CN101940572A - Composition of cefamandole nafate and tazobactam sodium and proportioning thereof - Google Patents
Composition of cefamandole nafate and tazobactam sodium and proportioning thereof Download PDFInfo
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- CN101940572A CN101940572A CN2010100026605A CN201010002660A CN101940572A CN 101940572 A CN101940572 A CN 101940572A CN 2010100026605 A CN2010100026605 A CN 2010100026605A CN 201010002660 A CN201010002660 A CN 201010002660A CN 101940572 A CN101940572 A CN 101940572A
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- cefamandole nafate
- sodium
- tazobactam
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- RRJHESVQVSRQEX-SUYBPPKGSA-N O-formylcefamandole Chemical group CN1N=NN=C1SCC1=C(C(O)=O)N2C(=O)[C@@H](NC(=O)[C@H](OC=O)C=3C=CC=CC=3)[C@H]2SC1 RRJHESVQVSRQEX-SUYBPPKGSA-N 0.000 title claims abstract description 62
- 229960002440 cefamandole nafate Drugs 0.000 title claims abstract description 62
- 239000000203 mixture Substances 0.000 title claims abstract description 16
- NDIURPSCHWTXDC-UHFFFAOYSA-N 2-(4,5-dimethoxy-2-nitrophenyl)acetohydrazide Chemical compound COC1=CC(CC(=O)NN)=C([N+]([O-])=O)C=C1OC NDIURPSCHWTXDC-UHFFFAOYSA-N 0.000 title abstract description 13
- 229960000373 tazobactam sodium Drugs 0.000 title abstract description 13
- 229960003865 tazobactam Drugs 0.000 claims description 46
- OJMNTWPPFNMOCJ-CFOLLTDRSA-M cefamandole sodium Chemical compound [Na+].CN1N=NN=C1SCC1=C(C([O-])=O)N2C(=O)[C@@H](NC(=O)[C@H](O)C=3C=CC=CC=3)[C@H]2SC1 OJMNTWPPFNMOCJ-CFOLLTDRSA-M 0.000 claims description 13
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 28
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- 238000012360 testing method Methods 0.000 abstract description 8
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- 208000035473 Communicable disease Diseases 0.000 abstract 1
- 229940126573 antibacterial therapeutic Drugs 0.000 abstract 1
- 230000001225 therapeutic effect Effects 0.000 abstract 1
- 238000002560 therapeutic procedure Methods 0.000 abstract 1
- 241000588724 Escherichia coli Species 0.000 description 12
- 229940088710 antibiotic agent Drugs 0.000 description 8
- 229960003012 cefamandole Drugs 0.000 description 8
- OLVCFLKTBJRLHI-AXAPSJFSSA-N cefamandole Chemical compound CN1N=NN=C1SCC1=C(C(O)=O)N2C(=O)[C@@H](NC(=O)[C@H](O)C=3C=CC=CC=3)[C@H]2SC1 OLVCFLKTBJRLHI-AXAPSJFSSA-N 0.000 description 8
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- 230000002401 inhibitory effect Effects 0.000 description 5
- 229940031000 streptococcus pneumoniae Drugs 0.000 description 5
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
- 241000588747 Klebsiella pneumoniae Species 0.000 description 4
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- 239000003781 beta lactamase inhibitor Substances 0.000 description 4
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- 235000015424 sodium Nutrition 0.000 description 3
- 229960005256 sulbactam Drugs 0.000 description 3
- FKENQMMABCRJMK-RITPCOANSA-N sulbactam Chemical compound O=S1(=O)C(C)(C)[C@H](C(O)=O)N2C(=O)C[C@H]21 FKENQMMABCRJMK-RITPCOANSA-N 0.000 description 3
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- CZTQZXZIADLWOZ-CRAIPNDOSA-N cefaloridine Chemical compound O=C([C@@H](NC(=O)CC=1SC=CC=1)[C@H]1SC2)N1C(C(=O)[O-])=C2C[N+]1=CC=CC=C1 CZTQZXZIADLWOZ-CRAIPNDOSA-N 0.000 description 2
- ICZOIXFFVKYXOM-YCLOEFEOSA-M cefamandole nafate Chemical compound [Na+].CN1N=NN=C1SCC1=C(C([O-])=O)N2C(=O)[C@@H](NC(=O)[C@H](OC=O)C=3C=CC=CC=3)[C@H]2SC1 ICZOIXFFVKYXOM-YCLOEFEOSA-M 0.000 description 2
