It is known that 5-aminolevulinic acid is useful in the field of microorganisms for vitamin B12 production, heme enzyme production, microbial culturing, porphyrin production and the like, in the field of animals and the field of medical treatment for infectious disease treatment, sterilization, Haemophilus diagnosis, derivatives material, depilation, rheumatism therapy, cancer therapy, thrombus therapy, intraoperative diagnosis of cancer, animal cell culturing, heme metabolism studies, hair growth tonic, diagnosis of heavy metal intoxication porphyria, prevention of anemia and the like, and in the field of agriculture for plant growth regulation, salt resistance and the like.
On the other hand, production methods of 5-aminolevulinic acid are roughly classified into chemical synthesis and microbial fermentation. Regarding the chemical synthesis, methods have been reported which use, as the materials, hippuric acid (cf. Patent Reference 1), succinic acid monoester chloride (cf. Patent Reference 2), furfurylamine (e.g., see Patent Reference 3), hydroxymethylfurfural (cf. Patent Reference 4), oxovaleric acid methyl ester (cf. Patent Reference 5) and succinic acid anhydride (cf. Patent Reference 6). Regarding the microbial fermentation, methods which use anaerobic microbes, algae, photosynthetic bacteria, various recombinant microbes and the like have been reported. Particularly, a fermentation method by using a photosynthetic bacterium belonging to the genus Rhodobacter is typical (cf. Patent Reference 7).
However, there are cases in which the 5-aminolevulinic acid crude solutions produced by the aforementioned methods are used by purifying them in response to the purposes. The microbial fermentation method is known as an inexpensive industrial production method of 5-aminolevulinic acid, but saccharides, protein, amino acids, organic acids, metal ions and the like various compounds coexist in the culture. Particularly, glycine and the like amino acids whose chemical properties are close to those of 5-aminolevulinic acid are difficult to remove from the 5-aminolevulinic acid crude solution. In addition, in producing crystals of 5-aminolevulinic acid hydrochloride, it is crystallized by mixing a 5-amino levulinic acid hydrochloride aqueous solution with a poor solvent, but this crystallization step has a problem in that when glycine and the like amino acids and other contaminants are present, they inhibit the crystallization of 5-aminolevulinic acid hydrochloride. Accordingly, it is necessary to remove these contaminants before the crystallization step.
On the other hand, salts of 5-aminolevulinic acid have markedly high water-solubility, and the solubility in the case of 5-aminolevulinic acid hydrochloride is 3 M or more at room temperature, though it depends on the pH and temperature of the aqueous solution, solute coexisting in the aqueous solution and the like. Thus, it is desirable that the aqueous solution of 5-aminolevulinic acid hydrochloride to be used in the crystallization step is highly concentrated to a level close to its saturation solubility. As described in the foregoing, in order to produce crystals of 5-aminolevulinic acid hydrochloride, it is necessary to remove impurities which prevent crystallization and also to concentrate 5-aminolevulinic acid hydrochloride by dehydration. A vacuum concentrator can be exemplified as such a dehydration concentration technique, but in the case of the concentration of a large volume of a 5-aminolevulinic acid hydrochloride aqueous solution for its industrial production, it is necessary to heat the 5-aminolevulinic acid hydrochloride aqueous solution for a long time under the low pressure, so that operation of the apparatus requires large calories accompanied by the heating and cooling. In addition, since chloride ions are contained in the 5-aminolevulinic acid hydrochloride, it is necessary to take into consideration not only pressure resistance property of the vacuum concentrator but also its corrosion resistance. Accordingly, a technique for the dehydration concentration of aqueous solution of 5-aminolevulinic acid hydrochloride, which is different from the vacuum concentration have been desired.    Patent Reference 1: JP-A-48-92328    Patent Reference 2: JP-A-62-111954    Patent Reference 3: JP-A-2-76841    Patent Reference 4: JP-A-6-172281    Patent Reference 5: JP-A-7-188133    Patent Reference 6: JP-A-9-316041    Patent Reference 7: JP-A-11-42083
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