CN113549089A - Method for purifying latamoxef sodium - Google Patents
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- CN113549089A CN113549089A CN202110741803.2A CN202110741803A CN113549089A CN 113549089 A CN113549089 A CN 113549089A CN 202110741803 A CN202110741803 A CN 202110741803A CN 113549089 A CN113549089 A CN 113549089A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D505/00—Heterocyclic compounds containing 5-oxa-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. oxacephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D505/10—Heterocyclic compounds containing 5-oxa-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. oxacephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring with a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2
- C07D505/12—Heterocyclic compounds containing 5-oxa-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. oxacephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring with a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2 substituted in position 7
- C07D505/14—Heterocyclic compounds containing 5-oxa-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. oxacephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring with a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2 substituted in position 7 with hetero atoms directly attached in position 7
- C07D505/16—Nitrogen atoms
- C07D505/18—Nitrogen atoms further acylated by radicals derived from carboxylic acids or by nitrogen or sulfur analogues thereof
- C07D505/20—Nitrogen atoms further acylated by radicals derived from carboxylic acids or by nitrogen or sulfur analogues thereof with the acylating radicals further substituted by hetero atoms or by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D505/00—Heterocyclic compounds containing 5-oxa-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. oxacephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
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Abstract
The invention discloses a method for purifying latamoxef sodium, which comprises the following steps: (1) mixing latamoxef sodium with ethanol, filtering to obtain a precipitate, drying the precipitate, mixing with sephadex, loading into a column, and eluting by adopting a sodium carbonate aqueous solution with the pH value of 7.0-8.0 to obtain an eluent; (2) drying the eluent, mixing the dried eluent with macroporous adsorption resin, loading the mixture into a column, eluting with ethyl acetate, then eluting with a methanol solution with the pH value of 5.0-6.0, collecting the eluent which takes the methanol solution as an eluent, concentrating the eluent, and drying to obtain a pure latamoxef sodium product; the macroporous adsorption resin is selected from at least one of S-8, NKA-9, ASD-17 and AB-8. The method comprehensively adopts the modes of ethanol soaking, sephadex elution, macroporous resin elution and the like, can effectively remove main impurities in the latamoxef sodium product, has excellent purification effect, reduces the impurity content by at least more than 70 percent, and improves the safety of the product.
Description
Technical Field
The invention belongs to the technical field of medicine processing, and particularly relates to a method for purifying latamoxef sodium.
Background
Latamoxef sodium, alias latamoxef disodium salt, oxacephamycin disodium and the like, and the molecular formula is as follows: c20H18N6Na2O9S, chemical name (6R, 7R) -7- [ 2-carboxy-2- (4-hydroxyphenyl) acetamido]-7-methoxy-3- [ (1-methyl-1H-tetrazol-5-yl) thiomethyl]-8-oxo-5-oxa-1-azabicyclo [4.2.0]The structural formula of the octa-2-dilute-2-formic acid disodium salt is shown in the specification
Latamoxef sodium is third generation cephalosporin antibiotics used for allergySepticemia caused by gram-negative bacilli, lower respiratory system infection, celiac and biliary system infection, complicated urinary tract infection, severe skin soft tissue infection and the like.
Latamoxef sodium is unstable in property, and easily generates various impurities in the synthesis or storage process, wherein the main impurities comprise decarboxylated latamoxef, mercaptomethyltetrazole, latamoxef lactone, latamoxef methyl ester, latamoxef polymer and the like. The presence of impurities directly affects the safety of the drug for the patient, wherein the polymer impurities are the main cause of allergic reactions when the patient takes latamoxef sodium. Therefore, strict purification treatment of latamoxef sodium is necessary.
At present, there are few reports on methods for purifying latamoxef sodium products, most of which are methods for synthesizing latamoxef sodium, and there is no method for further purification when the amount and content of impurities during synthesis or storage is increased. Patent document CN105037394A discloses a preparation method of high-purity latamoxef sodium. The method comprises the following steps: subjecting a compound I to deprotection reaction, washing with water to remove impurities and alkali washing in an organic solvent to obtain an aqueous solution of latamoxef sodium, degrading to remove impurities and adjusting acid to obtain a crude latamoxef monosodium salt aqueous solution, and extracting to remove impurities to obtain a fine latamoxef monosodium salt aqueous solution; acidifying the refined monosodium salt aqueous solution, extracting with an organic solvent, removing water from an organic layer, distilling to recover the solvent, and crystallizing to obtain refined solid latamoxef acid; and (3) adjusting the alkali of the refined solid latamoxef acid into a sodium salt aqueous solution, decoloring and freeze-drying to obtain the high-purity latamoxef sodium. The method controls the purity of the product in the synthesis process, mainly reduces the impurity content by methods such as organic solvent extraction, crystallization and the like, and does not purify the latamoxef sodium product which has changed in quality in the synthesis and storage processes.