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- LHNIIDJCEODSHA-OQRUQETBSA-N (6r,7r)-3-[(e)-2-(2,4-dinitrophenyl)ethenyl]-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound N([C@H]1[C@H]2SCC(=C(N2C1=O)C(=O)O)\C=C\C=1C(=CC(=CC=1)[N+]([O-])=O)[N+]([O-])=O)C(=O)CC1=CC=CS1 LHNIIDJCEODSHA-OQRUQETBSA-N 0.000 description 1
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- 241000588986 Alcaligenes Species 0.000 description 1
- LSBDFXRDZJMBSC-UHFFFAOYSA-N Amide-Phenylacetic acid Natural products NC(=O)CC1=CC=CC=C1 LSBDFXRDZJMBSC-UHFFFAOYSA-N 0.000 description 1
- 241000606124 Bacteroides fragilis Species 0.000 description 1
- 108020004256 Beta-lactamase Proteins 0.000 description 1
- GBOHXXNQZXUYHZ-UHFFFAOYSA-N CC1(C(N2C(CC2C1S(=O)(=O)O)=O)C(=O)O)CN1N=NC=C1 Chemical compound CC1(C(N2C(CC2C1S(=O)(=O)O)=O)C(=O)O)CN1N=NC=C1 GBOHXXNQZXUYHZ-UHFFFAOYSA-N 0.000 description 1
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- 241000606768 Haemophilus influenzae Species 0.000 description 1
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 1
- AYDQIZKZTQHYIY-UHFFFAOYSA-N OC(=O)C1(C)CC(C(O)=O)=CC=C1 Chemical compound OC(=O)C1(C)CC(C(O)=O)=CC=C1 AYDQIZKZTQHYIY-UHFFFAOYSA-N 0.000 description 1
- 241000283898 Ovis Species 0.000 description 1
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- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
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- 241000607768 Shigella Species 0.000 description 1
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- HVYLDJKDVOOTHV-UHFFFAOYSA-N acetic acid;2-iminoethanethiol Chemical compound CC(O)=O.CC(O)=O.SCC=N HVYLDJKDVOOTHV-UHFFFAOYSA-N 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
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- 229960000603 cefalotin Drugs 0.000 description 1
- 229960001139 cefazolin Drugs 0.000 description 1
- MLYYVTUWGNIJIB-BXKDBHETSA-N cefazolin Chemical compound S1C(C)=NN=C1SCC1=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CN3N=NN=C3)[C@H]2SC1 MLYYVTUWGNIJIB-BXKDBHETSA-N 0.000 description 1
- FLKYBGKDCCEQQM-WYUVZMMLSA-M cefazolin sodium Chemical compound [Na+].S1C(C)=NN=C1SCC1=C(C([O-])=O)N2C(=O)[C@@H](NC(=O)CN3N=NN=C3)[C@H]2SC1 FLKYBGKDCCEQQM-WYUVZMMLSA-M 0.000 description 1
- 229960003408 cefazolin sodium Drugs 0.000 description 1
- VUFGUVLLDPOSBC-XRZFDKQNSA-M cephalothin sodium Chemical compound [Na+].N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC(=O)C)C([O-])=O)C(=O)CC1=CC=CS1 VUFGUVLLDPOSBC-XRZFDKQNSA-M 0.000 description 1
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- 210000001503 joint Anatomy 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
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- LPQZKKCYTLCDGQ-WEDXCCLWSA-N tazobactam Chemical compound C([C@]1(C)S([C@H]2N(C(C2)=O)[C@H]1C(O)=O)(=O)=O)N1C=CN=N1 LPQZKKCYTLCDGQ-WEDXCCLWSA-N 0.000 description 1
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Abstract
The invention relates to composition of cefamandole nafate and tazobactam sodium and proportioning thereof. The composition is characterized by consisting of the cefamandole nafate and the tazobactam sodium, wherein the weight ratio of the cefamandole nafate to the tazobactam sodium is 1:1-8:1. In infectious diseases caused by bacteria, some bacteria are found to be resistant against the cefamandole nafate due to produced beta-lactamase, so the therapy is ineffective; and after the cefamandole nafate and the tazobactam sodium are combined, strong antibacterial activity is generated to gram negative bacilli and gram positive bacilli for producing the beta-lactamase. The composition is sensitive to bacterial strains which are resistant against the cefamandole nafate and has a powerful antibacterial therapeutic effect, full testing basis and clear clinical antibacterial effect without increasing untoward reaction.
