Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
1998-06-11
2002-07-16
Solola, T. A. (Department: 1626)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C549S477000, C549S479000, C549S497000
Reexamination Certificate
active
06420419
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a novel L-ascorbic acid 2-phosphate salt, a process for manufacturing the salt and a method of use thereof. More specifically, the present invention relates to L-ascorbic acid 2-phosphate zinc salt or a salt hydrate of zinc L-ascorbic acid 2-phosphate (hereinafter, unless otherwise indicated, the salt including the salt hydrate thereof is referred to as an “L-ascorbic acid 2-phosphate zinc salt”) which is a soluble L-ascorbic acid 2-phosphate salt having improved stability. L-ascorbic acid 2-phosphate zinc salt does not cause an extreme alkaline condition on dissolving in water and also exhibits antimicrobial activity. The present invention also relates to a method for manufacturing the salt and a method of use thereof. By using this salt, an L-ascorbic acid 2-phosphate-containing preparation (e.g., a cosmetic preparation, medical preparation, agricultural chemical preparation, animal drug preparation, foodstuff preparation and feedstuff preparation) having improved solubility, stability and antimicrobial properties (including antiseptic, deodorizing and antidandruff effects) and which is stable under weakly acidic conditions, can be obtained.
BACKGROUND OF THE INVENTION
L-Ascorbic acid (vitamin C) imparts many physiological effects. For example, vitamin C restrains lipid peroxide, accelerates the formation of collagen, retards the formation of melanin and enhances immune functions, and has hitherto been used to achieve these effects in the fields of medicine, agricultural chemicals, animal drugs, foodstuffs, feedstuffs and cosmetic preparations. Many preparations containing L-ascorbic acid are commercially available. However, L-ascorbic acid has poor aging stability, and the effect of vitamin C cannot be always obtained even if such a preparation is used.
In order to improve stability, derivatives obtained by converting the hydroxyl groups in the enediol moiety at the 2- or 3-position each into a glycosyl group (for example, JP-A-5-117290 (the term “JP-A” as used herein means an “unexamined published Japanese patent application”)) or into a phosphoric acid ester (for example, JP-B-52-18191 (the term “JP-B” as used herein means an “examined Japanese patent publication”) and JP-A-2-279690) have been proposed.
However, L-ascorbic acid 2-glycoside salts are converted into L-ascorbic acid in vivo (particularly in humans) at a low rate as compared with L-ascorbic acid 2-phosphates. Therefore, a prompt effect cannot be achieved and an adequately high vitamin C effect can hardly be obtained.
L-Ascorbic acid 2-phosphates provide a prompt effect, and an adequately high vitamin C effect can be easily obtained. However, conventionally known L-ascorbic acid 2-phosphates are a magnesium salt, a calcium salt and a sodium salt, and among these salts, L-ascorbic acid 2-phosphate magnesium salt having excellent stability does not have sufficiently high solubility in water and is difficult to form into an aqueous solution having a concentration of 30% or more. The calcium salt scarcely dissolves in water.
Sodium L-ascorbic acid 2-phosphate having satisfactorily improved solubility can be easily formed into an aqueous solution having a concentration of about 30%, but does not have a stability that is comparable with that of the magnesium salt. Furthermore, when dissolving any of these salts, the pH of the resulting solution is in an alkaline region of approximately from 8 to 10. When the pH is adjusted to a weakly acidic condition, the stability is disadvantageously lowered.
Although the above-described L-ascorbic acid derivatives have been proposed, an L-ascorbic acid 2-phosphate having excellent solubility and which is sufficiently stable even under weakly acidic conditions has not yet been obtained.
In obtaining a salt in general, neutralization of an acid or base is used in many cases. However, this method is not appropriate for manufacturing an L-ascorbic acid 2-phosphate salt on an industrial scale. This is because an L-ascorbic acid 2-phosphate solution is strongly acidic and unstable.
