CN106589075A - Teicoplanin purifying method - Google Patents
Teicoplanin purifying method Download PDFInfo
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- CN106589075A CN106589075A CN201710058393.5A CN201710058393A CN106589075A CN 106589075 A CN106589075 A CN 106589075A CN 201710058393 A CN201710058393 A CN 201710058393A CN 106589075 A CN106589075 A CN 106589075A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K9/00—Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof
- C07K9/006—Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof the peptide sequence being part of a ring structure
- C07K9/008—Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof the peptide sequence being part of a ring structure directly attached to a hetero atom of the saccharide radical, e.g. actaplanin, avoparcin, ristomycin, vancomycin
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Abstract
The invention provides a teicoplanin purifying method. The purifying method includes steps of orderly performing resin gathering, resin purification, film concentration, and spraying drying operations on teicoplanin fermentation liquor. Compared with the prior art, polarity macroporous adsorbing rein is combined with a medium-sized polarity chromatography resin with uniform grain diameter, thus the product yield is high and decoloring effect is good; the spraying drying technology avoids the massive use of acetone, so that environment is protected, cost is reduced and problem of residue of organic solvent in the prior art can be further avoided; the ratio of every component of the teicoplanin obtained through the purifying method can meet standard, the purifying process is high-efficient and convenient, the preparation amount is big; the teicoplanin purifying method is applicable to industrial production.
Description
【Technical field】
The invention belongs to field of pharmaceutical engineering, and in particular to a kind of method of purification of teicoplanin.
【Background technology】
Teicoplanin (teicoplanin) is the glycopeptide class antibiosis of another kind of antimicrobial agent developed after vancomycin
Element.In existing teicoplanin production method, typically adopt based on fermentable production teicoplanin, drawing is impersonated in zymotic fluid
Rather, including TAl～TA2, wherein TA2 are the main actives of teicoplanin, mainly by the change that 5 chemical constitutions are quite similar
Compound (TA2-1, TA2-2, TA2-3, TA2-4, TA2-5) is constituted；Also contain an active component in its crude product and highly finished product
TA3-1, the compound is that TA2 removes acyl glucose amine product；Additionally, wherein also containing the analog that 2 lipophilicitys are stronger.
Teicoplanin chemical constitution is as shown in following formula one.At present, in the standard that pharmaceutical field is followed,《European Pharmacopoeia》(EP) to each group
Point be made that clearly regulation, A2 groups sum is not less than 80.0%, wherein A2-2 be 35.0%～55.0%, A2-1, A2-3,
A2-4, A2-5 are not more than 15.0% no more than 20.0%, A3-1, and pure component is not more than 5.0%.
The main method of purification of existing teicoplanin has：Solvent extraction, absorption method, ion-exchange and chromatography
Deng.Solvent extraction isolates and purifies that effect is poor, and yield is low, and at present the method is seldom adopted；Document [reference M.R. Ba Erdun (M.R,
) etc. Bardon Journal of Antibiotics, volume 31, No. 3, the 170-177 page (in March, 1978)] state from
The impact that sub- exchange process is purified to teicoplanin, strong-acid ion exchange resin can make the part sugar composition of teicoplanin occur to divide
Solution, using strong basic ion exchange resin, can make teicoplanin that epimerization occurs, and BA is reduced；Publication No.
The Chinese patent of CN101302248A, the United States Patent (USP) of Publication No. US2005245481A1 disclose liquid chromatography purification
Teicoplanin, but the method for purification disclosed in these patents can not be controlled well for A2 each components ratio, it is impossible to reach Europe
The standard of continent pharmacopeia, and the purification time is long, long the production cycle.The Chinese patent of Application No. CN201210221636.X is disclosed
A kind of method that utilization nanometer polymer microballoon prepares teicoplanin fine powder, the method part realizes containing for one-component in product
Amount is controllable；However, nanometer polymer microballoon is relatively costly, it is difficult to large-scale promotion.Additionally, Chinese Patent Application No. is
CN200710107185.6 discloses a kind of sephadex of employing GE companies or agarose gellike chromatography prepares high-purity
The production method of teicoplanin, but because sephadex and agarose gellike are expensive, it is not appropriate for industrialized production.
