CN103102267A - Preparation method of pharmaceutic adjuvant grade Glyceryl Behenate - Google Patents
Preparation method of pharmaceutic adjuvant grade Glyceryl Behenate Download PDFInfo
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- CN103102267A CN103102267A CN2011103550090A CN201110355009A CN103102267A CN 103102267 A CN103102267 A CN 103102267A CN 2011103550090 A CN2011103550090 A CN 2011103550090A CN 201110355009 A CN201110355009 A CN 201110355009A CN 103102267 A CN103102267 A CN 103102267A
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- Prior art keywords
- glyceryl behenate
- behenic acid
- acid
- add
- glycerine
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- OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 title claims abstract description 34
- 229940049654 glyceryl behenate Drugs 0.000 title claims abstract description 34
- 239000000546 pharmaceutical excipient Substances 0.000 title claims abstract description 21
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- UKMSUNONTOPOIO-UHFFFAOYSA-N docosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCCCC(O)=O UKMSUNONTOPOIO-UHFFFAOYSA-N 0.000 claims abstract description 68
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims abstract description 42
- 235000021357 Behenic acid Nutrition 0.000 claims abstract description 34
- 229940116226 behenic acid Drugs 0.000 claims abstract description 34
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 22
- 238000000034 method Methods 0.000 claims abstract description 22
- 235000011187 glycerol Nutrition 0.000 claims abstract description 21
- 229940124531 pharmaceutical excipient Drugs 0.000 claims abstract description 20
- 238000006297 dehydration reaction Methods 0.000 claims abstract description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000005886 esterification reaction Methods 0.000 claims abstract description 11
- 230000018044 dehydration Effects 0.000 claims abstract description 8
- 238000001816 cooling Methods 0.000 claims abstract description 5
- 238000002425 crystallisation Methods 0.000 claims abstract description 5
- 230000008025 crystallization Effects 0.000 claims abstract description 3
- 238000001035 drying Methods 0.000 claims abstract description 3
- 238000003756 stirring Methods 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 16
- 239000008213 purified water Substances 0.000 claims description 11
- 238000007605 air drying Methods 0.000 claims description 10
- 230000032050 esterification Effects 0.000 claims description 10
- 230000035484 reaction time Effects 0.000 claims description 4
- 238000001953 recrystallisation Methods 0.000 claims description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 abstract description 5
- 239000003814 drug Substances 0.000 abstract description 4
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- 239000007810 chemical reaction solvent Substances 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract description 2
- 238000000746 purification Methods 0.000 abstract description 2
- 239000011973 solid acid Substances 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- 239000002699 waste material Substances 0.000 abstract description 2
- 239000003054 catalyst Substances 0.000 abstract 1
- 238000005119 centrifugation Methods 0.000 abstract 1
- 238000004042 decolorization Methods 0.000 abstract 1
- 238000001914 filtration Methods 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- 238000007670 refining Methods 0.000 abstract 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 abstract 1
- 239000002253 acid Substances 0.000 description 18
- 238000005100 correlation spectroscopy Methods 0.000 description 16
- 150000002148 esters Chemical class 0.000 description 10
- 125000005456 glyceride group Chemical group 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 8
- 229910000831 Steel Inorganic materials 0.000 description 8
- 150000005690 diesters Chemical class 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 238000007127 saponification reaction Methods 0.000 description 8
- 239000010959 steel Substances 0.000 description 8
- 238000010792 warming Methods 0.000 description 8
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 230000001276 controlling effect Effects 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 3
- QHZLMUACJMDIAE-UHFFFAOYSA-N 1-monopalmitoylglycerol Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(O)CO QHZLMUACJMDIAE-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- ARIWANIATODDMH-UHFFFAOYSA-N rac-1-monolauroylglycerol Chemical compound CCCCCCCCCCCC(=O)OCC(O)CO ARIWANIATODDMH-UHFFFAOYSA-N 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- DMBUODUULYCPAK-UHFFFAOYSA-N 1,3-bis(docosanoyloxy)propan-2-yl docosanoate Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCCCCCC DMBUODUULYCPAK-UHFFFAOYSA-N 0.000 description 1
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 description 1
