CA2439123A1 - 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
- CA2439123A1 CA2439123A1 CA002439123A CA2439123A CA2439123A1 CA 2439123 A1 CA2439123 A1 CA 2439123A1 CA 002439123 A CA002439123 A CA 002439123A CA 2439123 A CA2439123 A CA 2439123A CA 2439123 A1 CA2439123 A1 CA 2439123A1
- Authority
- CA
- Canada
- Prior art keywords
- hemoglobin
- whole blood
- blood
- solution
- red blood
- 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
- 210000004369 blood Anatomy 0.000 title claims abstract 42
- 239000008280 blood Substances 0.000 title claims abstract 42
- 108010054147 Hemoglobins Proteins 0.000 title claims abstract 39
- 102000001554 Hemoglobins Human genes 0.000 title claims abstract 39
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 title claims abstract 12
- 239000001301 oxygen Substances 0.000 title claims abstract 12
- 229910052760 oxygen Inorganic materials 0.000 title claims abstract 12
- 238000004519 manufacturing process Methods 0.000 title claims 2
- 210000003743 erythrocyte Anatomy 0.000 claims abstract 24
- 238000011026 diafiltration Methods 0.000 claims abstract 8
- 238000001914 filtration Methods 0.000 claims abstract 5
- 239000000701 coagulant Substances 0.000 claims abstract 3
- 239000000126 substance Substances 0.000 claims abstract 2
- 238000000034 method Methods 0.000 claims 48
- 239000000243 solution Substances 0.000 claims 18
- 108010064719 Oxyhemoglobins Proteins 0.000 claims 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims 4
- 238000004132 cross linking Methods 0.000 claims 4
- 238000007865 diluting Methods 0.000 claims 4
- 230000035699 permeability Effects 0.000 claims 4
- -1 anionic phospholipid Chemical class 0.000 claims 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims 3
- 230000003635 deoxygenating effect Effects 0.000 claims 3
- 239000012510 hollow fiber Substances 0.000 claims 3
- 239000000644 isotonic solution Substances 0.000 claims 3
- 239000012528 membrane Substances 0.000 claims 3
- 230000000379 polymerizing effect Effects 0.000 claims 3
- 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 claims 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims 2
- 102000008186 Collagen Human genes 0.000 claims 2
- 108010035532 Collagen Proteins 0.000 claims 2
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 claims 2
- 239000004743 Polypropylene Substances 0.000 claims 2
- 102000002262 Thromboplastin Human genes 0.000 claims 2
- 108010000499 Thromboplastin Proteins 0.000 claims 2
- 230000004888 barrier function Effects 0.000 claims 2
- 239000011575 calcium Substances 0.000 claims 2
- 229910052791 calcium Inorganic materials 0.000 claims 2
- 210000004027 cell Anatomy 0.000 claims 2
- 239000006285 cell suspension Substances 0.000 claims 2
- 238000005119 centrifugation Methods 0.000 claims 2
- 239000003638 chemical reducing agent Substances 0.000 claims 2
- 229920001436 collagen Polymers 0.000 claims 2
- 108010002255 deoxyhemoglobin Proteins 0.000 claims 2
- 230000002934 lysing effect Effects 0.000 claims 2
- 229920001155 polypropylene Polymers 0.000 claims 2
- 239000011780 sodium chloride Substances 0.000 claims 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims 2
- 239000001509 sodium citrate Substances 0.000 claims 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 2
- 239000008215 water for injection Substances 0.000 claims 2
- 229930024421 Adenine Natural products 0.000 claims 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims 1
- 239000005995 Aluminium silicate Substances 0.000 claims 1
- 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 claims 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 claims 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims 1
- 229960000643 adenine Drugs 0.000 claims 1
- 235000012211 aluminium silicate Nutrition 0.000 claims 1
- 239000003146 anticoagulant agent Substances 0.000 claims 1
- 229940127219 anticoagulant drug Drugs 0.000 claims 1
- 229940072107 ascorbate Drugs 0.000 claims 1
- 235000010323 ascorbic acid Nutrition 0.000 claims 1
- 239000011668 ascorbic acid Substances 0.000 claims 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 claims 1
- 210000001772 blood platelet Anatomy 0.000 claims 1
- 150000001768 cations Chemical class 0.000 claims 1
- 239000002801 charged material Substances 0.000 claims 1
