WO2002067957A1 - Use of defibrinated blood for manufacture of a hemoglobin-based oxygen carrier - Google Patents
Use of defibrinated blood for manufacture of a hemoglobin-based oxygen carrier Download PDFInfo
- Publication number
- WO2002067957A1 WO2002067957A1 PCT/US2002/006719 US0206719W WO02067957A1 WO 2002067957 A1 WO2002067957 A1 WO 2002067957A1 US 0206719 W US0206719 W US 0206719W WO 02067957 A1 WO02067957 A1 WO 02067957A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- hemoglobin
- blood
- whole blood
- solution
- red blood
- Prior art date
Links
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Classifications
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- C12N5/0641—Erythrocytes
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- C12N2509/00—Methods for the dissociation of cells, e.g. specific use of enzymes
-
- 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
- Y10S530/81—Carrier - bound or immobilized peptides or proteins and the preparation thereof, e.g. biological cell or cell fragment as carrier
- Y10S530/812—Peptides or proteins is immobilized on, or in, an organic carrier
-
- 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
Abstract
Description
Claims
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
NZ527882A NZ527882A (en) | 2001-02-28 | 2002-02-28 | Manufacture of a hemoglobin-based oxygen carrier |
AU2002250229A AU2002250229B2 (en) | 2001-02-28 | 2002-02-28 | Manufacture of a hemoglobin-based oxygen carrier |
CA2439123A CA2439123C (en) | 2001-02-28 | 2002-02-28 | Use of defibrinated blood for manufacture of a hemoglobin-based oxygen carrier |
JP2002567323A JP2004535368A (en) | 2001-02-28 | 2002-02-28 | Production of hemoglobin-based oxygen carriers |
EP02719129A EP1443947A1 (en) | 2001-02-28 | 2002-02-28 | Use of defibrinated blood for the manufacture of a hemoglobin-based oxygen carrier |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/795,821 US6518010B2 (en) | 2001-02-28 | 2001-02-28 | Use of defibrinated blood for manufacture of a hemoglobin-based oxygen carrier |
US09/795,821 | 2001-02-28 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2002067957A1 true WO2002067957A1 (en) | 2002-09-06 |
WO2002067957A8 WO2002067957A8 (en) | 2004-07-29 |
Family
ID=25166541
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2002/006719 WO2002067957A1 (en) | 2001-02-28 | 2002-02-28 | Use of defibrinated blood for manufacture of a hemoglobin-based oxygen carrier |
Country Status (8)
Country | Link |
---|---|
US (3) | US6518010B2 (en) |
EP (1) | EP1443947A1 (en) |
JP (1) | JP2004535368A (en) |
CN (1) | CN1269955C (en) |
AU (1) | AU2002250229B2 (en) |
CA (2) | CA2756609C (en) |
NZ (1) | NZ527882A (en) |
WO (1) | WO2002067957A1 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103861161A (en) * | 2012-12-18 | 2014-06-18 | 苏州排头兵药业科技有限公司 | Red blood cell washing device and preparation method for washing red blood cells |
Families Citing this family (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6518010B2 (en) * | 2001-02-28 | 2003-02-11 | Biopure Corporation | Use of defibrinated blood for manufacture of a hemoglobin-based oxygen carrier |
CA2476177C (en) * | 2002-02-28 | 2011-06-14 | Biopure Corporation | Purification of red blood cells by separation and diafiltration |
US7001715B2 (en) * | 2002-02-28 | 2006-02-21 | Biopure Corporation | Purification of red blood cells by separation and diafiltration |
