CN103788028A - Orlistat industrial liquid chromatogram preparation method - Google Patents
Orlistat industrial liquid chromatogram preparation method Download PDFInfo
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- CN103788028A CN103788028A CN201210425170.5A CN201210425170A CN103788028A CN 103788028 A CN103788028 A CN 103788028A CN 201210425170 A CN201210425170 A CN 201210425170A CN 103788028 A CN103788028 A CN 103788028A
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- orlistat
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D305/00—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms
- C07D305/02—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D305/10—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms not condensed with other rings having one or more double bonds between ring members or between ring members and non-ring members
- C07D305/12—Beta-lactones
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Abstract
The invention discloses an orlistat preparation method, the orlistat synthesis crude product is employed as a raw material, and is performed through a HPLC optimization condition to obtain an appropriate mobile phase and column separating condition, and is amplified to an industrial preparation scale liquid chromatogram separating system for further to obtain the orlistat with high purity. The orlistat industrial liquid chromatogram preparation method has the advantages that industrial preparation scale liquid chromatogram separating system is directely used on the crude product after synthesis to obtain the required substance, so that good separating and purification effects can be reached, the orlistat industrial liquid chromatogram preparation method has the advantages of simple operation, short period and high efficiency, the purity can reach more than 99.5%, and the individual impurity can be controlled below 0.3%.
Description
Technical field
The invention belongs to biological medicine technology field, be specifically related to a kind of preparation method of orlistat.
Background technology
Orlistat (orlistat) is a kind of stomach and intestine lipase inhibitor, the clinical treatment that is mainly used in overweight and obesity.Along with the diet pill such as Phenfluoramine, sibutramine are successively quit listing because of serious adverse reaction, orlistat becomes diet pill market unique survivor at present with its unique security, validity.The general mode purifying orlistat that adopts low-pressure column chromatography and crystallization, production efficiency and yield are lower.The preparative liquid chromatography purifying orlistat that the present invention is based on dynamic axial compression column (dynamical axial compression, DAC), has significantly improved purification efficiency and yield.
Summary of the invention
The object of the invention is to for the current long and not high problem of purity of existing time in orlistat crude product refining process, provide a kind of and adopt industrial preparation scale liquid chromatographic separation system to prepare the novel method of high purity orlistat, the method comprises the following steps:
A. after orlistat crude product being mixed with 80% methanol solution, filter, generally orlistat crude product is configured to 5% sample solution, while specifically enforcement, can adjust according to actual solute effect;
B. adopt HPLC to optimize the optimal separation elution requirement of orlistat, its equal proportion is amplified, be applied on the dynamic axial compression column of filling reverse phase silica gel filler and separate, collect online the cut of the corresponding bands of a spectrum of orlistat;
C. by the corresponding bands of a spectrum elutriant drying under reduced pressure of collecting in step b, can obtain chromatographically pure and be 99.5% orlistat.
The invention has the beneficial effects as follows that direct employing orlistat crude product prepares orlistat, do not need a large amount of pretreatment process, simple, easy to control, Technology is simplified, and is applicable to extensive preparation.In high-performance liquid chromatogram determination, purity is more than 99.5%, and single assorted caning be controlled in below 0.3%, can be used for the exploitation of food and medicine completely.
Accompanying drawing explanation
Fig. 1 is orlistat crude product liquid chromatography for measuring collection of illustrative plates.
Fig. 2 is the high-efficient liquid phase chromatogram with the dynamic axial compression column separation and purification orlistat of filling 10 μ m octadecyl reverse phase silica gel fillers, sample introduction 1g.
Fig. 3 is the high-efficient liquid phase chromatogram with the dynamic axial compression column separation and purification orlistat of filling 10 μ m octyl reverse phase silica gel fillers, sample introduction 1g.
Fig. 4 is the high-efficient liquid phase chromatogram with the dynamic axial compression column separation and purification orlistat of filling 10 μ m octadecyl reverse phase silica gel fillers, sample introduction 2g.
Embodiment
Embodiment 1
1. get 1g orlistat crude product and mix with 80% methanol solution, be configured to 5% sample solution, be placed in filtration unit, solids removed by filtration particle;
2. orlistat solution is injected to dynamic axial compression column preparing chromatography system, dynamic axial compression column is of a size of Φ 50 × 250mm, and octadecyl reverse phase silica gel packing material size is 10 μ m, applied sample amount 1g, and flow rate of mobile phase is 80ml/min.Mobile phase methanol and water volume ratio scope are 80/20, wash-out 45min, and a separation cycle finishes.The detection wavelength of the New UV Spectrophotometric detector adopting is 195nm, collects the cut of retention time at 33 ~ 40min, as shown in Figure 2, and through HPLC purity assay >=99.5%.
