| PATENT NUMBER | This data is not available for free |
| PATENT GRANT DATE | December 1, 1998 |
| PATENT TITLE |
Glucosamine sulfate potassium chloride and process of preparation thereof |
| PATENT ABSTRACT | A composition comprising the compound glucosamine sulfate potassium chloride having a purity level of at least about 97% and water present in a maximum amount of about 10 wt. %, based on the weight of the composition. The compound is prepared by contacting glucosamine hydrochloride with potassium sulfate in the presence of water to form an aqueous solution of glucosamine sulfate potassium chloride and thereafter freeze-drying the solution at a temperature and at a reduced pressure for such period of time that at least about 90 wt. % of the water is removed and decomposition of the compound glucosamine sulfate potassium chloride is limited to a maximum of about 3% |
| PATENT INVENTORS | This data is not available for free |
| PATENT ASSIGNEE | This data is not available for free |
| PATENT FILE DATE | May 22, 1998 |
| PATENT CLAIMS |
What is claimed is: 1. A composition comprising: (a) the compound glucosamine sulfate potassium chloride, said compound having a purity level of at least about 97%; and (b) water, present in a maximum amount of about 10 wt. %, based on the weight of the composition. 2. The composition of claim 1 wherein the purity level is at least 99%. 3. The composition of claim 1 wherein water is present in a maximum amount of 5 wt. %, based on the weight of the composition. 4. The composition of claim 3 wherein the water is present in a maximum amount of 3 wt. %, based on the weight of the composition. 5. The composition of claim 1 having a density of less than about 1.10 g/cc. 6. The composition of claim 5 wherein the density is in the range of 0.90 to 1.00 g/cc. 7. A process for preparing a composition comprising the compound glucosamine sulfate potassium chloride, said compound having a purity level of at least about 97%, which comprises the steps of: (a) contacting glucosamine hydrochloride with potassium sulfate in the presence of water to form an aqueous solution of glucosamine sulfate potassium chloride; and (b) recovering the compound by freeze-drying the solution from step (a) at a temperature and at a reduced pressure for such period of time that: (i) at least about 90 wt. % of the water is removed and (ii) decomposition of the compound glucosamine sulfate potassium chloride is limited to a maximum of about 3%. 8. The process of claim 7 wherein the glucosamine hydrochloride and potassium sulfate are contacted in stoichiometric quantities in the presence of sufficient water to form a concentration of solids of about 15 to 40 wt. %, and the contact takes place for a period of about 15 minutes to 2 hours. 9. The process of claim 8 wherein the water is present in an amount such that the concentration of solids is in the range of 20 to 30 wt. %, based on the weight of water plus solids. 10. The process of claim 7 wherein step (a) takes place at a temperature in the range of 20.degree. to 50.degree. C. 11. The process of claim 7 wherein the freeze-drying is carried out at a pressure of not greater than about 800 milliTorr and at a temperature in the range of about -60.degree. C. to 0.degree. C. 12. The process of claim 11 wherein the freeze-drying is carried out at a pressure in the range of 300 to 500 milliTorr and a temperature in the range of -40.degree. to -5.degree. C. -------------------------------------------------------------------------------- |
| PATENT DESCRIPTION |
FIELD OF INVENTION The invention relates to a composition comprising glucosamine sulfate potassium chloride and a process for preparing same. The glucosamine sulfate potassium chloride is a pure compound having a purity level of at least about 97%. BACKGROUND OF THE INVENTION Glucosamine sulfate is a well known and widely used substance for the treatment of rheumatic fever, arthritic and arthosic complaints, in the acute as well as chronic forms, as well as in the treatment of pathological conditions originating from metabolic disorders of the osteo-articular tissue. Mixed salts of glucosamine sulfate and alkaline or earth alkaline metal halides such as potassium chloride, and sodium chloride are well known. Such mixed salts are used rather than glucosamine sulfate alone since the latter is unstable in view of its highly hygroscopic nature and the facility with which its amino group oxidizes if not completely saltified, see e.g. U.S. Pat. No. 4,642,340. U.S. Pat. No. 3,683,076 discloses a mixture of glucosamine sulfate and glucosamine hydroiodide for the treatment of osteoarthritis and rheumatoid arthritis. Free glucosamine base may be prepared by the method recited in Chem. Ber., volume 75, page 1274. Such method involves the treatment of glucosamine hydrochloride with an ethanolic solution of a tertiary base such as triethylamine. Triethylamine hydrochloride is filtered off and the free glucosamine is then recovered from the reaction mixture. However, triethylamine is a toxic material even in small quantities and the yield of the free glucosamine base is quite low. In EP 0 214 642, free glucosamine base is converted to a mixed salt of glucosamine sulfate and potassium chloride by dissolving the glucosamine base in water, adding a stoichiometric quantity of concentrated sulfuric acid to form a solution of glucosamine sulfate in water and dissolving a stoichiometric amount