CN102453011A - Preparation method of high-purity naringenin - Google Patents
Preparation method of high-purity naringenin Download PDFInfo
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- CN102453011A CN102453011A CN2010105302724A CN201010530272A CN102453011A CN 102453011 A CN102453011 A CN 102453011A CN 2010105302724 A CN2010105302724 A CN 2010105302724A CN 201010530272 A CN201010530272 A CN 201010530272A CN 102453011 A CN102453011 A CN 102453011A
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Abstract
The invention provides a preparation method of naringenin. The preparation method comprises the following steps: (1) preparing solution of naringin in lower alcohol or lower ketone solvent, leading the naringin in the prepared solution to be subjected to acid hydrolysis in an acidic condition to obtain naringenin, distilling under reduced pressure to remove solvent to obtain a naringenin crude product; (2) dissolving the naringenin crude product in absolute ethanol or absolute methanol, adding active carbon, stirring to decolor; and (3) filtering the active carbon, separating and purifying the prepared solution to obtain the naringenin. The preparation method has the advantages of few reaction steps, less used solvent, less emission of the 'three wastes', mild reaction condition and complete reaction and easy operation, is suitable for industrial production, and has higher practical value; and the prepared product has more stable quality, the purity is higher than 99 percent, which is higher than the drug standard.
Description
Technical field
Present invention relates in general to a kind of preparation method of naringenin, relate in particular to and adopt the hydrolysis naringin to prepare the method for high purity naringenin.
Background technology
Naringenin is the aglycon of naringin, and another name salipurpol, Naringenin, former, the naringenin of naringin are flavanone kind composition, are present in the various plants; Can from various plants, extract, also can obtain from the naringin hydrolysis.That naringenin has is antibiotic, anti-inflammatory, antitumor, remove effects such as radical, spasmolysis and cholagogic.Owing to naringenin content in natural phant is not high, need complicated extraction, separating technology, big and difficult recovery of three wastes discharge amount; And the naringin relative content is high and easy the extraction.
Liu Yaping discloses a kind of preparation method of naringenin (referring to Liu Yaping in " preparing method's research of naringenin "; Preparing method's research of naringenin, spectrographic laboratory, the 25th the 6th phase of volume; In November, 2008; The 1292-1294 page or leaf), it adopts direct water heating and extracting naringin earlier, and the acid hydrolysis naringin obtains naringenin again.But this method " the gained aglycon must just can obtain highly purified naringenin with the ethanol periodic crystallisation " (referring to conclusion part).
Patent CN1555793A also discloses and has a kind ofly prepared the method for naringenin through the hydrolysis naringin, but this method also needs repeatedly crystallization could obtain the higher naringenin of purity.
Summary of the invention
For addressing the above problem, the purpose of this invention is to provide a kind of preparation method of naringenin, improve product yield, and use the reaction product purity of this method preparation higher, steady quality.
For realizing above-mentioned purpose, the preparation method of naringenin of the present invention comprises:
(1) obtain the solution of naringin in lower alcohol or lower ketones solvent earlier, make the naringin that obtains in the solution that acid hydrolysis acquisition naringenin takes place under acidic conditions then, solvent is removed in underpressure distillation, obtains the naringenin bullion;
(2) make the naringenin dissolving crude product in absolute ethyl alcohol or anhydrous methanol, add gac, stir decolouring;
(3) filtering gac separates purification to the solution that obtains, and obtains naringenin.
Lower alcohol described in the present invention or lower ketones refer to carbonatoms and are less than or equal to 4 alcohol or ketone, for example are methyl alcohol, ethanol, butanols, acetone etc.; Be preferably methyl alcohol and/or ethanol.Also can contain an amount of water in lower alcohol or the lower ketones described in the said step (1).Because contain lower alcohol or lower ketones in the reaction system in the step (1), with respect to simple use water as solvent, naringin can more disperse; And the naringenin that generates more is difficult to be gathered into glutinous group; Guarantee that reaction can carry out completely, in the product by product also still less, therefore; In the reaction system, the content of water with less for being prone to.In the step according to the invention (1), the water cut of reaction system preferably is no more than 20% (w/w), preferredly is no more than 10%.
