CN112645943A - Preparation method of ammonia-containing qunan amorphous system - Google Patents
Preparation method of ammonia-containing qunan amorphous system Download PDFInfo
- Publication number
- CN112645943A CN112645943A CN202011565182.9A CN202011565182A CN112645943A CN 112645943 A CN112645943 A CN 112645943A CN 202011565182 A CN202011565182 A CN 202011565182A CN 112645943 A CN112645943 A CN 112645943A
- Authority
- CN
- China
- Prior art keywords
- aztreonam
- amorphous
- sample
- amorphous system
- preparing
- 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.)
- Pending
Links
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 title claims abstract description 22
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- 229910021529 ammonia Inorganic materials 0.000 title claims abstract description 11
- WZPBZJONDBGPKJ-UHFFFAOYSA-N Antibiotic SQ 26917 Natural products O=C1N(S(O)(=O)=O)C(C)C1NC(=O)C(=NOC(C)(C)C(O)=O)C1=CSC(N)=N1 WZPBZJONDBGPKJ-UHFFFAOYSA-N 0.000 claims abstract description 89
- WZPBZJONDBGPKJ-VEHQQRBSSA-N aztreonam Chemical compound O=C1N(S([O-])(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(=N/OC(C)(C)C(O)=O)\C1=CSC([NH3+])=N1 WZPBZJONDBGPKJ-VEHQQRBSSA-N 0.000 claims abstract description 89
- 229960003644 aztreonam Drugs 0.000 claims abstract description 89
- 239000003814 drug Substances 0.000 claims abstract description 24
- 150000001413 amino acids Chemical class 0.000 claims abstract description 22
- 238000001816 cooling Methods 0.000 claims abstract description 18
- 238000002156 mixing Methods 0.000 claims abstract description 18
- 239000002994 raw material Substances 0.000 claims abstract description 18
- 229940079593 drug Drugs 0.000 claims abstract description 12
- 238000010438 heat treatment Methods 0.000 claims abstract description 9
- 238000002844 melting Methods 0.000 claims abstract description 9
- 230000008018 melting Effects 0.000 claims abstract description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 36
- 239000013078 crystal Substances 0.000 claims description 23
- 239000002245 particle Substances 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- -1 small molecule compound Chemical class 0.000 claims description 4
- 239000004475 Arginine Substances 0.000 claims description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 2
- 239000004472 Lysine Substances 0.000 claims description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 2
- 239000001110 calcium chloride Substances 0.000 claims description 2
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 2
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 2
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims description 2
- 235000019799 monosodium phosphate Nutrition 0.000 claims description 2
- 239000011780 sodium chloride Substances 0.000 claims description 2
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 11
- 239000012535 impurity Substances 0.000 description 28
- 238000005303 weighing Methods 0.000 description 11
- 230000000052 comparative effect Effects 0.000 description 9
- 238000004090 dissolution Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 238000007142 ring opening reaction Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 150000003952 β-lactams Chemical class 0.000 description 4
- IBLNMEMSULYOOK-VEHQQRBSSA-N SQ 26,992 Chemical compound OS(=O)(=O)N[C@@H](C)[C@@H](C(O)=O)NC(=O)C(=N/OC(C)(C)C(O)=O)\C1=CSC(N)=N1 IBLNMEMSULYOOK-VEHQQRBSSA-N 0.000 description 3
- 238000011835 investigation Methods 0.000 description 3
- 206010002198 Anaphylactic reaction Diseases 0.000 description 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Substances CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 2
- 208000003455 anaphylaxis Diseases 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 2
- 235000019796 monopotassium phosphate Nutrition 0.000 description 2
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 229940124350 antibacterial drug Drugs 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 239000003782 beta lactam antibiotic agent Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 238000010829 isocratic elution Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000002132 β-lactam antibiotic Substances 0.000 description 1
- 229940124586 β-lactam antibiotics Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention belongs to the field of medicine processing, and particularly relates to a preparation method of an ammonia-containing qunan amorphous system, which comprises the following steps: heating and melting aztreonam raw material medicines, and cooling to prepare an aztreonam amorphous sample; and uniformly mixing the crushed aztreonam amorphous sample and the basic amino acid and/or the micromolecular compound, and cooling to obtain the aztreonam co-amorphous system. The preparation process of the amorphous system containing aztreonam reduces the requirements on raw material medicines, improves the solubility of aztreonam, improves the stability of products and saves the production cost.
Description
Technical Field
The invention belongs to the field of medicine processing, and particularly relates to a preparation method of an ammonia-containing qunan amorphous system.