SUMMARY OF THE INVENTION
It is therefore an object of the present invention to provide an L-ascorbic acid 2-phosphate having excellent solubility and which exhibits sufficiently improved stability even under weakly acidic conditions.
Under these circumstances, the present inventors have conducted extensive investigations and as a result, have found that hitherto unknown L-ascorbic acid 2-phosphate zinc salt is a compound having highly improved solubility and stability even under weakly acidic conditions, and also provides an antimicrobial (antiseptic) effect.
The above object of the present invention has been achieved by providing L-ascorbic acid 2-phosphate zinc salt and a salt hydrate of zinc L-ascorbic acid 2-phosphate which, in addition to the above properties, has also been found to have an antimicrobial effect. The present invention further provides a process for manufacturing the L-ascorbic acid 2-phosphate zinc salt and salt hydrate thereof and a method of using the salt and salt hydrate thereof in cosmetic and medical preparations, agricultural chemical preparations, animal drug preparations, foodstuff preparations and feedstuff preparations so as to increase the action of vitamin C or to provide an antimicrobial, antiseptic, deodorizing or antidandruff effect.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
Examples of the process for manufacturing the compound of the present invention include a manufacturing process starting from a soluble L-ascorbic acid 2-phosphate salt and using an ion exchange technique or the like, and a combination of this manufacturing process with other purification methods, as needed. However, the present invention is by no means limited thereto.
If L-ascorbic acid 2-phosphoric acid is represented by ApH
3
, the zinc salt of the present invention is represented by Ap
2
Zn
3
and has a structure as shown in formula (1) below:
Ap
2
Zn
3
is white powder and can be obtained as an anhydrite or salt hydrate. The salt hydrate is considered to be a hydrate Ap
2
Zn
3
.nH
2
O of Ap
2
Zn
3
.
In a preferred embodiment of the L-ascorbic acid 2-phosphate zinc salt or salt hydrate thereof of the present invention, 95 mol % or more of the entire cationic charge constitutes zinc ion and 95 mol % or more of the entire anionic charge constitutes L-ascorbic acid 2-phosphate ion. The Zn cation and Ap anion are present in sufficient amounts if each is contained in total in the above-described amounts. For example, when Ap
2
Zn
3
is present in an amount of 95 mol % or more of the total L-ascorbic acid 2-phasphate salt content, Ap
2
Zn
2
Mg or the like may be present in part. However, this is acceptable if the zinc ion content is 95 mol % or more of the total cation content.
The L-ascorbic acid 2-phosphate zinc salt of the present invention may be manufactured by a process using, for example, a soluble L-ascorbic acid 2-phosphate salt other than the zinc salt, such as Ap
2
Mg
3
, as a starting material and replacing the magnesium with zinc by chemical reaction or using an ion exchange technique (e.g., treating with an ion exchange resin). This process may also be combined with a purification method. Examples of the chemical reaction include:
Ap
2
Mg
3
+3ZnCl
2
→Ap
2
Zn
3
+3MgCl
2
In a manufacturing process using an ion exchange technique, the soluble L-ascorbic acid 2-phosphate salt used as a starting material is not necessarily purified, but may be, for example, an L-ascorbic acid 2-phosphate-containing solution obtained by reacting L-ascorbic acid with phosphorus oxychloride. The ion exchange step may employ, for example, cation exchange column chromatography or anion exchange chromatography.
When using cation exchange column chromatography, an aqueous L-ascorbic acid 2-phosphate zinc salt solution may be eluted by passing an L-ascorbic acid 2-phosphate solution through a column containing a zinc type cation exchange resin (preferably a strong cationic exchange resin).
In the case of using anion exchange chromatography, a sol
Ito Shinobu
Ogata Eiji
Suzuki Masahiro
Tsuzuki Toshi
Showa Denko Kabushiki Kaisha
Solola T. A.
Sughrue & Mion, PLLC
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