Transdermal Pharmaceutical Delivery Composition

Abstract

A pharmaceutically delivery system is described comprising a pharmaceutically active agent and acidified nitrite as an agent to produce local production of nitric oxide at the skin surface. The dosage form may be in any pharmaceutically acceptable carrier means and comprises an acidifying agent adapted to reduce the pH at the environment. In one embodiment, a barrier consisting of a membrane allows diffusions of the anaesthetic and nitrite ions while preventing direct contact of the skin and acidifying agent.

1 - 20 . (canceled) 
     
     
         21 . A membrane associated with a pharmaceutically active agent, a pharmacologically acceptable acidifying agent, and a pharmacologically acceptable source of nitrite ions or a nitrite precursor therefor. 
     
     
         22 . The membrane of  claim 21 , wherein the pharmacologically acceptable source of nitrite ions is an alkali metal nitrite or an alkaline earth metal nitrite. 
     
     
         23 . The membrane of  claim 21 , wherein the pharmacologically acceptable acidifying agent is an organic acid. 
     
     
         24 . The membrane of  claim 23 , wherein the organic acid is chosen from ascorbic acid, salicylic acid, acetyl salicylic acid, a (C 1 -C 6 ) alkyl carboxylic acid, and citric acid, or a salt or derivative thereof. 
     
     
         25 . The membrane of  claim 21 , wherein the pharmaceutically active agent is chosen from an anaesthetic, an analgesic, a hormone, an immunosuppressant drug, a steroid, an antibiotic, a protein, a peptide, a proteoglycan, a nucleotide, an oligonucleotide, a vitamin, a mineral, a growth factor, a non-steroidal anti-inflammatory drug (NSAID), and an antihistamine. 
     
     
         26 . The membrane of  claim 25 , wherein the pharmaceutically active agent is an anaesthetic chosen from amethocaine (tetracaine), lignocaine (lidocaine), xylocaine, bupivacaine, prilocaine, ropivacaine, benzocaine, mepivocaine, and cocaine, or any mixture thereof. 
     
     
         27 . The membrane of  claim 25 , wherein the pharmaceutically active agent is an analgesic selected from the group consisting of ibuprofen, indomethacin, diclofenac, acetylsalicylic acid, paracetamol, propranolol, metoprolol, and oxycodone. 
     
     
         28 . The membrane of  claim 25 , wherein the pharmaceutically active agent is a hormone selected from the group consisting of thyroid hormone releasing hormone, oestrogen, progesterone, testosterone, insulin, vasopressin, and hydrocortisone. 
     
     
         29 . The membrane of  claim 25 , wherein the pharmaceutically active agent is an antihistamine and is terfenadine. 
     
     
         30 . The membrane of  claim 25 , wherein the pharmaceutically active agent is an immunosuppressant drug and is cyclosporin. 
     
     
         31 . The membrane of  claim 25 , wherein the pharmaceutically active agent is selected from the group consisting of verapamil, scopolamine, nitroglycerine, isosorbide dinitrate, clonidine and nicotine. 
     
     
         32 . The membrane of  claim 21 , wherein the final nitrite ion concentration is up to 20%. 
     
     
         33 . The membrane of  claim 21 , wherein the membrane comprises a polymeric material. 
     
     
         34 . The membrane of  claim 33 , wherein the polymeric material is chosen from nitrocellulose, cellulose, agarose, polyethylene, and polyester. 
     
     
         35 . The membrane of  claim 34 , wherein the polyester is hydrophilic polyester block copolymer. 
     
     
         36 . The membrane of  claim 21 , wherein the membrane is fully or partially permeable to the passage of nitric oxide. 
     
     
         37 . A method of treating broken skin, open wounds, or burns in a patient in need thereof comprising applying the membrane of  claim 21  to the patient on the area of broken skin, open wound, or burn. 
     
     
         38 . A method of providing pain relief or preventing pain in a patient in need of localized anaesthesia comprising applying the membrane of  claim 26  to the patient at a localized painful region or on a region that will become painful. 
     
     
         39 . The method of  claim 38 , wherein the pharmaceutically acceptable acidifying agent and the pharmacologically acceptable source of nitrite ions are formulated in or on the membrane, further comprising applying the membrane on the patient for effecting a topical reaction on the patient's skin at the site of administration. 
     
     
         40 . The method of  claim 39 , wherein the pharmaceutically active agent is formulated in or on the membrane, or is administered to the patient with the membrane.