Naringin can hydrolytic reactions under acidic conditions, generates naringenin, and it is 2-5 that acidic conditions described in the present invention is preferably pH value, and more preferably 2.5.
Concrete, according to an embodiment of the invention, said step (1) drips acid for earlier naringin being dissolved in lower alcohol or the lower ketones under 0-15 ℃ condition, be warming up to 60-90 ℃ then, stirring reaction 30-48 hour.Preferably, in the step (1) consumption of lower alcohol or lower ketones be said naringin quality 3-5 doubly.Preferably, in the step (1), acid is concentrated hydrochloric acid, Glacial acetic acid min. 99.5, carbonic acid, nitric acid, the vitriol oil etc. for example, is preferably concentrated hydrochloric acid.
Preferably, in the said step (2), the consumption of absolute ethyl alcohol or anhydrous methanol is 3-5 a times of naringin quality, and the consumption of gac is naringin quality 3-5%.Concrete, said step (2) is heated to 50-60 ℃ and is dissolved to clarification for the naringenin dissolving crude product is joined in anhydrous methanol or the absolute ethyl alcohol, adds gac, stirs 1-2 hour.
More specifically, according to an embodiment of the invention, said step (1) is for being dissolved in naringin in anhydrous methanol or the absolute ethyl alcohol earlier, and dropping inorganic acid under 0-15 ℃ condition is warming up to 60-90 ℃ then, stirring reaction 30-48 hour.Preferably, in the step (1) quality of anhydrous methanol or absolute ethyl alcohol be said naringin 3-5 doubly.Preferably, in the step (1), mineral acid is concentrated hydrochloric acid, Glacial acetic acid min. 99.5, carbonic acid, nitric acid, the vitriol oil etc. for example, is preferably concentrated hydrochloric acid.
Separating and purifying method those skilled in the art in the said step (3) can select according to actual needs.Because naringin is dissolved in lower alcohol or the lower ketones solvent hydrolytic reactions more earlier in the step (1), is dissolved in merely in the water with respect to dissolving, disperse better, the by product of generation is few, and the separation that is beneficial to naringin is purified; Simultaneously, owing to before separating purification, added gac, gac obtains outside the high-quality naringenin except decolouring to solution, can also assist in removing the impurity in the naringenin simultaneously; Therefore follow-up separation is purified and is only needed the primary crystallization method usually, can obtain the product of satisfactory purity.Therefore, preferred, the separation in the said step (3) is purified and is purified for adopting crystallization process to separate.Preferred, the separation in the said step (3) is purified and is: in solution, add 3-5 purified water doubly, be cooled to room temperature; Left standstill crystallization 35-48 hour; Suction filtration, filter cake are with absolute ethyl alcohol or anhydrous methanol drip washing, and dry back obtains the naringenin of white or off-white color needle crystal.
The discovery that the present inventor is surprised is dissolved in naringin in anhydrous methanol or the absolute ethyl alcohol earlier, and then carries out acid hydrolysis; Perhaps be dissolved in acidolysis again in the water with respect to direct acidolysis of the prior art; It is easier to purify, and product purity is higher, and quality product is also more stable.And, before separation is purified, use earlier activated carbon decolorizing, can improve the quality that obtains naringenin on the one hand, can also reduce the difficulty of naringenin purification on the other hand, obtain highly purified naringenin.Usually need repeatedly recrystallization just can reach satisfied purity in the prior art, and the application's technical scheme only need primary crystallization, can obtain very high purity.
Therefore, compare with original method, it is few that the present invention has reactions step, and the use solvent is few, three waste discharge is few, and reaction conditions is gentle and more complete, easy and simple to handle, is fit to suitability for industrialized production, has high value of practical.The quality product that obtains is more stable, and purity can reach more than 99%, is higher than the drug standard.
Embodiment
Hereinafter combines specific embodiment further to set forth the present invention, the reagent that adopts among the embodiment be technical grade other.
Embodiment one
The 6kg naringin is dissolved in the 20kg methyl alcohol, and normal temperature stirred 30 minutes down.Be cooled to 0 ℃, drip a certain amount of concentrated hydrochloric acid, regulate pH value to 2.5, drip controlled temperature at 0～15 ℃.