In summary, the method for further purifying the latamoxef sodium sample containing various impurities, particularly polymer impurities, is significant, can supplement related technical blank, and can effectively improve the safety of the product.
Disclosure of Invention
In view of the defects of the prior art, the invention provides a method for purifying latamoxef sodium.
The technical scheme of the invention mainly comprises the following contents:
a method for purifying latamoxef sodium, which comprises the following steps:
(1) mixing latamoxef sodium with ethanol, filtering to obtain a precipitate, drying the precipitate, mixing with sephadex, loading into a column, and eluting by adopting a sodium carbonate aqueous solution with the pH value of 7.0-8.0 to obtain an eluent; firstly, removing partial impurities by using ethanol, and controlling the adsorption effect of each component in gel by using sodium carbonate and pH thereof to realize primary purification; the pH can be adjusted by acetic acid or sodium hydroxide.
(2) Drying the eluent, mixing the dried eluent with macroporous adsorption resin, loading the mixture into a column, eluting with ethyl acetate, then eluting with a methanol solution with the pH value of 5.0-6.0, collecting the eluent which takes the methanol solution as an eluent, concentrating the eluent, and drying to obtain a pure latamoxef sodium product; the resin is at least one selected from S-8, NKA-9, ASD-17 and AB-8. Tests show that the purification effects of different types of resins on products are inconsistent, and the test screening proves that the types of the resins can obtain the optimal purification effect.
Preferably, the mixing mass ratio of the dried precipitate to the sephadex is 1: 10 to 20.
Preferably, the Sephadex gel is Sephadex G-25.
Preferably, in step (1), at least 10mL of ethanol is mixed per g of latamoxef sodium.
Preferably, in the step (2), the mixing mass ratio of the dried eluent to the macroporous adsorption resin is 1: 10 to 20.
Preferably, in step (2), the volume of the ethyl acetate is at least 10 times that of the macroporous adsorption resin, and the volume of the methanol solution is at least 10 times that of the macroporous adsorption resin.
Preferably, in the step (2), the concentration of the sodium carbonate aqueous solution is 0.01-0.05M.
Preferably, in the step (2), the mass concentration of the methanol solution is 10-90%.
Preferably, in step (1), the mixing time of latamoxef sodium and ethanol is at least 30 min. Standing or stirring for about 30min, and standing for a prolonged period;
preferably, the macroporous adsorption resin is an equal volume mixture of S-8 and NKA-9.
The invention has the following effects:
at present, the prior art mainly controls the content of impurities in the synthesis process, and the control of polymer impurities is not reported. The method can effectively remove main impurities in the latamoxef sodium product, has a good purification effect on the product, obviously reduces the impurity content, particularly realizes effective control on polymer impurities, improves the safety of the product, and makes up the technical blank in the field in the aspect of polymer impurity research.
The scheme comprehensively adopts modes of ethanol soaking, sephadex elution, macroporous resin elution and the like, so that various impurities generated in the synthesis and storage processes are effectively removed, and the impurity content is reduced by at least more than 70%.
Detailed Description
In order to better understand the technical content of the invention, specific examples are provided below to further illustrate the invention.
Example 1
A method for purifying latamoxef sodium, which comprises the following steps:
(1) stirring and mixing latamoxef sodium and ethanol at 50rpm for 30min according to the feed-liquid ratio of 1G/10mL, filtering to obtain precipitate, drying the precipitate, mixing with Sephadex G-25 in a column (mass ratio of 1: 10), and eluting with 0.01M sodium carbonate aqueous solution with pH of 7.0 to obtain eluent;
(2) drying the eluent, mixing the eluent with S-8 type macroporous adsorption resin, loading the mixture into a column (mass ratio is 1: 10), eluting by ethyl acetate (the volume of the eluent is 10 times that of the macroporous adsorption resin), then eluting by 90% methanol solution with pH value of 5.0 (the volume of the eluent is 10 times that of the macroporous adsorption resin), collecting the eluent obtained by using the methanol solution as the eluent, concentrating the eluent, and drying to obtain a pure latamoxef sodium product (the water content is less than 5%).
