CN103626820B - A kind of high purity lanolin cholesterol preparation method - Google Patents
A kind of high purity lanolin cholesterol preparation method Download PDFInfo
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- CN103626820B CN103626820B CN201310510069.4A CN201310510069A CN103626820B CN 103626820 B CN103626820 B CN 103626820B CN 201310510069 A CN201310510069 A CN 201310510069A CN 103626820 B CN103626820 B CN 103626820B
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Abstract
The invention provides a kind of preparation method of feasible suitability for industrialized production high-purity cholesterol.The mode that the present invention adopts fusion-crystallization and solvent One-step crystallization to combine, utilize between cholesterol and other impurity desmesterol and there is larger different melting points (cholesterol fusing point 147 ~ 150 DEG C, desmesterol fusing point 119 ~ 121 DEG C) realize being separated, utilize the solubleness difference in a solvent of other impurity and cholesterol, crystallization obtains high-purity cholesterol.Meet the fields such as medicine, liquid crystal to use.Beneficial effect of the present invention is mainly reflected in: the inventive method is simple to operate, separation efficiency and yield are all higher, with the lanolin cholesterols of more than 95% commercially available purity for raw material, only need through fusion-crystallization, sweating, dissolving crystallized high-purity lanolin cholesterols that just can obtain content more than 99% purity, total yield of products is more than 60%.
Description
Technical field
The present invention relates to a kind of high purity lanolin cholesterol preparation method.
Background technology
Cholesterol has another name called cholesterol, cholesterol, courage steroid-5-alkene-3 β-ol, can produce by widespread use Vitamin D3 500,000 I.U/GM, field of medicaments, liquid crystal raw material etc.Simultaneously because cholesterol possesses good emulsifying and stability, the water-in-oil emulsifier of the product such as emulsion, face cream can also be used as.The cholesterol of low levels can be used for shrimp feed.The industrialization source of cholesterol mainly comprise in lanolin carry out extracting, animal brain stem extracts two kinds of modes, due to the generation of American-European countries TSE/BSE, the states such as America and Europe forbid use the cholesterol in brain stem source and use as raw material, and therefore current industrialized cholesterol is mainly in lanolin and extracts.
Vitamin D3 500,000 I.U/GM produces the purity requirement more than 95% of required cholesterol, the NF level cholesterol of corresponding American Pharmacopeia.But produce for medicine and liquid crystal material, then require that the purity of cholesterol is more than 99%.In recent years, the application of cholesterol on medicinal preparations is more and more extensive, and the application particularly on liposome technology receives much concern especially, and the consumption in pharmaceutical synthesis and Biochemical Research, in liquid crystal material is also increasing.Existing commercial cholesterol purity cannot meet the demands.
The cholesterol in brain stem source, because cholesterol mainly exists with the form of free state in brain stem, therefore its leaching process is relatively simple, and foreign matter content is few, is purified to more than 99% than being easier to.For the cholesterol in lanolin source, cholesterol mainly exists with the form of ester in lanolin, first lanolin is needed to carry out transesterification or saponification process, cholesterol is dissociated out from lanolin, then carry out being separated the lanosterol cut obtaining being rich in cholesterol, process (as operations such as post separation, selective crystallization, complexings) more further and obtain cholesterol crude product, obtain the lanolin cholesterols of commercial NF level (content more than 95%) through crystallization recrystallization.Therefore the production technique of lanolin cholesterols wants complicated many.Containing the cholesterol of more than 95% in NF level coprostenol, the desmesterol of 2 ~ 3%, the lathosterol of 0.5 ~ 2%, the Dihydrocholesterol of about 0.1 ~ 0.5%, 7, the 24-diene Dihydrocholesterols of 0.1 ~ 0.5%.These impurity structures and cholesterol are seemingly, especially the Nature comparison of desmesterol and cholesterol is close, adopts the method for crystallization and recrystallization cannot effectively both well be separated completely, in order to reach the purity of more than 99%, need through repeatedly crystallization, the yield of product is very low.Purity such as containing 2% desmesterol is the NF level cholesterol of 95%, and carry out 6 crystallizations with methyl alcohol, desmesterol content is wherein reduced to 0.8%, and content is 99.2%, and total recovery is 26%.
