# US 4,393,236 A · Production of nonhygroscopic salts of 4-hydroxybutyric acid > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 4,393,236 A - Document ID: US4393236A - Status: Granted - Kind: A - Application number: 06/282,419 - Filed: 1981-07-13 - Granted: 1983-07-12 - Earliest claimed: 1980-07-17 - Inventors: Joseph Klosa - Web page: https://patentgrep.com/patent/US4393236A ## CPC - A61K 31/60: Salicylic acid; Derivatives thereof - A61K 31/19: Carboxylic acids, e.g. valproic acid (salicylic acid A61K31/60) - A61K 31/415: 1,2-Diazoles - C07C 59/01: Saturated compounds having only one carboxyl group and containing hydroxy or O-metal groups - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS ## Abstract A method for the production of nonhygroscopic magnesium and/or calcium salts of 4-hydroxybutyric acid. A member of the group consisting of magnesium hydroxide, magnesium oxide, magnesium carbonate, calcium hydroxide, calcium oxide and calcium carbonate is reacted with 4-hydroxybutyric acid and/or 4-butyrolactone in an aqueous solution. The solution is crystallized at a sufficiently low temperature for producing a solid nonhygroscopic salt. Waterfree calcium-4-hydroxybutyrate and waterfree as well as hydrated magnesium-4-hydroxybutyrate are added to pharmaceutically acceptable carrier or filler material for production of tranquilizing and/or sleeping drugs. ## Claims ### Claim 1 Waterfree calcium-4-hydroxybutyrate of the formula Ca(COOCH.sub.2 CH.sub.2 CH.sub.2 OH).sub.2. ### Claim 2 Magnesium-4-hydroxybutyrate of the formula Mg(COOCH.sub.2 CH.sub.2 CH.sub.2 OH).sub.2. ### Claim 3 (depends on 2) Magnesium-4-hydroxybutyrate according to claim 2 furthermore free from water of hydration. ### Claim 4 (depends on 2) Magnesium-4-hydroxybutyrate according to claim 2 further comprising 4 molecules of water of hydration for each molecule of Mg(COOCH.sub.2 CH.sub.2 CH.sub.2 OH).sub.2 resulting in a composition of the formula Mg(COOCH.sub.2 CH.sub.2 CH.sub.2 OH).sub.2.4H.sub.2 O. ### Claim 5 (depends on 2) Magnesium-4-hydroxybutyrate according to claim 2 further comprising 5 molecules of water of hydration for each molecule of Mg(COOCH.sub.2 CH.sub.2 CH.sub.2 OH).sub.2 resulting in a composition of the formula Mg(COOCH.sub.2 CH.sub.2 CH.sub.2 OH).sub.2.5H.sub.2 O. ### Claim 6 A method for the production of magnesium and/or calcium salts of 4-hydroxybutyric acid comprising reacting a member of the group consisting of 4-hydroxybutyric acid, 4-butyrolactone and mixtures thereof with a member of the group consisting of magnesium hydroxide, magnesium oxide, magnesium carbonate, calcium hydroxide, calcium oxide, calcium carbonate and mixtures thereof in an aqueous solution; and crystallizing the resulting solution at initial temperatures of from about 40.degree. to 80.degree. C. sufficiently low to produce a solid nonhygroscopic salt. ### Claim 7 (depends on 6) The method according to claim 6 further comprising adding to the aqueous solution a nonsolvent for the respective 4-hydroxybutyrate before and/or during the crystallizing step. ### Claim 8 (depends on 7) The method according to claim 7 wherein the nonsolvent is acetone. ### Claim 9 (depends on 6) The method according to claim 6 further comprising recrystallizing calcium 4-hydroxybutyrate from an organic solution to provide nonhygroscopic, nonhydrated calcium 4-hydroxybutyrate. ### Claim 10 (depends on 6) The method according to claim 6 wherein the crystallizing of the magnesium 4-hydroxybutyrate is performed at a temperature below about 40.degree. C. to obtain a non-hygroscopic salt containing about 5 moles of water for each mole of magnesium 4-hydroxybutyrate Mg(COOCH.sub.2 CH.sub.2 CH.sub.2 OH).sub.2. ### Claim 11 (depends on 10) The method according to claim 10 further comprising drying the magnesium 4-hydroxybutyrate hydrated with about 5 molecules of water for removal of about 1 molecule of water to provide Mg(COOCH.sub.2 CH.sub.2 CH.sub.2 OH).4H.sub.2 O containing about 4 molecules of water of hydration for each molecule of magnesium 4-hydroxybutyrate. ### Claim 12 (depends on 6) The method of claim 6 further comprising drying the product according to claim 6 to remove all water of hydration for obtaining a nonhygroscopic salt. ### Claim 13 A pharmaceutical composition providing narcotic effects comprising a nonhygroscopic salt of 4-hydroxybutyric acid; and a pharmaceutically acceptable carrier and/or filler material. ### Claim 14 A method for the production of magnesium and/or calcium salts of 4-hydroxybutyric acid comprising reacting a member of the group consisting of 4-hydroxybutyric acid, 4 butyrolactone and mixtures thereof with a member of the group consisting of magnesium hydroxide, magnesium oxide, magnesium carbonate, calcium hydroxide, calcium oxide, calcium carbonate and mixtures thereof in an aqueous solution; and crystallizing the resulting material in the presence of a non-solvent at a temperature sufficiently low to produce a solid nonhygroscopic salt. ### Claim 15 (depends on 14) The method according to claim 14 wherein the nonsolvent is acetone. ### Claim 16 (depends on 14) The method according to claim 14 wherein the calcium 4-hydroxy butyrate is crystallized at a temperature of less than about 80.degree. C. ### Claim 17 (depends on 14) The method according to claim 14 further comprising recrystallizing calcium 4-hydroxybutyrate from an organic solution to provide nonhygroscopic, nonhydrated calcium 4-hydroxybutyrate. ### Claim 18 (depends on 14) The method according to claim 14 wherein the crystallizing of the magnesium 4-hydroxybutyrate is performed at a temperature below about 40.degree. C. to obtain a non-hygroscopic salt containing about 5 moles of water for each mole of magnesium 4-hydroxybutyrate Mg(COOCH.sub.2 CH.sub.2 CH.sub.2 OH).sub.2. ### Claim 19 (depends on 18) The method according to claim 18 further comprising drying the magnesium 4-hydroxybutyrate hydrated with about 5 molecules of water for removal of about 1 molecule of water to provide Mg(COOCH.sub.2 CH.sub.2 CH.sub.2 OH).4H.sub.2 O containing about 4 molecules of water of hydration for each molecule of magnesium 4-hydroxybutyrate. ### Claim 20 (depends on 14, 16) The method according to claim 14 further comprising drying the product according to claim 16 to remove all water of hydration for obtaining a nonhygroscopic salt. ### Claim 21 (depends on 14) The method according to claim 14 further comprising crystallizing the magnesium 4 hydroxybutyrate from an aqueous solution at a temperature up to about the boiling point of water.