Therefore, in the method for purification of existing teicoplanin, comparative maturity and conventional or resin adsorption method；It will fermentation
Filter after basified, filtrate desorbs with strippant Jing after resin adsorption to resin, stripping liquid through activated carbon decolorizing, so
Afterwards filtrate solubilizer precipitation, filters and obtains final product teicoplanin wet product, is finally further refined with resin or chromatography agent, therein
Resin is mainly macroporous absorbent resin, and strippant is the aqueous solution of organic solvent, finally adds substantial amounts of solvent to be precipitated.
Although above-mentioned resin adsorption method has obtained more sufficiently approving in specific industrial production, there is also
Following defect：The resin that first current resin adsorption method is adopted is mostly nonpolar macroporous adsorption resin, and it is to impersonating drawing
The control of peaceful each component ratio affects larger, and decolouring impurity elimination effect is preferable not to the utmost；Second is exactly last precipitation operation, is generally adopted
With acetone is added, to 90% acetone concentration, teicoplanin is separated out, so need to use substantial amounts of acetone, greatly increase environmental protection
Pressure, production environment and personnel health are affected again.
In view of this, a kind of tree that can be adapted to industrialized production and environment amenable purification teicoplanin is worked out
Fat absorption method be practitioner institute highly desirablely.
【The content of the invention】
The technical problem to be solved is to provide a kind of method of purification of teicoplanin, not only to environment friend
It is good, and industrialized production can be adapted to.
The present invention is to solve above-mentioned technical problem by the following technical programs：A kind of method of purification of teicoplanin, should
Method of purification specifically includes following operating procedure：
(1) resin concentration：Take teicoplanin zymotic fluid and its pH value is adjusted to into 10.0～12.0, then carrying out filtering to replace
The peaceful filtrate of koala；Afterwards teicoplanin filtrate pumps into pretreated polarity with the speed of 0.2～2 times per hour filling bed volume
Macroporous adsorption resin chromatography post, and the resin particle size of polar macroporous adsorption resin chromatographic column is 20～60 mesh；Then adopt
Purifying is washed to colourless, then makees with the elution rate of 0.2～2 times per hour filling bed volume, with the aqueous solution of intensive polar solvent
Desorbed solution carries out gradient elution, and the desorbed solution used by per gradient elution is 3～5 times of filling bed volumes, and collects pregnant solution, is obtained final product
Teicoplanin pregnant solution；
(2) purifying resin：By the teicoplanin pregnant solution obtained by step (1) using equal-volume purified water dilute, afterwards with
The middle polarity large pore resin absorption column that per hour speed of 0.2～2 times of filling bed volume passes through pretreatment, then using purifying
It is washed to colourless, then with the elution rate of 0.2～2 times per hour filling bed volume, the buffer salt with intensive polar solvent is water-soluble
Liquid carries out isocratic elution, and Fraction collection eluent as desorbed solution, merges effective eluent and obtains final product amalgamation liquid, using efficient liquid phase
The component ratio of chromatography detection gained amalgamation liquid, when teicoplanin each component meets EP requirements in measuring amalgamation liquid, then adjusts
Whole amalgamation liquid pH value is to 6.8～7.4；
(3) film concentration：The amalgamation liquid that step (2) is adjusted after pH value is concentrated using NF membrane, and during concentrating
The purified water of 3～5 times of amalgamation liquid volumes is added, then obtains teicoplanin concentrate；
(4) it is spray-dried：The teicoplanin concentrate Jing constant flow pumps that step (3) is obtained are pumped into 1～5L/h flow velocitys
It is spray-dried, you can the teicoplanin dry product of EP standards must be met.
Further, in the step (1), filtration adopts plate-frame filtering.
