Therapeutic compositions and methods of use
Compounds and methods useful for chemopreventative treatment of diseases such as cancer, Alzheimer's disease, Parkinson's disease, inflammatory bowel diseases, and multiple sclerosis.
1. A pharmaceutically acceptable composition comprising a compound having the formula:
wherein either A or B is a double bond such that when A is a double bond, C 11 has substituted thereon ═X, and when B is a double bond, C 12 has substituted thereon ═X; R 1 may be substituted anywhere on the six-membered ring denoted by positions 1 through 10; wherein an R 2 group may be substituted anywhere on the structure represented in formula (I); and n is a number from 0 to 100; wherein ═X, R 1 , R 2 , and R 3 are selected from the group consisting of —OR′, alkyl, alkylamino, alkoxy, aryl, aralkyl, aryloxy, alkylthio, alkylcarboxyl, hydrogen, halo, amino, cyano, nitro, thiol and hydroxyl, wherein R′ is H or alkyl, alkylamino, alkoxy, aryl, aralkyl, aryloxy, alkylthio, alkylcarboxyl, said compound being dispersed in a liposome.
2. The composition of claim 1 , wherein R 1 is a cyano group.
3. The composition of claim 1 , wherein B is double bond, X is O, R 3 is —OH, and R 1 is a cyano group.
4. The composition of claim 1 , wherein said composition is selected from the group consisting of 3,11-dioxoolean-1,12-dien-28oic acid, 2-cyano-3,11-dioxoolean-1,12-dien-28oic acid and 2-cyano-3,12-dioxoolean-1,9-dien-28oic acid.
5. The compound of claim 1 , wherein R 1 is selected from the group consisting of cyano, halo, or OR′.
6. The compound of claim 1 , wherein R 1 is at position 2.
7. The compound of claim 1 , wherein the compound has the formula:
8. The compound of claim 7 , wherein R x is methyl.
9. A composition comprising a triterpenoid compound effective for inhibiting IFN-γ-induced NO production in macrophages, said compound having an IC 50 value of at least less than 0.6 μM, said compound being dispersed in a liposome.
10. A pharmaceutically acceptable composition comprising a compound having the formula:
wherein either A or B is a double bond such that when A is a double bond, C 11 has substituted thereon ═X, and when B is a double bond, C 12 has substituted thereon ═X; R 1 may be substituted anywhere on the six-membered ring denoted by positions 1 through 10; wherein an R 2 group may be substituted anywhere on the structure represented in formula (I), and n is a number from 0 to 100, wherein ═X, R 1 , R 2 , and, R 3 are selected from the group consisting of —OR′, alkyl, alkylamino, alkoxy, aryl, aralkyl, aryloxy, alkylthio, alkylcarboxyl, hydrogen, halo, amino, cyano, nitro, thiol and hydroxyl, wherein R′ is H or alkyl, alkylamino, alkoxy, aryl, aralkyl, aryloxy, alkylthio, alkylcarboxyl,
said compound being dispersed in an oil and water emulsion.
11. A composition comprising a triterpenoid compound effective for inhibiting IFN-γ-induced NO production in macrophages, said compound having an IC 50 value of at least less than 0.6 μM, said compound being dispersed in an oil and water emulsion.
12. A pharmaceutically acceptable composition comprising a compound having the formula:
wherein either A or B is a double bond such that when A is a double bond, C 11 has substituted thereon ═X, when B is a double bond, C 12 has substituted thereon ═X; R 1 may be substituted anywhere on the six-membered ring denoted by positions 1 through 10; wherein an R 2 group may be substituted anywhere on the structure represented in formula (I), and n is a number from 0 to 100; wherein ═X, R 1 , R 2 , and R 3 are selected from the group consisting of —OR′, alkyl, alkylamino, alkoxy, aryl, aralkyl, aryloxy, alkylthio, alkylcarboxyl, hydrogen, halo, amino, cyano, nitro, thiol and hydroxyl, wherein R is H or alkyl, alkylamino, alkoxy, aryl, aralkyl, aryloxy, alkylthio, alkylcarboxyl,
said composition being formulated for oral delivery in a pharmaceutically acceptable carrier.
13. The composition of claim 12 , wherein R 1 is a cyano group.
14. The composition of claim 12 , wherein B is double bond, X is O, R 3 is —OH, and R 1 is a cyano group.
15. The composition of claim 12 , wherein said composition is selected from the group consisting of 3,11-dioxoolean-1,12-dien-28oic acid, 2-cyano-3,11-dioxoolean-1,12-dien-28oic acid and 2-cyano-3,12-dioxoolean-1,9-dien-28oic acid.
16. The compound of claim 12 , wherein R 1 is selected from the group consisting of cyano, halo, or OR′.
17. The compound of claim 12 , wherein R 1 is at position 2.
18. The compound of claim 17 , wherein the compound has the formula:
19. The compound of claim 18 , wherein R x is methyl.
20. The compound of claim 17 , wherein the composition is formulated as a hard or soft capsule, a tablet, a syrup, a suspension, a wafer, or an elixir.
21. The compound of claim 17 , wherein said composition comprises a protective coating.
22. The compound of claim 17 , wherein said composition comprises an agent that delays absorption.
23. A composition comprising a triterpenoid compound effective for inhibiting IFN-γ-induced NO production in macrophages, said compound having an IC 50 value of at least less than 0.6 μM, said composition being formulated for oral delivery.