Japanese Patent JP06239883 describes by commercialization cholesterol (being generally NF level cholesterol) being passed through to carry out hydrogenation reaction under catalyst action, desmesterol in cholesterol is converted into cholesterol, obtain the cholesterol of more than 98% purity, and then obtain the cholesterol of more than 99% purity through crystallization.
Foreign literature is reported that the method for other purification cholesterol comprises and commercial cholesterol is carried out bromination reaction, cholesterol bromide is utilized to carry out separating-purifying from the different of desmesterol bromide character, obtain pure cholesterol bromide, then carry out reduction with zinc and obtain highly purified bromide.But bromide poor stability in process of production, and pollution problem is relatively more serious, is not suitable for suitability for industrialized production.
Application number be 201210163046.6 Chinese patent " a kind of Purification method for lanolin cholesterol " describe and add charcoal absorption mode lanolin cholesterols purity is brought up to more than 99% lanolin cholesterols dissolving crude product is washed by pickling, alkali cleaning, neutrality in ethanol respectively.The method is method refining in brain stem cholesterol production process, is used in lanolin cholesterols and purifies and above there is larger problem, adopts alcohol crystal effectively cannot solve being separated of cholesterol and desmesterol.Application number be 201310057600.7 Chinese patent " a kind of production method of high purity lanolin cholesterol " then adopt 95% ethanol/N-Methyl pyrrolidone mixed solvent to carry out crystallization to crude product cholesterol to obtain more than 99% purity lanolin cholesterols, according to the contaminant characteristics analysis of lanolin cholesterols, being effectively separated of desmesterol and cholesterol cannot be realized by crystallization mode.
Summary of the invention
The invention provides the preparation method of another feasible suitability for industrialized production high-purity cholesterol, production process mild condition, product yield is high.
A kind of high purity (more than 99%) lanolin cholesterols preparation method, described method comprises:
(1) NF level lanolin cholesterols (purity is more than 95%) is put into melting crystallizer, go out the air in melting crystallizer with inert gas replacement, temperature in melting crystallizer is elevated to 150 ~ 155 DEG C raw material is all melted;
(2) by melting crystallizer with the speed slow cooling of 1 ~ 3 DEG C/h, cooling is stopped when temperature drops to 119 ~ 126 DEG C (higher than desmesterol fusing point about 5 DEG C) to melting crystallizer, after leaving standstill crystallization 2 ~ 24h, by screen plate expel liquid bottom melting crystallizer;
(3) fusion-crystallization actuator temperature is elevated to 140 ~ 145 DEG C and makes its sweating, sweating is collected and is repeated above-mentioned steps (1) ~ (3);
(4) fusion-crystallization actuator temperature is reduced to 60 ~ 70 DEG C, adding enough organic solvents makes the cholesterol of melting crystallizer dissolve, lysate is transferred in crystallisation vessel, crystallization at 15 ~ 20 DEG C (about 2 ~ 5 hours), after filtration, dry obtain described high purity lanolin cholesterol; Described organic solvent be selected from following in one or more: the alcohol of C1 ~ C2, the alkane of C5 ~ C7.
Preferably, step (1) described rare gas element is nitrogen or argon gas.
Preferably, step (4) described organic solvent is one of following: methyl alcohol, ethanol, methyl alcohol and hexane mixture, or ethanol and hexane mixture.
The present invention adopts the mode of fusion-crystallization, utilizes between cholesterol and other impurity and there is larger different melting points (cholesterol fusing point 147 ~ 150 DEG C, desmesterol fusing point 119 ~ 121 DEG C) realization separation.Gained high-purity cholesterol can meet the field such as medicine, liquid crystal and use.
Beneficial effect of the present invention is mainly reflected in: the inventive method is simple to operate, separation efficiency and yield are all higher, with the lanolin cholesterols of more than 95% commercially available purity for raw material, only need through fusion-crystallization, sweating, dissolving crystallized high-purity lanolin cholesterols that just can obtain content more than 99% purity, total yield of products is more than 60%.
