CN109651438A - A kind of preparation of modified oxidized magnesium and its application in L-Ascorbic Acid L-O-Phosphate - Google Patents
A kind of preparation of modified oxidized magnesium and its application in L-Ascorbic Acid L-O-Phosphate Download PDFInfo
- Publication number
- CN109651438A CN109651438A CN201910098383.3A CN201910098383A CN109651438A CN 109651438 A CN109651438 A CN 109651438A CN 201910098383 A CN201910098383 A CN 201910098383A CN 109651438 A CN109651438 A CN 109651438A
- Authority
- CN
- China
- Prior art keywords
- added
- phosphate
- ascorbic acid
- filtrate
- vitamin
- 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.)
- Pending
Links
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 title claims abstract description 138
- 229960005070 ascorbic acid Drugs 0.000 title claims abstract description 37
- 239000002211 L-ascorbic acid Substances 0.000 title claims abstract description 35
- 235000000069 L-ascorbic acid Nutrition 0.000 title claims abstract description 34
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 title claims abstract description 12
- 239000011777 magnesium Substances 0.000 title claims abstract description 12
- 229910052749 magnesium Inorganic materials 0.000 title claims abstract description 12
- CPLXHLVBOLITMK-UHFFFAOYSA-N Magnesium oxide Chemical compound [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 claims abstract description 54
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims abstract description 34
- 229930003268 Vitamin C Natural products 0.000 claims abstract description 34
- 235000019154 vitamin C Nutrition 0.000 claims abstract description 34
- 239000011718 vitamin C Substances 0.000 claims abstract description 34
- 239000000395 magnesium oxide Substances 0.000 claims abstract description 27
- 150000002148 esters Chemical class 0.000 claims abstract description 20
- 238000006243 chemical reaction Methods 0.000 claims abstract description 18
- 239000012535 impurity Substances 0.000 claims abstract description 14
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 9
- 229920000141 poly(maleic anhydride) Polymers 0.000 claims abstract description 9
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 9
- 230000007062 hydrolysis Effects 0.000 claims abstract description 7
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 7
- 239000000706 filtrate Substances 0.000 claims description 47
- 238000003756 stirring Methods 0.000 claims description 37
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 27
- 239000007787 solid Substances 0.000 claims description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 22
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 21
- 238000010828 elution Methods 0.000 claims description 21
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 20
- 238000001914 filtration Methods 0.000 claims description 20
- 239000012528 membrane Substances 0.000 claims description 20
- 238000001728 nano-filtration Methods 0.000 claims description 20
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 14
- 239000012043 crude product Substances 0.000 claims description 14
- 239000000047 product Substances 0.000 claims description 14
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 12
- 238000010992 reflux Methods 0.000 claims description 11
- 238000005096 rolling process Methods 0.000 claims description 10
- 239000000377 silicon dioxide Substances 0.000 claims description 10
- 239000006087 Silane Coupling Agent Substances 0.000 claims description 9
- JMXKSZRRTHPKDL-UHFFFAOYSA-N titanium ethoxide Chemical compound [Ti+4].CC[O-].CC[O-].CC[O-].CC[O-] JMXKSZRRTHPKDL-UHFFFAOYSA-N 0.000 claims description 9
- 235000019441 ethanol Nutrition 0.000 claims description 8
- UGTZMIPZNRIWHX-UHFFFAOYSA-K sodium trimetaphosphate Chemical compound [Na+].[Na+].[Na+].[O-]P1(=O)OP([O-])(=O)OP([O-])(=O)O1 UGTZMIPZNRIWHX-UHFFFAOYSA-K 0.000 claims description 8
- 239000007921 spray Substances 0.000 claims description 8
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 7
- 239000003957 anion exchange resin Substances 0.000 claims description 7
- 239000007864 aqueous solution Substances 0.000 claims description 7
- 239000008367 deionised water Substances 0.000 claims description 7
- 229910021641 deionized water Inorganic materials 0.000 claims description 7
- 235000006408 oxalic acid Nutrition 0.000 claims description 7
- 239000000376 reactant Substances 0.000 claims description 7
- 235000011121 sodium hydroxide Nutrition 0.000 claims description 7
- 238000007792 addition Methods 0.000 claims description 6
- 239000004359 castor oil Substances 0.000 claims description 6
- 235000019438 castor oil Nutrition 0.000 claims description 6
- 239000012065 filter cake Substances 0.000 claims description 6
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims description 6
- 239000002105 nanoparticle Substances 0.000 claims description 6
- 235000012239 silicon dioxide Nutrition 0.000 claims description 6
- 229960001866 silicon dioxide Drugs 0.000 claims description 6
- 229960004756 ethanol Drugs 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 11
- 238000005516 engineering process Methods 0.000 abstract description 4
- 238000005275 alloying Methods 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 230000008569 process Effects 0.000 abstract description 3
- 230000009257 reactivity Effects 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 239000003125 aqueous solvent Substances 0.000 abstract description 2
- 229960000074 biopharmaceutical Drugs 0.000 abstract description 2
- 239000000463 material Substances 0.000 abstract description 2
- 239000003960 organic solvent Substances 0.000 abstract description 2
- 239000000049 pigment Substances 0.000 abstract description 2
- 150000003384 small molecules Chemical class 0.000 abstract description 2
