Production of salts of 4-hydroxybutyrate using biobased raw materials

Abstract

Gamma-butyrolactone (“GBL”) and Gamma-hydroxybutyrate (“GHB”) having a unique carbon footprint as defined by the percent modern carbon (pmc) are described herein. The percent modern carbon can be controlled by varying the amounts of biobased, renewable starting materials and petroleum-based starting materials to prepare GBL or GHB having a defined pmc or by preparing mixtures of GBL or GHB prepared from biobased renewable starting materials and GBL or GHB prepared from petroleum-based starting materials.

1 . Gamma-hydroxybutyrate, deuterated gamma-hydroxybutyrate, or a pharmaceutically acceptable salt thereof, wherein a percentage of the carbon in the gamma-hydroxybutyrate, deuterated gamma-hydroxybutyrate, or salt thereof is modern carbon and the remaining percentage of carbon is fossil-carbon, wherein the ratio of modern carbon to fossil-carbon provides a unique carbon footprint which identifies the source of the gamma-hydroxybutyrate. 
     
     
         2 . The gamma-hydroxybutyrate or deuterated gamma-hydroxybutyrate of  claim 1 , wherein the percent modern carbon is about 0.1, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, or 95%. 
     
     
         3 . (canceled) 
     
     
         4 . The gamma-hydroxybutyrate or deuterated gamma-hydroxybutyrate of  claim 1 , wherein the gamma-hydroxybutyrate is in the form of an oligomer or polymer of gamma-hydroxybutyrate. 
     
     
         5 . The gamma-hydroxybutyrate or deuterated gamma-hydroxybutyrate of  claim 1 , wherein the gamma-hydroxybutyrate is in the form of an alkali metal salt. 
     
     
         6 . The gamma-hydroxybutyrate or deuterated gamma-hydroxybutyrate of  claim 5 , wherein the salt is a salt of a Group I metal, such as sodium or potassium. 
     
     
         7 . The gamma-hydroxybutyrate or deuterated gamma-hydroxybutyrate of  claim 5 , wherein the salt is a salt of a Group II metal, such as calcium or magnesium. 
     
     
         8 . The gamma-hydroxybutyrate or deuterated gamma-hydroxybutyrate of  claim 1 , wherein the gamma-hydroxybutyrate is partially or wholly deuterated. 
     
     
         9 . The gamma-hydroxybutyrate or deuterated gamma-hydroxybutyrate of  claim 1 , wherein the gamma-hydroxybutyrate is partially or wholly fluorinated. 
     
     
         10 . A pharmaceutical composition comprising the gamma-hydroxybutyrate or deuterated gamma-hydroxybutyrate of  claim 1  and one or more pharmaceutically acceptable carriers. 
     
     
         11 . The composition of  claim 10 , wherein the composition is formulated for enteral administration. 
     
     
         12 . The composition of  claim 11  comprising a solid dosage form which releases 90% by weight of the gamma-hydroxybutyrate or deuterated gamma-hydroxybutyrate within one hour as measured in de-ionized water using USP Apparatus 2 at 37° C.±2° C. with paddles at 50 rpm. 
     
     
         13 . The composition of  claim 12 , wherein the dosage form is a tablet. 
     
     
         14 . The composition of  claim 11  comprising a solid dosage form which releases 99% by weight or more of the gamma-hydroxybutyrate or deuterated gamma-hydroxybutyrate over a time period of six to eight hours as measured in de-ionized water using USP Apparatus 2 at 37° C.±2° C. with paddles at 50 rpm. 
     
     
         15 . The composition of  claim 14 , wherein the dosage form is a tablet. 
     
     
         16 . The composition of  claim 13  further comprising an outer coating on the solid tablet which releases 90% by weight of the gamma-hydroxybutyrate or deuterated gamma-hydroxybutyrate in the outer coating within one hour. 
     
     
         17 . The composition of  claim 10 , wherein the composition is formulated for parenteral administration. 
     
