CN113866330B - Separation and purification method and application of dehydrated daptomycin - Google Patents
Separation and purification method and application of dehydrated daptomycin Download PDFInfo
- Publication number
- CN113866330B CN113866330B CN202111247044.0A CN202111247044A CN113866330B CN 113866330 B CN113866330 B CN 113866330B CN 202111247044 A CN202111247044 A CN 202111247044A CN 113866330 B CN113866330 B CN 113866330B
- Authority
- CN
- China
- Prior art keywords
- daptomycin
- mobile phase
- dehydrated
- liquid
- pump
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
- G01N30/14—Preparation by elimination of some components
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
- G01N30/14—Preparation by elimination of some components
- G01N2030/146—Preparation by elimination of some components using membranes
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/10—Process efficiency
Abstract
The invention belongs to the technical field of daptomycin, and particularly relates to a separation and purification method and application of dehydrated daptomycin, which comprises the steps of carrying out destructive experiments on daptomycin feed liquid under the conditions of 55-60 ℃ and heating time of more than 10 hours; and a step of resolving with a C18 high pressure column with a mobile phase of a combination of 0.1wt% phosphate solution and 1wt% acetonitrile, and a combination of 0.1wt% TFA and 1wt% acetonitrile, respectively; and carrying out nanofiltration and freeze-drying on the collected liquid obtained by the analysis to obtain dehydrated daptomycin freeze-dried powder with the purity of more than or equal to 99 percent.
Description
Technical Field
The invention belongs to the technical field of daptomycin, and particularly relates to a separation and purification method and application of dehydrated daptomycin.
Background
Daptomycin has been produced industrially on a large scale at present, but little research has been done on its degradation of impurities, particularly dehydrated daptomycin. The dehydrated daptomycin serving as one of the degradation impurities of the daptomycin can obviously reduce the drug effect, however, the purity of the standard product of the existing dehydrated daptomycin is only about 98 percent, and the purity of the dehydrated daptomycin obtained by the method for separating and purifying the dehydrated daptomycin disclosed in the patent CN103724400B is not high enough, so that the purity of the dehydrated daptomycin is difficult to meet the purity requirement of serving as the impurity standard product of the dehydrated daptomycin in the preparation of the high-quality daptomycin, and the determination precision of the impurity of the high-quality daptomycin is seriously influenced.
Disclosure of Invention
In order to overcome the defects in the prior art, the technical problems to be solved by the invention are as follows: provides a separation and purification method for the dehydrated daptomycin with the separation purity of 99 percent;
further provides the application of the dehydrated daptomycin separated and purified by the separation and purification method of the dehydrated daptomycin in preparation or as at least one of a dehydrated daptomycin standard substance, a reference substance, a calibrator and a quality control substance.
In order to solve the technical problems, the invention adopts the following technical scheme: the separation and purification method of the dehydrated daptomycin comprises the following steps:
s1, carrying out destructive experiments on daptomycin feed liquid at 55-60 ℃ for more than 10 hours to obtain feed liquid A;
s2, carrying out C18 high-pressure column chromatography on the feed liquid A, wherein a mobile phase comprises a mobile phase A and a mobile phase B, the mobile phase A is 0.1wt% of phosphate solution, the mobile phase B is 1wt% of acetonitrile, and the opening ratio of an A pump corresponding to the mobile phase A to a B pump corresponding to the mobile phase B is 95:5, so as to obtain a collected liquid B;
s3, carrying out nanofiltration on the collected liquid B;
s4, performing C18 high-pressure column chromatography on the collected liquid B after nanofiltration, wherein a mobile phase comprises a mobile phase C and a mobile phase D, the mobile phase C is 0.1wt% TFA, the mobile phase D is 1wt% acetonitrile, and the aperture ratio of the pump A corresponding to the mobile phase C to the pump B corresponding to the mobile phase D is 70:30 to obtain a collected liquid C;
s5, carrying out nanofiltration on the collecting liquid C;
s6, freeze-drying the nanofiltration collected liquid C to obtain the dehydrated daptomycin freeze-dried powder with the purity of more than or equal to 99 percent.
Further provides application of the dehydrated daptomycin obtained by the separation and purification method of the dehydrated daptomycin in preparation or as at least one of a dehydrated daptomycin standard substance, a reference substance, a calibrator and a quality control substance.