CN1954883B (en) * | 2005-10-28 | 2011-06-15 | 陕西北美基因股份有限公司 | Method for stabilizing hemoglobin oxygen carrier sample |
CN101750244B (en) * | 2008-10-13 | 2014-03-12 | 艾博生物医药(杭州)有限公司 | Method for separating red cells from blood sample and application |
CN103760333B (en) * | 2009-10-13 | 2016-03-16 | 艾博生物医药(杭州)有限公司 | Erythrocytic method and utilization in a kind of separating blood sample |
US11864553B2 (en) * | 2009-10-23 | 2024-01-09 | Fenwal, Inc. | Methods and systems for providing red blood cell products with reduced plasma |
US7989593B1 (en) | 2010-05-27 | 2011-08-02 | Bing Lou Wong | Method for the preparation of a high-temperature stable oxygen-carrier-containing pharmaceutical composition and the use thereof |
WO2013043433A2 (en) * | 2011-09-22 | 2013-03-28 | Fenwal, Inc. | Disposable fluid circuits and methods for cell washing |
US9744498B2 (en) | 2011-03-11 | 2017-08-29 | Fenwal, Inc. | Disposable fluid circuits and methods for cell washing with on-line dilution of cell feed |
US8084581B1 (en) | 2011-04-29 | 2011-12-27 | Bing Lou Wong | Method for removing unmodified hemoglobin from cross-linked hemoglobin solutions including polymeric hemoglobin with a high temperature short time heat treatment apparatus |
EP2550973B1 (en) * | 2011-07-23 | 2013-08-28 | SastoMed GmbH | Wound spray |
US20130052232A1 (en) | 2011-08-31 | 2013-02-28 | Bing Lou Wong | Method for the preparation of a heat stable oxygen carrier-containing composition facilating beta-beta cross-linking |
AU2018304174A1 (en) | 2017-07-18 | 2020-02-06 | VirTech Bio, Inc. | Blood substitutes comprising hemoglobin and methods of making |
DE102018211281A1 (en) * | 2018-07-09 | 2020-01-09 | Robert Bosch Gmbh | Microfluidic device and method for diluting and separating particles of a sample |
WO2021034416A2 (en) | 2019-07-02 | 2021-02-25 | Hbo2 Therapeutics, Llc | Hemoglobin substitute mixtures including reconstituted plasma and platelets and their manufacture and use |
AU2021297879A1 (en) * | 2020-06-23 | 2023-02-09 | VirTech Bio, Inc. | Compositions and methods for treating hemorrhagic shock |
CN113769189B (en) * | 2021-09-02 | 2023-10-27 | 南通大学 | Non-isolated insulin controlled-release drug entrapment equipment and entrapment method |
CN117100905A (en) * | 2023-10-25 | 2023-11-24 | 润方(北京)生物医药研究院有限公司 | Dressing for promoting wound healing |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB824375A (en) * | 1955-12-13 | 1959-11-25 | Solco Basel Ag | Respiration-stimulant substances from blood |
WO1989006538A1 (en) * | 1988-01-13 | 1989-07-27 | Gebro Broschek Kg Pharmazeutische Fabrik | Process for producing a therapeutically active ingredient, in particular for cicatrization or for treatment in geriatry, and a therapeutic preparation containing said active ingredient |
WO1995022605A1 (en) * | 1994-02-22 | 1995-08-24 | Genzyme Corporation | Protein calibrator/control product |
WO1996029346A1 (en) * | 1995-03-23 | 1996-09-26 | Biopure Corporation | Stable polymerized hemoglobin blood-substitute |
Family Cites Families (34)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3973001A (en) * | 1954-04-27 | 1976-08-03 | Solco Basel Ag | Tissue cell stimulating blood extracts |
DE2248475C3 (en) | 1972-10-03 | 1978-09-28 | Biotest-Serum-Institut Gmbh, 6000 Frankfurt | Process for obtaining hepatic-safe, storage-stable and infusable hemoglobin solutions |
SU455738A1 (en) | 1972-12-25 | 1975-01-05 | Институт Экологии Растений И Животных Уральского Научного Центра Ан Ссср | The method of obtaining dry erythrocyte diagnosticum for the detection of species-specific antiglobulins |
