Transdermal compositions
The present invention is directed to transdermal compositions and the uses thereof. These compositions include at least one of the following components: a C 1 -C 6 dialkyl, C 12 -C 30 dialkyl quaternary ammonium salt, a C 12 -C 30 fatty acid, a nitrogenous organic base, C 12-30 fatty alcohol, monoglyceride or the reaction products thereof.
1. A tertiary amide of the formula:
or pharmaceutically acceptable salts thereof,
wherein R 4 is a fatty group of 11-29 carbon atoms;
R 5 is lower alkyl, aryl, aryl lower alkyl, or fatty group containing 11-29 carbon atoms or R 7 ;
R 6 is independently R 7 ;
R 7 is
R 1 —Ar—O—R 2 —O—R 3 —;
R 2 and R 3 are independently alkylene groups containing 1-6 carbon atoms,
R 1 is an alkyl group containing 1-15 carbon atoms and
Ar is aryl, said fatty group either being completely saturated or containing 1-8 carbon-carbon double bonds.
2. The tertiary amide of claim 1 wherein R 4 is a fatty group containing 15-21 carbon atoms.
3. The tertiary amide of claim 1 wherein R 5 is aryl or aryl lower alkyl; and R 6 is
R 1 —Ar—O—R 2 —O—R 3 —;
R 2 and R 3 are independently alkylene containing 1-3 carbon atoms; and
Ar is aryl.
4. The tertiary amide according to claim 3 wherein Ar is phenyl.
5. The tertiary amide according to claim 4 wherein R 5 is aryl lower alkyl.
6. The tertiary amide according to claim 5 wherein R 5 is benzyl.
7. The tertiary amide according to claim 5 wherein R 4 is saturated.
8. The tertiary amide according to claim 5 wherein R 4 is unsaturated.
9. The tertiary amide according to claim 8 wherein R 4 contains 1-6 carbon-carbon double bonds.
10. The tertiary amide according to claim 1 which is
11. A mixture comprising two or more different tertiary amides of the formula
or pharmaceutically acceptable salts thereof wherein
R 4 is a fatty group of 11-29 carbon atoms;
R 5 is lower alkyl, aryl, aryl lower alkyl, or fatty group containing 11-29 carbon atoms or R 7 ;
R 6 is independently R 7 ;
R 7 is
R 1 —Ar—O—R 2 —O—R 3 —;
R 2 and R 3 are independently alkylene groups containing 1-6 carbon atoms,
R 1 is an alkyl group containing 1-15 carbon atoms, and
Ar is aryl, said fatty group being completely saturated or containing 1-8 carbon-carbon double bonds.
12. The mixture of claim 11 wherein in at least one of the tertiary amides, R 5 is an unsaturated fatty group.
13. A pharmaceutical composition comprising a transdermal effective amount of the tertiary amide of claim 1 .
14. A tertiary amide hydrate formed from the process comprising heating a mixture of water, a quaternary surfactant, a fatty acid and an alkanolamine at a temperature greater than the melting point of said acid and less than 100° C. for sufficient time and under conditions effective to form a tertiary amide, cooling said tertiary amide to ambient temperature for sufficient time an under effective conditions for the pH of the water to stabilize and for said tertiary amide hydrate to form.
15. The product formed from the process of claim 14 wherein the alkanolamine is triethanolamine, trimethanolamine, tris (hydroxyethyl)aminomethane, or tris (hydroxyethyl methyl)aminoethane.
16. An amide hydrate of a tertiary amide, where the tertiary amide has the formula:
or pharmaceutically acceptable salts thereof wherein
R 4 is a fatty group of 11-29 carbon atoms;
R 5 and R 6 are independently lower alkyl, aryl, aryl lower alkyl, or fatty group containing 11-29 carbon atoms or R 7 ;
R 7 is
R 1 —Ar—O—R 2 —O—R 3 —;
R 2 and R 3 are independently alkylene groups containing 1-6 carbon atoms;
R 1 is an alkyl group containing 1-15 carbon atoms; and
Ar is aryl;
said fatty group being either completely saturated or containing 1-8 carbon-carbon double bonds.
17. The amide hydrate of claim 16 wherein R 4 is a fatty group containing 15-21 carbon atoms.
18. The amide hydrate of claim 16 wherein R 5 is aryl or aryl lower alkyl; and R 6 is
R 1 —Ar—O—R 2 —O—R 3 —;
R 2 and R 3 are independently alkylene containing 1-3 carbon atoms; and
Ar is aryl.
19. The amide hydrate according to claim 18 wherein Ar is phenyl.
20. The amide hydrate according to claim 19 wherein R 5 is aryl lower alkyl.
21. The amide hydrate according to claim 20 wherein R 5 is benzyl.
22. The amide hydrate according to claim 20 wherein R 4 is saturated.
23. The amide hydrate according to claim 20 wherein R 4 is unsaturated.
24. The amide hydrate according to claim 23 wherein R 4 contains 1-8 carbon-carbon double bonds.
25. The amide hydrate according to claim 16 which is the amide hydrate of a tertiary amide selected from the group consisting of distearyl stearamide, distearyl linoleamide,
26. A composition comprising a transdermal effective amount of the tertiary amide hydrate of any one claims 16 - 25 .
27. Distearyl linoleamide or pharmaceutically acceptable salt thereof.
28. A pharmaceutical composition comprising a transdermal effective amount of a tertiary amide of the formula
or pharmaceutically acceptable salts thereof wherein
R 4 is a fatty group of 11-29 carbon atoms;
R 5 is aryl, aryl lower alkyl, or fatty group containing 11-29 carbon atoms containing one to eight carbon-carbon double bonds or R 7 ;
R 6 is independently R 7
R 7 is
R 1 —Ar—O—R 2 —O—R 3 —;
R 2 and R 3 are independently lower alkyl alkylene groups containing 1-6 carbon atoms;
R 1 is an alkyl group containing 1-15 carbon atoms; and
Ar is aryl.
29. The pharmaceutical composition according to claim 28 wherein R 4 is a fatty group containing 15-21 carbon atoms.