Description
Invention field
The invention belongs to medical technical field, relate to the compositions and the proportioning thereof of a kind of antibiotic cefamandole nafate and sodium-tazobactam.
Background information
Cefamandole nafate
Cefamandole nafate has another name called Cefamandole Sodium, Cefamandole Nafate, cefadole, Cefamandole Nafate, cefadole.
English name: Cefamandole Nafate
Chemical name: 7-D-(2-methanoyl phenyl acetamide)-3-[(1-methyl isophthalic acid H-tetrazolium-5 base) sulfidomethyl]-3-cephem-4-carboxylic acid sodium salt.
Its chemical structural formula:
Molecular formula: C19H17N6NaO6S2
Molecular weight: 512.38
This product is semi-synthetic second generation cephalosporin, and antimicrobial spectrum is similar to cefaloridine, and gram positive coccus is not so good as cefaloridine.This product main feature is strong to the gram-negative bacteria effect, is better than cefazolin sodium.Stronger to effects such as the positive Bacillus proteuss of clostridium, meningococcus, gonococcus, escherichia coli, pneumobacillus, hemophilus influenza and indole that is sick of, particularly to haemophilus, this product is the most effective.Be used for the various infection due to the sensitive organism, as infection such as respiratory tract infection, biliary tract infection, pyelonephritis, urinary tract infection, peritonitis, septicemia and skin soft tissue, bone, joints.Because the urine drug level height has efficiently urinary tract infection.
Cefamandole has stronger antibacterial action to most gram negative bacillis, and it is active similar with cefalotin and cefazolin.This product has strong antibacterial activity to diphtheria corynebacterium, escherichia coli, proteus mirabilis, pneumobacillus, hemophilus influenza, part aerobacteria, the positive Bacillus proteus of indole, Pu Luweideng bacterium, Bacillus typhi, Shigella, gonococcus and meningococcus; Antibacterial action to bacteroides fragilis is relatively poor.Husky thunder bacterium, Bacillus alcaligenes, acinetobacter, pseudomonas, enterococcus and methicillin-resistant gold-coloured staphylococci are to this product drug resistance.Sodium-tazobactam Tazobactam Sodium
The sodium-tazobactam chemical name: (2S, 3S, 5R)-and 3-methyl-7-oxo-3-(1H-1,2,3-triazole-1-ylmethyl)-4-sulfo--1-azabicyclo [3.2.0] heptane-2-carboxylic acid 4, the 4-dioxide
Molecular formula: C
10H
11N
4NaO
5S
Molecular weight: 322.27
Chemical structural formula:
Sodium-tazobactam is a kind of beta-lactamase inhibitor, and it is low to have toxicity, and good stability presses down advantages such as enzymatic activity is strong.Various types of beta-lactamases (particularly ultraphotic spectrum beta-lactamase) all there is irreversible inhibitory action.
At present because the irrational application of antibiotics causes the Grain-positive bacillus increasing to cephalo Meng drug resistance how.Domestic and international up-to-date bacterial resistance monitoring result shows, 1-4 is risen respectively for the antibiotics resistant rate.Sodium-tazobactam (sulbactam) is a kind of wide spectrum beta-lactamase inhibitor, and is stronger to the inhibitory action of wide spectrum enzyme, and super wide spectrum enzyme is also had certain effect.With the two associating, by the enzyme effect that presses down of beta-lactamase inhibitor, stable and enhancing antimicrobial susceptibility; Stronger antibacterial activity is arranged, the antimicrobial spectrum expanded range to producing the beta-lactamase gram positive coccus simultaneously.
Summary of the invention
Purpose of the present invention: be to provide better compositions of a kind of antibacterial effect and proportioning thereof, after cefamandole nafate and sodium-tazobactam use in conjunction, the gram negative bacilli and the gram positive coccus of producing beta-lactamase produced stronger antibacterial activity.
Cefamandole is a second generation cephalosporin, and sterilizing power is strong, but to the beta-lactamase less stable, and the main resistance mechanism of enterobacteriaceae lactobacteriaceae is for producing beta-lactamase.The drug resistance monitoring result shows [3-7], and the escherichia coli, Klebsiella Pneumoniae and the Bacillus proteus that separate from the patient that is in hospital have reached 76.2%, 57.5% and 34.6% to the second generation cephalosporin resistant rate, increase 10-20 percentage point before 10 years.The beta-lactamase inhibitor Tazobactam Sodium can suppress the activity of wide spectrum enzyme and super wide spectrum enzyme, overcomes bacterial resistance by inhibitory enzyme, recovers the antibacterials effect.Therefore, antibacterial receives to Mandokef after the drug resistance, and the compositions of Mandokef and Tazobactam Sodium solves its drug resistance problem specially, has expanded its antibiotic curative effect.
