CN1075505C - Preparation method of saturated phosphatidate and its salts - Google Patents
Preparation method of saturated phosphatidate and its salts Download PDFInfo
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- CN1075505C CN1075505C CN99127182A CN99127182A CN1075505C CN 1075505 C CN1075505 C CN 1075505C CN 99127182 A CN99127182 A CN 99127182A CN 99127182 A CN99127182 A CN 99127182A CN 1075505 C CN1075505 C CN 1075505C
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- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- 150000008103 phosphatidic acids Chemical class 0.000 title claims abstract description 10
- 229920006395 saturated elastomer Polymers 0.000 title claims description 9
- 150000003839 salts Chemical class 0.000 title description 5
- 239000002904 solvent Substances 0.000 claims abstract description 69
- PORPENFLTBBHSG-MGBGTMOVSA-N 1,2-dihexadecanoyl-sn-glycerol-3-phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(O)=O)OC(=O)CCCCCCCCCCCCCCC PORPENFLTBBHSG-MGBGTMOVSA-N 0.000 claims abstract description 32
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 15
- 238000002425 crystallisation Methods 0.000 claims abstract description 13
- 230000008025 crystallization Effects 0.000 claims abstract description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 37
- BQFCCCIRTOLPEF-UHFFFAOYSA-N chembl1976978 Chemical compound CC1=CC=CC=C1N=NC1=C(O)C=CC2=CC=CC=C12 BQFCCCIRTOLPEF-UHFFFAOYSA-N 0.000 claims description 36
- 150000003904 phospholipids Chemical class 0.000 claims description 31
- 239000002253 acid Substances 0.000 claims description 29
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 27
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 20
- 239000000203 mixture Substances 0.000 claims description 17
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical class CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 16
- 239000000463 material Substances 0.000 claims description 16
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 16
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 16
- 229910052799 carbon Inorganic materials 0.000 claims description 15
- 229960001701 chloroform Drugs 0.000 claims description 15
- 238000006243 chemical reaction Methods 0.000 claims description 14
- 150000002576 ketones Chemical class 0.000 claims description 10
- 239000000243 solution Substances 0.000 claims description 10
- 239000000284 extract Substances 0.000 claims description 9
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 8
- 235000019253 formic acid Nutrition 0.000 claims description 8
- 229940075529 glyceryl stearate Drugs 0.000 claims description 8
- 239000007864 aqueous solution Substances 0.000 claims description 6
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 6
- 230000035484 reaction time Effects 0.000 claims description 6
- 238000010992 reflux Methods 0.000 claims description 6
- 238000009835 boiling Methods 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- 238000005507 spraying Methods 0.000 claims description 5
- 239000003513 alkali Substances 0.000 claims description 4
- 238000001704 evaporation Methods 0.000 claims description 4
- 230000008020 evaporation Effects 0.000 claims description 4
- 239000008187 granular material Substances 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 3
- 229940050176 methyl chloride Drugs 0.000 claims description 3
- 239000011707 mineral Substances 0.000 claims description 3
- NEHMKBQYUWJMIP-NJFSPNSNSA-N chloro(114C)methane Chemical compound [14CH3]Cl NEHMKBQYUWJMIP-NJFSPNSNSA-N 0.000 claims description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 abstract description 15
- 239000011574 phosphorus Substances 0.000 abstract description 15
- 229910052698 phosphorus Inorganic materials 0.000 abstract description 15
- 238000000034 method Methods 0.000 abstract description 14
- 238000004090 dissolution Methods 0.000 abstract description 2
- 239000007787 solid Substances 0.000 abstract description 2
- 238000003756 stirring Methods 0.000 abstract description 2
- 238000001291 vacuum drying Methods 0.000 abstract description 2
- 238000001914 filtration Methods 0.000 abstract 1
- UHUSDOQQWJGJQS-UHFFFAOYSA-N glycerol 1,2-dioctadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(CO)OC(=O)CCCCCCCCCCCCCCCCC UHUSDOQQWJGJQS-UHFFFAOYSA-N 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- 239000011259 mixed solution Substances 0.000 abstract 1