Further, in the step (1), the resin of polar macroporous adsorption resin chromatographic column is with acrylamide as matrix
's.
Further, in the step (1), the resin of polar macroporous adsorption resin chromatographic column is HT60 resins.
Further, in the step (1), the gradient of gradient elution respectively is volume ratio 10:90、20:80、30:
70、40:The solvent system of 60 intensive polar solvent-water.
Further, in the step (2), the resin of middle polarity large pore resin absorption column is with polyacrylate as base
Matter, and resin particle size is 100 mesh.
Further, in the step (2), the resin of middle polarity large pore resin absorption column is HN60 resins.
Further, in the step (2), the buffered saline solution of intensive polar solvent is to use volume ratio to be 40:60 it is strong
Polar solvent is formulated with buffered saline solution, and the concentration of buffered saline solution be 0.05mol/L, pH value be 2.5.
Further, in the step (1), step (2), intensive polar solvent is low alcohol；The buffered saline solution
In buffer salt be sodium dihydrogen phosphate or potassium dihydrogen phosphate one kind.
Further, the intensive polar solvent is one kind of methyl alcohol or ethanol.
Further, in the step (3), NF membrane is PA membrane, and its molecular cut off is 100～1000D；It is preferred that
Molecular cut off is 500D.
Further, in the step (4), spray drying is carried out using spray dryer, and its actual conditions is：Spraying
90～100 DEG C of drying machine inlet temperature, 70～80 DEG C of outlet temperature
The beneficial effects of the present invention is：
By being used cooperatively with the middle polarity chromatographic resin of uniform particle diameter using polar macroporous adsorption resin so that gained
Product meets the teicoplanin dry product high income of EP standards, good decolorizing effect；With reference to spray drying, it is to avoid organic solvent
Use, not only protect environment, reduces cost, more avoid the residue problem of organic solvent in prior art；In addition, of the invention
The teicoplanin each component ratio that method of purification is obtained meets EP standards, and operation is efficiently convenient, preparation amount is big, is suitable to scale metaplasia
Produce.
【Description of the drawings】
With reference to the accompanying drawings in conjunction with the embodiments the invention will be further described.
Fig. 1 is the HPLC collection of illustrative plates of the teicoplanin zymotic fluid that Streptomyces fermentation of the present invention is produced.
Fig. 2 is that embodiment 1 crosses HT60 resin teicoplanin pregnant solution HPLC collection of illustrative plates in the present invention.
Fig. 3 is that embodiment 1 crosses HN60 resin teicoplanin amalgamation liquid HPLC collection of illustrative plates in the present invention.
Fig. 4 is the HPLC collection of illustrative plates that embodiment 1 is spray-dried obtained teicoplanin in the present invention.
【Specific embodiment】
A kind of method of purification of teicoplanin of the present invention, the method for purification specifically includes following operating procedure：
(1) resin concentration：Take teicoplanin zymotic fluid and its pH value is adjusted to into 10.0～12.0, then carrying out filtering to replace
The peaceful filtrate of koala；Afterwards teicoplanin filtrate pumps into pretreated polarity with the speed of 0.2～2 times per hour filling bed volume
Macroporous adsorption resin chromatography post, and the resin particle size of polar macroporous adsorption resin chromatographic column is 20～60 mesh；Then adopt
Purifying is washed to colourless, then makees with the elution rate of 0.2～2 times per hour filling bed volume, with the aqueous solution of intensive polar solvent
Desorbed solution carries out gradient elution, and the desorbed solution used by per gradient elution is 3～5 times of filling bed volumes, and collects pregnant solution, is obtained final product
Teicoplanin pregnant solution；
(2) purifying resin：By the teicoplanin pregnant solution obtained by step (1) using equal-volume purified water dilute, afterwards with
The middle polarity large pore resin absorption column that per hour speed of 0.2～2 times of filling bed volume passes through pretreatment, then using purifying
It is washed to colourless, then with the elution rate of 0.2～2 times per hour filling bed volume, the buffer salt with intensive polar solvent is water-soluble
Liquid carries out isocratic elution, and Fraction collection eluent as desorbed solution, merges effective eluent (containing washing for teicoplanin each component
De- liquid is then effective eluent) amalgamation liquid is obtained final product, the component ratio of gained amalgamation liquid is detected using high performance liquid chromatography, work as survey
When teicoplanin each component meets EP and requires in amalgamation liquid, then adjust amalgamation liquid pH value to 6.8～7.4；
(3) film concentration：The amalgamation liquid that step (2) is adjusted after pH value is concentrated using NF membrane, and during concentrating
The purified water of 3～5 times of amalgamation liquid volumes is added, then obtains teicoplanin concentrate；
(4) it is spray-dried：The teicoplanin concentrate Jing constant flow pumps that step (3) is obtained are pumped into 1～5L/h flow velocitys
It is spray-dried, you can the teicoplanin dry product of EP standards must be met.
