Semifluorinated alkane compositions

• US 9,770,508 B2
• Filed: 09/12/2013
• Issued: 09/26/2017
• Est. Priority Date: 09/12/2012
• Status: Active Grant

• Current Assignee: Novaliq GmbH
• Original Assignee: Novaliq GmbH
• Inventors: Gnther, Bernhard, Scherer, Dieter, Pettigrew, Anthony
• Primary Examiner(s): West, Theodore R
• Application Number:
  US14/427,969
• Publication Number:
  US 20150238605A1
• Time in Patent Office: 1,475 Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/02 Halogenated hydrocarbons
• CPC Class Codes: A61K 31/07 Retinol compounds, e.g. vitamin A retinoic acids A61K31/203
• CPC Class Codes: A61K 31/11 Aldehydes
• CPC Class Codes: A61K 31/202 having three or more double bonds, e.g. linolenic eicosanoids, e.g. leukotrienes A61K31/557
• CPC Class Codes: A61K 31/203 Retinoic acids ; Salts thereof
• CPC Class Codes: A61K 31/232 having three or more double bonds, e.g. etretinate
• CPC Class Codes: A61K 31/351 not condensed with another ring
• CPC Class Codes: A61K 31/436 the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
• CPC Class Codes: A61K 31/4418 having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/06 Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/04 Artificial tears; Irrigation solutions
• CPC Class Codes: A61P 27/14 Decongestants or antiallergics
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/38 : of the suprarenal hormones
• CPC Class Codes: C08F 14/26 : Tetrafluoroethene
• CPC Class Codes: C09K 15/00 : Anti-oxidant compositions; Compositions inhibiting chemical change for use in well-specified applications, see the relevant places, e.g. in etching or pickling compositions C09K13/00, C23G , in foodstuffs A21D, A23, in association with organic compounds C07C, C07D , in macromolecular compositions C08; in liquid fuels or lubricants C10; in fats, fatty substances, fatty oils or waxes C11B5/00; in detergents C11D; coating or impregnating carbon or graphite based bodies to protect them from oxidation C04B41/45 ; corrosion inhibiting compositions for metallic material C23F11/00

Abstract

The invention provides novel compositions comprising semifluorinated alkanes and at least one compound sensitive or prone to oxidation. The compositions can be used as medicines that are topically administered to an eye or ophthalmic tissue. The invention further provides kits comprising such compositions.

Claims

1. A stable liquid composition comprising an active compound with more than one aliphatic double bond prone to oxidation, wherein the active compound is dissolved in a liquid vehicle comprising a semifluorinated alkane of formula

F(CF₂)_n(CH₂)_mH

wherein n and m are integers independently selected from the range of 3 to 20, and wherein the liquid vehicle is substantially free of water;

and

wherein the active compound is an omega-3 or omega-6 fatty acid or derivative thereof, or a mixture of omega-3 or omega-6 fatty acids or derivatives thereof;

and wherein the composition comprises about 0.01-10 wt. % of the active compound.

2. The composition of claim 1, wherein the active compound is a polyunsaturated fatty acid derivative which is an ester.

3. The composition of claim 1, wherein the active compound is an omega-3 fatty acid selected from α

-linolenic acid, docosahexaenoic acid, eicosapentaenoic acid, and ester derivatives thereof.

4. The composition of claim 3, wherein the composition consists essentially of the one or more omega-3 fatty acids or ester derivatives thereof dissolved in the liquid semifluorinated alkane.

5. The composition of claim 4, wherein the composition consists essentially of docosahexaenoic acid and/or eicosapentaenoic acid or alkyl ester derivatives thereof dissolved in a semifluorinated alkane of the formula F(CF₂)₆(CH₂)₈H.