Example 2
A method for purifying latamoxef sodium, which comprises the following steps:
(1) stirring and mixing latamoxef sodium and ethanol at 50rpm for 30min according to the feed-liquid ratio of 1G/10mL, filtering to obtain precipitate, drying the precipitate, mixing with Sephadex G-25 in a column (mass ratio of 1: 20), and eluting with 0.01M sodium carbonate aqueous solution with pH of 7.0 to obtain eluent;
(2) drying the eluent, mixing the eluent with S-8 type macroporous adsorption resin, loading the mixture into a column (mass ratio is 1: 20), eluting by ethyl acetate (the volume of the eluent is 10 times that of the macroporous adsorption resin), then eluting by 90% methanol solution with pH value of 5.0 (the volume of the eluent is 10 times that of the macroporous adsorption resin), collecting the eluent obtained by using the methanol solution as the eluent, concentrating the eluent, and drying to obtain a pure latamoxef sodium product (the water content is less than 5%).
Example 3
A method for purifying latamoxef sodium, which comprises the following steps:
(1) stirring and mixing latamoxef sodium and ethanol at 50rpm for 30min according to the feed-liquid ratio of 1G/10mL, filtering to obtain precipitate, drying the precipitate, mixing with Sephadex G-25 in a column (mass ratio of 1: 10), and eluting with 0.01M sodium carbonate aqueous solution with pH of 7.0 to obtain eluent;
(2) drying the eluent, mixing the eluent with NKA-9 type macroporous adsorption resin, loading the mixture into a column (mass ratio is 1: 10), eluting by ethyl acetate (the volume of the eluent is 10 times that of the macroporous adsorption resin), eluting by 90% methanol solution with pH5.0 (the volume of the eluent is 10 times that of the macroporous adsorption resin), collecting the eluent which takes the methanol solution as eluent, concentrating the eluent, and drying to obtain a pure latamoxef sodium product (the water content is less than 5%).
Example 4
A method for purifying latamoxef sodium, which comprises the following steps:
(1) stirring and mixing latamoxef sodium and ethanol at 50rpm for 30min according to the feed-liquid ratio of 1G/10mL, filtering to obtain precipitate, drying the precipitate, mixing with Sephadex G-25 in a column (mass ratio of 1: 10), and eluting with 0.01M sodium carbonate aqueous solution with pH of 8.0 to obtain eluent;
(2) drying the eluent, mixing the eluent with S-8 type macroporous adsorption resin, loading the mixture into a column (mass ratio is 1: 10), eluting by ethyl acetate (the volume of the eluent is 10 times that of the macroporous adsorption resin), then eluting by 90% methanol solution with pH of 6.0 (the volume of the eluent is 10 times that of the macroporous adsorption resin), collecting the eluent which takes the methanol solution as the eluent, concentrating the eluent, and drying to obtain a pure latamoxef sodium product (the water content is less than 5%).
Example 5
A method for purifying latamoxef sodium, which comprises the following steps:
(1) stirring and mixing latamoxef sodium and ethanol at 50rpm for 30min according to the feed-liquid ratio of 1G/10mL, filtering to obtain precipitate, drying the precipitate, mixing with Sephadex G-25 in a column (mass ratio of 1: 10), and eluting with 0.01M sodium carbonate aqueous solution with pH of 7.0 to obtain eluent;
(2) drying the eluent, mixing the eluent with S-8 type macroporous adsorption resin, loading the mixture into a column (mass ratio is 1: 10), eluting by ethyl acetate (the volume of the eluent is 10 times that of the macroporous adsorption resin), then eluting by 10% methanol solution with pH5.0 (the volume of the eluent is 10 times that of the macroporous adsorption resin), collecting the eluent which takes the methanol solution as eluent, concentrating the eluent, and drying to obtain a pure latamoxef sodium product (the water content is less than 5%).
