IL87707A - Hemoglobin-based blood substitute substantially similar to human blood and method for preparation thereof - Google Patents

Hemoglobin-based blood substitute substantially similar to human blood and method for preparation thereof

Info

Publication number: IL87707A
Authority: IL; Israel
Prior art keywords: hemoglobin; blood substitute; blood; stroma; based blood
Prior art date: 1988-09-08

Application number

IL8770788A

Other languages

English (en)

Other versions

IL87707A0 (en

Inventor

Ehud Ilan

Noah Lotan

Tova Cohen

Shmuel Sideman

Original Assignee

Technion Inst For Research And

Mini Defence

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.)

1988-09-08

Filing date

1988-09-08

Publication date

1994-06-24

1988-09-08 Application filed by Technion Inst For Research And, Mini Defence filed Critical Technion Inst For Research And

1988-09-08 Priority to IL8770788A priority Critical patent/IL87707A/en

1989-02-28 Publication of IL87707A0 publication Critical patent/IL87707A0/xx

1989-09-07 Priority to JP1230593A priority patent/JPH02115200A/ja

1989-09-08 Priority to AT89309169T priority patent/ATE99950T1/de

1989-09-08 Priority to EP89309169A priority patent/EP0361719B1/fr

1989-09-08 Priority to DE68912259T priority patent/DE68912259T2/de

1994-06-24 Publication of IL87707A publication Critical patent/IL87707A/en

Links

108010054147 Hemoglobins Proteins 0.000 title claims abstract description 69
102000001554 Hemoglobins Human genes 0.000 title claims abstract description 69
239000003633 blood substitute Substances 0.000 title claims abstract description 62
210000004369 blood Anatomy 0.000 title claims abstract description 31
239000008280 blood Substances 0.000 title claims abstract description 31
238000000034 method Methods 0.000 title claims abstract description 29
238000002360 preparation method Methods 0.000 title abstract description 5
238000006116 polymerization reaction Methods 0.000 claims abstract description 25
108010001708 stroma free hemoglobin Proteins 0.000 claims abstract description 24
239000003153 chemical reaction reagent Substances 0.000 claims abstract description 15
229910019142 PO4 Inorganic materials 0.000 claims abstract description 5
239000010452 phosphate Substances 0.000 claims abstract description 5
239000000463 material Substances 0.000 claims description 15
238000006243 chemical reaction Methods 0.000 claims description 14
230000006641 stabilisation Effects 0.000 claims description 7
238000011105 stabilization Methods 0.000 claims description 7
SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 claims description 5
239000003795 chemical substances by application Substances 0.000 claims description 5
150000001412 amines Chemical group 0.000 claims description 4
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 3
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
230000002016 colloidosmotic effect Effects 0.000 claims description 3
210000003743 erythrocyte Anatomy 0.000 claims description 3
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 2
239000004472 Lysine Substances 0.000 claims description 2
150000001298 alcohols Chemical class 0.000 claims description 2
230000000379 polymerizing effect Effects 0.000 claims description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims 2
101100063957 Caenorhabditis elegans doxa-1 gene Proteins 0.000 claims 2
RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical class S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 claims 1
229940031098 ethanolamine Drugs 0.000 claims 1
239000012948 isocyanate Substances 0.000 claims 1
150000002513 isocyanates Chemical class 0.000 claims 1
239000002243 precursor Substances 0.000 claims 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract description 43
239000001301 oxygen Substances 0.000 abstract description 43
229910052760 oxygen Inorganic materials 0.000 abstract description 43
108010061951 Methemoglobin Proteins 0.000 abstract description 4
239000002904 solvent Substances 0.000 abstract description 3
231100000331 toxic Toxicity 0.000 abstract description 3
