ZA200604657B - A pharmaceutical composition comprising an active principle sulphobetaine - Google Patents

A pharmaceutical composition comprising an active principle sulphobetaine Download PDF

Info

Publication number: ZA200604657B
Authority: ZA; South Africa
Prior art keywords: pharmaceutical composition; ndsb; protein; csf; composition according
Prior art date: 2003-12-23

Application number

ZA200604657A

Other languages

English (en)

Inventor

Menart Viktor

Gaberc Porekar Vladka

Podobnik Barbara

Original Assignee

Lek Pharmaceuticals

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.)

2003-12-23

Filing date

2006-06-07

Publication date

2007-10-31

2006-06-07 Application filed by Lek Pharmaceuticals filed Critical Lek Pharmaceuticals

2007-10-31 Publication of ZA200604657B publication Critical patent/ZA200604657B/en

Links

239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 85
IZWSFJTYBVKZNK-UHFFFAOYSA-O N-dodecyl-N,N-dimethyl-3-ammonio-1-propanesulfonic acid Chemical compound CCCCCCCCCCCC[N+](C)(C)CCCS(O)(=O)=O IZWSFJTYBVKZNK-UHFFFAOYSA-O 0.000 title abstract description 6
239000003599 detergent Substances 0.000 claims abstract description 10
108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 claims description 71
102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 claims description 71
102000004169 proteins and genes Human genes 0.000 claims description 44
108090000623 proteins and genes Proteins 0.000 claims description 44
239000008186 active pharmaceutical agent Substances 0.000 claims description 18
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 16
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 16
239000000600 sorbitol Substances 0.000 claims description 16
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 15
239000000546 pharmaceutical excipient Substances 0.000 claims description 15
238000002360 preparation method Methods 0.000 claims description 15
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 12
238000000034 method Methods 0.000 claims description 10
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 9
239000000203 mixture Substances 0.000 claims description 9
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 8
239000003381 stabilizer Substances 0.000 claims description 8
229920005862 polyol Polymers 0.000 claims description 7
150000003077 polyols Chemical class 0.000 claims description 7
102000004877 Insulin Human genes 0.000 claims description 6
108090001061 Insulin Proteins 0.000 claims description 6
CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 claims description 6
229960000367 inositol Drugs 0.000 claims description 6
229940125396 insulin Drugs 0.000 claims description 6
230000008569 process Effects 0.000 claims description 6
CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 claims description 6
HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 claims description 5
SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 claims description 5
108010025020 Nerve Growth Factor Proteins 0.000 claims description 5
HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 claims description 5
HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 claims description 5
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 5
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
PSBDWGZCVUAZQS-UHFFFAOYSA-N (dimethylsulfonio)acetate Chemical compound C[S+](C)CC([O-])=O PSBDWGZCVUAZQS-UHFFFAOYSA-N 0.000 claims description 4
108090000103 Relaxin Proteins 0.000 claims description 4
102000003743 Relaxin Human genes 0.000 claims description 4
150000003863 ammonium salts Chemical class 0.000 claims description 4
229940117986 sulfobetaine Drugs 0.000 claims description 4
102000007350 Bone Morphogenetic Proteins Human genes 0.000 claims description 3
108010007726 Bone Morphogenetic Proteins Proteins 0.000 claims description 3
102000004127 Cytokines Human genes 0.000 claims description 3
108090000695 Cytokines Proteins 0.000 claims description 3
102000016911 Deoxyribonucleases Human genes 0.000 claims description 3
108010053770 Deoxyribonucleases Proteins 0.000 claims description 3
102000003951 Erythropoietin Human genes 0.000 claims description 3
108090000394 Erythropoietin Proteins 0.000 claims description 3
102000018233 Fibroblast Growth Factor Human genes 0.000 claims description 3
108050007372 Fibroblast Growth Factor Proteins 0.000 claims description 3
108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 claims description 3
102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 claims description 3
108010050904 Interferons Proteins 0.000 claims description 3
102000014150 Interferons Human genes 0.000 claims description 3
102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 claims description 3
108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 claims description 3
PAMIQIKDUOTOBW-UHFFFAOYSA-N N-methylcyclohexylamine Natural products CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 claims description 3
102000015336 Nerve Growth Factor Human genes 0.000 claims description 3