- 238000001694 spray drying Methods 0.000 abstract 1
- GNTDGMZSJNCJKK-UHFFFAOYSA-N divanadium pentaoxide Chemical group O=[V](=O)O[V](=O)=O GNTDGMZSJNCJKK-UHFFFAOYSA-N 0.000 description 12
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 8
- 238000006386 neutralization reaction Methods 0.000 description 8
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 235000019198 oils Nutrition 0.000 description 7
- 239000011591 potassium Substances 0.000 description 7
- 229910052700 potassium Inorganic materials 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 150000001982 diacylglycerols Chemical class 0.000 description 6
- 230000032050 esterification Effects 0.000 description 6
- 238000005886 esterification reaction Methods 0.000 description 6
- 239000012046 mixed solvent Substances 0.000 description 6
- 229910021529 ammonia Inorganic materials 0.000 description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium group Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 4
- 150000003863 ammonium salts Chemical class 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000005469 granulation Methods 0.000 description 2
- 230000003179 granulation Effects 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 235000015320 potassium carbonate Nutrition 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 235000017550 sodium carbonate Nutrition 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 description 1
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 description 1
- 235000019484 Rapeseed oil Nutrition 0.000 description 1
- HEAFLBOWLRRIHV-UHFFFAOYSA-N [Na].[P] Chemical compound [Na].[P] HEAFLBOWLRRIHV-UHFFFAOYSA-N 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000003084 food emulsifier Nutrition 0.000 description 1
- 238000009413 insulation Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 229910052750 molybdenum Inorganic materials 0.000 description 1
- 239000011733 molybdenum Substances 0.000 description 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Abstract
The present invention relates to a preparation method for saturated phosphatidic acid and phosphatidic acid salts. Firstly, distearin reacts with a phosphatizing agent, the obtained product is dissolved in a solvent 1, a solvent 2 is used for extracting the mixed solution, and raw phosphatidic acid is obtained; a solvents 3 is used for dissolving the raw phosphatidic acid, and refined phosphatidic acid containing solvents is obtained by stir, dissolution, crystallization and filtration; the refined phosphatidic acid containing solvents are processed by removing the solvents by vacuum or spray-drying, the refined phosphatidic acid are directly granulated, and the phosphatidic acid or phosphatidic acid salts is prepared. The method has the advantage of simple preparation process, and is easy to realize industrial production. A product of the method is solid, and the granulated product is convenient for users; the phosphorus content of the product is high, the phosphorus content generally is more than 3.5%, and the highest phosphorus content can reach 5%.
Description
The present invention relates to the preparation method of a kind of saturated phosphatidate and its esters, be mainly used in industries such as food, makeup, medicine, chemical industry, belong to chemical technology field.
The chemical structural formula of phosphatidic acid is as follows:
R is a fatty acid acyl in the formula.
With in the alkali and phosphatidic acid, just can obtain the corresponding phospholipids hydrochlorate.
At present, the main rapeseed oil that adopts in Europe is produced phosphatidic acid, and further obtains ammonium salts of phosphatidic acid with the ammonia neutralization, sees " food emulsifier ", China Light Industry Press, version in 1993.Its main technique flow process is as follows:
Though this technology Production Flow Chart is short, cost is lower, and gained phosphatidic acid product is semi-solid (paste), and the user uses inconvenience.This method is not seen patent report as yet.
In addition, it is raw material that Japanese Patent 1992-145088,1992-267882 also provide with the soybean phospholipid, by the method for enzymolysis production phosphatidic acid, but its raw materials used price height, technology is wayward.
The objective of the invention is to propose the preparation method of a kind of saturated phosphatidate and its esters, make production technique simple, and product is easy to use.
