Spinosyn formulations for treatment of demodex-induced ocular and facial conditions

Abstract

The present invention concerns materials and methods for treating an ocular Demodex mite infestation of an eye of a human or animal subject, or for treating a condition of the eye or skin associated with ocular Demodex mite infestation, the method comprising topically administering a composition comprising one or more spinosyn compounds to the ocular surface (conjunctiva and/or cornea) or other anatomical structure of the eye, or to an area adjacent the eye.

What is claimed is: 
     
         1 . A topical composition comprising 0.1% to 10% (w/v) of one or more spinosyn compounds. 
     
     
         2 . The topical composition of  claim 1 , wherein the one or more spinosyn compounds have the chemical structure of formula (I) or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
       where R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , and R 16 , can be independently selected from the group consisting of: null; H; F; Cl; Br; I; OH; CN; (C 1-4 )alkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl; (C 2-4 )alkenyl, such as ethenyl, propenyl, butenyl, where the double bond can be located at any position in the alkenyl carbon chain, and including any alkenyl conformational isomers; alkynyl; aralkyl; alkaryl; halogenated alkyl; heteroalkyl; aryl; heterocyclyl; cycloalkyl; cycloalkenyl; cycloalkynyl; hydroxyalkyl; aminoalkyl; amino; alkylamino; arylamino; dialkylamino; alkylarylamino; diarylamino; acylamino; hydroxyl; thiol; thioalkyl; alkoxy; alkylthio; alkoxyalkyl; aryloxy; arylalkoxy; acyloxy; nitro; carbamoyl; trifluoromethyl; phenoxy; benzyloxy; phosphonic acid; phosphate ester; sulfonic acid (—SO 3 H); sulfonate ester; sulfonamide; alkaryl; arylalkyl; carbamate; amino; alkylamino; arylamino; dialkylamino; alkylarylamino; diarylamino; alkylthio; heteroalkyl; alkyltriphenylphosphonium; heterocyclyl; ketone (═O); ether (—OR 17 ); and ester (—COOR 18  and —OC(═O)R 18 );
 where R 5  and R 7  can be a double bond within the cyclopentane ring; 
 where R 11  and R 13  can be a double bond within the cyclohexane ring; 
 where R 17  can be independently selected from the group consisting of: a (C 1-4 )alkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl; (C 2-4 )alkenyl, such as ethenyl, propenyl, butenyl, where the double bond can be located at any position in the alkenyl carbon chain, and including any alkenyl conformational isomers; and alkynyl; 
 where R 18  can be independently selected from the group consisting of: a (C 1-4 )alkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl; (C 2-4 )alkenyl, such as ethenyl, propenyl, butenyl, where the double bond can be located at any position in the alkenyl carbon chain, and including any alkenyl conformational isomers; and alkynyl. 
 
     
     
         3 . The topical composition of  claim 1 , wherein the one or more spinosyn compounds comprise a combination of spinosyn A and spinosyn D. 
     
     
         4 . The topical composition of  claim 1 , wherein the composition includes no active agent other than the one or more spinosyn compounds. 
     
     
         5 . The topical composition of  claim 1 , wherein the composition comprises no additional agent that has miticidal activity against the  Demodex  mite. 
     
     
         6 . The topical composition of  claim 1 , wherein the composition further comprises an additional agent having miticidal activity against the  Demodex  mite. 
     
     
         7 . The topical composition of  claim 6 , wherein the additional agent having miticidal activity against the  Demodex  mite is one or more agents selected from among ivermectin, pyrethrin, pyrethroid (e.g., permethrin, resmethrin, or D-phenothrin), tea tree oil (TTO), TTO component (e.g., terpinen-4-ol (T4O)), metronidazole, hypochlorous acid (HOCl), essential oil (e.g., peppermint oil or  Salvia ), alkali metal salt (e.g., lithium salt), phosphorothioate (e.g., a non-volatile, fat soluble phosphorothioate such as coumaphos), or formamidine (e.g., amitraz). 
     
     
         8 . The topical composition of  claim 1 , further comprising an antibiotic agent. 
     
     
         9 . The topical composition of  claim 8 , wherein the antibiotic agent has antibacterial activity against one or more of  Streptococci, Staphylococci , or  Bacillus oleronius.    
     
     
         10 . The topical composition of  claim 1 , wherein the composition is a suspension or emulsion. 
     
     
         11 . The topical composition of  claim 1 , wherein the composition is an ointment and further comprises one or more excipients selected from among petrolatum, mineral oil, propylparaben, methylparaben, lanolin, chlorobutanol, water, lanolin alcohol, sodium thiosulfate, sodium phosphate monobasic, phenylmercuric acetate, mannitol, zinc chloride, sodium phosphate, potassium acetate, hypromelloses, gentamcicin sulfate, boric acid, sodium hydroxide, lanolin oil, carbomer homopolymer tybe b (allyl pentaerythritol crosslinked), or benzalkonium chloride, or wherein the composition is an emulsion and further comprises one or more excipients selected from among water, sodium hydroxide, polysorbate 80, glycerine, castor oil, carbomer copolymer type A, sodium acetate, boric acid, sorbic acid, edetate disodium, carbomer copolymer type a (allyl pentaerythritol crosslinked), or silicone oil or silicone polymer gel (e.g., dimethicone or cyclomethicone). 
     
     
         12 . The topical composition of  claim 1 , wherein the composition is a composition of one of Table 1, Table 2, Table 3, Table 4, or Table 5. 
     
     
         13 . An ocular or facial applicator pre-treated with, or containing, the topical composition of  claim 1 . 
     
     
         14 . The ocular or facial applicator of  claim 13 , wherein the applicator is a swab, cosmetic pad, wipe, wipe stick, towelette, sponge, gauze, puff, wand, brush, or comb. 
     
     
         15 . A kit comprising the topical composition of  claim 1 ; and an ocular or facial applicator. 
     
     
         16 . A method for treating an ocular  Demodex  mite infestation of an eye of a human or animal subject, or for treating a condition of the eye or skin associated with ocular  Demodex  mite infestation, comprising topically administering a composition comprising one or more spinosyn compounds to the ocular surface (conjunctiva and/or cornea) or other anatomical structure of the eye, or to an area adjacent the eye. 
     
     
         17 . The method of  claim 16 , wherein the composition comprises 0.1% to 10% (w/v) of the one or more spinosyn compounds. 
     
     
         18 . The method of  claim 16 , wherein the subject has the condition, and the condition is one or more from among  Demodex -induced blepharitis (also called  Demodex  blepharitis),  Demodex -induced ocular rosacea,  Demodex -induced facial rosacea, dry eye, meibomian gland dysfunction, chalazion, hordeolum, follicular inflammation, non-specific facial dermatitis, infiltrative keratoconjunctivitis, nodular scar deposition, or corneal neovascularization. 
     
     
         19 . The method of  claim 16 , wherein the treatment alleviates one or more signs or symptoms in the subject selected from among: itching, burning, foreign body sensation, crusting and redness of the lid margin, blurry vision, cylindrical dandruff, eyelash misalignment, eyelash trichiasis, eyelash madarosis, lid margin inflammation, meibomian gland dysfunction, blepharoconjunctivitis, and blepharokeratitis. 
     
     
         20 . The method of  claim 16 , wherein the composition is topically administered to an area adjacent to the eye, wherein the area comprises one or more of an eyelid, eyelid margin, eyelashes, eyelash follicles, eyebrow, or eyebrow follicles.