Background
Aztreonam is an antibacterial drug stable to beta-lactam enzyme and has stronger antibacterial activity to gram-negative bacilli. It was developed by schip corporation of america and marketed in italy in 1984. Aztreonam is a monocyclic beta-lactam antibiotic, and is widely applied clinically due to its unique structure and good antibacterial performance.
The aztreonam is white or yellowish polycrystalline powder, the raw material of the aztreonam has four crystal forms, namely alpha crystal form, beta crystal form, gamma crystal form and delta crystal form, the alpha crystal form is an aqueous crystal form, usually contains 7-14% of water, is easy to dissolve in water, is easy to absorb moisture, is poor in stability, is easy to open a ring under the conditions of moisture and heat to form open-ring aztreonam, the open-ring aztreonam is a main impurity of the aztreonam, and the existence of the open-ring aztreonam reduces the content of a medicament, so that the titer of the medicament is reduced, and the sterilization and bacteriostasis effects of the aztreonam are reduced. On the other hand, similar to other beta-lactam drugs, the beta-lactam forms an active target after ring opening, and self-polymerization is easy to occur to form a high polymer (high molecular impurities). The content of high polymer or high molecular impurities directly influences the incidence rate of anaphylactic reaction, reduces the content of ring-opening aztreonam impurities, and is an important factor for controlling the incidence rate of endogenous anaphylactic reaction. In the production of raw materials, aztreonam is often converted into a beta crystal form, the beta crystal form is not easy to absorb moisture, the fluidity is good, and the solid stability of the aztreonam is better than that of the alpha crystal form, so the medicinal aztreonam is generally the beta crystal form, but the solubility of the beta crystal form aztreonam in water is very small, and the stability is only that compared with the alpha crystal form, the beta-lactam medicine is easy to open the ring and is the essential characteristic of the aztreonam.
Aztreonam has four crystal forms of alpha, beta, gamma and delta, wherein the alpha type crystal has crystal water, is unstable when placed at room temperature, is easy to generate ring-opening impurities, the gamma and delta type crystal particles are too fine and are not suitable for medicinal production, and the beta type crystal has the advantages of good fluidity, relative stability at room temperature, easy preparation and the like, and is widely used for industrial production. The requirement of aztreonam preparation for bulk drug and the low solubility of aztreonam bring many limitations to the preparation process. The measures which can be taken are mainly to obtain the stable crystal form of the aztreonam in the medicine and improve the solubility of the aztreonam.
At present, the aztreonam preparation generates more impurities in the production and placement processes, and particularly, the aztreonam ring-opening impurities account for a larger proportion. In addition, the prior art has higher requirements on raw material medicines, higher requirements on production lines, higher requirements on production operation and high production cost.
Disclosure of Invention
In order to solve the problems, the invention provides a preparation method of an amorphous system containing aztreonam, which can improve the solubility of the aztreonam and improve the stability of the aztreonam.
The technical scheme provided by the invention is as follows:
a preparation method of an ammonia-containing qunan amorphous system comprises the following steps: heating and melting aztreonam raw material medicines, and cooling to prepare an aztreonam amorphous sample; and uniformly mixing the crushed aztreonam amorphous sample and the basic amino acid and/or the micromolecular compound, and cooling to obtain the aztreonam co-amorphous system.
A preparation method of an ammonia-containing qunan amorphous system comprises the following steps:
1. weighing aztreonam raw material medicines, heating at a certain temperature, melting for a period of time, taking down, cooling at a certain specific temperature, and preparing an aztreonam amorphous sample.
2. The aztreonam amorphous sample is crushed.
3. Weighing amino acid and/or small molecular compound, and pulverizing.
4. Mixing the aztreonam amorphous sample and the basic amino acid and/or the small molecular compound at a certain temperature according to a certain proportion, uniformly mixing, and cooling at a certain specific temperature to obtain the aztreonam co-amorphous system.
The crystal form of the aztreonam raw material medicine in the step 1 can be one or more of alpha, beta, gamma and delta crystal forms.
The heating temperature in the step 1 can be 40-240 ℃, the melting time can be 0.5-10 min, and the cooling temperature can be-30-40 ℃.
The crushed particle size of the amorphous sample of aztreonam in the step 2 can be 1-50 μm.
The amino acid in step 3 may be one or more of basic amino acids (lysine, arginine, histidine), and the small molecule compound may be common adjuvants, such as citric acid, disodium hydrogen phosphate, sodium dihydrogen phosphate, sodium chloride, and calcium chloride.