Embodiment 2
1. get 1g orlistat crude product and mix with 80% methanol solution, be configured to 5% sample solution, be placed in filtration unit, solids removed by filtration particle;
2. orlistat solution is injected to dynamic axial compression column preparing chromatography system, dynamic axial compression column is of a size of Φ 50 × 250mm, and octyl reverse phase silica gel packing material size is 10 μ m, applied sample amount 1g, and flow rate of mobile phase is 80ml/min.Mobile phase methanol and water volume ratio are 78/22, wash-out 60min, and a separation cycle finishes.The detection wavelength of the New UV Spectrophotometric detector adopting is 195nm, collects the cut of retention time at 40 ~ 48min, as shown in Figure 3, and through HPLC purity assay >=99.6%.
Embodiment 3
1. get 2g orlistat crude product and mix with 80% methanol solution, be configured to 5% sample solution, be placed in filtration unit, solids removed by filtration particle;
2. orlistat solution is injected to dynamic axial compression column preparing chromatography system, dynamic axial compression column is of a size of Φ 150 × 250mm, and octadecyl reverse phase silica gel packing material size is 10 μ m, applied sample amount 2g, and flow rate of mobile phase is 600ml/min.Mobile phase methanol and water volume ratio are 78/22, and after wash-out 85min, a separation cycle finishes.The detection wavelength of the New UV Spectrophotometric detector adopting is 195nm, collects the cut of retention time at 64 ~ 74min, as shown in Figure 4, and through HPLC purity assay >=99.5%.
Claims (3)
1. a preparation method for orlistat, is characterized in that comprising the following steps:
(1) filter after orlistat crude product is mixed with 80% methanol solution, remove small solid insoluble, obtain filtrate as separating crude product;
(2) filtration product is injected to dynamic axial compression preparing chromatography system by sampling pump or sampling valve;
(3) adopt first alcohol and water to do moving phase wash-out, effluent liquid corresponding chromatographic peak is carried out to drying under reduced pressure, can obtain highly purified orlistat product.
2. method according to claim 1, it is characterized in that: in described step (2), in preparing chromatography system, adopt dynamic axial compression column, specification is Φ 50 × 250mm ~ Φ 150 × 250mm, and the stationary phase of filling is reverse phase silica gel filler, bonding octadecyl or octyl, particle diameter is 10 μ m.
3. method according to claim 1, is characterized in that: in described step (3), when wash-out, the volume ratio of mobile phase methanol and water (V/V) scope is 80:20 ~ 78:22.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210425170.5A CN103788028A (en) | 2012-10-31 | 2012-10-31 | Orlistat industrial liquid chromatogram preparation method |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210425170.5A CN103788028A (en) | 2012-10-31 | 2012-10-31 | Orlistat industrial liquid chromatogram preparation method |
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| CN103788028A true CN103788028A (en) | 2014-05-14 |
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| CN201210425170.5A Pending CN103788028A (en) | 2012-10-31 | 2012-10-31 | Orlistat industrial liquid chromatogram preparation method |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105510312A (en) * | 2015-11-20 | 2016-04-20 | 山东省食品药品检验研究院 | Orlistat rapid detection method |
| CN105738506A (en) * | 2016-02-03 | 2016-07-06 | 中山万汉医药科技有限公司 | Method for measuring degraded impurities in orlistat capsules |
| CN106188225A (en) * | 2016-07-25 | 2016-12-07 | 浙江汇能生物股份有限公司 | A kind of technical grade preparative liquid chromatography separation method converging promise peptide |
| 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 |
-
2012
- 2012-10-31 CN CN201210425170.5A patent/CN103788028A/en active Pending
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105510312A (en) * | 2015-11-20 | 2016-04-20 | 山东省食品药品检验研究院 | Orlistat rapid detection method |
| CN105738506A (en) * | 2016-02-03 | 2016-07-06 | 中山万汉医药科技有限公司 | Method for measuring degraded impurities in orlistat capsules |
| CN105738506B (en) * | 2016-02-03 | 2016-11-02 | 中山万汉医药科技有限公司 | A kind of measure the method for degradation impurity in orlistat capsule |
| CN106188225A (en) * | 2016-07-25 | 2016-12-07 | 浙江汇能生物股份有限公司 | A kind of technical grade preparative liquid chromatography separation method converging promise peptide |
| 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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Application publication date: 20140514 |