- VTDOEFXTVHCAAM-UHFFFAOYSA-N 4-methylpent-3-ene-1,2,3-triol Chemical compound CC(C)=C(O)C(O)CO VTDOEFXTVHCAAM-UHFFFAOYSA-N 0.000 description 1
- -1 acetonylidene glyceryl Chemical group 0.000 description 1
- OGBUMNBNEWYMNJ-UHFFFAOYSA-N batilol Chemical class CCCCCCCCCCCCCCCCCCOCC(O)CO OGBUMNBNEWYMNJ-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 229940068939 glyceryl monolaurate Drugs 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000000654 isopropylidene group Chemical group C(C)(C)=* 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000005461 lubrication Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 1
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- DCBSHORRWZKAKO-UHFFFAOYSA-N rac-1-monomyristoylglycerol Chemical compound CCCCCCCCCCCCCC(=O)OCC(O)CO DCBSHORRWZKAKO-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明涉及药物合成领域，具体地涉及一种药用辅料级山嵛酸甘油酯的制备方法。根据本发明的方法包括步骤：(1)在反应器中加入山嵛酸和甘油搅拌均匀；(2)直接升温脱水酯化反应；(3)加入活性炭脱色、趁热过滤；(4)加纯化水冷却结晶，离心，干燥，粉碎得到药用辅料级山嵛酸甘油酯。本发明采用山嵛酸和甘油直接脱水酯化制备山嵛酸甘油酯，无需像常规酯化反应时加入催化剂，如：浓硫酸、对甲苯磺酸、固体酸等；也无需加入其它反应溶剂；此外产品精制较为方便。该工艺“三废”产生少，操作简单，收率可达89％以上，适宜工业化生产，质量可满足药用辅料级要求。The invention relates to the field of drug synthesis, in particular to a preparation method of pharmaceutical excipient grade glyceryl behenate. The method according to the present invention comprises the steps: (1) adding behenic acid and glycerin in the reactor and stirring evenly; (2) directly raising the temperature for dehydration esterification reaction; (3) adding activated carbon for decolorization and filtering while hot; (4) adding purification Cooling with water for crystallization, centrifugation, drying, and crushing to obtain pharmaceutical excipient grade glyceryl behenate. The present invention uses behenic acid and glycerin to directly dehydrate and esterify glyceryl behenate to prepare glyceryl behenate, without adding catalysts such as concentrated sulfuric acid, p-toluenesulfonic acid, solid acid, etc.; and without adding other reaction solvents; In addition, product refining is more convenient. The process produces less "three wastes", is simple to operate, and has a yield of more than 89%, which is suitable for industrial production, and the quality can meet the requirements of pharmaceutical excipients.
Description
Technical field
The present invention relates to medicine and synthesize the field, relate to particularly a kind of preparation method of pharmaceutical excipient level Glyceryl Behenate.
Background technology
Glyceryl Behenate is nonionogenic tenside, has emulsification, dispersion, froth breaking and lubrication; Can be used as emulsifying agent and emulsion stabilizer, for the preparation of emulsion, ointment, salve.The main application of Glyceryl Behenate in medicament is to be used as lubricant in tablet, pill, granule and capsule manufacturing; Make dispersion agent, also have been widely used in solid, semisolid and liquid preparation; Also can be used for slow releasing tablet, and as the skeleton of water-soluble drug sustained-release preparation.
The method of at present synthetic Glyceryl Behenate has: 1, make isopropylidene glycerol-4-methanol with glycerine and acetone reaction, react to get the different acetonylidene glyceryl ester of behenic acid with behenic acid again, further with its hydrolysis single Glyceryl Behenate (universal will, Huang Tianhe, " study on the synthesis of single Glyceryl Behenate ", " chemical reagent ", 2009,31); 2, the one-pot synthesis of protecting with acetone; namely make isopropylidene glycerine by glycerine and acetone reaction; (Gu Yujie, horse are firm etc. to have prepared glyceryl monolaurate, single tetradecanoic acid glyceryl ester, monopalmitin, glyceryl monostearate, 5 kinds of monoglycerides of single Glyceryl Behenate with fatty acid response under the Catalyzed by p-Toluenesulfonic Acid effect; " synthesizing series high purity monoglyceride "; " daily chemical industry "; 2006,36).
Above-mentioned synthetic method is all synthetic single Glyceryl Behenate or mixes Glyceryl Behenate, and the pharmaceutical grade Glyceryl Behenate is a kind of mixture that contains behenic acid monoglyceride, dibasic acid esters and three esters, wherein single Glyceryl Behenate content should be 12%～18%, and acid number must be below 4.Therefore, above-mentioned literature method can not be used for directly preparing pharmaceutical excipient level Glyceryl Behenate.
Have no at present document and the patent report of pharmaceutical grade Glyceryl Behenate production technique both at home and abroad, the synthetic of similar derivative only arranged.
Summary of the invention
The present inventor proposes and has completed the present invention in order to address the above problem.
Purpose of the present invention is for providing a kind of preparation method of pharmaceutical excipient level Glyceryl Behenate.
