ligand Substances 0.000 claims description 6
- 241000282412 Homo Species 0.000 claims description 5
- 206010012601 diabetes mellitus Diseases 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 150000001450 anions Chemical class 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 241000894007 species Species 0.000 claims description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 2
- 101000993800 Sus scrofa Insulin Proteins 0.000 claims 1
- 239000011230 binding agent Substances 0.000 claims 1
- 238000009472 formulation Methods 0.000 claims 1
- 230000002608 insulinlike Effects 0.000 claims 1
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 20
- 239000000243 solution Substances 0.000 description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 230000000694 effects Effects 0.000 description 12
- 238000002347 injection Methods 0.000 description 12
- 239000007924 injection Substances 0.000 description 12
- 208000013016 Hypoglycemia Diseases 0.000 description 9
- 241000283973 Oryctolagus cuniculus Species 0.000 description 8
- BSUSEPIPTZNHMN-UHFFFAOYSA-L cobalt(2+);diperchlorate Chemical compound [Co+2].[O-]Cl(=O)(=O)=O.[O-]Cl(=O)(=O)=O BSUSEPIPTZNHMN-UHFFFAOYSA-L 0.000 description 8
- 102000007327 Protamines Human genes 0.000 description 7
- 108010007568 Protamines Proteins 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 6
- 229920005654 Sephadex Polymers 0.000 description 5
- 239000012507 Sephadex™ Substances 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- 101001011741 Bos taurus Insulin Proteins 0.000 description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000007983 Tris buffer Substances 0.000 description 4
- IXIBAKNTJSCKJM-BUBXBXGNSA-N bovine insulin 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)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)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(C)C)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 IXIBAKNTJSCKJM-BUBXBXGNSA-N 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 4
- 230000002218 hypoglycaemic effect Effects 0.000 description 4
- 230000002163 immunogen Effects 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 229940070353 protamines Drugs 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 238000002523 gelfiltration Methods 0.000 description 3
- 238000004255 ion exchange chromatography Methods 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 229940048914 protamine Drugs 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 238000011993 High Performance Size Exclusion Chromatography Methods 0.000 description 2
- 102000003746 Insulin Receptor Human genes 0.000 description 2
- 108010001127 Insulin Receptor Proteins 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 241000282887 Suidae Species 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 210000001789 adipocyte Anatomy 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000001142 circular dichroism spectrum Methods 0.000 description 2
- 239000010941 cobalt Substances 0.000 description 2
- 229910017052 cobalt Inorganic materials 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000010874 in vitro model Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000008223 sterile water Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- XFNJVJPLKCPIBV-UHFFFAOYSA-N trimethylenediamine Chemical compound NCCCN XFNJVJPLKCPIBV-UHFFFAOYSA-N 0.000 description 2
- 238000000108 ultra-filtration Methods 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 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 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 241000282414 Homo sapiens Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 101710186643 Insulin-2 Proteins 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
- 229930064664 L-arginine Natural products 0.000 description 1
- 235000014852 L-arginine Nutrition 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 108010005991 Pork Regular Insulin Proteins 0.000 description 1
- 239000012614 Q-Sepharose Substances 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- GVPFVAHMJGGAJG-UHFFFAOYSA-L cobalt dichloride Chemical compound [Cl-].[Cl-].[Co+2] GVPFVAHMJGGAJG-UHFFFAOYSA-L 0.000 description 1