Cefamandole nafate in clinical practice for many years, be used for pulmonary infection, urinary tract infection, biliary tract infection, skin soft-tissue infection, bone and the infection of joint due to the sensitive bacterial and septicemia, abdominal cavity infection etc., but because clinical abuse, the clinical efficacy that drug resistance causes descends, and sees from national drug resistance monitoring.
Developing this product, also meet the current policy that clinical antibacterials are used by turns of implementing in the world, increase the selectivity of clinical antibiotics, is significant.
By to 4 kinds of variable concentrations mass ratioes (1: 1,2: 1,4: 1,8: 1) cefamandole nafate and the vitro antibacterial activity that carries out of Tazobactam Sodium composition of sodium studies show that cefamandole nafate and sodium-tazobactam use in conjunction can significantly improve the sensitivity of cefamandole nafate to gram negative bacilli.
The also stronger antibacterial activity of gram positive coccus to the beta-lactamase that produces.
The cefamandole nafate and the sodium-tazobactam of different proportionings all have bigger bactericidal action, and the proportioning of 1: 1 and 2: 1 obviously is better than the independent medication of cefamandole nafate to the bactericidal action of gram positive coccus.
Result of the test shows, cefamandole nafate/sodium-tazobactam 1: 1-8: 1 all has good in-vitro antimicrobial than cefamandole nafate; The cefamandole nafate of 2: 1 proportionings+Tazobactam Sodium composition of sodium has stronger vitro antibacterial activity, and is suitable with 1: 1 proportioning, and 1: 1-8: which is more reasonable for 1 proportioning, can compare diversity by clinical efficacy in the clinical trial afterwards.
Specific embodiment:
Further set forth the present invention below by embodiment, but be not limited to the present invention.
Embodiment: different proportioning cefamandole nafate and the research of sodium-tazobactam vitro antibacterial activity
Materials and methods
1. test drug:
(1) cefamandole nafate (Cefamandole Nafate): Xintai City, Shenzhen medicine company limited provides, and lot number 090604 tires 89.1%.Production unit: Suzhou Erye Pharmaceutical Co., Ltd.
(2) sodium-tazobactam (Tazobactam Sodium): Xintai City, Shenzhen medicine company limited provides, and lot number 0481-9801 tires: 93.7%.Available from Nat'l Pharmaceutical ﹠ Biological Products Control Institute
Following ratio proportioning is calculated by weight, and wherein cefamandole nafate weight is given money as a gift with cefamandole nafate and purely calculated by cefamandole, and Tazobactam Sodium weight is given money as a gift with sodium-tazobactam and purely calculated by Tazobactam Sodium.
2. test proportioning:
(1) cefamandole nafate
(2) sodium-tazobactam
(2) cefamandole nafate+sodium-tazobactam (1: 1)
(3) cefamandole nafate+sodium-tazobactam (2: 1)
(4) cefamandole nafate+sodium-tazobactam (4: 1)
(5) cefamandole nafate+sodium-tazobactam (8: 1)
3. test strain:
3.1 reference culture: large intestine dust antibacterial ATCC25922, ATCC700603, staphylococcus aureus ATCC29213, ATCC25923, streptococcus pneumoniae ATCC49619.
3.2 produce 143 strains of beta-lactamase gram-negative bacteria, measure whether produce enzyme with nitrocefin:
Escherichia coli Escherichia coli (45 strain)
Klebsiella Pneumoniae Klebsiella peumoniae (32 strain)
Enterobacter cloacae Enterobacter cloacae (30 strain)
Proteus mirabilis Proteus mirabilis (26 strain)
Hemophilus influenza Haemophilus influenzae (10 strain)
3.3 produce 69 strains of beta-lactamase gram positive bacteria:
MSSA MSSA (21 strain)
Methicillin-sensitivity staphylococcus epidermidis MSSE (27 strain)
The responsive streptococcus pneumoniae Penicillin-Susceptibility Streptococcus pneumoniae (21 strain) of penicillin
Every strain antibacterial all passes through dull and stereotyped commentaries on classics branch alive before test pure, is used for test with new fresh thalli.Each experiment all uses reference culture as sensitive experiment Quality Control bacterium; With the plate that does not contain antibacterials as the test strain growth control.
