CN1216061C - Ascorbic acid 2-phosphate metal salt with low calcium content - Google Patents
Ascorbic acid 2-phosphate metal salt with low calcium content Download PDFInfo
- Publication number
- CN1216061C CN1216061C CN 02805868 CN02805868A CN1216061C CN 1216061 C CN1216061 C CN 1216061C CN 02805868 CN02805868 CN 02805868 CN 02805868 A CN02805868 A CN 02805868A CN 1216061 C CN1216061 C CN 1216061C
- Authority
- CN
- China
- Prior art keywords
- xitix
- phosphoric acid
- acid ester
- salt
- metal
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
- C07F9/65515—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a five-membered ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
- A61K8/676—Ascorbic acid, i.e. vitamin C
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
Abstract
One of the object of the present invention is to provide an L-ascorbic acid 2-phosphate metal salt, which causes no clouding and scarcely precipitates or deposits even when added to a cosmetic material or the like having blended therein an organic acid. Disclosed herein is an L-ascorbic acid-2-phosphate metal salt with a low calcium content characterized in that the content of a calcium compound is 500 ppm or less in terms of calcium ion, and production process thereof.
Description
The cross reference of related application
The application is the application of submitting according to 35U.S.C. § 111 (a), requires the rights and interests of the applying date of the previous application 60/275,033 of submitting in March 13 calendar year 2001 according to 35U.S.C. § 111 (b) according to 35U.S.C. § 119 (e) (1).
Detailed Description Of The Invention
Industrial Application Areas
The present invention relates to L-ascorbic acid derivates of calcium contents reduction and preparation method thereof.More particularly, the present invention relates to the L-xitix 2-phosphoric acid ester metal-salt of low ca content, it can be used as the additive of makeup, medicine, food and feed substances and is widely used in various industrial circles, particularly when it being joined when containing in the organic acid makeup, even in the storage process of makeup, also can not produce muddiness or can occur precipitation hardly or deposition, and relate to its preparation method.
Background technology
Up to now, L-xitix (vitamins C) is because of its various physiology and pharmacological activity, such as suppressing fatty superoxide, promoting formation, the formation that delays melanocyte and the raise immunity of collagen to be applied to various fields, such as makeup, pharmaceutical preparation, food and feed.
Yet the L-xitix is unsettled to oxygen, heat, light etc. by generally acknowledging, and is easy to painted or degraded.Therefore, the L-xitix that is generally used for cosmetic field is not the L-vitamin c itself, improves derivative to the stability of oxygen, heat etc. but introduce phosphoric acid ester or phosphate ester salt by the hydroxyl on the 2-position that will be positioned at the L-xitix.In these derivatives, L-xitix-2-phosphoric acid ester metal-salt, particularly magnesium salts is widely used as has excellent stability and vitamin C derivatives soluble in water.
The method of the many L-of preparation xitix 2-phosphoric acid ester metal-salts is disclosed.About preparing the method for such L-xitix 2-phosphoric acid ester magnesium salts (following be called sometimes " APM "), the method that for example L-xitix-2-phosphate ester salt (following be called sometimes " 2-AP ") and reactions such as magnesium oxide, magnesium hydroxide, magnesiumcarbonate is generated L-xitix 2-phosphoric acid ester magnesium salts is known.The preparation method of this APM is recorded in a large amount of publications, such as among JP-B-52-18191 (term of Shi Yonging " JP-B " is meant " Japanese Patent of having examined open " in this article), JP-A-59-51293 (term of Shi Yonging " JP-A " is meant " unexamined disclosed Japanese patent application " in this article) and the JP-A-2-286693.
Yet, the problem of resulting APM be when it is sneaked into makeup, such as the makeup washing lotion in the time, it is easy to produce muddy, precipitation or deposition at memory period.Think that one of its reason is the gathering of composition in the APM preparation process.More particularly, in the production of APM, when with APM solution poor solvent such as methyl alcohol in when crystallization or vacuum-drying, take place easily to assemble and granularity increases.If the APM that this granularity increases mixes with makeup, muddiness, precipitation etc. then take place easily owing to the alcohols that contains in the makeup.
In order to prevent this haze problem, proposed the whole bag of tricks so far, for example in above-mentioned makeup, sneaked into Citrate trianion, oxalate, gluconate or L-Ala and resulting APM is carried out cryodesiccated method (referring to JP-A-2-231496) or use preceding the spray-dired method of resulting AMP (referring to JP-A-7-112914) to method (referring to JP-A-1-213212, JP-A-4-283593), the use of high density are preceding.
The high density of Citrate trianion, oxalate, gluconate or L-Ala is mixed and is just postponed precipitation or the deposition of APM slightly, although by using lyophilize or spray-dired APM can improve precipitation or the deposition of APM a little, effect is good inadequately.