230000002588 toxic effect Effects 0.000 abstract description 3
239000000243 solution Substances 0.000 description 55
239000000047 product Substances 0.000 description 24
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 15
210000001519 tissue Anatomy 0.000 description 9
NGVDGCNFYWLIFO-UHFFFAOYSA-N pyridoxal 5'-phosphate Chemical compound CC1=NC=C(COP(O)(O)=O)C(C=O)=C1O NGVDGCNFYWLIFO-UHFFFAOYSA-N 0.000 description 7
235000007682 pyridoxal 5'-phosphate Nutrition 0.000 description 7
239000011589 pyridoxal 5'-phosphate Substances 0.000 description 7
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
229910052757 nitrogen Inorganic materials 0.000 description 6
230000005587 bubbling Effects 0.000 description 5
210000003734 kidney Anatomy 0.000 description 5
210000000056 organ Anatomy 0.000 description 5
230000004962 physiological condition Effects 0.000 description 5
229910000033 sodium borohydride Inorganic materials 0.000 description 5
239000012279 sodium borohydride Substances 0.000 description 5
KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 4
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 description 4
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 4
238000013459 approach Methods 0.000 description 4
239000008103 glucose Substances 0.000 description 4
229960000587 glutaral Drugs 0.000 description 4
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
210000004072 lung Anatomy 0.000 description 4
239000000203 mixture Substances 0.000 description 4
238000010791 quenching Methods 0.000 description 4
238000003860 storage Methods 0.000 description 4
206010021138 Hypovolaemic shock Diseases 0.000 description 3
235000010323 ascorbic acid Nutrition 0.000 description 3
229960005070 ascorbic acid Drugs 0.000 description 3
239000011668 ascorbic acid Substances 0.000 description 3
150000001875 compounds Chemical class 0.000 description 3
238000000502 dialysis Methods 0.000 description 3
239000000385 dialysis solution Substances 0.000 description 3
229910001873 dinitrogen Inorganic materials 0.000 description 3
238000002146 exchange transfusion Methods 0.000 description 3
239000012530 fluid Substances 0.000 description 3
-1 heterocyclic triazines Chemical class 0.000 description 3
230000008569 process Effects 0.000 description 3
102000004169 proteins and genes Human genes 0.000 description 3
108090000623 proteins and genes Proteins 0.000 description 3
230000000171 quenching effect Effects 0.000 description 3
230000009467 reduction Effects 0.000 description 3
206010040560 shock Diseases 0.000 description 3
238000011282 treatment Methods 0.000 description 3
WEEMDRWIKYCTQM-UHFFFAOYSA-N 2,6-dimethoxybenzenecarbothioamide Chemical compound COC1=CC=CC(OC)=C1C(N)=S WEEMDRWIKYCTQM-UHFFFAOYSA-N 0.000 description 2
RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 2
229930182566 Gentamicin Natural products 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
241000699670 Mus sp. Species 0.000 description 2
241000283973 Oryctolagus cuniculus Species 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
208000007536 Thrombosis Diseases 0.000 description 2
239000002518 antifoaming agent Substances 0.000 description 2
FCPVYOBCFFNJFS-LQDWTQKMSA-M benzylpenicillin sodium Chemical compound [Na+].N([C@H]1[C@H]2SC([C@@H](N2C1=O)C([O-])=O)(C)C)C(=O)CC1=CC=CC=C1 FCPVYOBCFFNJFS-LQDWTQKMSA-M 0.000 description 2
229910002092 carbon dioxide Inorganic materials 0.000 description 2
210000004027 cell Anatomy 0.000 description 2
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
238000010494 dissociation reaction Methods 0.000 description 2
230000005593 dissociations Effects 0.000 description 2
230000000694 effects Effects 0.000 description 2
230000001747 exhibiting effect Effects 0.000 description 2
239000007789 gas Substances 0.000 description 2
230000036512 infertility Effects 0.000 description 2
238000011835 investigation Methods 0.000 description 2
239000004310 lactic acid Substances 0.000 description 2
235000014655 lactic acid Nutrition 0.000 description 2
230000014759 maintenance of location Effects 0.000 description 2
230000004060 metabolic process Effects 0.000 description 2
