CN107868120A - A kind of purification process of Daptomycin - Google Patents
A kind of purification process of Daptomycin Download PDFInfo
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- CN107868120A CN107868120A CN201711415420.6A CN201711415420A CN107868120A CN 107868120 A CN107868120 A CN 107868120A CN 201711415420 A CN201711415420 A CN 201711415420A CN 107868120 A CN107868120 A CN 107868120A
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Abstract
The invention provides a kind of purification process of Daptomycin.The purification process of the Daptomycin of the present invention, comprises the following steps：1) Daptomycin crude extract is subjected to pretreatment removal of impurities；2) daptomycin solution after step 1) pretreatment removal of impurities is loaded in chromatographic column and chromatographed, isocratic elution is carried out to daptomycin solution using mobile phase；3) daptomycin solution of purpose peak value of the Fractional Collections after step 2) chromatography, elution.The purification process of the Daptomycin of the present invention, it is only necessary to which a step chromatographic purifying can meet that Daptomycin purity is higher than 91%, and the rate of recovery is higher than 92% requirement.The purification process of Daptomycin of the present invention, method is simple and convenient, available for the large-scale production of Daptomycin, greatly reduces production cost.
Description
Technical field
The invention belongs to medicine technical field of purification, is related to a kind of purification process of Daptomycin.
Background technology
Daptomycin is that extraction obtains a kind of cyclic lipopeptide of brand new from streptomycete (S.reseosporus) zymotic fluid
Class antibiotic.It not only has a novel chemical constitution, and its binding mode also antibiotic granted with any one
It is all different：It is by upsetting transhipment of the cell membrane to amino acid, so as to hinder the biosynthesis of bacteria cell wall peptide glycan, changes
The property of cytoplasma membrane, bacterial cell membrane function can be destroyed in many aspects, and kill gram-positive bacteria rapidly, therefore bacterium
Producing drug resistance to Daptomycin may be relatively difficult.Treatment is clinically used for as caused by some Gram-positive sensitive strains
Concurrency skin and skin structure infection.Treatment gram-positive bacteria cause complexity skin and skin structure infection, as abscess,
Surgery cut infection and skin ulcer, including the staphylococcus to methicillin-sensitivity (resistance).For by Staphylococcus aureus
Microbial right side infectivity heart film is scorching；With RIE or complexity skin and soft tissue infection it is concurrent by staphylococcus aureus
Caused bacteremia.
Daptomycin is in addition to it can act on most of clinically relevant gram-positive bacterias, it is often more important that it is right in vitro
The isolated strains of the resistance properties such as methicillin (methicillin), vancomycin and linwzolid, which have been presented, has strength living
Property, this characteristic has very important clinical meaning for critical infected patient.Wherein, the structural formula of Daptomycin is as follows：
Patent, document etc. are mostly synthetic method patent to the report of Daptomycin both at home and abroad at present, and isolation and purification method is fresh
Have been reported that.
US6696412 discloses a kind of highly purified Daptomycin and the pharmaceutical composition comprising the compound.The hair
Bright to disclose a kind of method for purifying Daptomycin, including anion-exchange chromatography, hydrophobic interaction chromatograph and anion are handed over
The consecutive steps of colour changing spectrum, the invention also disclose mould up to holding in the palm by the buffer solution enhancing anion-exchange chromatography purifying of improvement
The method of element.
CN101830970A discloses a kind of method for preparing purified of high-purity daptomycin, and this method uses cushioning liquid
Sample solution is made into Daptomycin crude product, and upper compound YT-01 reverse phase silica gels column of material absorption is water-soluble with intensive polar solvent
Liquid makees parsing agent and carries out gradient elution or constant density elution, and its chromatographic purity is more than 98%.
CN102276696A discloses a kind of purification process of Daptomycin, and the loading of semipurified Daptomycin is attached to
Eluted after gel-type weakly anionic resin.The purification process of the present invention, obtained Daptomycin purity are higher than 98%, and former
Material is easy to get, is relatively inexpensive, being easy to industrial application.
