Dermal penetration enhancers and drug delivery systems involving same

Abstract

The invention relates to a method for treatment or prophylaxis of a disease or condition in an animal comprising administering to a mucosal membrane of said animal in need of such treatment a therapeutically effective amount of a drug delivery system comprising at least one physiologically active agent or prodrug thereof and at least one penetration enhancer selected from safe ester sunscreens.

1 - 38 . (canceled)  
   
   
       39 . A method of contraception in a human or other animal, comprising administering to a dermal surface of said human or other animal a metered dose spray of a transdermal delivery system comprising: 
 (i) an effective amount of at least one physiologically active agent for male or female contraception, or a prodrug thereof;    (ii) at least one non-volatile penetration enhancer; and    (iii) at least one volatile solvent;    wherein said dermal surface becomes touch dry within 3 minutes of application of the spray.    
   
   
       40 . The method according to  claim 39 , wherein said physiologically active agent comprises at least one active agent selected from the group consisting of oestrogens, progesterone, and progestagens other than progesterone.  
   
   
       41 . The method according to  claim 40 , wherein said physiologically active agent comprises a progestagen other than progesterone.  
   
   
       42 . The method according to  claim 41 , wherein said progestagen other than progesterone comprises at least one active agent selected from the group consisting of allyloestrenol, dydrogesterone, lynoestrenol, norethisterone, norethisterone acetate, norgestrel, norethyndrel, gestodene, levonorgestrel, medroxyprogesterone, and megestrol.  
   
   
       43 . The method according to  claim 40 , wherein said physiologically active agent comprises at least one oestrogen selected from the group consisting of oestradiol, oestrone, oestriol, ethynylestradiol, mestranol, stilboestrol, dienoestrol, epioestriol, estropipate, and zeranol.  
   
   
       44 . The method according to  claim 39 , wherein said physiologically active agent comprises at least one active agent selected from the group consisting of oestradiol, progesterone, and norethisterone acetate.  
   
   
       45 . The method according to  claim 39 , wherein said metered dose spray is administered from an applicator selected from the group consisting of an aerosol and a spray pump-pack.  
   
   
       46 . The method according to  claim 45 , wherein said applicator is a fixed or variable metered dose applicator.  
   
   
       47 . The method according to  claim 39 , wherein said metered dose spray is administered from an applicator selected from the group consisting of a metered dose aerosol, a stored energy metered dose pump, and a manual metered dose pump.  
   
   
       48 . The method according to  claim 39 , wherein said metered dose spray is administered from a topical metered dose aerosol combined with an actuator nozzle shroud, whereby the amount and uniformity of the dose of said transdermal delivery system applied to said dermal surface is accurately controlled.  
   
   
       49 . The method according to  claim 39 , wherein said penetration enhancer is selected from the group consisting of laurocapram, laurocapram derivatives, oleic acid, fatty acid esters, long chain alkylesters of 2-pyrrolidone, dodecyl (N, N-dimethylamino) acetate, dodecyl (N,N-dimethylamino) propionate, 2-N-nonyl-1,3-dioxolane, and sunscreen esters.  
   
   
       50 . The method according to  claim 39 , wherein said penetration enhancer is selected from the group consisting of laurocapram, laurocapram derivatives, oleic acid, oleic acid ester derivatives, sorbitan esters, isopropyl laurate, isopropyl myristate, isopropyl palmitate, diisopropyl adipate, propylene glycol monolaurate, propylene glycol monooleate, long chain alkyl esters of 2-pyrrolidone, dodecyl (N, N-dimethylamino) acetate, dodecyl (N, N-dimethylamino) propionate, 2-N-nonyl-1,3-dioxolane, and sunscreen esters.  
   
   
       51 . The method according to  claim 39 , wherein said penetration enhancer is a sunscreen ester of formula (I)  
     
       
         
         
             
             
         
       
       wherein R 1  is hydrogen, lower alkyl, lower alkoxy, halide, hydroxy or NR 3 R 4 ;  
       R 2  is a long chain alkyl; R 3  and R 4  are each independently hydrogen, lower alkyl or R 3  and R 4  together with the nitrogen atom to which they are attached form a 5- or 6- membered heterocyclic ring;  
       n is 0 or 1; and  
       q is 1 or2.  
     
   
   
       52 . The method according to  claim 51 , wherein said compound of formula I is selected from the group consisting of octyldimethyl-paraminobenzoate, octyl paramethoxycinnamate, octyl salicylate, and isoamyl salicylate.  
   
   
       53 . The method according to  claim 39 , wherein said volatile solvent is selected from the group consisting of ethanol and isopropanol.  
   
   
       54 . The method according to  claim 39 , wherein said transdermal delivery system is in a single phase system.  
   
   
       55 . The method according to  claim 39 , wherein said transdermal delivery system is not supersaturated with respect to said contraceptive agent.  
   
   
       56 . The method according to  claim 39 , wherein said transdermal delivery system further comprises a propellant.  
   
   
       57 . The method according to  claim 56 , wherein said propellant is selected from the group consisting of hydrocarbons, hydroflourocarbons, nitrogen, nitrous oxide, carbon dioxide, and ethers.  
   
   
       58 . The method according to  claim 39 , wherein said transdermal delivery system is administered from a metered dose container.