초록 ▼

By carrying out the depolymerization of stabilized solutions of highly polymerized and nicked polydeoxyribonucleotides, as obtained through stabilizing aggregation of raw nucleic acids, the depolymerization being carried out by heating at controlled temperature and being controlled as a function of

By carrying out the depolymerization of stabilized solutions of highly polymerized and nicked polydeoxyribonucleotides, as obtained through stabilizing aggregation of raw nucleic acids, the depolymerization being carried out by heating at controlled temperature and being controlled as a function of the variation of the reversible hyperchromicity, followed by the removal of the hydrogen bonds in the double stranded filaments and by thermal stabilization of the single stranded filaments, the polydeoxyribonucleotide, known as Defibrotide is obtained. Defibrotide has the following formula of random sequence: P1-5,(dAp)12-24,(dGp)10-20, (dTp)13-26,(dCP)10-20, wherein P=phosphoric radical dAp=deoxyadenylic monomer dGp=deoxyguanylic monomer dTp=deoxythymidylic monomer dCp=deoxycytidylic monomer and has well defined chemico-physical properties, reproducible in the industrial production.

대표청구항 ▼

A process for producing the polydeoxyribonucleotide Defibrotide from a solution of raw nucleic acids obtained from mammalian cells, said solution being substantially free of polysaccharides and proteins, said process comprising the steps of: (1) forming highly polymerized nicked polydeoxyribonucleot

A process for producing the polydeoxyribonucleotide Defibrotide from a solution of raw nucleic acids obtained from mammalian cells, said solution being substantially free of polysaccharides and proteins, said process comprising the steps of: (1) forming highly polymerized nicked polydeoxyribonucleotides by stabilizing an aggregation of the raw nucleic acids by adjusting the ionic strength and the pH of the solution until the maximum reversible hyperchromicity has been reached; (2) depolymerizing the polydeoxyribonucleotides until the reversible hyperchromicity of the solution is at a value of h=15±5, measured as a percent in native DNA, by heating the resulting solution to a depolymerizing temperature for the said polydeoxyribonucleotide, and maintaining the solution at a depolymerizing temperature until said specified reversible hyperchromicity value has been achieved; (3) terminating the depolymerization reaction by cooling, and removing the hydrogen bonds in any double filament fragment in the depolymerized solution by making the medium alkaline, thereby forming single filament polydeoxyribonucleotide fragments; and (4) stabilizing the resulting single filament fragments of polydeoxyribonucleotides by heating the resulting solution at a temperature and pH higher than those of the depolymerization reaction to prevent hydrogen bond reformation.