Method for purifying norvancomycin by using polymer filler

Abstract

The invention provides a method for purifying norvancomycin by using a polymer filler, and belongs to the technical field of medicine preparation and purification, the method comprises the following treatment steps of: filtering, decolorizing, finely purifying, centrifugally precipitating, redissolving and freeze-drying norvancomycin fermentation liquor, and the finely purifying step is finely purifying by using the polymer filler. According to the method for purifying norvancomycin by using the polymer filler, the production period can be effectively shortened, and the product purity can be effectively improved.

Description

Technical Field

[0001] The invention relates to a purification method, in particular to a purification method of norvancomycin, and belongs to the technical field of drug preparation and purification. Background Art

[0002] Norvancomycin is a new antibiotic independently discovered in my country. It has one less methyl group on the terminal amino group than vancomycin. The chemical structure, pharmacological properties and antibacterial spectrum of Norvancomycin are similar to those of vancomycin, but Norvancomycin has slightly stronger antibacterial activity. It mainly has significant antibacterial effects on Gram-positive bacteria, and is more sensitive to methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. Its efficacy on membranous enteritis caused by Bacillus difficile is the same as that of vancomycin. It can act on the bacterial cell wall and inhibit protein synthesis, and is a fast-acting bactericidal drug.

[0003] At present, the purification process of norvancomycin usually includes filtration, decolorization, macroporous resin adsorption, desorption, precipitation, re-dissolution, and freeze-drying. Since the macroporous resin usually requires a low flow rate of 1-2CV / h, the process time of this method is relatively long; and the macroporous resin is purified by the principle of non-specific adsorption, which usually leads to low product purity. Summary of the invention

[0004] In view of the above problems, the present invention provides a method for purifying norvancomycin using a polymer filler to improve the purification efficiency and product purity of norvancomycin.

[0005] To achieve the above object, the technical solution of the present invention is: a method for purifying norvancomycin using a polymer filler, comprising subjecting the fermentation broth of norvancomycin to the following treatment steps in sequence: filtration, decolorization, purification, centrifugal precipitation, re-dissolution, and freeze-drying, wherein the purification step is purification using a polymer filler.

[0006] Furthermore, the matrix of the polymer filler is styrene-divinylbenzene, polyacrylate, butyl methacrylate or hydroxyethyl methacrylate, and the ligand is flavonyl+phenylpropyl, hydrophilized polymer+octanoic acid, hydrophilic group+carboxymethyl or other groups with similar properties.

[0007] Furthermore, the polymer filler is UniMSP 30XS (matrix polyacrylate, ligand yellow propyl + phenylpropyl), UniMSP 50XS (matrix polyacrylate, ligand yellow propyl + phenylpropyl), POROS Caprylate (matrix styrene-divinylbenzene, ligand hydrophilized polymer + octanoic acid), Seplife LXMS 30GCM (matrix styrene-divinylbenzene, ligand hydrophilic group + carboxymethyl), etc.

[0008] Furthermore, the purification comprises the following steps: flushing the filler, loading the sample, flushing the filler again, washing impurities, eluting, and collecting the sample.

[0009] Further, the step of washing the filler is to use 10mM-100mM potassium dihydrogen phosphate-dipotassium hydrogen phosphate buffer, sodium dihydrogen phosphate-disodium hydrogen phosphate buffer, acetic acid-sodium acetate buffer, acetic acid-ammonium acetate buffer, glycine-hydrochloric acid buffer, citric acid-disodium hydrogen phosphate buffer solution or citric acid-sodium citrate buffer with a pH of 3.0-6.0 to wash the filler for 1-10CV.

[0010] Furthermore, the loading is to adjust the pH of the decolorized norvancomycin fermentation broth to 3.0-6.0 with 1M HCl or 1M NaOH, and load it on the chromatography column, with a loading amount of 10-70 g / L gel.

[0011] Further, the re-rinsing of the filler is to use 10mM-100mM potassium dihydrogen phosphate-dipotassium hydrogen phosphate buffer, sodium dihydrogen phosphate-disodium hydrogen phosphate buffer, acetic acid-sodium acetate buffer, acetic acid-ammonium acetate buffer, glycine-hydrochloric acid buffer, citric acid-disodium hydrogen phosphate buffer or citric acid-sodium citrate buffer with a pH of 3.0-6.0 to rinse the filler for 1-10CV.

