CN116284050A - Method for converting high-efficiency crystalline cefuroxime axetil into amorphous powder and product - Google Patents
Method for converting high-efficiency crystalline cefuroxime axetil into amorphous powder and product Download PDFInfo
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- CN116284050A CN116284050A CN202211640279.0A CN202211640279A CN116284050A CN 116284050 A CN116284050 A CN 116284050A CN 202211640279 A CN202211640279 A CN 202211640279A CN 116284050 A CN116284050 A CN 116284050A
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- KEJCWVGMRLCZQQ-YJBYXUATSA-N Cefuroxime axetil Chemical compound N([C@@H]1C(N2C(=C(COC(N)=O)CS[C@@H]21)C(=O)OC(C)OC(C)=O)=O)C(=O)\C(=N/OC)C1=CC=CO1 KEJCWVGMRLCZQQ-YJBYXUATSA-N 0.000 title claims abstract description 71
- 229960002620 cefuroxime axetil Drugs 0.000 title claims abstract description 71
- 239000000843 powder Substances 0.000 title claims abstract description 42
- 238000000034 method Methods 0.000 title claims abstract description 26
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 38
- 238000003756 stirring Methods 0.000 claims abstract description 27
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims abstract description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000013078 crystal Substances 0.000 claims abstract description 12
- 238000001035 drying Methods 0.000 claims abstract description 10
- 238000001914 filtration Methods 0.000 claims abstract description 10
- 239000007788 liquid Substances 0.000 claims abstract description 10
- 238000005406 washing Methods 0.000 claims abstract description 10
- 239000012296 anti-solvent Substances 0.000 claims abstract description 9
- 239000002904 solvent Substances 0.000 claims abstract description 7
- 239000002245 particle Substances 0.000 claims abstract description 4
- 238000006243 chemical reaction Methods 0.000 abstract description 2
- 239000012535 impurity Substances 0.000 description 18
- 239000000203 mixture Substances 0.000 description 15
- 230000000844 anti-bacterial effect Effects 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 5
- 229960001668 cefuroxime Drugs 0.000 description 4
- JFPVXVDWJQMJEE-IZRZKJBUSA-N cefuroxime Chemical compound N([C@@H]1C(N2C(=C(COC(N)=O)CS[C@@H]21)C(O)=O)=O)C(=O)\C(=N/OC)C1=CC=CO1 JFPVXVDWJQMJEE-IZRZKJBUSA-N 0.000 description 4
- 108010051152 Carboxylesterase Proteins 0.000 description 2
- 102000013392 Carboxylesterase Human genes 0.000 description 2
- 238000002441 X-ray diffraction Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000857 drug effect Effects 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- 206010018612 Gonorrhoea Diseases 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- 206010037596 Pyelonephritis Diseases 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 208000013223 septicemia Diseases 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/02—Preparation
- C07D501/12—Separation; Purification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
- C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
- C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
- C07D501/24—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with hydrocarbon radicals, substituted by hetero atoms or hetero rings, attached in position 3
- C07D501/26—Methylene radicals, substituted by oxygen atoms; Lactones thereof with the 2-carboxyl group
- C07D501/34—Methylene radicals, substituted by oxygen atoms; Lactones thereof with the 2-carboxyl group with the 7-amino radical acylated by carboxylic acids containing hetero rings
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Cephalosporin Compounds (AREA)
Abstract
The invention discloses a method for converting high-efficiency crystalline cefuroxime axetil into amorphous powder and a product thereof, wherein the method comprises the following steps: s1, adding cefuroxime axetil crystal powder into anhydrous acetone, stirring and dissolving, and controlling the temperature; s2, concentrating to a semi-molten state at a low temperature in vacuum; s3, pouring the semi-molten liquid into a crystallizer at one time, wherein the crystallizer contains isopropyl ether or water, and stirring rapidly; s4, stirring for a period of time, filtering, washing and drying to obtain an amorphous cefuroxime axetil product with the particle size of 300-800 nm, wherein the invention can greatly improve the conversion rate, reduce the residual of crystalline cefuroxime axetil and improve the bioavailability of the cefuroxime axetil; meanwhile, the dosage of the anti-solvent isopropyl ether or water is reduced, and the solvent system is small.