Wherein, in step (1), teicoplanin filtering fermentation liquor adopts plate-frame filtering；Polar macroporous adsorption resin chromatographic column
Resin be such as HT60 resins with acrylamide as matrix；The gradient of gradient elution respectively is volume ratio 10:90、
20:80、30:70、40:The solvent system of 60 intensive polar solvent-water；Intensive polar solvent is low in the aqueous solution of intensive polar solvent
First alcohol, such as from methyl alcohol or one kind of ethanol.
In step (2), the resin of middle polarity large pore resin absorption column is such as HN60 with polyacrylate as matrix
Resin, and resin particle size is 100 mesh；The buffered saline solution of intensive polar solvent is to use volume ratio to be 40:60 it is highly polar
Solvent is formulated with buffered saline solution, and intensive polar solvent is low alcohol (as from one kind of methyl alcohol or ethanol), and is buffered
The concentration of saline solution is 0.05mol/L, pH value is 2.5, and specifically, the buffer salt in buffered saline solution is sodium dihydrogen phosphate
Or one kind of potassium dihydrogen phosphate.
In step (3), NF membrane is PA membrane, and its molecular cut off is 100～1000D；It is preferred that molecular cut off is
500D.In step (4), spray drying is carried out using spray dryer, and its actual conditions is：Spray dryer inlet temperature 90
～100 DEG C, 70～80 DEG C of outlet temperature.
It should be noted that teicoplanin zymotic fluid involved in the present invention is produced by streptomycete fermentation, and replace
The peaceful zymotic fluid of koala carries out high performance liquid chromatography detection, and testing result so as to what is not only produced to fermenting as shown in figure 1, impersonate drawing
Peaceful each component ratio has sufficiently understanding, and behind being easy to compare and check resin used wash-out effect.
In order to preferably be described to the present invention, the present invention illustrates following several embodiments, and in order that place
The effect of reason is preferable, in various embodiments：Polar macroporous adsorption resin is bought by Shang Hai Min with middle polarity chromatographic resin
Industrial corporation's production forever；In addition, removing the impurity that is filled in chromatographic column in resin and activating the mesh such as its ion to reach
, resin need to be pre-processed, conventional processing method is used, concrete operations are：The resin that dress post is used will be prepared
First cleaned repeatedly with 50-60 DEG C of hot water (running water of cleaning also can), embathe to embathe water without brown, foam it is little when be
Only, then the resin that hot water treatment is crossed is fitted in chromatographic column, afterwards using the acetone treatment resin of 5～8 column volumes, is washed till stream
Go out liquid add water it is not white muddiness till, be then washed to without acetone taste with purifying, that is, obtain pretreated resin column or layer
Analysis post, it is standby.