With precipitation or deposit the particular problem that relevant problem is not only APM, and see various L-xitix 2-phosphoric acid ester metal-salts.
Goal of the invention
Making the present invention is in order to address the above problem, one of purpose of the present invention provides the L-xitix 2-phosphoric acid ester metal-salt of low ca content, even when this salt being joined when wherein being mixed with in the organic acid makeup etc., it can not produce muddiness yet and can precipitate or deposit hardly.Purpose of the present invention comprises provides its preparation method.
Another object of the present invention provides makeup, pharmaceutical preparation, beverage, food and feed, and they all contain L-xitix 2-phosphoric acid ester metal-salt and can not produce muddiness, precipitation or deposition.
Summary of the invention
As the result of further investigation to address the above problem, the current latest find of the inventor, in the storage process of the makeup that contain L-xitix 2-phosphoric acid ester metal-salt, the muddiness that produces in the makeup is not only because because of the sedimentary L-xitix of alcohol contained in makeup 2-phosphoric acid ester metal-salt causes, and be since between the organic acid (for example citric acid) that exists in the makeup and the impurity calcium in the raw material L-xitix 2-phosphoric acid ester metal-salt salt of reaction generation cause; When the calcium contents of this L-xitix 2-phosphoric acid ester metal-salt is high, be easy to generate muddiness; Calcium is from the metallic compound as raw material; When reducing, can obtain can not producing muddy makeup washing lotion etc. with content when the impurity calcium that contains in the feed metal compound.The present invention is based on these discoveries and be accomplished.
More particularly, the present invention relates to following aspect.
(1) a kind of L-of low ca content xitix-2-phosphoric acid ester metal-salt, the content that it is characterized in that calcium cpd is 500ppm or littler, according to the calcium ion meter.
(2) according to the L-xitix-2-phosphoric acid ester metal-salt of the low ca content described in (1), wherein L-xitix-2-phosphoric acid ester metal-salt is alkaline earth salt, an alkali metal salt, zinc salt, aluminium salt or the titanium salt outside the deliming.
(3) according to the L-xitix-2-phosphoric acid ester metal-salt of the low ca content described in (1), wherein L-xitix-2-phosphoric acid ester metal-salt is sodium salt, sylvite, magnesium salts, zinc salt or aluminium salt.
(4) according to the L-xitix-2-phosphoric acid ester metal-salt of the low ca content described in (1), wherein L-xitix-2-phosphoric acid ester metal-salt is sylvite, magnesium salts or zinc salt.
(5) according to the L-xitix-2-phosphoric acid ester metal-salt of the low ca content described in (1), wherein L-xitix-2-phosphoric acid ester metal-salt is a magnesium salts.
(6) a kind of method for preparing the L-xitix-2-phosphoric acid ester metal-salt of low ca content, wherein according to the calcium ion meter, the content of calcium cpd is 500ppm or littler, and described method is characterised in that and will joins in the solution that contains L-xitix-2-phosphoric acid ester in the metallic compound that 2000ppm or littler amount (according to calcium ion) contain calcium cpd.
(7) according to the method for the L-xitix-2-phosphoric acid ester metal-salt of the preparation low ca content described in (6), wherein metallic compound is any in potassium compound, sodium compound, magnesium compound or the zn cpds, and the L-xitix-2-phosphoric acid ester metal-salt that forms is any in sylvite, sodium salt, magnesium salts or the zinc salt.
(8) according to the method for the L-xitix-2-phosphoric acid ester metal-salt of the preparation low ca content described in (6), wherein metallic compound is any in magnesium oxide or the magnesium hydroxide, and the L-xitix-2-phosphoric acid ester metal-salt that forms is a magnesium salts.
(9) according to the method for the L-xitix-2-phosphoric acid ester metal-salt of any one described preparation low ca content in (6) to (8), the solution that wherein contains L-xitix-2-phosphoric acid ester contains alkalimetal ion or alkaline-earth metal ions with 10ppm or littler amount, in L-xitix-2-phosphoric acid ester.
(10) according to the method for the L-xitix-2-phosphoric acid ester metal-salt of the preparation low ca content described in (9), the solution that wherein contains L-xitix-2-phosphoric acid ester contains alkalimetal ion or alkaline-earth metal ions with 1ppm or littler amount, in L-xitix-2-phosphoric acid ester.
(11) according to the method for the L-xitix-2-phosphoric acid ester metal-salt of the preparation low ca content described in (9) or (10), the solution that wherein contains L-xitix-2-phosphoric acid ester prepares by the following method: this method comprises reacts L-xitix, alkali metal hydroxide and phosphorylation agent in the presence of water, then by making spent ion exchange resin remove metal ion from the solution of the L-xitix-2-phosphoric acid ester metal-salt of formation.