Description
Technical Field
The invention relates to a method for converting high-efficiency crystalline cefuroxime axetil into amorphous powder and a product thereof, belonging to the field of medicine preparation.
Background
Cefuroxime axetil is a second-generation cephalosporin produced by the company gram-orchid-smith, which has a broad-spectrum antibacterial activity against both gram-positive and gram-negative bacteria. Is a prodrug of cefuroxime, and can be rapidly hydrolyzed by nonspecific esterase in gastrointestinal tract mucosa cells to release cefuroxime after oral administration to exert drug effect. The traditional Chinese medicine composition is widely used for treating respiratory tract infection, urinary tract infection, pyelonephritis, meningitis, septicemia, gonococcal infection and the like clinically. The antibacterial activity of cefuroxime axetil is very low, and after 3-4 minutes of oral absorption, it is rapidly hydrolyzed by nonspecific esterase in intestinal mucosa and portal circulation, releasing cefuroxime to exert its antibacterial effect, so that the antibacterial spectrum and antibacterial activity of cefuroxime axetil are the same as those of cefuroxime.
The cefuroxime axetil with biological utilization value is an amorphous product, and thus, the preparation of the amorphous product is an indispensable part in the production process of cefuroxime axetil. Liao Yong amorphous ultrafine cefuroxime axetil is prepared by an antisolvent precipitation method using crystalline cefuroxime axetil as a raw material, acetone as a solvent, and water as an antisolvent. Experiments were carried out in a kettle reactor, and it was determined that acetone-water was the appropriate solvent-antisolvent system, and that the volume ratio of acetone-water was 1:20, the concentration of cefuroxime axetil was 10%, the reaction temperature was 4℃and the stirring speed was 2 000 r/min. Amorphous ultrafine products were obtained from crystalline cefuroxime axetil by the anti-solvent precipitation method, and the molecular structure of cefuroxime axetil was not changed before and after the ultrafine purification by analysis.
However, the antisolvent method has the problems of large solvent system, high energy consumption, low amorphous ratio in the obtained product and low drug effect.
Disclosure of Invention
The invention aims to solve the technical problems and provide a method for converting high-efficiency crystalline cefuroxime axetil into amorphous powder and a product thereof, which can greatly improve the ratio of amorphous cefuroxime axetil in the product, reduce the residue of crystalline cefuroxime axetil and improve the bioavailability of cefuroxime axetil; meanwhile, the solvent system is small, and the dosage of isopropyl ether or water is reduced.
In order to solve the technical problems, the first technical scheme adopted by the invention is as follows:
a method for converting high-efficiency crystalline cefuroxime axetil into amorphous powder, which comprises the following steps:
s1, adding cefuroxime axetil crystal powder into anhydrous acetone, stirring and dissolving, and controlling the temperature;
s2, concentrating to a semi-molten state at a low temperature in vacuum;
s3, pouring the semi-molten liquid into a crystallizer at one time, wherein the crystallizer contains isopropyl ether or water, and stirring rapidly;
s4, stirring for a period of time, filtering, washing and drying to obtain the amorphous cefuroxime axetil.
The technical scheme of the invention is further improved as follows: the volume ratio of the cefuroxime axetil crystalline powder to the anhydrous acetone in the step S1 is 1:5-20, and the stirring and dissolving temperature is 10-30 ℃.
The technical scheme of the invention is further improved as follows: and in the step S2, the temperature of the low-temperature vacuum concentration is 2-30 ℃, and the concentration is carried out until the original volume is 20-40%.
The technical scheme of the invention is further improved as follows: and in the step S3, the time for pouring the semi-molten liquid into the crystallizer is 2-20S.