US4001200A (en) | 1975-02-27 | 1977-01-04 | Alza Corporation | Novel polymerized, cross-linked, stromal-free hemoglobin |
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 |
US4053590A (en) | 1975-02-27 | 1977-10-11 | Alza Corporation | Compositions of matter comprising macromolecular hemoglobin |
US3991181A (en) | 1975-06-18 | 1976-11-09 | Warner-Lambert Company | Injectable stroma free hemoglobin solution and its method of manufacture |
US4401652A (en) | 1980-12-31 | 1983-08-30 | Allied Corporation | Process for the preparation of stroma-free hemoglobin solutions |
DE3130770C2 (en) | 1981-08-04 | 1986-06-19 | Biotest-Serum-Institut Gmbh, 6000 Frankfurt | Process for obtaining hepatitis-safe, sterile, pyrogen-free and stroma-free hemoglobin solutions |
DE3675588D1 (en) | 1985-06-19 | 1990-12-20 | Ajinomoto Kk | HAEMOGLOBIN TIED TO A POLY (ALKENYLENE OXIDE). |
US5194590A (en) | 1986-06-20 | 1993-03-16 | Northfield Laboratories, Inc. | Acellular red blood cell substitute |
US4826811A (en) | 1986-06-20 | 1989-05-02 | 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 |
US5753616A (en) | 1986-11-10 | 1998-05-19 | Biopure Corporation | Method for producing a stable polymerized hemoglobin blood-substitute |
US5854209A (en) | 1995-03-23 | 1998-12-29 | Biopure Corporation | Method for oxygenating tissue having reduced red blood cell flow |
US5084558A (en) | 1987-10-13 | 1992-01-28 | Biopure Corporation | Extra pure semi-synthetic blood substitute |
WO1988003408A1 (en) | 1986-11-10 | 1988-05-19 | Biopure Corporation | Extra pure semi-synthetic blood substitute |
GB8710598D0 (en) | 1987-05-05 | 1987-06-10 | Star Medical Diagnostics Ltd | Hemoglobin based blood substitute |
US5189146A (en) | 1987-05-05 | 1993-02-23 | Her Majesty The Queen In Right Of Canada, As Represented By The Minister Of National Defence | Pasteurizable, freeze-driable hemoglobin-based blood substitute |
US4861867A (en) | 1988-02-03 | 1989-08-29 | Baxter International, Inc. | Purified hemoglobin solutions and method for making same |
WO1989012456A1 (en) | 1988-06-15 | 1989-12-28 | Baxter International Inc. | Method of purifying cross-linked hemoglobin |
US5045529A (en) | 1989-03-27 | 1991-09-03 | Bionostics, Inc. | Tonometric fluid for blood gas and co-oximetry instruments |
US5439882A (en) | 1989-12-29 | 1995-08-08 | Texas Tech University Health Sciences Center | Blood substitute |
US5296466A (en) | 1992-02-19 | 1994-03-22 | Board Of Regents, The University Of Texas System | Inhibition of nitric oxide-mediated hypotension and septic shock with iron-containing hemoprotein |
US5264555A (en) | 1992-07-14 | 1993-11-23 | Enzon, Inc. | Process for hemoglobin extraction and purification |
WO1994022482A1 (en) | 1993-03-26 | 1994-10-13 | Biorelease Technologies, Inc. | Compositions including heme-containing proteins and methods relating thereto |
US5545328A (en) | 1993-09-21 | 1996-08-13 | Hemosol Inc. | Purification of hemoglobin by displacement chromatography |
US5691452A (en) | 1995-03-23 | 1997-11-25 | Biopure Corporation | Method for preserving a hemoglobin blood substitute |
US6271351B1 (en) | 1995-03-23 | 2001-08-07 | Biopure Corporation | Method for preserving a hemoglobin blood substitute |
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 |
US5808011A (en) | 1996-07-01 | 1998-09-15 | Biopure Corporation | Method for chromatographic removal of prions |
