CN102558103A - Method for separating and purifying Orlistat - Google Patents
Method for separating and purifying Orlistat Download PDFInfo
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- CN102558103A CN102558103A CN2010105843621A CN201010584362A CN102558103A CN 102558103 A CN102558103 A CN 102558103A CN 2010105843621 A CN2010105843621 A CN 2010105843621A CN 201010584362 A CN201010584362 A CN 201010584362A CN 102558103 A CN102558103 A CN 102558103A
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Abstract
The invention belongs to the field of separation and purification and relates to a method for separating and purifying Orlistat by reverse-phase high-performance preparative liquid chromatography. The Orlistat prepared by using the method has purity of more than 99.6%, recovery rate of above 90% and the largest single impurity content of not more than 0.1%. The method has the advantages of simplicity in process operation, easiness in quality control and suitability for wide industrial scale application.
Description
Technical field
The invention belongs to the separation and purification field, relate to a kind of separation purification method of chemical substance, specifically, relate to a kind of method through reversed phase high efficiency preparative liquid chromatography separation and purification orlistat.
Background technology
Orlistat (Orlistat; Tetrahydolipstat); Chemistry N-formyl radical by name-L leucine-(S)-1-{ [(2S, 3S)-3-hexyl-4-oxo-2-oxa-cyclobutyl] methyl } dodecyl ester ((S)-N-formyl leuine (S)-1-[[(2S, 3S)-3-hexyl-4-oxo-2oxetanyl] methyl] dodecyl ester); CAS number is 96829-58-2, and structural formula is following:
Orlistat is a specific specificity gi tract lipase inhibitor; The sickness rate of other disease that can reduce the Hazard Factor relevant and be correlated with obesity with obesity; Comprise hypercholesterolemia, type ii diabetes, impaired glucose tolerance, hyperinsulinemia, hypertension, and can reduce the lipid content in the internal organs.Be applicable to that obesity and overweight person comprise that those the patient's of the Hazard Factor relevant with obesity long-term treatment occurred.
The working method of orlistat has two kinds at present, and a kind of is to obtain fat statin lipstatin through fermentation, after catalytic reduction obtains orlistat; Another kind of approach is through the directly synthetic orlistat of chemical process.Two kinds of approach gained orlistats all need further to separate purification and just can reach medicinal standard.What use always in the separation and purification mode of orlistat at present is crystallization process, like CN200510094601, and CN00101172.3.Chinese patent CN00101172.3 discloses the method that a kind of reextraction bonded method of liquid-liquid extraction and the counter-current extraction form through double fluid extraction form is come purifying orlistat midbody lipstatin.This method is very high to the purity requirement of orlistat precursor lipstatin, and weight content is up to 90%, otherwise can't purify at all obtain can medicinal purity orlistat.And along with the raising of medical standard, twice back of this method crystallization purity can reach 97% content and also not meet existing medical standard.
CN200510094601 discloses a kind of method of purification of orlistat, and this method is filtered earlier with the solvent dissolution with solvents of orlistat bullion with middle polarity; After the filtrating crystallization, carry out recrystallization with nonpolar solvent.Look the particular case of impurity, repeat the first step or two steps, meet the purity of medicinal standard up to orlistat purity.The advantage of this method is that the purity range of the orlistat that is suitable for is big, 50%-85%, and in the low-purity scope, refining effect is obvious.But this method of purification need be used high amounts of solvents, has not only increased the purifying cost, and has increased the environmental treatment cost; In addition must multiple times of filtration before and after the crystallization in the crystallization process, steps such as transfer, washing, and have the existence of orlistat in the mother liquor surely, what is more along with the increase of impurity, mother liquor reclaims the difficulty more that becomes, these factors cause the loss of output remarkable.Often need repeatedly crystallization just can reach expectation purity in the real operation, need heating and cooling in the crystallisation process, this all will increase the complicacy of technology greatly, use more organic solvent, and product loss is also bigger.More regrettably when higher degree, the effect of crystallization process is also not obvious.Orlistat content after the crystallization three times is not more than 98.6%, and maximum single assorted only less than 0.5%, the effect that continues to make with extra care down is also also not obvious.