The technical scheme of the invention is further improved as follows: and in the step S3, the adding volume of isopropyl ether or water in the crystallizer is 5-10 times of that of the semi-molten liquid, and the temperature is 0-2 ℃.
The technical scheme of the invention is further improved as follows: the stirring speed in the step is 40-50HZ, and the stirring time is 2-20 min.
The technical scheme of the invention is further improved as follows: the addition amount of the anti-solvent isopropyl ether or water can be obviously reduced by concentrating to a semi-molten state in vacuum at low temperature, and the solvent system is small.
In order to solve the technical problems, the second technical scheme adopted by the invention is as follows:
the cefuroxime axetil product is amorphous powder, the amorphous ratio is more than 99.8%, and the cefuroxime axetil product is obtained from crystalline cefuroxime axetil and has a particle size of 300-800 nm. .
By adopting the technical scheme, the invention has the following technical progress:
the invention makes cefuroxime axetil reach a semi-molten state by vacuum concentration of the cefuroxime axetil acetone solution at low temperature, can greatly improve the quantity of the cefuroxime axetil in acetone, and simultaneously limit the adding speed in a crystallizer and the dissolving temperature of the cefuroxime axetil crystal powder, can greatly reduce a crystallization system, reduce the residual of the crystalline cefuroxime axetil and improve the bioavailability of the cefuroxime axetil; meanwhile, the addition amount of the anti-solvent isopropyl ether or water can be obviously reduced by concentrating to a semi-molten state in vacuum at a low temperature, and the solvent system is small.
Drawings
Figure 1 is an XRD pattern of example 1 of the present invention.
Detailed Description
The invention is further illustrated by the following examples:
a method for converting high-efficiency crystalline cefuroxime axetil into amorphous powder, which comprises the following steps:
s1, adding cefuroxime axetil crystal powder into anhydrous acetone, wherein the volume ratio of the cefuroxime axetil crystal powder to the anhydrous acetone is 1:5-10, stirring and dissolving, and controlling the temperature to be 10-30 ℃;
s2, concentrating the mixture to 20-40% of the original volume at a low temperature of 2-30 ℃ in vacuum, and taking the mixture to be in a semi-molten state;
s3, pouring the semi-molten liquid into a crystallizer at one time, wherein the crystallizer contains isopropyl ether or water at 0-2 ℃ and the addition amount of isopropyl ether or water is 5-20 times of that of the semi-molten liquid, and rapidly stirring for 2-20min at 40-50 HZ;
s4, stirring for a period of time, filtering, washing and drying to obtain the amorphous cefuroxime axetil, wherein the particle size is 300-800 nm, and the amorphous ratio is more than 99.9%.
Example 1
500g of cefuroxime axetil crystal powder is added into 5000ml of anhydrous acetone, stirred and dissolved, and the temperature is controlled to be 20 ℃; then concentrating to 1500ml semi-molten state at 2-30 ℃ in vacuum, pouring into a rapidly stirred crystallizer for 10s, wherein the crystallizer contains 15000ml isopropyl ether at 0-2 ℃, rapidly stirring for 2-5 min, filtering, washing and drying to obtain 300-800 nm amorphous cefuroxime axetil, which is white powder, wherein the XRD pattern is shown in figure 1, the amorphous ratio is 99.9%, the content is 82.8%, and the single impurity is that: 0.02%, total impurities: 0.25%.
Example 2
500g of cefuroxime axetil crystal powder is added into 7000ml of anhydrous acetone, stirred and dissolved, and the temperature is controlled to be 10 ℃; then concentrating to 1500ml in vacuum at low temperature of 2-30 ℃ until the mixture is in a semi-molten state, pouring the mixture into a rapidly stirred crystallizer once for 15s, wherein the crystallizer contains 15000ml of water at 0-2 ℃, rapidly stirring for 2-5 min, filtering, washing and drying to obtain 300-700 nm amorphous cefuroxime axetil which is white powder, wherein the amorphous content is 99.9%, the content is 82.7%, the single impurity is 0.02% and the total impurity is 0.26%.
