http://rdf.ncbi.nlm.nih.gov/pubchem/patent/PT-95812-B

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assignee http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_7283083724734f6a6e47be3c4e7925b7
classificationIPCInventive http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61K9-127
filingDate 1990-11-06-04:00^^<http://www.w3.org/2001/XMLSchema#date>
inventor http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_b89906fd9c6cecb290566cc36df4d247
http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_0cbb019a342f23dfbafed65f9e36100e
publicationDate 1997-11-28-04:00^^<http://www.w3.org/2001/XMLSchema#date>
publicationNumber PT-95812-B
titleOfInvention PROCESSES FOR THE PREPARATION OF LIPOSOMES WITH HYDROFOBAS PROTEINS
abstract This invention relates to the preparation of liposomes with hydrophobic proteins. L-asparaginase (L-ASNase - l-asparagine amido hydrolase E.C.3.5.1.1.) is a protein with therapeutic action in the treatment of acute lymphoblastic leukaemias in human beings. Its use is limited, however, by the severe side effects, principally acute allergic reactions which in some cases can go as far as anaphylactic shock and even death. Liposomes have been used as vehicles for transport of L- ASNase and have shown evidence of protecting against said allergic reactions. The efficiency of encapsulation of the formulations developed hitherto, however, is low. With the development of a new derivative of L-ASNase, palmitoyl-L-ASNase, it has become possible to incorporate it into the lipid matrix of liposomes, increasing the activity of these vehicles while they remain in circulation in intact form. The objective of this invention was to obtain a process for preparation of liposomes which would lead to palmitoyl-L-ASNase liposomal formulations with high encapsulation efficiency, maximum stable activity while in circulation in the blood, and high antitumoral activity. This new preparation process can also be used in many other situations with other enzymes and drugs in which the same aims are sought. The present invention is based on the addition of freeze- dried hydrophobic protein to preformed liposomes, followed by a freeze-drying process. After this the powder obtained is dissolved (hydration) and passed through polycarbonate filters, under nitrogen flow pressure. The principal inventive characteristics of the process are the addition of empty multilamellar liposomes to modified freeze-dried protein and also the introduction of a step involving density gradient ultracentrifugation followed by another ultracentrifugation, the first with the aim of separating the protein not incorporated in the liposomes and the second with the aim of eliminating the gradient constituent from the final working medium.
priorityDate 1990-11-06-04:00^^<http://www.w3.org/2001/XMLSchema#date>
type http://data.epo.org/linked-data/def/patent/Publication

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