The weight ratio of the amino acid, the aztreonam and the small molecular compound in the step 4 can be 0.5-1.0: 1.0-1.5: 0.001 to 1.0.
The mixing temperature in the step 4 is 30-100 ℃, and the cooling temperature is-30-40 ℃.
Advantageous effects
The preparation process of the amorphous system containing aztreonam reduces the requirements on raw material medicines, improves the solubility of aztreonam, improves the stability of products and saves the production cost.
According to the preparation process of the aztreonam-containing amorphous system, the requirement on aztreonam raw material medicines is reduced by preparing the aztreonam amorphous sample, the stable aztreonam amorphous sample is obtained, the stability and the solubility of aztreonam are improved, and the aztreonam amorphous system is mixed with the basic amino acid and the common small molecular auxiliary materials to obtain the stable amorphous system, so that the stability and the solubility of aztreonam are further improved, the difficulty of preparation production is reduced, the requirement on the raw material medicines is reduced, and the production cost is saved.
Detailed Description
Example 1
The preparation method of the ammonia-containing qunan amorphous system comprises the following steps:
1. weighing 5.0g of aztreonam raw material medicine, heating at 120 ℃, melting for 0.5min, taking down, cooling at 15 ℃, and preparing an aztreonam amorphous sample.
2. And crushing an aztreonam amorphous sample to obtain a sample with the particle size of 5-25 mu m.
3. 3.0g of amino acid, and crushing to obtain a sample with the particle size of 5-25 mu m.
4. 2.5g of citric acid, and crushing to obtain a sample with the particle size of 5-25 mu m.
5. And mixing the obtained aztreonam amorphous sample, amino acid and citric acid at 30 ℃, uniformly mixing, and cooling at 15 ℃ to obtain the aztreonam co-amorphous system.
Example 2
The preparation method of the ammonia-containing qunan amorphous system comprises the following steps:
1. weighing 5.0g of aztreonam raw material medicine, heating at 140 ℃, melting for 2min, taking down, cooling at 0 ℃, and preparing an aztreonam amorphous sample.
2. And crushing an aztreonam amorphous sample to obtain a sample with the particle size of 5-15 mu m.
3. 3.5g of amino acid, and crushing to obtain a sample with the particle size of 5-15 mu m.
4. And 1.5g of citric acid is crushed to obtain a sample with the particle size of 5-15 mu m.
5. And mixing the obtained aztreonam amorphous sample, amino acid and citric acid at 30 ℃, uniformly mixing, and cooling at 0 ℃ to obtain the aztreonam co-amorphous system.
Example 3
The preparation method of the ammonia-containing qunan amorphous system comprises the following steps:
1. weighing 5.0g of aztreonam raw material medicine, heating at 140 ℃, melting for 0.5min, taking down, cooling at-10 ℃, and preparing an aztreonam amorphous sample.
2. And crushing an aztreonam amorphous sample to obtain a sample with the particle size of 5-25 mu m.
3. 4.0g of amino acid, and crushing to obtain a sample with the particle size of 5-25 mu m.
4. 0.05g of citric acid is crushed to obtain a sample with the particle size of 5-25 mu m.
5. Mixing the obtained aztreonam amorphous sample, amino acid and citric acid at 30 ℃, uniformly mixing, and cooling at-10 ℃ to obtain an aztreonam co-amorphous system.
Comparative example 1
1. Weighing 5.0g of aztreonam raw material medicine, and crushing to obtain a sample with the particle size of 5-25 mu m.
2. Weighing 4.0g of amino acid, and crushing to obtain a sample with the particle size of 5-25 mu m.
3. Weighing 0.05g of citric acid, and crushing to obtain a sample with the particle size of 5-25 mu m.
4. Mixing the pulverized aztreonam, the amino acid and the citric acid at room temperature, and uniformly mixing.
Comparative example 2
1. Weighing 5.0g of aztreonam raw material medicine, and crushing to obtain a sample with the particle size of 5-25 mu m.
2. Weighing 3.0g of amino acid, and crushing to obtain a sample with the particle size of 5-25 mu m.
3. Weighing 2.5g of citric acid, and crushing to obtain a sample with the particle size of 5-25 mu m.
4. Mixing the pulverized aztreonam, the amino acid and the citric acid at room temperature, and uniformly mixing.
Investigation of sample Properties
1. Dissolution Properties
The samples prepared in example 1, example 2, example 3, comparative example 1 and comparative example 2 were taken, and their dissolution properties were examined.
Volume of solvent: 100 ml;
dissolution temperature: 18-26 ℃;
the dissolving method comprises the following steps: stirring (stirring speed 100rpm)
The results are shown in Table 1.
