http://rdf.ncbi.nlm.nih.gov/pubchem/patent/ES-2527608-T3
Outgoing Links
| Predicate | Object |
|---|---|
| assignee | http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_1ea6c33784b9ee0ebc9d20c12b2ff315 |
| classificationCPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K35-12 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P9-10 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07K14-805 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K47-08 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P7-06 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P7-08 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K38-42 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P39-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P35-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P7-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P35-02 |
| classificationIPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61K35-14 |
| filingDate | 2011-04-15-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| grantDate | 2015-01-27-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| inventor | http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_d05d5efa8c5fccaba3d127d2efddbe6a http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_11b301c9f2a0168337a7a0165984808d |
| publicationDate | 2015-01-27-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationNumber | ES-2527608-T3 |
| titleOfInvention | Pharmaceutical composition containing a stable oxygen vehicle at elevated temperature |
| abstract | Method for the preparation of a pharmaceutical composition containing a highly purified and stable high temperature oxygen carrier, including the pharmaceutical composition containing a non-polymeric crosslinked tetrameric hemoglobin oxygen vehicle, and the method comprising the following steps: a) providing blood mammalian complete that includes at least erythrocytes and plasma; b) separating erythrocytes from plasma in mammalian whole blood; c) filter the erythrocytes that separated from the plasma to obtain a fraction of filtered erythrocytes; d) wash the filtered erythrocyte fraction to remove plasma protein impurities, resulting in washed erythrocytes; e) disintegrate the washed erythrocytes by a controlled hypotonic lysis for a sufficient time to lyse the erythrocytes without lysing the leukocytes in an instantaneous cytolysis apparatus at a flow rate of 50-1000 liter / h to create a solution comprising a lysate of disintegrated erythrocytes ; f) carry out a filtration to remove at least a portion of the waste retention from the lysate; g) extracting a first hemoglobin solution from the lysate; h) carry out a first ultrafiltration procedure using an ultrafiltration filter configured to remove impurities that have a molecular weight greater than tetrameric hemoglobin to further remove any virus and retain residual waste from the first hemoglobin solution to obtain a second hemoglobin solution; i) carry out a continuous flow column chromatography on the second hemoglobin solution to remove phospholipids, protein impurities and dimeric hemoglobin and to form a phospholipid-free hemoglobin solution, low in protein impurities and low in dimers; j) carry out a second ultrafiltration procedure on the phospholipid-free hemoglobin solution, low in protein impurities and low in dimers using a filter configured to remove impurities, resulting in a purified phospholipid-free concentrated hemoglobin solution, low in protein impurities and low in dimers; k) blocking the sulfhydryl groups of the hemoglobin molecules in the purified phospholipid-concentrated concentrated hemoglobin solution low in protein impurities and low in dimers by means of a sulfhydryl reagent in a completely oxygenated environment so that the hemoglobin molecules each present at less a cysteine residue that includes a thiol protecting group so that hemoglobin molecules cannot bind to the relaxing factor derived from the endothelium at the cysteine site; l) cross-link protected thiol hemoglobin by bis-3,5-dibromosalicyl fumarate (DBSF) with a molar ratio of protected thiol hemoglobin to DBSF greater than 1: 2.5 to less than 1: 5.0 in a deoxygenated environment to form stable crosslinked tetrameric hemoglobin at elevated temperature without the formation of polymeric hemoglobin, such that the molecular weight of the resulting crosslinked tetrameric hemoglobin is 60-70 kDa and consists essentially of non-polymeric crosslinked tetrameric hemoglobin; m) exchanging a suitable physiological buffer for the cross-linked tetrameric hemoglobin; n) remove any residual uncrosslinked tetrameric hemoglobin and any residual chemicals by washing; o) add N-acetylcysteine at a concentration of 0.2-0.4% to the cross-linked tetrameric hemoglobin to maintain a methemoglobin level below 5%; and p) adding the low dimeric crosslinked tetrameric hemoglobin, free of phospholipids, protected thiol, stable at elevated temperature up to a temperature of 80 ° C, free of polymeric hemoglobin, to a pharmaceutically acceptable carrier |
| priorityDate | 2010-05-27-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| type | http://data.epo.org/linked-data/def/patent/Publication |
Incoming Links
Total number of triples: 31.