# US 5,347,035 A · Method for crystallizing .alpha.-L-aspartyl-L-phenylalanine methyl ester > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 5,347,035 A - Document ID: US5347035A - Status: Granted - Kind: A - Application number: 08/125,193 - Filed: 1993-09-23 - Granted: 1994-09-13 - Earliest claimed: 1992-04-13 - Assignees: Tosoh Corporation - Inventors: Hidetoshi Wakamatsu; Tsuneo Harada; Yukio Kunisawa; Kiyotaka Oyama - Web page: https://patentgrep.com/patent/US5347035A ## CPC - C07K 5/0613: {Aspartame} - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) ## Abstract A method for crystallizing .alpha.-L-aspartyl-L-phenylalanine methyl ester from a hot aqueous solution containing .alpha.-L-aspartyl-L-phenylalanine methyl ester by cooling is disclosed, which comprises (i) continuously supplying a hot aqueous solution of .alpha.-L-aspartyl-L-phenylalanine methyl ester having a concentration such that the content of L-aspartyl-L-aspartyl-L-phenylalanine methyl esters is less than 0.6% by weight based on the weight of .alpha.-L-aspartyl-L-phenylalanine methyl ester in said solution, or if the content of L-aspartyl-L-aspartyl-L-phenylalanine methyl esters is 0.6% by weight or more based on the weight of .alpha.-L-aspartyl-L-phenylalanine methyl ester in said solution, to a crystallization vessel the temperature of which is lowered to that corresponding to the solubility of .alpha.-L-aspartyl-L-phenylalanine methyl ester or less, and (ii) continuously discharging the formed slurry from the crystallization vessel. ## Claims ### Claim 1 A method for crystallizing .alpha.-L-aspartyl-L-phenylalanine methyl ester from a hot aqueous solution containing .alpha.-L-aspartyl-L-phenylalanine methyl ester by cooling, which comprises the steps of: (i) continuously supplying a hot aqueous solution of .alpha.-L-aspartyl-L-phenylalanine methyl ester to a crystallization vessel; (ii) monitoring the content of L-aspartyl-L-aspartyl-L-phenylalanine methyl esters in said solution and adjusting the concentration of said solution so that (a) the content of L-aspartyl-L-aspartyl-L-phenylalanine methyl esters is less than 0.6% by weight based on the weight of .alpha.-L-aspartyl-L-phenylalanine methyl ester in said solution, or (b) if the content of L-aspartyl-L-aspartyl-L-phenylalanine methyl esters is 0.6% by weight or more based on the weight of .alpha.-L-aspartyl-L-phenylalanine methyl ester in said solution, the concentration of L-aspartyl-L-aspartyl-L-phenylalanine methyl esters in said solution is adjusted to be 150 ppm by weight or less; (ii) lowering the temperature of said solution to at least a solubility temperature of .alpha.-L-aspartyl-L-phenylalanine methyl ester to thereby form a slurry; and (iii) continuously discharging the formed slurry from the crystallization vessel. ### Claim 2 (depends on 1) A method as in claim 1, wherein said solution is an aqueous solution obtained by purifying .alpha.-L-aspartyl-L-phenylalanine methyl ester containing, as impurities, L-aspartyl-L-aspartyl-L-phenylalanine methyl esters to a level where the content of the impurity is less than 0.6% by weight, based on the weight of .alpha.-L-aspartyl-L-phenylalanine methyl ester. ### Claim 3 (depends on 2) A method as in claim 2, wherein the content of L-aspartyl-L-aspartyl-L-phenylalanine methyl esters is 0.35% by weight or less based on the weight of .alpha.-L-aspartyl-L-phenylalanine methyl ester in said solution. ### Claim 4 (depends on 2) A method as in claim 2, wherein the crystallization is carried out under forced flow conditions. ### Claim 5 (depends on 2) A method as in claim 2, wherein the crystallization is carried out under mechanical stirring at a rate of from 0.5 to 5 m/sec in terms of the tip speed of stirrer blades. ### Claim 6 (depends on 9) A method as in claim 9, wherein the crystallization is carried out under mechanical stirring at a rate of from 1.0 to 4 m/sec in terms of the tip speed of stirrer blades. ### Claim 7 (depends on 1) A method as in claim 1, wherein the content of L-aspartyl-L-aspartyl-L-phenylalanine methyl esters is 0.35% by weight or less based on the weight of .alpha.-L-aspartyl-L-phenylalanine methyl ester in said solution. ### Claim 8 (depends on 1) A method as in claim 1, wherein the crystallization is carried out under forced flow conditions. ### Claim 9 (depends on 5) A method as in claim 5, wherein the crystallization is carried out under mechanical stirring at a rate of from 0.5 to 5 m/sec in terms of the tip speed of stirrer blades. ### Claim 10 (depends on 7) A method as in claim 7, wherein the crystallization is carried out under mechanical stirring at a rate of from 1.0 to 4 m/sec in terms of the tip speed of stirrer blades.