PT85949B - Processo para a preparacao de composicoes de insulina contendo ioes magnesio - Google Patents

Processo para a preparacao de composicoes de insulina contendo ioes magnesio Download PDF

Info

Publication number: PT85949B
Authority: PT; Portugal
Prior art keywords: insulin; solution; magnesium; zinc; derivative
Prior art date: 1986-10-20

Application number

PT85949A

Other languages

English (en)

Portuguese (pt)

Other versions

PT85949A (en

Inventor

Klavs Holger Jorgensen

Original Assignee

Novo Nordisk As

Priority date (The priority date 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 date listed.)

1986-10-20

Filing date

1987-10-19

Publication date

1990-07-31

1986-10-20 Priority claimed from DK503386A external-priority patent/DK503386D0/da

1987-07-10 Priority claimed from DK356987A external-priority patent/DK356987D0/da

1987-10-19 Application filed by Novo Nordisk As filed Critical Novo Nordisk As

1987-11-01 Publication of PT85949A publication Critical patent/PT85949A/pt

1990-07-31 Publication of PT85949B publication Critical patent/PT85949B/pt

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 abstract description 259
102000004877 Insulin Human genes 0.000 title claims abstract description 123
108090001061 Insulin Proteins 0.000 title claims abstract description 123
229940125396 insulin Drugs 0.000 title claims abstract description 120
238000002360 preparation method Methods 0.000 title claims abstract description 18
238000000034 method Methods 0.000 title claims description 13
230000008569 process Effects 0.000 title claims description 11
239000000203 mixture Substances 0.000 title claims description 9
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 title claims description 5
239000011777 magnesium Substances 0.000 title claims description 5
229910052749 magnesium Inorganic materials 0.000 title claims description 5
JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 claims abstract description 25
229910001425 magnesium ion Inorganic materials 0.000 claims abstract description 24
238000007911 parenteral administration Methods 0.000 claims abstract description 3
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 36
229940048914 protamine Drugs 0.000 claims description 19
239000011701 zinc Substances 0.000 claims description 19
229910052725 zinc Inorganic materials 0.000 claims description 19
102000007327 Protamines Human genes 0.000 claims description 18
108010007568 Protamines Proteins 0.000 claims description 18
150000003839 salts Chemical class 0.000 claims description 17
239000004026 insulin derivative Substances 0.000 claims description 14
PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 claims description 9
230000009471 action Effects 0.000 claims description 8
230000000694 effects Effects 0.000 claims description 7
239000002244 precipitate Substances 0.000 claims description 4
230000002035 prolonged effect Effects 0.000 claims description 4
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
239000000243 solution Substances 0.000 description 63
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 20
239000007924 injection Substances 0.000 description 20
238000002347 injection Methods 0.000 description 20
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 description 17
101000976075 Homo sapiens Insulin Proteins 0.000 description 15
239000012085 test solution Substances 0.000 description 15
238000010521 absorption reaction Methods 0.000 description 12
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
239000012088 reference solution Substances 0.000 description 11
238000012360 testing method Methods 0.000 description 11
241000282414 Homo sapiens Species 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 8
RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 8
238000001556 precipitation Methods 0.000 description 7
239000000725 suspension Substances 0.000 description 7
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 6
229910001424 calcium ion Inorganic materials 0.000 description 6
239000008103 glucose Substances 0.000 description 6
239000011780 sodium chloride Substances 0.000 description 6
BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 5
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 5
239000013078 crystal Substances 0.000 description 5
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
239000008280 blood Substances 0.000 description 4
210000004369 blood Anatomy 0.000 description 4
238000002474 experimental method Methods 0.000 description 4
229910001629 magnesium chloride Inorganic materials 0.000 description 4
159000000003 magnesium salts Chemical class 0.000 description 4
230000007935 neutral effect Effects 0.000 description 4
210000000689 upper leg Anatomy 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
241000282887 Suidae Species 0.000 description 3
125000000539 amino acid group Chemical group 0.000 description 3
239000011575 calcium Substances 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical compound [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 description 3
239000011654 magnesium acetate Substances 0.000 description 3
235000011285 magnesium acetate Nutrition 0.000 description 3
229940069446 magnesium acetate Drugs 0.000 description 3
239000003755 preservative agent Substances 0.000 description 3
239000000126 substance Substances 0.000 description 3
229910021653 sulphate ion Inorganic materials 0.000 description 3
238000011282 treatment Methods 0.000 description 3
241000251468 Actinopterygii Species 0.000 description 2
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
108010092217 Long-Acting Insulin Proteins 0.000 description 2
102000016261 Long-Acting Insulin Human genes 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
229940024606 amino acid Drugs 0.000 description 2
150000001413 amino acids Chemical class 0.000 description 2
230000002051 biphasic effect Effects 0.000 description 2
229910052791 calcium Inorganic materials 0.000 description 2
239000001569 carbon dioxide Substances 0.000 description 2