Example 3
500g of cefuroxime axetil crystal powder is added into 4000 ml anhydrous acetone, stirred and dissolved, and the temperature is controlled at 30 ℃; then concentrating to 1400ml semi-molten state at 2-30 ℃ in vacuum, pouring into a fast stirring crystallizer for 5s, wherein the crystallizer contains 10000ml of water at 0-2 ℃, fast stirring for 2-5 min, filtering, washing and drying to obtain 300-700 nm amorphous cefuroxime axetil which is white powder, wherein the amorphous content is 99.8%, the content is 82.5%, the single impurity is 0.03% and the total impurity is 0.28%.
Example 4
500g of cefuroxime axetil crystal powder is added into 4500ml of anhydrous acetone, stirred and dissolved, and the temperature is controlled at 25 ℃; then concentrating to 1500ml in vacuum at low temperature of 2-30 ℃ until the mixture is in a semi-molten state, pouring the mixture into a rapidly stirred crystallizer once, and filtering the mixture for 13s when the crystallizer contains 15000ml of water at 0-2 ℃ and is rapidly stirred for 2-5 min, washing and drying the mixture to obtain 300-700 nm amorphous cefuroxime axetil which is white powder, wherein the amorphous content is 99.9%, the content is 82.7%, the single impurity is 0.03% and the total impurity is 0.27%.
Comparative example 1 [ no low temperature vacuum concentration ]
500g of cefuroxime axetil crystalline powder is added into 5000ml of anhydrous acetone, stirred and dissolved, the temperature is controlled to be 20 ℃, the mixture is poured into a stirred crystallizer once and rapidly, 120s is used, the crystallizer contains 100000ml of isopropyl ether, the mixture is stirred for 2-5 min and filtered, washed and dried, and 200-800 nm of cefuroxime axetil is obtained, which is white powder, the amorphous ratio is 93.2%, the content is 82.4%, the single impurity is 0.03%, and the total impurity is 0.27%.
Comparative example 2 [ concentration of low-temperature vacuum concentration is small ]
500g of cefuroxime axetil crystal powder is added into 5000ml of anhydrous acetone, stirred and dissolved, and the temperature is controlled to be 20 ℃; then concentrating to 3500ml semi-molten state at low temperature 2-30 ℃ in vacuum, pouring into a quick stirring crystallizer for 30s, wherein the crystallizer contains 15000ml isopropyl ether at 0-2 ℃, quick stirring for 2-5 min, filtering, washing and drying to obtain 300-800 nm amorphous cefuroxime axetil which is white powder, wherein the amorphous content is 96.3%, the content is 82.6%, the single impurity is 0.02% and the total impurity is 0.25%.
Comparative example 3 [ high dissolution temperature ]
500g of cefuroxime axetil crystalline powder is added into 5000ml of anhydrous acetone, stirred and dissolved, the temperature is controlled to be 45 ℃, then the mixture is concentrated to a semi-molten state of 1500ml in vacuum at a low temperature of 2-30 ℃, the mixture is poured into a stirred crystallizer once and rapidly, the crystallizer contains 15000ml of isopropyl ether at 0-2 ℃ and is stirred for 2-5 min, filtered, washed and dried, and 300-800 nm of cefuroxime axetil is obtained, and the product is pale yellow powder, the amorphous ratio of which is 99.7%, the content of single impurity is 0.08%, and the total impurity is 0.34%.
Comparative example 4 [ dissolution temperature is low ]
500g of cefuroxime axetil crystalline powder is added into 8000ml of anhydrous acetone, stirred and dissolved, the temperature is controlled to be 0 ℃, then the mixture is concentrated to a semi-molten state of 1500ml in vacuum at a low temperature of 2-30 ℃, the mixture is poured into a stirred crystallizer once and rapidly, the crystallizer contains 15000ml of isopropyl ether at 0-2 ℃ and is stirred for 2-5 min, filtered, washed and dried, and 100-500 nm of cefuroxime axetil is obtained, and the product is white powder, the amorphous ratio of which is 99.9%, the content of single impurity is 0.02%, and the total impurity is 0.25%.
