Therapeutic compositions
Ingenol angelate is a potent anticancer agent, and can be stabilized by dissolving it in an aprotic solvent in the presence of an acidic buffer.
1. A pharmaceutical formulation of ingenol-3-angelate (isoform ‘b’), said pharmaceutical formulation comprising ingenol-3-angelate (isoform ‘b’) and a pharmaceutically acceptable solvent, said pharmaceutical formulation further comprising a pharmaceutically acceptable acidifying agent, wherein said pharmaceutical formulation retains at least about 95% of said ingenol-3-angelate (isoform ‘b’) after twelve months of storage at a temperature within the range of about 2° C. to about 8° C.
2. The pharmaceutical formulation of claim 1 , wherein said solvent is selected from the group consisting of polyethylene glycol, methyl ethyl ketone, ethyl acetate, diethyl ether, benzyl alcohol, and mixtures thereof.
3. The pharmaceutical formulation of claim 1 , wherein said solvent consists essentially of benzyl alcohol.
4. The pharmaceutical formulation of claim 1 , wherein said acidifying agent is an acid buffer.
5. The pharmaceutical formulation of claim 4 , wherein said acid buffer is a citrate or phosphate buffer.
6. The pharmaceutical formulation of claim 1 , wherein said pharmaceutical formulation comprises:
a) isopropyl alcohol;
b) hydroxyethylcellulose;
c) benzyl alcohol; and
d) citrate buffer.
7. The pharmaceutical formulation of claim 1 , wherein said pharmaceutical formulation retains at least 97.5% of said ingenol-3-angelate (isoform ‘b’) after twelve months of storage at a temperature within the range of about 2° C. to about 8° C.
8. The pharmaceutical formulation of claim 1 , wherein said pharmaceutical formulation retains at least 99.0% of said ingenol-3-angelate (isoform ‘b’) after twelve months of storage at a temperature within the range of about 2° C. to about 8° C.
9. The pharmaceutical formulation of claim 1 , wherein said pharmaceutical formulation retains at least 97.5% of said ingenol-3-angelate (isoform ‘b’)
after three months of storage at a temperature within the range of about 2° C. to about 8° C.
10. The pharmaceutical formulation of claim 1 , wherein said pharmaceutical formulation retains at least 99.0% of said ingenol-3-angelate (isoform ‘b’)
after three months of storage at a temperature within the range of about 2° C. to about 8° C.
11. A pharmaceutical formulation of ingenol-3-angelate (isoform ‘b’), said pharmaceutical formulation comprising ingenol-3-angelate (isoform ‘b’) and a pharmaceutically acceptable solvent, said pharmaceutical formulation further comprising a pharmaceutically acceptable acidifying agent, wherein said pharmaceutical formulation retains at least about 95% of said ingenol-3-angelate (isoform ‘b’) after two weeks of storage at about 25° C.
12. The pharmaceutical formulation of claim 11 , wherein said pharmaceutical formulation retains at least 97.5% of said ingenol-3-angelate (isoform ‘b’) after two weeks of storage at about 25° C.
13. The pharmaceutical formulation of claim 11 , wherein said pharmaceutical formulation retains at least 98.5% of said ingenol-3-angelate (isoform ‘b’) after two weeks of storage at about 25° C.
14. A pharmaceutical formulation of ingenol-3-angelate (isoform ‘b’), said pharmaceutical formulation comprising ingenol-3-angelate (isoform ‘b’) and a pharmaceutically acceptable solvent, said pharmaceutical formulation further comprising a pharmaceutically acceptable acidifying agent, wherein said pharmaceutical formulation retains at least about 95% of said ingenol-3-angelate (isoform ‘b’) after four weeks of storage at about 40° C.
15. A pharmaceutical formulation of ingenol-3-angelate (isoform ‘b’), said pharmaceutical formulation comprising ingenol-3-angelate (isoform ‘b’) and a pharmaceutically acceptable solvent, said pharmaceutical formulation further comprising a pharmaceutically acceptable acidifying agent, wherein said pharmaceutical formulation retains at least about 95% of said ingenol-3-angelate (isoform ‘b’) after two weeks of storage at about 40° C.
16. The pharmaceutical formulation of claim 15 , wherein said pharmaceutical formulation retains at least 97.5% of said ingenol-3-angelate (isoform ‘b’) after two weeks of storage at about 40° C.
17. The pharmaceutical formulation of any one of claims 1 , 11 , 14 , or 15 , wherein said pharmaceutical formulation is a gel.
18. The pharmaceutical formulation of any one of claims 1 , 11 , 14 , or 15 , wherein said acidifying agent is an organic acid.