230000004048 modification Effects 0.000 description 2
238000012986 modification Methods 0.000 description 2
239000005297 pyrex Substances 0.000 description 2
238000011160 research Methods 0.000 description 2
241000894007 species Species 0.000 description 2
239000007858 starting material Substances 0.000 description 2
229960002385 streptomycin sulfate Drugs 0.000 description 2
238000001356 surgical procedure Methods 0.000 description 2
210000005166 vasculature Anatomy 0.000 description 2
QZCJOXAIQXPLNS-UHFFFAOYSA-N 1,1,2,2,3,3,4,4,4a,5,5,6,6,7,7,8,8,8a-octadecafluoronaphthalene 4-(2-aminoethyl)benzene-1,2-diol Chemical compound NCCc1ccc(O)c(O)c1.FC1(F)C(F)(F)C(F)(F)C2(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C2(F)C1(F)F QZCJOXAIQXPLNS-UHFFFAOYSA-N 0.000 description 1
INZBQWPDNWVYFR-OWOJBTEDSA-N 3,5-dibromo-2-[(e)-4-(2,4-dibromo-6-carboxyphenoxy)-4-oxobut-2-enoyl]oxybenzoic acid Chemical compound OC(=O)C1=CC(Br)=CC(Br)=C1OC(=O)\C=C\C(=O)OC1=C(Br)C=C(Br)C=C1C(O)=O INZBQWPDNWVYFR-OWOJBTEDSA-N 0.000 description 1
MRDWEURGLFYDAO-UHFFFAOYSA-N 3,5-dibromo-2-[4-(2,4-dibromo-6-carboxyphenoxy)-4-oxobutanoyl]oxybenzoic acid Chemical compound OC(=O)C1=CC(Br)=CC(Br)=C1OC(=O)CCC(=O)OC1=C(Br)C=C(Br)C=C1C(O)=O MRDWEURGLFYDAO-UHFFFAOYSA-N 0.000 description 1
WGKPASURHIWGTN-UHFFFAOYSA-N 3,5-dibromo-2-[5-(2,4-dibromo-6-carboxyphenoxy)-5-oxopentanoyl]oxybenzoic acid Chemical compound OC(=O)C1=CC(Br)=CC(Br)=C1OC(=O)CCCC(=O)OC1=C(Br)C=C(Br)C=C1C(O)=O WGKPASURHIWGTN-UHFFFAOYSA-N 0.000 description 1
QFRFWUKCGAEAOD-UHFFFAOYSA-N 3,5-dibromo-2-[6-(2,4-dibromo-6-carboxyphenoxy)-6-oxohexanoyl]oxybenzoic acid Chemical compound OC(=O)C1=CC(Br)=CC(Br)=C1OC(=O)CCCCC(=O)OC1=C(Br)C=C(Br)C=C1C(O)=O QFRFWUKCGAEAOD-UHFFFAOYSA-N 0.000 description 1
208000030507 AIDS Diseases 0.000 description 1
206010067484 Adverse reaction Diseases 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
102000014702 Haptoglobin Human genes 0.000 description 1
108050005077 Haptoglobin Proteins 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
241000699666 Mus <mouse, genus> Species 0.000 description 1
238000011887 Necropsy Methods 0.000 description 1
108010064719 Oxyhemoglobins Proteins 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
FHNINJWBTRXEBC-UHFFFAOYSA-N Sudan III Chemical compound OC1=CC=C2C=CC=CC2=C1N=NC(C=C1)=CC=C1N=NC1=CC=CC=C1 FHNINJWBTRXEBC-UHFFFAOYSA-N 0.000 description 1
QRSFFHRCBYCWBS-UHFFFAOYSA-N [O].[O] Chemical compound [O].[O] QRSFFHRCBYCWBS-UHFFFAOYSA-N 0.000 description 1
230000003187 abdominal effect Effects 0.000 description 1
230000002159 abnormal effect Effects 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
230000002411 adverse Effects 0.000 description 1
230000006838 adverse reaction Effects 0.000 description 1
238000001042 affinity chromatography Methods 0.000 description 1
239000011543 agarose gel Substances 0.000 description 1
150000001299 aldehydes Chemical class 0.000 description 1
230000004075 alteration Effects 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
230000003254 anti-foaming effect Effects 0.000 description 1
210000001367 artery Anatomy 0.000 description 1
230000033228 biological regulation Effects 0.000 description 1
HMVBUCRJXYETAA-OWOJBTEDSA-N bis[(3,5-dibromo-2-hydroxyphenyl)methyl] (e)-but-2-enedioate Chemical compound OC1=C(Br)C=C(Br)C=C1COC(=O)\C=C\C(=O)OCC1=CC(Br)=CC(Br)=C1O HMVBUCRJXYETAA-OWOJBTEDSA-N 0.000 description 1
JAPGYWPTQQJZSJ-OWOJBTEDSA-N bis[(3,5-dichloro-2-hydroxyphenyl)methyl] (e)-but-2-enedioate Chemical compound OC1=C(Cl)C=C(Cl)C=C1COC(=O)\C=C\C(=O)OCC1=CC(Cl)=CC(Cl)=C1O JAPGYWPTQQJZSJ-OWOJBTEDSA-N 0.000 description 1
239000010836 blood and blood product Substances 0.000 description 1
210000000601 blood cell Anatomy 0.000 description 1
229940125691 blood product Drugs 0.000 description 1
239000008366 buffered solution Substances 0.000 description 1
235000013877 carbamide Nutrition 0.000 description 1
239000001569 carbon dioxide Substances 0.000 description 1
238000007675 cardiac surgery Methods 0.000 description 1
230000002490 cerebral effect Effects 0.000 description 1
239000013626 chemical specie Substances 0.000 description 1