- 229960004106 citric acid Drugs 0.000 claims 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims 1
- 235000018417 cysteine Nutrition 0.000 claims 1
- 238000006392 deoxygenation reaction Methods 0.000 claims 1
- 239000008121 dextrose Substances 0.000 claims 1
- 239000004744 fabric Substances 0.000 claims 1
- 239000011521 glass Substances 0.000 claims 1
- 239000000819 hypertonic solution Substances 0.000 claims 1
- 229940021223 hypertonic solution Drugs 0.000 claims 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 claims 1
- 210000000265 leukocyte Anatomy 0.000 claims 1
- 239000004033 plastic Substances 0.000 claims 1
- 229920003023 plastic Polymers 0.000 claims 1
- 238000006116 polymerization reaction Methods 0.000 claims 1
- 238000009738 saturating Methods 0.000 claims 1
- 230000002000 scavenging effect Effects 0.000 claims 1
- 229960000999 sodium citrate dihydrate Drugs 0.000 claims 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 claims 1
- 239000001488 sodium phosphate Substances 0.000 claims 1
- 229910000162 sodium phosphate Inorganic materials 0.000 claims 1
- 230000000087 stabilizing effect Effects 0.000 claims 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 claims 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims 1
- 238000005406 washing Methods 0.000 claims 1
- 239000000725 suspension Substances 0.000 abstract 2
- 238000013019 agitation Methods 0.000 abstract 1
- 238000000926 separation method Methods 0.000 abstract 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/41—Porphyrin- or corrin-ring-containing peptides
- A61K38/42—Haemoglobins; Myoglobins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- 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
-
- 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
- A61P7/06—Antianaemics
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0641—Erythrocytes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- 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
Red blood cells are purified by defibrinating whole blood and then filtering the defibrinated whole blood, whereby at least a portion of a plasma component is separated from the red blood cells to form a suspension of red blood cells, thereby purifying the red blood cells. Whole blood is defibrinated by, for example, using a chemical coagulating agent or mechanical agitation.
Separation of the plasma component from red blood cells can be completed by, for example, diafiltration. The suspension of red blood cells can then be employed to produce a hemoglobin-based oxygen carrier.
Separation of the plasma component from red blood cells can be completed by, for example, diafiltration. The suspension of red blood cells can then be employed to produce a hemoglobin-based oxygen carrier.
Claims (48)
1. A method for purifying red blood cells, comprising the steps of:
a) defibrinating whole blood, the whole blood including red blood cells and a plasma component; and thereafter b) filtering the whole blood, whereby at least a portion of the plasma is separated from the red blood cells to form a red blood cell suspension, thereby purifying the red blood cells.
a) defibrinating whole blood, the whole blood including red blood cells and a plasma component; and thereafter b) filtering the whole blood, whereby at least a portion of the plasma is separated from the red blood cells to form a red blood cell suspension, thereby purifying the red blood cells.
2. The method of Claim 1, wherein the whole blood is defibrinated by contacting the whole blood with a coagulating agent.
3. The method of Claim 1, wherein the coagulating agent is selected from the group consisting of collagen, tissue extract, tissue factor, tissue thromboplastin, anionic phospholipid, calcium, or negatively charged materials (e.g., glass, kaolin, some synthetic plastics, fabrics).
4. The method of Claim 1, wherein the whole blood is defibrinated by agitating said blood.
5. The method of Claim 1, wherein the whole blood is filtered by diafiltration.
6. The method of Claim 5, wherein the whole blood is diafiltered across a membrane having a permeability limit in a range of between about 0.01 µm and about 5 µm.
7. The method of Claim 6, further including the step of diluting the whole blood.
8. The method of Claim 7, further including the step of diluting the whole blood with an isotonic or a hypertonic solution.