229910002092 carbon dioxide Inorganic materials 0.000 description 2
238000006243 chemical reaction Methods 0.000 description 2
-1 citrates Chemical class 0.000 description 2
150000001875 compounds Chemical class 0.000 description 2
230000007423 decrease Effects 0.000 description 2
238000001802 infusion Methods 0.000 description 2
235000012054 meals Nutrition 0.000 description 2
VLKZOEOYAKHREP-UHFFFAOYSA-N methyl pentane Natural products CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
239000003381 stabilizer Substances 0.000 description 2
238000003756 stirring Methods 0.000 description 2
238000010254 subcutaneous injection Methods 0.000 description 2
239000007929 subcutaneous injection Substances 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
210000001519 tissue Anatomy 0.000 description 2
JXPHLUCMHXXHEJ-UHFFFAOYSA-N 2-(aminomethyl)-4-bromoaniline Chemical compound NCC1=CC(Br)=CC=C1N JXPHLUCMHXXHEJ-UHFFFAOYSA-N 0.000 description 1
KYARBIJYVGJZLB-UHFFFAOYSA-N 7-amino-4-hydroxy-2-naphthalenesulfonic acid Chemical compound OC1=CC(S(O)(=O)=O)=CC2=CC(N)=CC=C21 KYARBIJYVGJZLB-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
KWTQSFXGGICVPE-WCCKRBBISA-N Arginine hydrochloride Chemical compound Cl.OC(=O)[C@@H](N)CCCN=C(N)N KWTQSFXGGICVPE-WCCKRBBISA-N 0.000 description 1
108010065691 Biphasic Insulins Proteins 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
101001011741 Bos taurus Insulin Proteins 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 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
241000282412 Homo Species 0.000 description 1
208000013016 Hypoglycemia Diseases 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
238000012404 In vitro experiment Methods 0.000 description 1
229940100066 Long-acting insulin Drugs 0.000 description 1
241001077660 Molo Species 0.000 description 1
241000277329 Oncorhynchus keta Species 0.000 description 1
108010005991 Pork Regular Insulin Proteins 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
206010042674 Swelling Diseases 0.000 description 1
ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 description 1
239000003929 acidic solution Substances 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
235000019270 ammonium chloride Nutrition 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
150000001450 anions Chemical class 0.000 description 1
229940009098 aspartate Drugs 0.000 description 1
230000008901 benefit Effects 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
239000000189 biphasic insulin Substances 0.000 description 1
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 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
230000002308 calcification Effects 0.000 description 1
229910000019 calcium carbonate Inorganic materials 0.000 description 1
229940043430 calcium compound Drugs 0.000 description 1
150000001674 calcium compounds Chemical class 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
150000001860 citric acid derivatives Chemical class 0.000 description 1
230000006240 deamidation Effects 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
238000004925 denaturation Methods 0.000 description 1
230000036425 denaturation Effects 0.000 description 1
238000009792 diffusion process Methods 0.000 description 1
230000008034 disappearance Effects 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
229960001484 edetic acid Drugs 0.000 description 1
210000003722 extracellular fluid Anatomy 0.000 description 1
229930195712 glutamate Natural products 0.000 description 1
PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
239000010931 gold Substances 0.000 description 1
229910052737 gold Inorganic materials 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
239000008241 heterogeneous mixture Substances 0.000 description 1
239000002933 immunoreactive insulin Substances 0.000 description 1
230000006872 improvement Effects 0.000 description 1
239000003978 infusion fluid Substances 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
239000000644 isotonic solution Substances 0.000 description 1
230000003902 lesion Effects 0.000 description 1
239000003509 long acting drug Substances 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
239000000463 material Substances 0.000 description 1
108010066090 neutral insulin Proteins 0.000 description 1
230000010412 perfusion Effects 0.000 description 1
150000003904 phospholipids Chemical class 0.000 description 1
230000004962 physiological condition Effects 0.000 description 1
239000011148 porous material Substances 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000001103 potassium chloride Substances 0.000 description 1
235000011164 potassium chloride Nutrition 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
239000000047 product Substances 0.000 description 1
229950008679 protamine sulfate Drugs 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
238000003127 radioimmunoassay Methods 0.000 description 1
230000008439 repair process Effects 0.000 description 1
230000010410 reperfusion Effects 0.000 description 1
238000011160 research Methods 0.000 description 1
230000000979 retarding effect Effects 0.000 description 1
238000004062 sedimentation Methods 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000007787 solid Substances 0.000 description 1
230000003381 solubilizing effect Effects 0.000 description 1
230000006641 stabilisation Effects 0.000 description 1
238000011105 stabilization Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
238000011146 sterile filtration Methods 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
230000008961 swelling Effects 0.000 description 1
OKUCEQDKBKYEJY-UHFFFAOYSA-N tert-butyl 3-(methylamino)pyrrolidine-1-carboxylate Chemical compound CNC1CCN(C(=O)OC(C)(C)C)C1 OKUCEQDKBKYEJY-UHFFFAOYSA-N 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
230000002792 vascular Effects 0.000 description 1
239000004246 zinc acetate Substances 0.000 description 1
150000003752 zinc compounds Chemical class 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
- 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