235000012000 cholesterol Nutrition 0.000 description 1
230000015271 coagulation Effects 0.000 description 1
238000005345 coagulation Methods 0.000 description 1
238000004132 cross linking Methods 0.000 description 1
239000013078 crystal Substances 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
230000006735 deficit Effects 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
238000010586 diagram Methods 0.000 description 1
150000001991 dicarboxylic acids Chemical class 0.000 description 1
150000002009 diols Chemical class 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
239000012153 distilled water Substances 0.000 description 1
239000003814 drug Substances 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
239000012467 final product Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
238000005187 foaming Methods 0.000 description 1
238000001641 gel filtration chromatography Methods 0.000 description 1
JFCQEDHGNNZCLN-UHFFFAOYSA-N glutaric acid Chemical compound OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
238000001631 haemodialysis Methods 0.000 description 1
210000002216 heart Anatomy 0.000 description 1
230000002489 hematologic effect Effects 0.000 description 1
230000000322 hemodialysis Effects 0.000 description 1
230000001951 hemoperfusion Effects 0.000 description 1
208000006454 hepatitis Diseases 0.000 description 1
231100000283 hepatitis Toxicity 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
210000000987 immune system Anatomy 0.000 description 1
239000011261 inert gas Substances 0.000 description 1
238000001802 infusion Methods 0.000 description 1
208000028867 ischemia Diseases 0.000 description 1
230000000302 ischemic effect Effects 0.000 description 1
230000003907 kidney function Effects 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
201000004792 malaria Diseases 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
239000012528 membrane Substances 0.000 description 1
208000010125 myocardial infarction Diseases 0.000 description 1
239000013618 particulate matter Substances 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
150000003904 phospholipids Chemical class 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
230000037452 priming Effects 0.000 description 1
150000003180 prostaglandins Chemical class 0.000 description 1
239000003223 protective agent Substances 0.000 description 1
238000000746 purification Methods 0.000 description 1
229960001327 pyridoxal phosphate Drugs 0.000 description 1
238000012552 review Methods 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
210000000813 small intestine Anatomy 0.000 description 1
210000002460 smooth muscle Anatomy 0.000 description 1
210000000952 spleen Anatomy 0.000 description 1
230000001954 sterilising effect Effects 0.000 description 1
238000004659 sterilization and disinfection Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
238000012360 testing method Methods 0.000 description 1
TXEYQDLBPFQVAA-UHFFFAOYSA-N tetrafluoromethane Chemical compound FC(F)(F)F TXEYQDLBPFQVAA-UHFFFAOYSA-N 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
231100000820 toxicity test Toxicity 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
238000000108 ultra-filtration Methods 0.000 description 1
150000003672 ureas Chemical class 0.000 description 1
210000003932 urinary bladder Anatomy 0.000 description 1
230000002792 vascular Effects 0.000 description 1
210000003462 vein Anatomy 0.000 description 1
230000035899 viability Effects 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/08—Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
Chemical Kinetics & Catalysis (AREA)
Gastroenterology & Hepatology (AREA)
Hematology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Diabetes (AREA)
Pharmacology & Pharmacy (AREA)
Bioinformatics & Cheminformatics (AREA)
Animal Behavior & Ethology (AREA)
Engineering & Computer Science (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Biochemistry (AREA)
Biophysics (AREA)
Genetics & Genomics (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Medicinal Preparation (AREA)
Peptides Or Proteins (AREA)

