CN117417389A - Purification method of clindamycin phosphate - Google Patents
Purification method of clindamycin phosphate Download PDFInfo
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- CN117417389A CN117417389A CN202311384141.3A CN202311384141A CN117417389A CN 117417389 A CN117417389 A CN 117417389A CN 202311384141 A CN202311384141 A CN 202311384141A CN 117417389 A CN117417389 A CN 117417389A
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- clindamycin phosphate
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- UFUVLHLTWXBHGZ-MGZQPHGTSA-N [(2r,3r,4s,5r,6r)-6-[(1s,2s)-2-chloro-1-[[(2s,4r)-1-methyl-4-propylpyrrolidine-2-carbonyl]amino]propyl]-4,5-dihydroxy-2-methylsulfanyloxan-3-yl] dihydrogen phosphate Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@H](C)Cl)[C@@H]1[C@H](O)[C@H](O)[C@@H](OP(O)(O)=O)[C@@H](SC)O1 UFUVLHLTWXBHGZ-MGZQPHGTSA-N 0.000 title claims abstract description 58
- 229960002291 clindamycin phosphate Drugs 0.000 title claims abstract description 58
- 238000000034 method Methods 0.000 title claims abstract description 24
- 238000000746 purification Methods 0.000 title claims abstract description 23
- 239000000047 product Substances 0.000 claims abstract description 27
- 238000001914 filtration Methods 0.000 claims abstract description 25
- 239000003960 organic solvent Substances 0.000 claims abstract description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 23
- 238000010438 heat treatment Methods 0.000 claims abstract description 20
- 238000003756 stirring Methods 0.000 claims abstract description 20
- 238000001816 cooling Methods 0.000 claims abstract description 18
- 239000012046 mixed solvent Substances 0.000 claims abstract description 18
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 14
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 12
- 239000003513 alkali Substances 0.000 claims abstract description 8
- 239000000706 filtrate Substances 0.000 claims abstract description 8
- 238000004090 dissolution Methods 0.000 claims abstract description 6
- 238000004537 pulping Methods 0.000 claims abstract description 6
- 238000001035 drying Methods 0.000 claims abstract description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 15
- 238000010009 beating Methods 0.000 claims description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- 238000001291 vacuum drying Methods 0.000 claims description 8
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical group [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
- 150000007529 inorganic bases Chemical class 0.000 claims description 4
- 150000007530 organic bases Chemical class 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- SUAKHGWARZSWIH-UHFFFAOYSA-N N,N‐diethylformamide Chemical compound CCN(CC)C=O SUAKHGWARZSWIH-UHFFFAOYSA-N 0.000 claims description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 2
- 239000011736 potassium bicarbonate Substances 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 235000011181 potassium carbonates Nutrition 0.000 claims description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 2
- 235000017550 sodium carbonate Nutrition 0.000 claims description 2
- 239000012535 impurity Substances 0.000 abstract description 18
- 239000003814 drug Substances 0.000 abstract description 4
- 238000002425 crystallisation Methods 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract description 3
- 230000008025 crystallization Effects 0.000 abstract description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- KDLRVYVGXIQJDK-AWPVFWJPSA-N clindamycin Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@H](C)Cl)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 KDLRVYVGXIQJDK-AWPVFWJPSA-N 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 239000007791 liquid phase Substances 0.000 description 4
- 229960002227 clindamycin Drugs 0.000 description 3
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 229910021641 deionized water Inorganic materials 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229960001200 clindamycin hydrochloride Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 241001148471 unidentified anaerobic bacterium Species 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
- C07H1/06—Separation; Purification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/02—Acyclic radicals, not substituted by cyclic structures
- C07H15/14—Acyclic radicals, not substituted by cyclic structures attached to a sulfur, selenium or tellurium atom of a saccharide radical
- C07H15/16—Lincomycin; Derivatives thereof
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Crystallography & Structural Chemistry (AREA)
- Saccharide Compounds (AREA)
Abstract
A purification method of clindamycin phosphate belongs to the technical field of crude drug purification. The invention aims to solve the problems of low crystallization yield, low product purity and more impurities of the existing clindamycin phosphate. The method comprises the following steps: adding the crude clindamycin phosphate into a mixed solvent of an organic solvent I/water, controlling a certain temperature, heating, stirring and pulping for a certain time, cooling, and filtering to obtain a wet product; adding the wet product into a mixed solvent of an organic solvent II/water, adding a certain amount of organic alkali or inorganic alkali, heating for dissolution, decoloring by active carbon, filtering while the wet product is hot, cooling the filtrate to 8-10 ℃ in a gradient manner, crystallizing, filtering, and drying in vacuum to obtain the finished clindamycin phosphate. The finished clindamycin phosphate obtained by the method has the advantages of high purity, small content of other single impurities, good fluidity and difficult caking.
