TOPICAL FORMULATIONS AND USES THEREOF

• US 20180133217A1
• Filed: 04/27/2016
• Published: 05/17/2018
• Est. Priority Date: 05/04/2015
• Status: Abandoned Application

• Current Assignee: Sun Pharma Global Fze (Sun Pharmaceutical Industries Limited)
• Original Assignee: Ocular Technologies SARL (Sun Pharmaceutical Industries Limited)
• Inventors: WEISS, Sidney L.
• Application Number:
  US15/571,482
• Publication Number:
  US 20180133217A1
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/404 Indoles, e.g. pindolol
• CPC Class Codes: A61K 31/416 condensed with carbocyclic ring systems, e.g. indazole
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 38/13 Cyclosporins
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/44 Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/1075 Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers A61K9/0026 takes precedence
• CPC Class Codes: A61P 27/02 Ophthalmic agents

Abstract

Provided herein include formulations for topical administration, such as ophthalmic formulations, and methods of using such formulations. In some aspects and embodiments the formulations may include a polyoxyl lipid or fatty acid, and or a polyalkoxylated alcohol and may include nanomicelles. Also included are methods of treating or preventing diseases or conditions, such as ocular diseases or conditions.

Claims

1. An ophthalmic formulation, comprising (a) a receptor tyrosine kinase (RTK) inhibitor, and (b) a polyoxyl lipid or fatty acid.

2. The ophthalmic formulation of claim 1, wherein the polyoxyl lipid is a n≥

40 polyoxyl lipid.

3. The ophthalmic formulation of claim 1, wherein said polyoxyl lipid or fatty acid is present in an amount equal to greater than 1% of said formulation.

4. The ophthalmic formulation of claim 1, further comprising nanomicelles.

5. The ophthalmic formulation of claim 1, wherein said polyoxyl lipid or fatty acid is selected from the group consisting of HCO-40, HCO-60, HCO-80, HCO-100, polyoxyl 40 stearate and polyoxyl 35 castor oil;

and about 0.01-0.1% octoxynol-40, and is present in the formulation as 0.5 to 5 percent of the formulation.

6. The ophthalmic formulation of claim 1, wherein said ophthalmic formulation further comprises at least one active agent selected from the group consisting of calcineurin inhibitors, mTOR inhibitors, peptides, eicosanoids (e.g. prostacyclins and prostaglandins), anti-inflammatory drugs (such as NSAIDS), autonomic drugs (e.g. beta-blockers, alpha-blockers, beta-agonists, and alpha-agonists), biologics, gene therapy agents (e.g. viral vectors), anti-infectives (e.g. antifungals, antibiotics, and antivirals), retinoids, RNAi, photo sensitizers, steroids (e.g., estrogens and derivatives thereof, and corticosteriods), mixture drugs, immuno-modulators, chemotherapeutic agents, G-coupled protein receptor antagonists, growth hormone inhibitors, integrin inhibitors, Sdf1/CXCR4 pathway inhibitors, and nACh receptor antagonists, resolvins (or resolvin-like compounds), lipoxins, and oxylipins.

7. The ophthalmic formulation of claim 1, wherein said receptor tyrosine kinase (RTK) inhibitor is a receptor tyrosine kinase (RTK) inhibitor having anti-VEGF activity.

8. The ophthalmic formulation of claim 1, wherein said receptor tyrosine kinase (RTK) inhibitor is a receptor tyrosine kinase (RTK) inhibitor having anti-PDGF activity.

9. The ophthalmic formulation of claim 1, wherein said receptor tyrosine kinase (RTK) inhibitor is one or more selected from sunitinib, regorafenib, sorafenib, imatinib, dasatinib, dovitinib, nilotinib, or linifinib, an analog thereof, or a pharmaceutically acceptable salt thereof.

10. The ophthalmic formulation of claim 1, wherein said receptor tyrosine kinase (RTK) inhibitor is sunitinib, an analog thereof, or a pharmaceutically acceptable salt thereof.

11. The ophthalmic formulation of claim 1, wherein said receptor tyrosine kinase (RTK) inhibitor is regorafenib, an analog thereof, or a pharmaceutically acceptable salt thereof.

12. The ophthalmic formulation of claim 1, wherein said receptor tyrosine kinase (RTK) inhibitor is sorafenib, an analog thereof, or a pharmaceutically acceptable salt thereof.

13. The ophthalmic formulation of claim 1, wherein said receptor tyrosine kinase (RTK) inhibitor is imatinib, an analog thereof, or a pharmaceutically acceptable salt thereof.

14. The ophthalmic formulation of claim 1, wherein said receptor tyrosine kinase (RTK) inhibitor is dasatinib, an analog thereof, or a pharmaceutically acceptable salt thereof.

15. The ophthalmic formulation of claim 1, wherein said receptor tyrosine kinase (RTK) inhibitor is dovitinib, an analog thereof, or a pharmaceutically acceptable salt thereof.

16. The ophthalmic formulation of claim 1, wherein said receptor tyrosine kinase (RTK) inhibitor is nilotinib, an analog thereof, or a pharmaceutically acceptable salt thereof.

17. The ophthalmic formulation of claim 1, wherein said receptor tyrosine kinase (RTK) inhibitor is linifinib, an analog thereof, or a pharmaceutically acceptable salt thereof.

18. A method of treating or preventing an ocular disease or condition, said method comprising topically administering a formulation of claim 1.

20. The ophthalmic formulation of claim 1, further comprising a polyalkoxylated alcohol.

19. A method of manufacturing an ophthalmic formulation comprising liquefying/melting and mixing (a) a polyoxyl lipid or fatty acid, (b) a polyalkoxylated alcohol and (c) an active agent and subsequently adding a buffer and saline.