NO130939B - - Google Patents

Info

Publication number

NO130939B

NO130939B NO141370A NO141370A NO130939B NO 130939 B NO130939 B NO 130939B NO 141370 A NO141370 A NO 141370A NO 141370 A NO141370 A NO 141370A NO 130939 B NO130939 B NO 130939B

Authority

NO

Norway

Prior art keywords

protamine

zinc

insulin

suspension

amount

Prior art date

1969-09-01

Links

• Espacenet
• Global Dossier
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• 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 claims description 130
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 104
• 102000007327 Protamines Human genes 0.000 claims description 93
• 108010007568 Protamines Proteins 0.000 claims description 93
• 229940048914 protamine Drugs 0.000 claims description 93
• 102000004877 Insulin Human genes 0.000 claims description 65
• 108090001061 Insulin Proteins 0.000 claims description 65
• 229940125396 insulin Drugs 0.000 claims description 65
• 239000011701 zinc Substances 0.000 claims description 54
• 229910052725 zinc Inorganic materials 0.000 claims description 54
• 238000002360 preparation method Methods 0.000 claims description 33
• 239000000725 suspension Substances 0.000 claims description 31
• 239000013078 crystal Substances 0.000 claims description 24
• 239000008363 phosphate buffer Substances 0.000 claims description 8
• 238000000034 method Methods 0.000 claims description 7
• 238000004519 manufacturing process Methods 0.000 claims description 6
• 238000006243 chemical reaction Methods 0.000 claims description 3
• 230000000694 effects Effects 0.000 description 11
• 239000000243 solution Substances 0.000 description 11
• 229910019142 PO4 Inorganic materials 0.000 description 10
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 10
• 239000010452 phosphate Substances 0.000 description 10
• 239000000203 mixture Substances 0.000 description 9
• 238000002474 experimental method Methods 0.000 description 8
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 7
• RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 7
• 229940100630 metacresol Drugs 0.000 description 7
• 239000001488 sodium phosphate Substances 0.000 description 6
• 229910000162 sodium phosphate Inorganic materials 0.000 description 6
• RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 6
• JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 6
• 239000002244 precipitate Substances 0.000 description 5
• 239000000872 buffer Substances 0.000 description 4
• 238000002156 mixing Methods 0.000 description 3
• 239000002245 particle Substances 0.000 description 3
• 239000011592 zinc chloride Substances 0.000 description 3
• 235000005074 zinc chloride Nutrition 0.000 description 3
• LRXTYHSAJDENHV-UHFFFAOYSA-H zinc phosphate Chemical compound [Zn+2].[Zn+2].[Zn+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O LRXTYHSAJDENHV-UHFFFAOYSA-H 0.000 description 3
• 229910000165 zinc phosphate Inorganic materials 0.000 description 3
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
• XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
• 239000007864 aqueous solution Substances 0.000 description 2
• 238000002425 crystallisation Methods 0.000 description 2
• 230000008025 crystallization Effects 0.000 description 2
• 108010000947 protamine zinc Proteins 0.000 description 2
• 238000001179 sorption measurement Methods 0.000 description 2
• 239000000126 substance Substances 0.000 description 2
• 229910021653 sulphate ion Inorganic materials 0.000 description 2
• 239000000375 suspending agent Substances 0.000 description 2
• 150000003751 zinc Chemical class 0.000 description 2
• 238000010521 absorption reaction Methods 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 230000007812 deficiency Effects 0.000 description 1
• 239000000706 filtrate Substances 0.000 description 1
• 239000012467 final product Substances 0.000 description 1
• 238000012423 maintenance Methods 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• 108010066090 neutral insulin Proteins 0.000 description 1
• -1 pH = 6-8 Chemical compound 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• 150000003839 salts Chemical class 0.000 description 1
• 239000002002 slurry Substances 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 239000013589 supplement Substances 0.000 description 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
• 239000011787 zinc oxide Substances 0.000 description 1
• 229940077935 zinc phosphate Drugs 0.000 description 1