- 238000001035 drying Methods 0.000 description 13
- XGZNHFPFJRZBBT-UHFFFAOYSA-N ethanol;titanium Chemical compound [Ti].CCO.CCO.CCO.CCO XGZNHFPFJRZBBT-UHFFFAOYSA-N 0.000 description 5
- 238000001694 spray drying Methods 0.000 description 5
- 229940088594 vitamin Drugs 0.000 description 5
- 229930003231 vitamin Natural products 0.000 description 5
- 235000013343 vitamin Nutrition 0.000 description 5
- 239000011782 vitamin Substances 0.000 description 5
- 150000003722 vitamin derivatives Chemical class 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 229910019142 PO4 Inorganic materials 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 229960001777 castor oil Drugs 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 239000010452 phosphate Substances 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 229920000388 Polyphosphate Polymers 0.000 description 1
- 235000004443 Ricinus communis Nutrition 0.000 description 1
- 240000000528 Ricinus communis Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000010612 desalination reaction Methods 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 125000000654 isopropylidene group Chemical group C(C)(C)=* 0.000 description 1
- GVALZJMUIHGIMD-UHFFFAOYSA-H magnesium phosphate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O GVALZJMUIHGIMD-UHFFFAOYSA-H 0.000 description 1
- 239000003595 mist Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000002715 modification method Methods 0.000 description 1
- 150000004712 monophosphates Chemical group 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000001205 polyphosphate Substances 0.000 description 1
- 235000011176 polyphosphates Nutrition 0.000 description 1
- 238000013094 purity test Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000036632 reaction speed Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940048102 triphosphoric acid Drugs 0.000 description 1
- 150000003700 vitamin C derivatives Chemical class 0.000 description 1
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 Table
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a kind of preparation of modified oxidized magnesium and its applications in L-Ascorbic Acid L-O-Phosphate, are related to biopharmaceutical technology.Phosphating reaction of the present invention carries out in aqueous solvent, does not use organic solvent, simple process, and environmentally safe, finished product L-Ascorbic Acid L-O-Phosphate purity is high, stability are good；Magnesia can form alloying structure in mgo surface by modified, and then can be improved the reactivity of magnesia and vitamin C phosphoric ester, accelerate reaction rate；There is stronger suction-operated to small molecule inorganic matter, pigment using polyethylene glycol, hydrolysis of polymaleic anhydride as the scarvenger of Material synthesis, the impurity in vitamin C phosphoric ester can be adsorbed, improves purity.
Description
Technical field:
The present invention relates to biopharmaceutical technologies, and in particular to the preparation of a kind of modified oxidized magnesium and its in vitamin C
Application in phosphate magnesium.
Background technique:
L-Ascorbic Acid L-O-Phosphate is a kind of vitamin C derivatives, and 2 hydroxyls, which are derived as phosphate, can be improved dimension life
The stability of plain C can regenerate vitamin C after being formed by the phosphate hydrolysis that derivative is widely present in vivo, because
It is a kind of valuable fine chemicals as the main component that feed addictive, food additive and superior cosmetics brighten.
Up to now, vitamin C phosphoric esterization mainly has two methods: first is that the phosphorylation of phosphorus oxychloride is (as Europe is public
Open patent 388869 and 582924, United States Patent (USP) 4179445, the descriptions such as Japanese Unexamined Patent Publication No. 60-69079), with vitamin
C is raw material, and the hydroxyl protection on 5 and 6 carbon gets up before esterification, i.e., it is raw first to carry out ketal reaction with acetone for vitamin C
At 5,6- oxygen, one isopropylidene, one L, mono- ascorbic acid (5,6-0 mono- isopropylidene-L-ascorbic acid), then use pyrrole
The dissolution of pyridine solution, KOH adjust pH value, and phosphorus oxychloride reaction is added dropwise, boils off multiple desalination after pyridine, are concentrated, then carry out cation
Resins exchange collects eluent, MgO is added to react, and last low-carbon alcohols partial crystallization filtration drying is completed.Its product is mainly L- Vitamin C
Acid -2- phosplate, by-product are mainly L-AA -3- phosphate and 2- pyrophosphate and two (ascorbic acid) -2, and 2 ' -
Bisphosphate.Reaction product needs cumbersome procedure purify, and it is mixed that all reactions can not be dried with straightforward procedure
Close object.Second method is to carry out phosphorylation using phosphate to obtain such as the method for United States Patent (USP) 4647672 and 5110950
Primary product is L-AA -2- polyphosphate, and when such as using sodium trimetaphosphate, product is L-AA -2- triphosphoric acid
Ester, but also contain a certain proportion of L-AA -2- phosplate.The former can be monophosphate by excessive alkaline degradation
Ester, stoichiometric ratio and specific reaction condition of the ratio depending on starting material.The purifying L-ascorbic acid-from mixture
2- phosplate, which is also not, can simply accomplish, the inorganic salts residual in product is often very high.Although this method synthetic route is short,
By-product is more, and product separating-purifying is difficult, and total yield of products is low.The synthesis technology of traditional L-Ascorbic Acid L-O-Phosphate is complicated, miscellaneous
Matter is more, and is damaged using organic solutions such as acetone to environment.