(12) according to the method for the L-xitix-2-phosphoric acid ester metal-salt of the preparation low ca content described in (11), wherein ion exchange resin is the anionite-exchange resin of weakly alkaline or medium basic.
(13) a kind of makeup of low turbidity is characterized in that wherein being mixed with the L-xitix 2-phosphoric acid ester metal-salt of the low ca content described in (1).
(14) according to the makeup of the low turbidity described in (13), wherein makeup are washing lotions.
(15), wherein be mixed with the organic acid of 0.1-10 weight % in the makeup according to the makeup of the low turbidity described in (13) or (14).
(16) a kind of pharmaceutical preparation of low turbidity is characterized in that wherein being mixed with the L-xitix 2-phosphoric acid ester metal-salt of the low ca content described in (1).
(17) a kind of beverage of low turbidity is characterized in that wherein being mixed with the L-xitix 2-phosphoric acid ester metal-salt of the low ca content described in (1).
Detailed Description Of The Invention
L-xitix 2-phosphoric acid ester metal-salt of detailed hereafter low ca content of the present invention and preparation method thereof.
The L-xitix 2-phosphoric acid ester metal-salt of low ca content
According to the present invention, the high purity L-xitix 2-phosphoric acid ester metal-salt of low ca content is characterised in that the content as the calcium cpd of impurity is 500ppm or littler, according to the calcium ion meter.In this article, L-xitix-2-phosphoric acid ester metal-salt is the salt of the metal outside the deliming, salt, an alkali metal salt, zinc salt, aluminium salt or the titanium salt of the alkaline-earth metal outside the preferred deliming, more preferably sodium salt, sylvite, magnesium salts, zinc salt or aluminium salt, further more preferably sylvite, magnesium salts or zinc salt, most preferably magnesium salts.
This L-xitix 2-phosphoric acid ester metal-salt even also can not produce muddiness when containing in organic acid (such as citric acid) or the alcoholic acid makeup washing lotion and can precipitate or deposit hardly when being added into.Therefore, when this L-xitix 2-phosphoric acid ester metal-salt is mixed, can obtain various makeup, pharmaceutical preparation, food and feeds with excellent storage stability.
In the L-of highly purified low ca content of the present invention xitix 2-phosphoric acid ester metal-salt, be suitably 500ppm or littler as the content of the calcium cpd of impurity, preferred 300ppm or littler is according to the calcium ion meter.If the content of calcium cpd surpasses 500ppm, then when L-xitix 2-phosphoric acid ester metal-salt being sneaked into makeup etc., it with makeup in the organic acid (for example citric acid) that contains form salt, thereby be easy to produce muddy, precipitate or deposit.
The preparation of the L-xitix 2-phosphoric acid ester metal-salt of low ca content
According to the present invention, in the preferred embodiment of method of the L-xitix 2-phosphoric acid ester metal-salt of preparation low ca content, will join (this solution also is known as " solution that contains 2-AP " hereinafter sometimes) in the solution that contains L-xitix-2-phosphoric acid ester (2-AP) to be equal to or less than the metallic compound that described subsequently amount contains the impurity calcium cpd.In this article, metallic compound is the compound of the metal outside the deliming, alkaline earth metal compound, alkali metal compound, zn cpds, aluminum compound or titanium compound outside the preferred deliming, more preferably sodium compound, potassium compound, magnesium compound, zn cpds or aluminum compound, further more preferably potassium compound, sodium compound, magnesium compound or zn cpds, most preferably magnesium compound.
By adding such metallic compound, content as the calcium cpd of impurity in the L-xitix 2-phosphoric acid ester metal-salt that finally obtains can be reduced, and the L-xitix 2-phosphoric acid ester metal-salt by using such calcium contents to reduce can prevent that makeup washing lotion or medicine or food from becoming turbid etc.
2-AP metallizing thing in the present invention, metallic compound can be joined in the solution that contains 2-AP, addition means is had no particular limits, as long as can contact and react.
For example, by metallic compound being joined in the solution that contains 2-AP and 2-AP metallizing thing being reacted in the process of producing APM, can use the known method commonly used that is recorded among JP-B-52-18191, JP-A-59-51293, the JP-A-2-286693 etc.
More particularly, above-mentioned reaction can be carried out by the following method: metallic compound is joined in the solution that contains 2-AP such as having fixedly calcium contents or littler metallic compound, regulate pH to 8.5-10.5 after adding, and this solution was placed 3-5 hour down at 5-25 ℃.
The solution that contains 2-AP
The solution (material solution) that is used for the 2-AP of containing of the present invention is had no particular limits, for example can use following solution.