Pierre Barbier and Fernand Schneider (J.Org.Chem.1988,53,1218-1221) adopt the synthetic orlistat of chemical synthesis; Behind final step reaction solution evaporate to dryness; Cross silicagel column, with 4: 1 toluene/ethyl acetate wash-out, gained orlistat purity was 80%.U.S.Pat.No.4; Among 598089 (Eur.Pat.Appl.129748) earlier with orlistat presoma lipstatin through one or many silica gel and chromatographic column purifying; Get orlistat then after the catalytic hydrogenation more further through a silica gel short column, chloroform drip washing realizes purification to a certain degree.But the orlistat that finally obtains is cured shape light yellow solid, and the high orlistat of purity should be white or off-white color, explain promptly to use this method purifying gained orlistat still purity is not high, and output is not high.Cross the post shortcoming and comprise that technology is loaded down with trivial details, level of automation is low, dissolving, cross post, connect operations such as liquid, detection and will make the operator be exposed to more in the deleterious organic solvent atmosphere, and formation is to the dependence of Engineering Control and individual protection equipment.These operations possibly be dull and dull.Also having a shortcoming is that of the prior art to cross silicagel column or cross chromatographic column all be to cross post earlier, and the back is detected, and promptly detects to lag behind, and this not only makes complex operation, and is not directly perceived, has also prolonged the production cycle greatly, has reduced production efficiency.Separating effect based on crossing the post method in the prior art is limited; In the application that separates orlistat; Often need repeatedly to cross post, further increased labour intensity and production cost, and very undesirable to the purification effect of the orlistat of purity higher (like mass content greater than 95%).
Above separation method all exists sepn process to use a large amount of organic solvents to pollute the cost rising; Sepn process is complicated, can not carry out continuous production; Foreign matter content is big and can not be used for being further purified of certain purity product, confirms therefore that a kind of process is directly perceived, easy and simple to handle, safety and environmental protection, the preparation technology that is suitable for the high purity orlistat on the technical scale have crucial meaning.
Summary of the invention
In order to overcome the defective that complex process, purifying scope are little, environmental pollution big, the sample loss rate is high that existing orlistat purification process exists; The invention provides a kind of separation purification method that from the orlistat bullion, reclaims the high purity orlistat; This separation purification method technology is simple, the organic solvent usage quantity is little, and the product purity and the recovery are high.
The present invention adopts the preparative high performance liquid chromatography system that the orlistat bullion is carried out separation and purification; The contriver has confirmed suitable chromatographic condition through a large amount of experiments; Adopt the UV-detector on-line monitoring; The purity of the orlistat after the separation and purification can be reached more than 99.6%, and maximum single assorted content is lower than 0.1%.
Concrete, the present invention adopts following technical scheme:
The orlistat bullion is separated filtration with moving phase; Then through the high performance preparative liquid chromatography separation and purification; With the online detection of UV-detector, specific aim is collected the preparation component of orlistat, gets orlistat solution; The orlistat solution that makes is removed organic solvent and water through underpressure distillation and lyophilization successively, promptly get the orlistat product.Specifically may further comprise the steps:
(1) dissolving, filtration:
According to orlistat bullion quality: mobile phase volume=(5g-30g): the ratio of 1L is with the orlistat dissolving crude product, and the dissolving back is with organic filtering with microporous membrane of 0.45 μ m, and filtrating prepares the raw material of purifying orlistat as next step.
Described moving phase is made up of organic solvent and water, and described organic solvent comprises one or more in methyl alcohol, ethanol, acetonitrile, the THF, particular methanol, acetonitrile, and methyl alcohol more preferably, the volume of organic solvent mark is about 70%-90% in the moving phase;
Wherein, based on the protection filler, to keep its performance, to prolong its work-ing life, so said orlistat bullion purity is preferably more than 95%; But do not represent that the purifying technique of the present invention content that is not available to purify is lower than 95% orlistat bullion.
(2) separation and purification:
With filtrating 0.3L-3L in the step (1), inject the reversed phase high efficiency preparative liquid chromatograph, isocratic elution, the online detection of UV-detector, specific aim is collected the preparation component of orlistat, gets orlistat solution.
In the high performance preparative liquid chromatography sepn process, the selection of chromatographic condition is extremely important, and it is to decisive role such as the peak sequence of each material in the sample solution, peak shape, separating effects; Chromatographic condition mainly comprises chromatographic column (comprising filler, column length and internal diameter etc.), moving phase (comprise form and flow velocity etc.), column temperature, detection wavelength, detector etc., the selection of each chromatographic condition and make up most important.
The contriver has confirmed suitable chromatographic condition through great deal of experimental and comparative analysis, makes the optimizations such as appearance time, peak shape, separating effect of each material in the sample solution, helps orlistat monomer and each separate impurities and shortening production cycle.
