CN103102267A - Preparation method of pharmaceutic adjuvant grade Glyceryl Behenate - Google Patents
Preparation method of pharmaceutic adjuvant grade Glyceryl Behenate Download PDFInfo
- Publication number
- 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
- Authority
- CN
- China
- Prior art keywords
- glyceryl behenate
- behenic acid
- acid
- add
- glycerine
- 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.)
- Granted
Links
- 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
Claims (7)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201110355009.0A CN103102267B (en) | 2011-11-10 | 2011-11-10 | A kind of preparation method of pharmaceutic adjuvant grade Glyceryl Behenate |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201110355009.0A CN103102267B (en) | 2011-11-10 | 2011-11-10 | A kind of preparation method of pharmaceutic adjuvant grade Glyceryl Behenate |
Publications (2)
Publication Number | Publication Date |
---|---|
CN103102267A true CN103102267A (en) | 2013-05-15 |
CN103102267B CN103102267B (en) | 2015-08-05 |
Family
ID=48310502
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201110355009.0A Active CN103102267B (en) | 2011-11-10 | 2011-11-10 | A kind of preparation method of pharmaceutic adjuvant grade Glyceryl Behenate |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN103102267B (en) |
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 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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 |
-
2011
- 2011-11-10 CN CN201110355009.0A patent/CN103102267B/en active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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)
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 |
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 |
Also Published As
Publication number | Publication date |
---|---|
CN103102267B (en) | 2015-08-05 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN101235067B (en) | A kind of preparation method of phytosterol ester | |
CN108265089B (en) | Oil and fat composition containing 1, 3-dioleoyl-2-palmitic acid triglyceride and preparation method thereof | |
CN111094312B (en) | Preparation method of sucrose ester | |
CN104003894A (en) | Method for preparing N-acetyl-beta-chlorine-L-alanine methyl ester | |
JP2023507463A (en) | Treatment of purified 2,5-furandicarboxylic acid with organic acid and heat | |
CN103102267A (en) | Preparation method of pharmaceutic adjuvant grade Glyceryl Behenate | |
CN101774997B (en) | Method for completely and continuously extracting natural vitamin E and phytosterol | |
CN106349197A (en) | Preparing method of emulsifier Span-80 for emulsion explosive | |
CN102795960B (en) | Large-scale preparation method of high-purity octacosanol and triacontanol | |
CN101270124B (en) | Novel method for purifying and preparing high-purity fluorandiol and fluorandiol salt | |
CN101544589A (en) | Preparation for medicinal intermediate 6-chloro-5-fluroindole for synthesizing anti-cancer medicament | |
CN103922925B (en) | A kind of production technique of Fenofibric Acid | |
CN103980481B (en) | The preparation method of watermiscible vitamin E | |
CN107417522B (en) | Method for catalytically synthesizing glyceryl behenate used as pharmaceutical adjuvant | |
CN101781215A (en) | Method for preparing propyl gallate bulk drug by chemical semi-synthesis | |
CN107573237A (en) | A kind of method that high-purity gossypol acetate is prepared in cotton oil refining process | |
CN102094050B (en) | Method for preparing hexadecanoic acid propylene glycol ester | |
CN103570786B (en) | A kind of n-amyl alcohol segmentation purifies cupreol and the method for stigmasterol | |
CN114920642A (en) | Separation process for obtaining high-purity fatty acid monoglyceride and fatty acid diglyceride | |
CN107473963B (en) | Chemical synthesis method of OPO structural lipid | |
KR101813207B1 (en) | Purification method of crude glycerine by distiiiation | |
CN102786541A (en) | Preparation method and application of potassium (iso)quinoline thifluoroborate | |
CN102344392B (en) | Method for refining histone deacetylase (HDAC) inhibitor vorinostat | |
CN103772241B (en) | A kind of preparation method of sulfonated dehydro sylvate | |
CN102206185B (en) | Process for refining bendazac lysine and analogs thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Preparation method of pharmaceutic adjuvant grade Glyceryl Behenate Effective date of registration: 20171108 Granted publication date: 20150805 Pledgee: Shangli Jiangxi rural commercial bank Limited by Share Ltd. Pledgor: JIANGXI ALPHA HI-TECH PHARMACEUTICAL Co.,Ltd. Registration number: 2017360000023 |
|
PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20191206 Granted publication date: 20150805 Pledgee: Shangli Jiangxi rural commercial bank Limited by Share Ltd. Pledgor: JIANGXI ALPHA HI-TECH PHARMACEUTICAL Co.,Ltd. Registration number: 2017360000023 |
|
PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Preparation method of pharmaceutic adjuvant grade Glyceryl Behenate Effective date of registration: 20191224 Granted publication date: 20150805 Pledgee: Shangli Jiangxi rural commercial bank Limited by Share Ltd. Pledgor: JIANGXI ALPHA HI-TECH PHARMACEUTICAL Co.,Ltd. Registration number: Y2019980001253 |
|
PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20211214 Granted publication date: 20150805 Pledgee: Shangli Jiangxi rural commercial bank Limited by Share Ltd. Pledgor: JIANGXI ALPHA HI-TECH PHARMACEUTICAL Co.,Ltd. Registration number: Y2019980001253 |
|
PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Preparation method of medicinal auxiliary material grade behenic acid glyceride Effective date of registration: 20211215 Granted publication date: 20150805 Pledgee: Shangli Jiangxi rural commercial bank Limited by Share Ltd. Pledgor: JIANGXI ALPHA HI-TECH PHARMACEUTICAL Co.,Ltd. Registration number: Y2021980015254 |
|
PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20221212 Granted publication date: 20150805 Pledgee: Shangli Jiangxi rural commercial bank Limited by Share Ltd. Pledgor: JIANGXI ALPHA HI-TECH PHARMACEUTICAL Co.,Ltd. Registration number: Y2021980015254 |
|
PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A preparation method of medical excipient behenic acid glyceride Effective date of registration: 20221227 Granted publication date: 20150805 Pledgee: Shangli Jiangxi rural commercial bank Limited by Share Ltd. Pledgor: JIANGXI ALPHA HI-TECH PHARMACEUTICAL Co.,Ltd. Registration number: Y2022980029287 |
|
PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20231129 Granted publication date: 20150805 Pledgee: Shangli Jiangxi rural commercial bank Limited by Share Ltd. Pledgor: JIANGXI ALPHA HI-TECH PHARMACEUTICAL Co.,Ltd. Registration number: Y2022980029287 |
|
PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Preparation method of a medicinal excipient grade glyceryl valerate Effective date of registration: 20231206 Granted publication date: 20150805 Pledgee: Shangli Jiangxi rural commercial bank Limited by Share Ltd. Pledgor: JIANGXI ALPHA HI-TECH PHARMACEUTICAL Co.,Ltd. Registration number: Y2023980069762 |
|
PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
PC01 | Cancellation of the registration of the contract for pledge of patent right |
Granted publication date: 20150805 Pledgee: Shangli Jiangxi rural commercial bank Limited by Share Ltd. Pledgor: JIANGXI ALPHA HI-TECH PHARMACEUTICAL Co.,Ltd. Registration number: Y2023980069762 |
|
PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Preparation method of medicinal excipient grade succinic acid glyceride Granted publication date: 20150805 Pledgee: Shangli Jiangxi rural commercial bank Limited by Share Ltd. Pledgor: JIANGXI ALPHA HI-TECH PHARMACEUTICAL Co.,Ltd. Registration number: Y2024980052039 |
|
PE01 | Entry into force of the registration of the contract for pledge of patent right |