Summary of the invention:
Technical problem to be solved by the present invention lies in the preparation for providing a kind of modified oxidized magnesium and its in vitamin C phosphoric acid
Application in ester magnesium.
The following technical solution is employed for the technical problems to be solved by the invention to realize:
The modification method for preparing of magnesia are as follows: magnesia is added in dehydrated alcohol, 40 DEG C of ultrasonic disperse stirrings
Then Ni nanoparticle (OH) is added in 10min2, silane coupling agent be heated to reflux state insulated and stirred 30-50min, be cooled to 50 DEG C
Silicon-dioxide powdery is added, continues insulated and stirred 1-2h, filters while hot, filter cake washes away impurity with dehydrated alcohol, and 50 DEG C of vacuum are dry
It is dry to constant weight.
The magnesia, silicon-dioxide powdery, Ni (OH)2, silane coupling agent mass ratio be 1-2:0.1-0.3:0.1-
0.2:0.05-0.08.
Preferably, the concentration of silicon-dioxide powdery is 1-8g/L, partial size 70-120nm.
Magnesia passes through silicon-dioxide powdery, Ni (OH)2, silane coupling agent it is modified, can be formed in mgo surface
Alloying structure, and then can be improved the reactivity of magnesia and L-AA, accelerate reaction rate；
Application of the modified oxidized magnesium in L-Ascorbic Acid L-O-Phosphate preparation, comprising the following steps:
(1) by vitamin C, anhydrous calcium chloride, deionized water according to 1: (0.08-0.4): temperature is added in the mass ratio of (1-5)
To stir 2-3 hours, then the sodium hydrate aqueous solution of concentration 30-70% is added dropwise in -10-20 DEG C of reaction kettle, adjust PH is degree
5-10.5 adds the sodium trimetaphosphate of 1-2.5 times of vitamin C dosage, maintains the temperature at 25-45 DEG C, reacts 2-6 hours, mistake
Filter obtains solid；
(2) obtained solid is added in charging basket washer and is washed with water, at 30 DEG C of oxalic acid of addition solid masses 60-70%
2h is stirred, filtering, gained filtrate is vitamin C phosphoric ester crude product；
(3) vitamin C phosphoric ester crude product is subjected to nanofiltration membrane through rolling nano-filtration membrane filter；
(4) filtrate that step (3) is obtained by filtration is added in reaction kettle, through weak-base anion-exchange resin, successively uses
0.05M hydrochloric acid and the elution of 0.5M-1.5M hydrochloric acid, collect elution fraction, and elution fraction adjusts pH with magnesia under constant stirring
For 7-11, obtained reactant is L-Ascorbic Acid L-O-Phosphate filtrate；
(5) scarvenger of filtrate quality 3-5%, 35-40 DEG C of stirring 20- are added into L-Ascorbic Acid L-O-Phosphate filtrate
40min is filtered while hot；Filtrate is concentrated under reduced pressure into 1/5th of original volume in 30 DEG C, and it is that 3-6 times of filtrate of concentration contains that volume, which is added,
Then the ethyl alcohol that amount is 95% is dried by spray dryer to get L-Ascorbic Acid L-O-Phosphate finished product is arrived.
The temperature of the rolling nano-filtration membrane filter import is 120-140 DEG C, the temperature of rolling nano-filtration membrane filter outlet
It is 30-50 DEG C；Nanofiltration membrane has nanoscale aperture, and the molecular cut off of nanofiltration membrane is 500-1500, rolling nano-filtration membrane filter
There is higher removal efficiency to inorganic salts, removal efficiency is 90~98%.
The drying temperature of the spray drying is 140-160 DEG C, drying time 30-40min.
The scarvenger the preparation method comprises the following steps: polyethylene glycol is added in pure water, then 30 stirring 10min are added
Hydrolysis of polymaleic anhydride and tetraethyl titanate are heated to reflux state insulated and stirred 05-2h, are cooled to 60-65 DEG C, and castor-oil plant is added
Oil stirring 20-30min, is filtered while hot, and solid washes away impurity with pure water, dry to constant weight.