Embodiment 1
Teicoplanin zymotic fluid 10L is taken, pH value 11.0 is adjusted, then teicoplanin filtrate is obtained using plate-frame filtering；Impersonate drawing
Peaceful filtrate pumps into pretreated polar macroporous absorption HT60 (20-60 mesh) tree with the speed of 1.2 times per hour filling bed volumes
Fat chromatographic column (10 × 120cm of Φ)；Then purifying is washed to colourless, afterwards with the elution rate of 1.5L/h, is divided successively with gradient
Wei not volume ratio 10:90、20:80、30:70、40:60 ethanol-water solution (desorbed solution) carries out gradient elution, and washes per gradient
De- desorbed solution used is 3 times of filling bed volumes, and collects pregnant solution, teicoplanin pregnant solution is obtained final product, using high performance liquid chromatography
Method detects the teicoplanin pregnant solution, then testing result is as shown in Figure 2；
By gained teicoplanin pregnant solution using middle polarity HN60 (100 that pretreatment is crossed after the dilution of equal-volume purified water
Mesh) large pore resin absorption column (10 × 120cm of Φ)；Then purifying is washed to colourless, afterwards with the elution rate of 1.5L/h, uses body
Product is than being 40:60 ethanol-biphosphate sodium water solution (sodium dihydrogen phosphate concentration of aqueous solution is 0.05mol/L, pH 2.5) enters
Row isocratic elution, and Fraction collection eluent, merge effective eluent, using the component of high performance liquid chromatography combining data detection liquid
Ratio, testing result is as shown in figure 3, then teicoplanin each component meets EP requirements, adjustment amalgamation liquid pH value to 6.8 in amalgamation liquid
～7.4；Amalgamation liquid after adjustment pH value adopts molecular cut off and is concentrated for the PA membrane of 500D, and 3 are added during concentration
The purified water of～5 times of amalgamation liquid volumes, then obtain teicoplanin concentrate；Last teicoplanin concentration concentrated liquor Jing constant flow pumps
Pump in spray dryer and be spray-dried that (condition of spray drying is with 1L/h flow velocitys：Spray dryer inlet temperature 90
～100 DEG C, 70～80 DEG C of outlet temperature), teicoplanin dry product is obtained, detect that the teicoplanin is done using high performance liquid chromatography
Product, testing result is weighed as shown in figure 4, i.e. gained teicoplanin dry product meets EP standards, and the present embodiment obtains teicoplanin
Dry product 15.7g.
Embodiment 2
Teicoplanin zymotic fluid 100L is taken, pH value 10.0 is adjusted, then teicoplanin filtrate is obtained using plate-frame filtering；Impersonate drawing
Peaceful filtrate pumps into pretreated polar macroporous absorption HT60 (20-60 mesh) tree with the speed of 0.2 times per hour filling bed volume
Fat chromatographic column (25 × 200cm of Φ)；Then purifying is washed to colourless, afterwards with the elution rate of 20L/h, is distinguished successively with gradient
For volume ratio 10:90、20:80、30:70、40:60 ethanol-water solution (desorbed solution) carries out gradient elution, and per gradient elution
Desorbed solution used is 5 times of filling bed volumes, and collects pregnant solution, obtains final product teicoplanin pregnant solution；
By gained teicoplanin pregnant solution using middle polarity HN60 (100 that pretreatment is crossed after the dilution of equal-volume purified water
Mesh) large pore resin absorption column (25 × 200cm of Φ)；Then purifying is washed to colourless, afterwards with the elution rate of 15L/h, uses body
Product is than being 40:60 ethanol-potassium dihydrogen phosphate aqueous solution (potassium dihydrogen phosphate aqueous solution concentration is 0.05mol/L, pH 2.5) enters
Row isocratic elution, and Fraction collection eluent, merge effective eluent, using the component of high performance liquid chromatography combining data detection liquid
Ratio, measures teicoplanin each component in amalgamation liquid and meets EP requirements, adjustment amalgamation liquid pH value to 6.8～7.4；After adjustment pH value
Amalgamation liquid adopt molecular cut off and concentrated for the PA membrane of 100D, 3～5 times of amalgamation liquid volumes are added during concentration
Purified water, then obtain teicoplanin concentrate；Last teicoplanin concentration concentrated liquor Jing constant flow pumps pump into spray with 2L/h flow velocitys
It is spray-dried in mist drying machine, the condition of spray drying is：90～100 DEG C of spray dryer inlet temperature, outlet temperature
70～80 DEG C, the teicoplanin dry product 185.2g of EP standards must be met.