The invention has the beneficial effects that: the daptomycin in the daptomycin feed liquid can be effectively promoted to be dehydrated by carrying out destructive experiments on the daptomycin feed liquid, so that the content of the dehydrated daptomycin in the feed liquid A is improved; the method has the advantages that the combination of the phosphate solution with the mobile phase of 1wt% acetonitrile and the combination of the TFA with the mobile phase of 1wt% acetonitrile are used for eluting the dehydrated daptomycin respectively, so that the retention capacity of the C18 filler can be effectively improved, the dehydrated daptomycin is prevented from being further degraded in the purification process, and the purity of the dehydrated daptomycin freeze-dried powder of a final product is improved to 99%.
Drawings
FIG. 1 shows a liquid phase diagram of the collected liquid C after nanofiltration in a specific embodiment of the present invention;
FIG. 2 shows a liquid phase diagram of a daptomycin solution in an embodiment of the invention.
Detailed Description
In order to describe the technical contents, the achieved objects and effects of the present invention in detail, the following description will be made with reference to the embodiments in conjunction with the accompanying drawings.
The separation and purification method of the dehydrated daptomycin comprises the following steps:
s1, carrying out destructive experiments on daptomycin feed liquid at 55-60 ℃ for more than 10 hours to obtain feed liquid A;
s2, carrying out C18 high-pressure column chromatography on the feed liquid A, wherein a mobile phase comprises a mobile phase A and a mobile phase B, the mobile phase A is 0.1wt% of phosphate solution, the mobile phase B is 1wt% of acetonitrile, and the opening ratio of an A pump corresponding to the mobile phase A to a B pump corresponding to the mobile phase B is 95:5, so as to obtain a collected liquid B;
s3, carrying out nanofiltration on the collected liquid B;
s4, performing C18 high-pressure column chromatography on the collected liquid B after nanofiltration, wherein a mobile phase comprises a mobile phase C and a mobile phase D, the mobile phase C is 0.1wt% TFA, the mobile phase D is 1wt% acetonitrile, and the aperture ratio of the pump A corresponding to the mobile phase C to the pump B corresponding to the mobile phase D is 70:30 to obtain a collected liquid C;
s5, carrying out nanofiltration on the collecting liquid C;
s6, freeze-drying the nanofiltration collected liquid C to obtain the dehydrated daptomycin freeze-dried powder with the purity of more than or equal to 99 percent.
The C18 high pressure chromatography column had an a pump (port) and a B pump (port). Wherein in S2, mobile phase a is pumped from pump a into the C18 high pressure chromatography column and mobile phase B is pumped from pump B into the C18 high pressure chromatography column; in S4, mobile phase C is pumped from pump a into the C18 high pressure chromatography column and mobile phase D is pumped from pump B into the C18 high pressure chromatography column.
In S4, the C18 high pressure column may be a C18 high pressure column used continuously in S2 or a new C18 high pressure column.
The C18 high pressure chromatography column preferably has 60LC18 A chromatography column with a packing of 10um (purchased from nanotechnology) has a specification of 10mm by 100mm.
Wherein the phosphate solution is sodium phosphate, potassium phosphate, ammonium phosphate or any other aqueous solution of phosphate, and the pH value of the phosphate solution is preferably 6.
In S3 and S5, nanofiltration concentration is carried out by adopting a nanofiltration membrane of 300D, the temperature is controlled below 18 ℃, and the concentration is carried out until the volume is 1L.
The phosphate solution, TFA and 1wt% acetonitrile are all aqueous solutions with pure water as a solvent.
Preferably, the destructive test is carried out under conditions of heating at 60℃for 12 hours.
Specifically, the destructive experiment is: the daptomycin feed solution was mixed in phosphate buffer at ph=6 and subjected to an experiment at 60 ℃ for 12 hours to obtain feed solution a containing 16.87% of dehydrated daptomycin.
Further, the method also comprises the step of adjusting the pH value of the feed liquid A back to 6.0-6.5 between S1 and S2.
Specifically, 1mol/L hydrochloric acid is adopted to adjust the pH value of the feed liquid A to be recovered to 6.0-6.5.
Specifically, in S2, the collecting time of the collecting liquid B is 160 to 180 minutes.