[0012] Further, the washing is performed using 10mM-100mM potassium dihydrogen phosphate-dipotassium hydrogen phosphate buffer, sodium dihydrogen phosphate-disodium hydrogen phosphate buffer, acetic acid-sodium acetate buffer, acetic acid-ammonium acetate buffer, glycine-hydrochloric acid buffer, citric acid-disodium hydrogen phosphate buffer or citric acid-sodium citrate buffer with a pH of 3.0-6.0, and adding 10mM-100mM NaCl or KCl buffer for 1-5CV.

[0013] Furthermore, the elution is performed using 10mM-100mM potassium dihydrogen phosphate-dipotassium hydrogen phosphate buffer, sodium dihydrogen phosphate-disodium hydrogen phosphate buffer, acetic acid-sodium acetate buffer, acetic acid-ammonium acetate buffer, glycine-hydrochloric acid buffer, citric acid-disodium hydrogen phosphate buffer or citric acid-sodium citrate buffer with a pH of 3.0-6.0, and eluting with 100mM-500mM NaCl or KCl buffer.

[0014] Furthermore, the sample collection starts when the UV280 absorption value is greater than 500 mAu and ends when the UV280 absorption value is less than 1000 mAu, and the collected sample is the purified norvancomycin.

[0015] The beneficial effects of the method for purifying norvancomycin using a polymer filler of the present invention are:

[0016] The method for purifying norvancomycin using a polymer filler of the present invention can effectively shorten the production cycle and effectively improve the purity of the product.

[0017] The purification method of the present invention uses a polymer filler as a purifier, and its matrix is ​​styrene-divinylbenzene, polyacrylate, butyl methacrylate, hydroxyethyl methacrylate, etc., and its ligand is flavonyl+phenylpropyl, hydrophilized polymer+octanoic acid, hydrophilic group+carboxymethyl or other groups with similar properties; the polymer filler used in the present invention has high resolution and less nonspecific adsorption, and can greatly improve the purity of the product.

[0018] The purification steps of the invention include filtration, decolorization, purification, precipitation, redissolution and freeze drying, and the composite filler is used for purification instead of the macroporous resin adsorption in the original process.

[0019] Patent CN1113886552A discloses a method for purification using a new type of polymer filler, which uses a reverse phase polymer filler and requires the use of organic solvents such as methanol, ethanol, and isopropanol as a balance solution and eluent. However, the use of organic solvents is costly, and as current regulations become increasingly stringent, organic solvents need to be stored in separate explosion-proof areas; in addition, organic solvents are toxic, and protective measures must be taken to prevent danger when used. The method of using polymer fillers in the present invention can effectively shorten the production cycle and effectively improve the purity of the product. In addition, the present invention does not use organic solvents, and does not require the construction of additional explosion-proof areas during factory production, which reduces factory construction costs and is more environmentally friendly and safe.

[0020] The purification method of the present invention can replace the macroporous resin adsorption process in the traditional process. The macroporous resin adsorption flow rate is relatively low at 1-3CV / h, while the flow rate of the present invention is 5-15CV / h, which can greatly shorten the process time. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] The present invention will be further described in detail below in conjunction with the accompanying drawings and specific embodiments.

[0022] Figure 1 is the HPLC chart of the final product in Example 1 of the present invention;

[0023] Figure 2 is the HPLC chart of the final product in Example 2 of the present invention;

[0024] Figure 3 It is the HPLC chart of the final product in Comparative Example 1 of the present invention;

[0025] Figure 4 It is the HPLC chart of the final product in Comparative Example 2 of the present invention. DETAILED DESCRIPTION

[0026] The technical scheme in the embodiment of the present invention is described clearly and completely below in conjunction with the accompanying drawings in the embodiment of the present invention. In the following description, many specific details are set forth to facilitate a full understanding of the present invention, but the present invention can also be implemented in other ways different from those described herein, and those skilled in the art can make similar generalizations without violating the connotation of the present invention, so the present invention is not limited by the specific embodiments disclosed below.

[0027] A method for purifying norvancomycin using a polymer filler comprises subjecting a fermentation broth of norvancomycin to the following treatment steps in sequence: filtration, decolorization, purification, centrifugal precipitation, re-dissolution, and freeze-drying, wherein the purification step is purification using a polymer filler.

[0028] The matrix of the polymer filler is styrene-divinylbenzene, polyacrylate, butyl methacrylate or hydroxyethyl methacrylate, and the ligand is flavonyl+phenylpropyl, hydrophilized polymer+octanoic acid, hydrophilic group+carboxymethyl or other groups with similar properties.

