IL99785A - Imidoester cross-linked hemoglobin compositions - Google Patents
Imidoester cross-linked hemoglobin compositionsInfo
- Publication number
- IL99785A IL99785A IL9978591A IL9978591A IL99785A IL 99785 A IL99785 A IL 99785A IL 9978591 A IL9978591 A IL 9978591A IL 9978591 A IL9978591 A IL 9978591A IL 99785 A IL99785 A IL 99785A
- Authority
- IL
- Israel
- Prior art keywords
- hemoglobin
- cross
- linked
- molecular weight
- imidoester
- Prior art date
Links
- 108010054147 Hemoglobins Proteins 0.000 title claims abstract description 282
- 102000001554 Hemoglobins Human genes 0.000 title claims abstract description 282
- 150000002463 imidates Chemical class 0.000 title claims abstract description 34
- 239000000203 mixture Substances 0.000 title claims abstract description 24
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 36
- 239000001301 oxygen Substances 0.000 claims abstract description 36
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 35
- 239000012535 impurity Substances 0.000 claims abstract description 9
- ZLFRJHOBQVVTOJ-UHFFFAOYSA-N dimethyl hexanediimidate Chemical group COC(=N)CCCCC(=N)OC ZLFRJHOBQVVTOJ-UHFFFAOYSA-N 0.000 claims description 48
- 238000004132 cross linking Methods 0.000 claims description 47
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 28
- 238000000034 method Methods 0.000 claims description 26
- 239000011780 sodium chloride Substances 0.000 claims description 15
- 239000000872 buffer Substances 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 239000006166 lysate Substances 0.000 claims description 8
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 238000006116 polymerization reaction Methods 0.000 claims description 6
- FRTGEIHSCHXMTI-UHFFFAOYSA-N dimethyl octanediimidate Chemical compound COC(=N)CCCCCCC(=N)OC FRTGEIHSCHXMTI-UHFFFAOYSA-N 0.000 claims description 5
- 230000007717 exclusion Effects 0.000 claims description 4
- 239000008213 purified water Substances 0.000 claims description 3
- 238000011282 treatment Methods 0.000 claims description 2
- 241000124008 Mammalia Species 0.000 abstract description 8
- 239000012530 fluid Substances 0.000 abstract description 8
- 239000003633 blood substitute Substances 0.000 abstract description 6
- 238000006701 autoxidation reaction Methods 0.000 abstract description 5
- 241000283690 Bos taurus Species 0.000 description 54
- 210000004027 cell Anatomy 0.000 description 31
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 26
- 239000000243 solution Substances 0.000 description 23
- 108010061951 Methemoglobin Proteins 0.000 description 20
- 210000004369 blood Anatomy 0.000 description 17
- 239000008280 blood Substances 0.000 description 17
- 238000006243 chemical reaction Methods 0.000 description 14
- 239000007983 Tris buffer Substances 0.000 description 13
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 13
- 238000005571 anion exchange chromatography Methods 0.000 description 12
- 239000000523 sample Substances 0.000 description 12
- 241000282414 Homo sapiens Species 0.000 description 10
- 210000003743 erythrocyte Anatomy 0.000 description 10
- 238000011534 incubation Methods 0.000 description 10
- 238000000746 purification Methods 0.000 description 10
- INGWEZCOABYORO-UHFFFAOYSA-N 2-(furan-2-yl)-7-methyl-1h-1,8-naphthyridin-4-one Chemical compound N=1C2=NC(C)=CC=C2C(O)=CC=1C1=CC=CO1 INGWEZCOABYORO-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 238000007792 addition Methods 0.000 description 9
- 238000005119 centrifugation Methods 0.000 description 9
- 238000011068 loading method Methods 0.000 description 9
- 235000018102 proteins Nutrition 0.000 description 9
- 102000004169 proteins and genes Human genes 0.000 description 9
- 108090000623 proteins and genes Proteins 0.000 description 9
- 239000001488 sodium phosphate Substances 0.000 description 9
- 229910000162 sodium phosphate Inorganic materials 0.000 description 9
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 9
- 150000001450 anions Chemical class 0.000 description 8
- 238000005277 cation exchange chromatography Methods 0.000 description 8