Alternatively, in S2, the flow rates of mobile phase A and mobile phase B are 5.0.+ -. 0.5L/min.
Specifically, in S4, the collecting time of the collecting liquid C is 200 to 230 minutes.
Alternatively, in S4, the flow rates of mobile phase C and mobile phase D are 5.0.+ -. 0.5L/min.
The application of the dehydrated daptomycin prepared by the separation and purification method of the dehydrated daptomycin in preparation or as at least one of a dehydrated daptomycin standard substance, a reference substance, a calibrator and a quality control substance.
At present, when the dehydrated daptomycin is separated and purified, the dehydrated daptomycin is easy to be further degraded to generate other impurities or rehydrated to form the daptomycin, and the existing buffer salt is sodium acetate, so that the dehydrated daptomycin cannot be completely separated, and the purity of the dehydrated daptomycin is difficult to reach 95 percent, only very few of the dehydrated daptomycin can reach 98 percent, and the purity of the dehydrated daptomycin cannot reach 99 percent or more in the separation and purification. The purity of the dehydrated daptomycin provided by the invention can reach 99%, so that the detection or contrast precision can be effectively improved when the dehydrated daptomycin is used as a dehydrated daptomycin standard substance, a reference substance, a calibrator or a quality control substance, and the measurement precision of the purity of a high-quality daptomycin finished product can be further improved. And can also be used as a detection product for continuously researching the pharmacological and toxicological characteristics of the compound.
Unless otherwise indicated, all reagents such as TRA, sodium phosphate, and hydrochloric acid are at least analytically pure.
Example 1
The separation and purification method of the dehydrated daptomycin comprises the following steps:
s1, 200g of daptomycin is taken and is prepared into daptomycin feed liquid with the concentration of 10mg/mL in phosphate buffer solution (sodium phosphate buffer solution, pH=6), and the daptomycin feed liquid is heated for 12 hours at 60 ℃ to obtain feed liquid A with the purity of 0.97% of dehydrated daptomycin;
s2, adjusting the pH value of the feed liquid A to 6.2 by using 1mol/L hydrochloric acid;
s3, 60L of filler is filledC18 10 um) was packed in a high pressure column (10 mm. Times.100 mm), the C18 high pressure column was equilibrated with an equilibration solution comprising 0.1wt% sodium phosphate solution and 1wt% acetonitrile, wherein the sodium phosphate solution was pumped from pump A into the C18 high pressure column, 1wt% ethylPumping nitrile into C18 from pump B, wherein the opening degree of pump A and pump B is 99:1, the balance flow rate is 5.0+/-0.5L/min, and the balance time is 30min;
s4, feeding the feed liquid A with the pH value of 6.2 into a column at the flow rate of 5.0+/-0.5L/min, and top-washing with 80-90L of a 1wt% acetonitrile water solution at the flow rate of 5.0+/-0.5L/min;
s5, eluting the top-washed C18 high-pressure column with 0.1wt% sodium phosphate solution and 1wt% acetonitrile, wherein 0.1wt% sodium phosphate solution is pumped into the C18 high-pressure column from a pump A, 1wt% acetonitrile is pumped into the C18 high-pressure column from a pump B, at the moment, the opening ratio of the pump A to the pump B is 95:5, the flow rate is 5.0+/-0.5L/min, and the eluent of 160-180 min is collected to obtain a collection liquid B;
s6, carrying out nanofiltration concentration on the collection liquid B by using a nanofiltration membrane of 300D, controlling the temperature below 18 ℃, and concentrating to a volume of 1L to obtain nanofiltration liquid A;
s7, diluting and stirring the nanofiltration solution A with 300L of pure water to obtain a feed liquid B;
s8, re-balancing the C18 high pressure column in S5 with 0.1wt% TFA and 1wt% acetonitrile, wherein 0.1wt% TFA is pumped into the C18 high pressure column from a pump A, and 1wt% acetonitrile is pumped into the C18 high pressure column from a pump B, and the opening ratio of the pump A to the pump B is 90:10, the balance flow rate is 5.0+/-0.5L/min, and the balance time is 30min;
s9, feeding the feed liquid B into a column, wherein the flow rate of the column is 5.0+/-0.5L/min, and performing top washing with 80-90L of 1wt% acetonitrile, and the flow rate of the top washing is 5.0+/-0.5L/min;
s10, eluting the C18 high-pressure column subjected to top washing by using 0.1wt% of TFA and 1wt% of acetonitrile, wherein 0.1wt% of TFA is pumped into the CA18 high-pressure column from a pump A, 1wt% of acetonitrile is pumped into the C18 high-pressure column from a pump B, the opening ratio of the pump A to the pump B is 70:30, and collecting eluent at a flow rate of 5.0+/-0.5L/min for 200-230 min to obtain a collection liquid C;
s11, carrying out nanofiltration concentration on the collection liquid C by using a nanofiltration membrane of 300D, controlling the temperature below 18 ℃, and concentrating to a volume of 1L to obtain nanofiltration liquid B;
s12, freeze-drying the nanofiltration liquid B, wherein the freeze-drying conditions are as follows: pre-freezing at-70 deg.c for 2 hr and freeze drying at 0 deg.c for 60 hr to obtain 14g of dewatered daptomycin freeze dried powder with purity of 99.5%.