108010038512 Platelet-Derived Growth Factor Proteins 0.000 claims description 3
102000010780 Platelet-Derived Growth Factor Human genes 0.000 claims description 3
102000036693 Thrombopoietin Human genes 0.000 claims description 3
108010041111 Thrombopoietin Proteins 0.000 claims description 3
108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 claims description 3
102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims description 3
108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims description 3
229940112869 bone morphogenetic protein Drugs 0.000 claims description 3
229940105423 erythropoietin Drugs 0.000 claims description 3
229940126864 fibroblast growth factor Drugs 0.000 claims description 3
229940047124 interferons Drugs 0.000 claims description 3
229940053128 nerve growth factor Drugs 0.000 claims description 3
OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 claims description 3
102000005606 Activins Human genes 0.000 claims description 2
108010059616 Activins Proteins 0.000 claims description 2
102000055006 Calcitonin Human genes 0.000 claims description 2
108060001064 Calcitonin Proteins 0.000 claims description 2
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 2
102000009465 Growth Factor Receptors Human genes 0.000 claims description 2
108010009202 Growth Factor Receptors Proteins 0.000 claims description 2
108090000723 Insulin-Like Growth Factor I Proteins 0.000 claims description 2
108010063738 Interleukins Proteins 0.000 claims description 2
102000015696 Interleukins Human genes 0.000 claims description 2
102000004895 Lipoproteins Human genes 0.000 claims description 2
108090001030 Lipoproteins Proteins 0.000 claims description 2
102000009571 Macrophage Inflammatory Proteins Human genes 0.000 claims description 2
108010009474 Macrophage Inflammatory Proteins Proteins 0.000 claims description 2
229930195725 Mannitol Natural products 0.000 claims description 2
102000003729 Neprilysin Human genes 0.000 claims description 2
108090000028 Neprilysin Proteins 0.000 claims description 2
102000007072 Nerve Growth Factors Human genes 0.000 claims description 2
108010076181 Proinsulin Proteins 0.000 claims description 2
102000013275 Somatomedins Human genes 0.000 claims description 2
102000019197 Superoxide Dismutase Human genes 0.000 claims description 2
108010012715 Superoxide dismutase Proteins 0.000 claims description 2
108090000190 Thrombin Proteins 0.000 claims description 2
239000012190 activator Substances 0.000 claims description 2
239000000488 activin Substances 0.000 claims description 2
102000015395 alpha 1-Antitrypsin Human genes 0.000 claims description 2
108010050122 alpha 1-Antitrypsin Proteins 0.000 claims description 2
229940024142 alpha 1-antitrypsin Drugs 0.000 claims description 2
KVAWKSIMYXQBIM-UHFFFAOYSA-N benzyl(dimethyl)azanium;propane-1-sulfonate Chemical compound CCCS([O-])(=O)=O.C[NH+](C)CC1=CC=CC=C1 KVAWKSIMYXQBIM-UHFFFAOYSA-N 0.000 claims description 2
239000003114 blood coagulation factor Substances 0.000 claims description 2
210000000988 bone and bone Anatomy 0.000 claims description 2
239000006172 buffering agent Substances 0.000 claims description 2
BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 claims description 2
229960004015 calcitonin Drugs 0.000 claims description 2
239000000122 growth hormone Substances 0.000 claims description 2
108091008039 hormone receptors Proteins 0.000 claims description 2
239000000893 inhibin Substances 0.000 claims description 2
ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 claims description 2
102000006495 integrins Human genes 0.000 claims description 2
108010044426 integrins Proteins 0.000 claims description 2
229940047122 interleukins Drugs 0.000 claims description 2
239000003446 ligand Substances 0.000 claims description 2
239000000594 mannitol Substances 0.000 claims description 2
235000010355 mannitol Nutrition 0.000 claims description 2
238000002156 mixing Methods 0.000 claims description 2
239000003900 neurotrophic factor Substances 0.000 claims description 2
239000002243 precursor Substances 0.000 claims description 2
108010087851 prorelaxin Proteins 0.000 claims description 2
108020003175 receptors Proteins 0.000 claims description 2
102000005962 receptors Human genes 0.000 claims description 2
229960004072 thrombin Drugs 0.000 claims description 2
VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 claims description 2
108010039209 Blood Coagulation Factors Proteins 0.000 claims 1
102000015081 Blood Coagulation Factors Human genes 0.000 claims 1
102100037840 Dehydrogenase/reductase SDR family member 2, mitochondrial Human genes 0.000 claims 1
101800003838 Epidermal growth factor Proteins 0.000 claims 1
102400001368 Epidermal growth factor Human genes 0.000 claims 1
102000003864 Human Follicle Stimulating Hormone Human genes 0.000 claims 1
108010082302 Human Follicle Stimulating Hormone Proteins 0.000 claims 1
CNXPCGBLGHKAIL-UHFFFAOYSA-N NSDB 211 Chemical class OCC[N+](C)(C)CCCS([O-])(=O)=O CNXPCGBLGHKAIL-UHFFFAOYSA-N 0.000 claims 1
