Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
1999-06-07
2001-08-07
Vollano, Jean F. (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
C549S218000
Reexamination Certificate
active
06271397
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to L-ascorbic acid-2-phosphoric acid potassium crystal (hereinafter “L-ascorbic acid-2-phosphoric acid potassium” is sometimes simply referred to as “APK”) and a method for producing the APK crystal, particularly high-purity APK crystal.
High-purity APK crystal is useful as a stabilized derivative of L-ascorbic acid and can be used in various industrial fields such as cosmetic materials, medical products, food additives and feedstuff.
BACKGROUND OF THE INVENTION
L-Ascorbic acid (vitamin C) is known to have diverse physiological actions and pharmacological actions and particularly by virtue of its effect of preventing deposition of melamine dye, L-ascorbic acid has been used in whitening cosmetics. However, L-ascorbic acid is unstable to oxygen or heat and has heretofore been formed into a derivative stabilized against oxygen or heat by converting the hydroxyl group at the 2-position of L-ascorbic acid into a phosphoric acid ester. A salt, particularly a magnesium salt of L-ascorbic acid-2-phosphoric acid ester (hereinafter “L-ascorbic acid-2-phosphoric acid magnesium” is sometimes simply referred to as “APM”) is being used as a stabilized vitamin C derivative.
The currently used APM occasionally deposits during the storage of a cosmetic material and causes the problem of a rough feeling on use of the cosmetic material. In order to prevent deposition of APM, an organic acid such as citric acid or an amino acid such as glycine is added, however, deposition cannot be completely prevented. Thus, a stabilized vitamin C derivative free of deposition in a cosmetic material, particularly, APK having a high solubility in water is demanded.
Conventionally, APK has a very high solubility in water, and in turn it has not been possible to obtain APK crystals. As such, very few publications on the properties of APK crystal, such as melting point (decomposition point), exist. Furthermore, almost no production method is known for the formation of APK powder. Merely, reports on L-ascorbic acid-2-phosphoric acid ester (hereinafter “L-ascorbic acid-2-phosphoric acid ester” is sometimes simply referred to as “2-AP”) partly refer to the APK powder.
For example, JP-A-59-51293 (the term “JP-A” as used herein means an “unexamined published Japanese patent application”) describes a method for purifying 2-AP using activated carbon, where it is stated that after decationization, 2-AP is preferably formed into a salt such as the magnesium salt, calcium salt, sodium salt or potassium salt, and further that the product obtained is subjected to usual processes such as condensation and crystallization to obtain a product almost free of coloring. However, the salt used in all Examples is the magnesium salt and the potassium salt is not described at all. The present inventors have attempted to isolate the potassium salt by the method described in this Japanese patent publication, however, APK crystal could not be isolated and only a glutinous and partly agar-like product was obtained.
JP-A-8-12693 describes the production of APK in more detail, where a solution containing APK is concentrated to an APK concentration of about 10% and the crystals precipitated are collected by filtration and dried at room temperature to obtain APK. The present inventors faithfully repeated this method to isolate crystallized APK, however, crystallized APK could not be isolated and only a glutinous and partly agar-like product was obtained. In this Japanese patent publication, methanol, ethanol, propanol, acetone and the like are described as examples of water-soluble solvents for crystallizing APK. Accordingly, the present inventors attempted to isolate crystallized APK by the method of this Japanese patent publication using these water-soluble solvents individually or as a mixture, however, only a glutinous and partly agar-like product was obtained.
The glutinous APK obtained by these methods has a very high solubility in water of about 50% (wt/V). A cosmetic material produced using this glutinous APK exhibits excellent storage stability, for example, even when a lotion produced using such a glutinous APK is stored in at room temperature or 40° C. for 8 months, APK was not deposited. However, the glutinous APK has low purity. Moreover, due to its high viscosity, APK adheres to the container on handling such as weighing or charging and this results in a great loss and is not profitable.
As described in the foregoing, APK is difficult to obtain as a crystal and therefore, use thereof has been heretofore limited despite its extremely high solubility in water and remarkably high stability in cosmetic materials. Thus, APK crystals easy to handle are needed.
The present invention provides a novel APK crystal with reduced coloring and also provides a method for simply producing APK as a crystal in high yield.
As a result of extensive investigations to overcome the above-described problems, the present inventors have surprisingly found that when methanol is used and a solution containing APK is added to the methanol or methanol and a solution containing APK are simultaneously mixed, such that methanol substantially accounts for 30% (V/V) or more of the sum of the solution and methanol, APK can be easily crystallized in a high yield, and further that the APK crystals obtained have remarkable stability in cosmetic materials. The present invention has been accomplished based on these findings.
SUMMARY OF THE INVENTION
The present invention provides a method for producing APK comprising adding an APK-containing solution to methanol at a temperature of from −30 to 80° C. preferably over 0.5 hour such that the methanol concentration in the solution becomes from 30 to 95% (V/V) at the completion of addition and thereby APK is crystallized, or a method for producing APK comprising simultaneously mixing methanol and an APK-containing solution at a temperature of from −30 to 80° C. such that methanol substantially always accounts for from 30 to 95% (V/V) of the sum of the solution and methanol and thereby APK is crystallized.
The production method of the present invention comprises adding a solution containing APK is added to methanol or methanol and a solution containing APK are simultaneously mixed. In this case, it is necessary to substantially maintain the condition such that methanol is always present in a concentration of 30% (V/V) or more. In the case of producing the APK crystal of the present invention in a batch system, a method of dropwise adding a solution containing APK to methanol may be used, and in the case of producing the APK in a continuous system, a method of simultaneously mixing methanol and a solution containing APK may be used.
The present invention provides a APK crystal having a molecular formula: C
6
H
6
O
9
PK
3
.H
2
O. Furthermore, the present invention provides a APK crystal obtainable by producing according to the above-described production method.
REFERENCES:
patent: 3671549 (1972-06-01), Hinkley
patent: 5202445 (1993-04-01), Dobler
patent: 5420302 (1995-05-01), Kaiser et al.
patent: 5516919 (1996-05-01), Sano et al.
patent: 0 508 233 A2 (1992-10-01), None
patent: 0 679 655 A2 (1995-11-01), None
CA:110:160221 abs of JP62298508, Jun. 1986.*
CA:111:12539 abs of NL 8700518, Oct. 1988.*
H. Nomura et al., “X-Ray Analysis of L-Ascorbic Acid 2-0-Phosphate”,Chemical and Pharmaceutical Bulletin, vol. 30, No. 3, pp. 1024-1029, Mar. 3, 1982.
Kobayashi Yuji
Oomori Kazuhiro
Soya Sumio
Utsukihara Takamitsu
Showa Denko Kabushiki Kaisha
Sughrue Mion Zinn Macpeak & Seas, PLLC
Vollano Jean F.
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