CA2346825A1 - Method for production of stroma-free hemoglobin - Google Patents
Method for production of stroma-free hemoglobin Download PDFInfo
- Publication number
- CA2346825A1 CA2346825A1 CA002346825A CA2346825A CA2346825A1 CA 2346825 A1 CA2346825 A1 CA 2346825A1 CA 002346825 A CA002346825 A CA 002346825A CA 2346825 A CA2346825 A CA 2346825A CA 2346825 A1 CA2346825 A1 CA 2346825A1
- Authority
- CA
- Canada
- Prior art keywords
- blood
- stroma
- red
- solution
- centrifuge
- 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.)
- Granted
Links
- 108010001708 stroma free hemoglobin Proteins 0.000 title abstract 2
- 238000004519 manufacturing process Methods 0.000 title 1
- 210000004369 blood Anatomy 0.000 abstract 5
- 239000008280 blood Substances 0.000 abstract 5
- 238000000034 method Methods 0.000 abstract 3
- 108010054147 Hemoglobins Proteins 0.000 abstract 2
- 102000001554 Hemoglobins Human genes 0.000 abstract 2
- 210000003743 erythrocyte Anatomy 0.000 abstract 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 abstract 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract 1
- 210000000601 blood cell Anatomy 0.000 abstract 1
- 239000012503 blood component Substances 0.000 abstract 1
- 239000003633 blood substitute Substances 0.000 abstract 1
- 239000000969 carrier Substances 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 abstract 1
- 210000000170 cell membrane Anatomy 0.000 abstract 1
- 230000001413 cellular effect Effects 0.000 abstract 1
- 239000003153 chemical reaction reagent Substances 0.000 abstract 1
- 239000000306 component Substances 0.000 abstract 1
- 238000001914 filtration Methods 0.000 abstract 1
- 239000012467 final product Substances 0.000 abstract 1
- 238000011065 in-situ storage Methods 0.000 abstract 1
- 230000036512 infertility Effects 0.000 abstract 1
- 238000002955 isolation Methods 0.000 abstract 1
- 239000006166 lysate Substances 0.000 abstract 1
- 229910052760 oxygen Inorganic materials 0.000 abstract 1
- 239000001301 oxygen Substances 0.000 abstract 1
- 239000002994 raw material Substances 0.000 abstract 1
- 230000035939 shock Effects 0.000 abstract 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
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/3693—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits using separation based on different densities of components, e.g. centrifuging
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/3692—Washing or rinsing blood or blood constituents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/3693—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits using separation based on different densities of components, e.g. centrifuging
- A61M1/3696—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits using separation based on different densities of components, e.g. centrifuging with means for adding or withdrawing liquid substances during the centrifugation, e.g. continuous centrifugation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/3693—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits using separation based on different densities of components, e.g. centrifuging
- A61M1/3698—Expressing processed fluid out from the turning rotor using another fluid compressing the treatment chamber; Variable volume rotors
-
- 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
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2202/00—Special media to be introduced, removed or treated
- A61M2202/04—Liquids
- A61M2202/0413—Blood
- A61M2202/0429—Red blood cells; Erythrocytes
- A61M2202/0433—Free haemoglobin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2205/00—General characteristics of the apparatus
- A61M2205/33—Controlling, regulating or measuring
- A61M2205/3306—Optical measuring means
- A61M2205/331—Optical measuring means used as turbidity change detectors, e.g. for priming-blood or plasma-hemoglubine-interface detection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2205/00—General characteristics of the apparatus
- A61M2205/33—Controlling, regulating or measuring
- A61M2205/3317—Electromagnetic, inductive or dielectric measuring means
Landscapes
- Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Hematology (AREA)
- Animal Behavior & Ethology (AREA)
- Anesthesiology (AREA)
- Cardiology (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Biophysics (AREA)
- Diabetes (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Gastroenterology & Hepatology (AREA)
- Molecular Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- External Artificial Organs (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Apparatus For Disinfection Or Sterilisation (AREA)
- Centrifugal Separators (AREA)
Abstract
The method employs a commercially-available blood cell separator comprising a computer-controlled centrifuge (2) having a rotor (24) into which a blood processing bag (6) containing donor blood is placed. Once the blood is collected, the process is performed entirely within the enclosed centrifuge bowl, preferably in situ at the donor collection site. In the first step, the blood is centrifuged to separate the plasma from the cellular components.
After isolation of the red blood cells from other blood components, the red cells are washed with normal saline or other solution. The red blood cells are then lysed by hypotonic shock to separate the red cell membranes (stroma) and the lysate is collected in a sterile container (44), leaving only the stroma in the centrifuge bowl. The final product can be used as raw material for any of the hemoglobin-based oxygen carriers currently being developed as red cell substitutes. All of the steps are performed within a processing container or blood bag (6) in the bowl centrifuge to minimize handling and maintain sterility. A method for preparing a modified hemoglobin solution incorporates the steps for producing stroma-free hemoglobin, then adding pre-measured reagents to react with the solution and filtering the solution.
After isolation of the red blood cells from other blood components, the red cells are washed with normal saline or other solution. The red blood cells are then lysed by hypotonic shock to separate the red cell membranes (stroma) and the lysate is collected in a sterile container (44), leaving only the stroma in the centrifuge bowl. The final product can be used as raw material for any of the hemoglobin-based oxygen carriers currently being developed as red cell substitutes. All of the steps are performed within a processing container or blood bag (6) in the bowl centrifuge to minimize handling and maintain sterility. A method for preparing a modified hemoglobin solution incorporates the steps for producing stroma-free hemoglobin, then adding pre-measured reagents to react with the solution and filtering the solution.