Example 6
A method for purifying latamoxef sodium, which comprises the following steps:
(1) stirring and mixing latamoxef sodium and ethanol at 50rpm for 30min according to the feed-liquid ratio of 1G/10mL, filtering to obtain precipitate, drying the precipitate, mixing with Sephadex G-25 in a column (mass ratio of 1: 10), and eluting with 0.05M sodium carbonate aqueous solution with pH of 7.0 to obtain eluent;
(2) drying the eluent, mixing the eluent with S-8 type macroporous adsorption resin, loading the mixture into a column (mass ratio is 1: 10), eluting by ethyl acetate (the volume of the eluent is 10 times that of the macroporous adsorption resin), then eluting by 90% methanol solution with pH value of 5.0 (the volume of the eluent is 10 times that of the macroporous adsorption resin), collecting the eluent obtained by using the methanol solution as the eluent, concentrating the eluent, and drying to obtain a pure latamoxef sodium product (the water content is less than 5%).
Example 7
A method for purifying latamoxef sodium, which comprises the following steps:
(1) stirring and mixing latamoxef sodium and ethanol at 50rpm for 30min according to the feed-liquid ratio of 1G/10mL, filtering to obtain precipitate, drying the precipitate, mixing with Sephadex G-25 in a column (mass ratio of 1: 10), and eluting with 0.1M sodium carbonate aqueous solution with pH of 7.0 to obtain eluent;
(2) drying the eluent, mixing the eluent with S-8 type macroporous adsorption resin, loading the mixture into a column (mass ratio is 1: 10), eluting by ethyl acetate (the volume of the eluent is 10 times that of the macroporous adsorption resin), then eluting by 90% methanol solution with pH value of 5.0 (the volume of the eluent is 10 times that of the macroporous adsorption resin), collecting the eluent obtained by using the methanol solution as the eluent, concentrating the eluent, and drying to obtain a pure latamoxef sodium product (the water content is less than 5%).
Example 8
A method for purifying latamoxef sodium, which comprises the following steps:
(1) stirring and mixing latamoxef sodium and ethanol at 50rpm for 30min according to the feed-liquid ratio of 1G/10mL, filtering to obtain precipitate, drying the precipitate, mixing with Sephadex G-25 in a column (mass ratio of 1: 10), and eluting with 0.01M sodium carbonate aqueous solution with pH of 7.0 to obtain eluent;
(2) drying the eluent, mixing the eluent with combined macroporous adsorption resin (the mass ratio is 1: 10) with S-8, NKA-9 and the like, loading the mixture into a column (the mass ratio is 1: 10), eluting the column with ethyl acetate (the volume of the eluent is 10 times that of the macroporous adsorption resin), eluting the column with 90% methanol solution (the volume of the eluent is 10 times that of the macroporous adsorption resin) with pH5.0, collecting the eluent with the methanol solution as an eluent, concentrating the eluent, and drying the eluent to obtain a pure latamoxef sodium product (the water content is less than 5%).
Comparative example 1
A method for purifying latamoxef sodium, which comprises the following steps:
(1) stirring and mixing latamoxef sodium and ethanol at 50rpm for 30min according to the feed-liquid ratio of 1G/10mL, filtering to obtain precipitate, drying the precipitate, mixing with Sephadex G-25 in a column (mass ratio of 1: 10), and eluting with 0.01M sodium carbonate aqueous solution with pH of 5.0 to obtain eluent;
(2) drying the eluent, mixing the eluent with S-8 type macroporous adsorption resin, loading the mixture into a column (mass ratio is 1: 10), eluting by ethyl acetate (the volume of the eluent is 10 times that of the macroporous adsorption resin), then eluting by 90% methanol solution with pH7.0 (the volume of the eluent is 10 times that of the macroporous adsorption resin), collecting the eluent which takes the methanol solution as the eluent, concentrating the eluent, and drying to obtain latamoxef sodium (the water content is less than 5%).
Comparative example 2
A method for purifying latamoxef sodium, which comprises the following steps:
(1) stirring and mixing latamoxef sodium and ethanol at 50rpm for 30min according to the feed-liquid ratio of 1G/10mL, filtering to obtain precipitate, drying the precipitate, mixing with Sephadex G-25 in a column (mass ratio of 1: 10), and eluting with water of pH7.0 to obtain eluent;
(2) drying the eluent, mixing the eluent with S-8 type macroporous adsorption resin, loading the mixture into a column (mass ratio is 1: 10), eluting by ethyl acetate (the volume of the eluent is 10 times that of the macroporous adsorption resin), then eluting by 90% methanol solution with pH value of 5.0 (the volume of the eluent is 10 times that of the macroporous adsorption resin), collecting the eluent which takes the methanol solution as the eluent, concentrating the eluent, and drying to obtain latamoxef sodium (the water content is less than 5%).