The preparation method of the saturated phosphatidate of the present invention's design comprises following each step:
(1) with two glyceryl stearates and phosphotidic agent reaction, the weight ratio that feeds intake is: two glyceryl stearates: phosphotidic agent=3～10: 1, and temperature of reaction is 110～170 ℃, and the reaction times is 1～5 hour, and reaction pressure is 10～760mmHg;
(2) above-mentioned products therefrom is dissolved in the solvent orange 2 A, solvent orange 2 A is that any and second kind of material in first kind of material alcohol that is low-carbon (LC), ketone, the acid is any mixture in the methyl chloride, both mixed volume ratios are: 1: 0.5～5, and the consumption of solvent orange 2 A is: two glyceryl stearate gram numbers: solvent orange 2 A milliliter number=1: 3～10;
(3) with solvent B above-mentioned mixing solutions is extracted, to remove unreacted phosphotidic agent in the product, solvent B is the aqueous solution that contains solvent orange 2 A, and the consumption of solvent B is: two glyceryl stearate gram numbers: solvent B milliliter number=1: 4～12 extract 2～4 times at normal temperatures;
(4) with the above-mentioned solution that contains product at 10～80 ℃, the pressure of 10～400mmHg down evaporation removes and desolvates, and obtains raw phospholipid acid;
(5) dissolve above-mentioned raw phospholipid acid with solvent C, solvent C is lower boiling organic solvent, and its consumption is: raw phospholipid acid gram number: solvent C milliliter number=1: 4～13 are stirred to dissolving under reflux temperature;
(6), filter then and obtain containing the smart phosphatidic acid of solvent-10 ℃～30 ℃ following crystallizations 2～10 hours;
(7) under 10～80 ℃, pressure be under the condition of 1～200mmHg to the said products solvent removed in vacuo or spraying drying, directly granulate, be phosphatidic acid of the present invention.
In the above-mentioned steps, first material in the used solvent orange 2 A is: any in methyl alcohol, ethanol, propyl alcohol, acetone, formic acid, the acetate; Second kind of material is: methylene dichloride, trichloromethane, tetracol phenixin any.Used solvent C is: the mixture of one or both in low-carbon alkanes, sherwood oil, low-carbon alcohol, the ketone.
The present invention also designs the preparation method of saturated phospholipid hydrochlorate, comprises following each step:
(1) with two glyceryl stearates and phosphotidic agent reaction, the weight ratio that feeds intake is: two glyceryl stearates: phosphotidic agent=3～10: 1, and temperature of reaction is 110～170 ℃, and the reaction times is 1～5 hour, and reaction pressure is 10～760mmHg;
(2) instead neutralize with mineral alkali with regard to product to above-mentioned, making its pH value is 6～8;
(3) above-mentioned products therefrom is dissolved in the solvent orange 2 A, solvent orange 2 A is any mixture in any and second kind of material methyl chloride in first kind of material alcohol that is low-carbon (LC), ketone, the acid, both mixed volume ratios are: 1: 0.5～5, and the consumption of solvent orange 2 A is: two glyceryl stearate gram numbers: solvent orange 2 A milliliter number=1: 3～10;
(4) with solvent B above-mentioned mixing solutions is extracted, to remove unreacted phosphotidic agent in the product, solvent B is the aqueous solution that contains solvent orange 2 A, and the consumption of solvent B is: two glyceryl stearate gram numbers: solvent B milliliter number=1: 4～12 extract 2～4 times at normal temperatures;
(5) with the above-mentioned solution that contains product at 10～80 ℃, the pressure of 10～400mmHg down evaporation removes and desolvates, and obtains the raw phospholipid hydrochlorate;
(6) dissolve above-mentioned raw phospholipid hydrochlorate with solvent C, solvent C is lower boiling organic solvent, and its consumption is: raw phospholipid acid gram number: solvent C milliliter number=1: 4～13 are stirred to dissolving under reflux temperature;
(7), filter then and obtain containing the smart phosphotidats of solvent-10 ℃～30 ℃ following crystallizations 2～10 hours;
(8) under 10～80 ℃, pressure be under the condition of 1～200mmHg to the said products solvent removed in vacuo or spraying drying, directly granulate, be phosphotidats of the present invention.
In the above-mentioned steps, first material in the used solvent orange 2 A is: any in methyl alcohol, ethanol, propyl alcohol, acetone, formic acid, the acetate; Second kind of material is: methylene dichloride, trichloromethane, tetracol phenixin any.Used solvent C is: the mixture of one or both in low-carbon alkanes, sherwood oil, low-carbon alcohol, the ketone.