Comparative example 1
The difference from example 1 is that: in S3 to S5, the packing of the C18 high pressure column was replaced with a strong base type Q-F packing (Q Focuse 6BB available from Wuhan Hui research science Co., ltd.) and equilibrated and eluted with 0.12mol/L aqueous ammonium chloride solution and 1wt% acetonitrile, respectively, wherein 0.12mol/L aqueous ammonium chloride solution was pumped from pump A into the high pressure column and 1wt% acetonitrile was pumped from pump B into the high pressure column; and replacing the packing of the C18 high-pressure chromatographic column in S8 to S11 with C18-50 mu m, and respectively balancing and eluting with 0.02mol/L ammonium bicarbonate aqueous solution and 1wt% acetonitrile, wherein the 0.02mol/L ammonium bicarbonate aqueous solution is pumped into the C18 high-pressure chromatographic column from a pump A, and the 1wt% acetonitrile is pumped into the C18 high-pressure chromatographic column from a pump B, and the aperture ratio of the pump A to the pump B is 70:35. The purity of the obtained dehydrated daptomycin in the dehydrated daptomycin freeze-dried powder is detected to be about 92 percent.
Detection example 1
Based on S1 in example 1, daptomycin was subjected to destructive experiments in sodium phosphate buffers with different pH values (2, 4, 6, 8 and 10), and the obtained feed liquid A was subjected to dehydrated daptomycin content measurement, and the test results are shown in Table 1.
TABLE 1
Project | The content (%) | Content of dehydrated daptomycin in feed liquid A (%) |
pH=2 | 0.79% | 10.67% |
pH=4 | 0.79% | 11.45% |
pH=6 | 0.79% | 16.87% |
pH=8 | 0.79% | 14.55% |
pH=10 | 0.79% | 9.63% |
As can be seen from table 1, the content of dehydrated daptomycin in the feed liquid a obtained by the destructive experiment was significantly increased to 16.87% when the pH of the sodium phosphate buffer was 6.
Detection example 2
The daptomycin feed liquid and the dehydrated daptomycin freeze-dried powder in the embodiment 1 are respectively subjected to liquid phase spectrum detection, and the detection results are shown in fig. 1 and 2.
As can be seen from fig. 1, the chromatographic peak corresponding to daptomycin in the daptomycin feed liquid is significantly higher than the chromatographic peak corresponding to dehydrated daptomycin, and the separation degree of the two is high; the figure 2 shows that the chromatographic peak corresponding to the dehydrated daptomycin in the feed liquid is remarkably higher than the chromatographic peak corresponding to Yu Da daptomycin, which indicates that the separation and purification method of the dehydrated daptomycin provided by the invention can effectively separate the dehydrated daptomycin from the daptomycin feed liquid.
Detection example 3
The purity of the dehydrated daptomycin in the collection liquid B and the purity of the collection liquid C in the example 1 are respectively detected, and the detection result shows that the purity of the dehydrated daptomycin in the collection liquid B is improved from 16.87% to 86.72%, and the purity of the dehydrated daptomycin in the collection liquid C is improved from 86.72% to more than 98%.