Description
Technical Field
The invention belongs to the technical field of crude drug purification, and particularly relates to a clindamycin phosphate purification method.
Background
Clindamycin phosphate is a semisynthetic antibiotic drug, chemical name: 6- (1-methyl-trans-4-propyl-L-2-pyrrolidinecarboxamido) -1-thio-7 (S) -chloro-6, 7, 8-trideoxy-L-threo-a-D-galacto Xin Binan glycoside-2-phosphate. In 1970, the Chinese medicine was marketed. Clindamycin phosphate has no antibacterial activity in vitro, and is rapidly hydrolyzed into clindamycin to exert pharmacological action after entering the body. The antibacterial spectrum, antibacterial activity and treatment effect of the antibacterial composition are the same as those of clindamycin, but the antibacterial composition has stronger ester solubility and penetrability than clindamycin, good absorption and high bone tissue concentration, and has strong antibacterial activity on gram-positive cocci and anaerobic bacteria. The common crystallization method of clindamycin phosphate comprises the steps of heating and dissolving crude clindamycin phosphate in ethanol and aqueous solution, decoloring, thermally filtering, rapidly cooling, crystallizing, filtering, washing and drying to obtain needle-like fine crystals, wherein the product has more impurities and low purity.
Disclosure of Invention
The invention aims to solve the problems of low crystallization yield, low product purity and more impurities of the existing clindamycin phosphate, and provides a purification method of clindamycin phosphate.
The purification method of clindamycin phosphate is specifically completed by the following steps:
1. adding the crude clindamycin phosphate into a mixed solvent of an organic solvent I/water, controlling a certain temperature, heating, stirring and pulping for a certain time, cooling, and filtering to obtain a wet product;
2. adding the wet product into a mixed solvent of an organic solvent II/water, adding a certain amount of organic alkali or inorganic alkali, heating for dissolution, decoloring by active carbon, filtering while the wet product is hot, cooling the filtrate to 8-10 ℃ in a gradient manner, crystallizing, filtering, and drying in vacuum to obtain a finished product, namely the purification method of clindamycin phosphate is completed.
The clindamycin phosphate has the structural formula:
the invention has the advantages that:
1. the invention has the advantages of strong process amplification adaptability, high product purity, less other impurities, uniform crystal dispersion, good fluidity and difficult caking;
2. the method has the advantages that the impurities and the content meet the internal control index, and the impurities are purified and qualified.
Detailed Description
The first embodiment is as follows: the purification method of clindamycin phosphate in the embodiment is specifically completed by the following steps:
1. adding the crude clindamycin phosphate into a mixed solvent of an organic solvent I/water, controlling a certain temperature, heating, stirring and pulping for a certain time, cooling, and filtering to obtain a wet product;
2. adding the wet product into a mixed solvent of an organic solvent II/water, adding a certain amount of organic alkali or inorganic alkali, heating for dissolution, decoloring by active carbon, filtering while the wet product is hot, cooling the filtrate to 8-10 ℃ in a gradient manner, crystallizing, filtering, and drying in vacuum to obtain a finished product, namely the purification method of clindamycin phosphate is completed.
The second embodiment is as follows: the present embodiment differs from the specific embodiment in that: the organic solvent I in the first step is N, N-dimethylformamide, N-dimethylacetamide or N, N-diethylformamide. The other steps are the same as in the first embodiment.
And a third specific embodiment: this embodiment differs from the first or second embodiment in that: the mass ratio of the organic solvent I to the water in the mixed solvent of the organic solvent I and the water in the first step is 100 (2-3). The other steps are the same as those of the first or second embodiment.
The specific embodiment IV is as follows: one difference between this embodiment and the first to third embodiments is that: the mass ratio of the organic solvent I to the clindamycin phosphate crude product in the first step is 100 (20-30). The other steps are the same as those of the first to third embodiments.
Fifth embodiment: one to four differences between the present embodiment and the specific embodiment are: the temperature of heating, stirring and beating in the first step is 60-70 ℃, the rotating speed of stirring and beating is 150-250 rpm, and the time of stirring and beating is 5-6 h. Other steps are the same as those of the first to fourth embodiments.
Specific embodiment six: the present embodiment differs from the first to fifth embodiments in that: the organic solvent II in the second step is methanol, ethanol, acetone, isopropanol or n-butanol; and in the second step, the mass fraction of the organic solvent II in the mixed solvent of the organic solvent II and water is 70-80%. Other steps are the same as those of the first to fifth embodiments.