(1) embodiment
Below in conjunction with specific embodiment, the present invention is described further, but protection scope of the present invention is not limited in this:
Embodiment 1:
By 20.0 grams of purity be 95.5% NF level cholesterol (sample 1) put into melting crystallizer, with nitrogen, (nitrogen is divided into High Purity Nitrogen >=99.999%; Technical grade one-level >=99.5%; Technical grade secondary >=98.5%, in embodiment 1 ~ 5 be 99.999% High Purity Nitrogen) replace air in melting crystallizer.Then temperature in melting crystallizer is elevated to 152 DEG C, crude product lanolin cholesterols is all melted.Then by melting crystallizer with the temperature slow cooling of 1 DEG C per hour, to crystallizer, stop cooling during temperature 131 DEG C, leave standstill crystallization more than 3 hours, then retain crystal by screen plate expel liquid bottom melting crystallizer.Temperature in melting crystallizer is elevated to 145 DEG C and makes crystal sweating.Finally fusion-crystallization actuator temperature is reduced to 60 DEG C, add 100 milliliters of anhydrous alcohol solution crystal, lysate is transferred in flask slowly to stir at 15 DEG C and carries out crystallization, after filtration, drying obtains the high purity lanolin cholesterol (sample 2) of 12.8 grams of content 99.6%, and product weight yield is 64%.
Embodiment 2:
By 20.0 grams of purity be 95.5% NF level cholesterol (sample 1) put into melting crystallizer, with the air in nitrogen replacement melting crystallizer.Then temperature in melting crystallizer is elevated to 150 DEG C, crude product lanolin cholesterols is all melted.Then by melting crystallizer with the temperature slow cooling of 2 DEG C per hour, to crystallizer, stop cooling during temperature 131 DEG C, leave standstill crystallization 2 hours, then retain crystal by screen plate expel liquid bottom melting crystallizer.Fusion-crystallization actuator temperature is elevated to 141 DEG C and makes crystal sweating.Finally fusion-crystallization actuator temperature is reduced to 60 DEG C, add 100 milliliters of dissolve with ethanol crystal, lysate is transferred in flask slowly to stir at 15 DEG C and carries out crystallization, and after filtration, drying obtains the high purity lanolin cholesterol (sample 3) of 14.1 grams of content 99.2%, and product weight yield is 70.5%.
Embodiment 3:
By 20.0 grams of purity be 95.5% NF level cholesterol (sample 1) put into melting crystallizer, with the air in argon replaces melting crystallizer.Then temperature in melting crystallizer is elevated to 152 DEG C, crude product lanolin cholesterols is all melted.Then by melting crystallizer with the temperature slow cooling of 3 DEG C per hour, to crystallizer, stop cooling during temperature 126 DEG C, leave standstill crystallization 4 hours, then retain crystal by screen plate expel liquid bottom melting crystallizer.Fusion-crystallization actuator temperature is elevated to 140 DEG C and makes crystal sweating.Finally fusion-crystallization actuator temperature is reduced to 70 DEG C, add 100 milliliters of dissolve with ethanol crystal, lysate is transferred in flask slowly to stir at 15 DEG C and carries out crystallization, and after filtration, drying obtains the high purity lanolin cholesterol (sample 4) of 14.8 grams of content 99.0%, and product weight yield is 74.0%.
Embodiment 4:
By 20.0 grams of purity be 95.5% NF level cholesterol (sample 1) put into melting crystallizer, with the air in nitrogen replacement melting crystallizer.Then temperature in melting crystallizer is elevated to 150 DEG C, crude product lanolin cholesterols is all melted.Then by melting crystallizer with the temperature slow cooling of 2 DEG C per hour, to crystallizer, stop cooling during temperature 126 DEG C, leave standstill crystallization 3 hours, then retain crystal by screen plate expel liquid bottom melting crystallizer.Fusion-crystallization actuator temperature is elevated to 144 DEG C and makes crystal sweating.Finally fusion-crystallization actuator temperature is reduced to 65 DEG C, add 100 ml methanol alcohol and dissolve crystal, lysate is transferred in flask slowly to stir at 15 DEG C and carries out crystallization, after filtration, drying obtains the high purity lanolin cholesterol (sample 5) of 13.7 grams of content 99.3%, and product weight yield is 68.5%.
