NO320364B1 - Farmasoytisk akseptabelt, stabilt, frysetorket proteinpreparat og testsettanalysepakke - Google Patents
Farmasoytisk akseptabelt, stabilt, frysetorket proteinpreparat og testsettanalysepakke Download PDFInfo
- Publication number
- NO320364B1 NO320364B1 NO19951724A NO951724A NO320364B1 NO 320364 B1 NO320364 B1 NO 320364B1 NO 19951724 A NO19951724 A NO 19951724A NO 951724 A NO951724 A NO 951724A NO 320364 B1 NO320364 B1 NO 320364B1
- Authority
- NO
- Norway
- Prior art keywords
- freeze
- preparation
- protein
- mannitol
- dried
- Prior art date
Links
- 102000004169 proteins and genes Human genes 0.000 title claims abstract description 51
- 108090000623 proteins and genes Proteins 0.000 title claims abstract description 51
- 238000012360 testing method Methods 0.000 title claims abstract description 5
- 238000002360 preparation method Methods 0.000 title claims description 25
- 238000004458 analytical method Methods 0.000 title claims description 11
- 235000018102 proteins Nutrition 0.000 claims abstract description 50
- 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 abstract description 32
- 229930195725 Mannitol Natural products 0.000 claims abstract description 32
- 235000010355 mannitol Nutrition 0.000 claims abstract description 32
- 239000000594 mannitol Substances 0.000 claims abstract description 32
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims abstract description 26
- 235000004279 alanine Nutrition 0.000 claims abstract description 26
- 239000000872 buffer Substances 0.000 claims abstract description 9
- 108010092464 Urate Oxidase Proteins 0.000 claims description 18
- 229940005267 urate oxidase Drugs 0.000 claims description 18
- 102000004190 Enzymes Human genes 0.000 claims description 9
- 108090000790 Enzymes Proteins 0.000 claims description 9
- 229940088598 enzyme Drugs 0.000 claims description 9
- 102000003816 Interleukin-13 Human genes 0.000 claims description 5
- 108090000176 Interleukin-13 Proteins 0.000 claims description 5
- 102000004127 Cytokines Human genes 0.000 claims description 4
- 108090000695 Cytokines Proteins 0.000 claims description 4
- 239000008363 phosphate buffer Substances 0.000 claims description 4
- 239000005556 hormone Substances 0.000 claims description 3
- 229940088597 hormone Drugs 0.000 claims description 3
- 241001465754 Metazoa Species 0.000 claims description 2
- 229940102223 injectable solution Drugs 0.000 claims 1
- 239000000243 solution Substances 0.000 description 34
- 102000002265 Human Growth Hormone Human genes 0.000 description 28
- 108010000521 Human Growth Hormone Proteins 0.000 description 28
- 239000000854 Human Growth Hormone Substances 0.000 description 28
- 239000012071 phase Substances 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
- 239000000203 mixture Substances 0.000 description 18
- 230000000694 effects Effects 0.000 description 16
- 238000004108 freeze drying Methods 0.000 description 12
- 239000000546 pharmaceutical excipient Substances 0.000 description 10
- 235000001014 amino acid Nutrition 0.000 description 9
- 150000001413 amino acids Chemical class 0.000 description 9
- 230000008014 freezing Effects 0.000 description 8
- 238000007710 freezing Methods 0.000 description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 238000002425 crystallisation Methods 0.000 description 6
- 230000008025 crystallization Effects 0.000 description 6
- 230000002255 enzymatic effect Effects 0.000 description 6
- 238000000034 method Methods 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 229920005862 polyol Polymers 0.000 description 5
- 150000003077 polyols Chemical class 0.000 description 5