The example of solution that can the suitably used 2-AP of containing comprises the solution that contains 2-AP (referring to JP-B-43-9219, JP-B-45-23746 and JP-A-6-345786) that obtains by direct phosphorylation xitix, the preferred use passed through phosphorylase 15, the solution that contains 2-AP that 6-O-isopropylidene-L-xitix obtains (referring to JP-B-43-9219, JP-B-45-4497, JP-B-45-30328 and JP-B-59-4438).In addition, can also use under enzyme or action of microorganisms from the solution that contains 2-AP (referring to JP-A-2-42996) of L-xitix and phosphodonor preparation.
More particularly, the solution that contains 2-AP can for example obtain by the following method: L-xitix, alkali metal hydroxide and phosphorylation agent reacting under pH is the condition of 6-13, preferred 6-8 in the presence of the water, are handled 2-AP alkali metal salt soln (alkali metal salt soln of the L-xitix-2-phosphoric acid ester) spent ion exchange resin of gained to remove metal ion then.
Further more particularly, for example can obtain containing the solution of 2-AP by the following method: the L-xitix is dissolved in the mixed solvent of pyridine and water, with the phosphorylation agent reaction such as phosphoryl chloride, (for example use alkali metal hydroxide aqueous solution simultaneously, the aqueous solution of sodium hydroxide, potassium hydroxide or lithium hydroxide) with pH regulator to 6-13, preferred 6-8, then the 2-AP alkali metal salt soln spent ion exchange resin that obtains is handled to remove metal ion.
In the present invention, can replace containing the solution of 2-AP with 2-AP alkali metal salt soln or 2-AP alkaline-earth metal salt solution (alkaline-earth metal salt solution of L-xitix-2-phosphoric acid ester).In this case, these solution (aqueous solution) are preferably removed before use the processing (the following decationizingization that is called sometimes) of metal ion.The example of the method for decationizingization comprises the method with suitable ion exchange resin treatment 2-AP metal salt solution.
More particularly, for example, make the 2-AP metal salt solution process storng-acid cation exchange resin such as L-xitix 2-phosphoric acid ester magnesium salts (APM), then with water elution, thereby make the cationic moiety (metal ion) and hydrogen ion exchange of 2-AP metal salt solution, metal ion is retained on the exchange resin, and the result obtains the 2-AP solution of decationizingization.The solution that contains 2-AP also can obtain by ordinary method, the anionite-exchange resin that for example makes 2-AP metal salt solution (aqueous solution) process weakly alkaline or medium basic is to be adsorbed to 2-AP on the ion exchange resin, make the metal ion (positively charged ion) such as alkalimetal ion or alkaline-earth metal ions flow out simultaneously, then the 2-AP of absorption is used the dilute hydrochloric acid wash-out of acid such as 0.1-2N.
In the present invention, the high purity 2-AP that can use the metal ion content that so obtains to reduce significantly, wherein alkalimetal ion or alkaline-earth metal ions, such as Na ion or Ca ionic content 10ppm or littler normally, preferred 1ppm or littler is according to L-xitix-2-phosphoric acid ester meter.
Metallic compound
According to top description, in the preparation method of L-xitix 2-phosphoric acid ester metal-salt of the present invention, the metallic compound that can be used as raw material is the compound of the metal outside the deliming, alkaline earth metal compounds, alkali metal compound, zn cpds, aluminum compound or titanium compound outside the preferred deliming, more preferably sodium compound, potassium compound, magnesium compound, zn cpds or aluminum compound, further preferred potassium compound, sodium compound, magnesium compound or zn cpds, most preferably magnesium compound.Metallic compound can be for example metal oxide, metal hydroxides or metal carbonate, preferable alloy oxide compound or metal hydroxides.Therefore, the example of magnesium compound comprises for example magnesium oxide, magnesium hydroxide and magnesiumcarbonate.Wherein, preferred magnesium oxide and magnesium hydroxide.
In the metallic compound that the present invention uses, be suitably 2000ppm or littler as the content of the calcium cpd of impurity, preferred 1500ppm or littler, more preferably 750ppm or littler is according to the calcium ion meter.If the calcium contents in the feed metal salt surpasses 2000ppm, then use the L-xitix 2-phosphoric acid ester metal-salt of this metallic compound preparation to have high calcium concn, in the time of in it being sneaked into makeup etc., the organic acid that contains in the basic substance of makeup (for example citric acid) reacts to form salt with this compound, the result, be easy to generate muddiness, precipitation or deposition, this is not preferred.
When by being that 2000ppm or littler metallic compound (according to the calcium ion meter) join when making the reaction of 2-AP and metallic compound former state in the solution that contains 2-AP with impurity calcium cpd content, the calcium contents of the L-xitix 2-phosphoric acid ester metal-salt that obtains is low to moderate 500ppm, preferred 300ppm or littler is according to the calcium ion meter.