IL8770788A 1988-09-08 1988-09-08 Hemoglobin-based blood substitute substantially similar to human blood and method for preparation thereof IL87707A (en)

Priority Applications (5)

Application Number	Priority Date	Filing Date	Title
IL8770788A IL87707A (en)	1988-09-08	1988-09-08	Hemoglobin-based blood substitute substantially similar to human blood and method for preparation thereof
JP1230593A JPH02115200A (ja)	1988-09-08	1989-09-07	ヘモグロビン系血液代用物質およびその調製方法
AT89309169T ATE99950T1 (de)	1988-09-08	1989-09-08	Blutersatzmittel mit haemoglobinen als grundstoff und verfahren zur herstellung.
EP89309169A EP0361719B1 (fr)	1988-09-08	1989-09-08	Substitut du sang à base d'hémoglobine et méthode de préparation
DE68912259T DE68912259T2 (de)	1988-09-08	1989-09-08	Blutersatzmittel mit Hämoglobinen als Grundstoff und Verfahren zur Herstellung.

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
IL8770788A IL87707A (en)	1988-09-08	1988-09-08	Hemoglobin-based blood substitute substantially similar to human blood and method for preparation thereof

Publications (2)

Publication Number	Publication Date
IL87707A0 IL87707A0 (en)	1989-02-28
IL87707A true IL87707A (en)	1994-06-24

Family

ID=11059237

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL8770788A IL87707A (en)	1988-09-08	1988-09-08	Hemoglobin-based blood substitute substantially similar to human blood and method for preparation thereof

Country Status (5)

Country	Link
EP (1)	EP0361719B1 (fr)
JP (1)	JPH02115200A (fr)
AT (1)	ATE99950T1 (fr)
DE (1)	DE68912259T2 (fr)
IL (1)	IL87707A (fr)