of potassium chloride in the solution. The mixed salt is precipitated from the solution by addition of a precipitant such as isopropanol, stirring the mixture for about 14 hours to complete the precipitation, cooling the reaction mass to 0.degree. C. and recovering the precipitated salt by filtration. This process results in low yields. SUMMARY OF THE INVENTION It has now been found possible to prepare a composition comprising a pure compound, and not a salt mixture, of glucosamine sulfate potassium chloride. The compound will have a purity level of about 97%, preferably at least 99%. Moreover, the process of the invention avoids the use of toxic reagents such as triethylamine and also avoids the use of precipitants such as isopropanol, thereby permitting substantially quantitative yields with little or no impurities present other than very minor quantities of water. DETAILS OF THE INVENTION The invention pertains to a novel composition and a process for preparing same. The composition comprises: (a) the compound glucosamine sulfate potassium chloride having a purity level of at least about 97%; and (b) water, present in a maximum amount of about 10 wt. %, based on the weight of the composition. Preferably, the compound will have a purity level of at least 99%. Indeed, the process of the invention typically results in a compound having a purity level in excess of 99%. The principal impurity will be water which is preferably present in a maximum amount of 5 wt. %, based on the weight of the composition. Typically, the process of the invention will produce a composition with a water content of not greater than 3 wt. %. Any water present in the composition of the invention is not to be regarded as an "impurity" in the classical sense. The composition of the invention is intended to be ingested and minor adjustments in the dosage to be ingested can be readily made to account for such water. Commercially available compositions of glucosamine sulfate and potassium chloride will have a density in excess of 1.10 g/cc and, as discussed below, appear to be a mixture of glucosamine hydrochloride and potassium sulfate rather than the compound glucosamine sulfate potassium chloride. Glucosamine sulfate potassium chloride prepared using isopropanol or acetone as a precipitant exhibited unacceptable glucosamine hydrochloride assay values of about 93% and densities of 0.55-0.65, indicating that some potassium chloride is abstracted from the composition and remains in the aqueous precipitant layer. The compound glucosamine sulfate potassium chloride of the invention has a density of less than about 1.10 g/cc, preferably in the range of 0.90 to 1.00 g/cc. As discussed below in respect to Table I, the glucosamine hydrochloride assay value of the compound of the invention remains about 100 wt. %, prior to and subsequent to nitrogen sparging, which indicates that a true compound, rather than a mixture of salts or a mixture of reacted components plus unreacted components has been prepared by the process of the invention. The process for preparing the novel composition of the invention is quite simple and straightforward and typically results in quantitative yields. The process involves the following steps: (a) contacting glucosamine hydrochloride with potassium sulfate in the presence of water to form an aqueous solution of glucosamine sulfate potassium chloride; and (b) recovering the compound by freeze-drying the solution from step (a) at a temperature and at a reduced pressure for such period of time that: (i) at least about 90 wt. % of the water is removed and (ii) decomposition of the compound glucosamine sulfate potassium chloride is limited to a maximum of about 3 wt. %. Typically, the glucosamine hydrochloride and potassium sulfate are contacted in stoichiometric quantities in the presence of sufficient water to form a concentration of solids of about 15 to 40 wt. %, preferably 20 to 30 wt. %, and the contacting takes place for a period of about 15 minutes to 2 hours. Step (a) takes place at temperatures, e.g. 20.degree. to 50.degree. C. The freeze-drying in step (b) is typically carried out at a pressure of not greater than about 800 milliTorr, preferably 300 to 500 milliTorr, and at a temperature in the range of about -60.degree. C. to 0.degree. C., preferably -40.degree. to -5.degree. C. The process of the invention avoids the use of precipitants such as isopropanol, acetone, dioxane, etc. in order to recover the glucosamine sulfate potassium chloride from the aqueous reaction mixture. It has also been found that if distillation instead of freeze-drying is used to recover the glucosamine sulfate potassium chloride, some decomposition of the product occurs, even if the distillation is carried out at moderate temperatures of about 65.degree. C. and under vacuum at a pressure of about 20 mm Hg. Decomposition of the product is evidenced by a yellowing of the product and a shift in taste from sweetish and slightly salty to a bitter taste. When the water was attempted to be removed under vacuum at a pressure of about 20 mm Hg at ambient temperatures, significant foaming of the reaction mass occurred which prevented the water from being distilled off without also causing the product to flow out of the flask containing the aqueous solution. |
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| PATENT PHOTOCOPY | available on request |
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