Progressively be warming up to 70 ℃ after dropwising, stirring reaction 38 hours.
Methyl alcohol is removed in decompression, obtains the naringenin bullion.
Add the 20kg absolute ethyl alcohol to the naringenin bullion that obtains, be heated to 52 ℃, be dissolved to clarification.Add 300 gram gacs; Stirred 1 hour.
The filtering gac adds the 20kg purified water then, is cooled to the normal temperature crystallization 36 hours.
Suction filtration, filter cake place 60 ℃ of vacuum drying oven oven dry 2 hours with an amount of absolute ethyl alcohol drip washing.Obtain 1.64kg white or off-white color needle crystal.
Using the naringenin purity of high effective liquid chromatography for measuring is 99.88%.
Embodiment two
The 10kg naringin is dissolved in the 34kg ethanol, and normal temperature stirred 20 minutes down.Be cooled to 0 ℃, drip a certain amount of concentrated hydrochloric acid and regulate pH value to 3.0, drip controlled temperature at 0～15 ℃.
Progressively be warming up to 75 ℃ after dropwising, stirring reaction 40 hours.
Ethanol is removed in decompression, obtains the naringenin bullion.Add the 35kg absolute ethyl alcohol to the naringenin bullion that obtains, be heated to 50 ℃, be dissolved to clarification.Add 400 gram gacs; Stirred 1 hour.
The filtering gac adds the 35kg purified water then, is cooled to the normal temperature crystallization 40 hours.
Suction filtration, filter cake place 60 ℃ of vacuum drying oven oven dry 2 hours with an amount of absolute ethyl alcohol drip washing.After obtain 2.69kg white or off-white color needle crystal.
Using the naringenin purity of high effective liquid chromatography for measuring is 99.28%.
Embodiment three
The 14kg naringin is dissolved in the 48kg methyl alcohol, and normal temperature stirred 30 minutes down.Be cooled to 0 ℃, drip a certain amount of dense acetic acid, regulate pH value to 4.0, drip controlled temperature at 0～15 ℃.
Progressively be warming up to 73 ℃ after dropwising, stirring reaction 40 hours.
Methyl alcohol is removed in decompression, obtains the naringenin bullion.
Add the 57kg anhydrous methanol to the naringenin bullion that obtains, be heated to 52 ℃, be dissolved to clarification.Add 560 gram gacs; Stirred 1 hour.
The filtering gac adds the 58kg purified water then, is cooled to the normal temperature crystallization 48 hours.
Suction filtration, filter cake place 60 ℃ of vacuum drying oven oven dry 2 hours with an amount of anhydrous methanol drip washing.After obtain 3.73kg white or off-white color needle crystal.
Using the naringenin purity of high effective liquid chromatography for measuring is 99.96%.
Embodiment four
The 14kg naringin is dissolved in the 48kg methyl alcohol, and normal temperature stirred 30 minutes down.Be cooled to 0 ℃, drip a certain amount of vitriol oil, regulate pH value to 3.5 and drip controlled temperature at 0～15 ℃.
Progressively be warming up to 73 ℃ after dropwising, stirring reaction 30 hours.
Methyl alcohol is removed in decompression, obtains the naringenin bullion.
Add the 57kg absolute ethyl alcohol to the naringenin bullion that obtains, be heated to 52 ℃, be dissolved to clarification.Add 560 gram gacs; Stirred 1 hour.
The filtering gac adds the 58kg purified water then, is cooled to the normal temperature crystallization 48 hours.
Suction filtration, filter cake place 60 ℃ of vacuum drying oven oven dry 2 hours with an amount of absolute ethyl alcohol drip washing.After obtain 4.27kg white or off-white color needle crystal.
Using the naringenin purity of high effective liquid chromatography for measuring is 99.6%.
Embodiment five
The 10kg naringin is dissolved in the 34kg propyl carbinol, and normal temperature stirred 20 minutes down.Be cooled to 0 ℃, drip a certain amount of concentrated nitric acid and regulate pH value to 4.5, drip controlled temperature at 0～15 ℃.
Progressively be warming up to 75 ℃ after dropwising, stirring reaction 32 hours.