The polyethylene glycol, hydrolysis of polymaleic anhydride, tetraethyl titanate, castor oil mass ratio be 1-2:1-2:0.01:
0.1-0.2。
The beneficial effects of the present invention are:
(1) magnesia can form alloying structure in mgo surface by modified, so can be improved magnesia with
The reactivity of vitamin C phosphoric ester accelerates reaction rate；Using polyethylene glycol, hydrolysis of polymaleic anhydride as the pure of Material synthesis
Agent has stronger suction-operated to small molecule inorganic matter, pigment, can adsorb the impurity in vitamin C phosphoric ester, improves pure
Degree；
(2) phosphating reaction of the present invention carries out in aqueous solvent, does not use organic solvent, entire simple process, not only
Phosphating reaction speed is accelerated, shortens the reaction time, and environmentally safe；Using nanofiltration membrane process, impurity removal
High-efficient, finished product L-Ascorbic Acid L-O-Phosphate is with high purity, and stability is good.
Specific embodiment:
In order to be easy to understand the technical means, the creative features, the aims and the efficiencies achieved by the present invention, tie below
Specific embodiment is closed, the present invention is further explained.
Embodiment 1
(1) temperature is added according to 1: 0.2: 2 mass ratio in vitamin C, anhydrous calcium chloride, deionized water is 10 DEG C anti-
It answers in kettle, stirs 2 hours, then the sodium hydrate aqueous solution of concentration 40% is added dropwise, adjusting PH is 7, adds 2 times of vitamin Cs and uses
The sodium trimetaphosphate of amount maintains the temperature at 30 DEG C, reacts 4 hours, solid is obtained by filtration；
(2) obtained solid is added in charging basket washer and is washed with water, stirred in 30 DEG C of oxalic acid that solid masses 60% is added
2h is mixed, is filtered, gained filtrate is vitamin C phosphoric ester crude product；
(3) vitamin C phosphoric ester crude product is subjected to nanofiltration membrane through rolling nano-filtration membrane filter；
(4) filtrate that step (3) is obtained by filtration is added in reaction kettle, through weak-base anion-exchange resin, successively uses
Elution fraction is collected in 0.05M hydrochloric acid and the elution of 1.5M hydrochloric acid, and it is 8 that elution fraction, which adjusts pH with magnesia under constant stirring, is obtained
The reactant arrived is L-Ascorbic Acid L-O-Phosphate filtrate；
(5) into L-Ascorbic Acid L-O-Phosphate filtrate be added filtrate quality 3% scarvenger, 35 DEG C of stirring 40min, while hot
Filtering；Filtrate is concentrated under reduced pressure into 1/5th of original volume in 30 DEG C, and it is that the second that 3 times of contents of filtrate are 95% is concentrated that volume, which is added,
Then alcohol is dried by spray dryer to get L-Ascorbic Acid L-O-Phosphate finished product is arrived；The drying temperature of spray drying is 140
DEG C, drying time 30min.
The modification of magnesia: 1.2 parts of magnesia is added in dehydrated alcohol, 40 DEG C of ultrasonic disperse stirrings
Then 0.1 part of Ni nanoparticle (OH) is added in 10min2, 0.05 part of silane coupling agent kh550 be heated to reflux state insulated and stirred
30min is cooled to 50 DEG C of additions, 0.2 part of silica powder, continues insulated and stirred 1.5h, filters while hot, filter cake dehydrated alcohol
Impurity is washed away, 50 DEG C are dried under vacuum to constant weight.
The preparation of scarvenger: 1.2 parts of polyethylene glycol are added in pure water, then 1 part of water is added in 30 stirring 10min
Polymaleic anhydride and 0.01 part of tetraethyl titanate are solved, reflux state insulated and stirred 2h is heated to, is cooled to 60 DEG C, is added 0.1 part
Castor oil stirs 20min, filters while hot, and solid washes away impurity with pure water, dry to constant weight.
Embodiment 2
(1) temperature is added according to 1: 0.1: 3 mass ratio in vitamin C, anhydrous calcium chloride, deionized water is 15 DEG C anti-
It answers in kettle, stirs 3 hours, then the sodium hydrate aqueous solution of concentration 50% is added dropwise, adjusting PH is 8, adds 2.5 times of vitamin Cs
The sodium trimetaphosphate of dosage maintains the temperature at 45 DEG C, reacts 5 hours, solid is obtained by filtration；
(2) obtained solid is added in charging basket washer and is washed with water, stirred in 30 DEG C of oxalic acid that solid masses 70% is added
2h is mixed, is filtered, gained filtrate is vitamin C phosphoric ester crude product；
(3) vitamin C phosphoric ester crude product is subjected to nanofiltration membrane through rolling nano-filtration membrane filter；
(4) filtrate that step (3) is obtained by filtration is added in reaction kettle, through weak-base anion-exchange resin, successively uses
Elution fraction is collected in 0.05M hydrochloric acid and the elution of 1M hydrochloric acid, and it is 8.5 that elution fraction, which adjusts pH with magnesia under constant stirring, is obtained
The reactant arrived is L-Ascorbic Acid L-O-Phosphate filtrate；
(5) into L-Ascorbic Acid L-O-Phosphate filtrate be added filtrate quality 5% scarvenger, 40 DEG C of stirring 30min, while hot
Filtering；Filtrate is concentrated under reduced pressure into 1/5th of original volume in 30 DEG C, and it is that the second that 4 times of contents of filtrate are 95% is concentrated that volume, which is added,
Then alcohol is dried by spray dryer to get L-Ascorbic Acid L-O-Phosphate finished product is arrived；The drying temperature of spray drying is 150
DEG C, drying time 40min.
