Pharmaceutical formulation of nicardipine and 1,2-dioxy-omega-trialkylammonium compounds

Claim 2

A pharmaceutical formulation comprising 0.05 to 10% nicardipine hydrochloride by weight, 1 to 20% surfactant component by weight of which a compound of formula I comprises 1 to 100% of this surfactant component wherein formula I is represented by the formula or an optical isomer thereof wherein R l and R 2 are the same or different and are an alkyl or alkenyl group of 6 to 22 carbons; R 3 , R 4 and R 5 are the same or different and are hydrogen, alkyl of 1 to 8 carbon atoms, aryl, aralkyl of 7 to 11 carbons or when two or three of R 3 , R 4 , and R 5 are taken together form quinuclidino, pyrrolidino, piperidino, or morpholino; n is 1 to 8; and X is a pharmaceutically acceptable anion; and an aqueous solution in a quantity sufficient to make 100% by volume.

Claim 3

A formulation according to claim 1 having a compound of formula I wherein R l and R 2 are the same and are alkyl of 10 to 20 carbon atoms; R 3 , R 4 , and R 5 are hydrogen, methyl or ethyl; n is 1 to 4; and X is a halide ion.

Claim 4

A formulation according to claim 2 wherein nicardipine hydrochloride comprises 1 to 5% and formula I comprises 50% or more of the surfactant component.

Claim 5

A formulation according to claim 3 having a compound of formula I which is (+) N-(2,3-di-hexadecyloxy)-propyl-N,N,N-trimethylammonium chloride or an optical isomer thereof, or (+) N-(2,3-di-octadecyloxy)-prop-1-yl-N,N,N-trimethylammonium chloride or an optical isomer thereof.

Claim 6

A formulation according to claim 4 comprised of 5% nicardipine hydrochloride by weight, 20% by weight of a compound of formula I according to claim 4 and an aqueous solution in a quantity sufficient to make 100% by volume.

Claim 7

A formulation according to claim 1 having a compound of formula I wherein R 1 and R 2 are the same and are alkenyl of 10 to 20 carbon atoms; R 3 , R 4 , and R 5 are hydrogen, methyl or ethyl; n is 1 to 4; and X is a halide ion.

Claim 8

A formulation according to claim 6 wherein nicardipine hydrochloride comprises 1 to 5% and a compound of formula I comprises 50% or more of the surfactant component.

Claim 9

A formulation according to claim 7 having a compound of formula I which is (+) N-(2,3-di-(9-(Z)-octadecenyloxy))-prop-1-yl-N,N,N-trimethylammonium chloride or an optical isomer thereof.

Claim 10

A formulation according to claim 8 comprises of 5% nicardipine hydrochloride by weight, 20% of a compound of formula I according to claim 8 by weight and an aqueous solution in a quantity sufficient to make 100% by volume.

Claim 11

A formulation accordinq to claim 1 having a compound of formula I wherein R 1 is alkyl or alkenyl of 14 to 22 carbon atoms and R 2 is a different alkyl or alkenyl group of 6 to 14 carbon atoms; R 3 , R 4 , and R 5 are hydrogen, methyl or ethyl; n is 1 to 4; and X is a halide ion.

Claim 12

CLAIMS 1. Use of a compound of formula I or an optical isomer thereof wherein R 1 and R 2 are the same or different and are an alkyl or alkenyl group of 6 to 22 carbons; R 3 , R 4 and R 5 are the same or different and are hydrogen, alkyl of 1 to 8 carbon atoms, aryl, aralkyl of 7 to 11 carbons or when two or three of R 3 , R 4 , and R 5 are taken together form quinuclidino, pyrrolidino, piperidino, or morpholino; n is 1 to 8; and X is a pharmaceutically acceptable anion; in the manufacture of a pharmaceutical formulation comprising 0.05 to 10% nicardipine hydrochloride by weight, 1 to 20% surfactant component by weight of which a compound of formula I comprises 1 to 100% of this surfactant component, and an aqueous solution in a quantity sufficient to make 100% by volume. 2. A process according to claim 1 wherein in the compound of formula I R 1 and R 2 are the same and are alkyl of 10 to 20 carbon atoms; R 3 , R 4 , and R 5 are hydrogen, methyl or ethyl; n is 1 to 4; and X is a halide ion.

Claim 13

A process according to claim 2 wherein nicardipine hydrochloride comprises 1 to 5% and formula I comprises 50% or more of the surfactant component.

Claim 14

A process accordinq to claim 3 wherein the compound of formula I is (+) N-(2,3-di-hexadecyloxy)-propyl-N,N,N-trimethylammonium chloride or an optical isomer thereof, or (+) N-(2,3-di-octadecyloxy)-prop-1-yl-N,N,N-trimethylammonium chloride or an optical isomer thereof.

Claim 15

A process according to claim 4 wherein the formulation comprises 5% nicardipine hydrochloride by weight, 20% by weight of a compound of formula I according to claim 4 and an aqueous solution in a quantity sufficient to make 100% by volume.

Claim 16

A process according to claim 1 wherein in the compound of formula I R 1 and R 2 are the same and are alkenyl of 10 to 20 carbon atoms; R 3 , R 4 , and R 5 are hydrogen, methyl or ethyl; n is 1 to 4; and X is a halide ion.

Claim 17

A process according to claim 6 wherein nicardipine hydrochloride comprises 1 to 5% and a compound of formula I comprises 50% or more of the surfactant component.

Claim 18

A process according to claim 7 wherein the compound of formula I is (+) N-(2,3-di-(9-(Z)-octadecenyloxy))-prop-l-yl-N,N,N-trimethylammonium chloride or an optical isomer thereof.

Claim 19

A process according to claim 8 wherein the formulation comprises 5% nicardipine hydrochloride by weight, 20% of a compound of formula I according to claim 8 by weight and an aqueous solution in a quantity sufficient to make 100% by volume. 10. A process according to claim 1 wherein in the compound of formula I R l is alkyl or alkenyl of 14 to 22 carbon atoms and R 2 is a different alkyl or alkenyl group of 6 to 14 carbon atoms; R 3 , R 4 , and R 5 are hydrogen, methyl or ethyl; n is 1 to 4; and X is a halide ion.