The application of the L-xitix 2-phosphoric acid ester metal-salt of low ca content
The L-xitix 2-phosphoric acid ester metal-salt of low ca content of the present invention can not cause muddiness, precipitation or deposition, even also is so, can be used for various makeup aptly thus when it being added in the makeup that especially are mixed with organic acid (for example citric acid, succsinic acid, oxysuccinic acid, tartrate) and long-time storage.
The example that the L-xitix 2-phosphoric acid ester metal-salt of the low ca content that the present invention can be obtained joins makeup wherein comprises:
Wherein with citric acid, Trisodium Citrate, epsilon-amino caproic acid, 1,3 butylene glycol, ethanol, glycerine, polyoxyethylene hydrogenated castor oil, purify waste water, washing lotion that spices etc. is mixed and made into;
Wherein with stearic acid, cetyl alcohol, 1,3 butylene glycol, p-Hydroxybenzoate, Dipentaerythritol fatty ester, purify waste water, missible oil that spices etc. is mixed and made into;
The milky lotion that stearic acid, cetyl alcohol, octyl group dodecyl eruciate, polyoxyethylene four oleic acid esters etc. are mixed and made into wherein; With
The weighting material that dipropylene glycol, pyrrolidone sodium carboxylate, polyvinyl alcohol, tetrasodium ethylenediamine tetraacetate etc. are mixed and made into wherein.But, the invention is not restricted to this.
The ratio that is mixed into the L-xitix 2-phosphoric acid ester metal-salt of the low ca content in these makeup changes according to the organic acid amount of sneaking into, dosage form etc., but, the total amount of supposing makeup is 100 weight %, this ratio 0.01-30 weight % normally in washing lotion then, preferred 0.1-20 weight %; This ratio 0.01-30 weight % normally in missible oil, preferred 0.1-15 weight %; This ratio 0.01-30 weight % normally in milky lotion, preferred 0.1-20 weight %; This ratio 0.01-30 weight % normally in weighting material, preferred 0.1-15 weight %.The organic acid amount that contains in the makeup changes according to the kind of makeup, but 0.1-10 weight % normally.
The pharmaceutical preparation that the L-xitix 2-phosphoric acid ester metal-salt that this calcium contents reduces also can suitably be used for especially containing organic acid (for example citric acid, succsinic acid, oxysuccinic acid, tartrate) (for example, preparation, eye drop, the body lotion in cavity in the oral cavity), beverage, animal-feed, food etc., and can obtain the effect identical with makeup.
Embodiment
Describe the present invention in more detail below by reference embodiment, still, the invention is not restricted to these embodiment.In the following embodiments, according to the preparation of L-xitix 2-phosphoric acid ester magnesium salts the present invention is described.Yet, as mentioned above, the invention is not restricted to magnesium salts, comprise the various metal-salts of L-xitix 2-phosphoric acid ester metal.
Embodiment 1
Dissolving 32g L-xitix 2-phosphoric acid ester magnesium salts in the 368ml pure water.With the solution that forms by being filled with 2000ml storng-acid cation exchange resin (Amberlite IR-120B is produced by Organo) pillar and further by the 1200ml pure water to obtain the aqueous solution that only contains 2-AP of 1600ml.The magnesium ion content of this solution is less than 1ppm, and the content of impurity calcium cpd is less than detection limit.
This 2-AP aqueous solution is remained on 10 ℃, and the content that adds the impurity calcium cpd simultaneously is that the magnesium hydroxide of 500ppm (according to the calcium ion meter) is so that the pH after adding is 9.2.With the solution left standstill that forms 4 hours, then with supernatant liquid filtering to remove insoluble substance.Filtrate is concentrated into 1/10th (1/10), adds the methyl alcohol of doubling dose, collect the solid part that generates by filtering then.Subsequently, solid part (wet body) water-recrystallizing methanol that obtains is dry then, obtain white dried product L-xitix 2-phosphoric acid ester magnesium salts.In this white dried product, the content of calcium cpd is 120ppm, according to the calcium ion meter.Carry out the stability test 1 and 2 in the solution of the following stated with this desciccate, the result does not observe muddiness.
The concentration of the impurity calcium cpd in feed hydrogen magnesium oxide and end product L-xitix 2-phosphoric acid ester magnesium salts detects (below also similarly detect) by ICP (being produced by Seiko Instruments K.K.) in embodiment 2 and Comparative Examples 1 to 2.
Comparative Examples 1
Obtain white dried product L-xitix 2-phosphoric acid ester magnesium salts according to the mode identical with embodiment 1, different is with impurity calcium cpd content is that the magnesium hydroxide of 2500ppm (according to the calcium ion meter) replaces that impurity calcium cpd content is the magnesium hydroxide of 500ppm (according to the calcium ion meter) among the embodiment 1.In this white dried product, the content of calcium cpd is 580ppm.Carry out the stability test 1 and 2 in the solution of the following stated with this desciccate.In the stability test 1 and 2 in solution, under room temperature (20 ℃), all observe muddiness, and under 50 ℃, also observe more obvious muddiness.
