JPS6025411B2 - ヘモグロビン溶液の製法 - Google Patents
ヘモグロビン溶液の製法Info
- Publication number
- JPS6025411B2 JPS6025411B2 JP48110633A JP11063373A JPS6025411B2 JP S6025411 B2 JPS6025411 B2 JP S6025411B2 JP 48110633 A JP48110633 A JP 48110633A JP 11063373 A JP11063373 A JP 11063373A JP S6025411 B2 JPS6025411 B2 JP S6025411B2
- Authority
- JP
- Japan
- Prior art keywords
- solution
- red blood
- propiolactone
- hemoglobin
- blood cells
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 102000001554 Hemoglobins Human genes 0.000 title claims description 27
- 108010054147 Hemoglobins Proteins 0.000 title claims description 27
- 238000004519 manufacturing process Methods 0.000 title claims description 11
- 239000000243 solution Substances 0.000 claims description 56
- 210000003743 erythrocyte Anatomy 0.000 claims description 25
- 229960000380 propiolactone Drugs 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 15
- 238000005406 washing Methods 0.000 claims description 10
- VEZXCJBBBCKRPI-UHFFFAOYSA-N beta-propiolactone Chemical compound O=C1CCO1 VEZXCJBBBCKRPI-UHFFFAOYSA-N 0.000 claims description 9
- 239000011347 resin Substances 0.000 claims description 7
- 229920005989 resin Polymers 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims description 6
- 239000012153 distilled water Substances 0.000 claims description 6
- 239000000654 additive Substances 0.000 claims description 5
- 238000005119 centrifugation Methods 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 239000003729 cation exchange resin Substances 0.000 claims description 4
- 230000006641 stabilisation Effects 0.000 claims description 4
- 238000011105 stabilization Methods 0.000 claims description 4
- 239000007858 starting material Substances 0.000 claims description 4
- 239000012670 alkaline solution Substances 0.000 claims description 3
- 239000013592 cell lysate Substances 0.000 claims description 3
- 239000007795 chemical reaction product Substances 0.000 claims description 3
- 230000007935 neutral effect Effects 0.000 claims description 3
- 239000013049 sediment Substances 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 238000011146 sterile filtration Methods 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- 230000001461 cytolytic effect Effects 0.000 claims description 2
- 230000003247 decreasing effect Effects 0.000 claims 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- 239000000047 product Substances 0.000 description 12
- 210000004369 blood Anatomy 0.000 description 11
- 239000008280 blood Substances 0.000 description 11
- 235000017557 sodium bicarbonate Nutrition 0.000 description 9
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
- 235000002639 sodium chloride Nutrition 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 8
- 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 5
- 239000008103 glucose Substances 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 239000001301 oxygen Substances 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 208000006454 hepatitis Diseases 0.000 description 4
- 231100000283 hepatitis Toxicity 0.000 description 4
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 4
- 206010018910 Haemolysis Diseases 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- 239000010425 asbestos Substances 0.000 description 3
- 239000003633 blood substitute Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000008588 hemolysis Effects 0.000 description 3
- 239000003456 ion exchange resin Substances 0.000 description 3
- 229920003303 ion-exchange polymer Polymers 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 229910052895 riebeckite Inorganic materials 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- XOHUEYCVLUUEJJ-UHFFFAOYSA-I 2,3-Diphosphoglycerate Chemical compound [O-]P(=O)([O-])OC(C(=O)[O-])COP([O-])([O-])=O XOHUEYCVLUUEJJ-UHFFFAOYSA-I 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- 241000282887 Suidae Species 0.000 description 2
- 229940081735 acetylcellulose Drugs 0.000 description 2
- 229920002301 cellulose acetate Polymers 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 229960002796 polystyrene sulfonate Drugs 0.000 description 2
- 239000011970 polystyrene sulfonate Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- ZAMLGGRVTAXBHI-UHFFFAOYSA-N 3-(4-bromophenyl)-3-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)NC(CC(O)=O)C1=CC=C(Br)C=C1 ZAMLGGRVTAXBHI-UHFFFAOYSA-N 0.000 description 1
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 1
- KNIUHBNRWZGIQQ-UHFFFAOYSA-N 7-diethoxyphosphinothioyloxy-4-methylchromen-2-one Chemical compound CC1=CC(=O)OC2=CC(OP(=S)(OCC)OCC)=CC=C21 KNIUHBNRWZGIQQ-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- 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 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000269851 Sarda sarda Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 244000144987 brood Species 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000008151 electrolyte solution Substances 0.000 description 1
- 229940021013 electrolyte solution Drugs 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical class FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000002926 oxygen Chemical class 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
