JPH11506738A - アシル化タンパク質粉末の製造 - Google Patents
アシル化タンパク質粉末の製造Info
- Publication number
- JPH11506738A JPH11506738A JP9500832A JP50083297A JPH11506738A JP H11506738 A JPH11506738 A JP H11506738A JP 9500832 A JP9500832 A JP 9500832A JP 50083297 A JP50083297 A JP 50083297A JP H11506738 A JPH11506738 A JP H11506738A
- Authority
- JP
- Japan
- Prior art keywords
- protein
- acylated
- insulin
- aqueous
- fatty
- 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.)
- Granted
Links
- 108091005647 acylated proteins Proteins 0.000 title claims abstract description 45
- 239000000843 powder Substances 0.000 title claims abstract description 27
- 238000004519 manufacturing process Methods 0.000 title description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 73
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 62
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 62
- 238000000034 method Methods 0.000 claims abstract description 49
- 239000007864 aqueous solution Substances 0.000 claims abstract description 26
- 238000001556 precipitation Methods 0.000 claims abstract description 19
- 239000002245 particle Substances 0.000 claims abstract description 10
- 238000002955 isolation Methods 0.000 claims abstract description 7
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical class 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 97
- 238000001914 filtration Methods 0.000 claims description 37
- 239000000203 mixture Substances 0.000 claims description 22
- 108010076181 Proinsulin Proteins 0.000 claims description 17
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 17
- 229930195729 fatty acid Natural products 0.000 claims description 17
- 239000000194 fatty acid Substances 0.000 claims description 17
- 239000000243 solution Substances 0.000 claims description 16
- 101000976075 Homo sapiens Insulin Proteins 0.000 claims description 13
- 150000004665 fatty acids Chemical class 0.000 claims description 13
- 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 13
- 230000010933 acylation Effects 0.000 claims description 8
- 238000005917 acylation reaction Methods 0.000 claims description 8
- 230000015572 biosynthetic process Effects 0.000 claims description 8
- 239000012460 protein solution Substances 0.000 claims description 8
- 238000001035 drying Methods 0.000 claims description 4
- 230000001376 precipitating effect Effects 0.000 claims description 2
- 230000001737 promoting effect Effects 0.000 claims description 2
- 102000004877 Insulin Human genes 0.000 description 56
- 108090001061 Insulin Proteins 0.000 description 56
- 235000018102 proteins Nutrition 0.000 description 42
- 229940125396 insulin Drugs 0.000 description 36
- 239000004026 insulin derivative Substances 0.000 description 20
- 239000002002 slurry Substances 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000002244 precipitate Substances 0.000 description 9
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 7
- -1 beef insulin Chemical compound 0.000 description 7
- 239000012065 filter cake Substances 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 125000000539 amino acid group Chemical group 0.000 description 6
- 125000003277 amino group Chemical group 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
- 238000012545 processing Methods 0.000 description 6
- 238000011084 recovery Methods 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 229940053200 antiepileptics fatty acid derivative Drugs 0.000 description 5
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 235000018417 cysteine Nutrition 0.000 description 4
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 239000004472 Lysine Substances 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 230000005484 gravity Effects 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 238000010979 pH adjustment Methods 0.000 description 3
- 239000002798 polar solvent Substances 0.000 description 3
- 238000011085 pressure filtration Methods 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000000967 suction filtration Methods 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 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 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- 235000021314 Palmitic acid Nutrition 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 235000015278 beef Nutrition 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- KEMQGTRYUADPNZ-UHFFFAOYSA-N heptadecanoic acid Chemical compound CCCCCCCCCCCCCCCCC(O)=O KEMQGTRYUADPNZ-UHFFFAOYSA-N 0.000 description 2
- 150000004668 long chain fatty acids Chemical class 0.000 description 2
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 2
- 229940119528 pork insulin Drugs 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- VDZOOKBUILJEDG-UHFFFAOYSA-M tetrabutylammonium hydroxide Chemical compound [OH-].CCCC[N+](CCCC)(CCCC)CCCC VDZOOKBUILJEDG-UHFFFAOYSA-M 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- TWJNQYPJQDRXPH-UHFFFAOYSA-N 2-cyanobenzohydrazide Chemical compound NNC(=O)C1=CC=CC=C1C#N TWJNQYPJQDRXPH-UHFFFAOYSA-N 0.000 description 1
- WSXGQYDHJZKQQB-UHFFFAOYSA-N 3-pyridin-4-ylpropanoic acid Chemical group OC(=O)CCC1=CC=NC=C1 WSXGQYDHJZKQQB-UHFFFAOYSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000619542 Homo sapiens E3 ubiquitin-protein ligase parkin Proteins 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
- 235000021360 Myristic acid Nutrition 0.000 description 1
- TUNFSRHWOTWDNC-UHFFFAOYSA-N Myristic acid Natural products CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000519999 Stachys Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 230000001851 biosynthetic effect Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000003245 coal Substances 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 238000009295 crossflow filtration Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 108091005632 fatty acylated proteins Proteins 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 230000009229 glucose formation Effects 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 230000003914 insulin secretion Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 238000005360 mashing Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 150000002942 palmitic acid derivatives Chemical class 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 102000045222 parkin Human genes 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 125000002958 pentadecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- XTUSEBKMEQERQV-UHFFFAOYSA-N propan-2-ol;hydrate Chemical compound O.CC(C)O XTUSEBKMEQERQV-UHFFFAOYSA-N 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 238000000164 protein isolation Methods 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 230000004850 protein–protein interaction Effects 0.000 description 1
- 239000002510 pyrogen Substances 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 150000004671 saturated fatty acids Chemical class 0.000 description 1
- 235000003441 saturated fatty acids Nutrition 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical compound [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 description 1
- 229910001948 sodium oxide Inorganic materials 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/30—Extraction; Separation; Purification by precipitation
-
- 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)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Zoology (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Analytical Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.アシル化タンパク質を水性混合物から粉末として回収する方法であって、 そのタンパク質の水溶液を、溶液中のそのタンパク質が不溶性になるpHに調節し 、該pHで濾過可能な粒子の形態にあるそのタンパク質の沈澱を助長するに足るア ルコールを、そのタンパク質の水性混合物に添加することからなる方法。 2.該タンパク質が脂肪酸誘導体でアシル化されている請求項1の方法。 3.アシル化タンパク質が等電沈澱によるタンパク質水溶液からの単離に抵抗 するタンパク質を含む請求項1の方法。 4.該アシル化タンパク質が、脂肪酸アシル化プロインスリン、脂肪酸アシル 化インスリン及び脂肪酸アシル化インスリン類縁体からなる群より選択される請 求項3の方法。 5.水溶液をpH約4.0〜6.0に調節する請求項4の方法。 6.アシル化タンパク質がN-パルミトイルLysB29ヒトインスリンである請求項5 の方法。 7.アルコールが水性混合物の20〜35容量%のアルコール濃度を与える量で添加 されるエタノールである請求項6の方法。 8.アルコール濃度が25〜30容量%である請求項7の方法。 9.アシル化タンパク質をそのタンパク質の水溶液から粉末として回収する方 法であって、該水溶液をそのタンパク質の等電点pH付近に調節すると共に、該pH で濾過可能な粒子の形態にあるそのタンパク質の沈澱を助長するのに適したアル コール濃度にすることからなる方法。 10.アシル化タンパク質が等電沈澱による該水溶液からの単離に抵抗するもの である請求項9の方法。 11.該アシル化タンパク質が脂肪酸アシル化プロインスリン、脂肪酸アシル化 インスリン及び脂肪酸アシル化インスリン類縁体からなる群より選択される請求 項10の方法。 12.水溶液をpH約4.0〜6.0に調節する請求項10の方法。 13.アシル化タンパク質がN-パルミトイルLysB29ヒトインスリンである請求項 12の方法。 14.アルコールが水性混合物の25〜30容量%のアルコール濃度を与える量で添 加されるエタノールである請求項13の方法。 15.(a)アシル化タンパク質の水溶液をそのタンパク質の等電点pH又はその付 近に調節することと、(b)該アシル化タンパク質の水性組成物中のアルコール濃 度を該pHでそのタンパク質の濾過可能な粒子の生成を助長するのに適した濃度に することとを組み合わせ、次いで、その水性タンパク質組成物の濾過及び乾燥に よってその濾過可能な粒子を沈澱タンパク質粉末として回収することにより製造 される粉末アシル化タンパク質。 16.アシル化タンパク質が等電沈澱による水溶液からの単離に抵抗するタンパ ク質を含む請求項15の粉末アシル化タンパク質。 17.該アシル化タンパク質が脂肪酸アシル化プロインスリン、脂肪酸アシル化 インスリン及び脂肪酸アシル化インスリン類縁体からなる群より選択される請求 項16の粉末アシル化タンパク質。 18.水溶液がpH約4.0〜6.0に調節された請求項17の粉末アシル化タンパク質。 19.アルコールがエタノールであり、そのエタノールが水性タンパク質組成物 の25〜30容量%のアルコール濃度を与える量で添加された請求項18のアシル化タ ンパク質。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/484,220 | 1995-06-07 | ||
US08/484,220 US5700904A (en) | 1995-06-07 | 1995-06-07 | Preparation of an acylated protein powder |
PCT/US1996/007963 WO1996040730A1 (en) | 1995-06-07 | 1996-06-04 | Preparation of an acylated protein powder |
Publications (2)
Publication Number | Publication Date |
---|---|
JPH11506738A true JPH11506738A (ja) | 1999-06-15 |
JP3844504B2 JP3844504B2 (ja) | 2006-11-15 |
Family
ID=23923252
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP50083297A Expired - Fee Related JP3844504B2 (ja) | 1995-06-07 | 1996-06-04 | アシル化タンパク質粉末の製造 |
Country Status (21)
Country | Link |
---|---|
US (1) | US5700904A (ja) |
EP (1) | EP0747391B1 (ja) |
JP (1) | JP3844504B2 (ja) |
KR (1) | KR19990022590A (ja) |
CN (1) | CN1192218A (ja) |
AT (1) | ATE263185T1 (ja) |
AU (1) | AU703032B2 (ja) |
BR (1) | BR9608729A (ja) |
CA (1) | CA2223389A1 (ja) |
CZ (1) | CZ388197A3 (ja) |
DE (1) | DE69631996T2 (ja) |
DK (1) | DK0747391T3 (ja) |
EA (1) | EA199800042A1 (ja) |
ES (1) | ES2216039T3 (ja) |
HU (1) | HUP9900877A3 (ja) |
IL (1) | IL122460A0 (ja) |
NO (1) | NO975583D0 (ja) |
NZ (1) | NZ309371A (ja) |
PL (1) | PL323994A1 (ja) |
TR (1) | TR199701528T1 (ja) |
WO (1) | WO1996040730A1 (ja) |
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-
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- 1995-06-07 US US08/484,220 patent/US5700904A/en not_active Expired - Fee Related
-
1996
- 1996-05-31 ES ES96303974T patent/ES2216039T3/es not_active Expired - Lifetime
- 1996-05-31 DE DE69631996T patent/DE69631996T2/de not_active Expired - Fee Related
- 1996-05-31 AT AT96303974T patent/ATE263185T1/de not_active IP Right Cessation
- 1996-05-31 DK DK96303974T patent/DK0747391T3/da active
- 1996-05-31 EP EP96303974A patent/EP0747391B1/en not_active Expired - Lifetime
- 1996-06-04 TR TR97/01528T patent/TR199701528T1/xx unknown
- 1996-06-04 BR BR9608729A patent/BR9608729A/pt not_active Application Discontinuation
- 1996-06-04 AU AU59513/96A patent/AU703032B2/en not_active Ceased
- 1996-06-04 KR KR1019970709071A patent/KR19990022590A/ko not_active Application Discontinuation
- 1996-06-04 CZ CZ973881A patent/CZ388197A3/cs unknown
- 1996-06-04 CN CN96195951A patent/CN1192218A/zh active Pending
- 1996-06-04 NZ NZ309371A patent/NZ309371A/en unknown
- 1996-06-04 WO PCT/US1996/007963 patent/WO1996040730A1/en not_active Application Discontinuation
- 1996-06-04 CA CA002223389A patent/CA2223389A1/en not_active Abandoned
- 1996-06-04 JP JP50083297A patent/JP3844504B2/ja not_active Expired - Fee Related
- 1996-06-04 IL IL12246096A patent/IL122460A0/xx unknown
- 1996-06-04 HU HU9900877A patent/HUP9900877A3/hu unknown
- 1996-06-04 EA EA199800042A patent/EA199800042A1/ru unknown
- 1996-06-04 PL PL96323994A patent/PL323994A1/xx unknown
-
1997
- 1997-12-03 NO NO975583A patent/NO975583D0/no not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
IL122460A0 (en) | 1998-06-15 |
JP3844504B2 (ja) | 2006-11-15 |
TR199701528T1 (xx) | 1998-03-21 |
ATE263185T1 (de) | 2004-04-15 |
CA2223389A1 (en) | 1996-12-19 |
EP0747391A2 (en) | 1996-12-11 |
NO975583L (no) | 1997-12-03 |
CZ388197A3 (cs) | 1998-05-13 |
DE69631996D1 (de) | 2004-05-06 |
NZ309371A (en) | 1999-09-29 |
WO1996040730A1 (en) | 1996-12-19 |
EA199800042A1 (ru) | 1998-08-27 |
DK0747391T3 (da) | 2004-07-19 |
CN1192218A (zh) | 1998-09-02 |
MX9709657A (es) | 1998-07-31 |
ES2216039T3 (es) | 2004-10-16 |
KR19990022590A (ko) | 1999-03-25 |
BR9608729A (pt) | 1999-06-29 |
EP0747391B1 (en) | 2004-03-31 |
HUP9900877A2 (hu) | 1999-07-28 |
EP0747391A3 (en) | 1997-05-21 |
DE69631996T2 (de) | 2005-01-27 |
US5700904A (en) | 1997-12-23 |
NO975583D0 (no) | 1997-12-03 |
AU703032B2 (en) | 1999-03-11 |
PL323994A1 (en) | 1998-04-27 |
AU5951396A (en) | 1996-12-30 |
HUP9900877A3 (en) | 1999-11-29 |
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