[0029] Further, the polymer filler is UniMSP 30XS (matrix polyacrylate, ligand yellow propyl + phenylpropyl), UniMSP 50XS (matrix polyacrylate, ligand yellow propyl + phenylpropyl), POROS Caprylate (matrix styrene-divinylbenzene, ligand hydrophilized polymer + octanoic acid), Seplife LXMS 30GCM (matrix styrene-divinylbenzene, ligand hydrophilic group + carboxymethyl), etc. The purification of the composite filler includes the following steps: washing the filler, loading the sample, washing the filler again, washing impurities, eluting, and collecting the sample.

[0030] Further, the step of washing the filler is to use 10mM-100mM potassium dihydrogen phosphate-dipotassium hydrogen phosphate buffer solution, sodium dihydrogen phosphate-disodium hydrogen phosphate buffer solution, acetic acid-sodium acetate buffer solution, acetic acid-ammonium acetate buffer solution, glycine-hydrochloric acid buffer solution, citric acid-disodium hydrogen phosphate buffer solution or citric acid-sodium citrate buffer solution with a pH of 3.0-6.0 to wash the filler for 1-10CV. The loading is to adjust the pH of the decolorized norvancomycin fermentation broth to 3.0-6.0 with 1M HCl or 1M NaOH, and load it on the chromatography column, with a loading amount of 10-70g / L gel. The packing is rinsed again by using 10mM-100mM potassium dihydrogen phosphate-dipotassium hydrogen phosphate buffer, sodium dihydrogen phosphate-disodium hydrogen phosphate buffer, acetic acid-sodium acetate buffer, acetic acid-ammonium acetate buffer, glycine-hydrochloric acid buffer, citric acid-disodium hydrogen phosphate buffer or citric acid-sodium citrate buffer with a pH of 3.0-6.0 for 1-10CV. The impurities are washed by using 10mM-100mM potassium dihydrogen phosphate-dipotassium hydrogen phosphate buffer, sodium dihydrogen phosphate-disodium hydrogen phosphate buffer, acetic acid-sodium acetate buffer, acetic acid-ammonium acetate buffer, glycine-hydrochloric acid buffer, citric acid-disodium hydrogen phosphate buffer or citric acid-sodium citrate buffer with a pH of 3.0-6.0, and adding 10mM-100mM NaCl or KCl buffer for 1-5CV. The elution is performed by using 10mM-100mM potassium dihydrogen phosphate-dipotassium hydrogen phosphate buffer, sodium dihydrogen phosphate-disodium hydrogen phosphate buffer, acetic acid-sodium acetate buffer, acetic acid-ammonium acetate buffer, glycine-hydrochloric acid buffer, citric acid-disodium hydrogen phosphate buffer or citric acid-sodium citrate buffer with a pH of 3.0-6.0, and adding 100mM-500mM NaCl or KCl buffer for elution. The sample collection starts after the UV280 absorption value is greater than 500mAu and ends after it is less than 1000mAu. The collected sample is the purified norvancomycin.

[0031] Example 1

[0032] A method for purifying norvancomycin using a polymer filler comprises subjecting a fermentation broth of norvancomycin to the following treatment steps in sequence: filtration, decolorization, purification, precipitation, reconstitution, and freeze drying. The specific steps are as follows:

[0033] Take 10L of fermentation broth with an expression level of 6.3g / L, add 5% perlite and 10% potassium hematite, and collect the supernatant by plate and frame filtration; adjust the supernatant pH to 5.5 with 1M HCl and load it on 1L of B001 decolorization resin at a flow rate of 1CV / h, and collect the flow-through.

[0034] Purification: Take 20g of the decolorizing resin flow-through liquid and purify it with 1L of filler UniMSP 50XS; balance it with 30mM acetic acid-ammonium acetate buffer at pH 5.0 for 3CV; adjust the pH of the sample to 5.0 with 1M HCl and load it; rinse it with 20mM acetic acid-ammonium acetate buffer at pH 5.0 for 3CV; wash it with 20mM acetic acid-ammonium acetate buffer at pH 4.0 plus 60mM NaCl buffer, and rinse it for 2CV; elute it with 15mM acetic acid-ammonium acetate buffer at pH 5.0 plus 200mM NaCl buffer; collect the starting and ending points of 700mAu-300mAu; obtain 18.2g of norvancomycin with a purity of 94.87% and a yield of 91.0%.

