Therapeutic compositions

• US 8,372,827 B2
• Filed: 07/31/2012
• Issued: 02/12/2013
• Est. Priority Date: 12/16/2005
• Status: Active Grant

• Current Assignee: LEO Laboratories Limited (Leo Fondet)
• Original Assignee: LEO Laboratories Limited (Leo Fondet)
• Inventors: Brown, Marc Barry, Crowthers, Michael Edward Donald, Nazir, Tahir
• Primary Examiner(s): Hui, San-Ming
• Assistant Examiner(s): CRUZ, KATHRIEN ANN
• Application Number:
  US13/563,716
• Publication Number:
  US 20120295970A1
• Time in Patent Office: 196 Days
• Field of Search: 514/183
• US Class Current: 514/183
• CPC Class Codes: A61K 31/215 of carboxylic acids
• CPC Class Codes: A61K 31/22 of acyclic acids, e.g. pravastatin
• CPC Class Codes: A61K 36/47 Euphorbiaceae (Spurge family), e.g. Ricinus (castorbean)
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

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.

Claims

1. A pharmaceutical formulation for topical use in treatment of a subject, said pharmaceutical formulation comprising ingenol angelate in an amount from about 0.001% to about 0.15% w/w, wherein at least about 97.5% of the ingenol angelate is ingenol-3-angelate (isoform ‘

b’

) and said pharmaceutical formulation has a pH of less than 4.

2. The pharmaceutical formulation of claim 1 having a pH of about 3.5 or less.

3. The pharmaceutical formulation of claim 1 having a pH of about 3.0.

4. The pharmaceutical formulation of claim 1 having a pH within the range of about 2.5 to less than 4.0.

5. The pharmaceutical formulation of claim 1, wherein said pharmaceutical formulation is a gel.

6. The pharmaceutical formulation of claim 1, wherein said pharmaceutical formulation is a cream.

7. The pharmaceutical formulation of claim 1, wherein said pharmaceutical formulation is an ointment.

8. The pharmaceutical formulation of claim 1, wherein said pharmaceutical formulation is a paint.

9. The pharmaceutical formulation of claim 1, wherein said pharmaceutical formulation is a lotion.

10. The pharmaceutical formulation of claim 1, wherein said pharmaceutical formulation is a foam.

11. The pharmaceutical formulation of claim 1, wherein said pharmaceutical formulation is a transdermal patch.

12. The pharmaceutical formulation of claim 1, wherein said pharmaceutical formulation is a sustained release formulation.

13. The pharmaceutical formulation of claim 1, wherein said pharmaceutical formulation is an emulsion.

14. The pharmaceutical formulation of claim 1, wherein said pharmaceutical formulation is an oil.

15. The pharmaceutical formulation of claim 1, wherein said pharmaceutical formulation is a buccal formulation.

16. The pharmaceutical formulation of claim 1, wherein said pharmaceutical formulation further comprises a penetration enhancer, a preservative, a gelling agent or a buffer.