Wherein the used chromatographic column of reversed phase high efficiency preparative liquid chromatography separation orlistat is a dynamic axial compression column, diameter 10mm-800mm, and preferred diameter is 200mm-800mm;
Packed height 25mm-1000mm is preferably 100mm-400mm in the dynamic axial compression column; Filler is an organic phase bonding inorganic matrix; Wherein organic bonding can be alkyl, phenyl, cyanic acid, amino and polymer-based carbon silane etc. mutually; Inorganic matrix comprises silica gel, titanium oxide, titanium, red oxide of iron, iron etc.; The filler shape can be unformed and ball-type, packing material size 5 μ m-50 μ m, the C1 in the alkyl of preferred 8 μ m-15 μ m, C4, C8, C16, C18 base silane bonded silica gel microballoon;
The flow velocity of performance liquid is 0.2L/min-15L/min, is preferably 1.5-2.5L/min;
In room temperature range, column temperature is to the not obviously influence of separating effect of this technology, and promptly column temperature can be selected room temperature;
On-line ultraviolet detects, and detects wavelength 190nm-220nm, and the preferred detection wavelength is 195nm-215nm.
Carrying out before reversed phase high efficiency prepares liquid phase separation, can confirm the appearance time and the peak shape of orlistat in the high performance preparative liquid chromatography through LC-MS, reference substance location or other present technique field method commonly used.
(3) product reclaims
Step (2) high performance preparative liquid chromatography is separated the orlistat elutriant that obtains remove wherein organic solvent and water through underpressure distillation and lyophilization successively, promptly get the orlistat product.
Compared with prior art, the present invention has following beneficial effect:
1) used organic solvent is all recyclable among the present invention utilizes again, and solvent consumption is few;
2) this method technology is simple, online detection, and quality product is controlled easily, and efficient is high;
3) chromatographic system is a closed system, and operating environment is polluted little;
4) the present invention is superior to prior art to orlistat content at the separation refining effect of the bullion more than 95%, and product purity is more than 99.6% after the separation and purification, and yield is more than 90%;
5) the orlistat product after separation and purification of the present invention, maximum single assorted less than 0.1% (analyze chromatographic condition: chromatographic column: the C18 post (4.6mm * 150mm, 5um); The mobile phase of acetonitrile and water volume ratio is 86: 14; Flow velocity: 1.0ml/min; Sample concentration 0.5mg/ml; Sample size: 10 μ l; Detect wavelength: 195nm; Column temperature: 30 ℃).
Description of drawings
The high-efficient liquid phase analysis collection of illustrative plates of used orlistat bullion among Fig. 1 embodiment 1
Fig. 2 prepares the high-efficient liquid phase analysis collection of illustrative plates of gained orlistat by the condition of embodiment 1
Embodiment
Below in conjunction with embodiment the present invention is made further detailed description, but protection domain of the present invention is not limited to following embodiment.
Embodiment 1
(1) dissolving, filtration:
According to orlistat bullion solid masses: the ratio of solvent volume=10g: 1L, with the dissolving of orlistat bullion solid, the dissolving back is with organic filtering with microporous membrane of 0.45 μ m with moving phase, and filtrating prepares the raw material of purifying orlistat as next step.
The purity of the orlistat of used bullion is 96% (HPLC area normalization method), and maximum single mixing is 0.6% (the principal constituent Self-control method of not correction up of the HPLC factor, Chinese Pharmacopoeia 2010 editions, P appendix 31), and moving phase selection volume ratio is 86: 14 a methanol-water solution
(2) separation and purification:
With filtrating 2L in the step (1), inject the reversed phase high efficiency preparative liquid chromatograph, isocratic elution, the online detection of UV-detector, specific aim is collected the preparation component of orlistat, gets orlistat solution.
Wherein chromatographic condition is column diameter 300mm, and packed height 250mm, filler are the C18 base silane bonded silica gel microballoon of particle diameter 10 μ m, flow velocity 0.8L/min, and on-line ultraviolet detects, and detects wavelength 195nm.
(3) product reclaims
Step (2) high performance preparative liquid chromatography separated in the orlistat solution obtain the first alcohol and water and remove through underpressure distillation and freeze-drying successively, promptly get the orlistat product, its moderate purity is 99.67%, and yield 91% maximumly singly mixes 0.09%.
Embodiment 2
(1) dissolving, filtration:
According to orlistat bullion solid masses: the ratio of solvent volume=15g: 1L, with the dissolving of orlistat bullion solid, the dissolving back is with organic filtering with microporous membrane of 0.45 μ m with moving phase, and filtrating prepares the raw material of purifying orlistat as next step.
The purity of the orlistat of used bullion is 97% (HPLC area normalization method), and maximum single mixing is 0.45% (the principal constituent Self-control method of not correction up of the HPLC factor, Chinese Pharmacopoeia 2010 editions, P appendix 31),
Moving phase selection volume ratio is 80: 20 a acetonitrile-aqueous solution.