9. The method of Claim 8, wherein the whole blood is diluted following defibrination and before diafiltration of the whole blood.
10. The method of Claim 7, wherein the defibrinated whole blood is diluted to a concentration in a range of between about 25% to about 75% of the initial concentration.
11. The method of Claim 8, wherein the isotonic solution includes an ionic solute.
12. The method of Claim 8, wherein the isotonic solution is aqueous.
13. The method of Claim 12, wherein the isotonic solution includes a solute selected from the group consisting of sodium citrate, sodium chloride, citric acid, dextrose, adenine, or sodium phosphate.
14. The method of Claim 8, further including the step of reconcentrating the whole blood before diafiltration.
15. The method of Claim 14, wherein diafiltration is conducted by diluting the whole blood across a hollow fiber membrane.
16. The method of Claim 9, wherein the hollow fiber membrane has a permeability in a range between about 0.1 and about 2.0 µm.
17. The method of Claim 8, further including the step of filtering the whole blood prior to diafiltering the whole blood, whereby solution debris is removed from the whole blood solution.
18. The method of Claim 17, wherein the blood is filtered through a cheesecloth.
19. The method of Claim 17, wherein the blood is filtered though a filter having an average permeability of less than about 800 µm.
20. The method of Claim 17, wherein the blood is filtered though a filter having an average permeability of less than about 50 µm.
21. The method of Claim 6, wherein the whole blood includes an anticoagulant and further includes the step of saturating the whole blood with a divalent canon.
22. The method of Claim 21, wherein the divalent cation is calcium.
23. A method for preparing a hemoglobin solution, comprising the steps of:
a) defibrinating whole blood;
b) separating red blood cells from the whole blood; and c) isolating hemoglobin molecules from the red blood cells, whereby a hemoglobin solution is formed.
a) defibrinating whole blood;
b) separating red blood cells from the whole blood; and c) isolating hemoglobin molecules from the red blood cells, whereby a hemoglobin solution is formed.
24. The method of Claim 23, wherein the step of separating the red blood cells from the whole blood includes centrifuging the whole blood.
25. The method of Claim 24, wherein centrifuging the whole blood causes at least a portion of the red blood cells to lyse, thereby releasing hemoglobin molecules.
26. The method of Claim 25, wherein the released hemoglobin is isolated by centrifugation.
27. The method of Claim 25, wherein the released hemoglobin is isolated by filtration.
28. The method of Claim 23, further including the step of lysing the separated red blood cells.
29. The method of Claim 28, wherein the red blood cells are lysed by centrifuging the red blood cells.
30. The method of Claim 28, wherein the red blood cells are lysed hypotonically.
31. The method of Claim 23, further including the step of deoxygenating the hemoglobin solution.
32. The method of Claim 31, wherein the content of an oxyhemoglobin component of the hemoglobin solution is reduced to less than about 20%.
33. The method of Claim 31, wherein the oxyhemoglobin component of the hemoglobin solution is reduced to less than about 10%.
34. The method of Claim 31, wherein the hemoglobin solution is deoxygenated by chemical scavenging with a reducing agent.
35. The method of Claim 34, wherein the reducing agent is selected from the group consisting of N-acetyl-L-cysteine (NAC), cysteine, sodium dithionite or ascorbate.
36. A method for preparing a hemoglobin-based oxygen carrier, comprising the steps of:
a) defibrinating whole blood;
b) separating red blood cells from whole blood;
c) isolating hemoglobin molecules of said cells to form a hemoglobin solution;
and d) stabilizing the hemoglobin, thereby preparing the hemoglobin-based oxygen carrier.
a) defibrinating whole blood;
b) separating red blood cells from whole blood;
c) isolating hemoglobin molecules of said cells to form a hemoglobin solution;
and d) stabilizing the hemoglobin, thereby preparing the hemoglobin-based oxygen carrier.
37. The method of Claim 36, further including the step of deoxygenating the hemoglobin solution.
38. The method of Claim 37, wherein the content of an oxyhemoglobin component of the hemoglobin solution is reduced to less than about 20%.