Comparative example 3
A method for purifying latamoxef sodium, which comprises the following steps:
(1) stirring and mixing latamoxef sodium and ethanol at 50rpm for 30min according to the feed-liquid ratio of 1G/10mL, filtering to obtain precipitate, drying the precipitate, mixing with Sephadex G-25 in a column (mass ratio of 1: 10), and eluting with sodium carbonate aqueous solution with pH of 7.0 to obtain eluent;
(2) drying the eluent, mixing the eluent with D101 type macroporous adsorption resin, loading the mixture into a column (mass ratio is 1: 10), eluting by ethyl acetate (the volume of the eluent is 10 times that of the macroporous adsorption resin), then eluting by 90% methanol solution with pH5.0 (the volume of the eluent is 10 times that of the macroporous adsorption resin), collecting the eluent which takes the methanol solution as the eluent, concentrating the eluent, and drying to obtain latamoxef sodium (the water content is less than 5%).
Comparative example 4
A method for purifying latamoxef sodium, which comprises the following steps:
mixing latamoxef sodium with S-8 type macroporous adsorbent resin, loading into column (mass ratio of 1: 10), eluting with ethyl acetate (eluent volume is 10 times of macroporous adsorbent resin), eluting with 90% methanol solution (pH 5.0 is 10 times of macroporous adsorbent resin), collecting eluent with methanol solution as eluent, concentrating the eluent, and drying to obtain latamoxef sodium (water content is less than 5%).
Comparative example 5
A method for purifying latamoxef sodium, which comprises the following steps:
(1) stirring and mixing latamoxef sodium and ethanol at 50rpm for 30min according to the feed-liquid ratio of 1G/10mL, filtering to obtain precipitate, drying the precipitate, mixing with Sephadex G-25 in a column (mass ratio of 1: 10), and eluting with 0.01M sodium carbonate aqueous solution with pH of 7.0 to obtain eluent;
(2) drying the eluent, mixing with S-8 type macroporous adsorbent resin, loading into column (mass ratio of 1: 10), eluting with 90% methanol solution (pH 5.0) (the volume of the eluent is 10 times of that of the macroporous adsorbent resin), collecting eluent, concentrating the eluent, and drying to obtain latamoxef sodium (the water content is less than 5%).
The conditions of the examples and comparative examples are summarized, and the results are as follows:
TABLE 1
Experimental example: impurity detection
And detecting impurities by adopting a high performance liquid phase.
Chromatographic conditions are as follows:
a chromatographic column: agilent ZORBAX SB-CN chromatography column (250 mm. times.4.6 mm, 5 μm);
mobile phase A: 0.01mol/L ammonium acetate solution (pH6.2) -methanol (60: 40, V/V);
mobile phase B: 0.025mol/L ammonium acetate solution-acetonitrile (90: 10, V/V);
sample concentration: 1.0mg/ml
Flow rate: 0.6 mL/min;
detection wavelength: 254 nm.
Sample introduction amount: 10 uL.
Temperature injection: at 30 ℃.
And (3) an elution mode: gradient elution;
elution procedure:
TABLE 2
| Time/min | Mobile phase A: mobile phase B |
| 0 | 78:22 |
| 10 | 55:45 |
| 16 | 30:70 |
| 20 | 30:70 |
| 25 | 45:55 |
| 30 | 78:22 |
The dimer impurity is detected by referring to chromatographic conditions of Liuxiayu 'high performance molecular exclusion chromatography for analyzing impurities such as polymer in latamoxef sodium'.
TABLE 3
Note: calculated by an external standard method, n is 3.
