Details for Patent: 9,539,330

Title:	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 gammahydroxybutyrate 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.
Inventor(s):	Cook; Harry (Eden Prairie, MN), Hamilton; Martha (St. Paul, MN), Danielson; Douglas (Wyoming, MI), Goderstad; Colette (St. Paul, MN), Reardan; Dayton T. (Shorewood, MN)
Assignee:	Jazz Pharmaceuticals, Inc. (Palo Alto, CA)
Filing Date:	Nov 09, 2015
Application Number:	14/936,496
Claims:	1. A pharmaceutical composition, comprising a solution of between 350 and 750 mg/ml of a salt of gamma-hydroxybutyrate, wherein the composition has a pH of between 7.0 to 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. 2. The composition in accordance with claim 1, wherein the preservative is methylparaben, butylparaben or ethylparaben. 3. The composition in accordance with claim 1, wherein the preservative is butylparaben. 4. The composition in accordance with claim 1, wherein the preservative is sodium benzoate. 5. The pharmaceutical composition of claim 1, wherein the salt is selected from the group consisting of sodium, ammonium, calcium and magnesium forms of gamma-hydroxybutyrate. 6. The pharmaceutical composition of claim 1, wherein the salt is selected from the group consisting of sodium and calcium forms of gamma-hydroxybutyrate. 7. The pharmaceutical composition of claim 1, wherein the composition additionally comprises a flavoring agent. 8. The pharmaceutical composition of claim 7, 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. 9. The pharmaceutical composition of claim 1, wherein the composition has a pH of between 7.3 to 8.5. 10. The pharmaceutical composition of claim 1, wherein the composition additionally comprises a pH adjusting or buffering agent. 11. The pharmaceutical composition of claim 10, wherein the pH adjusting or buffering agent is an acid. 12. The pharmaceutical composition of claim 11, wherein the acid is an inorganic acid. 13. The pharmaceutical composition of claim 11, wherein the acid is an organic acid. 14. The pharmaceutical composition of claim 11, 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. 15. The pharmaceutical composition of claim 14, wherein the acid is malic acid. 16. A pharmaceutical composition, comprising a solution of between 400 and 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 8.5 to 7.0, wherein the composition is chemically stable and resistant to microbial growth and comprises sodium benzoate. 17. A pharmaceutical composition, comprising a solution of between 400 and 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 8.5 to 7.0, wherein the composition is chemically stable and resistant to microbial growth and comprises butylparaben. 18. A set comprising the pharmaceutical composition of claim 1 in one or more container means. 19. The set of claim 18, 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. 20. The set of claim 19, 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. 21. The set of claim 20 wherein the first container means comprises the pharmaceutical composition, and the second container means comprises a diluent. 22. A pharmaceutical composition comprising a solution of between 400 and 600 mg/ml of a sodium salt of gamma-hydroxybutyrate, wherein the composition has a pH of between 8.5 to 7.0. 23. The pharmaceutical composition of claim 22, wherein the solution is between 450 and 550 mg/ml. 24. The pharmaceutical composition of claim 22, wherein the pH is between 7.0 and 8.2. 25. The pharmaceutical composition of claim 22, further comprising a preservative. 26. The pharmaceutical composition of claim 22, wherein the composition is an oral, aqueous solution that is diluted prior to oral administration.