The modification of magnesia: 1.2 parts of magnesia is added in dehydrated alcohol, 40 DEG C of ultrasonic disperse stirrings
Then 0.1 part of Ni nanoparticle (OH) is added in 10min2, 0.05 part of silane coupling agent kh550 be heated to reflux state insulated and stirred
30min is cooled to 50 DEG C of additions, 0.2 part of silica powder, continues insulated and stirred 1.5h, filters while hot, filter cake dehydrated alcohol
Impurity is washed away, 50 DEG C are dried under vacuum to constant weight.
The preparation of scarvenger: 1.2 parts of polyethylene glycol are added in pure water, then 1 part of water is added in 30 stirring 10min
Polymaleic anhydride and 0.01 part of tetraethyl titanate are solved, reflux state insulated and stirred 2h is heated to, is cooled to 60 DEG C, is added 0.1 part
Castor oil stirs 20min, filters while hot, and solid washes away impurity with pure water, dry to constant weight.
Reference examples 1
(1) temperature is added according to 1: 0.2: 2 mass ratio in vitamin C, anhydrous calcium chloride, deionized water is 10 DEG C anti-
It answers in kettle, stirs 2 hours, then the sodium hydrate aqueous solution of concentration 40% is added dropwise, adjusting PH is 7, adds 2 times of vitamin Cs and uses
The sodium trimetaphosphate of amount maintains the temperature at 30 DEG C, reacts 4 hours, solid is obtained by filtration；
(2) obtained solid is added in charging basket washer and is washed with water, stirred in 30 DEG C of oxalic acid that solid masses 60% is added
2h is mixed, is filtered, gained filtrate is vitamin C phosphoric ester crude product；
(3) vitamin C phosphoric ester crude product is subjected to nanofiltration membrane through rolling nano-filtration membrane filter；
(4) filtrate that step (3) is obtained by filtration is added in reaction kettle, through weak-base anion-exchange resin, successively uses
Elution fraction is collected in 0.05M hydrochloric acid and the elution of 1.5M hydrochloric acid, and it is 8 that elution fraction, which adjusts pH with magnesia under constant stirring, is obtained
The reactant arrived is L-Ascorbic Acid L-O-Phosphate filtrate；
(5) into L-Ascorbic Acid L-O-Phosphate filtrate be added filtrate quality 3% scarvenger, 35 DEG C of stirring 40min, while hot
Filtering；Filtrate is concentrated under reduced pressure into 1/5th of original volume in 30 DEG C, and it is that the second that 3 times of contents of filtrate are 95% is concentrated that volume, which is added,
Then alcohol is dried by spray dryer to get L-Ascorbic Acid L-O-Phosphate finished product is arrived；The drying temperature of spray drying is 140
DEG C, drying time 30min.
The preparation of scarvenger: 1.2 parts of polyethylene glycol are added in pure water, then 1 part of water is added in 30 stirring 10min
Polymaleic anhydride and 0.01 part of tetraethyl titanate are solved, reflux state insulated and stirred 2h is heated to, is cooled to 60 DEG C, is added 0.1 part
Castor oil stirs 20min, filters while hot, and solid washes away impurity with pure water, dry to constant weight.