The results show that:
the impurity levels in the examples were significantly lower than those in the pre-purification and comparative examples. Compared with the embodiment 1, the embodiment 8 adopts the combined macroporous resin, so that the decarboxylated latamoxef content can be effectively reduced. Comparing example 1 with comparative example 1, it was found that the contents of decarboxylated latamoxef, mercaptomethyltetrazole and latamoxef dimer were effectively reduced by controlling the pH of the eluents in step (1) and step (2). The results of comparative example 1 and comparative example 2 show that the addition of sodium carbonate to the eluent is advantageous for controlling the decarboxylated latamoxef and latamoxef dimer content. The results of comparative example 1 and comparative example 3 show that the effect of using the resin of S-8 type is superior to that of D101. Comparing the results of example 1 and comparative example 4, it was found that the ethanol soaking and the elution of the sephadex performed in step (1) are advantageous for controlling the respective impurity contents. Comparative example results of example 1 and comparative example 5 it was found necessary to elute with ethyl acetate before eluting with methanol water in step (2).
The above description is only exemplary of the present invention and should not be taken as limiting the invention, as any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. A method for purifying latamoxef sodium, which is characterized by comprising the following steps:
(1) mixing latamoxef sodium with ethanol, filtering to obtain a precipitate, drying the precipitate, mixing with sephadex, loading into a column, and eluting by adopting a sodium carbonate aqueous solution with the pH value of 7.0-8.0 to obtain an eluent;
(2) drying the eluent, mixing the dried eluent with macroporous adsorption resin, loading the mixture into a column, eluting with ethyl acetate, then eluting with a methanol solution with the pH value of 5.0-6.0, collecting the eluent which takes the methanol solution as an eluent, concentrating the eluent, and drying to obtain a pure latamoxef sodium product;
the large adsorption resin is at least one selected from S-8, NKA-9, ASD-17 and AB-8.
2. The method for purifying latamoxef sodium as claimed in claim 1, wherein in step (1), the mixing mass ratio of the dried precipitate to the sephadex gel is 1: 10 to 20.
3. The method for purifying latamoxef sodium as claimed in claim 1, wherein said Sephadex is Sephadex G-25.
4. The process for the purification of latamoxef sodium as claimed in claim 1, characterized in that in step (1) at least 10mL of ethanol is mixed per g of latamoxef sodium.
5. The method for purifying latamoxef sodium as claimed in claim 1, wherein in step (2), the mixing mass ratio of the dried eluent to the macroporous adsorbent resin is 1: 10 to 20.
6. The process for purifying latamoxef sodium as claimed in claim 1, wherein in step (2), the volume of ethyl acetate is at least 10 times that of the macroporous adsorbent resin, and the volume of the methanol solution is at least 10 times that of the macroporous adsorbent resin.
7. The method for purifying latamoxef sodium as claimed in claim 1, wherein in step (2), the concentration of the aqueous solution of sodium carbonate is 0.01-0.05M.
8. The method for purifying latamoxef sodium as claimed in claim 1, wherein in step (2), the mass concentration of the methanol solution is 10-90%.
9. The process for the purification of latamoxef sodium as claimed in claim 1, characterized in that in step (1) the mixing time of latamoxef sodium with ethanol is at least 30 min.
10. The method for purifying latamoxef sodium as claimed in claim 1, wherein the macroporous adsorbent resin is an equal volume mixture of S-8 and NKA-9.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| USH328H (en) * | 1984-02-02 | 1987-09-01 | Shionogi & Co., Ltd. | Purification of cephalosporins |
| CN104497011A (en) * | 2015-01-14 | 2015-04-08 | 芦红代 | Latamoxef sodium preparation method |
| CN111983067A (en) * | 2020-08-05 | 2020-11-24 | 河北省药品医疗器械检验研究院 | Detection method and detection method for on-line identification of latamoxef sodium polymer for injection |
-
2021
- 2021-06-30 CN CN202110741803.2A patent/CN113549089A/en active Pending
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| USH328H (en) * | 1984-02-02 | 1987-09-01 | Shionogi & Co., Ltd. | Purification of cephalosporins |
| CN104497011A (en) * | 2015-01-14 | 2015-04-08 | 芦红代 | Latamoxef sodium preparation method |
| CN111983067A (en) * | 2020-08-05 | 2020-11-24 | 河北省药品医疗器械检验研究院 | Detection method and detection method for on-line identification of latamoxef sodium polymer for injection |
Non-Patent Citations (2)
| Title |
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| 刘晓瑜等: "高效分子排阻色谱法分析拉氧头孢钠中的聚合物等杂质", 《中国药师》 * |
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