[0035] Precipitation, reconstitution, and freeze drying: adjust the pH to 8.5 with 1M NaOH, then centrifuge at 8000rpm for 20min, remove the supernatant and collect the precipitate; dissolve the precipitate in purified water adjusted to pH 3.5 with HCl, with a concentration of 25g / L; then freeze dry under the following conditions: pre-freeze at -40°C for 2h, then evacuate to below 20Pa, then heat and dry by increasing the temperature by 20°C for 2h, heat to 40°C and maintain for 30h, and after freeze drying, obtain 14.51g of norvancomycin powder with a purity of 99.61% (see the final product figure) Figure 1 ).

[0036] The above analysis method is: using a C18 column; mobile phase A: triethylamine buffer (3 ml of triethylamine, add 1000 ml of water, adjust the pH to 3.2 with phosphoric acid): acetonitrile: tetrahydrofuran = 96:3:1, mobile phase B: triethylamine buffer: acetonitrile: tetrahydrofuran = 70:29:1, linear gradient elution according to Table 1; flow rate 1 ml / min; wavelength 280 nm; injection volume 20 ul.

[0037] Table 1

[0038] Time (min) Mobile phase A (%) Mobile phase B (%) 0 100 0 23 100 0 38 0 100 40 0 100 41 100 0 50 100 0

[0039] Example 2

[0040] The same as Example 1, except that the purification conditions are as follows: 45 g of the decolorizing resin flow-through is purified with 1 L of filler UniMSP50XS; 50 mM glycine-hydrochloric acid buffer with a pH of 5.0 is used for equilibration for 3CV; the sample is adjusted to pH 5.0 with 1 M HCl and loaded; 50 mM glycine-hydrochloric acid buffer with a pH of 5.0 is used for washing for 3CV; 50 mM glycine-hydrochloric acid buffer with a pH of 4.0 plus 60 mM NaCl is used for washing, and washing for 2CV; 50 mM glycine-hydrochloric acid buffer with a pH of 5.0 plus 160 mM KCl is used for elution; the collection start and end points are 700 mAu-400 mAu; 40.2 g of vancomycin with a purity of 86.58% is obtained, and the yield is 89.3%.

[0041] After freeze-drying, 33.5 g of norvancomycin powder with a purity of 96.32% was obtained (see the final product picture). Figure 2 ).

[0042] Example 3

[0043] The same as Example 1, except that the purification conditions are as follows: 5 g of the decolorizing resin flow-through is purified with 200 ml of POROS Caprylate; 30 mM glycine-hydrochloric acid buffer with a pH of 4.5 is used for equilibration for 3CV; the sample is adjusted to pH 4.5 with 1 M HCl and loaded; 30 mM glycine-hydrochloric acid buffer with a pH of 4.5 is used for washing for 3CV; 50 mM glycine-hydrochloric acid with a pH of 4.5 plus 50 mM NaCl buffer is used for washing, and 2CV is used for washing; 30 mM glycine-hydrochloric acid with a pH of 4.5 plus 180 mM NaCl buffer is used for elution; the collection start and end points are 800 mAu-100 mAu; 4.3 g of norvancomycin with a purity of 88.55% is obtained, and the yield is 86.0%.

[0044] After freeze-drying, 3.5 g of norvancomycin powder with a purity of 94.19% was obtained.

[0045] Example 4

[0046] The same as Example 1, except that the purification conditions are as follows: 6 g of the decolorizing resin flow-through is purified with 200 ml of Seplife LXMS 30GCM filler; 3CV is balanced with 30 mM acetic acid-ammonium acetate buffer at pH 5.5; the sample is adjusted to pH 5.5 with 1 M HCl and loaded; 3CV is washed with 30 mM acetic acid-ammonium acetate buffer at pH 5.5; 2CV is washed with 50 mM acetic acid-ammonium acetate plus 50 mM NaCl buffer at pH 5.5; 3CV is eluted with 30 mM acetic acid-ammonium acetate plus 200 mM NaCl buffer at pH 6.0; the collection start and end points are 500 mAu-300 mAu; 5.3 g of norvancomycin with a purity of 90.38% is obtained, and the yield is 88.3%.

[0047] After freeze-drying, 4.5 g of norvancomycin powder with a purity of 93.74% was obtained.