Comparative example 5 [ slow addition ]
500g of cefuroxime axetil crystal powder is added into 5000ml of anhydrous acetone, stirred and dissolved, and the temperature is controlled to be 20 ℃; then concentrating under vacuum at a low temperature of 2-30 ℃ to 1500ml of semi-molten state, slowly pouring the semi-molten liquid into a fast stirring crystallizer, taking 20min, wherein the crystallizer contains 15000ml of isopropyl ether at 0-2 ℃, fast stirring for 2-5 min, filtering, washing and drying to obtain 300-800 nm amorphous cefuroxime axetil which is white-like powder, wherein the amorphous content is 95.1%, the content is 82.7%, the single impurity is 0.02% and the total impurity is 0.25%.
Claims (8)
1. A method for converting high-efficiency crystalline cefuroxime axetil into amorphous powder is characterized in that: the method comprises the following steps:
s1, adding cefuroxime axetil crystal powder into anhydrous acetone, stirring and dissolving, and controlling the temperature;
s2, concentrating to a semi-molten state at a low temperature in vacuum;
s3, pouring the semi-molten liquid into a crystallizer at one time, wherein the crystallizer contains isopropyl ether or water, and stirring rapidly;
s4, stirring for a period of time, filtering, washing and drying to obtain the amorphous cefuroxime axetil.
2. The method for converting high-efficiency crystalline cefuroxime axetil into amorphous powder according to claim 1, wherein the method comprises the following steps: the volume ratio of the cefuroxime axetil crystalline powder to the anhydrous acetone in the step S1 is 1:5-20, and the stirring and dissolving temperature is 10-30 ℃.
3. The method for converting high-efficiency crystalline cefuroxime axetil into amorphous powder according to claim 1, wherein the method comprises the following steps: and in the step S2, the temperature of the low-temperature vacuum concentration is 2-30 ℃, and the concentration is carried out until the original volume is 20-40%.
4. The method for converting high-efficiency crystalline cefuroxime axetil into amorphous powder according to claim 1, wherein the method comprises the following steps: and in the step S3, the time for pouring the semi-molten liquid into the crystallizer is 2-20S.
5. The method for converting high-efficiency crystalline cefuroxime axetil into amorphous powder according to claim 1, wherein the method comprises the following steps: and in the step S3, the adding volume of isopropyl ether or water in the crystallizer is 5-10 times of that of the semi-molten liquid, and the temperature is 0-2 ℃.
6. The method for converting high-efficiency crystalline cefuroxime axetil into amorphous powder according to claim 1, wherein the method comprises the following steps: the stirring speed in the step is 40-50HZ, and the stirring time is 2-20 min.
7. The method for converting high-efficiency crystalline cefuroxime axetil into amorphous powder according to claim 1, wherein the method comprises the following steps: the addition amount of the anti-solvent isopropyl ether or water can be obviously reduced by concentrating to a semi-molten state in vacuum at low temperature, and the solvent system is small.
8. The cefuroxime axetil product prepared by the process according to any one of claims 1 to 7, wherein: the cefuroxime axetil product is amorphous powder, the amorphous ratio is more than 99.8%, and the cefuroxime axetil product is obtained from crystalline cefuroxime axetil and has a particle size of 300-800 nm.