Preparation method according to pharmaceutical excipient level Glyceryl Behenate of the present invention said method comprising the steps of:
(1) add behenic acid and glycerine to stir in reactor, wherein, the molar ratio of behenic acid and glycerine is 1～2.5: 1;
(2) the dehydration esterification that directly heats up does not need catalyzer, and temperature of reaction is 105～200 ℃, and the reaction times is 5-12 hour;
(3) add activated carbon decolorizing, filtered while hot;
(4) crystallisation by cooling, centrifugal, drying is pulverized and is obtained pharmaceutical excipient level Glyceryl Behenate.
The present invention is take behenic acid and glycerine as raw material, and the Direct Dehydration esterification obtains the requirement of pharmaceutical excipient level Glyceryl Behenate, and its reaction scheme is as follows:
The method according to this invention, wherein, in the esterification process of step (1), the molar ratio of behenic acid and glycerine is 1.35～1.9: 1, is preferably 1.6～1.9: 1.Behenic acid and glycerine ratio control can be produced the qualified product of behenic acid direactive glyceride content well under these processing condition.
The method according to this invention, wherein, in step (2) directly heated up the dehydration esterification, temperature of reaction was 120～180 ℃, is preferably 140～160 ℃; Reaction times is 6-10 hour, is preferably 7-8 hour.The high temperature dehydration esterification temperature is too high can affect product color, and too low reaction not exclusively.
According to power method of the present invention, wherein, in step (3), add the gac of behenic acid weight ratio 1% to decolour, elimination discoloring agent gac should be while hot.
According to method of the present invention, wherein, in step (4), add the purified water cooling crystallization of 2～5 times of amounts of behenic acid weight, be preferably 3～4 times of amounts, purified water is good.
According to method of the present invention, wherein, the recrystallization temperature of step (4) is 10～40 ℃, is preferably 20～30 ℃.
The consumption of gac is too low can affect product color, does not reach decolorizing effect.As too high in consumption, adsorb excessively, yield reduces.
The method according to this invention wherein, is selected the normal pressure forced air drying when dry in step (4).
The present invention adopts behenic acid and the esterification of glycerine Direct Dehydration to prepare Glyceryl Behenate, adds catalyzer when need not as conventional esterification, as: the vitriol oil, tosic acid, solid acid etc.; Also need not to add other reaction solvent; Product purification more in addition.This technique " three wastes " produces few, and simple to operate, yield can reach more than 89%, suitability for industrialized production, but the requirement of quality fulfilling medicinal auxiliary material level.
Embodiment
Embodiment 1
Drop into 50.1kg behenic acid and 13.5kg glycerine (mol ratio is 1: 1) in glassed steel reaction vessels, being warming up to 105 ℃ of dehydration reactions 10 hours (controls acid number＜4.0=, adds the 5.0kg activated carbon decolorizing, filtered while hot, add the 250.0kg purified water in filtrate, be cooled to 40 ℃ of crystallizatioies 24 hours, centrifugal rejection filter, forced air drying, pulverize, cross 80 mesh sieves, obtain 57.2kg pharmaceutical excipient level Glyceryl Behenate, molar yield: 89.9%.Acid number 1.7; Saponification value 147.3; Behenic acid direactive glyceride 17.8% (by the two ministerial standard tests of 2010 editions Chinese Pharmacopoeias), warp
1H-NMR;
13C-NMR; The C-H Correlated Spectroscopy; Long-range C-H Correlated Spectroscopy conclusive evidence is the mixture of monoesters, diester, three esters.
Embodiment 2
Drop into 50.0kg behenic acid and 10.0kg glycerine (mol ratio is 1.35: 1) in glassed steel reaction vessels, being warming up to 120 ℃ of dehydration reactions 8 hours (controls acid number＜4.0=, adds the 5.0kg activated carbon decolorizing, filtered while hot, add the 200.0kg purified water in filtrate, be cooled to 30 ℃ of crystallizatioies 24 hours, centrifugal rejection filter, forced air drying, pulverize, cross 80 mesh sieves, obtain 54.5kg pharmaceutical excipient level Glyceryl Behenate, molar yield: 90.8%.Acid number 2.5; Saponification value 150.6; Behenic acid direactive glyceride 16.1% (by the two ministerial standard tests of 2010 editions Chinese Pharmacopoeias), warp
1H-NMR;
13C-NMR; The C-H Correlated Spectroscopy; Long-range C-H Correlated Spectroscopy conclusive evidence is the mixture of monoesters, diester, three esters.
