Microbiologically sound and stable solutions of gamma-hydroxybutyrate salt for the treatment of narcolepsy

Abstract

Disclosed are formulations of gamma-hydroxybutyrate in an aqueous medium that are resistant to microbial growth. Also disclosed are formulations of gamma-hydroxybutyrate that are also resistant to the conversion into GBL. Disclosed are methods to treat sleep disorders, including narcolepsy, with these stable formulations of GHB. The present invention also provides methods to treat alcohol and opiate withdrawal, reduced levels of growth hormone, increased intracranial pressure, and physical pain in a patient.

1 - 20 . (canceled) 
     
     
         21 . A pharmaceutical composition, comprising a solution of between about 350 and 750 mg/ml of a salt of gamma-hydroxybutyrate, wherein the composition has a pH of between about 7.0 to about 9.0, wherein the composition is chemically stable and resistant to microbial growth and further consists of a preservative selected from the group consisting of sodium benzoate, methylparaben, propyl gallate BP, sorbic acid, chlorobutanol, dihydroacetic acid, monothioglycerol, potassium benzoate, benzoic acid, benzalkonium chloride, benzethonium chloride, benzyl alcohol, butylparaben, cetylpyridinium chloride, ethylenediamine, ethylparaben, glycerin, hypophosphorus acid, phenylmercuric nitrate, sassafras oil, sodium propionate, thimerosal, magnesium stearate, magnesium carbonate and potassium sorbate. 
     
     
         22 . The composition in accordance with  claim 21 , wherein the preservative is sodium benzoate. 
     
     
         23 . The pharmaceutical composition of  claim 21 , wherein the salt is selected from the group consisting of sodium, ammonium, calcium and magnesium forms of gamma-hydroxybutyrate. 
     
     
         24 . The pharmaceutical composition of  claim 21 , wherein the salt is selected from the group consisting of sodium and calcium forms of gamma-hydroxybutyrate. 
     
     
         25 . The pharmaceutical composition of  claim 21 , wherein the composition additionally comprises a flavoring agent. 
     
     
         26 . The pharmaceutical composition of  claim 25 , wherein the flavoring agent is selected from the group consisting of acacia syrup, anethole, anise oil, caraway, caraway oil, cardamom oil, cardamom seed, cherry juice, cherry syrup, cinnamon, cinnamon oil, cinnamon water, citric acid, citric acid syrup, clove oil, coca, coca syrup, coriander oil, dextrose, eriodictyon, eriodictyon fluid extract, eriodictyon syrup-aromatic, ethyl acetate, fennel oil, ginger, ginger fluid extract, ginger oleoresin, glucose, glycerin, glycyrrhiza, glycyrrhiza extract, glycyrrhiza extract-pure, glycyrrhiza syrup, honey, lavender oil, citrus extract or oil, lemon oil, mannitol, methyl salicylate, nutmeg oil, orange-bitter-oil, orange flower oil, orange flower water, orange oil, orange peel-bitter, orange syrup, peppermint, peppermint oil, peppermint water, raspberry juice, raspberry syrup, rosemary oil, rose oil, rose water, saccharin, saccharin calcium, saccharin sodium, sarsaparilla syrup, sorbitol, spearmint, spearmint oil, sucrose, syrup, thyme oil, tolu balsam, tolu balsam syrup and vanilla. 
     
     
         27 . The pharmaceutical composition of  claim 21 , wherein the composition has a pH of between about 7.3 to about 8.5. 
     
     
         28 . The pharmaceutical composition of  claim 21 , wherein the composition additionally comprises a pH adjusting or buffering agent. 
     
     
         29 . The pharmaceutical composition of  claim 28 , wherein the pH adjusting or buffering agent is an acid. 
     
     
         30 . The pharmaceutical composition of  claim 29 , wherein the acid is an inorganic acid. 
     
     
         31 . The pharmaceutical composition of  claim 29 , wherein the acid is an organic acid. 
     
     
         32 . The pharmaceutical composition of  claim 29 , wherein the acid is selected from the group consisting of malic acid, citric acid, acetic acid, boric acid, lactic acid, hydrochloric acid, phosphoric acid, sulfuric acid, and nitric acid or combinations thereof. 
     
     
         33 . The pharmaceutical composition of  claim 32 , wherein the acid is malic acid. 
     
     
         34 . A pharmaceutical composition, comprising a solution of between about 400 and about 600 mg/ml of a salt of gamma-hydroxybutyrate, selected from the group consisting of potassium, sodium, calcium, and magnesium, wherein the composition has a pH of between about 8.5 to about 7.0, wherein the composition is chemically stable and resistant to microbial growth and comprises sodium benzoate. 
     
     
         35 . A set comprising the pharmaceutical composition of  claim 21  in one or more container means. 
     
     
         36 . The set of  claim 35 , wherein the one or more container means are selected from the group consisting of a drinking cup, a dosing cup, a syringe, a pipette, a vial, an ampule, a test tube, a flask, a bottle, and a pouch syringe. 
     
     
         37 . The set of  claim 36 , comprising a third container means capable of retaining a first container means, a second container means, and one or more delivery vehicles capable of administering the pharmaceutical composition to a patient. 
     
     
         38 . The set of  claim 37  wherein the first container means comprises the pharmaceutical composition, and the second container means comprises a diluent.