TABLE 1 investigation of sample dissolution Properties
2. Stability performance
The samples prepared in example 1, example 2, example 3, comparative example 1 and comparative example 2 were taken, and the relevant substances were examined.
A chromatographic column: a C18 column;
mobile phase: mobile phase A: 0.05mol/L potassium dihydrogen phosphate (pH3.0) -acetonitrile 90: 10; mobile phase B: 0.05mol/L potassium dihydrogen phosphate (pH3.0) -acetonitrile 60: 40.
The elution method comprises the following steps: isocratic elution with mobile phase a first: and linear elution is carried out after the aztreonam peak is eluted.
Detection wavelength: 270 nm.
TABLE 2 substances related to 3 month acceleration
| Point in time | Example 1 | Example 2 | Example 3 | Comparative example 1 | Comparative example 2 |
| 0 month | Total impurities: 1.0 percent | Total impurities: 1.0 percent | Total impurities: 1.1 percent | Total impurities: 1.0 percent | Total impurities: 1.2 percent of |
| Accelerated for 1 month | Total impurities: 1.2 percent of | Total impurities: 1.3 percent of | Total impurities: 1.3 percent of | Total impurities: 1.9 percent | Total impurities: 1.7 percent |
| Accelerated for 3 months | Total impurities: 1.7 percent | Total impurities: 1.6 percent | Total impurities: 1.8 percent | Total impurities: 2.3 percent of | Total impurities: 2.6 percent |
| Accelerated for 6 months | Total impurities: 2.0 percent | Total impurities: 2.3 percent of | Total impurities: 2.1 percent of | Total impurities: 3.1 percent of | Total impurities: 2.9 percent of |
The investigation on the solubility and stability of the examples and the comparative examples shows that the preparation method of the amorphous system containing aztreonam can effectively improve the solubility of the aztreonam composition, reduce impurities in the aztreonam composition and improve the stability of the aztreonam composition in the production process. The preparation method of the amorphous system containing aztreonam can improve the stability of the aztreonam composition by expediting the storage of the examples for 6 months.
Claims (8)
1. A preparation method of an ammonia-containing qunan amorphous system is characterized by comprising the following steps:
heating and melting aztreonam raw material medicines, and cooling to prepare an aztreonam amorphous sample; and uniformly mixing the crushed aztreonam amorphous sample and the basic amino acid and/or the micromolecular compound, and cooling to obtain the aztreonam co-amorphous system.
2. The method for preparing an ammonia-containing qunan amorphous system according to claim 1, wherein the amino acid is one or more of lysine, arginine and histidine.
3. The method for preparing an amazon amorphous system according to claim 1, wherein the small molecule compound is one or more of citric acid, disodium hydrogen phosphate, sodium dihydrogen phosphate, sodium chloride and calcium chloride.
4. The method for preparing an amorphous system containing aztreonam according to claim 1, wherein the weight ratio of the amino acid to the aztreonam to the small molecule compound is 0.5-1.0: 1.0-1.5: 0.001 to 1.0.
5. The method for preparing an amorphous system containing aztreonam according to claim 1, wherein the mixing temperature of the pulverized amorphous sample of aztreonam and the basic amino acid and/or the small molecule compound is 30 to 100 ℃, and the cooling temperature after mixing is-30 to 40 ℃.
6. The method for preparing an amorphous system containing aztreonam according to claim 1, wherein the heating temperature of aztreonam is 40 to 240 ℃, the melting time is 0.5 to 10min, and the cooling temperature is-30 to 40 ℃.
7. The method for preparing an amorphous system containing aztreonam according to claim 1, wherein the crystal form of aztreonam raw material drug is one or more of alpha, beta, gamma and delta crystal forms.
