Details for Patent: 9,603,822

Title:	Therapeutic compositions
Abstract:	Ingenol angelate is a potent anticancer agent, and can be stabilised by dissolving it in an aprotic solvent in the presence of an acidic buffer.
Inventor(s):	Brown; Marc Barry (Watford, GB), Crothers; Michael Edward Donald (Hillsborough, GB), Nazir; Tahir (Middlesex, GB)
Assignee:	LEO Laboratories Limited (Dublin, IE)
Filing Date:	May 24, 2016
Application Number:	15/163,410
Claims:	1. A method of preparing a formulation, comprising: mixing ingenol-3-angelate with a first mixture comprising an acidifying agent and a pharmaceutically acceptable solvent to form a second mixture; and mixing a penetration enhancer and a gelling agent with the second mixture to form the formulation; wherein the formulation is a topical formulation and comprises from 0.001% by weight to 0.15% by weight ingenol-3-angelate. 2. The method of claim 1, wherein the acidifying agent is an acid buffer. 3. The method of claim 2, wherein the acid buffer is selected from the group consisting of a citrate buffer, a phosphate buffer, an acetate buffer, and a citrate-phosphate buffer. 4. The method of claim 3, wherein the acid buffer is a citrate buffer. 5. The method of claim 2, wherein the formulation comprises from 0.5% by weight to 10% by weight acid buffer. 6. The method of claim 1, wherein the solvent is selected from the group consisting of polyethylene glycol, methyl ethyl ketone, ethyl acetate, diethyl ether, and benzyl alcohol. 7. The method of claim 6, wherein the solvent is benzyl alcohol. 8. The method of claim 7, wherein the formulation comprises 0.9% by weight benzyl alcohol. 9. The method of claim 1, wherein the penetration enhancer is selected from the group consisting of isopropyl alcohol, a sulphoxide, an azone, a pyrrolidone, and an alkanol. 10. The method of claim 9, wherein the penetration enhancer is isopropyl alcohol. 11. The method of claim 10, wherein the formulation comprises 30% by weight isopropyl alcohol. 12. The method of claim 1, wherein the gelling agent is selected from the group consisting of a hydroxyalkyl cellulose polymer, carboxymethyl cellulose, methylhydroxyethyl cellulose, methyl cellulose, a carbomer, and a carrageenan. 13. The method of claim 12, wherein the gelling agent is hydroxyethylcellulose. 14. The method of claim 13, wherein the formulation comprises 1.5% by weight hydroxyethylcellulose. 15. The method of claim 1, wherein the formulation comprises from 1% by weight to 5% by weight gelling agent. 16. The method of claim 1, wherein the formulation has a pH of no greater than 4.5. 17. The formulation of claim 1, wherein the formulation has a pH of no less than 2.5. 18. The method of claim 1, wherein ingenol-3-angelate is the only active ingredient in the formulation. 19. The method of claim 1, wherein the formulation comprises from 0.01% by weight to 0.1% by weight ingenol-3-angelate. 20. The method of claim 1, wherein the formulation is selected from the group consisting of a gel, a cream, an ointment, a paint, a lotion, and a foam. 21. The method of claim 1, further comprising sterilizing the formulation by heating the formulation in an autoclave. 22. The method of claim 1, wherein the formulation is suitable for storage at 2-8.degree. C. 23. The method of claim 1, wherein the formulation is suitable for storage at 2-8.degree. C. for at least one year.