Above-mentioned patent document describes the purification process of Daptomycin, but technique is extremely complex and yield is low, cost is high,
Product loss is big, and commercial Application is limited.It is therefore desirable to the separation to Daptomycin, purifying and preparation to make further research.
The content of the invention
In view of the shortcomings of the prior art, it is an object of the invention to provide a kind of purification process of Daptomycin, it is only necessary to one
Step chromatographic purifying can meet that Daptomycin purity is higher than 91%, and the rate of recovery is higher than 92% requirement, while the inventive method letter
Just, collected volume is small for folk prescription, available for the large-scale production of Daptomycin, greatly reduces production cost.
To use following technical scheme up to this purpose, the present invention：
A kind of purification process of Daptomycin, the purification process comprise the following steps：
1) Daptomycin crude extract is subjected to pretreatment removal of impurities；
2) daptomycin solution after step 1) pretreatment removal of impurities is loaded in chromatographic column and chromatographed, using flowing
Isocratic elution is carried out with respect to daptomycin solution；
3) daptomycin solution of purpose peak value of the Fractional Collections after step 2) chromatography, elution.
The detailed process of step 1) is：Daptomycin crude extract is dissolved in the water to obtain daptomycin solution, used
Filter membrane filters to the daptomycin solution；
Preferably, the pH value of the daptomycin solution is 6~7, for example, daptomycin solution pH value for 6,6.1,
6.2、6.3、6.4、6.5、6.6、6.7、6.8、6.9、7。
Preferably, the aperture of the filter membrane be 0.1~0.5 μm, such as filter membrane aperture for 0.1 μm, 0.2 μm, 0.3 μm,
0.4μm、0.5μm。
The detailed process of step 2) is：Daptomycin solution after step 1) pretreatment removal of impurities is loaded to equipped with poly- third
Chromatographed in the chromatographic column of olefin(e) acid ester microsphere, using aqueous sodium acetate solution and salting liquid as mobile phase to daptomycin solution
Carry out isocratic elution.
The polyacrylic acid ester microsphere is microballoon that is monodispersed, having pore passage structure.
Preferably, the model of the microballoon is UniQ50-XS.UniQ50-XS is that polyacrylate and divinylbenzene are handed over
The particle diameter that connection is formed is 50 μm or so, aperturePolymer microsphere, surface carries quaternary amine base strong anion cation exchange groups,
The particle size and aperture structure (such as Fig. 1) that the microballoon strictly controls, have good specific aim when making it as chromatograph packing material,
Preferably agree with the molecular size and structure of Daptomycin, therefore particularly suitable for purifying Daptomycin.This color simultaneously
Spectrum filler has very high dynamic carrying capacity, and the compressed coefficient is small, far below flexible glue matrix such as glucan, agarose plugs.It is meanwhile poly-
The microballoon of acrylate matrix can tolerate 2~14pH scopes, and can carry out the thorough cleaning under high pH to chromatographic column in the later stage,
It is easy to industrially recycle, filler long lifespan, reduces cost.The present invention using monodispersed UniQ50-XS as stationary phase,
Only need step chromatography that Daptomycin purity can be made to be higher than 92%, yield is up to 95%.
The present invention, as mobile phase, can be only completed up to support using salting liquid and aqueous sodium acetate solution with 4~6 column volumes
The elution of mycin main peak, therefore mobile phase used in this process is safe and pollution-free and cost is relatively low, and the flowing phasor used compared with
Few, collection liquid concentration is high, and purification cycle is shorter.
In the present invention, the concentration of the aqueous sodium acetate solution is 10~50mmol/L, such as the concentration of aqueous sodium acetate solution
For 10mmol/L, 15mmol/L, 20mmol/L, 25mmol/L, 30mmol/L, 35mmol/L, 40mmol/L.
Preferably, the pH value of the aqueous sodium acetate solution is 5~6, for example, aqueous sodium acetate solution pH value for 5,5.1,
5.2、5.3、5.4、5.5、5.6、5.7、5.8、5.9、6。
The salting liquid is the aqueous solution that concentration is 0.5mol/L sodium chloride or the sodium acetate that concentration is 10~50mmol/L
The aqueous solution.