101710188053 Protein D Proteins 0.000 claims 1
101710132893 Resolvase Proteins 0.000 claims 1
102000007562 Serum Albumin Human genes 0.000 claims 1
108010071390 Serum Albumin Proteins 0.000 claims 1
229940019700 blood coagulation factors Drugs 0.000 claims 1
229940116977 epidermal growth factor Drugs 0.000 claims 1
210000002950 fibroblast Anatomy 0.000 claims 1
239000003102 growth factor Substances 0.000 claims 1
239000003002 pH adjusting agent Substances 0.000 claims 1
125000001453 quaternary ammonium group Chemical group 0.000 claims 1
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
238000004458 analytical method Methods 0.000 description 16
238000003998 size exclusion chromatography high performance liquid chromatography Methods 0.000 description 13
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
239000000243 solution Substances 0.000 description 11
230000004071 biological effect Effects 0.000 description 10
239000000872 buffer Substances 0.000 description 10
238000004128 high performance liquid chromatography Methods 0.000 description 10
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
238000000338 in vitro Methods 0.000 description 8
238000004007 reversed phase HPLC Methods 0.000 description 8
239000012141 concentrate Substances 0.000 description 7
239000000539 dimer Substances 0.000 description 7
238000012423 maintenance Methods 0.000 description 7
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
239000013074 reference sample Substances 0.000 description 6
238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 6
238000003860 storage Methods 0.000 description 6
230000001225 therapeutic effect Effects 0.000 description 6
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
239000002253 acid Substances 0.000 description 5
229940024606 amino acid Drugs 0.000 description 5
150000001413 amino acids Chemical class 0.000 description 5
238000001514 detection method Methods 0.000 description 5
201000010099 disease Diseases 0.000 description 5
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
239000012535 impurity Substances 0.000 description 5
238000011282 treatment Methods 0.000 description 5
108010029961 Filgrastim Proteins 0.000 description 4
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
238000002347 injection Methods 0.000 description 4
239000007924 injection Substances 0.000 description 4
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 4
229940029345 neupogen Drugs 0.000 description 4
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 4
229920000053 polysorbate 80 Polymers 0.000 description 4
230000006641 stabilisation Effects 0.000 description 4
239000004094 surface-active agent Substances 0.000 description 4
238000012360 testing method Methods 0.000 description 4
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 3
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
229910019142 PO4 Inorganic materials 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
238000002512 chemotherapy Methods 0.000 description 3
230000000694 effects Effects 0.000 description 3
238000001962 electrophoresis Methods 0.000 description 3
230000002209 hydrophobic effect Effects 0.000 description 3
238000005259 measurement Methods 0.000 description 3
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
239000010452 phosphate Substances 0.000 description 3
230000002265 prevention Effects 0.000 description 3
230000009467 reduction Effects 0.000 description 3
239000000523 sample Substances 0.000 description 3
235000000346 sugar Nutrition 0.000 description 3
150000008163 sugars Chemical class 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
VJXFRTYYDHNNKO-UHFFFAOYSA-N 3-[tert-butyl(dimethyl)azaniumyl]propane-1-sulfonate Chemical class CC(C)(C)[N+](C)(C)CCCS([O-])(=O)=O VJXFRTYYDHNNKO-UHFFFAOYSA-N 0.000 description 2
206010011409 Cross infection Diseases 0.000 description 2
241000588724 Escherichia coli Species 0.000 description 2
108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 2
102100031706 Fibroblast growth factor 1 Human genes 0.000 description 2
102100024785 Fibroblast growth factor 2 Human genes 0.000 description 2
108090000379 Fibroblast growth factor 2 Proteins 0.000 description 2
102000012673 Follicle Stimulating Hormone Human genes 0.000 description 2
108010079345 Follicle Stimulating Hormone Proteins 0.000 description 2
239000007995 HEPES buffer Substances 0.000 description 2
101000746367 Homo sapiens Granulocyte colony-stimulating factor Proteins 0.000 description 2
102000008100 Human Serum Albumin Human genes 0.000 description 2
108091006905 Human Serum Albumin Proteins 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
102000004083 Lymphotoxin-alpha Human genes 0.000 description 2
108090000542 Lymphotoxin-alpha Proteins 0.000 description 2
SEQKRHFRPICQDD-UHFFFAOYSA-N N-tris(hydroxymethyl)methylglycine Chemical compound OCC(CO)(CO)[NH2+]CC([O-])=O SEQKRHFRPICQDD-UHFFFAOYSA-N 0.000 description 2
206010059482 Neutropenic infection Diseases 0.000 description 2
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
239000007983 Tris buffer Substances 0.000 description 2
238000010521 absorption reaction Methods 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
229910000147 aluminium phosphate Inorganic materials 0.000 description 2
239000007853 buffer solution Substances 0.000 description 2
210000004027 cell Anatomy 0.000 description 2
230000008859 change Effects 0.000 description 2
150000001875 compounds Chemical class 0.000 description 2
239000007857 degradation product Substances 0.000 description 2
238000013461 design Methods 0.000 description 2
238000010790 dilution Methods 0.000 description 2
239000012895 dilution Substances 0.000 description 2
239000003814 drug Substances 0.000 description 2
NNCRHRDBFDCWPA-UHFFFAOYSA-N ethyl dimethyl ammonio propane sulfonate Chemical class CC[N+](C)(C)CCCS([O-])(=O)=O NNCRHRDBFDCWPA-UHFFFAOYSA-N 0.000 description 2
230000002349 favourable effect Effects 0.000 description 2
229940028334 follicle stimulating hormone Drugs 0.000 description 2
230000006870 function Effects 0.000 description 2
229940049906 glutamate Drugs 0.000 description 2
229930195712 glutamate Natural products 0.000 description 2
229960002989 glutamic acid Drugs 0.000 description 2
208000015181 infectious disease Diseases 0.000 description 2
239000007788 liquid Substances 0.000 description 2
239000011976 maleic acid Substances 0.000 description 2
208000004235 neutropenia Diseases 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
125000004433 nitrogen atom Chemical group N* 0.000 description 2
238000001139 pH measurement Methods 0.000 description 2
229940124531 pharmaceutical excipient Drugs 0.000 description 2
238000009512 pharmaceutical packaging Methods 0.000 description 2
229920001983 poloxamer Polymers 0.000 description 2
229920000136 polysorbate Polymers 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
239000001267 polyvinylpyrrolidone Substances 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
239000013636 protein dimer Substances 0.000 description 2
229940124272 protein stabilizer Drugs 0.000 description 2
239000011734 sodium Substances 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
239000002904 solvent Substances 0.000 description 2
239000000126 substance Substances 0.000 description 2
238000006467 substitution reaction Methods 0.000 description 2
239000003643 water by type Substances 0.000 description 2
239000008215 water for injection Substances 0.000 description 2
JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical class OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
GOZMBJCYMQQACI-UHFFFAOYSA-N 6,7-dimethyl-3-[[methyl-[2-[methyl-[[1-[3-(trifluoromethyl)phenyl]indol-3-yl]methyl]amino]ethyl]amino]methyl]chromen-4-one;dihydrochloride Chemical compound Cl.Cl.C=1OC2=CC(C)=C(C)C=C2C(=O)C=1CN(C)CCN(C)CC(C1=CC=CC=C11)=CN1C1=CC=CC(C(F)(F)F)=C1 GOZMBJCYMQQACI-UHFFFAOYSA-N 0.000 description 1
102000009027 Albumins Human genes 0.000 description 1
108010088751 Albumins Proteins 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
102000004506 Blood Proteins Human genes 0.000 description 1
108010017384 Blood Proteins Proteins 0.000 description 1
101001135732 Bos taurus Parathyroid hormone Proteins 0.000 description 1
102100031092 C-C motif chemokine 3 Human genes 0.000 description 1
101710155856 C-C motif chemokine 3 Proteins 0.000 description 1
102100022641 Coagulation factor IX Human genes 0.000 description 1
208000028399 Critical Illness Diseases 0.000 description 1
GUBGYTABKSRVRQ-CUHNMECISA-N D-Cellobiose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-CUHNMECISA-N 0.000 description 1
101710101803 DNA-binding protein J Proteins 0.000 description 1
108010076282 Factor IX Proteins 0.000 description 1
108010054218 Factor VIII Proteins 0.000 description 1
102000001690 Factor VIII Human genes 0.000 description 1
108010039471 Fas Ligand Protein Proteins 0.000 description 1
208000002633 Febrile Neutropenia Diseases 0.000 description 1
229940123457 Free radical scavenger Drugs 0.000 description 1
239000006173 Good's buffer Substances 0.000 description 1
108010051696 Growth Hormone Proteins 0.000 description 1
102000018997 Growth Hormone Human genes 0.000 description 1
101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 1
101001076292 Homo sapiens Insulin-like growth factor II Proteins 0.000 description 1
101100369992 Homo sapiens TNFSF10 gene Proteins 0.000 description 1
108010000521 Human Growth Hormone Proteins 0.000 description 1
102000002265 Human Growth Hormone Human genes 0.000 description 1
239000000854 Human Growth Hormone Substances 0.000 description 1
229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
206010020751 Hypersensitivity Diseases 0.000 description 1
102100037852 Insulin-like growth factor I Human genes 0.000 description 1
102100025947 Insulin-like growth factor II Human genes 0.000 description 1
102100026720 Interferon beta Human genes 0.000 description 1
102100037850 Interferon gamma Human genes 0.000 description 1
108090000467 Interferon-beta Proteins 0.000 description 1
108010074328 Interferon-gamma Proteins 0.000 description 1
108010002352 Interleukin-1 Proteins 0.000 description 1
108010002350 Interleukin-2 Proteins 0.000 description 1
108010002386 Interleukin-3 Proteins 0.000 description 1
108090000978 Interleukin-4 Proteins 0.000 description 1
108010002616 Interleukin-5 Proteins 0.000 description 1
AYRXSINWFIIFAE-SCLMCMATSA-N Isomaltose Natural products OC[C@H]1O[C@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)[C@@H](O)[C@@H](O)[C@@H]1O AYRXSINWFIIFAE-SCLMCMATSA-N 0.000 description 1
ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
229920002274 Nalgene Polymers 0.000 description 1
208000012902 Nervous system disease Diseases 0.000 description 1
AYRXSINWFIIFAE-UHFFFAOYSA-N O6-alpha-D-Galactopyranosyl-D-galactose Natural products OCC1OC(OCC(O)C(O)C(O)C(O)C=O)C(O)C(O)C1O AYRXSINWFIIFAE-UHFFFAOYSA-N 0.000 description 1
102000008108 Osteoprotegerin Human genes 0.000 description 1
108010035042 Osteoprotegerin Proteins 0.000 description 1
206010033661 Pancytopenia Diseases 0.000 description 1
102000003982 Parathyroid hormone Human genes 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
229920001213 Polysorbate 20 Polymers 0.000 description 1
239000004372 Polyvinyl alcohol Substances 0.000 description 1
101800004937 Protein C Proteins 0.000 description 1
102000017975 Protein C Human genes 0.000 description 1
MUPFEKGTMRGPLJ-RMMQSMQOSA-N Raffinose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MUPFEKGTMRGPLJ-RMMQSMQOSA-N 0.000 description 1
101800001700 Saposin-D Proteins 0.000 description 1
206010040047 Sepsis Diseases 0.000 description 1
206010040070 Septic Shock Diseases 0.000 description 1
206010040943 Skin Ulcer Diseases 0.000 description 1
108010023197 Streptokinase Proteins 0.000 description 1
UZMAPBJVXOGOFT-UHFFFAOYSA-N Syringetin Natural products COC1=C(O)C(OC)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 UZMAPBJVXOGOFT-UHFFFAOYSA-N 0.000 description 1
239000007994 TES buffer Substances 0.000 description 1
108700012411 TNFSF10 Proteins 0.000 description 1
108010000499 Thromboplastin Proteins 0.000 description 1
102000002262 Thromboplastin Human genes 0.000 description 1
208000007536 Thrombosis Diseases 0.000 description 1
108050006955 Tissue-type plasminogen activator Proteins 0.000 description 1
102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
108010009583 Transforming Growth Factors Proteins 0.000 description 1
102000009618 Transforming Growth Factors Human genes 0.000 description 1
239000007997 Tricine buffer Substances 0.000 description 1
108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
102100040247 Tumor necrosis factor Human genes 0.000 description 1
102100024598 Tumor necrosis factor ligand superfamily member 10 Human genes 0.000 description 1
102100031988 Tumor necrosis factor ligand superfamily member 6 Human genes 0.000 description 1
MUPFEKGTMRGPLJ-UHFFFAOYSA-N UNPD196149 Natural products OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(COC2C(C(O)C(O)C(CO)O2)O)O1 MUPFEKGTMRGPLJ-UHFFFAOYSA-N 0.000 description 1
108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
230000004913 activation Effects 0.000 description 1
239000013543 active substance Substances 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
239000004411 aluminium Substances 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
230000003110 anti-inflammatory effect Effects 0.000 description 1
230000000259 anti-tumor effect Effects 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
230000003078 antioxidant effect Effects 0.000 description 1
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
238000003556 assay Methods 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
230000008901 benefit Effects 0.000 description 1
OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 1
108010006025 bovine growth hormone Proteins 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
230000004663 cell proliferation Effects 0.000 description 1
239000002738 chelating agent Substances 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
208000037976 chronic inflammation Diseases 0.000 description 1
208000037893 chronic inflammatory disorder Diseases 0.000 description 1
238000011109 contamination Methods 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
230000004069 differentiation Effects 0.000 description 1
KCFYHBSOLOXZIF-UHFFFAOYSA-N dihydrochrysin Natural products COC1=C(O)C(OC)=CC(C2OC3=CC(O)=CC(O)=C3C(=O)C2)=C1 KCFYHBSOLOXZIF-UHFFFAOYSA-N 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
230000010437 erythropoiesis Effects 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
230000007717 exclusion Effects 0.000 description 1
229960004222 factor ix Drugs 0.000 description 1
229960000301 factor viii Drugs 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000012634 fragment Substances 0.000 description 1
230000008014 freezing Effects 0.000 description 1
238000007710 freezing Methods 0.000 description 1
108020001507 fusion proteins Proteins 0.000 description 1
102000037865 fusion proteins Human genes 0.000 description 1
