Method of crystallizing aspartame

Abstract: Aspartame is crystallized out in the presence of a crystal growth inhibitor comprising one or more of dipeptides, amino acids, saccharides, organic acids and inorganic salts. Aspartame crystals having a thick and firm crystal habit are crystallized out. The crystals may well be separated by solid-liquid separation, and the drying load of them is low. After dried, the dried aspartame powder may be handled with ease and it has excellent powdery characteristics.

Description: The present invention relates to a method of crystallizing aspartame or L-α-aspartyl-L-phenylalanine methyl ester. Prior Art : Aspartame which is well known as a low-calory sweetener having a high sweetness is produced by various methods. Regarding industrial production of aspartame, crystallization of aspartame is indispensable in any method for isolating it from a reaction solution to finally obtain aspartame. For such crystallization, in general, a method has heretofore been employed in which a crude product containing aspartame is re-dissolved in water, an organic solvent or a water-containing organic solvent, the resulting solution is cooled by heat-exchange with a coolant (forced circulation, indirect cooling system) or by evaporating a part of the solvent under reduced pressure (self-evaporation system), in a crystallizer equipped with a stirrer so as to precipitate crystals, and the thus formed crystals are taken out by filtration and dewatering with a centrifugal separator or the like. However, the aspartame to be obtained by the method is of a fine needle-like and extremely fine cotton whisker-like crystal habit so that the solid-liquid separability by means of filtration and dewatering is extremely low. Because of this reason, the above-mentioned method has serious problems when being put to practical use. In addition, also in the drying step which follows the crystallization step, the drying load of the cake of the crystals is naturally high in view of the water content therein, and the bulk specific volume of the dried powder to be obtained is large so that the handling of the powder is extremely difficult. Further, since such crystals are fine powdery after being dried, they easily scatter, or that is, powdering and scattering of the dried powder from the crystals is noticeable. Moreover, the dried powder in such a fine powdery form has a small dissolution rate as it contains much air in the voids between the fine particles of the powder. Because of these reasons, the powdery aspartame has still another problem with respect to the powdery characteristic of it. Therefore, if aspartame crystals having a thick and firm crystal habit could be obtained, they would be extremely advantageous in view of the process of producing them and the product itself. As a means of overcoming the above-mentioned problems, a method (static crystallization method) of crystallizing aspartame from its aqueous solution by cooling the solution has already been proposed, in which an aqueous solution of aspartame is cooled by conductive heat transfer without imparting any forced flow, for example by mechanical stirring, thereto whereby the aspartame is crystallized out as bundle-like crystals where a plurality of needle-like crystals are bundled up to form seemingly one crystal having a thick and firm crystal habit. For the prior art, Japanese Patent Publication No. 2-45638 is referred to. A method for preparing α-APM having improved solubilization wherein α-APM is isolated from an aqueous medium containing at least one additive selected from the group consisting of sodium alginate, the sodium salt of carboxymethylcellulose, sodium starch glycolate and sodium polyacrylate is disclosed in EP-A-0 311 985. The object of the present invention is to overcome the problems in the prior art to provide a further improved static crystallization method of crystallizing aspartame from its aqueous solution. The present inventor earnestly studied for the purpose of obtaining a further improved means for solving the above-mentioned problems and, as a result, has found that when aspartame is crystallized out from its supersaturated aqueous solution in the presence of a crystal growth inhibitor as defined in claim 1, aspartame crystals having a thicker and firmer crystal habit can be obtained. On the basis of this finding, he has completed the present invention. Specifically, the present invention relates to a method of crystallizing aspartame from its