Process for producing immobilized L-asparaginase preparations fo

Details Process for producing immobilized L-asparaginase preparations fo Process for producing immobilized L-asparaginase preparations fo

1983-12-16

1986-10-14

Marantz, Sidney

Chemistry: molecular biology and microbiology

Carrier-bound or immobilized enzyme or microbial cell;...

Enzyme or microbial cell is immobilized on or in an organic...

435177, 435180, 435229, C12N 1104, C12N 1102, C12N 1108, C12N 982

Patent

active

046172718

DESCRIPTION:

BRIEF SUMMARY
FIELD OF THE INVENTION

This invention relates to a process for producing immobilized L-asparaginase preparations for the therapy of leukemia. Particularly, it is concerned with a process for preparing enzymatical leukemia-curing agents by embedding (immobilizing) asparaginase, an antileukemic enzyme (L-asparaginase) in a highly hydrous gel excellent in antithrombogenicity and mechanical strength.


BACKGROUND OF THE INVENTION

It has long been pointed out that asparagine is essential (an essential amino acid) for the growth of leukemic cells. Extensive studies have been on the therapy of leukemia by eliminating asparagine which is not necessarily essential (non-essential) for normal cells from blood, which therapy is expected to cause no damage to normal cells (L. T. Mashburn et al., Biochem. Biophys. Res. Commun., 12, 50 (1963)). Whereas normal cells in which asparagine is formed from aspartic acid or aspartates with asparagine synthetase, an asparagine-synthesizing enzyme, leukemic cells which is deficient in the asparagine-synthesizing activity due to tumorigenesis and in which no asparagine is formed make use of the asparagine existing in plasma in a very small amount for the protein synthesis. Therefore, the therapy is based upon the idea that the protein synthesis (growth) of leukemic cells will be inhibited by introducing asparaginase into blood of the patient in order to decompose the asparagine in blood (achieve and maintain asparagine deficiency).
It is demonstrated that a variety of asparaginases are useful for the therapy of certain leukemias and solid tumors including acute lymphatic leukemia. This therapy was called attention as a specific and favorable therapeutic idea which represents inhibition (prevention) of the growth of leukemic cells without damaging normal cells (H. Marquardt, Arzneimittel-Forsch., 18, 1380 (1968)). Clinical trials were extensively carried out using asparaginase from Escherichia coli B (R. H. Adamson et al., Cancer Chemother. Rep., (1) 52, 617 (1968)). It was pointed out as a result of the trials that antigen-antibody reaction (immunoreaction) due to administration of a foreign protein in the human body was a problem; side effects such as vomiting, nausea, anorexia, pyrexia, bodyweight decrease, hypohepatia, pancreatitis, oligochromemia, uremia, fibrinogenopenia, hyponoia, skin rash, diarrhea, pararitium, anemia, leukopenia, thrombocytopenia, anaphylaxic shock, cephalalgia, angiodynia, irritation and cramp were observed (P. Laboureur, Pathol. Biol. (Paris), 17, 885 (1969)). Accordingly, the therapeutic method has been considered to be of little practical usefulness despite its causing little damage to normal cells, and, contrary to earlier expectation, there has been applied to some extent combination therapy with chemotherapeutic agents such as prednisone, vincristine, methotrexate, 6-mercaptopurine, cytarabine and cyclophosphamide, and radiotherapy. If there were provided means for avoiding the immunoreaction caused by the foreign protein, it is expected that the therapy will recover great hope. As a means of the solution there has been proposed a scheme in which blood is temporarily drawn out of the body, contacted with immobilized asparaginase (macromolecular material with the enzyme embedded or bound) to decompose the asparagine dissolved in the blood and then returned to the body (extracorporeal circulation) (D. Sampson et al., Trans. Am. Soc. Artif. Intern. Organs, 18, 54 (1972)). In this scheme, however, coagulation of the circulated blood by contact with the enzyme-immobilizing material (macromolecular material) is a newly caused problem, although the immunoreaction with the foreign protein (enzyme) is greatly weakened (or abolished) by employing an adequate enzyme-immobilization technique.
An expedient may be adopted to add an anti-coagulant such as heparin to the blood stream in consideration of poor antithrombogenicity in any of the known enzyme-immobilizing macromolecular materials. Combined use of drugs including heparin in a large amount for a long pe

REFERENCES:
patent: 3859169 (1975-01-01), O'Driscoll et al.

Affiliated with

Also associated with

Rating

Process for producing immobilized L-asparaginase preparations fo does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Process for producing immobilized L-asparaginase preparations fo, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for producing immobilized L-asparaginase preparations fo will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1340316