Embodiment 2
Under nitrogen atmosphere, add 100g L-xitix and it is dissolved in the mixed solvent that contains 1350ml pure water and 150g pyridine, be cooled to 0-10 ℃ then, add 10% aqueous sodium hydroxide solution then and be about 12 to regulate pH.In the solution that forms, drip the 150g phosphoryl chloride, use 10% aqueous sodium hydroxide solution simultaneously, react by temperature being remained on 0-10 ℃ then pH regulator to 12.After drip finishing, with 35% hydrochloric acid with pH regulator to being about 7, and underpressure distillation goes out pyridine.Then, add 35% hydrochloric acid to regulate pH to 4.
To dilute through the reaction soln after the above-mentioned pH regulator by adding the 6500ml pure water, make it by being filled with 2000ml medium basic anionite-exchange resin (Amberlite IRA-68, produce by Organo) pillar, also further use the 0.2N hydrochloric acid wash-out of 11000ml then with the 0.05N hydrochloric acid wash-out of 23500ml, obtain containing the fraction of 2-AP.
With aqueous solution electrodialyzer (Model DU-Ob is by the Asahi Glass K.K.) dialysis of this fraction, reduce to 500ppm up to chlorion.Dialyzate is remained on 15 ℃ simultaneously, adding impurity calcium cpd content is that the magnesium oxide of 1000ppm (according to the calcium ion meter) is so that the pH after adding is 10.1.With this solution left standstill 2 hours, then with supernatant liquid filtering to remove insoluble substance.With solution concentration to ten/one (1/10) who forms, add the methyl alcohol of doubling dose, collect the solid part that generates by filtering then.Subsequently, the wet solid water-recrystallizing methanol that obtains is dry then, obtain white dried product L-xitix 2-phosphoric acid ester magnesium salts.In this white dried product, the content of impurity calcium cpd is 280ppm, according to the calcium ion meter.Carry out the stability test 1 and 2 in the solution of the following stated with this desciccate, the result does not observe muddiness.
Comparative Examples 2
Obtain white dried product L-xitix 2-phosphoric acid ester magnesium salts according to the mode identical with embodiment 2, different is with impurity calcium cpd content is that to replace the impurity calcium cpd content among the embodiment 2 be the magnesium oxide of 1000ppm (according to the calcium ion meter) for the magnesium oxide of 3000ppm (according to the calcium ion meter).In this white dried product, the content of calcium cpd is 750ppm, according to the calcium ion meter.Carry out the stability test in the liquid of the following stated with this desciccate.As a result, in the stability test 1 in solution, when at room temperature placing, desciccate observes muddiness, when when placing down for 50 ℃, observing more obvious muddiness.In the stability test 2 in liquid, under room temperature and 50 ℃, all observe tangible muddiness.
Stability test 1 in the solution
In the Erlenmeyer of 200ml volume flask, add 2g sample (APM), 0.4g two hydration Trisodium Citrates and 0.05g citric acid.To wherein adding 16g glycerine 1,3 butylene glycol alcoholic acid mixing solutions (volume ratio is 3: 5: 8), and with the solution stirring that forms 30 minutes.To wherein adding the 82g pure water, and the solution that forms continued to stir 2 hours.After by strainer this solution being filtered, half solution was placed 1 month down in room temperature (20 ℃), will be remaining half 50 ℃ of placements 10 days down.The cloudy state of every kind of solution of visual observations.
Observations is listed in the table 1.
Stability test 2 in the solution
In the Erlenmeyer of 200ml volume flask, add 2g sample (APM), 0.4g two hydration Trisodium Citrates and 0.05g citric acid.To wherein adding 15g glycerine 1,3 butylene glycol alcoholic acid mixing solutions (volume ratio is 3: 5: 8), and with the solution stirring that forms 30 minutes.To wherein adding the 82g pure water, and the solution that forms continued to stir 2 hours.After by strainer this solution being filtered, half solution was placed 1 month down in room temperature (20 ℃), will be remaining half 50 ℃ of placements 10 days down.The cloudy state of every kind of solution of visual observations.
Observations is listed in the table 1.
Table 1
| Stability test 1 in the solution | Stability test 2 in the solution | |||
| Room temperature (20 ℃) | 50℃ | Room temperature (20 ℃) | 50℃ | |
| Embodiment 1 | A | A | A | A |
| Embodiment 2 | A | A | A | A |
| Comparative Examples 1 | B | C | B | C |
| Comparative Examples 2 | B | C | C | C |
A: do not have muddiness, B: muddy, C: significantly muddy
Effect of the present invention
Preparation in accordance with the present invention, can make the L-AA 2-phosphate slaine of low calcium content, the content that is contained in the impurity calcium compound in the L-AA 2-phosphate slaine that wherein will cause producing muddiness, precipitation or deposition is down to 500ppm or less, according to the calcium ion meter. When the L-AA 2-phosphate slaine of low calcium content of the present invention being sneaked into when especially containing in the organic acid cosmetics, the L-AA 2-phosphate slaine of low calcium content of the present invention at room temperature or in the storing process under high temperature (for example 50 ℃) can not produce muddiness, precipitation or deposition, so be suitable for this purposes. In addition, even sneaked into when especially containing in organic acid medicine, feed or the food substance when this L-AA 2-phosphate slaine, with above identical storing process in also show stability, it can be widely used for various industrial circles thus.