Embodiment 5(comparative example):
By 20.0 grams of purity be 95.5% NF level cholesterol (sample 1) put into melting crystallizer, with the air in nitrogen replacement melting crystallizer.Then temperature in melting crystallizer is elevated to 152 DEG C, crude product lanolin cholesterols is all melted.Then by melting crystallizer with the temperature slow cooling of 2 DEG C per hour, to crystallizer, stop cooling during temperature 126 DEG C, leave standstill crystallization 3 hours, then retain crystal by screen plate expel liquid bottom melting crystallizer.Fusion-crystallization actuator temperature is reduced to 70 DEG C, add 100 milliliters of dissolve with ethanol crystal, lysate is transferred in flask slowly to stir at 15 DEG C and carries out crystallization, and after filtration, drying obtains the lanolin cholesterols (sample 6) of 15.5 grams of content 98.7%, and product weight yield is 77.5%.
Attached: the analytical results of cholesterol sample 1 ~ 6 is as follows:
Claims (3)
1. a high purity lanolin cholesterol preparation method, described method comprises:
(1) NF level lanolin cholesterols is put into melting crystallizer, go out the air in melting crystallizer with inert gas replacement, temperature in melting crystallizer is elevated to 150 ~ 155 DEG C raw material is all melted;
(2) by melting crystallizer with the speed slow cooling of 1 ~ 3 DEG C/h, stop cooling when temperature drops to 119 ~ 126 DEG C to melting crystallizer, after leaving standstill crystallization 2 ~ 24h, by screen plate expel liquid bottom melting crystallizer;
(3) fusion-crystallization actuator temperature is elevated to 140 ~ 145 DEG C and makes its sweating, sweating is collected;
(4) fusion-crystallization actuator temperature is reduced to 60 ~ 70 DEG C, adds enough organic solvents and the cholesterol of melting crystallizer is dissolved, lysate is transferred in crystallisation vessel, crystallization at 15 ~ 20 DEG C, after filtration, dry obtain described high purity lanolin cholesterol; Described organic solvent be selected from following in one or more: the alcohol of C1 ~ C2, the alkane of C5 ~ C7.
2. the method for claim 1, is characterized in that step (1) described rare gas element is nitrogen or argon gas.
3. the method for claim 1, is characterized in that step (4) described organic solvent is one of following: methyl alcohol, ethanol, methyl alcohol and hexane mixture, or ethanol and hexane mixture.
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| WO2020095888A1 (en) * | 2018-11-05 | 2020-05-14 | 日本精化株式会社 | Method for producing high-purity cholesterol |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1958596A (en) * | 2006-11-22 | 2007-05-09 | 浙江大学 | Method for extracting cholesterol from lanoline |
| CN101817859A (en) * | 2010-06-02 | 2010-09-01 | 天津大学 | Method for separating and extracting cholesterol in lanolin alcohol |
| CN102464573A (en) * | 2010-11-09 | 2012-05-23 | 浙江龙盛化工研究有限公司 | Method for preparing high-purity resorcinol through melt crystallization |
| CN103102380A (en) * | 2013-02-25 | 2013-05-15 | 上海艾韦特医药科技有限公司 | Production method of high purity lanolin cholesterol |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1958596A (en) * | 2006-11-22 | 2007-05-09 | 浙江大学 | Method for extracting cholesterol from lanoline |
| CN101817859A (en) * | 2010-06-02 | 2010-09-01 | 天津大学 | Method for separating and extracting cholesterol in lanolin alcohol |
| CN102464573A (en) * | 2010-11-09 | 2012-05-23 | 浙江龙盛化工研究有限公司 | Method for preparing high-purity resorcinol through melt crystallization |
| CN103102380A (en) * | 2013-02-25 | 2013-05-15 | 上海艾韦特医药科技有限公司 | Production method of high purity lanolin cholesterol |
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Effective date of registration: 20190816 Address after: Room 1 # 581, Yatai Incubation Base, 697 Yongkang Street, Wucheng District, Jinhua City, Zhejiang Province, 321000 Patentee after: Zhejiang Garden Nutrition Technology Co., Ltd. Address before: 310018 166 No. 20 Street, Hangzhou Economic and Technological Development Zone, Zhejiang Province Patentee before: Down biological Science Technologies Co., Ltd. of the sand in Hangzhou |