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Organic Chemistry (AREA)
Medicinal Chemistry (AREA)
Diabetes (AREA)
Gastroenterology & Hepatology (AREA)
Zoology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Endocrinology (AREA)
General Health & Medical Sciences (AREA)
Genetics & Genomics (AREA)
Biophysics (AREA)
Molecular Biology (AREA)
Biochemistry (AREA)
Toxicology (AREA)
Pharmacology & Pharmacy (AREA)
Bioinformatics & Cheminformatics (AREA)
Immunology (AREA)
Engineering & Computer Science (AREA)
Epidemiology (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Medicinal Preparation (AREA)
Peptides Or Proteins (AREA)

PT85949A 1986-10-20 1987-10-19 Processo para a preparacao de composicoes de insulina contendo ioes magnesio PT85949B (pt)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DK503386A DK503386D0 (da)	1986-10-20	1986-10-20	Peptidpraeparater
DK356987A DK356987D0 (2)	1987-07-10	1987-07-10

Publications (2)

Publication Number	Publication Date
PT85949A PT85949A (en)	1987-11-01
PT85949B true PT85949B (pt)	1990-07-31

Family

ID=26067111

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
PT85949A PT85949B (pt)	1986-10-20	1987-10-19	Processo para a preparacao de composicoes de insulina contendo ioes magnesio

Country Status (18)

Country	Link
US (1)	US5070186A (2)
EP (1)	EP0265213B1 (2)
KR (1)	KR880004819A (2)
CN (1)	CN87107049A (2)
AU (1)	AU616381B2 (2)
CA (1)	CA1316819C (2)
DE (1)	DE3778287D1 (2)
ES (1)	ES2033871T3 (2)
FI (1)	FI86254C (2)
GR (1)	GR3004912T3 (2)
HU (1)	HU201475B (2)
IE (1)	IE60264B1 (2)
IL (1)	IL84203A (2)
NO (1)	NO170754C (2)
NZ (1)	NZ222214A (2)
PH (1)	PH23446A (2)
PT (1)	PT85949B (2)
YU (1)	YU46665B (2)

