Macrocyclic lactone compounds and methods for their use
The present invention provides a pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of the general formula:
1. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of the formula:
and
salts, isomers, and N-oxides thereof.
2. The composition of claim 1 , wherein the pharmaceutically acceptable excipient is a member selected from the group consisting of a polymer, a solvent, an antioxidant, a binder, a filler, a disintegrant, a lubricant, a coating, a sweetener, a flavor, a stabilizer, a colorant, a metal, a ceramic and a semi-metal.
3. The composition of claim 2 , wherein the pharmaceutically acceptable excipient is a polymer.
4. The composition of claim 3 , wherein the polymer is selected from the group consisting of polyurethane, polyethylene imine, ethylene vinyl alcohol copolymer, silicone, C-flex, nylons, polyamide, polyimide, polytetrafluoroethylene (PTFE), parylene, parylast, poly(methacrylate), poly(vinyl chloride), poly(dimethyl siloxane), poly(ethylene vinyl acetate), polycarbonate, polyacrylamide gels, poly (methyl methacrylate), poly(n-butyl methacrylate), poly (butyl methacrylate) copolymer or blended with poly(ethylene vinyl acetate), poly(methyl methacrylate), poly (2-hydroxy ethyl methacrylate), poly(ethylene glycol methacrylates), poly(ethylene carbonate), Poly L lactide-glycolide copolymer, poly L lactide-trimethylene carbonate copolymer and Poly L-lactide.
5. The composition of claim 4 , wherein the polymer is poly(n-butylmethacrylate).
6. The composition of claim 4 , wherein the compound is present in an amount of at least 25 % (w/w) in a mixture of the compound and the polymer.
7. The composition of claim 6 , wherein the compound is present in an amount of at least 50 % (w/w).
8. The composition of claim 6 , wherein the compound is present in an amount of at least 75 % (w/w).
9. The composition of claim 1 , wherein less than about 5 % of the compound is metabolized to rapamycin.
10. The composition of claim 1 , wherein less than about 1 % of the compound is metabolized to rapamycin.
11. The composition of claim 1 , wherein less than about 0.1 % of the compound is metabolized to rapamycin.
12. The composition of claim 1 in a dosage form, having a daily systemic dose of the compound of from about 0.1 mg to about 20 mg.
13. The composition of claim 12 , wherein the daily systemic dose of the compound is from about 0.5 mg to about 10 mg.
14. The composition of claim 12 , wherein the daily systemic dose of the compound is from about 1 mg to about 5 mg.
15. The composition of claim 1 , wherein the isomers are steroisomers at the C-16 position.