- 239000002158 endotoxin Substances 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 150000003904 phospholipids Chemical class 0.000 description 8
- 238000003998 size exclusion chromatography high performance liquid chromatography Methods 0.000 description 8
- 241000894007 species Species 0.000 description 8
- 239000003431 cross linking reagent Substances 0.000 description 7
- 239000012528 membrane Substances 0.000 description 7
- 238000000108 ultra-filtration Methods 0.000 description 7
- 241000700605 Viruses Species 0.000 description 6
- 239000000539 dimer Substances 0.000 description 6
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 6
- 238000001471 micro-filtration Methods 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 238000001542 size-exclusion chromatography Methods 0.000 description 6
- 230000003612 virological effect Effects 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- 239000004971 Cross linker Substances 0.000 description 5
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical group [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 5
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 5
- 239000000356 contaminant Substances 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 235000018977 lysine Nutrition 0.000 description 5
- 230000002934 lysing effect Effects 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 102000004506 Blood Proteins Human genes 0.000 description 4
- 108010017384 Blood Proteins Proteins 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- -1 IPO ESTER Chemical class 0.000 description 4
- 239000012564 Q sepharose fast flow resin Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 150000001768 cations Chemical class 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 238000009826 distribution Methods 0.000 description 4
- 238000001802 infusion Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 239000008363 phosphate buffer Substances 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 4
- 229920002684 Sepharose Polymers 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000002939 deleterious effect Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 150000003278 haem Chemical group 0.000 description 3
- 229910052742 iron Inorganic materials 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 238000005498 polishing Methods 0.000 description 3
- 239000002510 pyrogen Substances 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 230000035939 shock Effects 0.000 description 3
- 239000012064 sodium phosphate buffer Substances 0.000 description 3
- 108010001708 stroma free hemoglobin Proteins 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- INEWUCPYEUEQTN-UHFFFAOYSA-N 3-(cyclohexylamino)-2-hydroxy-1-propanesulfonic acid Chemical compound OS(=O)(=O)CC(O)CNC1CCCCC1 INEWUCPYEUEQTN-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 206010029155 Nephropathy toxic Diseases 0.000 description 2
- 239000012614 Q-Sepharose Substances 0.000 description 2
- 108010016797 Sickle Hemoglobin Proteins 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 150000001412 amines Chemical group 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 229940124574 antisickling agent Drugs 0.000 description 2
- 239000003939 antisickling agent Substances 0.000 description 2
- 230000001588 bifunctional effect Effects 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 238000011143 downstream manufacturing Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 230000007694 nephrotoxicity Effects 0.000 description 2
- 231100000417 nephrotoxicity Toxicity 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 210000002381 plasma Anatomy 0.000 description 2
- 239000003058 plasma substitute Substances 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 239000012266 salt solution Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000002798 spectrophotometry method Methods 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 230000006641 stabilisation Effects 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- SGTOKVHOVUZTIK-OWOJBTEDSA-N (e)-4-[(3,5-dibromo-2-hydroxyphenyl)methoxy]-4-oxobut-2-enoic acid Chemical compound OC(=O)\C=C\C(=O)OCC1=CC(Br)=CC(Br)=C1O SGTOKVHOVUZTIK-OWOJBTEDSA-N 0.000 description 1