Propyl carbinol is removed in decompression, obtains the naringenin bullion.Add the 35kg anhydrous methanol to the naringenin bullion that obtains, be heated to 50 ℃, be dissolved to clarification.Add 400 gram gacs; Stirred 1 hour.
The filtering gac adds the 35kg purified water then, is cooled to the normal temperature crystallization 40 hours.
Suction filtration, filter cake place 60 ℃ of vacuum drying oven oven dry 2 hours with an amount of anhydrous methanol drip washing.After obtain 2.69kg white or off-white color needle crystal.
Using the naringenin purity of high effective liquid chromatography for measuring is 99.1%.
Embodiment six
The 6kg naringin is dissolved in the 19kg acetone, and normal temperature stirred 30 minutes down.Be cooled to 0 ℃, drip a certain amount of concentrated hydrochloric acid, regulate pH value to 3, drip controlled temperature at 0～15 ℃.
Progressively be warming up to 70 ℃ after dropwising, stirring reaction 34 hours.
Acetone is removed in decompression, obtains the naringenin bullion.
Add the 20kg anhydrous methanol to the naringenin bullion that obtains, be heated to 52 ℃, be dissolved to clarification.Add 260 gram gacs; Stirred 1 hour.
The filtering gac adds the 20kg purified water then, is cooled to the normal temperature crystallization 36 hours.
Suction filtration, filter cake place 60 ℃ of vacuum drying oven oven dry 2 hours with an amount of anhydrous methanol drip washing.Obtain 1.7kg white or off-white color needle crystal.
Using the naringenin purity of high effective liquid chromatography for measuring is 99.2%.
Claims (11)
1. the preparation method of a naringenin comprises:
(1) obtain the solution of naringin in lower alcohol or lower ketones solvent earlier, make the naringin that obtains in the solution that acid hydrolysis acquisition naringenin takes place under acidic conditions then, solvent is removed in underpressure distillation, obtains the naringenin bullion;
(2) make the naringenin dissolving crude product in absolute ethyl alcohol or anhydrous methanol, add gac, stir decolouring;
(3) filtering gac separates purification to the solution that obtains, and obtains naringenin.
2. preparation method according to claim 1 is characterized in that said lower alcohol or lower ketones are methyl alcohol and/or ethanol.
3. preparation method according to claim 1 is characterized in that, acidic conditions described in the step (1) is that the pH value is 2-5; More preferably 2.5.
4. preparation method according to claim 1 is characterized in that, in the said step (1), the water cut of reaction system is no more than 20% (w/w), more preferably no more than 10% (w/w).
5. preparation method according to claim 1 is characterized in that, the consumption of middle lower alcohol of said step (1) or lower ketones is 3-5 a times of said naringin quality.
6. preparation method according to claim 1 is characterized in that, said step (1) drips acid for adjusting pH for earlier naringin being dissolved in lower alcohol or the lower ketones under 0-15 ℃ condition, be warming up to 60-90 ℃ then, stirring reaction 30-48 hour.
7. preparation method according to claim 6 is characterized in that said acid is selected from concentrated hydrochloric acid, Glacial acetic acid min. 99.5, carbonic acid, nitric acid, the vitriol oil; Be preferably concentrated hydrochloric acid.
8. preparation method according to claim 1, said step (2) are heated to 50-60 ℃ and are dissolved to clarification for the naringenin dissolving crude product is joined in anhydrous methanol or the absolute ethyl alcohol, add gac, stir 1-2 hour.
9. according to arbitrary described preparation method among the claim 1-8, in the said step (2), the consumption of absolute ethyl alcohol or anhydrous methanol is 3-5 a times of naringin quality, and the consumption of gac is naringin quality 3-5%.
10. preparation method according to claim 1 is characterized in that, the separation in the said step (3) is purified to purifying with the crystallization process separation through adding hydromining.
11. preparation method according to claim 1 is characterized in that, the separation in the said step (3) is purified and is: in solution, add 3-5 water doubly; Be cooled to room temperature, left standstill suction filtration crystallization 35-48 hour; Filter cake is with absolute ethyl alcohol or anhydrous methanol drip washing, and dry back obtains the solid naringenin.
