Method for producing 5-aminolevulinic acid hydrochloride
View Patent ↗A method for producing crystals of 5-aminolevulinic acid hydrochloride wherein, in carrying out adsorption of 5-aminolevulinic acid contained in a crude 5-aminolevulinic acid solution by a cation exchange resin and its subsequent desorption with an aqueous solution containing ammonium ion, a high purity 5-aminolevulinic acid aqueous solution is obtained using a change in electric conductivity or pH of the desorption liquid as the index, and chloride ion is added to the aqueous solution which is then mixed with an organic solvent.
1. A method for producing a 5-aminolevulinic acid aqueous solution, comprising the steps of:
adjusting the pH of the crude solution comprising 5-aminolevulinic acid to a pH of about 2.5 to about 5.0;
contacting the crude solution with a strong acid, ammonium ion-binding cation exchange resin, wherein the 5-aminolevulinic acid is adsorbed to the cation exchange resin;
eluting the 5-aminolevulinic acid from the cation exchange resin with an aqueous solution containing a cation to obtain an eluate; and
recovering the 5-aminolevulinic acid using a change in electric conductivity or pH of the eluate as an index.
2. A method for producing 5-aminolevulinic acid hydrochloride, comprising contacting the eluted aqueous solution of 5-aminolevulinic acid obtained by the method of claim 1 with chloride ions.
3. A method for producing crystals of 5-aminolevulinic acid hydrochloride, comprising the steps of:
contacting the eluted aqueous solution of 5-aminolevulinic acid obtained by the method of claim 1 with chloride ions, and
mixing the thus obtained solution with an organic solvent comprising an alcohol or ketone.
4. The method according to claim 3 , wherein the organic solvent comprises methanol, ethanol, isopropanol, normal propanol or acetone.
5. The method for producing a 5-aminolevulinic acid aqueous solution according to claim 1 , wherein the adsorption of 5-aminolevulinic acid from the crude 5-aminolevulinic acid solution onto the cation exchange resin, and the elution of the 5-aminolevulinic acid from the cation exchange resin with an aqueous solution containing a cation is repeated two or more times.
6. The method for producing a 5-aminolevulinic acid aqueous solution according to claim 1 , wherein the cation is ammonium ion.
7. A method for producing 5-aminolevulinic acid hydrochloride, from a crude solution comprising the steps of:
adjusting the pH of a crude solution comprising 5-aminolevulinic acid to a pH of about 2.5 to about 5.0;
contacting the crude with a strong acid, ammonium ion-binding cation exchange resin, wherein the 5-aminolevulinic acid is adsorbed to the cation exchange resin;
eluting the 5-aminolevulinic acid from the cation exchange resin with an aqueous solution containing a cation;
contacting the eluted aqueous solution of purified 5-aminolevulinic acid with chloride ions; and
recovering the 5-aminolevulinic acid using a change in electric conductivity or pH of the eluate as an index.
8. The method for producing a 5-aminolevulinic acid hydrochloride according to claim 7 ,
wherein the adsorption of 5-aminolevulinic acid from the crude 5-aminolevulinic acid solution onto the cation exchange resin, and the elution of the 5-aminolevulinic acid from the cation exchange resin with a solution containing a cation, is repeated two or more times.
9. The method for producing a 5-aminolevulinic acid hydrochloride according to claim 8 ,
wherein a change in electric conductivity or pH of the eluate, in a respective value of 0.5 mS/cm or more or pH 0.5 or more per 1 column volume, is used as the index of recovery commencement, and a respective value of 2.5 mS/cm or more or pH 1 or more per 1 column volume is used as the index of recovery completion.
10. The method for producing a 5-aminolevulinic acid aqueous solution according to claim 1 , wherein a change in electric conductivity or pH of the eluate, in a respective value of 0.5 mS/cm or more or a pH of 0.5 or more per 1 column volume, is used as the index of recovery commencement, and a respective value of 2.5 mS/cm or more or a pH of 1 or more per 1 column volume is used as the index of recovery completion.
11. The method for producing 5-aminolevulinic acid hydrochloride according to claim 2 , wherein a change in electric conductivity or pH of the eluate, in a respective value of 0.5 mS/cm or more or a pH of 0.5 or more per 1 column volume, is used as the index of recovery commencement, and a respective value of 2.5 mS/cm or more or a pH of 1 or more per 1 column volume is used as the index of recovery completion.
12. The method or producing crystals of 5-aminolevulinic acid hydrochloride according to claim 3 , wherein a change in electric conductivity or pH of the eluate, in a respective value of 0.5 mS/cm or more or a pH of 0.5 or more per 1 column volume, is used as the index of recovery commencement, and a respective value of 2.5 mS/cm or more or a pH of 1 or more per 1 column volume is used as the index of recovery completion.
13. The method for producing 5-aminolevulinic acid hydrochloride, from a crude solution, according to claim 7 , wherein a change in electric conductivity or pH of the eluate, in a respective value of 0.5 mS/cm or more or a pH of 0.5 or more per 1 column volume, is used as the index of recovery commencement, and a respective value of 2.5 mS/cm or more or a pH of 1 or more per 1 column volume is used as the index of recovery completion.