39. The method of Claim 37, wherein the oxyhemoglobin component of the hemoglobin solution is reduced to less than about 10%.
40. The method of Claim 36, wherein the hemoglobin molecules are stabilized by polymerizing the hemoglobin molecules.
41. The method of Claim 36, wherein the deoxygenation of the hemoglobin solution occurs prior to polymerizing the hemoglobin.
42. The method of Claim 36, wherein the hemoglobin is stabilized by pyridoxylation.
43. The method of Claim 36, wherein the hemoglobin is stabilized by crosslinking the hemoglobin molecules.
44. The method of Claim 43, wherein the hemoglobin is stabilized by intermolecular crosslinking.
45. The method of Claim 43, wherein the hemoglobin is stabilized by intramolecular crosslinking.
46. The method of Claim 36, further including the step of preserving the hemoglobin-based oxygen carrier.
47. The method of Claim 46, wherein the hemoglobin-based oxygen carrier is preserved by containing the hemoglobin-based oxygen carrier in an oxygen barrier film primary package.
48. The method of using defibrinated blood to manufacture a hemoglobin-based oxygen carrier, comprising the steps of:
a) using collagen to defibrinate blood, thereby forming defibrinated blood;
b) filtering the defibrinated blood through an 800 µm polypropylene filter and a 50 µm polypropylene filter;
c) diluting the blood with sodium citrate solution (6.0 g/l sodium citrate dihydrate and 8.0 g/l sodium chloride in water for injection);
d) reconcentrating the diluted blood solution back to its original volume through a 0.2 µm hollow fiber diafilter;
e) diafiltering the reconcentrated blood solution, thereby washing the cells;
f) separating the red blood cells from the white blood cells and platelets by centrifugation, thereby forming a red blood cell suspension;
g) lysing the red blood cells to release hemoglobin by centrifugaton;
h) mixing the red blood cell phase with water for injection and centrifuging, thereby forming a hemoglobin solution;
i) deoxygenating the hemoglobin solution;
j) polymerizing the deoxy-hemoglobin in a polymerization apparatus;
k) crosslinking the polymerized deoxyhemoglobin with glutaraldehyde, thereby preparing a hemoglobin-based hemoglobin-based oxygen carrier; and l) preserving the hemoglobin-based oxygen carrier in a oxygen barrier primary package.
a) using collagen to defibrinate blood, thereby forming defibrinated blood;
b) filtering the defibrinated blood through an 800 µm polypropylene filter and a 50 µm polypropylene filter;
c) diluting the blood with sodium citrate solution (6.0 g/l sodium citrate dihydrate and 8.0 g/l sodium chloride in water for injection);
d) reconcentrating the diluted blood solution back to its original volume through a 0.2 µm hollow fiber diafilter;
e) diafiltering the reconcentrated blood solution, thereby washing the cells;
f) separating the red blood cells from the white blood cells and platelets by centrifugation, thereby forming a red blood cell suspension;
g) lysing the red blood cells to release hemoglobin by centrifugaton;
h) mixing the red blood cell phase with water for injection and centrifuging, thereby forming a hemoglobin solution;
i) deoxygenating the hemoglobin solution;
j) polymerizing the deoxy-hemoglobin in a polymerization apparatus;
k) crosslinking the polymerized deoxyhemoglobin with glutaraldehyde, thereby preparing a hemoglobin-based hemoglobin-based oxygen carrier; and l) preserving the hemoglobin-based oxygen carrier in a oxygen barrier primary package.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA2756609A CA2756609C (en) | 2001-02-28 | 2002-02-28 | Use of defibrinated blood for manufacture of a hemoglobin-based oxygen carrier |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/795,821 | 2001-02-28 | ||
| US09/795,821 US6518010B2 (en) | 2001-02-28 | 2001-02-28 | Use of defibrinated blood for manufacture of a hemoglobin-based oxygen carrier |
