Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acid esters
Reexamination Certificate
2000-06-13
2002-02-12
Killos, Paul J. (Department: 1623)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acid esters
C560S040000
Reexamination Certificate
active
06346642
ABSTRACT:
TECHNICAL FIELD OF INVENTION
The present invention relates to a novel mixed crystal comprising the sweetening substances of aspartame (APM) and N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine methyl ester, which hereinafter may be abbreviated to “N-(3,3-dimethylbutyl)-APM” and simply referred to as “APM derivative”, and a process for production thereof.
BACKGROUND OF ART
In recent years, as eating habits have been improved to a high level, fatness caused by excessive sugar intake and diseases accompanied by fatness have been at issue. Accordingly, the development of a low-calory sweetening agent (sweetener) that replaces sugar has been in demand. The aspartame (APM) which is excellent in safety and quality of sweetness, is widely used as a sweetening agent. However, this is somewhat problematic in stability.
Under these circumstances, in the French Patent No.2697844 specification, it is stated that derivatives in which an alkyl group is introduced on an amino group of aspartic acid constituting the APM are studied in one approach to improve slightly the stability and to improve the sweetening potency, and among them and N-(3,3-dimethylbutyl)-APM is markedly improved in the sweetening potency. For the production of N-(3,3-dimethylbutyl)-APM, a process for alkylating APM reductively under the coexistence of 3,3-dimethylbutylaldehyde with sodium cyanoborohydride in methanol (refer to FR 2697844 specification), and a process for alkylating APM reductively under the coexistence of 3,3-dimethylbutylaldehyde with platinum carbon as the catalyst in a mixed solvent of water and methanol at a pH value in a range of 4.5 to 5 (refer to the above-mentioned WO95/30689 specification) are known.
The sweetening potencies of N-(3,3-dimethylbutyl)-APM being a sweetener having sweetness in a high degree and APM being an amino acid based sweetener, are reported to be 10,000 times by weight ratio (refer to Japanese Patent Kohyou Publication JP-A-8-503206) and about 200 times by weight ratio (refer to Japanese Patent Kokoku Publication JP-B-47-31031) that of sucrose, respectively.
The properties in quality of sweetness for N-(3,3-dimethylbutyl)-APM are not reported in details, and however such compound is extremely weak in early taste (which means that a sweetener when put in the mouth tastes sweet as early as sucrose), and extremely strong in later taste (which means that a sweetener tastes sweet later than sucrose), according to the present inventors, findings. It is strong in astringency (astringent taste) and badly-balanced for quality of sweetness as compared to sucrose. On the other hand, with respect to APM, its properties for quality of sweetness is weak in early taste, and strong in later taste, although they are not so bad as those in N-(3,3-dimethylbuty)-APM. Therefore, any one of both compounds has the properties for quality of sweetness which is weak in early taste, and strong in later taste, and thus is out of quality of sweetness, taking into account the fact that sucrose is natural in sweetness.
With respect to improvement in the properties for quality of sweetness, there are various proposals for improvement mainly in later taste (For example, refer to Japanese Patent Kokai Publication JP-A-56-148255, JP-A-58-141760, JP-A-58-220668, etc.). Methods for obtaining a natural quality of sweetness closer to that in sucrose, for example, by the combination with sucrose (refer to Japanese Patent Kokai Publication JP-A-57-152862), etc. are found among the proposals. On the other hand, it is possible that early taste is intensified, later taste is weakened, and also intringency is weakened to take a good balance in quality of sweetness by combining homogeneously and properly N-(3,3-dimethylbutyl)-APM being a sweetener having sweetness in a high degree with APM being an amino acid based sweetener, according to the findings found by the inventors in the present invention. For example, by combining homogeneously and properly N-(3,3-dimethylbutyl)-APM which is weak in early taste with APM, it is improved in early taste and thereby is expected to give a sweetener having sweetness in a high degree and quality of sweetness totally good in balance, closer to that of sucrose, as compared to N-(3,3-dimethylbutyl)-APM or APM each alone.
The sweetening potency of N-(3,3-dimethylbutyl)-APM is 10,000 times by weight ratio (refer to Japanese Patent Kohyou Publication JP-A-8-503206) as much as that of sucrose, and therefore it is problematic in adjusting a degree of sweetness while using it. Accordingly, a combination of N-(3,3-dimethylbutyl)-APM with APM which is proper for sweeteners is expected in view of not only improvement in quality of sweetness, but also uses thereof. Under these circumstances, it may be considered that an improvement in quality of sweetness, etc. based on these proper combinations is a problem to be solved at present.
OBJECT OF INVENTION
An object of the present invention is, in considering the properties in quality of sweetness present in APM and N-(3,3-dimethylbutyl)-APM described in the previous section, to provide an appropriate combination of APM with N-(3,3-dimethylbutyl)-APM which is improved in quality of sweetness, etc. and thereby to solve the above-mentioned problem.
DISCLOSURE OF INVENTION
In order to solve the problem and achieve the object of the present invention, the present inventors have studied earnestly and found the fact that a novel mixed crystal comprising N-(3,3-dimethylbutyl)-APM and aspartame (APM) can be obtained by subjecting a solution containing N-(3,3-dimethylbutyl)-APM and APM to crystallization, and further that thus obtained mixed crystal can achieve the above-mentioned object, is homogeneous and can improve considerably quality of sweetness, etc., in different from a simple mixture of both (two kinds of) crystals, each obtained separately from the 2 compounds.
The powder X-ray diffraction pattern for the crystal (CuK&agr;-ray; and so forth) is the same pattern to that for APM alone (For example, in the wet crystal thereof it is a crystal in IA type, and in the dry crystal thereof it is a crystal in IB type, as seen from the Japanese Patent Kokoku Publication JP-B-6-31312.). However, in the analysis of the high performance liquid chromatography, N-(3,3-dimethylbutyl)-APM is detected. On the other hand, in the case of a mixture wherein the crystals of N-(3,3-dimethylbutyl)-APM and the crystals of APM are simply mixed, peaks based on the both crystals of 2 compounds are found in the powder X-ray diffraction pattern therefor. However, from the facts that N-(3,3-dimethylbutyl)-APM is detected in the analysis of the high performance liquid chromatography, although the powder X-ray diffraction pattern therefor is the same pattern to that for APM alone, it has been found that the obtained crystal mentioned above is a novel mixed crystal comprising N-(3,3-dimethylbutyl)-APM and APM.
Further, it has been found that a novel mixed crystal comprising APM and N-(3,3-dimethylbutyl)-APM can be easily obtained by subjecting a solution containing APM and N-(3,3-dimethylbutyl)-APM to crystallization in a crystallizing operation followed by the separation of the crystals precipitated.
Based on these findings, the present invention has been completed.
That is to say, the present invention is directed to a novel mixed crystal comprising at least N-(3,3-dimethylbutyl)-APM and APM, and also to a process for producing a novel mixed crystal comprising at least N-(3,3-dimethylbutyl)-APM and APM, which comprises: subjecting a solution containing said 2 types of the compounds to a crystallizing operation.
Further, the present invention contains the followings:
1. The above mixed crystal, wherein said APM and said APM derivative is contained in a weight ratio of APM to said APM derivative being about 100 to 0.1-10, and preferably about 100 to 0.3-3 for a sweetener.
The crystals containing the mixed crystal or the crystals made of the mixed crystal under these ranges can be easily produced by selecting properly a condition for crystallization thereof when p
Kishishita Akihiro
Nagashima Kazutaka
Ajinomoto Co. Inc.
Chaudhry Mahreen
Killos Paul J.
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