US6518010B2 (en) | 2001-02-28 | 2003-02-11 | Biopure Corporation | Use of defibrinated blood for manufacture of a hemoglobin-based oxygen carrier |
-
2001
- 2001-02-28 US US09/795,821 patent/US6518010B2/en not_active Expired - Lifetime
-
2002
- 2002-02-28 EP EP02719129A patent/EP1443947A1/en not_active Withdrawn
- 2002-02-28 JP JP2002567323A patent/JP2004535368A/en active Pending
- 2002-02-28 WO PCT/US2002/006719 patent/WO2002067957A1/en active IP Right Grant
- 2002-02-28 CN CNB028073584A patent/CN1269955C/en not_active Expired - Fee Related
- 2002-02-28 NZ NZ527882A patent/NZ527882A/en unknown
- 2002-02-28 CA CA2756609A patent/CA2756609C/en not_active Expired - Fee Related
- 2002-02-28 CA CA2439123A patent/CA2439123C/en not_active Expired - Fee Related
- 2002-02-28 AU AU2002250229A patent/AU2002250229B2/en not_active Ceased
- 2002-11-26 US US10/306,819 patent/US6986984B2/en not_active Expired - Fee Related
-
2005
- 2005-11-29 US US11/289,048 patent/US7553613B2/en not_active Expired - Fee Related
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB824375A (en) * | 1955-12-13 | 1959-11-25 | Solco Basel Ag | Respiration-stimulant substances from blood |
WO1989006538A1 (en) * | 1988-01-13 | 1989-07-27 | Gebro Broschek Kg Pharmazeutische Fabrik | Process for producing a therapeutically active ingredient, in particular for cicatrization or for treatment in geriatry, and a therapeutic preparation containing said active ingredient |
WO1995022605A1 (en) * | 1994-02-22 | 1995-08-24 | Genzyme Corporation | Protein calibrator/control product |
WO1996029346A1 (en) * | 1995-03-23 | 1996-09-26 | Biopure Corporation | Stable polymerized hemoglobin blood-substitute |
Non-Patent Citations (4)
Title |
---|
BRITISH JOURNAL OF HAEMATOLOGY. ENGLAND APR 1977, vol. 35, no. 4, April 1977 (1977-04-01), pages 551 - 559, ISSN: 0007-1048 * |
DATABASE MEDLINE April 1977 (1977-04-01), BRAY P J ET AL: "Defibrination of normal human blood in vitro: a method giving a high recovery of untraumatized cells.", XP002203643, Database accession no. NLM871408 * |
KAY H D ET AL: "Rapid recovery of non-hemolyzed serum and untraumatized cells by using a new method of blood defibrination in vitro.", JOURNAL OF IMMUNOLOGICAL METHODS. NETHERLANDS 27 SEP 1986, vol. 92, no. 2, 27 September 1986 (1986-09-27), pages 251 - 260, XP001061451, ISSN: 0022-1759 * |
TOPPING D T ET AL: "EFFECTS OF INSULIN ON THE METABOLISM OF THE ISOLATED WORKING RAT HEART PERFUSED WITH UNDILUTED RAT BLOOD", BIOCHIMICA ET BIOPHYSICA ACTA, vol. 844, no. 2, 1985, pages 113 - 118, XP001083907, ISSN: 0006-3002 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103861161A (en) * | 2012-12-18 | 2014-06-18 | 苏州排头兵药业科技有限公司 | Red blood cell washing device and preparation method for washing red blood cells |
Also Published As
Publication number | Publication date |
---|---|
JP2004535368A (en) | 2004-11-25 |
US20060084137A1 (en) | 2006-04-20 |
WO2002067957A8 (en) | 2004-07-29 |
US7553613B2 (en) | 2009-06-30 |
US6518010B2 (en) | 2003-02-11 |
CA2439123A1 (en) | 2002-09-06 |
NZ527882A (en) | 2006-03-31 |
AU2002250229B2 (en) | 2004-11-25 |
US20020161197A1 (en) | 2002-10-31 |
CN1499978A (en) | 2004-05-26 |
CA2756609C (en) | 2015-06-09 |
US20030113707A1 (en) | 2003-06-19 |
CA2756609A1 (en) | 2002-09-06 |
EP1443947A1 (en) | 2004-08-11 |
US6986984B2 (en) | 2006-01-17 |
CA2439123C (en) | 2012-02-21 |
CN1269955C (en) | 2006-08-16 |
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