- 102000004196 processed proteins & peptides Human genes 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- 239000000539 dimer Substances 0.000 description 4
- 230000009477 glass transition Effects 0.000 description 4
- 229920001184 polypeptide Polymers 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 238000000859 sublimation Methods 0.000 description 4
- 230000008022 sublimation Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 230000002195 synergetic effect Effects 0.000 description 4
- 239000008215 water for injection Substances 0.000 description 4
- 239000004471 Glycine Substances 0.000 description 3
- 238000002441 X-ray diffraction Methods 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 239000002577 cryoprotective agent Substances 0.000 description 3
- 238000004455 differential thermal analysis Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 230000006641 stabilisation Effects 0.000 description 3
- 238000011105 stabilization Methods 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 241000228197 Aspergillus flavus Species 0.000 description 2
- 102000000588 Interleukin-2 Human genes 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- 102000004388 Interleukin-4 Human genes 0.000 description 2
- 108090000978 Interleukin-4 Proteins 0.000 description 2
- 102000004889 Interleukin-6 Human genes 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 2
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 2
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 2
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- POJWUDADGALRAB-UHFFFAOYSA-N allantoin Chemical compound NC(=O)NC1NC(=O)NC1=O POJWUDADGALRAB-UHFFFAOYSA-N 0.000 description 2
- LFVGISIMTYGQHF-UHFFFAOYSA-N ammonium dihydrogen phosphate Chemical compound [NH4+].OP(O)([O-])=O LFVGISIMTYGQHF-UHFFFAOYSA-N 0.000 description 2
- 229910000387 ammonium dihydrogen phosphate Inorganic materials 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 230000008094 contradictory effect Effects 0.000 description 2
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 229940028885 interleukin-4 Drugs 0.000 description 2
- 229940100601 interleukin-6 Drugs 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 235000019837 monoammonium phosphate Nutrition 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 238000002798 spectrophotometry method Methods 0.000 description 2
- 230000000087 stabilizing effect Effects 0.000 description 2
- 229960000187 tissue plasminogen activator Drugs 0.000 description 2
- 229940116269 uric acid Drugs 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 102000057234 Acyl transferases Human genes 0.000 description 1
- 108700016155 Acyl transferases Proteins 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- POJWUDADGALRAB-PVQJCKRUSA-N Allantoin Natural products NC(=O)N[C@@H]1NC(=O)NC1=O POJWUDADGALRAB-PVQJCKRUSA-N 0.000 description 1
- 239000004254 Ammonium phosphate Substances 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 239000002028 Biomass Substances 0.000 description 1
- 102000013585 Bombesin Human genes 0.000 description 1
- 108010051479 Bombesin Proteins 0.000 description 1
- 101000904177 Clupea pallasii Gonadoliberin-1 Proteins 0.000 description 1
- 229920002307 Dextran Polymers 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
- 108010051021 Eledoisin Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 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 1
- 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 1
- 102000006771 Gonadotropins Human genes 0.000 description 1
- 108010086677 Gonadotropins Proteins 0.000 description 1