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Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4562181A (en) * | 1982-07-30 | 1985-12-31 | Glaxo Group Limited | Amorphous form of cefuroxime ester |
| NZ299077A (en) * | 1996-07-26 | 1998-06-26 | Apotex Inc | Preparation of amorphous cefuroxime axetil (a cephalosporin derivative) by dissolving crystalline cefuroxim axetil in a highly polar solvent, typically dmso and/or dmf |
| KR19980075529A (en) * | 1997-03-31 | 1998-11-16 | 서치영 | Preparation method of low melting point amorphous cefuroxime axetil |
| DE19907521A1 (en) * | 1998-02-20 | 1999-11-04 | Fako Ilaclari A S | New crystalline form of (R,S)-cefuroxime axetil |
| KR20000013423A (en) * | 1998-08-08 | 2000-03-06 | 정지석 | Synthesis of amorphous cephroxim acetyl |
| KR20020016052A (en) * | 2000-08-24 | 2002-03-04 | 최현식 | New method for the manufacture of amorphous cefuroxime axetil |
| CN1367683A (en) * | 1999-08-04 | 2002-09-04 | 韩美药品工业株式会社 | Non-crystalline cefuroxime axetil solid dispersant, process for preparing same and composition for oral administration thereof |
| CN1439013A (en) * | 2000-05-19 | 2003-08-27 | 兰贝克赛实验室有限公司 | Process for preparing a pure, pharmacopoeial grade amorphous form of cefuroxime axetil |
| CN1600785A (en) * | 2004-07-22 | 2005-03-30 | 北京化工大学 | Method for preparing unformed cefuroxime axetil |
| CN1637001A (en) * | 2003-12-26 | 2005-07-13 | 上海华联制药有限公司 | Process of preparing amorphous cefuroxin axetil |
| CN101284839A (en) * | 2008-06-02 | 2008-10-15 | 河北科技大学 | Method and device for preparing superfine amorphousn cefuroxime axetil |
-
2022
- 2022-12-19 CN CN202211640279.0A patent/CN116284050B/en active Active
Patent Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4562181A (en) * | 1982-07-30 | 1985-12-31 | Glaxo Group Limited | Amorphous form of cefuroxime ester |
| NZ299077A (en) * | 1996-07-26 | 1998-06-26 | Apotex Inc | Preparation of amorphous cefuroxime axetil (a cephalosporin derivative) by dissolving crystalline cefuroxim axetil in a highly polar solvent, typically dmso and/or dmf |
| KR19980075529A (en) * | 1997-03-31 | 1998-11-16 | 서치영 | Preparation method of low melting point amorphous cefuroxime axetil |
| DE19907521A1 (en) * | 1998-02-20 | 1999-11-04 | Fako Ilaclari A S | New crystalline form of (R,S)-cefuroxime axetil |
| KR20000013423A (en) * | 1998-08-08 | 2000-03-06 | 정지석 | Synthesis of amorphous cephroxim acetyl |
| CN1367683A (en) * | 1999-08-04 | 2002-09-04 | 韩美药品工业株式会社 | Non-crystalline cefuroxime axetil solid dispersant, process for preparing same and composition for oral administration thereof |
| CN1439013A (en) * | 2000-05-19 | 2003-08-27 | 兰贝克赛实验室有限公司 | Process for preparing a pure, pharmacopoeial grade amorphous form of cefuroxime axetil |
| KR20020016052A (en) * | 2000-08-24 | 2002-03-04 | 최현식 | New method for the manufacture of amorphous cefuroxime axetil |
| CN1637001A (en) * | 2003-12-26 | 2005-07-13 | 上海华联制药有限公司 | Process of preparing amorphous cefuroxin axetil |
| CN1600785A (en) * | 2004-07-22 | 2005-03-30 | 北京化工大学 | Method for preparing unformed cefuroxime axetil |
| CN101284839A (en) * | 2008-06-02 | 2008-10-15 | 河北科技大学 | Method and device for preparing superfine amorphousn cefuroxime axetil |
Non-Patent Citations (1)
| Title |
|---|
| JI-YAO ZHANG ET AL.: "Preparation of amorphous cefuroxime axetil nanoparticles by controlled nanoprecipitation method without surfactants", 《INTERNATIONAL JOURNAL OF PHARMACEUTICS》, vol. 323, 2 June 2006 (2006-06-02), pages 153 - 160 * |
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