- IVLXQGJVBGMLRR-UHFFFAOYSA-N 2-aminoacetic acid;hydron;chloride Chemical compound Cl.NCC(O)=O IVLXQGJVBGMLRR-UHFFFAOYSA-N 0.000 description 1
- PMUNIMVZCACZBB-UHFFFAOYSA-N 2-hydroxyethylazanium;chloride Chemical compound Cl.NCCO PMUNIMVZCACZBB-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 235000011470 Adenanthera pavonina Nutrition 0.000 description 1
- 240000001606 Adenanthera pavonina Species 0.000 description 1
- 208000019300 CLIPPERS Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- PJWWRFATQTVXHA-UHFFFAOYSA-N Cyclohexylaminopropanesulfonic acid Chemical compound OS(=O)(=O)CCCNC1CCCCC1 PJWWRFATQTVXHA-UHFFFAOYSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 239000006173 Good's buffer Substances 0.000 description 1
- 108010081925 Hemoglobin Subunits Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- 241000239218 Limulus Species 0.000 description 1
- MKWKNSIESPFAQN-UHFFFAOYSA-N N-cyclohexyl-2-aminoethanesulfonic acid Chemical compound OS(=O)(=O)CCNC1CCCCC1 MKWKNSIESPFAQN-UHFFFAOYSA-N 0.000 description 1
- 229920002302 Nylon 6,6 Polymers 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000012506 Sephacryl® Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 230000003281 allosteric effect Effects 0.000 description 1
- 239000012637 allosteric effector Substances 0.000 description 1
- 150000001409 amidines Chemical class 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 239000003957 anion exchange resin Substances 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000005341 cation exchange Methods 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000010382 chemical cross-linking Methods 0.000 description 1
- 239000012501 chromatography medium Substances 0.000 description 1
- 208000021930 chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids Diseases 0.000 description 1
- 238000002983 circular dichroism Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006392 deoxygenation reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 239000012470 diluted sample Substances 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229960001484 edetic acid Drugs 0.000 description 1
- 108010072542 endotoxin binding proteins Proteins 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical compound FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000001879 gelation Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 102000018146 globin Human genes 0.000 description 1
- 108060003196 globin Proteins 0.000 description 1
- 230000001434 glomerular Effects 0.000 description 1
- ZFGMDIBRIDKWMY-PASTXAENSA-N heparin Chemical compound CC(O)=N[C@@H]1[C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O[C@@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O[C@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@@H](O[C@@H]3[C@@H](OC(O)[C@H](OS(O)(=O)=O)[C@H]3O)C(O)=O)O[C@@H]2O)CS(O)(=O)=O)[C@H](O)[C@H]1O ZFGMDIBRIDKWMY-PASTXAENSA-N 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 238000000703 high-speed centrifugation Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000013627 low molecular weight specie Substances 0.000 description 1
- 238000000464 low-speed centrifugation Methods 0.000 description 1
- 230000010874 maintenance of protein location Effects 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 210000000885 nephron Anatomy 0.000 description 1
- 229940021317 other blood product in atc Drugs 0.000 description 1
- 238000006213 oxygenation reaction Methods 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 230000000379 polymerizing effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 238000011046 pyrogen test Methods 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 230000013878 renal filtration Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 210000005239 tubule Anatomy 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 238000001429 visible spectrum Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/795—Porphyrin- or corrin-ring-containing peptides