(2) separation and purification:
With filtrating 2.5L in the step (1), inject the reversed phase high efficiency preparative liquid chromatograph, isocratic elution, the online detection of UV-detector, specific aim is collected the preparation component of orlistat, gets orlistat solution.
Wherein chromatographic condition is column diameter 500mm, and packed height 300mm, filler are the C18 silane group silica gel microball of particle diameter 8 μ m, flow velocity 1.6L/min, and on-line ultraviolet detects, and detects wavelength 200nm.
(3) product reclaims
Step (2) high performance preparative liquid chromatography separated in the orlistat solution obtain acetonitrile and water and remove through underpressure distillation and freeze-drying successively, promptly get the orlistat product.Total recovery is 92.2%, and product is measured through HPLC, and purity is 99.75%, maximum single assorted 0.07%.
Embodiment 3
(1) dissolving, filtration:
According to orlistat bullion solid masses: the ratio of solvent volume=20g: 1L, with the dissolving of orlistat bullion solid, the dissolving back is with organic filtering with microporous membrane of 0.45 μ m with moving phase, and filtrating prepares the raw material of purifying orlistat as next step.
The purity of the orlistat of used bullion is 98% (HPLC area normalization method), and maximum single mixing is 0.44% (the principal constituent Self-control method of not correction up of the HPLC factor, Chinese Pharmacopoeia 2010 editions, P appendix 31),
Moving phase selection volume ratio is 88: 12 a ethanol-water solution.
(2) separation and purification:
With filtrating 2.5L in the step (1), inject the reversed phase high efficiency preparative liquid chromatograph, isocratic elution, the online detection of UV-detector, specific aim is collected the preparation component of orlistat, gets orlistat solution.
Wherein chromatographic condition is column diameter 600mm, and packed height 500mm, filler are the C8 silane group silica gel microball of particle diameter 10 μ m, flow velocity 2.5L/min, and on-line ultraviolet detects, and detects wavelength 210nm.
(3) product reclaims
Step (2) high performance preparative liquid chromatography separated in the orlistat solution obtain the second alcohol and water and remove through underpressure distillation and freeze-drying successively, promptly get the orlistat product.Total recovery is 93%, and product is measured through HPLC, and purity is 99.83%, and maximum single mixing is 0.05%.
Claims (10)
1. the preparation method of an orlistat product, it comprises the steps:
(1) dissolution filter: with moving phase dissolving orlistat bullion, filter, said moving phase is made up of organic solvent and water, and described organic solvent is one or more in methyl alcohol, ethanol, acetonitrile, the THF;
(2) separation and purification: reversed phase high efficiency preparative liquid chromatography technology separating filtrate, with the online detection of UV-detector, collect the preparation component of orlistat; The chromatographic column of wherein said reversed phase high efficiency preparative liquid chromatography is a dynamic axial compression column, and filler is an organic phase bonding inorganic matrix;
(3) product reclaims: separate dry orlistat with lyophilization with underpressure distillation successively and prepare component.
2. preparation method as claimed in claim 1, the massfraction that it is characterized in that orlistat in the said orlistat bullion is greater than 95%.
3. preparation method as claimed in claim 1, the volume ratio of the quality of orlistat bullion and moving phase is (5-30) g: 1L when it is characterized in that dissolving.
4. preparation method as claimed in claim 1 is characterized in that the volume of organic solvent mark is 70%-90% in the moving phase.
5. preparation method as claimed in claim 1 is characterized in that said dynamic axial compression column diameter is 10mm-800mm.
6. preparation method as claimed in claim 1 is characterized in that the organic bonding in the used filler comprises alkyl, phenyl, cyanic acid, amino and polymer-based carbon silane mutually; Inorganic matrix comprises silica gel, titanium oxide, titanium, red oxide of iron, iron; The filler shape comprises unformed and ball-type; Packing material size 5 μ m-50 μ m.
7. preparation method as claimed in claim 6 is characterized in that used packed height is 25mm-1000mm.
8. preparation method as claimed in claim 1 is characterized in that reversed phase high efficiency preparative liquid chromatography flow velocity is 0.2L/min-15L/min.
9. preparation method as claimed in claim 1, the detection wavelength of wherein said ultraviolet detection is 190nm-220nm.