Families Citing this family (35)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5534488A (en) *	1993-08-13	1996-07-09	Eli Lilly And Company	Insulin formulation
YU18596A (sh) *	1995-03-31	1998-07-10	Eli Lilly And Company	Analogne formulacije monomernog insulina
EP1044016B1 (en) *	1998-01-09	2005-03-16	Novo Nordisk A/S	Stabilised insulin compositions
US7678364B2 (en)	1999-08-25	2010-03-16	Alkermes, Inc.	Particles for inhalation having sustained release properties
DE10114178A1 (de) *	2001-03-23	2002-10-10	Aventis Pharma Gmbh	Zinkfreie und zinkarme Insulinzubereitungen mit verbesserter Stabilität
IL160044A0 (en) *	2001-08-27	2004-06-20	Novo Nordisk As	A cartridge and a medical delivery system accommodating such cartridge
EP2460530A3 (en) *	2002-12-31	2012-08-29	Althea Technologies, Inc.	Human growth hormone crystals and methods for preparing them
NZ554885A (en) *	2002-12-31	2009-07-31	Altus Pharmaceuticals Inc	Complexes of hgh crystals and protamine polymers
US20090023629A1 (en) *	2005-12-23	2009-01-22	Altus Pharmaceuticals Inc.	Compositions comprising polycation-complexed protein crystals and methods of treatment using them
ES2542146T3 (es)	2006-07-31	2015-07-31	Novo Nordisk A/S	Insulinas extendidas PEGiladas.
DK2074141T3 (en)	2006-09-22	2016-11-28	Novo Nordisk As	The protease resistant insulin analogues.
US9387176B2 (en)	2007-04-30	2016-07-12	Novo Nordisk A/S	Method for drying a protein composition, a dried protein composition and a pharmaceutical composition comprising the dried protein
WO2008132229A2 (en) *	2007-04-30	2008-11-06	Novo Nordisk A/S	Highly concentrated insulin solutions and compositions
WO2009112583A2 (en)	2008-03-14	2009-09-17	Novo Nordisk A/S	Protease-stabilized insulin analogues
CN102037008B (zh)	2008-03-18	2016-08-31	诺沃-诺迪斯克有限公司	蛋白酶稳定化的、酰化胰岛素类似物
CN102256618A (zh)	2008-10-17	2011-11-23	赛诺菲-安万特德国有限公司	胰岛素和glp-1激动剂的组合
PL2451437T3 (pl)	2009-07-06	2017-05-31	Sanofi-Aventis Deutschland Gmbh	Wodne preparaty insuliny zawierające metioninę
NZ599847A (en)	2009-11-13	2013-09-27	Sanofi Aventis Deutschland	Pharmaceutical composition comprising a glp-1 agonist and methionine
TR201809460T4 (tr)	2009-11-13	2018-07-23	Sanofi Aventis Deutschland	Bir GLP- 1-agonisti, bir insülin ve metiyonin içeren farmasötik bileşim.
CN101912600B (zh) *	2010-01-11	2014-01-29	杨国汉	改善胰岛素在溶液中稳定性的方法
US8637458B2 (en) *	2010-05-12	2014-01-28	Biodel Inc.	Insulin with a stable basal release profile
AU2011202239C1 (en)	2010-05-19	2017-03-16	Sanofi	Long-acting formulations of insulins
WO2012028172A1 (en)	2010-08-30	2012-03-08	Sanofi-Aventis Deutschland Gmbh	Use of ave0010 for the manufacture of a medicament for the treatment of diabetes mellitus type 2
US9821032B2 (en)	2011-05-13	2017-11-21	Sanofi-Aventis Deutschland Gmbh	Pharmaceutical combination for improving glycemic control as add-on therapy to basal insulin
AR087693A1 (es)	2011-08-29	2014-04-09	Sanofi Aventis Deutschland	Combinacion farmaceutica para uso en el control glucemico en pacientes con diabetes de tipo 2
TWI559929B (en)	2011-09-01	2016-12-01	Sanofi Aventis Deutschland	Pharmaceutical composition for use in the treatment of a neurodegenerative disease
US9481721B2 (en)	2012-04-11	2016-11-01	Novo Nordisk A/S	Insulin formulations
US9381247B2 (en) *	2012-04-16	2016-07-05	Biodel Inc.	Magnesium compositions for modulating the pharmacokinetics and pharmacodynamics of insulin and insulin analogs, and injection site pain
US9399065B2 (en)	2012-04-16	2016-07-26	Biodel Inc.	Magnesium compositions for modulating the pharmacokinetics and injection site pain of insulin
EP2983697B1 (en)	2013-04-03	2018-10-31	Sanofi	Treatment of diabetes mellitus by long acting formulations of insulins
AU2014333979B2 (en)	2013-10-07	2018-02-15	Novo Nordisk A/S	Novel derivative of an insulin analogue
PE20171622A1 (es)	2014-12-12	2017-11-02	Sanofi Aventis Deutschland	Formulacion de relacion fija de insulina glargina/lixisenatida
TWI748945B (zh)	2015-03-13	2021-12-11	德商賽諾菲阿凡提斯德意志有限公司	第２型糖尿病病患治療
TW201705975A (zh)	2015-03-18	2017-02-16	賽諾菲阿凡提斯德意志有限公司	第２型糖尿病病患之治療
TWI700091B (zh)	2016-12-16	2020-08-01	丹麥商諾佛儂迪克股份有限公司	含胰島素醫藥組成物