- C07K14/805—Haemoglobins; Myoglobins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US61984090A | 1990-11-29 | 1990-11-29 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL99785A0 IL99785A0 (en) | 1992-08-18 |
| IL99785A true IL99785A (en) | 1996-05-14 |
Family
ID=24483529
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL9978591A IL99785A (en) | 1990-11-29 | 1991-10-18 | Imidoester cross-linked hemoglobin compositions |
Country Status (22)
| Country | Link |
|---|---|
| US (2) | US5362855A (pl) |
| EP (1) | EP0559655B1 (pl) |
| JP (1) | JPH06502848A (pl) |
| AT (1) | ATE119917T1 (pl) |
| AU (1) | AU650287B2 (pl) |
| CA (1) | CA2093650A1 (pl) |
| CZ (1) | CZ281912B6 (pl) |
| DE (1) | DE69108258T2 (pl) |
| DK (1) | DK0559655T3 (pl) |
| ES (1) | ES2069908T3 (pl) |
| FI (1) | FI932461A (pl) |
| HU (2) | HUT64571A (pl) |
| IE (1) | IE914144A1 (pl) |
| IL (1) | IL99785A (pl) |
| MX (1) | MX9102239A (pl) |
| NO (1) | NO931956L (pl) |
| NZ (1) | NZ240377A (pl) |
| PL (1) | PL167340B1 (pl) |
| PT (1) | PT99666A (pl) |
| SK (1) | SK54993A3 (pl) |
| WO (1) | WO1992009630A1 (pl) |
| ZA (1) | ZA918348B (pl) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994021682A1 (en) * | 1993-03-16 | 1994-09-29 | Hemosol Inc. | Selective crosslinking of hemoglobins by oxidized, ring-opened saccharides |
| US5631219A (en) * | 1994-03-08 | 1997-05-20 | Somatogen, Inc. | Method of stimulating hematopoiesis with hemoglobin |
| US6242417B1 (en) | 1994-03-08 | 2001-06-05 | Somatogen, Inc. | Stabilized compositions containing hemoglobin |
| DE4418973A1 (de) * | 1994-05-31 | 1995-12-14 | Barnikol Wolfgang | Verfahren zur Herstellung molekular-einheitlicher hyperpolymerer Hämoglobine |
| US6150507A (en) * | 1995-03-23 | 2000-11-21 | Biopure Corporation | Method for producing a purified hemoglobin product |
| US5981716A (en) * | 1995-06-07 | 1999-11-09 | Gruppo Lepettit, S.P.A. | Process for the purification of proteins |
| FR2736930B1 (fr) * | 1995-07-17 | 1997-09-19 | Biocem | Procede de production, par des cellules vegetales, de proteines heminiques, proteines ainsi obtenues et produits contenant ces proteines |
| US5872015A (en) * | 1996-05-10 | 1999-02-16 | Board Of Trustees Of The University Of Illinois | Molecular diversity screening method |
| US7282220B1 (en) | 1996-11-05 | 2007-10-16 | Hsing-Wen Sung | Genipin-crosslinked gelatin microspheres as drug carrier |
| EP0941130B1 (en) * | 1996-11-05 | 2003-03-26 | Challenge Bioproducts Co., Ltd. | Chemical modification of biomedical materials with genipin |
| US6949384B2 (en) * | 2001-12-21 | 2005-09-27 | Spectromedical Inc. | Method for monitoring degradation of Hb-based blood substitutes |
| US7449339B2 (en) * | 1999-11-23 | 2008-11-11 | Nir Diagnostics Inc. | Spectroscopic method and apparatus for total hemoglobin measurement |
| MXPA05007885A (es) * | 2003-01-29 | 2005-09-21 | Northfield Lab | Soluciones de hemoglobina polimerizada que tienen cantidad reducida de tetramero y metodo para prepararlas. |
| US7135554B1 (en) | 2004-01-27 | 2006-11-14 | Biopure Corporation | Method of forming a polymerized hemoglobin solution from stabilized hemoglobin |
| DE102011105525B4 (de) * | 2011-06-24 | 2015-03-26 | Sartorius Stedim Biotech Gmbh | Verfahren zur Abtrennung von Biopolymer-Aggregaten und Viren aus einem Fluid |
| EP3655019A4 (en) | 2017-07-18 | 2021-04-21 | Virtech Bio, Inc. | BLUTER SUBSTITUTES CONTAINING HEMOGLOBIN AND PROCESS FOR THEIR PRODUCTION |
| US20200393472A1 (en) * | 2018-04-18 | 2020-12-17 | Sekisui Medical Co., Ltd. | Haemoglobin analysis method |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3925344A (en) * | 1973-04-11 | 1975-12-09 | Community Blood Council | Plasma protein substitute |
| US4001401A (en) * | 1975-02-02 | 1977-01-04 | Alza Corporation | Blood substitute and blood plasma expander comprising polyhemoglobin |
| US4061736A (en) * | 1975-02-02 | 1977-12-06 | Alza Corporation | Pharmaceutically acceptable intramolecularly cross-linked, stromal-free hemoglobin |
| US4001200A (en) * | 1975-02-27 | 1977-01-04 | Alza Corporation | Novel polymerized, cross-linked, stromal-free hemoglobin |