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5449759A (en) *	1987-05-16	1995-09-12	Somatogen, Inc.	Hemoglobins with intersubunit desulfide bonds
NL8901174A (nl) *	1989-05-10	1990-12-03	Het Hoofd Van De Afdeling Mili	Hemoglobine-preparaat en gebruik daarvan.
EP0459788A3 (en) *	1990-06-01	1992-01-22	Common Services Agency	Modified proteins and methods of producing same
WO1992003153A1 (fr) *	1990-08-17	1992-03-05	Baxter International Inc.	Composition a base d'hemoglobine-oligomere et procede de preparation
US5248766A (en) *	1990-08-17	1993-09-28	Baxter International Inc.	Oxirane-modified hemoglobin based composition
US5900477A (en) *	1992-01-30	1999-05-04	Baxter International, Inc.	Use of hemoglobin in the treatment of hemorrhagic shock
US5334706A (en) *	1992-01-30	1994-08-02	Baxter International	Administration of low dose hemoglobin to increase perfusion
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US5631219A (en) *	1994-03-08	1997-05-20	Somatogen, Inc.	Method of stimulating hematopoiesis with hemoglobin
US6458762B1 (en)	1994-03-28	2002-10-01	Baxter International, Inc.	Therapeutic use of hemoglobin for preserving tissue viability and reducing restenosis
AU692249B2 (en) *	1994-03-28	1998-06-04	Baxter International Inc.	Therapeutic use of hemoglobin in the treatment of blood vessel blockage
EP0767675A4 (fr) *	1995-04-10	1998-08-05	Baxter Int	Utilisation d'hemoglobine reticulee dans le traitement des hemorragies sous-arachnoidiennes
US5733869A (en) *	1995-10-06	1998-03-31	Baxter International, Inc.	Therapeutic administration of hemoglobin in cardiac arrest
WO1997033914A1 (fr) *	1996-03-15	1997-09-18	Staat Der Nederlanden, De Minister Van Defensie	Procedes de productions de preparations d'hemoglobine et preparations ainsi obtenues
US5814601A (en) *	1997-02-28	1998-09-29	The Regents Of The University Of California	Methods and compositions for optimization of oxygen transport by cell-free systems
ATE302019T1 (de)	1997-02-28	2005-09-15	Univ California	Verfahren und zusammensetzungen zur optimierung des sauerstofftransportes in zellfreien systemen
EP2292657A1 (fr)	1999-11-12	2011-03-09	Baxter Biotech Technology S.A.R.L.	Compositions d'hémoglobine à effets secondaires réduits
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US4584130A (en) *	1985-03-29	1986-04-22	University Of Maryland	Intramolecularly cross-linked hemoglobin and method of preparation
US4826811A (en) *	1986-06-20	1989-05-02	Northfield Laboratories, Inc.	Acellular red blood cell substitute
EP0277289B8 (fr) *	1986-11-10	2003-05-21	Biopure Corporation	Substitut du sang, semi-synthétique, extrêmement pur

1988
- 1988-09-08 IL IL8770788A patent/IL87707A/en not_active IP Right Cessation
1989
- 1989-09-07 JP JP1230593A patent/JPH02115200A/ja active Pending
- 1989-09-08 DE DE68912259T patent/DE68912259T2/de not_active Expired - Fee Related
- 1989-09-08 AT AT89309169T patent/ATE99950T1/de not_active IP Right Cessation
- 1989-09-08 EP EP89309169A patent/EP0361719B1/fr not_active Expired - Lifetime

Also Published As

Publication number	Publication date
JPH02115200A (ja)	1990-04-27
IL87707A0 (en)	1989-02-28
DE68912259T2 (de)	1994-05-26
EP0361719A1 (fr)	1990-04-04
EP0361719B1 (fr)	1994-01-12
DE68912259D1 (de)	1994-02-24
ATE99950T1 (de)	1994-01-15

Legal Events

Date	Code	Title	Description
1999-09-22	RH	Patent void

Publication	Publication Date	Title
EP0361719B1 (fr)	1994-01-12	Substitut du sang à base d'hémoglobine et méthode de préparation
US4529719A (en)	1985-07-16	Modified crosslinked stroma-free tetrameric hemoglobin
IL87708A (en)	1994-04-12	Hemoglobin-based blood substitute possessing a colloid oncotic pressure substantially similar to human blood and method for the preparation thereof
US4826811A (en)	1989-05-02	Acellular red blood cell substitute
CA1273294A (fr)	1990-08-28	Production d'hemoglobines a liaison croisee a-a en grandes quantites
US5194590A (en)	1993-03-16	Acellular red blood cell substitute
CA1056728A (fr)	1979-06-19	Polyhemoglobine
US4598064A (en)	1986-07-01	Alpha-alpha cross-linked hemoglobins
US5464814A (en)	1995-11-07	Acellular red blood cell substitute
USRE34271E (en)	1993-06-01	Production of alpha-alpha cross-linked hemoglobins in high yield
US5248766A (en)	1993-09-28	Oxirane-modified hemoglobin based composition
EP0496866B1 (fr)	1996-07-17	Composition a base d'hemoglobine-oligomere et procede de preparation
IL87706A (en)	1994-04-12	Hemoglobin-based non-pyridoxylated blood substitute and method for the preparation thereof
US5804551A (en)	1998-09-08	Pretraumatic use of hemoglobin
US6046170A (en)	2000-04-04	Therapeutic use of hemoglobin to treat head injury