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 238000002633 shock therapy Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 229940001496 tribasic sodium phosphate Drugs 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 210000002700 urine Anatomy 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
-
- 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
- Y10S530/00—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof
- Y10S530/827—Proteins from mammals or birds
- Y10S530/829—Blood
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2248475A DE2248475C3 (de) | 1972-10-03 | 1972-10-03 | Verfahren zur Gewinnung von hepatitissicheren, lagerungsstabilen und infundierbaren Hämoglobinlösungen |
| DE2248475.9 | 1972-10-03 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5012223A JPS5012223A (ru) | 1975-02-07 |
| JPS6025411B2 true JPS6025411B2 (ja) | 1985-06-18 |
Family
ID=5858076
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP48110633A Expired JPS6025411B2 (ja) | 1972-10-03 | 1973-10-03 | ヘモグロビン溶液の製法 |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US3864478A (ru) |
| JP (1) | JPS6025411B2 (ru) |
| DE (1) | DE2248475C3 (ru) |
| FR (1) | FR2201102B1 (ru) |
| GB (1) | GB1430217A (ru) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4001200A (en) * | 1975-02-27 | 1977-01-04 | Alza Corporation | Novel polymerized, cross-linked, stromal-free hemoglobin |
| US3991181A (en) * | 1975-06-18 | 1976-11-09 | Warner-Lambert Company | Injectable stroma free hemoglobin solution and its method of manufacture |
| GB1578776A (en) * | 1976-06-10 | 1980-11-12 | Univ Illinois | Hemoglobin liposome and method of making the same |
| US4401652A (en) * | 1980-12-31 | 1983-08-30 | Allied Corporation | Process for the preparation of stroma-free hemoglobin solutions |
| DE3130770C2 (de) * | 1981-08-04 | 1986-06-19 | Biotest-Serum-Institut Gmbh, 6000 Frankfurt | Verfahren zur Gewinnung von hepatitissicheren, sterilen, pyrogenfreien und stromafreien Hämoglobinlösungen |
| DE3225408A1 (de) * | 1982-07-07 | 1984-01-12 | Biotest-Serum-Institut Gmbh, 6000 Frankfurt | Waessrige loesung zum suspendieren und lagern von zellen, insbesondere erythrozyten |
| JPS61501510A (ja) * | 1984-03-23 | 1986-07-24 | バクスタ−、トラベノ−ル、ラボラトリ−ズ、インコ−ポレイテッド | ビ−ルスリスクを減らしたヘモグロビンおよびその製造方法 |
| US5281579A (en) * | 1984-03-23 | 1994-01-25 | Baxter International Inc. | Purified virus-free hemoglobin solutions and method for making same |
| DE3412144A1 (de) * | 1984-03-31 | 1985-10-10 | Biotest Pharma GmbH, 6000 Frankfurt | Verfahren zur herstellung hochgereinigter, stromafreier, hepatitissicherer human- und tierhaemoglobinloesungen |
| US4908350A (en) * | 1985-10-31 | 1990-03-13 | The Regents Of The University Of California | Hyperosmotic/hyperoncotic solutions for resuscitation of hypodynamic shock |
| US5955581A (en) * | 1986-11-10 | 1999-09-21 | Biopure Corporation | Method for producing a stable polymerized hemoglobin blood-substitute |
| US5753616A (en) * | 1986-11-10 | 1998-05-19 | Biopure Corporation | Method for producing a stable polymerized hemoglobin blood-substitute |
| US4927806A (en) * | 1987-04-23 | 1990-05-22 | The Regents Of The University Of California | Saturated salt/concentrated dextran formulation to treat hemorrhage |
| US5439882A (en) * | 1989-12-29 | 1995-08-08 | Texas Tech University Health Sciences Center | Blood substitute |
| SE9301188D0 (sv) * | 1993-04-08 | 1993-04-08 | Gramineer Ab | New process |
| US5895810A (en) * | 1995-03-23 | 1999-04-20 | Biopure Corporation | Stable polymerized hemoglobin and use thereof |
| US5691453A (en) * | 1995-06-07 | 1997-11-25 | Biopure Corporation | Separation of polymerized hemoglobin from unpolymerized hemoglobin on hydroxyapatite using HPLC |
| US5741894A (en) * | 1995-09-22 | 1998-04-21 | Baxter International, Inc. | Preparation of pharmaceutical grade hemoglobins by heat treatment in partially oxygenated form |
| US6518010B2 (en) * | 2001-02-28 | 2003-02-11 | Biopure Corporation | Use of defibrinated blood for manufacture of a hemoglobin-based oxygen carrier |
| US7001715B2 (en) * | 2002-02-28 | 2006-02-21 | Biopure Corporation | Purification of red blood cells by separation and diafiltration |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2527210A (en) * | 1944-01-25 | 1950-10-24 | John O Bower | Hemoglobin solution and method |
| US3634290A (en) * | 1969-08-06 | 1972-01-11 | Tipton L Golias | Method of preparing hemolysates for hemoglobin and other types of electrophoresis using chelating agents |
-
1972
- 1972-10-03 DE DE2248475A patent/DE2248475C3/de not_active Expired
-
1973
- 1973-10-02 FR FR7335228A patent/FR2201102B1/fr not_active Expired
- 1973-10-03 JP JP48110633A patent/JPS6025411B2/ja not_active Expired
- 1973-10-03 GB GB4615773A patent/GB1430217A/en not_active Expired
- 1973-10-03 US US403141A patent/US3864478A/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| GB1430217A (en) | 1976-03-31 |
| DE2248475A1 (de) | 1974-04-25 |
| FR2201102B1 (ru) | 1977-01-28 |
| FR2201102A1 (ru) | 1974-04-26 |
| DE2248475B2 (de) | 1978-02-23 |
| JPS5012223A (ru) | 1975-02-07 |
| DE2248475C3 (de) | 1978-09-28 |
| US3864478A (en) | 1975-02-04 |
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