6. The composition of claim 3, wherein the semifluorinated alkane is selected from F(CF₂)₄(CH₂)₅H, F(CF₂)₄(CH₂)₆H, F(CF₂)₄(CH₂)₈H, F(CF₂)₆(CH₂)₄H, F(CF₂)₆(CH₂)₆H, F(CF₂)₆(CH₂)₈H, F(CF₂)₆(CH₂)₁₀H, F(CF₂)₈(CH₂)₁₀₁₄ and F(CF₂)₁₀(CH₂)₁₂H.

7. The composition of claim 6, wherein the active compound is an omega-3 fatty acid or derivative thereof.

8. The composition of claim 7, wherein the omega-3 fatty acid or derivative thereof is selected from one or more of docosahexaenoic acid, eicosapentaenoic acid, and alkyl ester derivatives thereof.

9. The composition of claim 8, wherein the omega-3 fatty acid or derivative thereof is selected from docosahexaenoic acid ethyl ester or eicosapentaenoic acid ethyl ester.

10. The composition of claim 1, wherein the semifluorinated alkane is selected from F(CF₂)₄(CH₂)₅H, F(CF₂)₄(CH₂)₆H, F(CF₂)₄(CH₂)₈H, F(CF₂)₆(CH₂)₄H, F(CF₂)₆(CH₂)₆H, F(CF₂)₆(CH₂)₈H, F(CF₂)₆(CH₂)₁₀H, F(CF₂)₈(CH₂)₁₀H and F(CF₂)₁₀(CH₂)₁₂H.

11. The composition of claim 1, further comprising a lipid or oily excipient selected from triglyceride oils, mineral oil, medium chain triglycerides, oily fatty acids, isopropyl myristate, oily fatty alcohols, esters of sorbitol and fatty acids, oily sucrose esters, oily cholesterol esters, oily wax esters, glycerophospholipids, and sphingolipids.

12. The composition of claim 1, further comprising an anti-inflammatory compound selected from the group of NSAIDs, corticosteroids and immunomodulators.

13. The composition of claim 1, wherein the composition comprises an omega-3 fatty acid or derivative thereof, and wherein the omega-3 fatty acid or derivative thereof is the only active ingredient in the composition.

14. The composition of claim 1, wherein the composition comprises an omega-3 fatty acid derivative selected from a derivative of eicosapentaenoic acid, a derivative of docosahexaenoic acid, a resolvin, and a neuroprotectin.

15. The composition of claim 1, wherein the composition is microbiologically stable and does not comprise a preservative.

16. A method of treating a disease or condition of a patient in need of such treatment, comprising administering an effective amount of the composition of claim 1 to the patient, wherein the composition is topically administered to an eye or ophthalmic tissue, to the skin, or to the buccal, anal, vaginal, or nasal mucosa.

17. The method of claim 16, wherein the disease or condition is a condition or disease of an eye or ophthalmic tissue.

18. The method of claim 17, wherein the disease or condition is an inflammatory condition of the ophthalmic tissue or keratoconjunctivitis sicca (dry eye).

19. A method of stabilising an active compound with more than one aliphatic double bond prone to oxidation comprising the step of dissolving the active compound in a liquid vehicle comprising a semifluorinated alkane of formula

F(CF₂)_n(CH₂)_mH

wherein n and m are integers independently selected from the range of 3 to 20 and wherein the liquid vehicle is substantially free of water;

wherein the active compound is an omega-3 or omega-6 fatty acid or derivative thereof, or a mixture of omega-3 or omega-6 fatty acids or derivatives thereof;

and wherein the composition comprises about 0.01-10 wt. % of the active compound.

20. The method of claim 19, wherein the semifluorinated alkane is selected from F(CF₂)₄(CH₂)₅H, F(CF₂)₄(CH₂)₆H, F(CF₂)₄(CH₂)₈H, F(CF₂)₆(CH₂)₄H, F(CF₂)₆(CH₂)₆H, F(CF₂)₆(CH₂)₈H, F(CF₂)₆(CH₂)₁₀H, F(CF₂)₈(CH₂)₁₀₁₄ and F(CF₂)₁₀(CH₂)₁₂H.