| PCT/US2002/006719 WO2002067957A1 (en) | 2001-02-28 | 2002-02-28 | Use of defibrinated blood for manufacture of a hemoglobin-based oxygen carrier |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2756609A Division CA2756609C (en) | 2001-02-28 | 2002-02-28 | Use of defibrinated blood for manufacture of a hemoglobin-based oxygen carrier |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2439123A1 true CA2439123A1 (en) | 2002-09-06 |
| CA2439123C CA2439123C (en) | 2012-02-21 |
Family
ID=25166541
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2439123A Expired - Fee Related CA2439123C (en) | 2001-02-28 | 2002-02-28 | Use of defibrinated blood for manufacture of a hemoglobin-based oxygen carrier |
| CA2756609A Expired - Fee Related CA2756609C (en) | 2001-02-28 | 2002-02-28 | Use of defibrinated blood for manufacture of a hemoglobin-based oxygen carrier |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2756609A Expired - Fee Related CA2756609C (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) | CA2439123C (en) |
| NZ (1) | NZ527882A (en) |
| WO (1) | WO2002067957A1 (en) |
Families Citing this family (20)
| 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 |
| US7001715B2 (en) * | 2002-02-28 | 2006-02-21 | Biopure Corporation | Purification of red blood cells by separation and diafiltration |
| WO2003074077A1 (en) * | 2002-02-28 | 2003-09-12 | 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 |
| 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 |
| ES2432075T3 (en) * | 2011-07-23 | 2013-11-29 | 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 |
| US9717842B2 (en) * | 2011-09-22 | 2017-08-01 | Fenwal, Inc. | Disposable fluid circuits and methods for cell washing |
| CN103861161B (en) * | 2012-12-18 | 2016-06-08 | 苏州排头兵药业科技有限公司 | The preparation method of Washed Red Blood Cells device and Washed Red Blood Cells |
| 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 |
| US20220354930A1 (en) | 2019-07-02 | 2022-11-10 | Hbo2 Therapeutics, Llc | Hemoglobin Substitute Mixtures Including Reconstituted Plasma and Platelets and Their Manufacture and Use |
| WO2021262803A1 (en) * | 2020-06-23 | 2021-12-30 | 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 |
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2001
- 2001-02-28 US US09/795,821 patent/US6518010B2/en not_active Expired - Lifetime
-
2002
- 2002-02-28 CN CNB028073584A patent/CN1269955C/en not_active Expired - Fee Related
- 2002-02-28 WO PCT/US2002/006719 patent/WO2002067957A1/en active IP Right Grant
- 2002-02-28 AU AU2002250229A patent/AU2002250229B2/en not_active Ceased
- 2002-02-28 NZ NZ527882A patent/NZ527882A/en unknown
- 2002-02-28 JP JP2002567323A patent/JP2004535368A/en active Pending
- 2002-02-28 CA CA2439123A patent/CA2439123C/en not_active Expired - Fee Related
- 2002-02-28 EP EP02719129A patent/EP1443947A1/en not_active Withdrawn
- 2002-02-28 CA CA2756609A patent/CA2756609C/en not_active Expired - Fee Related
- 2002-11-26 US US10/306,819 patent/US6986984B2/en not_active Expired - Fee Related
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2005
- 2005-11-29 US US11/289,048 patent/US7553613B2/en not_active Expired - Fee Related
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|---|---|
| CA2756609C (en) | 2015-06-09 |
| CN1269955C (en) | 2006-08-16 |
| WO2002067957A8 (en) | 2004-07-29 |
| CA2439123C (en) | 2012-02-21 |
| NZ527882A (en) | 2006-03-31 |
| US7553613B2 (en) | 2009-06-30 |
| AU2002250229B2 (en) | 2004-11-25 |
| CA2756609A1 (en) | 2002-09-06 |
| JP2004535368A (en) | 2004-11-25 |
| US20060084137A1 (en) | 2006-04-20 |
| US6518010B2 (en) | 2003-02-11 |
| US6986984B2 (en) | 2006-01-17 |
| CN1499978A (en) | 2004-05-26 |
| WO2002067957A1 (en) | 2002-09-06 |
| US20030113707A1 (en) | 2003-06-19 |
| US20020161197A1 (en) | 2002-10-31 |
| EP1443947A1 (en) | 2004-08-11 |
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