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US2076082A (en) *	1935-04-08	1937-04-06	Nordisk Insulinlab	Therapeutic product and process
US2179384A (en) *	1937-04-05	1939-11-07	Univ Alberta	Therapeutic composition and process of making it
US2190134A (en) *	1939-06-09	1940-02-13	Norton Co	Grinding machine
US2538018A (en) *	1944-04-04	1951-01-16	Nordisk Insulinlab	Crystalline product of insulin and alkaline protein and process of making it
US2474729A (en) *	1945-01-03	1949-06-28	Rhone Poulenc Sa	Insulin preparations
US2801953A (en) *	1952-02-28	1957-08-06	Hoechst Ag	Process of preparing crystallized insulin preparations
US3102077A (en) *	1953-08-19	1963-08-27	Christensen Henry Marinus	Preparation of insulin containing 2.75 to 8 percent zinc content
DK98342C (da) *	1959-06-16	1964-03-31	Henry Marinus Dr Christensen	Fremgangsmåde til fremstilling af et insulinpræparat til peroral applikation.
US3868358A (en) *	1971-04-30	1975-02-25	Lilly Co Eli	Protamine-insulin product
GB1426061A (en) *	1972-12-28	1976-02-25	Ici Ltd	Polypeptides
US3856771A (en) *	1973-07-16	1974-12-24	Lilly Co Eli	Process for manufacturing alkali metal or ammonium insulin
US4196196A (en) *	1978-06-19	1980-04-01	Tiholiz Ivan C	Divalen/monovalent bipolar cation therapy for enhancement of tissue perfusion and reperfusion in disease states
AU550068B2 (en) *	1981-03-10	1986-02-27	Novo Nordisk A/S	Zinc insulin stabilized with calcium or magnesium salts
US4839341A (en) *	1984-05-29	1989-06-13	Eli Lilly And Company	Stabilized insulin formulations
US4764592A (en) *	1987-04-23	1988-08-16	Eli Lilly And Company	Crystalline human proinsulin and process for its production

1987
- 1987-10-14 PH PH35937A patent/PH23446A/en unknown
- 1987-10-19 DE DE8787309229T patent/DE3778287D1/de not_active Expired - Lifetime
- 1987-10-19 NO NO874347A patent/NO170754C/no unknown
- 1987-10-19 YU YU191887A patent/YU46665B/sh unknown
- 1987-10-19 HU HU874683A patent/HU201475B/hu not_active IP Right Cessation
- 1987-10-19 FI FI874596A patent/FI86254C/fi not_active IP Right Cessation
- 1987-10-19 EP EP87309229A patent/EP0265213B1/en not_active Expired - Lifetime
- 1987-10-19 AU AU79907/87A patent/AU616381B2/en not_active Ceased
- 1987-10-19 IL IL84203A patent/IL84203A/xx not_active IP Right Cessation
- 1987-10-19 ES ES198787309229T patent/ES2033871T3/es not_active Expired - Lifetime
- 1987-10-19 IE IE279987A patent/IE60264B1/en not_active IP Right Cessation
- 1987-10-19 NZ NZ222214A patent/NZ222214A/xx unknown
- 1987-10-19 PT PT85949A patent/PT85949B/pt unknown
- 1987-10-20 KR KR870011644A patent/KR880004819A/ko not_active Ceased
- 1987-10-20 CA CA000549713A patent/CA1316819C/en not_active Expired - Fee Related
- 1987-10-20 CN CN198787107049A patent/CN87107049A/zh not_active Withdrawn
1989
- 1989-04-19 US US07/340,331 patent/US5070186A/en not_active Expired - Fee Related
1992
- 1992-06-11 GR GR920401262T patent/GR3004912T3/el unknown

