N-(.omega., (.omega.-1)-dialkyloxy)- and N-(.omega., (.omega.-1)-dialkenyloxy)-alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor
AssigneeSyntex (U.S.A.) Inc.
InventorsDeborah A. Eppstein, Philip L. Felgner, Thomas R. Gadek, Gordon H. Jones, Richard B. Roman
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Abstract
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.
Claims30
A polyanion-lipid complex formed from a compound of Formula I and a polyanion, wherein Formula I is represented by the formula:
- ##STR8## 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 quinoclidino, pyrrolidono, piperidino or morpholino;
- n is 1 to 8;
- and X is a pharmaceutically acceptable atom;
- and an aqueous solution in a quantity sufficient to make 100% by volume.
The complex of claim 9 wherein the RNA is double stranded.
A method for forming a polyanion-lipid complex, said method comprising the step of contacting a liposomal composition prepared from a compound of Formula I with a negatively charged polyanion, wherein Formula I is represented by the formula:
- ##STR9## 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 quinoclidino, pyrrolidono, piperidino or morpholino;
- n is 1 to 8;
- and X is a pharmaceutically acceptable atom and an aqueous solution in a quantity sufficient to make 100% by volume.
A positively-charged polynucleotide-liposome complex, comprising:
- a polynucleotide;
- and
- a lipid of the Formula:
- ##STR10## 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 quinculidino, pyrrolidino, piperidino, or morpholino;
- n is 1 to 8;
- and X is a pharmaceutically acceptable anion.
A method for preparing a positively-charged polynucleotide-lipid complex, said method comprising the steps of:
- forming a liposome from a positively charged lipid of Formula I ##STR11## 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, pyrrolidino, piperidino, or morpholino;
- n is 1 to 8;
- and X is a pharmaceutically acceptable anion;
- and
- contacting the liposome with a polynucleotide to obtain a polynucleotide-lipid complex.
A positively-charged polynucleotide liposome complex, comprising:
- a polynucleotide
- a lipid of the Formula:
- ##STR12## 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 carbons;
- 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 quinoclidino, pyrrolidino, piperidino, or morpholino;
- n is 1 to 8;
- and x is a pharmaceutically acceptable anion.
Dependencies are inferred from the claim text.