Seventh embodiment: one difference between the present embodiment and the first to sixth embodiments is that: the usage amount of the active carbon in the second step is 1-2% of the mass of the crude clindamycin phosphate product; the decoloring time is 30-60 min; the gradient cooling rate is 0.2-0.3 ℃/min; the temperature of the vacuum drying is 60 ℃, and the time of the vacuum drying is 10-15 h. Other steps are the same as those of embodiments one to six.
Eighth embodiment: one difference between the present embodiment and the first to seventh embodiments is that: the organic base in the second step is pyridine, triethylamine or piperidine; the inorganic base is sodium carbonate, sodium bicarbonate, potassium carbonate or potassium bicarbonate. The other steps are the same as those of embodiments one to seven.
Detailed description nine: one of the differences between this embodiment and the first to eighth embodiments is: the mass ratio of the mixed solvent of the organic solvent II/water and the clindamycin phosphate crude product in the second step is 100 (20-30). Other steps are the same as those of embodiments one to eight.
Detailed description ten: the present embodiment differs from the first to ninth embodiments in that: the addition amount of the organic base or the inorganic base in the second step is 0.5-0.6% of the mass of the crude clindamycin phosphate. The other steps are the same as those of embodiments one to nine.
The following examples are used to verify the benefits of the present invention:
the crude clindamycin phosphate used in the following experiments is prepared by a traditional synthesis method: the clindamycin hydrochloride alcoholized compound is obtained by esterification, hydrolysis, adsorption, elution and concentration (provided by Ningxia Taiyi biological technology Co., ltd.).
Example 1: clindamycin phosphate purification experiment-1:
1. adding 60g of clindamycin phosphate crude product into a mixed solvent of N, N-dimethylformamide/water, heating, stirring and pulping for a certain time, cooling to 10 ℃, and filtering to obtain a wet product;
300g of N, N-dimethylformamide and 6.0g of deionized water are mixed in the mixed solvent of N, N-dimethylformamide/water;
the temperature of heating, stirring and beating in the first step is 60 ℃, the rotating speed of stirring and beating is 200 revolutions per minute, and the stirring and beating time is 5 hours;
2. adding all the wet products into 300mL of ethanol water solution with the mass fraction of 75%, adding 0.36g of pyridine, heating for dissolution, adding 0.6g of active carbon for decoloration for 30min, filtering while the active carbon is hot, cooling the filtrate to 10 ℃ with the gradient of 0.3 ℃/min, crystallizing for 1 hour, filtering, and vacuum drying at 60 ℃ for 10 hours to obtain 52.6g of finished clindamycin phosphate with the yield of 87.66%.
The finished clindamycin phosphate obtained in the example 1 is white crystalline powder, the melting point is 113.6-114 ℃ (literature reference 114 ℃), and the high performance liquid phase test result is shown in the table 1;
TABLE 1
Remarks: the impurity and the content accord with the internal control index, and the impurity purification is qualified.
Example 2: clindamycin phosphate purification experiment-2:
1. adding 60g of clindamycin phosphate crude product into a mixed solvent of N, N-dimethylacetamide/water, heating, stirring and pulping for a certain time, cooling to 10 ℃, and filtering to obtain a wet product;
300g of N, N-dimethylacetamide and 6.0g of deionized water in the mixed solvent of the N, N-dimethylacetamide and water;
the temperature of heating, stirring and beating in the first step is 70 ℃, the rotating speed of stirring and beating is 200 revolutions per minute, and the stirring and beating time is 6 hours;
2. adding all the wet products into 300mL of ethanol water solution with the mass fraction of 75%, adding 0.3g of sodium carbonate, heating for dissolution, adding 0.6g of active carbon for decoloration for 30min, filtering while the active carbon is hot, cooling the filtrate to 10 ℃ at a gradient of 0.3 ℃/min, crystallizing for 1 hour, filtering, and vacuum drying at 60 ℃ for 10 hours to obtain 53.0g of finished clindamycin phosphate with the yield of 88.30%.
The finished clindamycin phosphate obtained in the example 2 is white crystalline powder, the melting point is 113.5-114 ℃ (literature reference 114 ℃), and the high performance liquid phase test result is shown in the table 2;
TABLE 2
Remarks: the impurity and the content accord with the internal control index, and the impurity purification is qualified.
Comparative example 3: clindamycin phosphate purification experiment-3:
taking 60g of clindamycin phosphate crude product, adding 350mL of ethanol water solution with the mass fraction of 75%, heating for dissolving, adding 0.6g of active carbon for decoloring for 30min, filtering while the active carbon is hot, cooling the filtrate to 10 ℃, crystallizing, filtering, and vacuum drying at 60 ℃ for 10 hours to obtain 50.0g of finished clindamycin phosphate with the yield of 83.33%.