The used bi-tristearin of the present invention is hereinafter to be referred as diacylglycerol, and used phosphotidic agent is Vanadium Pentoxide in FLAKES or phosphoric acid or phosphorus oxychloride.In the esterification process: feed ratio: 3～10: 1 (diacylglycerol weight: phosphotidic agent weight, phosphoric acid and phosphorus oxychloride are converted to Vanadium Pentoxide in FLAKES).
Mineral alkali commonly used all can be used for the neutralization of phosphatidic acid as the aqueous solution of ammonia, ammoniacal liquor or sodium hydroxide, potassium hydroxide, yellow soda ash, salt of wormwood or the like.
Solvent orange 2 A is low-carbon alcohol, ketone, acid as any and methyl chloride of methyl alcohol, ethanol, propyl alcohol, acetone, formic acid, acetate any mixture as, methylene dichloride, trichloromethane (chloroform), tetracol phenixin, and ratio of mixture is 1: 0.5～5 (volume ratios).The consumption of solvent orange 2 A is 1: 3～10 (diacylglycerol weight: the solvent orange 2 A volume).
Solvent B is the aqueous solution that contains solvent orange 2 A, and it can constitute the liquid-liquid equilibrium system with solvent orange 2 A, and does not change the organic solvent ratio of solvent orange 2 A phase substantially.Extraction times is generally 2～4 times, and the consumption of each extraction solvent B is 1: 4～12 (diacylglycerol weight: solvent B volume), operate at normal temperatures.
The solution that will contain raw phospholipid acid (salt) is in room temperature～80 ℃, and 10～400mmHg pressure removes down and desolvates, and obtains raw phospholipid acid (salt).
Solvent C is lower boiling organic solvent, as low-carbon alkanes, sherwood oil, low-carbon alcohol, ketone and their mixture etc.The operational condition of dissolving 2 processes is as follows:
Solvent C consumption: 1: 4～12[raw phospholipid acid (salt) weight: solvent C volume]
Dissolution conditions: be stirred to dissolving under the reflux temperature.
The operational condition of crystallisation process is under-10 ℃～room temperature 2～10 hours, filters then to obtain containing the smart phosphatide (salt) of solvent.
Product removes and to desolvate: room temperature～80 ℃, solvent removed in vacuo or the direct granulation of spraying drying under pressure 1～200mmHg condition.
The saturated phosphatidate that the present invention proposes and the preparation method of its esters have the following advantages:
(1) preparation technology of the present invention is simple, is easy to realize suitability for industrialized production.
(2) adopting the phosphatidic acid or the phosphotidats of the present invention's preparation is solid phase prod, user-friendly after the granulation.
(3) adopt the phosphatidic acid of the present invention's preparation or the phosphorus content height of phosphotidats product, generally, be up to 5% more than 3.5%.And the requirement of the phosphatidic acid ammonia quality index (Dok.4979/82, the Agrileg29 draft is referring to document [1]) in Europe is: phosphorus content 3.0～3.4%.
Introduce embodiments of the invention below:
(1) (wherein content of monoglyceride is 15.5% to take by weighing the high-purity diacylglycerol of 30 gram solvent crystallizations, glycerol content is 3.2%) and 5 gram Vanadium Pentoxide in FLAKESs, place there-necked flask, be placed in the oil bath then and heat, after treating the diacylglycerol fusing, the control oil bath temperature is about 145 ℃, is constantly reacting 3.5 hours under the stirring condition.Remove oil bath, when treating that the product temperature is reduced to 70 ℃, dropping ammonia to product pH be 7.0.With this product with 100 milliliters of solvent orange 2 As (methyl alcohol: methylene dichloride=1: 3) dissolving, use then 200 milliliters of solvent B (methyl alcohol: methylene dichloride: water=2: 1: 4) extraction, remove the water layer liquid phase.After so extracting 3 times, solution control pressure 50mmHg in 50 ℃ of water-baths that will contain product carries out solvent removed in vacuo, obtains 31.2 gram raw phospholipids acid ammoniums.After this raw phospholipid acid ammonium is heated to the reflux temperature dissolving with 200 milliliters of sherwood oils, be chilled to room temperature (20 ℃), the ammonium salts of phosphatidic acid crystallization is separated out, insulation was left standstill 5 hours, filtered, and crystal is vacuum-drying under the 100mmHg in 50 ℃ of water-baths, 24.1 restrain smart ammonium salts of phosphatidic acid.Record raw phospholipid acid ammonium and smart phosphatidic acid sodium phosphorus content is respectively 2.9% and 3.6% with molybdenum blue colorimetric fixing phosphorus method.
