Liquid pharmaceutical composition for the treatment of a posterior eye disease

• US 9,241,900 B2
• Filed: 11/10/2011
• Issued: 01/26/2016
• Est. Priority Date: 11/11/2010
• Status: Active Grant

• Current Assignee: Novaliq GmbH
• Original Assignee: Novaliq GmbH
• Inventors: Wilson, Clive G.
• Primary Examiner(s): Shibuya, Mark
• Assistant Examiner(s): Shiao, Yih-Horng
• Application Number:
  US13/884,785
• Publication Number:
  US 20130303473A1
• Time in Patent Office: 1,538 Days
• Field of Search: 424/78.04, 514/747, 514/754, 514/756, 514/912, 514/29, 514/152, 514/174, 514/179, 514/180, 514/182, 514/226.5
• US Class Current: 1/1
• CPC Class Codes: A61K 31/405 Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
• CPC Class Codes: A61K 31/4168 having a nitrogen attached in position 2, e.g. clonidine
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61K 47/06 Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
• CPC Class Codes: A61K 47/24 containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• 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 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

The invention provides pharmaceutical compositions based on liquid vehicles whose density is substantially higher than that of aqueous physiological fluids. The compositions are useful as medicines in ophthalmology, in particular for the treatment of conditions affecting the posterior segment of an eye. They may be administered topically into the eye or in a minimally invasive manner by periocular injection. Preferred liquid carriers are selected from semifluorinated alkanes.

Claims

1. A method for treatment of a tissue associated with a posterior segment of an eye of a patient, comprising periocular injection of a pharmaceutical composition comprising an active ingredient and a non-aqueous, physiologically tolerable, liquid vehicle having a density of at least 1.2 g/ml, wherein the liquid vehicle comprises a semifluorinated alkane.

2. The method of claim 1, wherein the treatment further includes a time period subsequent to the injection of the composition during which period the patient is in a supine position facing upwards, said period being sufficient to allow the composition to migrate from the periocular site to a site in the posterior segment of the eye.

3. The method of claim 1, wherein the patient is affected by a disease or condition selected from the group consisting of age-related macular degeneration, diabetic retinopathy, glaucoma, retinitis pigmentosa, and cytomegalovirus retinitis.

4. The method of claim 1, wherein the liquid vehicle is further comprises one or more compounds selected from the group consisting of perfluorocarbons, polysiloxanes, and mixtures thereof.

5. The method of claim 1, wherein the semifluorinated alkane is of formula

RFRH

or of formula

RFRHRF

wherein RF is a perfluorinated hydrocarbon segment with 20 or less carbon atoms, and wherein RH is a non-fluorinated hydrocarbon segment with 3 to 20 carbon atoms.

6. The method of claim 5, wherein the semifluorinated alkane is a compound of formula

RFRH

wherein RF is a linear perfluorinated hydrocarbon segment with 3 to 10 carbon atoms, and wherein RH is a linear alkyl group with 3 to 10 carbon atoms.

7. The method of claim 6, wherein the semifluorinated alkane is selected from the group consisting of F4H5, F6H6 and F6H8.

8. The method of claim 1, wherein the liquid vehicle has a density of at least about 1.35 g/ml.

9. The method of claim 1, wherein the liquid vehicle has a boiling point of at least about 120°

C.

11. The method of claim 1, wherein the liquid vehicle has a refractive index in a range from 1.29 to 1.35 at 20°

C.

12. The method of claim 1, wherein the pharmaceutical composition comprises the active ingredient in dissolved or dispersed form, which active ingredient is optionally selected from the group consisting of latanoprost, bimatoprost, tafluprost, travoprost, unoprostone, triamcinolone, dexamethasone, fluorometholone, hydrocortisone, prednisolone, rimexolone, aureomycin, azithromycin, gentamycin, ciprofloxacin, ofloxacin, fusidic acid, kanamycin, levofloxacin, lomefloxacin, oxytetracyclin, tobramycin, natamycin, moxifloxacin, carteolol, timolol, metipranolol, betaxolol, pindolol, levobunolol, brimonidine, clonidine, dipivefrine, apraclonidine, carbachol, pilocarpine, brinzolamide, dorzolamide, aciclovir, trifluridine, ganciclovir, diclofenac, bromfenac, ketorolac, flurbiprofen, and indometacin, and any salts and solvates thereof.

13. The method of claim 1, wherein the pharmaceutical composition further comprises one or more excipients selected from the group consisting of cosolvents, surfactants, stabilisers, antioxidants, preservatives, and colouring agents.

14. The method of claim 1, wherein the pharmaceutical composition is formulated so as to provide for a sustained release of the active ingredient over a period of at least about 24 hours.

10. The method of 1, wherein the pharmaceutical composition has a dynamic viscosity of not more than about 5 mPa·

s.

15. A method for treating a disease or condition of a tissue associated with a posterior segment of an eye of a patient, comprising (a) administering a pharmaceutical composition comprising an active ingredient and a non-aqueous, physiologically tolerable, liquid vehicle comprising a semifluorinated alkane and having a density of at least 1.2 g/ml, by periocular injection, and subsequently (b) bringing the patient into a supine position facing upwards for a sufficiently long time period to allow the composition to migrate from the periocular site to a site in a posterior segment of the eye.

16. The method of claim 15, wherein the supine position is maintained over a time period selected from the group consisting of at least 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, and 6 hours.

17. The method of claim 16, wherein the disease or condition is selected from the group consisting of age-related macular degeneration, diabetic retinopathy, glaucoma, retinitis pigmentosa, and cytomegalovirus retinitis.

18. The method of claim 15, wherein the liquid vehicle is further comprises one or more compounds selected from the group consisting of perfluorocarbons, polysiloxanes, and mixtures thereof.

19. The method of claim 15, wherein the semifluorinated alkane is of formula

RFRH

or of formula

RFRHRF

wherein RF is a perfluorinated hydrocarbon segment with 20 or less carbon atoms, and wherein RH is a non-fluorinated hydrocarbon segment with 3 to 20 carbon atoms.

20. The method of claim 19, wherein the semifluorinated alkane is a compound of formula

RFRH

wherein RF is a linear perfluorinated hydrocarbon segment with 3 to 10 carbon atoms, and wherein RH is a linear alkyl group with 3 to 10 carbon atoms.

21. The method of claim 20, wherein the semifluorinated alkane is selected from the group consisting of F4H5, F6H6 and F6H8.