supersaturated aqueous solutions, which is characterized in that an aspartame crystal growth inhibitor comprising one or more selected from L-glycyl-L-valine, L-glycyl-L-isoleucine, L-glycyl-L-serine, L-glycyl-L-tyrosine, L-glycyl-L-glutamine, L-alanyl-L-tryptophan, L-alanyl-L-threonine, L-alanyl-L-tyrosine, L-alanyl-L-glutamine, L-aspartyl-L-valine, L-aspartyl-L-leucine, L-aspartyl-L-tyrosine, L-aspartyl- L-tyrosine methyl ester, L-aspartyl-L-glutamine, L-cysteine, L-glutamic acid, L-isoleucine, L-aspartic acid, L-asparagine, L-glutamine, L-lysine, L-tyrosine, L-tryptophane, saccharose, amylose, amylopectine, citric acid and potassium chloride is added to the aqueous solution. Next, the present invention will be explained in more detail hereunder. The aspartame crystal growth inhibitor as referred to herein stands for a substance which may specifically inhibit growth of aspartame crystals in the length direction of each crystal. Such crystal growth inhibitors are L-glycyl-L-valine, L-glycyl-L-isoleucine, L-glycyl-L-serine, L-glycyl-L-tyrosine, L-glycyl-L-glutamine, L-alanyl-L-tryptophan, L-alanyl-L-threonine, L-alanyl-L-tyrosine, L-alanyl-L-glutamine, L-aspartyl-L-valine, L-aspartyl-L-leucine, L-aspartyl-L-tyrosine, L-aspartyl-L-tyrosine methyl ester, and L-aspartyl-L-glutamine; L-cysteine, L-glutamic acid, L-isoleucine, L-aspartic acid, L-asparagine, L-glutamine, L-lysine, L-tyrosine, and L-tryptophane; saccharose, amylose, and amylopectine; citric acid; and potassium chloride. Among the above-mentioned compound, the mentioned aspartyl dipeptides are generally preferred as having a large inhibiting activity. Among them, L-aspartyl-L-tyrosine and its methyl ester as well as L-aspartyl-L-glutamine are especially preferred, as having a noticeable inhibiting activity. Also L-cysteine, L-glutamic acid, amylose and amylopectine have a noticeable inhibiting activity. Incorporation of the crystal growth inhibitor into an aqueous aspartame solution may be effected by dissolving the inhibitor into the aqueous solution, for which either the inhibitor agent itself or a raw material containing the inhibitor agent may be added to the solution. The amount of the inhibitor agent in the aqueous solution is such that thicker and firmer aspartame crystals than those obtained by a conventional crystallization method in the absence of the inhibitor agent are obtained from the solution under the determined crystallization condition. The amount may extremely easily be determined by anyone skilled in the art through some pre-experiments. For instance, when L-aspartyl-L-tyrosine is used, the amount thereof is practically from 0.1 to 5 % by weight of the aspartame as being dissolved in the solution. As a crystallization solvent, water may be used. The water as a crystallizing solvent may contain any other solvent such as methanol or ethanol, provided that the additional solvent does not interfere with the essential object of the present invention or it does not specifically hinder the realization of the present invention. In the present invention, the presence of an aspartame growth inhibitor in the aqueous solution of aspartame from which aspartame is crystallized out is indispensable, and any other conventional crystallization conditions may apply to the present invention. For instance, for supersaturating aspartame in the aqueous solution thereof, any known means for cooling, condensation and addition of organic solvents may be employed. As a matter of course, the crystallization system may by kept static during the crystallization step, which, however, is not indispensable. In any case, the system may well be stirred, if desired. When the crystal growth inhibitor Of the invention is used in a static crystallization method, thicker and firmer bundle-like aspartame crystals than those to be obtained in the absence of the inhibitor can be obtained. Where the inhibitor is used in a non-static crystallization method, thicker and firmer aspartame crystals than those to be obtained in the absence of the inhibitor can be obtained. As a result, solid-liquid separatability of the crystals from the mother solution is improved and elevated so that the drying load onto the crystals is lowered and the powdery characteristics of the dried powder from the separated crystals are also improved. Separation of the aspartame crystals as crystallized out in accordance with the method of the present invention from the crystallization mother liquid as well as drying of the thus separated