The step of also including in step 2), before the loading to being pre-processed before chromatographic column progress post.
Preferably, detailed process is pre-processed before the post is：It is 10~50mmol/L's by chromatographic column concentration before loading
Aqueous sodium acetate solution is balanced processing.
In step 2), the isocratic elution process is first to be washed with 8% flushed, 12~18 column volumes miscellaneous, then is used
The 30% column volume main elution peak of flushed 4~6, finally rinse 2~3 column volumes with 1mol/L sodium-chloride water solution
Regeneration.
Preferably, the purification process of Daptomycin of the invention, comprises the following steps：
1) Daptomycin crude extract is dissolved in the water to obtain daptomycin solution, uses aperture as 0.1~0.5 μm
Filter membrane filters to the daptomycin solution；
2) daptomycin solution after step 1) filtering is loaded to the layer equipped with polyacrylic acid ester microsphere UniQ50-XS
Chromatographed in analysis post, before loading, chromatographic column be balanced processing with the aqueous sodium acetate solution that concentration is 10~50mmol/L,
The aqueous solution for the sodium chloride that concentration is 0.5mol/L for 10~50mmol/L aqueous sodium acetate solution and concentration is used as flowing
Isocratic elution is carried out with respect to daptomycin solution, the isocratic elution process is, first with 8% flushed, 12~18 cylinders
Product is washed miscellaneous, then with 30% flushed, 4~6 column volume main elution peaks, finally rinses 2 with 1mol/L sodium-chloride water solution
~3 column volume regeneration；
3) daptomycin solution of purpose peak value of the Fractional Collections after step 2) chromatography, elution, to satisfactory group
Part liquid is collected.
Compared with prior art, beneficial effects of the present invention are：
(1) purification process of Daptomycin of the present invention, using single dispersing polymethacrylates strong anion displacement chromatography
Fillers of the medium UniQ as chromatographic column, is not only advantageous to do mobile phase with the aqueous solution and isolates and purifies Daptomycin crude product, reaches
High-purity and high-recovery, and chromatographic column will not change with the change of salinity and flow velocity, and chromatographic stuffing can be high pressure resistant
With high flow rate and possess high carrying capacity.
(2) purification process of Daptomycin of the present invention, it is only necessary to which a step chromatographic purifying can meet that Daptomycin purity is higher than
91%, the rate of recovery is higher than 92% requirement.
(3) purification process of Daptomycin of the present invention, method is simple and convenient, available for the large-scale production of Daptomycin,
Greatly reduce production cost.
Brief description of the drawings
Fig. 1 is the scanning electron microscope (SEM) photograph of the UniQ50-XS polyacrylic acid ester microspheres used in embodiments of the invention 1；
Fig. 2 is the efficient liquid phase chromatographic analysis schematic diagram of the crude product before embodiments of the invention 1 purify；
Fig. 3 is the efficient liquid phase chromatographic analysis schematic diagram after the purification of daptomycin of embodiments of the invention 1.
Embodiment
Technical scheme is further illustrated below by embodiment.
Unless specific instructions, various raw materials of the invention are commercially available buys, or is prepared according to the conventional method of this area
Obtain.
A kind of purification process of Daptomycin of the present invention, the purification process comprise the following steps：
1) Daptomycin crude extract is subjected to pretreatment removal of impurities；
2) daptomycin solution after step 1) pretreatment removal of impurities is loaded in chromatographic column and chromatographed, using flowing
Isocratic elution is carried out with respect to daptomycin solution；
3) daptomycin solution of purpose peak value of the Fractional Collections after step 2) chromatography, elution.