8. The method for preparing an amorphous system containing aztreonam according to claim 1, wherein the amorphous sample of aztreonam is pulverized to a particle size of 1 to 50 μm.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011565182.9A CN112645943A (en) | 2020-12-25 | 2020-12-25 | Preparation method of ammonia-containing qunan amorphous system |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011565182.9A CN112645943A (en) | 2020-12-25 | 2020-12-25 | Preparation method of ammonia-containing qunan amorphous system |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112645943A true CN112645943A (en) | 2021-04-13 |
Family
ID=75363597
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011565182.9A Pending CN112645943A (en) | 2020-12-25 | 2020-12-25 | Preparation method of ammonia-containing qunan amorphous system |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112645943A (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0070024A1 (en) * | 1981-07-13 | 1983-01-19 | E.R. Squibb & Sons, Inc. | The crystalline anhydrous form of (3S-(3 alpha(z),4 beta))-3-(((2-amino-4-thiazolyl)(1-carboxy-1-methylethoxy)-imino)-acetyl)-amino)-4-methyl-2-oxo-1-azetidinesulfonic acid, method for its preparation, mixture and pharmaceutical composition containing it |
| CN101172974A (en) * | 2007-11-16 | 2008-05-07 | 西南合成制药股份有限公司 | Method for producing aztreonam amino acid salt |
| CN104856958A (en) * | 2014-02-21 | 2015-08-26 | 海南灵康制药有限公司 | Special aztreonam ultra-fine powder preparation and preparation method thereof |
| CN105055406A (en) * | 2015-08-10 | 2015-11-18 | 青岛蓝盛洋医药生物科技有限责任公司 | Antibacterial drug aztreonam composition |
| CN105085511A (en) * | 2015-05-29 | 2015-11-25 | 石药集团中诺药业（石家庄）有限公司 | Novel aztreonam compound |
-
2020
- 2020-12-25 CN CN202011565182.9A patent/CN112645943A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0070024A1 (en) * | 1981-07-13 | 1983-01-19 | E.R. Squibb & Sons, Inc. | The crystalline anhydrous form of (3S-(3 alpha(z),4 beta))-3-(((2-amino-4-thiazolyl)(1-carboxy-1-methylethoxy)-imino)-acetyl)-amino)-4-methyl-2-oxo-1-azetidinesulfonic acid, method for its preparation, mixture and pharmaceutical composition containing it |
| CN101172974A (en) * | 2007-11-16 | 2008-05-07 | 西南合成制药股份有限公司 | Method for producing aztreonam amino acid salt |
| CN104856958A (en) * | 2014-02-21 | 2015-08-26 | 海南灵康制药有限公司 | Special aztreonam ultra-fine powder preparation and preparation method thereof |
| CN105085511A (en) * | 2015-05-29 | 2015-11-25 | 石药集团中诺药业（石家庄）有限公司 | Novel aztreonam compound |
| CN105055406A (en) * | 2015-08-10 | 2015-11-18 | 青岛蓝盛洋医药生物科技有限责任公司 | Antibacterial drug aztreonam composition |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108420797B (en) | Vitamin D analogue preparation and preparation method thereof | |
| CN108096191A (en) | Florfenicol pre-mixing agent and preparation method thereof | |
| CN110464846A (en) | A kind of Meloxicam composition, preparation and the preparation method and application thereof | |
| KR20010020163A (en) | Stabilized tibolone compositions | |
| CN112645943A (en) | Preparation method of ammonia-containing qunan amorphous system | |
| CN103110595B (en) | Cefdinir dispersible tablet and preparation method thereof | |
| CN103110596B (en) | Cefprozil dispersible tablet and preparation method thereof | |
| CN101297809B (en) | Preparation of cefoperazone and sulbactam sodium mixed powder | |
| CN113520994A (en) | Mupirocin ointment preparation | |
| CN104173303B (en) | Linezolid-containing composition and preparation method thereof | |
| CN104873501A (en) | Sulbactam sodium composition for treating infectious diseases | |
| CN102743369A (en) | N-acetylcysteine pharmaceutical composition and preparation method thereof | |
| CN104739792B (en) | Preparation method of roxithromycin dispersible tablet | |
| CN103301468B (en) | The luteolin composition of high-load | |
| CN117503719A (en) | Meisartan potassium tablet and preparation method thereof | |
| CN114681404B (en) | Repaglinide granule pharmaceutical composition and preparation method thereof | |
| CN113662919B (en) | Stable cefixime tablet and preparation method thereof | |
| CN103720666B (en) | A kind of preparation method of injection bortezomib lyophilized formulations | |
| CN111377947B (en) | Amoxicillin trihydrate pharmaceutical composition with low water activity and preparation method thereof | |
| WO2022172076A1 (en) | Preparation of microwave dried novel co-processed excipient of sucrose and tablet formulation of canagliflozin tablets using co- processed excipient | |
| CN113797171A (en) | Pegylated recombinant human granulocyte colony stimulating factor freeze-dried preparation | |
| CN115282123A (en) | Preparation method of stable nicorandil preparation | |
| CN114159398A (en) | Procaterol hydrochloride oral solid composition and preparation method thereof | |
| CN114315897B (en) | Novel crystals of tedizolid phosphate and preparation method thereof | |
| CN103610654B (en) | Micronized tinidazole powder injection |
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 | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20210413 |
|
| RJ01 | Rejection of invention patent application after publication |