Reference examples 2
(1) temperature is added according to 1: 0.2: 2 mass ratio in vitamin C, anhydrous calcium chloride, deionized water is 10 DEG C anti-
It answers in kettle, stirs 2 hours, then the sodium hydrate aqueous solution of concentration 40% is added dropwise, adjusting PH is 7, adds 2 times of vitamin Cs and uses
The sodium trimetaphosphate of amount maintains the temperature at 30 DEG C, reacts 4 hours, solid is obtained by filtration；
(2) obtained solid is added in charging basket washer and is washed with water, stirred in 30 DEG C of oxalic acid that solid masses 60% is added
2h is mixed, is filtered, gained filtrate is vitamin C phosphoric ester crude product；
(3) vitamin C phosphoric ester crude product is subjected to nanofiltration membrane through rolling nano-filtration membrane filter；
(4) filtrate that step (3) is obtained by filtration is added in reaction kettle, through weak-base anion-exchange resin, successively uses
Elution fraction is collected in 0.05M hydrochloric acid and the elution of 1.5M hydrochloric acid, and it is 8 that elution fraction, which adjusts pH with magnesia under constant stirring, is obtained
The reactant arrived is L-Ascorbic Acid L-O-Phosphate filtrate；
(5) into L-Ascorbic Acid L-O-Phosphate filtrate be added filtrate quality 3% scarvenger, 35 DEG C of stirring 40min, while hot
Filtering；Filtrate is concentrated under reduced pressure into 1/5th of original volume in 30 DEG C, and it is that the second that 3 times of contents of filtrate are 95% is concentrated that volume, which is added,
Then alcohol is dried by spray dryer to get L-Ascorbic Acid L-O-Phosphate finished product is arrived；The drying temperature of spray drying is 140
DEG C, drying time 30min.
The modification of magnesia: 1.2 parts of magnesia is added in dehydrated alcohol, 40 DEG C of ultrasonic disperse stirrings
Then 0.1 part of Ni nanoparticle (OH) is added in 10min2, 0.05 part of silane coupling agent kh550 be heated to reflux state insulated and stirred
30min is cooled to 50 DEG C of additions, 0.2 part of silica powder, continues insulated and stirred 1.5h, filters while hot, filter cake dehydrated alcohol
Impurity is washed away, 50 DEG C are dried under vacuum to constant weight.
Scarvenger: active carbon.
Reference examples 3
(1) temperature is added according to 1: 0.2: 2 mass ratio in vitamin C, anhydrous calcium chloride, deionized water is 10 DEG C anti-
It answers in kettle, stirs 2 hours, then the sodium hydrate aqueous solution of concentration 40% is added dropwise, adjusting PH is 7, adds 2 times of vitamin Cs and uses
The sodium trimetaphosphate of amount maintains the temperature at 30 DEG C, reacts 4 hours, solid is obtained by filtration；
(2) obtained solid is added in charging basket washer and is washed with water, stirred in 30 DEG C of oxalic acid that solid masses 60% is added
2h is mixed, is filtered, gained filtrate is vitamin C phosphoric ester crude product；
(3) vitamin C phosphoric ester crude product is subjected to nanofiltration membrane through rolling nano-filtration membrane filter；
(4) filtrate that step (3) is obtained by filtration is added in reaction kettle, through weak-base anion-exchange resin, successively uses
Elution fraction is collected in 0.05M hydrochloric acid and the elution of 1.5M hydrochloric acid, and it is 8 that elution fraction, which adjusts pH with magnesia under constant stirring, is obtained
The reactant arrived is L-Ascorbic Acid L-O-Phosphate filtrate；
(5) L-Ascorbic Acid L-O-Phosphate filtrate is concentrated under reduced pressure into 1/5th of original volume in 30 DEG C, it is dense that volume, which is added,
Then the ethyl alcohol that 3 times of contents of contracting filtrate are 95% is dried by spray dryer to get L-Ascorbic Acid L-O-Phosphate finished product is arrived；Spray
The dry drying temperature of mist is 140 DEG C, drying time 30min.
The modification of magnesia: 1.2 parts of magnesia is added in dehydrated alcohol, 40 DEG C of ultrasonic disperse stirrings
Then 0.1 part of Ni nanoparticle (OH) is added in 10min2, 0.05 part of silane coupling agent kh550 be heated to reflux state insulated and stirred
30min is cooled to 50 DEG C of additions, 0.2 part of silica powder, continues insulated and stirred 1.5h, filters while hot, filter cake dehydrated alcohol
Impurity is washed away, 50 DEG C are dried under vacuum to constant weight.
The preparation of L-Ascorbic Acid L-O-Phosphate is carried out using embodiment 1-2, reference examples 1-3, and its purity is measured,
The results are shown in Table 1.
The purity of 1 L-Ascorbic Acid L-O-Phosphate of table
| Test item | Purity | Free phosphorus hydrochlorate |
| Embodiment 1 | 99.7% | < 0.3% |
| Embodiment 2 | 99.8% | < 0.2% |
| Reference examples 1 | 91.9% | < 0.6% |
| Reference examples 2 | 92.3% | < 0.4% |
| Reference examples 3 | 85.4% | < 0.7% |
The purity test method is ultraviolet spectrophotometry.
The above shows and describes the basic principles and main features of the present invention and the advantages of the present invention.The technology of the industry
Personnel are it should be appreciated that the present invention is not limited to the above embodiments, and the above embodiments and description only describe this
The principle of invention, without departing from the spirit and scope of the present invention, various changes and improvements may be made to the invention, these changes
Change and improvement all fall within the protetion scope of the claimed invention.The claimed scope of the invention by appended claims and its
Equivalent thereof.