- 102000018997 Growth Hormone Human genes 0.000 description 1
- 108010051696 Growth Hormone Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 201000001431 Hyperuricemia Diseases 0.000 description 1
- 108060003951 Immunoglobulin Proteins 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
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 102000009151 Luteinizing Hormone Human genes 0.000 description 1
- 108010073521 Luteinizing Hormone Proteins 0.000 description 1
- 101710151321 Melanostatin Proteins 0.000 description 1
- 102000010909 Monoamine Oxidase Human genes 0.000 description 1
- 108010062431 Monoamine oxidase Proteins 0.000 description 1
- 102400000097 Neurokinin A Human genes 0.000 description 1
- 101800000399 Neurokinin A Proteins 0.000 description 1
- HEAUFJZALFKPBA-YRVBCFNBSA-N Neurokinin A Chemical compound C([C@@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)C(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC=1NC=NC=1)C(C)O)C1=CC=CC=C1 HEAUFJZALFKPBA-YRVBCFNBSA-N 0.000 description 1
- 102000046798 Neurokinin B Human genes 0.000 description 1
- NHXYSAFTNPANFK-HDMCBQFHSA-N Neurokinin B Chemical compound C([C@@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCSC)NC(=O)[C@@H](N)CC(O)=O)C1=CC=CC=C1 NHXYSAFTNPANFK-HDMCBQFHSA-N 0.000 description 1
- 101800002813 Neurokinin-B Proteins 0.000 description 1
- 102400000064 Neuropeptide Y Human genes 0.000 description 1
- 102400001103 Neurotensin Human genes 0.000 description 1
- 101800001814 Neurotensin Proteins 0.000 description 1
- 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 1
- 108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 1
- 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 description 1
- 101710145796 Staphylokinase Proteins 0.000 description 1
- 108010023197 Streptokinase Proteins 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose 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)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 102000005262 Sulfatase Human genes 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
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 229960000458 allantoin Drugs 0.000 description 1
- 229910000148 ammonium phosphate Inorganic materials 0.000 description 1
- 235000019289 ammonium phosphates Nutrition 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 238000005571 anion exchange chromatography Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- DNDCVAGJPBKION-DOPDSADYSA-N bombesin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC=1NC2=CC=CC=C2C=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1NC(=O)CC1)C(C)C)C1=CN=CN1 DNDCVAGJPBKION-DOPDSADYSA-N 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000002144 chemical decomposition reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000000959 cryoprotective effect Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- MNNHAPBLZZVQHP-UHFFFAOYSA-N diammonium hydrogen phosphate Chemical compound [NH4+].[NH4+].OP([O-])([O-])=O MNNHAPBLZZVQHP-UHFFFAOYSA-N 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- AYLPVIWBPZMVSH-FCKMLYJASA-N eledoisin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H]1NC(=O)CC1)C1=CC=CC=C1 AYLPVIWBPZMVSH-FCKMLYJASA-N 0.000 description 1
- 229950011049 eledoisin Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 description 1
- 239000002622 gonadotropin Substances 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 229940051026 immunotoxin Drugs 0.000 description 1
- 239000002596 immunotoxin Substances 0.000 description 1
- 231100000608 immunotoxin Toxicity 0.000 description 1
- 230000002637 immunotoxin Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229940040129 luteinizing hormone Drugs 0.000 description 1