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10431998P | 1998-10-15 | 1998-10-15 | |
US60/104,319 | 1998-10-15 | ||
US12218099P | 1999-03-01 | 1999-03-01 | |
US60/122,180 | 1999-03-01 | ||
PCT/US1999/024149 WO2000021591A1 (en) | 1998-10-15 | 1999-10-15 | Method for production of stroma-free hemoglobin |
Publications (2)
Publication Number | Publication Date |
---|---|
CA2346825A1 true CA2346825A1 (en) | 2000-04-20 |
CA2346825C CA2346825C (en) | 2008-07-29 |
Family
ID=26801402
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002346825A Expired - Fee Related CA2346825C (en) | 1998-10-15 | 1999-10-15 | Method for production of stroma-free hemoglobin |
Country Status (9)
Country | Link |
---|---|
EP (1) | EP1121165A1 (en) |
JP (1) | JP2002527149A (en) |
KR (1) | KR20010099700A (en) |
CN (1) | CN1332646A (en) |
AU (1) | AU771465B2 (en) |
BR (1) | BR9915734A (en) |
CA (1) | CA2346825C (en) |
MX (1) | MXPA01003836A (en) |
WO (1) | WO2000021591A1 (en) |
Families Citing this family (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005099858A1 (en) * | 2004-04-13 | 2005-10-27 | Sangart, Inc. | Methods and compositions for simultaneously isolating hemoglobin from red blood cells and inactivating viruses |
JP2006021121A (en) * | 2004-07-08 | 2006-01-26 | Hitachi Koki Co Ltd | Centrifugal separator |
ITLU20070013A1 (en) * | 2007-06-22 | 2008-12-23 | Kedrion Spa | PROCESS FOR PURIFICATION OF HUMAN APROGENAL HEMOGLOBIN AND INACTIVATED VIRUS. |
EP2433713B1 (en) * | 2007-12-07 | 2017-07-26 | Miltenyi Biotec GmbH | Cell processing systems and methods |
US9493616B2 (en) * | 2010-02-25 | 2016-11-15 | Sangart, Inc. | Methods for preparing PEG-hemoglobin conjugates using reduced reactant ratios |
WO2014070209A1 (en) * | 2012-11-05 | 2014-05-08 | Haemonetics Corporation | System and method for continuous separation of whole blood |
CN103091149B (en) * | 2013-01-10 | 2015-08-05 | 济南金域医学检验中心有限公司 | The preparation method of HE liquid |
EP2961760B1 (en) | 2013-02-26 | 2021-03-24 | EMD Millipore Corporation | Selective removal of a protein from a mixture of proteins using activated carbon by adjusting solution conditions |
EP3131589B1 (en) * | 2014-04-15 | 2023-05-17 | Boehringer Ingelheim International GmbH | Method and use for continuously inactivating a virus during manufacture of a biological product |
WO2019166998A1 (en) * | 2018-03-02 | 2019-09-06 | Thermo Electron Led Gmbh | Single-use centrifuge containers for separating biological suspensions and methods of use |
CN109298171B (en) * | 2018-11-15 | 2022-06-28 | 武汉中生毓晋生物医药有限责任公司 | Method for removing endotoxin in aldehyde red blood cell and application thereof |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4303193A (en) | 1979-01-22 | 1981-12-01 | Haemonetics Corporation | Apparatus for separating blood into components thereof |
US4401652A (en) * | 1980-12-31 | 1983-08-30 | Allied Corporation | Process for the preparation of stroma-free hemoglobin solutions |
US5464814A (en) * | 1986-06-20 | 1995-11-07 | Northfield Laboratories, Inc. | Acellular red blood cell substitute |
CA1312009C (en) | 1986-11-10 | 1992-12-29 | Carl W. Rausch | Extra pure semi-synthetic blood substitute |
JPH02121931A (en) * | 1988-10-29 | 1990-05-09 | Res Inst For Prod Dev | Preparation of concentrated hemoglobin |
US5646252A (en) * | 1992-02-10 | 1997-07-08 | Staat Der Nederlanden, De Minister Van Defensie, Voor Deze: Het Hoofd Van De Afdeling Militair Geneeskundig Beleid | Hemoglobin composition and preparation thereof |
US5676644A (en) | 1995-06-07 | 1997-10-14 | Cobe Laboratories, Inc. | Extracorporeal blood processing methods and apparatus |
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 |
-
1999
- 1999-10-15 EP EP99954950A patent/EP1121165A1/en not_active Withdrawn
- 1999-10-15 BR BR9915734-9A patent/BR9915734A/en not_active IP Right Cessation
- 1999-10-15 JP JP2000575563A patent/JP2002527149A/en not_active Withdrawn
- 1999-10-15 KR KR1020017004781A patent/KR20010099700A/en not_active Application Discontinuation
- 1999-10-15 CA CA002346825A patent/CA2346825C/en not_active Expired - Fee Related
- 1999-10-15 CN CN99813429A patent/CN1332646A/en active Pending
- 1999-10-15 AU AU11170/00A patent/AU771465B2/en not_active Ceased
- 1999-10-15 MX MXPA01003836A patent/MXPA01003836A/en unknown
- 1999-10-15 WO PCT/US1999/024149 patent/WO2000021591A1/en not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
BR9915734A (en) | 2001-10-02 |
MXPA01003836A (en) | 2002-09-18 |
KR20010099700A (en) | 2001-11-09 |
EP1121165A1 (en) | 2001-08-08 |
AU1117000A (en) | 2000-05-01 |
WO2000021591A1 (en) | 2000-04-20 |
AU771465B2 (en) | 2004-03-25 |
JP2002527149A (en) | 2002-08-27 |
CN1332646A (en) | 2002-01-23 |
CA2346825C (en) | 2008-07-29 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
EEER | Examination request | ||
MKLA | Lapsed |