(2) in embodiment (1), replace Vanadium Pentoxide in FLAKES with 10 milliliter of 85% phosphoric acid, hierarchy of control pressure is 400mmHg in the esterification process, 110 ℃ of temperature, in 5 hours reaction times, 0.1N sodium hydroxide is adopted in neutralization, recrystallisation solvent C is an acetone, 210 milliliters of consumptions, crystallization time 4 hours, all the other operations are identical with conditionally complete.Obtain 30.5 gram raw phospholipid acid sodium and the smart phosphatidic acid sodium of 21.6 grams, its phosphorus content is respectively 3.4% and 4.1%.
(3) in embodiment (1), replace Vanadium Pentoxide in FLAKES with 15 milliliters of phosphorus oxychloride, hierarchy of control pressure is 250mmHg in the esterification process, 130 ℃ of temperature, in 4.5 hours reaction times, 0.1N yellow soda ash is adopted in neutralization, recrystallisation solvent C is a hexanaphthene, 180 milliliters of consumptions, crystallization time 7 hours, all the other operations are identical with conditionally complete.Obtain 33.0 gram raw phospholipid acid and the smart phosphatidic acid of 22.2 grams, its phosphorus content is respectively 3.4% and 5.0%.
(4) in embodiment (1), 110 ℃ of esterification temperatures, save neutralization procedure, solvent orange 2 A changes ethanol and chloroform mixed solvent (ethanol: chloroform=1: 2) into, the ratio of mixture of solvent B is an ethanol: chloroform: water=2: 1: 3 extracts 5 ℃ of Tcs 4 times, crystallization time 3 hours, all the other operations are identical with conditionally complete.Obtain 29.5 gram raw phospholipid acid sodium and the smart phosphatidic acid sodium of 21.3 grams, its phosphorus content is respectively 3.2% and 4.2%.
(5) in embodiment (2), the phosphoric acid consumption changes 6 milliliters into, the neutralization of employing ammonia, solvent orange 2 A is that acetone mixes (acetone: chloroform=1: 3) with chloroform, the mixture of solvent B is an acetone: chloroform: water=1: 1: 4, and recrystallisation solvent C uses ethanol instead, and 40 ℃ of solvent temperatures are removed in crystallization, pressure 5mmHg, all the other operations are identical with conditionally complete.Obtain 30.6 gram raw phospholipid acid ammoniums and the smart ammonium salts of phosphatidic acid of 22.7 grams, its phosphorus content is respectively 3.1% and 4.0%.
(6) in embodiment (2), 165 ℃ of control reaction temperature, reaction pressure 500mmHg adopts the neutralization of 0.1N potassium hydroxide, and solvent orange 2 A is used acetate and tetracol phenixin mixed solvent (acetate: tetracol phenixin=1: 4.5) instead, the ratio of mixture of solvent B is an acetate: tetracol phenixin: water=2: 1: 2,150 milliliters of consumptions extract 4 times, and raw phospholipid acid potassium is removed 60 ℃ of solvent temperatures, pressure 30mmHg, all the other operations are identical with conditionally complete.Obtain 28.8 gram raw phospholipid acid potassium and the smart phosphatidic acid potassium of 23.4 grams, its phosphorus content is respectively 3.3% and 3.9%.