Embodiment 3
Teicoplanin zymotic fluid 800L is taken, pH value 12.0 is adjusted, then teicoplanin filtrate is obtained using plate-frame filtering；Impersonate drawing
Peaceful filtrate pumps into pretreated polar macroporous absorption HT60 (20-60 mesh) resin with the speed of 2 times per hour filling bed volumes
Chromatographic column (50 × 300cm of Φ)；Then purifying is washed to colourless, afterwards with the elution rate of 60L/h, respectively is with gradient
Volume ratio 10:90、20:80、30:70、40:60 ethanol-water solution (desorbed solution) carries out gradient elution, and per gradient elution institute
It is 5 times of filling bed volumes with desorbed solution, and collects pregnant solution, obtains final product teicoplanin pregnant solution；
By gained teicoplanin pregnant solution using middle polarity HN60 (100 that pretreatment is crossed after the dilution of equal-volume purified water
Mesh) large pore resin absorption column (60 × 250cm of Φ)；Then purifying is washed to colourless, afterwards with the elution rate of 40L/h, uses body
Product is than being 40:60 ethanol-biphosphate sodium water solution (sodium dihydrogen phosphate concentration of aqueous solution is 0.05mol/L, pH 2.5) enters
Row isocratic elution, and Fraction collection eluent, merge effective eluent, using the component of high performance liquid chromatography combining data detection liquid
Ratio, measures teicoplanin each component in amalgamation liquid and meets EP requirements, then adjust amalgamation liquid pH value to 6.8～7.4；Adjustment pH value
Amalgamation liquid afterwards adopts molecular cut off and is concentrated for the PA membrane of 1000D, and 3～5 times of merging liquid are added during concentration
Long-pending purified water, then obtain teicoplanin concentrate；Last teicoplanin concentrates concentrated liquor Jing constant flow pumps with 5L/h flow pumps
Enter in spray dryer and be spray-dried, the condition of spray drying is：90～100 DEG C of spray dryer inlet temperature, outlet
70～80 DEG C of temperature, must meet the teicoplanin dry product 486.8g of EP standards.
To sum up, the present invention is used cooperatively using polar macroporous adsorption resin with the middle polarity chromatographic resin of uniform particle diameter,
So that products obtained therefrom meets the teicoplanin dry product high income of EP standards, good decolorizing effect；With reference to spray drying, it is to avoid have
The use of machine solvent, not only protects environment, reduces cost, more avoids the residue problem of organic solvent in prior art；Separately
Outward, the teicoplanin each component ratio that method of purification of the present invention is obtained meets EP standards, and operation is efficiently convenient, preparation amount is big, fits
In large-scale production.
Although the foregoing describing the specific embodiment of the present invention, those familiar with the art should manage
Solution, the specific embodiment described by us is merely exemplary, rather than for the restriction to the scope of the present invention, is familiar with this
The technical staff in field should be covered the present invention's in the equivalent modification and change made according to the spirit of the present invention
In scope of the claimed protection.