Embodiment 3
Drop into 51.2kg behenic acid and 8.6kg glycerine (mol ratio is 1.6: 1) in glassed steel reaction vessels, be warming up to 140 ℃ of dehydration reactions 8 hours (controlling acid number＜4.0), add the 5.1kg activated carbon decolorizing, filtered while hot, add the 150.0kg purified water in filtrate, be cooled to 20 ℃ of crystallizatioies 24 hours, centrifugal rejection filter, forced air drying, pulverize, cross 80 mesh sieves, obtain 54.8kg pharmaceutical excipient level Glyceryl Behenate, molar yield: 91.6%.Acid number 2.6; Saponification value 154.5; Behenic acid direactive glyceride 15.3% (by the two ministerial standard tests of 2010 editions Chinese Pharmacopoeias), warp
1H-NMR;
13C-NMR; The C-H Correlated Spectroscopy; Long-range C-H Correlated Spectroscopy conclusive evidence is the mixture of monoesters, diester, three esters.
Embodiment 4
Drop into 50.5kg behenic acid and 7.2kg glycerine (mol ratio is 1.9: 1) in glassed steel reaction vessels, being warming up to 160 ℃ of dehydration reactions 7 hours (controls acid number＜4.0=, adds the 5.0kg activated carbon decolorizing, filtered while hot, add the 128.0kg purified water in filtrate, be cooled to 10 ℃ of crystallizatioies 24 hours, centrifugal rejection filter, forced air drying, pulverize, cross 80 mesh sieves, obtain 52.6kg pharmaceutical excipient level Glyceryl Behenate, molar yield: 911%.White powder; 69.5 ℃～72.1 ℃ of fusing points; Acid number 3.1; Saponification value 155.1; Behenic acid direactive glyceride 14.8% (by the two ministerial standard tests of 2010 editions Chinese Pharmacopoeias), warp
1H-NMR;
13C-NMR; The C-H Correlated Spectroscopy; Long-range C-H Correlated Spectroscopy conclusive evidence is the mixture of monoesters, diester, three esters.
Embodiment 5
Drop into 51.0kg behenic acid and 6.6kg glycerine (mol ratio is 2.1: 1) in glassed steel reaction vessels, be warming up to 180 ℃ of dehydration reactions 8 hours (controlling acid number＜4.0), add the 5.0kg activated carbon decolorizing, filtered while hot, add the 120.0kg purified water in filtrate, be cooled to 20 ℃ of crystallizatioies 24 hours, centrifugal rejection filter, forced air drying, pulverize, cross 80 mesh sieves, obtain 51.8kg pharmaceutical excipient level Glyceryl Behenate, molar yield: 90%.Acid number 2.5; Saponification value 158.5; Behenic acid direactive glyceride 14.6% (by the two ministerial standard tests of 2010 editions Chinese Pharmacopoeias), warp
1H-NMR;
13C-NMR; The C-H Correlated Spectroscopy; Long-range C-H Correlated Spectroscopy conclusive evidence is the mixture of monoesters, diester, three esters.
Embodiment 6
Drop into 50.1kg behenic acid and 5.4kg glycerine (mol ratio is 2.5: 1) in glassed steel reaction vessels, be warming up to 200 ℃ of dehydration reactions 6 hours (controlling acid number＜4.0), add the 5.0kg activated carbon decolorizing, filtered while hot, add the 100.0kg purified water in filtrate, be cooled to 25 ℃ of crystallizatioies 24 hours, centrifugal rejection filter, forced air drying, pulverize, cross 80 mesh sieves, obtain 50.6kg pharmaceutical excipient level Glyceryl Behenate, molar yield: 91%.Acid number 3.5; Saponification value 160.5; Behenic acid direactive glyceride 13.5% (by the two ministerial standard tests of 2010 editions Chinese Pharmacopoeias), warp
1H-NMR;
13C-NMR; The C-H Correlated Spectroscopy; Long-range C-H Correlated Spectroscopy conclusive evidence is the mixture of monoesters, diester, three esters.
Embodiment 7
Drop into 51.5kg behenic acid and 8.5kg glycerine (mol ratio is 1.6: 1) in glassed steel reaction vessels, be warming up to 140 ℃ of dehydration reactions 5 hours (controlling acid number＜4.0), add the 5.1kg activated carbon decolorizing, filtered while hot, add the 130.0kg purified water in filtrate, be cooled to 25 ℃ of crystallizatioies 24 hours, centrifugal rejection filter, forced air drying, pulverize, cross 80 mesh sieves, obtain 52.9kg pharmaceutical excipient level Glyceryl Behenate, molar yield: 88.0%.Acid number 3.4; Saponification value 156.5; Behenic acid direactive glyceride 14.5% (by the two ministerial standard tests of 2010 editions Chinese Pharmacopoeias), warp
1H-NMR;
13C-NMR; The C-H Correlated Spectroscopy; Long-range C-H Correlated Spectroscopy conclusive evidence is the mixture of monoesters, diester, three esters.
