Compositions and methods of use of phorbol esters
Methods and compositions containing a phorbol ester or a derivative of a phorbol ester are provided for the treatment of chronic and acute conditions. Such conditions may be caused by disease, be symptoms or sequelae of disease. Chronic and acute conditions may be due to viral infections such as HIV and AIDS, neoplastic diseases stroke, kidney disease, urinary incontinence, autoimmune disorders, Parkinson's disease, prostate hypertrophy, aging, or the treatment of such diseases. Additional compositions and methods are provided which employ a phorbol ester or derivative compound in combination with at least one additional agent to yield more effective treatment tools against acute and chronic conditions in mammalian subjects.
1. A method for treating or alleviating urinary incontinence in a mammalian subject comprising administering an effective amount of phorbol ester or derivative compound of Formula I, or a pharmaceutically-acceptable salt, isomer, enantiomer, solvate, hydrate, or polymorph thereof to said subject
wherein R 1 and R 2 are selected from the group consisting of hydrogen,
wherein the alkyl group contains 1 to 15 carbon atoms,
wherein the lower alkenyl group contains 1 to 7 carbon atoms,
and R 3 is selected from hydrogen or
2. A method for reducing recurrence of urinary incontinence in a mammalian subject comprising administering an effective amount of phorbol ester or derivative compound of Formula I, or a pharmaceutically-acceptable salt, isomer, enantiomer, solvate, hydrate, or polymorph thereof to said subject
wherein R 1 and R 2 are selected from the group consisting of hydrogen,
wherein the alkyl group contains 1 to 15 carbon atoms,
wherein the lower alkenyl group contains 1 to 7 carbon atoms,
and R 3 is selected from hydrogen or
3. The method of claim 1 or claim 2 , wherein R 1 or R 2 is
the remaining R 1 or R 2 is
and R 3 is hydrogen.
4. The method of claim 1 or claim 2 , wherein the phorbol ester is 12-O-tetradecanoylphobol-13-acetate.
5. The method of claim 1 or claim 2 , further comprising administering at least one secondary or adjunctive therapeutic agent that is effective in a combinatorial formulation or coordinate treatment regimen with said phorbol ester or derivative compound of Formula Ito treat or prevent symptoms of urinary incontinence.
6. The method of claim 5 or claim 2 , wherein the at least one secondary or adjunctive therapeutic agent is administered to said subject in a coordinate administration protocol, simultaneously with, prior to, or after, administration of said phorbol ester to said subject.
7. The method of claim 5 or claim 2 , wherein the at least one secondary or adjunctive therapeutic agent is an anticholinergic, topical estrogen, imipramine or duloxetine.
8. The method of claim 1 or claim 2 , wherein said effective amount comprises between about 10 μg and about 1500 μg of said phorbol ester or derivative compound of Formula I every day.
9. The method of claim 1 or claim 2 , wherein said effective amount comprises between about 125 μg to about 500 μg of said phorbol ester or derivative compound of Formula I every day.