(7) in embodiment (3), the phosphorus oxychloride consumption changes 12 milliliters into, 0.1N salt of wormwood is adopted in neutralization, solvent orange 2 A is used formic acid and chloroform mixed solvent (formic acid: chloroform=1: 4) instead, the ratio of mixture of solvent B is a formic acid: chloroform: water=1: 1: 1, extract 4 times, 150 milliliters of each solvent B consumptions, all the other operations are identical with conditionally complete.Obtain 31.3 gram raw phospholipid acid potassium and the smart phosphatidic acid potassium of 23.4 grams, its phosphorus content is respectively 3.3% and 4.3%.
(8) in embodiment (7), esterification temperature adopts 110 ℃, solvent orange 2 A is used propyl alcohol and methylene dichloride mixed solvent (propyl alcohol: methylene dichloride=1: 1) instead, the ratio of mixture of solvent B is a propyl alcohol: methylene dichloride: water=1: 1: 4, extract 3 times, 100 milliliters of each solvent B consumptions are removed 80 ℃ of solvent temperatures, pressure 50mmHg, all the other operations are identical with conditionally complete.Obtain 32.0 gram raw phospholipid acid potassium and the smart phosphatidic acid potassium of 23.6 grams, its phosphorus content is respectively 3.1% and 4.2%.
(9) in embodiment (4), recrystallisation solvent C uses ethanol and acetone mixed solvent (ethanol and acetone=1: 1) instead, and consumption is 120 milliliters, 5 ℃ of Tcs, and crystallization time 1 hour, all the other operations are identical with conditionally complete.Obtain 29.3 gram raw phospholipid acid and the smart phosphatidic acid of 20.7 grams, its phosphorus content is respectively 3.4% and 4.7%.
(10) in embodiment (1), the Vanadium Pentoxide in FLAKES consumption changes 10 grams into, esterification time 1.5 hours, and solvent B consumption is 300 milliliters, extracts 2 times, and solvent C changes normal hexane and methanol mixed solvent (ratio of mixture 1: 1) into, and all the other operations are identical with conditionally complete.Obtain 30.8 gram raw phospholipid acid and the smart phosphatidic acid of 21.9 grams, its phosphorus content is respectively 3.5% and 4.8%.
Claims (6)
1, a kind of preparation method of saturated phosphatidate is characterized in that, this preparation method comprises following each step:
(1) with two glyceryl stearates and phosphotidic agent reaction, the weight ratio that feeds intake is: two glyceryl stearates: phosphotidic agent=3～10: 1, and temperature of reaction is 110～170 ℃, and the reaction times is 1～5 hour, and reaction pressure is 10～760mmHg;
(2) above-mentioned products therefrom is dissolved in the solvent orange 2 A, solvent orange 2 A is that any and second kind of material in first kind of material alcohol that is low-carbon (LC), ketone, the acid is any mixture in the methyl chloride, both mixed volume ratios are: 1: 0.5～5, and the consumption of solvent orange 2 A is: two glyceryl stearate gram numbers: solvent orange 2 A milliliter number=1: 3～10;
(3) with solvent B above-mentioned mixing solutions is extracted, to remove unreacted phosphotidic agent in the product, solvent B is the aqueous solution that contains solvent orange 2 A, and the consumption of solvent B is: two glyceryl stearate gram numbers: solvent B milliliter number=1: 4～12 extract 2～4 times at normal temperatures;
(4) with the above-mentioned solution that contains product at 10～80 ℃, the pressure of 10～400mmHg down evaporation removes and desolvates, and obtains raw phospholipid acid;
(5) dissolve above-mentioned raw phospholipid acid with solvent C, solvent C is lower boiling organic solvent, and its consumption is: raw phospholipid acid gram number: solvent C milliliter number=1: 4～13 are stirred to dissolving under reflux temperature;
(6), filter then and obtain containing the smart phosphatidic acid of solvent-10 ℃～30 ℃ following crystallizations 2～10 hours;
(7) under 10～80 ℃, pressure be under the condition of 1～200mmHg to the said products solvent removed in vacuo or spraying drying, directly granulate, be phosphatidic acid of the present invention.
2, preparation method as claimed in claim 1 is characterized in that, first material in the wherein said solvent orange 2 A is: any in methyl alcohol, ethanol, propyl alcohol, acetone, formic acid, the acetate; Described second kind of material is: methylene dichloride, trichloromethane, tetracol phenixin any.