Claims (8)
1, a kind of method for preparing the L-xitix-2-phosphoric acid ester metal-salt of low ca content, wherein the content of calcium cpd is 500ppm or littler, according to the calcium ion meter, described method is characterised in that and will joins in the solution that contains L-xitix-2-phosphoric acid ester with the metallic compound that 2000ppm or littler amount contain calcium cpd according to the calcium ion meter.
2, according to the method for the L-xitix-2-phosphoric acid ester metal-salt of the described preparation low ca content of claim 1, wherein metallic compound is any in potassium compound, sodium compound, magnesium compound or the zn cpds, and the L-xitix-2-phosphoric acid ester metal-salt that forms is any in sylvite, sodium salt, magnesium salts or the zinc salt.
3, according to the method for the L-xitix-2-phosphoric acid ester metal-salt of the described preparation low ca content of claim 1, wherein metallic compound is any in magnesium oxide or the magnesium hydroxide, and the L-xitix-2-phosphoric acid ester metal-salt that forms is a magnesium salts.
4, according to the method for the L-xitix-2-phosphoric acid ester metal-salt of the described preparation low ca content of claim 1, the solution that wherein contains L-xitix-2-phosphoric acid ester contains alkalimetal ion or alkaline-earth metal ions with 10ppm or littler amount, in L-xitix-2-phosphoric acid ester.
5, according to the method for the L-xitix-2-phosphoric acid ester metal-salt of the described preparation low ca content of claim 4, the solution that wherein contains L-xitix-2-phosphoric acid ester contains alkalimetal ion or alkaline-earth metal ions with 1ppm or littler amount, in L-xitix-2-phosphoric acid ester.
6, according to the method for the L-xitix-2-phosphoric acid ester metal-salt of claim 4 or 5 described preparation low ca contents, the solution that wherein contains L-xitix-2-phosphoric acid ester prepares by the following method: this method comprises reacts L-xitix, alkali metal hydroxide and phosphorylation agent in the presence of water, then by making spent ion exchange resin remove metal ion from the solution of the L-xitix-2-phosphoric acid ester metal-salt of formation.
7, according to the method for the L-xitix-2-phosphoric acid ester metal-salt of the described preparation low ca content of claim 6, wherein ion exchange resin is the anionite-exchange resin of weakly alkaline or medium basic.
8, a kind of makeup of low turbidity is characterized in that wherein being mixed with the organic acid of L-xitix 2-phosphoric acid ester magnesium salts and 0.1-10 weight %, and described L-xitix 2-phosphoric acid ester magnesium salts has according to calcium ion meter 500ppm or littler calcium cpd content.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP57982/2001 | 2001-03-02 | ||
| JP2001057982A JP2002255981A (en) | 2001-03-02 | 2001-03-02 | Magnesium salt of ascorbic acid-2-phosphate having reduced content of calcium |
| US27503301P | 2001-03-13 | 2001-03-13 | |
| US60/275,033 | 2001-03-13 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1494547A CN1494547A (en) | 2004-05-05 |
| CN1216061C true CN1216061C (en) | 2005-08-24 |
Family
ID=26610496
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 02805868 Expired - Lifetime CN1216061C (en) | 2001-03-02 | 2002-03-01 | Ascorbic acid 2-phosphate metal salt with low calcium content |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP1368362A1 (en) |
| CN (1) | CN1216061C (en) |
| WO (1) | WO2002070531A1 (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101247834B (en) * | 2005-06-17 | 2013-10-30 | 生命健康科学公司 | Carrier comprising one or more di and/or mono-(electron transfer agent) phosphate derivatives or complexes thereof |
| CN101550163B (en) * | 2008-10-06 | 2011-09-07 | 北京贝丽莱斯生物化学有限公司 | Production process for preparing vitamin C-2-magnesium phosphate from vitamin C-2-magnesium phosphate crude product |
| CN101735274A (en) * | 2008-11-18 | 2010-06-16 | 高锦秋 | Technology for processing vitamin c phosphate magnesium |
| CN101735275A (en) * | 2008-11-18 | 2010-06-16 | 高锦秋 | Method for producing vitamin c phosphate magnesium |
