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Home Gene Therapy N-1-1-1-dialkyloxy-and-N-1-1-1-dialkenyloxy-alk-1-yl-N-N-N-tetrasubstituted-ammonium-lipids-and-uses-therefor

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 N-[1, (1-1) -dialkyloxy] - and N- [1, (1-1) -dialkenyloxy]- alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor

Details
Inventors: Eppstein, Deborah A.; Felgner, Philip L.; Gadek, Thomas R.; Jones, Gordon H.; Roman, Richard B.;
Assignee:
Primary Examiner: Kishore; Gollamudi S.
Assistant Examiner:
Attorney, Agent or Firm:

This invention relates to compounds of the formula ##STR1## or an optical isomer thereof wherein R.sup.1 and R.sup.2 are the same or different and are an alkyl or alkenyl group of 6 to 24 carbon atoms; R.sup.3, R.sup.4 and R.sup.5 are the same or different and are alkyl of 1 to 8 carbon atoms, aryl, aralkyl of 7 to 11 carbon atoms, or when two or three of R.sup.3, R.sup.4, and R.sup.5 are taken together to form quinuclidino, piperidino, pyrrolidino, or morpholino; n is 1 to 8; and X is a pharmaceutically acceptable anion.

DETAILED DESCRIPTION According to a first aspect of the invention, the compounds of this invention are illustrated by Formula (I): ##STR2## or an optical isomer thereof, wherein R.
sup.
1 and R.
sup.
2 are independently an alkyl, alkenyl, or alkynyl group of 6 to 24 carbon atoms; R.
sup.
3, R.
sup.
4 and R.
sup.
5 are independently hydrogen, alkyl of 1 to 8 carbon atoms, aryl or aralkyl of 6 to 11 carbon atoms; alternatively two or three of R.
sup.
3, R.
sup.
4 and R.
sup.
5 are combined with the positively charged nitrogen atom to form a cyclic structure having from 5 to 8 atoms, where, in addition to the positively charged nitrogen atom, the atoms in the structure are carbon atoms and can include one oxygen, nitrogen or sulfur atom; n is 1 to 8; and X is an anion.
According to other aspects of the invention, liposome and pharmaceutical formulations are claimed: said liposome formulations comprising up to lot by weight of a biologically active substance, 1% to 20% by weight of a lipid component comprising a compound of Formula I in a quantity of from about It to loot by weight, and an aqueous solution in a quantity sufficient to make 100% by volume; and said pharmaceutical formulations comprising a therapeutically effective amount of a drug, an optional pharmaceutically acceptable excipient, and a lipid component comprising a compound of Formula I in a quantity of from about 1% to 100% by weight.
According to another aspect of the invention, a polyanion-lipid complex, formed from a compound of formula I and a polyanion, is claimed.
According to yet another aspect of the invention, a method is claimed for forming a polyanion-lipid complex, said method comprising the steps of contacting a liposomal composition prepared from a positively charged liposome-forming lipid with a negatively charged polyanion.
According to still another aspect of the invention, a positively-charged polynucelotide-liposome complex is claimed, comprising a lipid of Formula I and a polynucleotide.
According to a further aspect of the invention, a method is claimed for preparing a positively-charged polynucleotide-lipid complex



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