The results of the high performance liquid phase test of the finished clindamycin phosphate obtained in comparative example 3 are shown in table 3;
TABLE 3 Table 3
Remarks: total impurities, impurity G, impurity I and other unknown single impurities exceed the internal control index, and the impurity purification is unqualified.
Comparative example 4: clindamycin phosphate purification experiment-4:
1. adding 60g of clindamycin phosphate crude product into a three-necked bottle, adding 300g of N, N-dimethylacetamide, 6g of water, heating and stirring at a rotating speed of 200 revolutions per minute, controlling the temperature to 70 ℃, stirring for 6 hours, cooling to 10 ℃, and filtering to obtain a wet product;
2. adding all the wet products into a reaction bottle, adding 300mL of ethanol aqueous solution with the mass fraction of 75%, heating, refluxing and dissolving, adding 0.6g of active carbon for decoloring for 30min, filtering while the wet products are hot, cooling the filtrate to 10 ℃ at a gradient of 0.3 ℃/min, crystallizing for 1 hour, filtering, and vacuum drying at 60 ℃ for 10 hours to obtain 53.0g of finished clindamycin phosphate with the yield of 88.33%.
The results of the high performance liquid phase test of the finished clindamycin phosphate obtained in comparative example 4 are shown in table 4;
TABLE 4 Table 4
Remarks: total mass and other unknown single impurities are out of limit, and the purification of impurities is not qualified.
Claims (10)
1. The purification method of clindamycin phosphate is characterized by comprising the following steps:
1. adding the crude clindamycin phosphate into a mixed solvent of an organic solvent I/water, controlling a certain temperature, heating, stirring and pulping for a certain time, cooling, and filtering to obtain a wet product;
2. adding the wet product into a mixed solvent of an organic solvent II/water, adding a certain amount of organic alkali or inorganic alkali, heating for dissolution, decoloring by active carbon, filtering while the wet product is hot, cooling the filtrate to 8-10 ℃ in a gradient manner, crystallizing, filtering, and drying in vacuum to obtain a finished product, namely the purification method of clindamycin phosphate is completed.
2. The method for purifying clindamycin phosphate according to claim 1, wherein the organic solvent I in the first step is N, N-dimethylformamide, N-dimethylacetamide or N, N-diethylformamide.
3. The method for purifying clindamycin phosphate according to claim 1, wherein the mass ratio of the organic solvent I to water in the mixed solvent of the organic solvent I/water in the step one is 100 (2-3).
4. The method for purifying clindamycin phosphate according to claim 1, wherein the mass ratio of the organic solvent I to the crude clindamycin phosphate in the step one is 100 (20-30).
5. The method for purifying clindamycin phosphate according to claim 1, wherein the temperature of heating, stirring and beating in the first step is 60-70 ℃, the rotation speed of stirring and beating is 150-250 rpm, and the time of stirring and beating is 5-6 h.
6. The method for purifying clindamycin phosphate according to claim 1, wherein the organic solvent II in the second step is methanol, ethanol, acetone, isopropanol or n-butanol; and in the second step, the mass fraction of the organic solvent II in the mixed solvent of the organic solvent II and water is 70-80%.
7. The purification method of clindamycin phosphate according to claim 1, wherein the amount of the activated carbon used in the second step is 1% -2% of the mass of the crude clindamycin phosphate; the decoloring time is 30-60 min; the gradient cooling rate is 0.2-0.3 ℃/min; the temperature of the vacuum drying is 60 ℃, and the time of the vacuum drying is 10-15 h.
8. The method for purifying clindamycin phosphate according to claim 1, wherein the organic base in the second step is pyridine, triethylamine or piperidine; the inorganic base is sodium carbonate, sodium bicarbonate, potassium carbonate or potassium bicarbonate.
9. The purification method of clindamycin phosphate according to claim 1, wherein the mass ratio of the mixed solvent of the organic solvent II/water to the crude clindamycin phosphate is 100 (20-30).
10. The method for purifying clindamycin phosphate according to claim 1, wherein the addition amount of the organic base or the inorganic base in the second step is 0.5% -0.6% of the crude mass of clindamycin phosphate.
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| Application Number | Priority Date | Filing Date | Title |
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| CN202311384141.3A CN117417389A (en) | 2023-10-24 | 2023-10-24 | Purification method of clindamycin phosphate |
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| Application Number | Priority Date | Filing Date | Title |
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| CN202311384141.3A CN117417389A (en) | 2023-10-24 | 2023-10-24 | Purification method of clindamycin phosphate |
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