In summary, the separation and purification method of the dehydrated daptomycin and the application thereof provided by the invention can effectively promote the dehydration of the daptomycin in the daptomycin feed liquid by carrying out destructive experiments on the daptomycin feed liquid so as to improve the content of the dehydrated daptomycin in the feed liquid A; the method has the advantages that the combination of the phosphate solution with the mobile phase of 1wt% acetonitrile and the combination of the TFA with the mobile phase of 1wt% acetonitrile are used for eluting the dehydrated daptomycin respectively, so that the retention capacity of the C18 filler can be effectively improved, the dehydrated daptomycin is prevented from being further degraded in the purification process, and the purity of the dehydrated daptomycin freeze-dried powder of a final product is improved to 99%.
The foregoing description is only illustrative of the present invention and is not intended to limit the scope of the invention, and all equivalent changes made by the specification and drawings of the present invention, or direct or indirect application in the relevant art, are included in the scope of the present invention.
Claims (6)
1. The separation and purification method of the dehydrated daptomycin is characterized by comprising the following steps:
s1, carrying out destructive experiments on daptomycin feed liquid at 55-60 ℃ for more than 10 hours to obtain feed liquid A, and regulating the pH value of the feed liquid A to 6.0-6.5;
s2, carrying out C18 high-pressure column chromatography on the feed liquid A, wherein a mobile phase comprises a mobile phase A and a mobile phase B, the mobile phase A is 0.1wt% of phosphate solution, the mobile phase B is 1wt% of acetonitrile, the opening ratio of an A pump corresponding to the mobile phase A to a B pump corresponding to the mobile phase B is 95:5, and eluent with the collection time of 160-180 min is collected to obtain a collection liquid B;
s3, carrying out nanofiltration on the collected liquid B;
s4, performing C18 high-pressure column chromatography on the collected liquid B after nanofiltration, wherein a mobile phase comprises a mobile phase C and a mobile phase D, the mobile phase C is 0.1wt% of TFA, the mobile phase D is 1wt% of acetonitrile, the opening ratio of the pump A corresponding to the mobile phase C to the pump B corresponding to the mobile phase D is 70:30, and collecting eluent with the collection time of 200-230 min to obtain a collected liquid C;
s5, carrying out nanofiltration on the collecting liquid C;
s6, freeze-drying the nanofiltration collected liquid C to obtain dehydrated daptomycin freeze-dried powder with the purity of more than or equal to 99%;
wherein the packing of the C18 high-pressure column isC18。
2. The method for separating and purifying dehydrated daptomycin according to claim 1, wherein the destructive testing is performed under the condition of heating at 60 ℃ for 12 hours.
3. The method for separating and purifying dehydrated daptomycin according to claim 1, wherein the destructive test is as follows: the daptomycin feed solution was mixed in phosphate buffer at ph=6 and subjected to an experiment at 60 ℃ for 12 hours to obtain feed solution a containing 16.87% of dehydrated daptomycin.
4. The method for separating and purifying dehydrated daptomycin according to claim 1, wherein in S2, the flow rate of mobile phase A and mobile phase B is 5.0.+ -. 0.5L/min.
5. The method for separating and purifying dehydrated daptomycin according to claim 1, wherein in S4, the flow rate of mobile phase C and mobile phase D is 5.0.+ -. 0.5L/min.