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 1
- 229940127554 medical product Drugs 0.000 description 1
- 229940100630 metacresol Drugs 0.000 description 1
- CWWARWOPSKGELM-SARDKLJWSA-N methyl (2s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s)-2-[[(2s)-5-amino-2-[[(2s)-5-amino-2-[[(2s)-1-[(2s)-6-amino-2-[[(2s)-1-[(2s)-2-amino-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-5 Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)OC)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 CWWARWOPSKGELM-SARDKLJWSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- PCJGZPGTCUMMOT-ISULXFBGSA-N neurotensin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 PCJGZPGTCUMMOT-ISULXFBGSA-N 0.000 description 1
- URPYMXQQVHTUDU-OFGSCBOVSA-N nucleopeptide y Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 URPYMXQQVHTUDU-OFGSCBOVSA-N 0.000 description 1
- 230000010494 opalescence Effects 0.000 description 1
- 230000010363 phase shift Effects 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 239000005297 pyrex Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 108010073863 saruplase Proteins 0.000 description 1
- 238000003998 size exclusion chromatography high performance liquid chromatography Methods 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 229960004532 somatropin Drugs 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 229960005202 streptokinase Drugs 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 108060007951 sulfatase Proteins 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 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
-
- 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
- A61K47/26—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
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S435/00—Chemistry: molecular biology and microbiology
- Y10S435/81—Packaged device or kit
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth 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)
- Chemical Kinetics & Catalysis (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Dermatology (AREA)
- Immunology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Enzymes And Modification Thereof (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9405486A FR2719479B1 (fr) | 1994-05-04 | 1994-05-04 | Formulation stable lyophilisée comprenant une protéine: kit de dosage. |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO951724D0 NO951724D0 (no) | 1995-05-03 |
| NO951724L NO951724L (no) | 1995-11-06 |
| NO320364B1 true NO320364B1 (no) | 2005-11-28 |
Family
ID=9462880
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19951724A NO320364B1 (no) | 1994-05-04 | 1995-05-03 | Farmasoytisk akseptabelt, stabilt, frysetorket proteinpreparat og testsettanalysepakke |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US5763409A (es) |
| EP (1) | EP0682944B1 (es) |
| JP (1) | JP2948125B2 (es) |
| KR (1) | KR100273053B1 (es) |
| CN (1) | CN1088583C (es) |
| AT (1) | ATE178484T1 (es) |
| AU (1) | AU694763B2 (es) |
| CA (1) | CA2148537C (es) |
| CZ (1) | CZ286195B6 (es) |
| DE (1) | DE69508837T2 (es) |
| DK (1) | DK0682944T3 (es) |
| ES (1) | ES2131781T3 (es) |
| FI (1) | FI117321B (es) |
| FR (1) | FR2719479B1 (es) |
| GR (1) | GR3030146T3 (es) |
| HU (1) | HU220220B (es) |
| IL (1) | IL113578A (es) |
| MX (1) | MX9502034A (es) |
| NO (1) | NO320364B1 (es) |
| NZ (1) | NZ272045A (es) |
| PL (1) | PL179240B1 (es) |
| RU (1) | RU2136306C1 (es) |
| SI (1) | SI0682944T1 (es) |
| TW (1) | TW397687B (es) |
| ZA (1) | ZA953596B (es) |
Families Citing this family (57)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6267958B1 (en) | 1995-07-27 | 2001-07-31 | Genentech, Inc. | Protein formulation |
| CN100360184C (zh) * | 1995-07-27 | 2008-01-09 | 基因技术股份有限公司 | 稳定等渗的冻干蛋白质制剂 |
| US6685940B2 (en) | 1995-07-27 | 2004-02-03 | Genentech, Inc. | Protein formulation |
| DE19539574A1 (de) * | 1995-10-25 | 1997-04-30 | Boehringer Mannheim Gmbh | Zubereitungen und Verfahren zur Stabilisierung biologischer Materialien mittels Trocknungsverfahren ohne Einfrieren |
| FR2740686B1 (fr) | 1995-11-03 | 1998-01-16 | Sanofi Sa | Formulation pharmaceutique lyophilisee stable |
| EP0852951A1 (de) * | 1996-11-19 | 1998-07-15 | Roche Diagnostics GmbH | Stabile lyophilisierte pharmazeutische Zubereitungen von mono- oder polyklonalen Antikörpern |
| FR2768341B1 (fr) * | 1997-09-18 | 2000-04-14 | Lab Francais Du Fractionnement | Composition pharmaceutique placebo lyophilisable destinee a imiter un medicament, notamment a base de proteines ou de polypeptides |
| EP0913178A1 (en) * | 1997-11-03 | 1999-05-06 | Boehringer Mannheim Gmbh | Process for the manufacture of dry, amorphous products comprising biologically active material by means of convection drying and products obtainable by the process |
| EP0913177A1 (de) * | 1997-11-03 | 1999-05-06 | Roche Diagnostics GmbH | Verfahren zur Herstellung trockener, amorpher Produkte enthaltend biologisch aktive Materialien mittels Konvektionstrocknung, insbesondere Sprühtrocknung |
| AU2945199A (en) * | 1998-03-18 | 1999-10-11 | Ronai, Peter | Amorphous glasses for stabilising sensitive products |
| JP5149470B2 (ja) | 1999-02-22 | 2013-02-20 | バクスター・インターナショナル・インコーポレイテッド | 新規のアルブミンを含有していない第ｖｉｉｉ因子処方物 |
| DE10085144T1 (de) * | 1999-10-28 | 2003-04-24 | Inst Neftechimicheskogo Sintez | Polypeptidkomposition |
| US6653062B1 (en) | 2000-07-26 | 2003-11-25 | Wisconsin Alumni Research Foundation | Preservation and storage medium for biological materials |
| JP4129178B2 (ja) | 2000-11-07 | 2008-08-06 | ノバルティス バクシンズ アンド ダイアグノスティックス，インコーポレーテッド | 安定化されたインターフェロン組成物 |
| US6887462B2 (en) * | 2001-04-09 | 2005-05-03 | Chiron Corporation | HSA-free formulations of interferon-beta |
| WO2003035030A1 (en) * | 2001-10-24 | 2003-05-01 | Pari Gmbh | Kit for the preparation of a pharmaceutical composition |
| EP2260942A3 (en) | 2002-05-13 | 2011-03-09 | Becton, Dickinson and Company | Protease Inhibitor Sample Collection System |
| US6803046B2 (en) * | 2002-08-16 | 2004-10-12 | Bracco International B.V. | Sincalide formulations |
| JP2008500942A (ja) * | 2003-01-08 | 2008-01-17 | カイロン コーポレイション | 組織因子経路インヒビターまたは組織因子経路インヒビター改変体を含有する安定化凍結乾燥組成物 |
| GB0304636D0 (en) * | 2003-02-28 | 2003-04-02 | Britannia Pharmaceuticals Ltd | Pharmaceutical composition for nasal delivery |
| DE10333317A1 (de) * | 2003-07-22 | 2005-02-17 | Biotecon Therapeutics Gmbh | Formulierung für Proteinarzneimittel ohne Zusatz von humanem Serumalbumin (HSA) |
| GB0404586D0 (en) * | 2004-03-01 | 2004-04-07 | Britannia Pharmaceuticals Ltd | Improvements in or relating to organic materials |
| US11229746B2 (en) | 2006-06-22 | 2022-01-25 | Excelsior Medical Corporation | Antiseptic cap |
| EP2851087B1 (en) | 2006-11-07 | 2017-04-19 | Sanofi Pasteur Biologics, LLC | Stabilization of vaccines by lyophilization |
| US7951368B2 (en) * | 2007-06-25 | 2011-05-31 | Amgen Inc. | Compositions of specific binding agents to hepatocyte growth factor |
| GB0715285D0 (en) * | 2007-08-06 | 2007-09-12 | Britannia Pharmaceuticals Ltd | Improvements in or relating to powdered medicaments for nasal delivery |
| US9078992B2 (en) | 2008-10-27 | 2015-07-14 | Pursuit Vascular, Inc. | Medical device for applying antimicrobial to proximal end of catheter |
| NZ593190A (en) | 2008-11-07 | 2013-01-25 | Baxter Int | Factor viii formulations |
| NZ606283A (en) * | 2008-11-28 | 2014-08-29 | Abbvie Inc | Stable antibody compositions and methods for stabilizing same |
| EP2496246B1 (en) * | 2009-11-03 | 2018-06-27 | Grifols Therapeutics LLC | Composition, method, and kit for alpha-1 proteinase inhibitor |
| EP3257525A3 (en) * | 2009-12-22 | 2018-02-28 | Celldex Therapeutics, Inc. | Vaccine compositions |
| RU2448156C1 (ru) * | 2011-03-17 | 2012-04-20 | Эспосито Трейдинг Лтд | Способ получения лиофилизированной субстанции |
| RU2448158C1 (ru) * | 2011-03-24 | 2012-04-20 | Эспосито Трейдинг Лтд | Способ получения препарата фортелизин, обладающего фибринолитическими свойствами, и его применение для лечения инфаркта миокарда |
| US10166381B2 (en) | 2011-05-23 | 2019-01-01 | Excelsior Medical Corporation | Antiseptic cap |
| WO2013009998A2 (en) | 2011-07-12 | 2013-01-17 | Pursuit Vascular, Inc. | Device for delivery of antimicrobial agent into trans-dermal catheter |
| CN103917643B (zh) * | 2011-11-22 | 2020-06-05 | 西门子医疗保健诊断公司 | 包含用于复原为校准和/或质量控制溶液的干燥试剂的设备，及其生产和使用方法 |
| US20140017318A1 (en) * | 2012-07-10 | 2014-01-16 | Kevin O'Connell | Method to produce a medicinal product comprising a biologically active protein and the resulting product |
| US9314519B2 (en) | 2012-08-21 | 2016-04-19 | Intervet Inc. | Liquid stable virus vaccines |
| US9393298B2 (en) | 2013-03-15 | 2016-07-19 | Intervet Inc. | Liquid stable bovine virus vaccines |
| US9480739B2 (en) | 2013-03-15 | 2016-11-01 | Intervet Inc. | Bovine virus vaccines that are liquid stable |
| AR097762A1 (es) | 2013-09-27 | 2016-04-13 | Intervet Int Bv | Formulaciones secas de vacunas que son estables a temperatura ambiente |
| MX2016003705A (es) | 2013-09-27 | 2016-05-16 | Hanmi Pharm Ind Co Ltd | Formulacion de un conjugado de hormona del crecimiento humana de accion prolongada. |
| AR099470A1 (es) | 2014-02-17 | 2016-07-27 | Intervet Int Bv | Vacunas de virus de aves de corral líquidas |
| TWI670085B (zh) | 2014-02-19 | 2019-09-01 | 荷蘭商英特威國際公司 | 液體穩定之豬病毒疫苗 |
| AU2015252808B2 (en) | 2014-05-02 | 2019-02-21 | Excelsior Medical Corporation | Strip package for antiseptic cap |
| WO2016182822A1 (en) | 2015-05-08 | 2016-11-17 | Icu Medical, Inc. | Medical connectors configured to receive emitters of therapeutic agents |
| ES2671844B1 (es) | 2015-06-11 | 2019-03-22 | Attwill Medical Solutions Inc | Dispositivos médicos, sistemas y métodos que utilizan composiciones de anti-trombina heparina. |
| SI3525865T1 (sl) | 2016-10-14 | 2023-01-31 | Icu Medical, Inc. | Razkuževalni pokrovčki za medicinske konektorje |
| WO2018204206A2 (en) | 2017-05-01 | 2018-11-08 | Icu Medical, Inc. | Medical fluid connectors and methods for providing additives in medical fluid lines |
| US11110063B2 (en) | 2017-08-25 | 2021-09-07 | MAIA Pharmaceuticals, Inc. | Storage stable sincalide formulations |
| US11541221B2 (en) | 2018-11-07 | 2023-01-03 | Icu Medical, Inc. | Tubing set with antimicrobial properties |
| US11400195B2 (en) | 2018-11-07 | 2022-08-02 | Icu Medical, Inc. | Peritoneal dialysis transfer set with antimicrobial properties |
| US11517732B2 (en) | 2018-11-07 | 2022-12-06 | Icu Medical, Inc. | Syringe with antimicrobial properties |
| US11534595B2 (en) | 2018-11-07 | 2022-12-27 | Icu Medical, Inc. | Device for delivering an antimicrobial composition into an infusion device |
| US11541220B2 (en) | 2018-11-07 | 2023-01-03 | Icu Medical, Inc. | Needleless connector with antimicrobial properties |
| JP2022513096A (ja) | 2018-11-21 | 2022-02-07 | アイシーユー・メディカル・インコーポレーテッド | リング及びインサートを有するキャップを備える抗菌装置 |
| AU2021396147A1 (en) | 2020-12-07 | 2023-06-29 | Icu Medical, Inc. | Peritoneal dialysis caps, systems and methods |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5822445B2 (ja) * | 1982-07-08 | 1983-05-09 | 株式会社 ミドリ十字 | 安定な固体の人血漿コリンエステラ−ゼ製剤の製法 |
| US5037644A (en) * | 1986-10-27 | 1991-08-06 | Cetus Corporation | Pharmaceutical compositions of recombinant interleukin-2 and formulation processes |
| US5096885A (en) * | 1988-04-15 | 1992-03-17 | Genentech, Inc. | Human growth hormone formulation |
| JPH0296536A (ja) * | 1988-09-29 | 1990-04-09 | Green Cross Corp:The | プラスミノゲン乾燥製剤 |
| ATE111585T1 (de) * | 1990-01-18 | 1994-09-15 | Cereria Amos Sgarbi Spa | Grablicht. |
| US5192743A (en) * | 1992-01-16 | 1993-03-09 | Genentech, Inc. | Reconstitutable lyophilized protein formulation |
| SE9201073D0 (sv) * | 1992-04-03 | 1992-04-03 | Kabi Pharmacia Ab | Protein formulation |
| DE4239877C1 (de) * | 1992-11-27 | 1994-03-17 | Boehringer Ingelheim Int | Stabilisierte Superoxid-Dismutase (SOD)-Zusammensetzung |
-
1994
- 1994-05-04 FR FR9405486A patent/FR2719479B1/fr not_active Expired - Lifetime
-
1995
- 1995-04-26 CZ CZ19951081A patent/CZ286195B6/cs not_active IP Right Cessation
- 1995-04-28 PL PL95308416A patent/PL179240B1/pl unknown
- 1995-04-28 JP JP7106227A patent/JP2948125B2/ja not_active Expired - Lifetime
- 1995-05-02 ES ES95401012T patent/ES2131781T3/es not_active Expired - Lifetime
- 1995-05-02 EP EP95401012A patent/EP0682944B1/fr not_active Expired - Lifetime
- 1995-05-02 DE DE69508837T patent/DE69508837T2/de not_active Expired - Lifetime
- 1995-05-02 NZ NZ272045A patent/NZ272045A/en not_active IP Right Cessation
- 1995-05-02 MX MX9502034A patent/MX9502034A/es unknown
- 1995-05-02 US US08/432,839 patent/US5763409A/en not_active Expired - Lifetime
- 1995-05-02 SI SI9530241T patent/SI0682944T1/xx unknown
- 1995-05-02 AU AU17774/95A patent/AU694763B2/en not_active Expired
- 1995-05-02 DK DK95401012T patent/DK0682944T3/da active
- 1995-05-02 AT AT95401012T patent/ATE178484T1/de active
- 1995-05-02 IL IL11357895A patent/IL113578A/xx not_active IP Right Cessation
- 1995-05-03 CA CA002148537A patent/CA2148537C/en not_active Expired - Lifetime
- 1995-05-03 NO NO19951724A patent/NO320364B1/no not_active IP Right Cessation
- 1995-05-03 RU RU95107153/14A patent/RU2136306C1/ru active
- 1995-05-03 FI FI952119A patent/FI117321B/fi not_active IP Right Cessation
- 1995-05-03 TW TW084104433A patent/TW397687B/zh not_active IP Right Cessation
- 1995-05-03 HU HU9501276A patent/HU220220B/hu unknown
- 1995-05-04 CN CN95104797A patent/CN1088583C/zh not_active Expired - Lifetime
- 1995-05-04 KR KR1019950011157A patent/KR100273053B1/ko not_active IP Right Cessation
- 1995-05-04 ZA ZA953596A patent/ZA953596B/xx unknown
-
1999
- 1999-05-06 GR GR990401232T patent/GR3030146T3/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO320364B1 (no) | Farmasoytisk akseptabelt, stabilt, frysetorket proteinpreparat og testsettanalysepakke | |
| US7074763B2 (en) | Stable formulations of nerve growth factor | |
| CA2037884C (en) | Stabilized gonadotropin containing preparations | |
| US7244426B2 (en) | Pharmaceutical compositions of fibrinolytic agent | |
| MXPA04004459A (es) | Composiciones liofilizadas de anticuerpo monoclonal. | |
| NO144057B (no) | Fremgangsmaate for aa minske vannbehovet og eliminere utslipp av forurensninger ved behandling av halm med alkali i vannopploesning for aa oeke dens forverdi | |
| AU2002337895A1 (en) | Lyophilized monoclonal antibody compositions | |
| AU2006200638A1 (en) | Pharmaceutical compositions of fibrinolytic agent |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK1K | Patent expired |