Claims (5)
1. a kind of preparation of modified oxidized magnesium, which is characterized in that the preparation method comprises the following steps: magnesia is added in dehydrated alcohol, 40
DEG C ultrasonic disperse stirs 10min, and Ni nanoparticle (OH) then is added2, silane coupling agent be heated to reflux state insulated and stirred 30-
50min is cooled to 50 DEG C of addition silicon-dioxide powderies, continues insulated and stirred 1-2h, filters while hot, filter cake is washed away with dehydrated alcohol
Impurity, 50 DEG C are dried under vacuum to constant weight.
2. the preparation of modified oxidized magnesium according to claim 1, it is characterised in that: the magnesia, silicon-dioxide powdery, Ni
(OH)2, silane coupling agent mass ratio be 1-2:0.1-0.3:0.1-0.2:0.05-0.08.
3. a kind of application of the modified oxidized magnesium in L-Ascorbic Acid L-O-Phosphate as described in claim 1, it is characterised in that: including
Following steps:
(1) by vitamin C, anhydrous calcium chloride, deionized water according to 1: (0.08-0.4): the mass ratio of (1-5) be added temperature be-
It in 10-20 DEG C of reaction kettle, stirs 2-3 hours, then the sodium hydrate aqueous solution of concentration 30-70% is added dropwise, adjusting PH is 5-
10.5, the sodium trimetaphosphate of 1-2.5 times of vitamin C dosage is added, maintains the temperature at 25-45 DEG C, is reacted 2-6 hours, filtering
Obtain solid；
(2) obtained solid is added in charging basket washer and is washed with water, in 30 DEG C of the oxalic acid stirrings that solid masses 60-70% is added
2h, filtering, gained filtrate is vitamin C phosphoric ester crude product；
(3) vitamin C phosphoric ester crude product is subjected to nanofiltration membrane through rolling nano-filtration membrane filter；
(4) filtrate that step (3) is obtained by filtration is added in reaction kettle, through weak-base anion-exchange resin, successively uses 0.05M
Elution fraction is collected in hydrochloric acid and the elution of 0.5M-1.5M hydrochloric acid, and it is 7- that elution fraction, which adjusts pH with magnesia under constant stirring,
11, obtained reactant is L-Ascorbic Acid L-O-Phosphate filtrate；
(5) into L-Ascorbic Acid L-O-Phosphate filtrate be added filtrate quality 3-5% scarvenger, 35-40 DEG C of stirring 20-40min,
It filters while hot；Filtrate is concentrated under reduced pressure into 1/5th of original volume in 30 DEG C, and it is that concentration 3-6 times of content of filtrate is that volume, which is added,
Then 95% ethyl alcohol is dried by spray dryer to get L-Ascorbic Acid L-O-Phosphate finished product is arrived.
4. application of the modified oxidized magnesium in L-Ascorbic Acid L-O-Phosphate according to claim 3, which is characterized in that described pure
Agent the preparation method comprises the following steps: polyethylene glycol is added in pure water, then hydrolysis of polymaleic anhydride is added in 30 stirring 10min
And tetraethyl titanate, it is heated to reflux state insulated and stirred 05-2h, is cooled to 60-65 DEG C, castor oil is added and stirs 20-
30min is filtered while hot, and solid washes away impurity with pure water, dry to constant weight.
5. application of the modified oxidized magnesium in L-Ascorbic Acid L-O-Phosphate according to claim 4, it is characterised in that: described poly-
Ethylene glycol, hydrolysis of polymaleic anhydride, tetraethyl titanate, castor oil mass ratio be 1-2:1-2:0.01:0.1-0.2.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910098383.3A CN109651438A (en) | 2019-01-31 | 2019-01-31 | A kind of preparation of modified oxidized magnesium and its application in L-Ascorbic Acid L-O-Phosphate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910098383.3A CN109651438A (en) | 2019-01-31 | 2019-01-31 | A kind of preparation of modified oxidized magnesium and its application in L-Ascorbic Acid L-O-Phosphate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109651438A true CN109651438A (en) | 2019-04-19 |
Family
ID=66122585
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910098383.3A Pending CN109651438A (en) | 2019-01-31 | 2019-01-31 | A kind of preparation of modified oxidized magnesium and its application in L-Ascorbic Acid L-O-Phosphate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109651438A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114456072A (en) * | 2022-03-02 | 2022-05-10 | 辽宁华星日化产业技术研究院有限公司 | Preparation method of 3- (3, 5-di-tert-butyl-4-hydroxyphenyl) methyl propionate |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101307075A (en) * | 2008-05-15 | 2008-11-19 | 无锡市跨克微营养素有限公司 | Method for preparing L-ascorbate-2-phosplate magnesium |