DLRVVLDZNNYCBX-CQUJWQHSSA-N gentiobiose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)C(O)O1 DLRVVLDZNNYCBX-CQUJWQHSSA-N 0.000 description 1
210000004602 germ cell Anatomy 0.000 description 1
239000011521 glass Substances 0.000 description 1
150000002314 glycerols Chemical class 0.000 description 1
230000003394 haemopoietic effect Effects 0.000 description 1
210000003958 hematopoietic stem cell Anatomy 0.000 description 1
210000000777 hematopoietic system Anatomy 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
239000001863 hydroxypropyl cellulose Substances 0.000 description 1
235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
210000000987 immune system Anatomy 0.000 description 1
230000006872 improvement Effects 0.000 description 1
239000005414 inactive ingredient Substances 0.000 description 1
238000001802 infusion Methods 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
230000003993 interaction Effects 0.000 description 1
238000002955 isolation Methods 0.000 description 1
DLRVVLDZNNYCBX-RTPHMHGBSA-N isomaltose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)C(O)O1 DLRVVLDZNNYCBX-RTPHMHGBSA-N 0.000 description 1
239000000644 isotonic solution Substances 0.000 description 1
230000003902 lesion Effects 0.000 description 1
210000000265 leukocyte Anatomy 0.000 description 1
239000012160 loading buffer Substances 0.000 description 1
238000011068 loading method Methods 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
239000012528 membrane Substances 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
239000000693 micelle Substances 0.000 description 1
239000000178 monomer Substances 0.000 description 1
XXUPLYBCNPLTIW-UHFFFAOYSA-N octadec-7-ynoic acid Chemical compound CCCCCCCCCCC#CCCCCCC(O)=O XXUPLYBCNPLTIW-UHFFFAOYSA-N 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
238000010979 pH adjustment Methods 0.000 description 1
229960001319 parathyroid hormone Drugs 0.000 description 1
239000000199 parathyroid hormone Substances 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
150000002978 peroxides Chemical class 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
238000002428 photodynamic therapy Methods 0.000 description 1
238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
229940068977 polysorbate 20 Drugs 0.000 description 1
229940068968 polysorbate 80 Drugs 0.000 description 1
229940068965 polysorbates Drugs 0.000 description 1
229920002451 polyvinyl alcohol Polymers 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000035755 proliferation Effects 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
229960000856 protein c Drugs 0.000 description 1
150000003242 quaternary ammonium salts Chemical group 0.000 description 1
239000002516 radical scavenger Substances 0.000 description 1
238000001959 radiotherapy Methods 0.000 description 1
MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 description 1
238000011084 recovery Methods 0.000 description 1
238000004153 renaturation Methods 0.000 description 1
150000003839 salts Chemical class 0.000 description 1
108010073863 saruplase Proteins 0.000 description 1
230000036303 septic shock Effects 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
206010040882 skin lesion Diseases 0.000 description 1
231100000444 skin lesion Toxicity 0.000 description 1
231100000019 skin ulcer Toxicity 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
229910000162 sodium phosphate Inorganic materials 0.000 description 1
ALZJERAWTOKHNO-UHFFFAOYSA-M sodium;dodecyl sulfate;3-morpholin-4-ylpropane-1-sulfonic acid Chemical compound [Na+].OS(=O)(=O)CCCN1CCOCC1.CCCCCCCCCCCCOS([O-])(=O)=O ALZJERAWTOKHNO-UHFFFAOYSA-M 0.000 description 1
238000001179 sorption measurement Methods 0.000 description 1
238000013112 stability test Methods 0.000 description 1
239000007858 starting material Substances 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
229960005202 streptokinase Drugs 0.000 description 1
150000005846 sugar alcohols Polymers 0.000 description 1
229910021653 sulphate ion Inorganic materials 0.000 description 1
-1 sulphate ions Chemical class 0.000 description 1
ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
238000010257 thawing Methods 0.000 description 1
238000002054 transplantation Methods 0.000 description 1
239000013638 trimer Substances 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
229960005356 urokinase Drugs 0.000 description 1
238000002255 vaccination Methods 0.000 description 1
230000003612 virological effect Effects 0.000 description 1
230000000007 visual effect Effects 0.000 description 1
108010047303 von Willebrand Factor Proteins 0.000 description 1
102100036537 von Willebrand factor Human genes 0.000 description 1
229960001134 von willebrand factor Drugs 0.000 description 1
210000005253 yeast cell Anatomy 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
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/193—Colony stimulating factors [CSF]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/186—Quaternary ammonium compounds, e.g. benzalkonium chloride or cetrimide
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin

Landscapes

Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical & Material Sciences (AREA)
Epidemiology (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Engineering & Computer Science (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Immunology (AREA)
Bioinformatics & Cheminformatics (AREA)
Gastroenterology & Hepatology (AREA)
Zoology (AREA)
Dermatology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Oil, Petroleum & Natural Gas (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Medicinal Preparation (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

ZA200604657A 2003-12-23 2006-06-07 A pharmaceutical composition comprising an active principle sulphobetaine ZA200604657B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
SI200300318A SI21639A (sl)	2003-12-23	2003-12-23	Farmacevtski pripravek, ki vsebuje nemicelarne sulfobetaine

Publications (1)

Publication Number	Publication Date
ZA200604657B true ZA200604657B (en)	2007-10-31

Family

ID=34709498

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ZA200604657A ZA200604657B (en)	2003-12-23	2006-06-07	A pharmaceutical composition comprising an active principle sulphobetaine

Country Status (14)

Country	Link
US (1)	US7906109B2 (de)
EP (1)	EP1729794B1 (de)
JP (1)	JP4971798B2 (de)
CN (1)	CN1897967B (de)
AT (1)	ATE400290T1 (de)
AU (1)	AU2004305421B2 (de)
BR (1)	BRPI0417265A (de)
CA (1)	CA2545632C (de)
DE (1)	DE602004014991D1 (de)
ES (1)	ES2308292T3 (de)
RU (1)	RU2380112C2 (de)
SI (2)	SI21639A (de)
WO (1)	WO2005060989A1 (de)
ZA (1)	ZA200604657B (de)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CN101116670B (zh) *	2006-08-01	2010-11-10	广州和竺生物科技有限公司	可提供活性甲基或参与甲基转移的化合物作为制备治疗病毒性疾病的药的应用
AU2007234612B2 (en)	2006-12-14	2013-06-27	Johnson & Johnson Regenerative Therapeutics, Llc	Protein stabilization formulations
US7678764B2 (en)	2007-06-29	2010-03-16	Johnson & Johnson Regenerative Therapeutics, Llc	Protein formulations for use at elevated temperatures
WO2009020744A1 (en)	2007-08-07	2009-02-12	Johnson & Johnson Regenerative Therapeutics, Llc	Protein formulations comprising gdf-5 in aqueous acidic solution
BRPI0911048A2 (pt)	2008-04-14	2015-12-29	Atrm Llc	formulações líquidas tamponadas de gdf-5
RU2435589C2 (ru) *	2009-06-02	2011-12-10	Федеральное государственное учреждение "Государственный научный центр дерматовенерологии и косметологии" Министерства здравоохранения и социального развития Российской Федерации (ФГУ "ГНЦДК Минздравсоцразвития России)	Состав консервирующей добавки к контрольным материалам, используемым при серодиагностике сифилиса
UY34105A (es)	2011-06-03	2012-07-31	Lg Life Sciences Ltd	Formulación líquida estable de etanercept
CA2853112C (en)	2011-10-25	2018-08-21	Onclave Therapeutics Limited	Antibody formulations and methods
GB201315321D0 (en) *	2013-08-28	2013-10-09	Koninklijke Nederlandse Akademie Van Wetenschappen	Transduction Buffer
JPWO2015079977A1 (ja) *	2013-11-26	2017-03-16	シャープ株式会社	抗体分離方法、抗体評価方法、医薬の評価方法、及び、抗体の２次元電気泳動用キット
GB201521101D0 (en)	2015-11-30	2016-01-13	Koninklijke Nederlandse Akademie Van Wetenschappen	Transduction buffer
CN112933039A (zh) *	2019-12-11	2021-06-11	深圳赛保尔生物药业有限公司	一种重组人促红细胞生成素液体制剂

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0086511B1 (de) *	1982-02-03	1986-07-02	THE PROCTER & GAMBLE COMPANY	Sauerstoff-Bleichmittel enthaltende flüssige Detergenszusammensetzungen
WO1988006041A1 (fr) *	1987-02-23	1988-08-25	Shiseido Company Ltd.	Stimulateur d'absorption percutanee et preparation dermatologique pour usage externe
NZ236819A (en) *	1990-02-03	1993-07-27	Max Planck Gesellschaft	Enzymatic cleavage of fusion proteins; fusion proteins; recombinant dna and pharmaceutical compositions
DE4242863A1 (de) *	1992-12-18	1994-06-23	Boehringer Mannheim Gmbh	Stabile lyophilisierte pharmazeutische Zubereitungen von G-CSF
US5550416A (en) *	1995-02-09	1996-08-27	Fanchang; We C.	Control mechanism of revolving speed of an electric tool
DE19549232C2 (de) *	1995-12-20	1998-05-20	Boehringer Mannheim Gmbh	Verwendung von G-CSF in Kombination mit einem Chemotherapeutikum bei der Behandlung von Erkrankungen, die eine periphere Stammzelltransplantation erfordern
AU1528997A (en) *	1996-01-12	1997-08-01	Procter & Gamble Company, The	Disinfecting compositions and processes for disinfecting surfaces
US6103683A (en) *	1996-01-12	2000-08-15	The Procter & Gamble Co.	Disinfecting compositions and processes for disinfecting surfaces
HUP9900960A3 (en) *	1996-02-23	2001-02-28	Procter & Gamble	Disinfecting compositions and method for disinfecting surfaces
SE9801288D0 (sv) *	1998-04-14	1998-04-14	Astra Ab	Vaccine delivery system and metod of production
SI21273A (sl) *	2002-07-31	2004-02-29	LEK farmacevtska dru�ba d.d.	Priprava inkluzijskih teles z visokim deležem pravilno zvitega prekurzorja heterolognega proteina

2003
- 2003-12-23 SI SI200300318A patent/SI21639A/sl not_active IP Right Cessation
2004
- 2004-12-22 BR BRPI0417265-5A patent/BRPI0417265A/pt not_active IP Right Cessation
- 2004-12-22 US US10/583,157 patent/US7906109B2/en not_active Expired - Fee Related
- 2004-12-22 EP EP04809251A patent/EP1729794B1/de not_active Expired - Lifetime
- 2004-12-22 SI SI200430881T patent/SI1729794T1/sl unknown
- 2004-12-22 CA CA2545632A patent/CA2545632C/en not_active Expired - Fee Related
- 2004-12-22 DE DE602004014991T patent/DE602004014991D1/de not_active Expired - Lifetime
- 2004-12-22 AU AU2004305421A patent/AU2004305421B2/en not_active Ceased
- 2004-12-22 AT AT04809251T patent/ATE400290T1/de active
- 2004-12-22 JP JP2006546933A patent/JP4971798B2/ja not_active Expired - Fee Related
- 2004-12-22 ES ES04809251T patent/ES2308292T3/es not_active Expired - Lifetime
- 2004-12-22 WO PCT/SI2004/000043 patent/WO2005060989A1/en not_active Ceased
- 2004-12-22 CN CN200480038901.4A patent/CN1897967B/zh not_active Expired - Fee Related
- 2004-12-22 RU RU2006126784/15A patent/RU2380112C2/ru not_active IP Right Cessation
2006
- 2006-06-07 ZA ZA200604657A patent/ZA200604657B/en unknown

Also Published As

Publication number	Publication date
DE602004014991D1 (de)	2008-08-21
WO2005060989A1 (en)	2005-07-07
US20070184019A1 (en)	2007-08-09
RU2006126784A (ru)	2008-01-27
SI1729794T1 (sl)	2008-12-31
CA2545632A1 (en)	2005-07-07
AU2004305421B2 (en)	2010-07-08
CN1897967A (zh)	2007-01-17
EP1729794B1 (de)	2008-07-09
ES2308292T3 (es)	2008-12-01
ATE400290T1 (de)	2008-07-15
BRPI0417265A (pt)	2007-03-06
RU2380112C2 (ru)	2010-01-27
JP2007516281A (ja)	2007-06-21
US7906109B2 (en)	2011-03-15
AU2004305421A1 (en)	2005-07-07
CA2545632C (en)	2014-10-14
EP1729794A1 (de)	2006-12-13
JP4971798B2 (ja)	2012-07-11
SI21639A (sl)	2005-06-30
CN1897967B (zh)	2010-09-08

Publication	Publication Date	Title
ES2326498T3 (es)	2009-10-13	Formulacion liquida de g-csf.
US8580246B2 (en)	2013-11-12	Surfactant-free stable pharmaceutical composition comprising granulocyte-colony stimulating factor
US20070244299A1 (en)	2007-10-18	Method of Stabilizing Proteins
CA2545632C (en)	2014-10-14	A pharmaceutical composition comprising an active principle and a non-detergent sulphobetaine
KR20070046791A (ko)	2007-05-03	안정성이 증가된 생체분자-함유 제형
CN101657187B (zh)	2012-07-18	稳定的水性g-csf制剂
MXPA06007308A (en)	2006-12-13	A pharmaceutical composition comprising an active principle and sulphobetaine
AU2011268944B2 (en)	2014-05-01	Long-term storage of non-glycosylated recombinant human G-CSF
JPH06247870A (ja)	1994-09-06	インターロイキン−６を含有する医薬製剤
KR101191536B1 (ko)	2012-10-15	안정화된 인터페론 액상 제제
KR20180049887A (ko)	2018-05-14	페길레이션된 에리스로포이에틴을 포함하는 신규한 제제