Also Published As

Publication number	Publication date
CN87107049A (zh)	1988-07-06
US5070186A (en)	1991-12-03
FI86254C (fi)	1992-08-10
KR880004819A (ko)	1988-06-27
IE60264B1 (en)	1994-06-29
FI874596A0 (fi)	1987-10-19
NO874347L (no)	1988-04-21
YU46665B (sh)	1994-01-20
EP0265213B1 (en)	1992-04-15
DE3778287D1 (de)	1992-05-21
PH23446A (en)	1989-08-07
HU201475B (en)	1990-11-28
NO170754C (no)	1992-12-02
AU7990787A (en)	1988-04-21
FI86254B (fi)	1992-04-30
NO170754B (no)	1992-08-24
YU191887A (en)	1989-04-30
IL84203A (en)	1993-04-04
CA1316819C (en)	1993-04-27
FI874596L (fi)	1988-04-21
NZ222214A (en)	1989-11-28
AU616381B2 (en)	1991-10-31
ES2033871T3 (es)	1993-04-01
IE872799L (en)	1988-04-20
EP0265213A2 (en)	1988-04-27
EP0265213A3 (en)	1988-11-09
GR3004912T3 (2)	1993-04-28
PT85949A (en)	1987-11-01
HUT46232A (en)	1988-10-28
NO874347D0 (no)	1987-10-19

Legal Events

Date	Code	Title	Description
1994-07-29	PD3A	Change of proprietorship

Publication	Publication Date	Title
PT85949B (pt)	1990-07-31	Processo para a preparacao de composicoes de insulina contendo ioes magnesio
US5382574A (en)	1995-01-17	Insulin preparations containing nicotinic acid or nicotinamide
US6174856B1 (en)	2001-01-16	Stabilized insulin compositions
CA2258097C (en)	2011-02-08	Insulin preparations containing nacl
US20100069292A1 (en)	2010-03-18	Insulin with a basal release profile
PT101723B (pt)	1997-02-28	Formulacoes de analogo de insulina monomerico
KR100589878B1 (ko)	2006-06-15	사람 성장 호르몬을 함유한 수성 의약 조성물
PT646379E (pt)	2002-03-28	Formulacao de insulina
JP2001199899A (ja)	2001-07-24	インスリン類似化合物複合体
WO1995005848A1 (en)	1995-03-02	Protracted glp-1
BRPI0710651A2 (pt)	2011-08-23	composições farmacêuticas de hglp-1, expedina-4 e seus análogos e uso das mesmas
JPH02101022A (ja)	1990-04-12	糖尿病治療用医薬組成物
JP2002504908A (ja)	2002-02-12	安定なインスリン製剤
JP2012233003A (ja)	2012-11-29	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
BG62913B1 (bg)	2000-11-30	Подобрени концентрирани инжекционни и инфузионни разтвори за интравазално прилагане
US5028587A (en)	1991-07-02	Mixed crystals of insulin and insulin derivatives
JP2021527084A (ja)	2021-10-11	テルリプレシン組成物及びその使用
JP2001518497A (ja)	2001-10-16	医療用溶液の濃縮物及びその使用
JPS63179831A (ja)	1988-07-23	インシュリン製剤
JPH02229119A (ja)	1990-09-11	動脈硬化予防および治療剤
DK157901B (da)	1990-03-05	Insulinpraeparat til parenteral administration indeholdende magnesiumioner
JP5561895B2 (ja)	2014-07-30	肝機能改善及び麻酔作用増強抑制剤
WO2006096079A2 (en)	2006-09-14	Pharmaceutical composition comprising a biosynthetic analog of human insulin, and its use in the treatment of diabetes mellitus.
JPH02202822A (ja)	1990-08-10	肝細胞増殖促進剤
JPH04145022A (ja)	1992-05-19	２―０―高級アルキルアスコルビン酸又はその誘導体含有製剤