Embodiment 1
The Daptomycin crude product (58% purity) for measuring 16mg/ml is dissolved in the aqueous solution, and solution ph control is left 6.5
The right side, it is 0.45 μm of membrane filtration with aperture, it is stand-by collects filtrate.Using 15 × 310mm chromatographic column, UniQ50-XS polypropylene
Acid esters microballoon (Suzhou Nano-micro Technology Co., Ltd.'s production) is as chromatography column packing, packed column volume 55ml.Before loading, acetic acid is used
Sodium water solution is balanced.Then isocratic elution, line flow velocity are carried out as mobile phase using aqueous sodium acetate solution and salting liquid
170cm/h.Isocratic degree elution process is that miscellaneous, rear 30% salting liquid mobile phase is first washed with 8% flushed, 13 column volumes
5 column volume main elution peaks are rinsed, then are regenerated with 1mol/L sodium chloride.The solution of Fractional Collections purpose peak value, to meeting the requirements
Component liquid collected, through efficient liquid phase chromatographic analysis, Daptomycin purity 91.89% in eluent, yield 96.74%.
Fig. 1 is the scanning electron microscope (SEM) photograph for the UniQ50-XS polyacrylic acid ester microspheres that the present embodiment uses, and Fig. 2 is before purifying
The efficient liquid phase chromatographic analysis of Daptomycin crude product, it is seen that impurity is very more and miscellaneous.Fig. 3 is the efficient liquid of Daptomycin after purification
Analysis of hplc, it is seen that impurity is few and content is low.
Embodiment 2
The Daptomycin crude product (58% purity) for measuring 16mg/ml is dissolved in the aqueous solution, and solution ph control is left 6.5
The right side, it is 0.45 μm of membrane filtration with aperture, it is stand-by collects filtrate.Using 70 × 310mm chromatographic column, UniQ50-XS polypropylene
Acid esters microballoon (Suzhou Nano-micro Technology Co., Ltd.'s production) is as chromatography column packing, packed column volume 1200ml.Before loading, second is used
Acid sodium aqueous solution is balanced.Then isocratic elution, line flow velocity are carried out as mobile phase using aqueous sodium acetate solution and salting liquid
170cm/h.Isocratic degree elution process is that miscellaneous, rear 30% salting liquid mobile phase is first washed with 8% flushed, 13 column volumes
5 column volume main elution peaks are rinsed, then are regenerated with 1mol/L sodium chloride.The solution of Fractional Collections purpose peak value, to meeting the requirements
Component liquid collected, through efficient liquid phase chromatographic analysis, Daptomycin purity 92.67% in eluent, yield 91.85%.
Embodiment 3
The Daptomycin crude product (58% purity) for measuring 16mg/ml is dissolved in the aqueous solution, and solution ph control is left 6.5
The right side, it is 0.45 μm of membrane filtration with aperture, it is stand-by collects filtrate.Using 70 × 310mm chromatographic column, UniQ50-XS polypropylene
Acid esters microballoon (Suzhou Nano-micro Technology Co., Ltd.'s production) is as chromatography column packing, packed column volume 1200ml.Before loading, second is used
Acid sodium aqueous solution is balanced, and then carries out isocratic elution, line flow velocity as mobile phase using aqueous sodium acetate solution and salting liquid
100cm/h.Isocratic degree elution process is that miscellaneous, rear 30% salting liquid mobile phase is first washed with 8% flushed, 13 column volumes
5 column volume main elution peaks are rinsed, then are regenerated with 1mol/L sodium chloride.The solution of Fractional Collections purpose peak value, to meeting the requirements
Component liquid collected, through efficient liquid phase chromatographic analysis, Daptomycin purity 93% in eluent, yield 97.43%.
Embodiment 4
The Daptomycin crude product (58% purity) for measuring 16mg/ml is dissolved in the aqueous solution, and solution ph control is left 6.5
The right side, it is 0.45 μm of membrane filtration with aperture, it is stand-by collects filtrate.Using 15 × 310mm chromatographic column, UniQ50-XS polypropylene
Acid esters microballoon (Suzhou Nano-micro Technology Co., Ltd.'s production) is as chromatography column packing, packed column volume 55ml.Before loading, acetic acid is used
Sodium water solution is balanced.Then isocratic elution, line flow velocity are carried out as mobile phase using aqueous sodium acetate solution and salting liquid
170cm/h.Isocratic degree elution process is that miscellaneous, rear 30% salting liquid mobile phase is first washed with 8% flushed, 13 column volumes
5 column volume main elution peaks are rinsed, then are regenerated with 1mol/L sodium chloride.The solution of Fractional Collections purpose peak value, to meeting the requirements
Component liquid collected, through efficient liquid phase chromatographic analysis, Daptomycin purity 93.091% in eluent, yield 97.8%.