3, preparation method as claimed in claim 1 is characterized in that, wherein said solvent C is: the mixture of one or both in low-carbon alkanes, sherwood oil, low-carbon alcohol, the ketone.
4, a kind of preparation method of saturated phospholipid hydrochlorate is characterized in that, this preparation method comprises following each step:
(1) with two glyceryl stearates and phosphotidic agent reaction, the weight ratio that feeds intake is: two glyceryl stearates: phosphotidic agent=3～10: 1, and temperature of reaction is 110～170 ℃, and the reaction times is 1～5 hour, and reaction pressure is 10～760mmHg;
(2) instead neutralize with mineral alkali with regard to product to above-mentioned, making its pH value is 6～8;
(3) above-mentioned products therefrom is dissolved in the solvent orange 2 A, solvent orange 2 A is any mixture in any and second kind of material methyl chloride in first kind of material alcohol that is low-carbon (LC), ketone, the acid, both mixed volume ratios are: 1: 0.5～5, and the consumption of solvent orange 2 A is: two glyceryl stearate gram numbers: solvent orange 2 A milliliter number=1: 3～10;
(4) with solvent B above-mentioned mixing solutions is extracted, to remove unreacted phosphotidic agent in the product, solvent B is the aqueous solution that contains solvent orange 2 A, and the consumption of solvent B is: two glyceryl stearate gram numbers: solvent B milliliter number=1: 4～12 extract 2～4 times at normal temperatures;
(5) with the above-mentioned solution that contains product at 10～80 ℃, the pressure of 10～400mmHg down evaporation removes and desolvates, and obtains the raw phospholipid hydrochlorate;
(6) dissolve above-mentioned raw phospholipid hydrochlorate with solvent C, solvent C is lower boiling organic solvent, and its consumption is: raw phospholipid acid gram number: solvent C milliliter number=1: 4～13 are stirred to dissolving under reflux temperature;
(7), filter then and obtain containing the smart phosphotidats of solvent-10 ℃～30 ℃ following crystallizations 2～10 hours;
(8) under 10～80 ℃, pressure be under the condition of 1～200mmHg to the said products solvent removed in vacuo or spraying drying, directly granulate, be phosphotidats of the present invention.
5, preparation method as claimed in claim 4 is characterized in that, first material in the wherein said solvent orange 2 A is: any in methyl alcohol, ethanol, propyl alcohol, acetone, formic acid, the acetate; Described second kind of material is: methylene dichloride, trichloromethane, tetracol phenixin any.
6, preparation method as claimed in claim 4 is characterized in that, wherein said solvent C is: the mixture of one or both in low-carbon alkanes, sherwood oil, low-carbon alcohol, the ketone.
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| CN99127182A CN1075505C (en) | 1999-12-30 | 1999-12-30 | Preparation method of saturated phosphatidate and its salts |
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|---|---|---|---|
| CN99127182A CN1075505C (en) | 1999-12-30 | 1999-12-30 | Preparation method of saturated phosphatidate and its salts |
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| CN1263098A CN1263098A (en) | 2000-08-16 |
| CN1075505C true CN1075505C (en) | 2001-11-28 |
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| CA2889116C (en) | 2012-10-31 | 2020-09-01 | Akzo Nobel Chemicals International B.V. | Phosphated compositions as adhesion promoters |
| CN104447853B (en) * | 2014-11-06 | 2017-01-18 | 江南大学 | Method for preparing calcium phosphatidate |
| CN104447854B (en) * | 2014-11-06 | 2017-01-18 | 江南大学 | Preparation method of phosphatidic acid sodium |
| CN111057100A (en) * | 2018-10-16 | 2020-04-24 | 合肥博思科创医药科技有限公司 | Preparation method of phosphatidylglycerol monosodium salt containing two different side chains |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0399544A1 (en) * | 1989-05-26 | 1990-11-28 | Kao Corporation | Process for the production of phosphatidic acid |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0399544A1 (en) * | 1989-05-26 | 1990-11-28 | Kao Corporation | Process for the production of phosphatidic acid |
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