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103467428A (en) * | 2013-09-30 | 2013-12-25 | 广西南宁百会药业集团有限公司 | Preparation method of naringenin |
| CN103896898A (en) * | 2014-03-07 | 2014-07-02 | 中国计量科学研究院 | Naringenin standard substance as well as preparation and application thereof |
| CN104277024A (en) * | 2014-09-29 | 2015-01-14 | 桂林莱茵生物科技股份有限公司 | Method for extracting naringenin from grapefruits |
| CN104829579A (en) * | 2015-04-07 | 2015-08-12 | 苏州凯祥生物科技有限公司 | Method for preparing naringenin by organic acid hydrolysis of naringin |
| CN106279088A (en) * | 2016-08-23 | 2017-01-04 | 湖南华诚生物资源股份有限公司 | A kind of method extracting high-purity naringenin for raw material with pomelo peel |
| CN109580604A (en) * | 2018-11-28 | 2019-04-05 | 江南大学 | A kind of method of high-throughput detection naringenin |
| CN114014829A (en) * | 2021-11-11 | 2022-02-08 | 河北维达康生物科技有限公司 | Method for synthesizing 7, 4' -dimethylnaringenin |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5008381A (en) * | 1987-11-03 | 1991-04-16 | Nestec S.A. | Selective cleavage of naringin |
| CN1555793A (en) * | 2004-01-08 | 2004-12-22 | 中山大学 | Naringin and its salt used for preparing cough suppressing phlegm tramsforming medicine |
| CN1640872A (en) * | 2004-01-14 | 2005-07-20 | 南京莱尔生物化工有限公司 | Novel semi-synthetic versulin preparing process |
-
2010
- 2010-10-29 CN CN2010105302724A patent/CN102453011A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5008381A (en) * | 1987-11-03 | 1991-04-16 | Nestec S.A. | Selective cleavage of naringin |
| CN1555793A (en) * | 2004-01-08 | 2004-12-22 | 中山大学 | Naringin and its salt used for preparing cough suppressing phlegm tramsforming medicine |
| CN1640872A (en) * | 2004-01-14 | 2005-07-20 | 南京莱尔生物化工有限公司 | Novel semi-synthetic versulin preparing process |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103467428A (en) * | 2013-09-30 | 2013-12-25 | 广西南宁百会药业集团有限公司 | Preparation method of naringenin |
| CN103467428B (en) * | 2013-09-30 | 2016-04-06 | 广西南宁百会药业集团有限公司 | A kind of preparation method of naringenin |
| CN103896898A (en) * | 2014-03-07 | 2014-07-02 | 中国计量科学研究院 | Naringenin standard substance as well as preparation and application thereof |
| CN103896898B (en) * | 2014-03-07 | 2016-04-20 | 中国计量科学研究院 | A kind of naringenin reference material and Synthesis and applications thereof |
| CN104277024A (en) * | 2014-09-29 | 2015-01-14 | 桂林莱茵生物科技股份有限公司 | Method for extracting naringenin from grapefruits |
| CN104277024B (en) * | 2014-09-29 | 2016-02-10 | 桂林莱茵生物科技股份有限公司 | A kind of method extracting naringenin from shaddock |
| CN104829579A (en) * | 2015-04-07 | 2015-08-12 | 苏州凯祥生物科技有限公司 | Method for preparing naringenin by organic acid hydrolysis of naringin |
| CN104829579B (en) * | 2015-04-07 | 2017-08-25 | 苏州凯祥生物科技有限公司 | A kind of method that organic acid hydrolysis aurantiin prepares naringenin |
| CN106279088A (en) * | 2016-08-23 | 2017-01-04 | 湖南华诚生物资源股份有限公司 | A kind of method extracting high-purity naringenin for raw material with pomelo peel |
| CN106279088B (en) * | 2016-08-23 | 2018-07-06 | 湖南华诚生物资源股份有限公司 | A kind of method that high-purity naringenin is extracted using pomelo peel as raw material |
| CN109580604A (en) * | 2018-11-28 | 2019-04-05 | 江南大学 | A kind of method of high-throughput detection naringenin |
| CN114014829A (en) * | 2021-11-11 | 2022-02-08 | 河北维达康生物科技有限公司 | Method for synthesizing 7, 4' -dimethylnaringenin |
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Application publication date: 20120516 |