10. preparation method as claimed in claim 1, it is characterized in that the chromatographic condition of reversed phase high efficiency preparative liquid chromatography is: the diameter of dynamic axial compression column is 200mm-800mm; Filler is C1, C4, C8, C16, the C18 alkyl silane bonded silica gel microballoon in the alkyl of 8 μ m-15 μ m in the chromatographic column, and packed height is 100mm-400mm; Moving phase is 70% the methyl alcohol and the aqueous solution; Flow velocity is 1.5-2.5L/min, and it is 195nm-215nm that UV-detector detects wavelength.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103739572A (en) * | 2014-01-09 | 2014-04-23 | 山东新时代药业有限公司 | Process for recovering orlistat crystallization mother solution |
| CN105510312A (en) * | 2015-11-20 | 2016-04-20 | 山东省食品药品检验研究院 | Orlistat rapid detection method |
| CN106543109A (en) * | 2016-10-21 | 2017-03-29 | 大邦(湖南)生物制药有限公司 | A kind of orlistat purifying process |
| CN108658900A (en) * | 2017-03-31 | 2018-10-16 | 江苏汉邦科技有限公司 | A method of isolating and purifying orlistat |
| CN109651301A (en) * | 2019-01-16 | 2019-04-19 | 苏州纳微科技股份有限公司 | A kind of purification process of orlistat |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6156911A (en) * | 1999-01-29 | 2000-12-05 | Hoffmann-La Roche Inc. | Purification of lipstatin |
| WO2003047531A2 (en) * | 2001-12-04 | 2003-06-12 | Biogal Gyogyszergyar Rt | Preparation of orlistat and orlistat crystalline forms |
| CN1763021A (en) * | 2005-09-29 | 2006-04-26 | 杭州华东医药集团生物工程研究所有限公司 | Method for purifying orlistat |
| WO2007039814A1 (en) * | 2005-10-05 | 2007-04-12 | Ranbaxy Laboratories Limited | Process for the preparation of orlistat |
| WO2008149321A2 (en) * | 2007-06-06 | 2008-12-11 | Ranbaxy Laboratories Limited | Process for the preparation of orlistat |
| CN101348475A (en) * | 2007-07-20 | 2009-01-21 | 重庆人本药物研究院 | Novel method for synthesizing orlistat, intermediate compound and preparation thereof |
-
2010
- 2010-12-13 CN CN201010584362.1A patent/CN102558103B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6156911A (en) * | 1999-01-29 | 2000-12-05 | Hoffmann-La Roche Inc. | Purification of lipstatin |
| WO2003047531A2 (en) * | 2001-12-04 | 2003-06-12 | Biogal Gyogyszergyar Rt | Preparation of orlistat and orlistat crystalline forms |
| CN1763021A (en) * | 2005-09-29 | 2006-04-26 | 杭州华东医药集团生物工程研究所有限公司 | Method for purifying orlistat |
| WO2007039814A1 (en) * | 2005-10-05 | 2007-04-12 | Ranbaxy Laboratories Limited | Process for the preparation of orlistat |
| WO2008149321A2 (en) * | 2007-06-06 | 2008-12-11 | Ranbaxy Laboratories Limited | Process for the preparation of orlistat |
| CN101348475A (en) * | 2007-07-20 | 2009-01-21 | 重庆人本药物研究院 | Novel method for synthesizing orlistat, intermediate compound and preparation thereof |
Non-Patent Citations (1)
| Title |
|---|
| 肖松: "高效液相色谱/质谱联用测定胶囊中奥利司他含量", 《药物分析杂质》 * |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103739572A (en) * | 2014-01-09 | 2014-04-23 | 山东新时代药业有限公司 | Process for recovering orlistat crystallization mother solution |
| CN103739572B (en) * | 2014-01-09 | 2016-01-27 | 山东新时代药业有限公司 | A kind of orlistat crystalline mother solution recovery process |
| CN105510312A (en) * | 2015-11-20 | 2016-04-20 | 山东省食品药品检验研究院 | Orlistat rapid detection method |
| CN106543109A (en) * | 2016-10-21 | 2017-03-29 | 大邦(湖南)生物制药有限公司 | A kind of orlistat purifying process |
| CN106543109B (en) * | 2016-10-21 | 2019-02-12 | 大邦(湖南)生物制药有限公司 | A kind of orlistat purifying process |
| CN108658900A (en) * | 2017-03-31 | 2018-10-16 | 江苏汉邦科技有限公司 | A method of isolating and purifying orlistat |
| CN109651301A (en) * | 2019-01-16 | 2019-04-19 | 苏州纳微科技股份有限公司 | A kind of purification process of orlistat |
| CN109651301B (en) * | 2019-01-16 | 2023-05-12 | 苏州纳微科技股份有限公司 | Purification method of orlistat |
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