To sum up, the purification process of Daptomycin of the invention, chromatographed, adopted in the chromatographic column of polyacrylic acid ester microsphere
Isocratic elution is carried out to daptomycin solution by the use of aqueous sodium acetate solution and salting liquid as mobile phase, it is only necessary to which a step chromatographic purifying is
It can meet that Daptomycin purity is higher than 91%, the rate of recovery is higher than 92% requirement.The purification process of Daptomycin of the present invention, method
It is simple and convenient, available for the large-scale production of Daptomycin, greatly reduce production cost.
Above example is only used for the method detailed for illustrating the present invention, the invention is not limited in above-mentioned method detailed, i.e.,
Do not mean that the present invention has to rely on above-mentioned method detailed and could implemented.Person of ordinary skill in the field is it will be clearly understood that right
Any improvement of the present invention, addition, the selection of concrete mode of equivalence replacement and auxiliary element to each raw material of product of the present invention
Deng within the scope of all falling within protection scope of the present invention and disclosing.
Claims (9)
1. a kind of purification process of Daptomycin, it is characterised in that the purification process comprises the following steps：
1) Daptomycin crude extract is subjected to pretreatment removal of impurities；
2) daptomycin solution after step 1) pretreatment removal of impurities is loaded in chromatographic column and chromatographed, using mobile phase pair
Daptomycin solution carries out isocratic elution；
3) daptomycin solution of purpose peak value of the Fractional Collections after step 2) chromatography, elution.
2. purification process according to claim 1, it is characterised in that the detailed process of step 1) is：Daptomycin is thick
Extract is dissolved in the water to obtain daptomycin solution, and the daptomycin solution is filtered using filter membrane；
Preferably, the pH value of the daptomycin solution is 6~7；
Preferably, the aperture of the filter membrane is 0.1~0.5 μm.
3. purification process according to claim 1 or 2, it is characterised in that the detailed process of step 2) is：Will be through step 1)
Daptomycin solution after pretreatment removal of impurities, which is loaded in the chromatographic column equipped with polyacrylic acid ester microsphere, to be chromatographed, using acetic acid
Sodium water solution and salting liquid carry out isocratic elution as mobile phase to daptomycin solution.
4. purification process according to claim 3, it is characterised in that the polyacrylic acid ester microsphere is monodispersed, tool
There is the microballoon of pore passage structure；
Preferably, the model of the microballoon is UniQ50-XS.
5. purification process according to claim 3, it is characterised in that the concentration of the aqueous sodium acetate solution be 10~
50mmol/L；
Preferably, the pH value of the aqueous sodium acetate solution is 5~6.
6. purification process according to claim 3, it is characterised in that the salting liquid is that concentration is 0.5mol/L sodium chloride
The aqueous solution or concentration be 10~50mmol/L aqueous sodium acetate solution.
7. according to the purification process described in one of claim 1-6, it is characterised in that in step 2), also include before the loading
The step of to being pre-processed before chromatographic column progress post；
Preferably, detailed process is pre-processed before the post is：Before loading, by the acetic acid that chromatographic column concentration is 10~50mmol/L
Sodium water solution is balanced processing.
8. according to the purification process described in one of claim 1-7, it is characterised in that in step 2), the isocratic elution process
For, first washed with 8% flushed, 12~18 column volumes it is miscellaneous, then with 30% flushed, 4~6 column volumes elution master
Peak, finally rinse 2~3 column volumes with 1mol/L sodium-chloride water solution and regenerate.