Claims (12)
1. a kind of method of purification of teicoplanin, it is characterised in that：The method of purification specifically includes following operating procedure：
(1) resin concentration：Take teicoplanin zymotic fluid and its pH value is adjusted to into 10.0～12.0, then carrying out filtering must impersonate drawing
Peaceful filtrate；Afterwards teicoplanin filtrate is pumped into pretreated polar macroporous with the speed of 0.2～2 times per hour filling bed volume
Polymeric adsorbent chromatographic column, and the resin particle size of polar macroporous adsorption resin chromatographic column is 20～60 mesh；Then using purifying
Be washed to it is colourless, then with the elution rate of 0.2～2 times per hour filling bed volume, parsed with the aqueous solution of intensive polar solvent
Liquid carries out gradient elution, and the desorbed solution used by per gradient elution is 3～5 times of filling bed volumes, and collects pregnant solution, obtains final product and impersonates
Draw peaceful pregnant solution；
(2) purifying resin：Teicoplanin pregnant solution obtained by step (1) is diluted using equal-volume purified water, afterwards with per little
When 0.2～2 times filling bed volume speed by pretreatment middle polarity large pore resin absorption column, then using purifying washing
To colourless, then with the elution rate of 0.2～2 times per hour filling bed volume, made with the buffered saline solution of intensive polar solvent
Desorbed solution carries out isocratic elution, and Fraction collection eluent, merges effective eluent and obtains final product amalgamation liquid, using high performance liquid chromatography
The component ratio of method detection gained amalgamation liquid, when teicoplanin each component meets EP requirements in measuring amalgamation liquid, then adjustment is closed
And liquid pH value is to 6.8～7.4；
(3) film concentration：The amalgamation liquid that step (2) is adjusted after pH value is concentrated using NF membrane, and is added 3 during concentrating
The purified water of～5 times of amalgamation liquid volumes, then obtain teicoplanin concentrate；
(4) it is spray-dried：The teicoplanin concentrate Jing constant flow pumps that step (3) is obtained are pumped into 1～5L/h flow velocitys and carried out
It is spray-dried, you can the teicoplanin dry product of EP standards must be met.
2. a kind of method of purification of teicoplanin according to claim 1, it is characterised in that：In the step (1), filtration is adopted
Use plate-frame filtering.
3. a kind of method of purification of teicoplanin according to claim 1, it is characterised in that：In the step (1), polarity is big
The resin of macroporous adsorbent resin chromatographic column is with acrylamide as matrix.
4. a kind of method of purification of teicoplanin according to claim 3, it is characterised in that：In the step (1), polarity is big
The resin of macroporous adsorbent resin chromatographic column is HT60 resins.
5. a kind of method of purification of teicoplanin according to claim 1, it is characterised in that：In the step (1), gradient is washed
De- gradient respectively is volume ratio 10:90、20:80、30:70、40:The solvent system of 60 intensive polar solvent-water.
6. a kind of method of purification of teicoplanin according to claim 1, it is characterised in that：In the step (2), medium pole
Property large pore resin absorption column resin be with polyacrylate as matrix, and resin particle size be 100 mesh.
7. a kind of method of purification of teicoplanin according to claim 6, it is characterised in that：In the step (2), medium pole
Property large pore resin absorption column resin be HN60 resins.
8. a kind of method of purification of teicoplanin according to claim 1, it is characterised in that：It is highly polar in the step (2)
The buffered saline solution of solvent is to use volume ratio to be 40:60 intensive polar solvent is formulated with buffered saline solution, and buffers
The concentration of saline solution is 0.05mol/L, pH value is 2.5.
9. a kind of method of purification of teicoplanin according to claim 1, it is characterised in that：The step (1), step (2)
In, intensive polar solvent is low alcohol；Buffer salt in the buffered saline solution is sodium dihydrogen phosphate or potassium dihydrogen phosphate
It is a kind of.
10. a kind of method of purification of teicoplanin according to claim 9, it is characterised in that：The intensive polar solvent is first
One kind of alcohol or ethanol.
A kind of 11. methods of purification of teicoplanin according to claim 1, it is characterised in that：In the step (3), nanofiltration
Film is PA membrane, and its molecular cut off is 100～1000D.
A kind of 12. methods of purification of teicoplanin according to claim 1, it is characterised in that：In the step (4), spraying
Drying is carried out using spray dryer, and its actual conditions is：90～100 DEG C of spray dryer inlet temperature, outlet temperature 70
～80 DEG C.
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