| US4053590A (en) * | 1975-02-27 | 1977-10-11 | Alza Corporation | Compositions of matter comprising macromolecular hemoglobin |
| DE3144705C2 (de) * | 1981-11-11 | 1983-12-08 | Biotest-Serum-Institut Gmbh, 6000 Frankfurt | Verfahren zur Herstellung eines lagerstabilen, vernetzten Hämoglobinpräparates mit hoher Sauerstoff-Transportkapazität, sowie das nach diesem Verfahren hergestellte Hämoglobinpräparat |
| US4600531A (en) * | 1984-06-27 | 1986-07-15 | University Of Iowa Research Foundation | Production of alpha-alpha cross-linked hemoglobins in high yield |
| US4711852A (en) * | 1984-11-05 | 1987-12-08 | Akzo N.V. | Control for blood gas analyzers and hemoglobin analysis |
| US4826811A (en) * | 1986-06-20 | 1989-05-02 | Northfield Laboratories, Inc. | Acellular red blood cell substitute |
| AU622610B2 (en) * | 1986-11-10 | 1992-04-16 | Biopure Corporation | Extra pure semi-synthetic blood substitute |
| GB8710598D0 (en) * | 1987-05-05 | 1987-06-10 | Star Medical Diagnostics Ltd | Hemoglobin based blood substitute |
| IL87708A (en) * | 1988-09-08 | 1994-04-12 | Technion Inst For Research And | Hemoglobin-based blood substitute possessing a colloid oncotic pressure substantially similar to human blood and method for the preparation thereof |
-
1991
- 1991-10-03 HU HU9301563A patent/HUT64571A/hu unknown
- 1991-10-03 AT AT91917174T patent/ATE119917T1/de not_active IP Right Cessation
- 1991-10-03 DK DK91917174.4T patent/DK0559655T3/da active
- 1991-10-03 SK SK54993A patent/SK54993A3/sk unknown
- 1991-10-03 ES ES91917174T patent/ES2069908T3/es not_active Expired - Lifetime
- 1991-10-03 CZ CZ93854A patent/CZ281912B6/cs unknown
- 1991-10-03 DE DE69108258T patent/DE69108258T2/de not_active Expired - Fee Related
- 1991-10-03 WO PCT/US1991/007155 patent/WO1992009630A1/en active Search and Examination
- 1991-10-03 EP EP91917174A patent/EP0559655B1/en not_active Expired - Lifetime
- 1991-10-03 AU AU85466/91A patent/AU650287B2/en not_active Ceased
- 1991-10-03 JP JP3516187A patent/JPH06502848A/ja active Pending
- 1991-10-03 CA CA002093650A patent/CA2093650A1/en not_active Abandoned
- 1991-10-03 PL PL91299380A patent/PL167340B1/pl unknown
- 1991-10-18 IL IL9978591A patent/IL99785A/en not_active IP Right Cessation
- 1991-10-18 ZA ZA918348A patent/ZA918348B/xx unknown
- 1991-10-29 NZ NZ240377A patent/NZ240377A/xx unknown
- 1991-11-27 MX MX9102239A patent/MX9102239A/es not_active IP Right Cessation
- 1991-11-28 IE IE414491A patent/IE914144A1/en unknown
- 1991-11-29 PT PT99666A patent/PT99666A/pt not_active Application Discontinuation
-
1993
- 1993-05-20 US US08/065,170 patent/US5362855A/en not_active Expired - Fee Related
- 1993-05-28 NO NO93931956A patent/NO931956L/no unknown
- 1993-05-28 FI FI932461A patent/FI932461A/fi unknown
-
1994
- 1994-06-15 US US08/260,173 patent/US5521154A/en not_active Expired - Fee Related
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1995
- 1995-06-30 HU HU95P/P00661P patent/HU211703A9/hu unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DE69108258T2 (de) | 1995-08-10 |
| DE69108258D1 (de) | 1995-04-20 |
| SK54993A3 (en) | 1993-10-06 |
| AU650287B2 (en) | 1994-06-16 |
| FI932461A0 (fi) | 1993-05-28 |
| ES2069908T3 (es) | 1995-05-16 |
| CA2093650A1 (en) | 1992-05-30 |
| US5362855A (en) | 1994-11-08 |
| WO1992009630A1 (en) | 1992-06-11 |
| JPH06502848A (ja) | 1994-03-31 |
| ZA918348B (en) | 1993-04-19 |
| EP0559655B1 (en) | 1995-03-15 |
| US5521154A (en) | 1996-05-28 |
| CZ85493A3 (en) | 1994-02-16 |
| ATE119917T1 (de) | 1995-04-15 |
| HU211703A9 (en) | 1995-12-28 |
| HU9301563D0 (en) | 1993-09-28 |
| IL99785A0 (en) | 1992-08-18 |
| NZ240377A (en) | 1993-01-27 |
| DK0559655T3 (da) | 1995-07-24 |
| CZ281912B6 (cs) | 1997-03-12 |
| IE914144A1 (en) | 1992-06-03 |
| FI932461A (fi) | 1993-05-28 |
| EP0559655A1 (en) | 1993-09-15 |
| NO931956D0 (no) | 1993-05-28 |
| MX9102239A (es) | 1992-07-08 |
| PL167340B1 (pl) | 1995-08-31 |
| NO931956L (no) | 1993-05-28 |
| PT99666A (pt) | 1992-10-30 |
| HUT64571A (en) | 1994-01-28 |
| AU8546691A (en) | 1992-06-25 |
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