9. according to the purification process described in one of claim 1-8, it is characterised in that the purification process comprises the following steps：
1) Daptomycin crude extract is dissolved in the water to obtain daptomycin solution, uses aperture as 0.1~0.5 μm of filter membrane
The daptomycin solution is filtered；
2) daptomycin solution after step 1) filtering is loaded to the chromatographic column equipped with polyacrylic acid ester microsphere UniQ50-XS
In chromatographed, before loading, by chromatographic column with concentration be 10~50mmol/L aqueous sodium acetate solution be balanced processing, use
The aqueous solution for the sodium chloride that the aqueous sodium acetate solution and concentration that concentration is 10~50mmol/L are 0.5mol/L is as mobile phase pair
Daptomycin solution carries out isocratic elution, and the isocratic elution process is first to be washed with 8% flushed, 12~18 column volumes
It is miscellaneous, then with 30% flushed, 4~6 column volume main elution peaks, finally rinse 2~3 with 1mol/L sodium-chloride water solution
Individual column volume regeneration；
3) daptomycin solution of purpose peak value of the Fractional Collections after step 2) chromatography, elution.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107413320A (en) * | 2017-04-12 | 2017-12-01 | 苏州纳微分离纯化技术有限公司 | A kind of application of protein A affinity chromatography medium |
| CN109503687A (en) * | 2018-11-22 | 2019-03-22 | 苏州纳微科技股份有限公司 | A kind of isolation and purification method of uridine triphosphate |
| WO2020147421A1 (en) * | 2019-01-18 | 2020-07-23 | 苏州纳微科技股份有限公司 | Sugammadex isolation and purification method |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102492024A (en) * | 2011-12-09 | 2012-06-13 | 厦门大学 | Method for extracting daptomycin from fermentation broth |
| CN102718839A (en) * | 2012-07-05 | 2012-10-10 | 鲁南新时代生物技术有限公司 | Method for separating and purifying daptomycin |
| CN104513286A (en) * | 2013-09-27 | 2015-04-15 | 博瑞生物医药技术(苏州)有限公司 | Method for separating and purifying fidaxomicin |
| CN105481950A (en) * | 2016-01-28 | 2016-04-13 | 丽珠集团福州福兴医药有限公司 | Daptomycin extraction method |
| CN106589065A (en) * | 2015-10-16 | 2017-04-26 | 江苏恒瑞医药股份有限公司 | Daptomycin purifying method |
| CN106622159A (en) * | 2016-12-22 | 2017-05-10 | 苏州楚博生物技术有限公司 | Affinity chromatography medium for purifying protein drug |
-
2017
- 2017-12-22 CN CN201711415420.6A patent/CN107868120B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102492024A (en) * | 2011-12-09 | 2012-06-13 | 厦门大学 | Method for extracting daptomycin from fermentation broth |
| CN102718839A (en) * | 2012-07-05 | 2012-10-10 | 鲁南新时代生物技术有限公司 | Method for separating and purifying daptomycin |
| CN104513286A (en) * | 2013-09-27 | 2015-04-15 | 博瑞生物医药技术(苏州)有限公司 | Method for separating and purifying fidaxomicin |
| CN106589065A (en) * | 2015-10-16 | 2017-04-26 | 江苏恒瑞医药股份有限公司 | Daptomycin purifying method |
| CN105481950A (en) * | 2016-01-28 | 2016-04-13 | 丽珠集团福州福兴医药有限公司 | Daptomycin extraction method |
| CN106622159A (en) * | 2016-12-22 | 2017-05-10 | 苏州楚博生物技术有限公司 | Affinity chromatography medium for purifying protein drug |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107413320A (en) * | 2017-04-12 | 2017-12-01 | 苏州纳微分离纯化技术有限公司 | A kind of application of protein A affinity chromatography medium |
| CN109503687A (en) * | 2018-11-22 | 2019-03-22 | 苏州纳微科技股份有限公司 | A kind of isolation and purification method of uridine triphosphate |
| WO2020103916A1 (en) * | 2018-11-22 | 2020-05-28 | 苏州纳微科技股份有限公司 | Separation and purification method for uridine triphosphate |
| CN109503687B (en) * | 2018-11-22 | 2022-03-08 | 苏州纳微科技股份有限公司 | Separation and purification method of uridine triphosphate |
| WO2020147421A1 (en) * | 2019-01-18 | 2020-07-23 | 苏州纳微科技股份有限公司 | Sugammadex isolation and purification method |
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| CN107868120B (en) | 2021-06-01 |
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