| CN101747376B (en) * | 2010-01-15 | 2012-05-23 | 北京化工大学 | Method for extracting ascorbyl-2-phosphate through bipolar membrane electrodialysis |
| CN108690076A (en) * | 2018-04-19 | 2018-10-23 | 安徽顺利生物有限公司 | The preparation method of the remaining Magnesium L-Ascorbyl Phosphate of organic solvent-free |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2694947B2 (en) * | 1987-03-31 | 1997-12-24 | ポーラ化成工業株式会社 | Whitening cosmetics |
| JP2877366B2 (en) * | 1988-08-25 | 1999-03-31 | 協和醗酵工業株式会社 | Method for producing crystalline L-ascorbic acid-2-phosphate sodium salt |
| DE3909198A1 (en) * | 1989-03-21 | 1990-09-27 | Basf Ag | METHOD FOR THE PRODUCTION OF ASCORBIN ACID-2-PHOSPHATE AND 5,6-ISORPROPYLIDENE-ASCORBIN ACID AS A BASE PRODUCT |
| CA2230774C (en) * | 1997-03-18 | 2007-06-26 | F. Hoffmann-La Roche Ag | Manufacture of ascorbyl monophosphates |
| JP3772468B2 (en) * | 1997-06-11 | 2006-05-10 | 昭和電工株式会社 | L-ascorbic acid-2-phosphate zinc salt and method for producing the same |
| DE19831056A1 (en) * | 1998-07-13 | 2000-01-20 | Basf Ag | Process for the preparation of salts of ascorbyl-2-phosphoric acid esters |
-
2002
- 2002-03-01 CN CN 02805868 patent/CN1216061C/en not_active Expired - Lifetime
- 2002-03-01 WO PCT/JP2002/001926 patent/WO2002070531A1/en active Application Filing
- 2002-03-01 EP EP02701682A patent/EP1368362A1/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| CN1494547A (en) | 2004-05-05 |
| WO2002070531A1 (en) | 2002-09-12 |
| EP1368362A1 (en) | 2003-12-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2009281655B2 (en) | Antimicrobial silver solutions | |
| CN109432507B (en) | Antibacterial hydroxyapatite composite material containing metal oxide and preparation method thereof | |
| CN1093131C (en) | Process for preparing ascorbic acid-2-phosphates | |
| CN1216061C (en) | Ascorbic acid 2-phosphate metal salt with low calcium content | |
| JP3772468B2 (en) | L-ascorbic acid-2-phosphate zinc salt and method for producing the same | |
| CN1805948A (en) | Stabilized derivatives of ascorbic acid. | |
| CN103827288A (en) | Method for cultivating seaweed and method for producing alginic acid-containing composition | |
| JP5822296B2 (en) | Silver ion antibacterial liquid production method, silver ion antibacterial liquid produced by the method, or silver ion antibacterial powder production method, silver ion antibacterial powder produced by the method | |
| CN1594265A (en) | Preparation method of gluconic acid and its salt | |
| RU2391119C1 (en) | Method of obtaining calcium phasphte nanoparticles, stabilised by salt matrix | |
| US4189474A (en) | Dextrin hydroxycarboxylato polyiron (III) olated complex and process for the manufacture thereof | |
| CN1803811A (en) | Nitro imidazole derivative, its preparation method and uses | |
| CN110669072A (en) | Method for refining tedizolid phosphate | |
| WO2020170840A1 (en) | CRYSTAL OF POTASSIUM SALT OF 2-O-α-D-GLUCOSYL-L-ASCORBIC ACID AND PRODUCTION METHOD THEREFOR | |
| US2856366A (en) | Stable alkaline metal solutions containing carboxymethyl dextran | |
| CN1149059A (en) | Preparation and application of sargassum polysaccharide complex | |
| CN114230454B (en) | Calcium complex of gallic acid natural active ingredient, and synthetic method and application thereof | |
| US20040092485A1 (en) | Ascorbic acid 2-phosphate metal salt with low calcium content | |
| CN1775733A (en) | Calcium nervonate and its preparing method and use | |
| US3277132A (en) | Tin(ii) salts of orthophosphoric-mono-(beta-aminoethanol)ester | |
| JP3750160B2 (en) | Amorphous L-ascorbic acid-2-phosphate ester sodium salt and method for producing the same | |
| CN1267096C (en) | Ginkgo leaf extract injection and its preparation method | |
| JP3378847B2 (en) | Crystals of L-ascorbic acid-2-phosphate sodium salt | |
| CN102946889B (en) | Calcium preparation and production method therefor | |
| RU2462254C2 (en) | Silver nanocomposite of sulphated arabinogalactan exhibiting antimicrobial and antithrombotic activity and method for preparing it |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CX01 | Expiry of patent term | ||
| CX01 | Expiry of patent term |
Granted publication date: 20050824 |