- -1 cobalt insulin complexes Chemical class 0.000 description 1
- JAWGVVJVYSANRY-UHFFFAOYSA-N cobalt(3+) Chemical compound [Co+3] JAWGVVJVYSANRY-UHFFFAOYSA-N 0.000 description 1
- 239000013632 covalent dimer Substances 0.000 description 1
- 229930003836 cresol Natural products 0.000 description 1
- 230000035418 detection of UV Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 230000004190 glucose uptake Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 239000002085 irritant Substances 0.000 description 1
- 231100000021 irritant Toxicity 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- AOHJOMMDDJHIJH-UHFFFAOYSA-N propylenediamine Chemical compound CC(N)CN AOHJOMMDDJHIJH-UHFFFAOYSA-N 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- BAZAXWOYCMUHIX-UHFFFAOYSA-M sodium perchlorate Chemical compound [Na+].[O-]Cl(=O)(=O)=O BAZAXWOYCMUHIX-UHFFFAOYSA-M 0.000 description 1
- 229910001488 sodium perchlorate Inorganic materials 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
Classifications
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/52—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an inorganic compound, e.g. an inorganic ion that is complexed with the active ingredient
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Diabetes (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Inorganic Chemistry (AREA)
- Zoology (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Chairs For Special Purposes, Such As Reclining Chairs (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DK045590A DK45590D0 (OSRAM) | 1990-02-21 | 1990-02-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PT96841A true PT96841A (pt) | 1991-11-29 |
Family
ID=8093754
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PT96841A PT96841A (pt) | 1990-02-21 | 1991-02-21 | Processo para a preparacao de composicoes farmaceuticas de insulina contendo novos complexos insulinicos de co(iii) |
Country Status (12)
| Country | Link |
|---|---|
| EP (1) | EP0516704B1 (OSRAM) |
| JP (1) | JPH05503940A (OSRAM) |
| AU (1) | AU641991B2 (OSRAM) |
| CA (1) | CA2075982A1 (OSRAM) |
| DE (1) | DE69100626D1 (OSRAM) |
| DK (1) | DK45590D0 (OSRAM) |
| HU (1) | HUT63858A (OSRAM) |
| IE (1) | IE910579A1 (OSRAM) |
| NZ (1) | NZ237176A (OSRAM) |
| PT (1) | PT96841A (OSRAM) |
| WO (1) | WO1991012817A1 (OSRAM) |
| ZA (1) | ZA911279B (OSRAM) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9316895D0 (en) * | 1993-08-13 | 1993-09-29 | Guy S And St Thomas Hospitals | Hepatoselective insulin analogues |
| US6342225B1 (en) | 1993-08-13 | 2002-01-29 | Deutshces Wollforschungsinstitut | Pharmaceutical active conjugates |
| US6011007A (en) * | 1993-09-17 | 2000-01-04 | Novo Nordisk A/S | Acylated insulin |
| US6869930B1 (en) | 1993-09-17 | 2005-03-22 | Novo Nordisk A/S | Acylated insulin |
| DE122004000035I2 (de) * | 1993-09-17 | 2009-08-06 | Novo Nordisk As | Acyliertes insulin |
| US6251856B1 (en) | 1995-03-17 | 2001-06-26 | Novo Nordisk A/S | Insulin derivatives |
| US6451762B1 (en) | 1997-10-24 | 2002-09-17 | Novo Nordisk A/S | Aggregates of human insulin derivatives |
| EP2107069B1 (en) | 2003-08-05 | 2013-01-16 | Novo Nordisk A/S | Novel insulin derivatives |
| PT2107069E (pt) | 2003-08-05 | 2013-04-23 | Novo Nordisk As | Novos derivados de insulina |
| EP2256130B1 (en) | 2005-02-02 | 2013-09-25 | Novo Nordisk A/S | Novel insulin derivatives |
| EP2505593A1 (en) | 2005-12-28 | 2012-10-03 | Novo Nordisk A/S | Compositions comprising an acylated insulin and zinc and method of making the said compositions |
| JP5550338B2 (ja) | 2006-07-31 | 2014-07-16 | ノボ・ノルデイスク・エー／エス | ペグ化持続型インスリン |
| EP2074141B1 (en) | 2006-09-22 | 2016-08-10 | Novo Nordisk A/S | Protease resistant insulin analogues |
| WO2008132224A2 (en) | 2007-04-30 | 2008-11-06 | Novo Nordisk A/S | Method for drying a protein composition, a dried protein composition and a pharmaceutical composition comprising the dried protein |
| CN101677947B (zh) | 2007-06-13 | 2013-07-17 | 诺沃-诺迪斯克有限公司 | 包含胰岛素衍生物的药物制剂 |