     
         18 . The composition of  claim 17 , wherein the gamma-hydroxybutyrate or deuterated gamma-hydroxybutyrate is formulated as a solution having a pH from about 3 to about 10.5, preferably from about 6 to about 8.5, more preferably from about 6 to about 7.5. 
     
     
         19 . The composition of  claim 18 , wherein the concentration of the gamma-hydroxybutyrate or deuterated gamma-hydroxybutyrate in the solution is from about 150 mg/ml to about 550 mg/ml. 
     
     
         20 .- 27 . (canceled) 
     
     
         28 . A method of tracing gamma-hydroxybutyrate or deuterated gamma-hydroxy butyrate, the method comprising preparing gamma-hydroxybutyrate or deuterated gamma-hydroxy butyrate having a defined ratio of modern carbon to fossil carbon, wherein the ratio of modern carbon to fossil carbon provides a unique carbon footprint which identifies the source of the gamma-hydroxybutyrate or deuterated gamma-hydroxy butyrate. 
     
     
         29 . A method of treating cataplexy and/or excessive daytime sleepiness narcolepsy, the method comprising administering an effective amount of the gamma-hydroxybutyrate or deuterated gamma-hydroxy butyrate of  claim 1 . 
     
     
         30 . (canceled) 
     
     
         31 . A composition comprising deuterated oligomers of gamma-butyrolactone in combination with deuterated poly(4-hydroxybutyrate) and deuterated gamma-butyrolactone monomer, wherein a percentage of the carbon in the compound or compounds is modern carbon and the remaining percentage of carbon is fossil-carbon, wherein the ratio of modern carbon to fossil-carbon provides a unique carbon footprint which identifies the source of the compound or compounds. 
     
     
         32 .- 34 . (canceled) 
     
     
         35 . A deuterated poly(4-hydroxybutyrate), wherein a percentage of the carbon in the deuterated poly(4-hydroxybutyrate) is modern carbon and the remaining percentage of carbon is fossil-carbon, wherein the ratio of modern carbon to fossil-carbon provides a unique carbon footprint which identifies the source of the deuterated poly(4-hydroxybutyrate). 
     
     
         36 . A method of production of a deuterated poly(4-hydroxybutyrate) (P4HB), comprising:
 providing a genetically modified organism designed to produce P4HB; and   growing the genetically modified organism on a growth media comprising one or more of deuterated water and deuterated glucose under the conditions and for the duration sufficient to produce P4HB, wherein P4HB is enriched for deuterium.   
     
     
         37 . A fiber comprising a deuterated poly(4-hydroxybutyrate). 
     
     
         38 . A mesh comprising the fiber of  claim 37 . 
     
     
         39 . A method of manufacturing a deuterated fiber, comprising:
 providing a genetically modified organism designed to produce P4H;   growing the genetically modified organism on a growth media comprising one or more of deuterated water and deuterated glucose under the conditions and for the duration sufficient to produce homo- or copolymer of 4-hydroxybutyrate (P4HB), wherein P4HB is enriched for deuterium (deuterated P4HB); and   producing a fiber comprising the deuterated P4HB.   
     
     
         40 . A suture comprising the fiber of  claim 37 . 
     
     
         41 . A deuterated poly(4-hydroxybutyrate). 
     
     
         42 . A method of production of a deuterated poly(4-hydroxybutyrate) (P4HB), comprising:
 providing a genetically modified organism designed to produce P4HB; and   growing the genetically modified organism on a growth media comprising one or more sources of deuterium under the conditions and for the duration sufficient to produce P4HB, wherein P4HB is enriched for deuterium.   
     
     
         43 . A method of manufacturing a deuterated fiber, comprising:
 providing a genetically modified organism designed to produce poly(4-hydroxybutyrate) P4HB;   growing the genetically modified organism on a growth media comprising one or more of sources of deuterium under the conditions and for the duration sufficient to produce P4HB, wherein P4HB is enriched for deuterium (deuterated P4HB); and   producing a fiber comprising the deuterated P4HB.