| CN101735275A (en) * | 2008-11-18 | 2010-06-16 | 高锦秋 | Method for producing vitamin c phosphate magnesium |
| CN101735274A (en) * | 2008-11-18 | 2010-06-16 | 高锦秋 | Technology for processing vitamin c phosphate magnesium |
| CN103665040A (en) * | 2012-09-16 | 2014-03-26 | 无锡市跨克微营养素有限公司 | Preparation method of vitamin C magnesium ascorbyl phosphate |
| CN106478722A (en) * | 2016-08-31 | 2017-03-08 | 安徽天寅生物技术有限公司 | High-purity L ascorbic acid 2 magnesium phosphorate salt production process |
-
2019
- 2019-01-31 CN CN201910098383.3A patent/CN109651438A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101307075A (en) * | 2008-05-15 | 2008-11-19 | 无锡市跨克微营养素有限公司 | Method for preparing L-ascorbate-2-phosplate magnesium |
| CN101735275A (en) * | 2008-11-18 | 2010-06-16 | 高锦秋 | Method for producing vitamin c phosphate magnesium |
| CN101735274A (en) * | 2008-11-18 | 2010-06-16 | 高锦秋 | Technology for processing vitamin c phosphate magnesium |
| CN103665040A (en) * | 2012-09-16 | 2014-03-26 | 无锡市跨克微营养素有限公司 | Preparation method of vitamin C magnesium ascorbyl phosphate |
| CN106478722A (en) * | 2016-08-31 | 2017-03-08 | 安徽天寅生物技术有限公司 | High-purity L ascorbic acid 2 magnesium phosphorate salt production process |
Non-Patent Citations (3)
| Title |
|---|
| 于守武等: "《高分子材料改性-原理及技术》", 31 May 2015, 知识产权出版社 * |
| 贾红兵: "《高分子材料》", 30 November 2009, 南京大学出版社 * |
| 郑水林等: "《非金属矿加工技术与应用手册》", 31 May 2005, 冶金工业出版社 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114456072A (en) * | 2022-03-02 | 2022-05-10 | 辽宁华星日化产业技术研究院有限公司 | Preparation method of 3- (3, 5-di-tert-butyl-4-hydroxyphenyl) methyl propionate |
| CN114456072B (en) * | 2022-03-02 | 2024-01-05 | 辽宁华星日化产业技术研究院有限公司 | Preparation method of 3- (3, 5-di-tert-butyl-4-hydroxyphenyl) methyl propionate |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101307075B (en) | Method for preparing L-ascorbate-2-phosplate magnesium | |
| US6121464A (en) | Preparation of salts of ascorbyl 2-phosphoric esters | |
| CN102140086A (en) | Method for synthesizing vitamin C crude product by adopting L-gulonic acid | |
| CN104311419A (en) | Method for catalytically synthesizing medicinal triethyl citrate by using mesoporous molecular sieve loaded heteropoly acid | |
| CN101284824A (en) | Preparation method of cenolate | |
| CN109651438A (en) | A kind of preparation of modified oxidized magnesium and its application in L-Ascorbic Acid L-O-Phosphate | |
| CN116333173A (en) | Cellulose acetate and preparation method thereof | |
| CN101139328A (en) | Novel process for synthesizing epoxy aliphatic acid methyl ester | |
| CN102115444B (en) | Process and device for continuously producing glyceryl triacetate | |
| CN103319537A (en) | Bifunctional-group-containing pentaerythritol ester antioxidant compound and synthesis method thereof | |
| CN102351933A (en) | Method for preparing hydroxycobalamin salt | |
| CN103665039A (en) | Preparation method of sodium ascorbyl phosphate | |
| CN105481895B (en) | A kind of preparation method of high-purity Vc-2- phosplate sodium and the high-purity Vc-2- phosplate sodium products thus prepared | |
| CN101654464B (en) | Vitamin B1Method for synthesizing phosphoric monoester | |
| CN114349630B (en) | Preparation method of deuterated trifluoroacetic acid | |
| CN1160050A (en) | Process for refining omeprazole | |
| CN115093305A (en) | Method for synthesizing dibromoethane by solid acid catalysis | |
| CN104803845A (en) | Synthetic method of medicinal citrate | |
| CN105732702B (en) | A kind of hydrogenated soy phosphatidyl choline and its production and use | |
| CN110327972B (en) | Hydroxyl polyether functionalized heteropoly acid polyion liquid and application thereof in one-pot synthesis of epoxy methyl oleate | |
| CN107056815A (en) | A kind of Cefixime and process for purification | |
| Claydon et al. | Metabolic products of Entomophthora virulenta | |
| CN109721626A (en) | A kind of preparation of L-AA -2- phosphate magnesium | |
| Yu et al. | Synthesis and Application of Starch 3, 5‐Dinitrobenzoate | |
| CN110066301A (en) | A kind of synthetic method of clindamycin phosphate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20190419 |
|
| RJ01 | Rejection of invention patent application after publication |