| CN101970477B (zh) | 2008-03-14 | 2014-12-31 | 诺沃-诺迪斯克有限公司 | 蛋白酶稳定的胰岛素类似物 |
| PT2910570T (pt) | 2008-03-18 | 2017-01-24 | Novo Nordisk As | Análogos de insulina acilados, estabilizados contra proteases |
| AU2009309623B9 (en) | 2008-10-30 | 2014-10-02 | Novo Nordisk A/S | Treating diabetes melitus using insulin injections with less than daily injection frequency |
| RU2013123515A (ru) | 2010-10-27 | 2014-12-10 | Ново Нордиск А/С | Лечение сахарного диабета с помощью инъекций инсулина, вводимых с различными интервалами |
| BR112014025132A2 (pt) | 2012-04-11 | 2017-07-11 | Novo Nordisk As | formulações de insulina |
| WO2014177623A1 (en) | 2013-04-30 | 2014-11-06 | Novo Nordisk A/S | Novel administration regime |
| PT3055325T (pt) | 2013-10-07 | 2018-04-06 | Novo Nordisk As | Novo derivado de um análogo de insulina |
| PT3554534T (pt) | 2016-12-16 | 2021-11-05 | Novo Nordisk As | Composições farmacêuticas contendo insulina |
| US10335464B1 (en) | 2018-06-26 | 2019-07-02 | Novo Nordisk A/S | Device for titrating basal insulin |
| US12343383B2 (en) | 2019-07-12 | 2025-07-01 | Novo Nordisk A/S | High concentration insulin formulation |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE971500C (de) * | 1950-11-22 | 1959-02-05 | Organon Nv | Verfahren zur Herstellung von Insulin-Suspensionen mit verlaengerter Wirkung |
| DE1107374B (de) * | 1958-01-31 | 1961-05-25 | Organon Nv | Verfahren zur Herstellung eines Insulin-Praeparates |
-
1990
- 1990-02-21 DK DK045590A patent/DK45590D0/da not_active Application Discontinuation
-
1991
- 1991-02-20 NZ NZ237176A patent/NZ237176A/en unknown
- 1991-02-20 IE IE057991A patent/IE910579A1/en unknown
- 1991-02-21 ZA ZA911279A patent/ZA911279B/xx unknown
- 1991-02-21 PT PT96841A patent/PT96841A/pt not_active Application Discontinuation
- 1991-02-21 AU AU73378/91A patent/AU641991B2/en not_active Expired - Fee Related
- 1991-02-21 JP JP3504590A patent/JPH05503940A/ja active Pending
- 1991-02-21 HU HU922721Q patent/HUT63858A/hu unknown
- 1991-02-21 EP EP91904980A patent/EP0516704B1/en not_active Expired - Lifetime
- 1991-02-21 CA CA002075982A patent/CA2075982A1/en not_active Abandoned
- 1991-02-21 DE DE91904980T patent/DE69100626D1/de not_active Expired - Lifetime
- 1991-02-21 WO PCT/DK1991/000052 patent/WO1991012817A1/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| CA2075982A1 (en) | 1991-08-22 |
| EP0516704B1 (en) | 1993-11-10 |
| WO1991012817A1 (en) | 1991-09-05 |
| IE910579A1 (en) | 1991-08-28 |
| DE69100626D1 (de) | 1993-12-16 |
| ZA911279B (en) | 1991-10-30 |
| EP0516704A1 (en) | 1992-12-09 |
| DK45590D0 (OSRAM) | 1990-02-21 |
| AU641991B2 (en) | 1993-10-07 |
| JPH05503940A (ja) | 1993-06-24 |
| HU9202721D0 (en) | 1992-12-28 |
| NZ237176A (en) | 1991-12-23 |
| AU7337891A (en) | 1991-09-18 |
| HUT63858A (en) | 1993-10-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| PT96841A (pt) | Processo para a preparacao de composicoes farmaceuticas de insulina contendo novos complexos insulinicos de co(iii) | |
| KR100539193B1 (ko) | 인간 인슐린 유도체의 응집체 | |
| JP6788139B2 (ja) | インスリン含有医薬組成物 | |
| RU2135205C1 (ru) | Инсулиновый препарат, способ получения препарата, способ лечения сахарного диабета | |
| Brange et al. | Neutral insulin solutions physically stabilized by addition of Zn2+ | |
| PT1881850E (pt) | Compostos peguilados de glp-1 | |
| HU201475B (en) | Process for producing liquide insulin compositions | |
| JPH10511365A (ja) | 遅延性ｇｌｐ−１組成物 | |
| EP2496213B1 (en) | Pharmaceutical solution of non covalently bound albumin and acylated insulin | |
| CA1335924C (en) | Mixed crystals of insulin and insulin derivatives, a process for the preparation of these mixed crystals, pharmaceutical agents containing these mixed crystals, and the use thereof for the treatment of diabetes mellitus | |
| US6451762B1 (en) | Aggregates of human insulin derivatives | |
| US20050222006A1 (en) | Aggregates of human insulin derivatives | |
| JP6005732B2 (ja) | 非ペプチド性重合体−インスリン多量体及びその製造方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| BB1A | Laying open of patent application |
Effective date: 19910828 |
|
| FC3A | Refusal |
Effective date: 19970701 |