[0048] Comparative Example 1

[0049] Comparative Example 1 is a comparative test of Example 1. Comparative Example 1 uses the purification method of the prior art to purify the fermentation broth of norvancomycin, including filtration, decolorization, macroporous resin adsorption, desorption, precipitation, re-dissolution, and freeze-drying.

[0050] Take 10L of fermentation broth, add 5% perlite and 10% potassium ferrate, collect the supernatant by plate and frame filtration; adjust the pH of the supernatant to 5.5 with 1M HCl, load it on B001 decolorization resin, flow rate 1CV / h, and collect the flow-through.

[0051] Take 15g of the decolorizing resin flow-through liquid and adsorb it with 1L of LX-38; balance with purified water for 3CV; adjust the pH of the sample to 4.5 with 1M HCl and load it; rinse with purified water for 5CV; desorb with 20% ethanol at pH 4.5, and collect the starting and ending points of 1000mAu-800mAu; obtain 8.6g of norvancomycin with a purity of 77.83% and a yield of 57.3%.

[0052] The desorption liquid of the macroporous resin was adjusted to pH 8.5 with 1M NaOH, and then centrifuged at 8000rpm for 20min, the supernatant was removed and the precipitate was collected; the precipitate was dissolved in purified water with HCl adjusted to pH 3.5, with a concentration of 25g / L; and then freeze-dried under the following conditions: pre-freeze at -40℃ for 2h, then evacuate to below 20Pa, and then heat and dry by increasing the temperature by 20℃ for 2h, and maintain the temperature at 20℃ for 30h to obtain 7.3g of norvancomycin powder with a yield of 84.9%.

[0053] The purity of freeze-dried norvancomycin was determined. Figure 3 As shown in the HPLC chart of the final product, the purity of norvancomycin was 90.58%.

[0054] Comparative Example 2

[0055] Comparative Example 2 is a comparative test of Example 1. Comparative Example 2 uses the purification method of the prior art to purify the fermentation broth of norvancomycin, including filtration, decolorization, polymer reverse phase purification, membrane concentration, precipitation, re-dissolution, and freeze-drying.

[0056] Take 10L of fermentation broth, add 5% perlite and 10% potassium ferrate, collect the supernatant by plate and frame filtration; adjust the pH of the supernatant to 5.5 with 1M HCl, load it on B001 decolorization resin, flow rate 1CV / h, and collect the flow-through.

[0057] 200 ml of UniPMM40 was rinsed with purified water for 2CV, and the decolorizing resin flow-through containing 4 g of norvancomycin was loaded, washed with 1% methanol solution for 2CV (pH adjusted to 7.2 with HCl), eluted with 10% methanol solution (pH adjusted to 7.0 with HCl), and the starting and ending points of the collection were 650 mAu-650 mAu; 2.5 g of vancomycin with a purity of 83.38% was obtained, and the yield was 62.5%.

[0058] The eluate from UniPMM40 was concentrated to a concentration of 10 g / L using a membrane and then eluted with 3 volumes of purified water.

[0059] The membrane concentrate was adjusted to pH 8.5 with 1M NaOH, then centrifuged at 8000rpm for 20min, the supernatant was removed and the precipitate was collected; the precipitate was dissolved in purified water with HCl adjusted to pH 3.5, with a concentration of 25g / L; then freeze-dried under the following conditions: pre-freezing at -40°C for 2h, then vacuuming to below 20Pa, then heating and drying with a temperature increase of 20°C for 2h, and maintaining the temperature at 40°C for 30h to obtain 1.9g of norvancomycin powder with a purity of 91.56 and a yield of 76%. The results are as follows: Figure 4 The final product is shown in HPLC.

[0060] Example 5

[0061] The process time of pure or macroporous resin adsorption in Examples 1-4 and Comparative Examples 1-2 is summarized as shown in Table 2.

[0062] Table 2

[0063] project Technology Flow rate Process time Example 1 UniMSP 50XS 10CV / h 2.6h Example 2 UniMSP 50XS 10CV / h 2.8h Example 3 POROS Caprylate 8CV / h 3.2 Example 4 Seplife LXMS 30GCM 10CV / h 2.6 Comparative Example 1 LX-38 1CV / h 22h Comparative Example 2 UniPMM40 2CV / h 7.5h

[0064] It can be seen from the statistical values ​​in the above table that the purification method of the present invention can replace the macroporous resin adsorption process in the traditional process. The macroporous resin adsorption flow rate is relatively low at 1-3CV / h, while the flow rate of the present invention is 5-15CV / h, which can greatly shorten the process time.