crystals may well be effected by any conventional methods. The method of the present invention may be applied not only to the purification of a crude product in the process of preparing aspartame but also to improve the crystal habit of aspartame crystals having a poor crystal habit by recrystallizing them in accordance with the method of the present invention. Where a crude aspartame containing impurities of diketopiperazine (DKP), which is a cyclized product of aspartame, or L-α-aspartyl-l-phenylalanine is subjected to crystallization by the method of the present invention, the amount of the mother solution as adhering to the solid after solid-liquid separation may be reduced and the cake washing efficiency may be elevated, so that aspartame crystals free from such impurities can be obtained. Because of the same reasons, incorporation of the used crystal growth inhibitor into the product crystals to be finally obtained by crystallization may be prevented. Examples: Next, the present invention will be explained further by way of the following examples. Example 1 : 2 g of aspartame, 10 mg (0.5 wt.% to aspartame) of L-aspartyl-L-tyrosine and 100 ml of water were put in a 200 ml-beaker and dissolved under heat at 65°C. The resulting solution was allowed to stand as it was at room temperature (24°C) without stirring (for static crystallization), and the crystals precipitated out were taken out by filtration and dried. The crystals had a mean diameter of 35 µm. For comparison, crystallization of aspartame from the aqueous solution was carried out in the same manner as above, except that no L-aspartyl-L-tyrosine was added to the solution. The crystals obtained had a mean diameter of 12.5 µm. Example 2 : 1 g of aspartame, 15 mg (1.5 wt.% to aspartame) of L-aspartyl-L-tyrosine and 50 ml of water were put in a 100 ml-beaker and dissolved under heat at 65°C under stirring at about 200 rpm with a magnetic stirrer. Then, the resulting solution was allowed to stand as it was overnight at room temperature (24°C) still under stirring. Of the aspartame crystals thus obtained, 70 % (by weight) of the larger ones had a mean diameter of 12.5 µm. For comparison, crystallization of aspartame from the aqueous solution was carried out in the same manner as above, except that no L-aspartyl-L-tyrosine was added to the solution. 70 % (by weight) of the larger ones of the aspartame crystals thus obtained had a mean diameter of 7 µm. In accordance with the present invention, there is provided a method of crystallizing aspartame crystals having a thick and firm crystal habit. The aspartame crystals as crystallized out by the method of the invention may well be separated by solid-liquid separation, and the drying load of them is low. After being dried, the dried aspartame powder may be handled with ease and it has excellent powdery characteristics.

Claims: A method of crystallizing aspartame from its supersaturated aqueous solutions, which is characterized in that an aspartame crystal growth inhibitor comprising one or more selected from L-glycyl-L-valine, L-glycyl-L-isoleucine, L-glycyl-L-serine, L-glycyl-L-tyrosine, L-glycyl-L-glutamine, L-alanyl-L-tryptophan, L-alanyl-L-threonine, L-alanyl-L-tyrosine, L-alanyl-L-glutamine, L-aspartyl-L-valine, L-aspartyl-L-leucine, L-aspartyl-L-tyrosine, L-aspartyl-L-tyrosine methyl ester, L-aspartyl-L-glutamine, L-cysteine, L-glutamic acid, L-isoleucine, L-aspartic acid, L-asparagine, L-glutamine, L-lysine, L-tyrosine, L-tryptophane, saccharose, amylose, amylopectine, citric acid and potassium chloride is added to the aqueous solution. The method as claimed in claim 1, in which the crystal growth inhibitor comprises one or more selected from L-aspartyl-L-valine, L-aspartyl-L-leucine, L-aspartyl-L-tyrosine, L-aspartyl-L-tyrosine methyl ester, L-aspartyl-L-glutamine, L-cysteine, L-glutamic acid, amylose and amylopectine. The method as claimed in claim 1 or 2, in which the crystal growth inhibitor comprises one or more selected from L-aspartyl-L-tyrosine, its methyl ester and L-aspartyl-L-glutamine.

Inventors: EBISAWA KAZUYOSHI, KAWAOKA RIE, KUMON SATOSHI, NAGASHIMA NOBUYA, EBISAWA, KAZUYOSHI, KAWAOKA, RIE, KUMON, SATOSHI, NAGASHIMA, NOBUYA, Ebisawa, Kazuyoshi, c/o Central Research Lab., Kawaoka, Rie, c/o Central Research Lab., Kumon, Satoshi, c/o Central Research Lab., Nagashima, Nobuya, c/o Central Research Lab.
Applicants: AJINOMOTO KK, AJINOMOTO CO., INC.
Application year: 1992
Main classification: C07K5
IPC codes: C07K1, C07K5