Embodiment 8
Drop into 51.7kg behenic acid and 8.6kg glycerine (mol ratio is 1.6: 1) in glassed steel reaction vessels, being warming up to 140 ℃ of dehydration reactions 12 hours (controls acid number＜4.0=, adds the 5.1kg activated carbon decolorizing, filtered while hot, add the 130.0kg purified water in filtrate, be cooled to 25 ℃ of crystallizatioies 24 hours, centrifugal rejection filter, forced air drying, pulverize, cross 80 mesh sieves, obtain 50.7kg pharmaceutical excipient level Glyceryl Behenate, molar yield: 84.0%.Acid number 2.1; Saponification value 158.5; Behenic acid direactive glyceride 15.3% (by the two ministerial standard tests of 2010 editions Chinese Pharmacopoeias), warp
1H-NMR;
13C-NMR; The C-H Correlated Spectroscopy; Long-range C-H Correlated Spectroscopy conclusive evidence is the mixture of monoesters, diester, three esters.
Claims (7)
1. the preparation method of a pharmaceutical excipient level Glyceryl Behenate, is characterized in that, said method comprising the steps of:
(1) add behenic acid and glycerine to stir in reactor, wherein, the molar ratio of behenic acid and glycerine is 1～2.5: 1;
(2) the dehydration esterification that directly heats up, temperature of reaction is 105～200 ℃, the reaction times is 5-12 hour;
(3) add activated carbon decolorizing, filtered while hot;
(4) crystallisation by cooling, centrifugal, drying is pulverized and is obtained pharmaceutical excipient level Glyceryl Behenate.
2. method according to claim 1, is characterized in that, in the esterification process of step (1), the molar ratio of behenic acid and glycerine is 1.35～1.9: 1, is preferably 1.6～1.9: 1.
3. method according to claim 1, is characterized in that, in step (2) directly heated up the dehydration esterification, temperature of reaction was 120～180 ℃, is preferably 140～160 ℃; Reaction times is 6-10 hour, is preferably 7-8 hour.
4. according to method claimed in claim 1, it is characterized in that, in step (3), add the gac of behenic acid weight ratio 1% to decolour.
5. according to method claimed in claim 1, it is characterized in that, in step (4), add the purified water cooling crystallization of 2～5 times of amounts of behenic acid weight, be preferably 3～4 times of amounts.
6. according to method claimed in claim 1, it is characterized in that, the recrystallization temperature of step (4) is 10～40 ℃, is preferably 20～30 ℃.
7. method according to claim 1, is characterized in that, selects the normal pressure forced air drying when dry in step (4).
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104557525A (en) * | 2013-10-21 | 2015-04-29 | 广东东阳光药业有限公司 | Method for preparing ester |
| CN107417522A (en) * | 2017-05-22 | 2017-12-01 | 武汉桀升生物科技有限公司 | A kind of method for catalyzing and synthesizing the Compritol 888 ATO for pharmaceutic adjuvant |
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| US4098706A (en) * | 1975-05-07 | 1978-07-04 | Sapchim-Fournier-Cimag | Lubricating agents for thermoplastic materials and process for preparing the same |
| CN101495538A (en) * | 2006-07-28 | 2009-07-29 | 日清奥利友集团株式会社 | Esterification reaction product, gelling agent containing the product, and cosmetic preparation containing them |
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2011
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| US4098706A (en) * | 1975-05-07 | 1978-07-04 | Sapchim-Fournier-Cimag | Lubricating agents for thermoplastic materials and process for preparing the same |
| CN101495538A (en) * | 2006-07-28 | 2009-07-29 | 日清奥利友集团株式会社 | Esterification reaction product, gelling agent containing the product, and cosmetic preparation containing them |
Cited By (3)
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|---|---|---|---|---|
| CN104557525A (en) * | 2013-10-21 | 2015-04-29 | 广东东阳光药业有限公司 | Method for preparing ester |
| CN104557525B (en) * | 2013-10-21 | 2019-01-04 | 广东东阳光药业有限公司 | A kind of preparation method of ester |
| CN107417522A (en) * | 2017-05-22 | 2017-12-01 | 武汉桀升生物科技有限公司 | A kind of method for catalyzing and synthesizing the Compritol 888 ATO for pharmaceutic adjuvant |
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| CN103102267B (en) | 2015-08-05 |
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