6. Use of anhydro-daptomycin prepared by the method for isolation and purification of anhydro-daptomycin of any one of claims 1 to 5 in the preparation or as at least one of an anhydro-daptomycin standard, a control, a calibrator, and a quality control.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111247044.0A CN113866330B (en) | 2021-10-26 | 2021-10-26 | Separation and purification method and application of dehydrated daptomycin |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111247044.0A CN113866330B (en) | 2021-10-26 | 2021-10-26 | Separation and purification method and application of dehydrated daptomycin |
Publications (2)
Publication Number | Publication Date |
---|---|
CN113866330A CN113866330A (en) | 2021-12-31 |
CN113866330B true CN113866330B (en) | 2023-08-22 |
Family
ID=78997697
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202111247044.0A Active CN113866330B (en) | 2021-10-26 | 2021-10-26 | Separation and purification method and application of dehydrated daptomycin |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN113866330B (en) |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5912226A (en) * | 1987-06-10 | 1999-06-15 | Eli Lilly And Company | Anhydro- and isomer-A-21978C cyclic peptides |
CN103724400A (en) * | 2012-10-10 | 2014-04-16 | 北大方正集团有限公司 | Method for separating and purifying dehydrated daptomycin |
CN106866790A (en) * | 2015-12-11 | 2017-06-20 | 北大方正集团有限公司 | The preparation method of Daptomycin RS-5/6, RS-7 and RS-7a/7b impurity |
CN112684043A (en) * | 2020-12-16 | 2021-04-20 | 南京健友生化制药股份有限公司 | Method for detecting daptomycin related substances |
CN113004373A (en) * | 2019-12-19 | 2021-06-22 | 鲁南制药集团股份有限公司 | Daptomycin purification method |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6696412B1 (en) * | 2000-01-20 | 2004-02-24 | Cubist Pharmaceuticals, Inc. | High purity lipopeptides, Lipopeptide micelles and processes for preparing same |
-
2021
- 2021-10-26 CN CN202111247044.0A patent/CN113866330B/en active Active
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5912226A (en) * | 1987-06-10 | 1999-06-15 | Eli Lilly And Company | Anhydro- and isomer-A-21978C cyclic peptides |
CN103724400A (en) * | 2012-10-10 | 2014-04-16 | 北大方正集团有限公司 | Method for separating and purifying dehydrated daptomycin |
CN106866790A (en) * | 2015-12-11 | 2017-06-20 | 北大方正集团有限公司 | The preparation method of Daptomycin RS-5/6, RS-7 and RS-7a/7b impurity |
CN113004373A (en) * | 2019-12-19 | 2021-06-22 | 鲁南制药集团股份有限公司 | Daptomycin purification method |
CN112684043A (en) * | 2020-12-16 | 2021-04-20 | 南京健友生化制药股份有限公司 | Method for detecting daptomycin related substances |
Non-Patent Citations (1)
Title |
---|
达托霉素在 不同酸碱条件下产生的杂质及其结构研究;张定丰等;中国抗生素杂志;第38卷(第10期);760-764 * |
Also Published As
Publication number | Publication date |
---|---|
CN113866330A (en) | 2021-12-31 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2018087207A (en) | Chromatographic method for isolating and purifying high-purity recombined human serum albumin | |
US4872987A (en) | Process for separating and producing chlorogenic acid | |
EP3064214A1 (en) | Separation and purification method for vancomycin hydrochloride of high purity | |
CN113866330B (en) | Separation and purification method and application of dehydrated daptomycin | |
CN105732738A (en) | Tobramycin purification method | |
CN113429462B (en) | Purification method of high-purity vancomycin | |
CN112979785B (en) | Method for preparing high-purity lactoferrin | |
CN106568620A (en) | Preparation method of high purity samples of vancomycin hydrochloride impurities 11, 13, and 15 | |
CN110862427B (en) | Purification method of gentamicin C1a | |
CN113801201A (en) | Preparation method of caspofungin acetate impurity B | |
CN107698676B (en) | Method for extracting and preparing high-purity menotrophin | |
CN109705174B (en) | Method for extracting tobramycin | |
CN107033236A (en) | A kind of Mixed-Modechromatography method that human serum albumin is separated from yeast fermentation broth | |
CN111983075A (en) | Method for detecting rasagiline and enantiomer thereof | |
CN108059603B (en) | Refining process of Voglibose impurity N-methyl Jinggang enzyme alcohol amine | |
CN116903703A (en) | Purification method of daptomycin | |
CN110330541B (en) | Method for separating 5 '-guanine nucleotide and 5' -cytosine nucleotide | |
CN116425810B (en) | Purification method of 3-fucosyllactose in mixed solution | |
CN113913415A (en) | Method for separating human urinary kallidinogenase and thrombin regulatory protein | |
CN113563424A (en) | Daptomycin purification method | |
CN114112612A (en) | Separation and purification method of teicoplanin I5 impurity and application thereof | |
CN114276416B (en) | Preparation process of caspofungin acetate impurity | |
CN113637050B (en) | Decoloration method of teicoplanin | |
CN111138524B (en) | Method for separating and purifying recombinant human lactoferrin with low iron saturation from genetically engineered rice seeds | |
CN109988211B (en) | Purification method of glycochenodeoxycholic acid sodium salt |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |