| PATENT NUMBER | This data is not available for free |
| PATENT GRANT DATE | May 11, 1999 |
| PATENT TITLE |
Glucosamine sulfate metal chloride compositions and process of preparing same |
| PATENT ABSTRACT | Glucosamine compositions comprising the compounds glucosamine sulfate metal chloride, wherein the metal, i.e. the cation, is lithium, sodium, magnesium, zinc or manganese. The compounds have purity levels of at least about 97%, with water present in a maximum amount of about 10 wt. %, based on the weight of the composition. The compounds are prepared by contacting glucosamine hydrochloride with the metal sulfate in the presence of water to form an aqueous solution of glucosamine sulfate metal 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 metal 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 | November 13, 1998 |
| PATENT PARENT CASE TEXT | This data is not available for free |
| PATENT CLAIMS |
What is claimed is: 1. A composition comprising: (a) the compound glucosamine sulfate metal chloride, wherein the metal is selected from the group consisting of lithium, sodium, magnesium, zinc and manganese, 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 wherein the metal comprises sodium. 6. The composition of claim 1 wherein the metal comprises manganese. 7. A process for preparing a composition comprising the compound glucosamine sulfate metal chloride, wherein the metal is selected from the group consisting of lithium, sodium, magnesium, zinc and manganese, said compound having a purity level of at least about 97%, which comprises the steps of: (a) contacting glucosamine hydrochloride with a sulfate of said metal in the presence of water to form an aqueous solution of glucosamine sulfate metal 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 metal chloride is limited to a maximum of about 3%. 8. The process of claim 7 wherein the glucosamine hydrochloride and metal 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 contacting in step (a) takes place for a period of about 15 minutes to 2 hours. 9. The process of claim 7 wherein the water is present in step (a) 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 about 20 to 45.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 to -5.degree. C. 13. The process of claim 7 wherein the metal sulfate comprises sodium sulfate. 14. The process of claim 7 wherein the metal sulfate comprises manganese sulfate. -------------------------------------------------------------------------------- |
| PATENT DESCRIPTION |
FIELD OF INVENTION The invention relates to glucosamine sulfate metal chloride compositions and processes for preparing same. The glucosamine sulfate metal chloride compositions of the invention are true compounds having a purity level of at least about 97%. BACKGROUND OF THE INVENTION Glucosamine 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. Although products in the market-place are labelled as, or referred to as, "glucosamine sulfate" or "stabilized glucosamine sulfate", they are misnomers, since such products are not true compounds, but rather unreacted mixtures of glucosamine hydrochloride and a salt such as potassium or sodium sulfate. Mixed salts of glucosamine hydrochloride and alkaline or earth alkaline metal sulfates such as potassium sulfate, and sodium sulfate 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 and U.S. Pat. No. 3,683,076 which discloses a mixture of glucosamine sulfate and glucosamine hydroiodide. 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 compositions comprising true compounds of glucosamine sulfate metal chlorides, wherein the metal, i.e. the cation, is lithium, sodium, magnesium, zinc or manganese. The compounds will have a purity level of about 97%, preferably at least 99%. Moreover, the processes 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. DETAILED DESCRIPTION OF THE INVENTION The invention pertains to novel compositions and processes for preparing same. The compositions comprise: (a) glucosamine sulfate metal chloride compounds having a purity level of at least about 97%, wherein the metal, i.e. the cation, is selected from the group consisting of lithium, sodium, magnesium, zinc and manganese; and (b) water, present in a maximum amount of about 10 wt.%, based on the weight of the composition. Preferably, the compounds will have purity levels of at least 99%. Indeed, the processes of the invention typically result in compounds having purity levels 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 processes of the invention will produce compositions with water contents of not greater than 3 wt. %. Any water present in the compositions of the invention is not to be regarded as an "impurity" in the classical sense. The compositions of the invention are intended to be ingested and minor adjustments in the dosage to be ingested can be readily made to account for such water. Prior art compositions referred to as glucosamine sulfate potassium chloride or glucosamine sulfate prepared using isopropanol or acetone as a precipitant exhibit unacceptable chloride assay values of about 93% and densities of 0.55-0.65, indicating that potassium chloride is abstracted from the composition and remains in the aqueous precipitant layer. The glucosamine sulfate metal chloride compounds of the invention have densities which vary depending on the particular metal chloride, and are set forth in the Examples below. The chloride assay value of the compounds of the invention remain about 100 wt. %, prior to and subsequent to nitrogen sparging, which indicates that true compounds, rather than mixtures of salts or mixtures of reacted components plus unreacted components have been prepared by the processes of the invention. Also as discussed below, a simple test involving the addition of the composition to a mixture of liquid halogenated aliphatic hydrocarbons with a density of about 2.0 g/cc will readily verify whether a composition alleged to be stabilized glucosamine sulfate, i.e. glucosamine sulfate metal chloride is a true compound or is a mixture of unreacted glucosamine hydrochloride and a metal sulfate. In the presence of the halogenated hydrocarbons, the true compound will float as a layer on the top, whereas some of the mixture of unreacted glucosamine hydrochloride and the metal sulfate will float on the top and some of such mixture will fall as a precipitate to the bottom. The processes for preparing the novel compositions of the invention are quite simple and straightforward and typically result in quantitative yields. The processes involves the following steps: (a) contacting glucosamine hydrochloride with a metal sulfate in the presence of water to form an aqueous solution of glucosamine sulfate metal chloride, wherein the metal is lithium, sodium, magnesium, zinc or manganese; and (b) recovering the compound glucosamine sulfate metal chloride 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 is limited to a maximum of about 3 wt. %. Typically, the glucosamine hydrochloride and metal 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 , i.e. step (a) takes place for a period of about 15 minutes to 2 hours. Step (a) takes place at temperatures, of about 20 to about 45.degree. C. Higher temperatures are undesirable since exposure to such higher temperatures for prolonged periods of time will lead to decomposition, as evidenced by a yellowing of the solution. 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 to -5.degree. C. The processes of the invention avoid the use of precipitants such as isopropanol, acetone, dioxane, etc. in order to recover the glucosamine sulfate metal chloride from the aqueous reaction mixture. It has also been found that if removal of the water by distillation is used to recover the glucosamine sulfate metal chloride, some decomposition of the product occurs, even if the distillation is carried out at moderate temperatures of about 50.degree. C. and 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 is attempted to be removed under vacuum at a pressure of about 20 mm Hg at ambient temperatures, significant foaming of the reaction mass occurs which prevents 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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