[0065] Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

Claims

1. A method for purifying norvancomycin using a polymer filler, characterized in that: The method comprises the following processing steps in sequence: filtering, decolorizing, purifying, centrifugal precipitation, re-dissolving and freeze-drying the fermentation liquid of norvancomycin, wherein the purifying step is to purify with a polymer filler.

2. The method for purifying norvancomycin using a polymer filler according to claim 1, characterized in that: The matrix of the polymer filler is styrene-divinylbenzene, polyacrylate, butyl methacrylate or hydroxyethyl methacrylate, and the ligand is xanthocyanin+phenylpropyl, hydrophilized polymer+octanoic acid, hydrophilic group+carboxymethyl.

3. The method for purifying norvancomycin using a polymer filler according to claim 2, characterized in that: The polymer fillers are UniMSP 30XS, UniMSP 50XS, POROS Caprylate, and Seplife LXMS 30GCM.

4. A method for purifying norvancomycin using a polymer filler according to any one of claims 1 to 3, characterized in that: The purification comprises the following steps: flushing the filler, loading the sample, flushing the filler again, washing impurities, eluting, and collecting the sample.

5. The method for purifying norvancomycin using a polymer filler according to claim 4, characterized in that: The step of flushing the filler is to flush the filler for 1-10CV using a 10mM-100mM buffer with a pH of 3.0-6.0, wherein the buffer is any one of the following: potassium dihydrogen phosphate-dipotassium hydrogen phosphate buffer, sodium dihydrogen phosphate-disodium hydrogen phosphate buffer, acetic acid-sodium acetate buffer, acetic acid-ammonium acetate buffer, glycine-hydrochloric acid buffer, citric acid-disodium hydrogen phosphate buffer solution or citric acid-sodium citrate buffer.

6. The method for purifying norvancomycin using a polymer filler according to claim 4, characterized in that: The loading is to adjust the pH of the decolorized norvancomycin fermentation broth to 3.0-6.0 with 1M HCl or 1M NaOH, and load the broth onto a chromatography column with a loading amount of 10-70 g / L gel.

7. The method for purifying norvancomycin using a polymer filler according to claim 4, characterized in that: The second flushing of the filler is to use a 10mM-100mM buffer with a pH of 3.0-6.0 to flush the filler for 1-10CV, and the buffer is selected from any one of the following: potassium dihydrogen phosphate-dipotassium hydrogen phosphate buffer, sodium dihydrogen phosphate-disodium hydrogen phosphate buffer, acetic acid-sodium acetate buffer, acetic acid-ammonium acetate buffer, glycine-hydrochloric acid buffer, citric acid-disodium hydrogen phosphate buffer or citric acid-sodium citrate buffer.

8. The method for purifying norvancomycin using a polymer filler according to claim 4, characterized in that: The washing is performed by using a 10mM-100mM buffer with a pH of 3.0-6.0 and a 10mM-100mM NaCl or KCl buffer for 1-5CV, wherein the buffer with a pH of 3.0-6.0 is selected from any one of the following: potassium dihydrogen phosphate-dipotassium hydrogen phosphate buffer, sodium dihydrogen phosphate-disodium hydrogen phosphate buffer, acetic acid-sodium acetate buffer, acetic acid-ammonium acetate buffer, glycine-hydrochloric acid buffer, citric acid-disodium hydrogen phosphate buffer or citric acid-sodium citrate buffer.

9. The method for purifying norvancomycin using a polymer filler according to claim 4, characterized in that: The elution is performed by using a 10mM-100mM buffer with a pH of 3.0-6.0 and a 100mM-500mM NaCl or KCl buffer, wherein the buffer with a pH of 3.0-6.0 is selected from any one of the following: potassium dihydrogen phosphate-dipotassium hydrogen phosphate buffer, sodium dihydrogen phosphate-disodium hydrogen phosphate buffer, acetic acid-sodium acetate buffer, acetic acid-ammonium acetate buffer, glycine-hydrochloric acid buffer, citric acid-disodium hydrogen phosphate buffer or citric acid-sodium citrate buffer.

10. The method for purifying norvancomycin using a polymer filler according to claim 4, characterized in that: The sample collection starts when the UV280 absorption value is greater than 500 mAu and ends when the UV280 absorption value is less than 1000 mAu. The collected sample is the purified norvancomycin.

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