Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acid esters
Reexamination Certificate
2000-09-01
2003-12-02
Richter, Johann (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acid esters
C560S041000
Reexamination Certificate
active
06657073
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a method for producing &agr;-L-aspartyl-L-phenylalanine methyl ester (“&agr;-APM” or “aspartame”). More particularly, this invention pertains to the crystallization of &agr;-APM from a metastable supersaturated solution.
2. Description of the Related Art
Aspartame or &agr;-APM is a well-known low calorie sweetener that is widely used in a variety of food and beverage products. Various methods for crystallizing &agr;-APM have been proposed, including cooling crystallization.
A typical cooling crystallization process begins with a hot unsaturated feed solution being charged to a reactor equipped with a heat exchanger for cooling. A supersaturated state is created shortly after cooling begins. Nucleation then occurs, crystals grow, and supersaturation is depleted. Because the crystal size distribution is dependent on the supersaturation profile of the crystallization process as it occurs, the cooling rate is of critical importance in determining the resulting crystal size distribution. Therefore, the cooling rate must be closely monitored and controlled in order to achieve optimal crystal size distribution.
However, such control can be difficult to achieve when the crystallization method utilizes an agitated crystallizer equipped with a cooling jacket or coil. In such a system, crystals are deposited on the cooling surface of the crystallizer. This has the effect of drastically reducing the heat transfer coefficient between the surface and solution, thereby reducing the efficiency of the cooling process and making it more difficult to control the cooling rate, and thus the crystal size distribution. Moreover, the crystals produced by such a method often display poor filterability, which makes further processing of the precipitated crystals difficult.
Another process known in the art for preparing &agr;-APM crystals comprises cooling an aqueous solution of &agr;-APM through conduction heat transfer without mechanical agitation. Such a method produces a sherbet-like pseudo-solid phase of &agr;-APM crystals. The crystals produced by such a method demonstrate better filterability than those produced by the conventional cooling process described above wherein the mixture is stirred during crystallization. However, a crystallization method involving cooling through heat transfer without mechanical agitation has the disadvantage of requiring a very long operation time.
SUMMARY OF THE INVENTION
Accordingly, in a first embodiment of the present invention, a method of producing crystals of &agr;-L-aspartyl-L-phenylalanine methyl ester (“&agr;-APM”) is provided, the method including the steps of forming a supersaturated solution of &agr;-APM, initiating nucleation of &agr;-APM crystal nuclei to form a suspension of crystal nuclei in the supersaturated solution, and growing the &agr;-APM crystal nuclei in the supersaturated solution to form the crystals without substantial formation of new crystal nuclei.
In aspects of this embodiment, the step of forming the supersaturated solution includes preparing a non-saturated &agr;-APM solution and cooling the non-saturated solution to form the supersaturated solution. The concentration of the non-saturated &agr;-APM solution may preferably be in the range from about 1.5 wt. % to about 7.0 wt. %, and more preferably from about 3.0 wt. % to about 5.5 wt. %. The temperature of the non-supersaturated &agr;-APM solution may preferably be in the range from about 35° C. to about 85° C. before cooling, more preferably from about 55° C. to about 75° C. before cooling. The cooling step may be conducted at less than a maximum allowable undercooling at a concentration, or by heat exchanging with a coolant. The solution may be an aqueous solution, and the concentration of &agr;-APM in the supersaturated aqueous solution prior to initiating nucleation may be greater than about 3.5 wt. %. The step of initiating nucleation may be conducted by mechanical forcing of the solution, such as by a pump, preferably a peristaltic pump. The step of initiating nucleation may also be conducted by introducing seed crystals into the solution. The step of initiating nucleation may be conducted at a solution temperature ranging from about 28° C. to about 80° C., more preferably from about 48° to about 66° C.
In further aspects of this embodiment, the step of growing the &agr;-APM crystal nuclei may include a spontaneous growing stage after the initiation of nucleation and a forced growing stage after the spontaneous growing stage. The spontaneous growing stage may proceed at a supersaturated solution temperature ranging from about 45° C. to 60° C. The forced growing stage may include cooling the suspension of crystal nuclei in the supersaturated solution. The cooling may be conducted at a temperature ranging from about 5° C. to 60° C., in a batch or continuous mode operation, or for a time of from about 50 to about 500 min. The suspension of crystal nuclei in the supersaturated solution may be stirred during the cooling, such as by an anchor type impeller or a ribbon type impeller, and a scraper may be attached to the impeller. The stirring may be conducted at from about 2 rpm to about 100 rpm. The suspension of crystal nuclei in the supersaturated solution should not be in contact with a gaseous atmosphere before the cooling.
In yet other aspects of this embodiment, the method further includes conducting a solid-liquid separation after growing the &agr;-APM crystal nuclei in the supersaturated solution to form &agr;-APM crystals. The &agr;-APM crystals may then be dried under elevated temperature.
In a second embodiment of the present invention, a method of continuously crystallizing a solute dissolved in a solution is provided, the method including continuously feeding a supersaturated solution to a peristaltic pump, continuously generating crystal nuclei of a solute in the supersaturated solution by rolling action of the pump to form a suspension of crystal nuclei in the supersaturated solution, continuously transferring the suspension to a crystallizer, and continuously growing the crystal nuclei by cooling the suspension in the crystallizer without substantial formation of new nuclei.
In aspects of this embodiment, the step of continuously feeding may include continuously cooling a non-saturated solution to form a supersaturated solution. The step of continuously growing may include continuously stirring the suspension or continuously scraping an internal surface of the crystallizer. The stirring may be provided by an anchor type impeller or a ribbon type impeller. The method may further include continuously withdrawing the suspension from the crystallizer.
In a third embodiment of the present invention, an apparatus for use in crystallization of a solute dissolved in a solvent is provided, the apparatus including a source of a supersaturated solution of a solute, a peristaltic pump in fluid communication with the supersaturated solution, and a crystallizer in fluid communication with the pump.
In aspects of this embodiment, the apparatus may further include a transfer line, optionally equipped with a heat exchanger, in fluid communication with the source and the pump. The crystallizer, optionally equipped with a heat exchanger, may include a cooling container adapted to receive and cool a suspension of crystal nuclei from the pump The apparatus may further include a stirrer, such as an anchor type impeller or a ribbon type impeller, or a scraper. The apparatus may further include a transfer line in fluid communication with the crystallizer and the pump.
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Daesang Corporation
Knobbe Martens Olson & Bear LLP
Richter Johann
Zucker Paul A.
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