4. culture medium and incubation conditions
Staphylococcus and enterobacteriaceae lactobacteriaceae are hatched 16-20h for 35 ℃ in the M-H culture medium; Streptococcus on blood meida (in the M-H culture medium add 5% defiber Sanguis caprae seu ovis make), 35 ℃ of 5%CO
2Environment (CO
2Incubator) hatches 20-24h in.
5. minimum inhibitory concentration (MIC) is measured
Employing standard plate doubling dilution.Antibacterials are measured concentration range 256-0.016mg/L.Tested bacteria suspension is inoculated with multiple spot inoculation instrument, and every some inoculum concentration is 10
4CFU.Measure the minimum inhibitory concentration of each antibacterials to various pathogenic bacterium.
The result
1. cefamandole nafate/the sodium-tazobactam of different proportionings is to MIC result's (table 1) of the clinical separation pathogenic bacterium of 212 strains
As can be seen from Table 1, for the escherichia coli, Klebsiella Pneumoniae, enterobacter cloacae and the proteus mirabilis that produce beta-lactamase, add the antibacterial activity that sulbactam can obviously improve cefamandole, MIC
50Value can descend 2-32 doubly, MIC
90Value decline 2-32 doubly.
For MSSA (MSSA) and methicillin-sensitivity staphylococcus epidermidis (MSSE), add the antibacterial activity that sulbactam can obviously improve cefamandole, MIC
50Value can descend 16 times, MIC
90Value decline 8-32 doubly.
Table 1. cefamandole/sodium-tazobactam is to the MIC result of the clinical separation pathogenic bacterium of 212 strains
2. cefamandole nafate/the sodium-tazobactam of different proportionings is to MBC result's (table 2) of the clinical separation pathogenic bacterium of 60 strains
MBC result shows, the cefamandole nafate of 4 kinds of different proportionings and sodium-tazobactam are to MBC/MIC≤2 of escherichia coli and streptococcus pneumoniae times, to MBC/MIC≤4 of staphylococcus aureus times, illustrate that the compositions of cefamandole nafate and sodium-tazobactam has typical bactericidal action.
Cefamandole nafate/the sodium-tazobactam of the different proportionings of table 2 is to the MBC of the clinical separation pathogenic bacterium of 40 strains
3. killing curve result:
Cefamandole nafate/the sodium-tazobactam of four kinds of proportionings and cefamandole nafate single dose are seen Fig. 1～2 to the killing curve of the 4 strain clinical isolates such as escherichia coli No.157 of product beta-lactamase.
Shown in Fig. 1,2, No.157 and No.198 are the escherichia colis of two strains to cefamandole nafate+sodium-tazobactam medium sensitivity, and the MIC of cefamandole nafate+sodium-tazobactam is respectively 8 and 4mg/L.When drug level is 8mg/L and 4mg/L, cefamandole nafate+the sodium-tazobactam of 1: 1 proportioning can 24 hours can be respectively with 2 strain bacterium from 4.67 and 4.71Lg CFU/ml reduce to 0.2 and 0.3Lg CFU/ml, 2: 1 proportioning can be reduced to 2 strain bacterium 0.5 and 0.5Lg CFU/ml at 24 hours respectively.
Fig. 3,4 is for producing the MSSA killing curve of beta-lactamase, cefamandole nafate+the sodium-tazobactam of 1: 1 proportioning to the bactericidal action of No.188 and No.164 when concentration is 4mg/L and 8mg/L, can be in 24 hours with this bacterium by 4.7 with 4.68Lg CFU/ml reduces to 0.3,0.1Lg CFU/ml, the cefamandole nafate+sodium-tazobactam of 2: 1 proportionings can be reduced to this bacterium 0.7 in 24 hours, 0.7Lg CFU/ml was better than 4: 1 and 8: 1 proportionings.
4. to the influence factor of vitro antibacterial activity:
(1) as shown in table 3, the cefamandole nafate/sodium-tazobactam of different proportionings is respectively 10 at bacterial load
4, 10
5, 10
6With 10
7During CFU/ml, to escherichia coli, Klebsiella Pneumoniae and staphylococcus aureus MIC value.Illustrate that bacterial load is 10
4～10
7CFU/ml does not have obviously influence to the MIC value of the anti-3 kinds of bacterium of cefamandole nafate/sodium-tazobactam of different proportionings.
Table 3 cefamandole nafate+sodium-tazobactam is to the influence of bacterial load
(2) as seen from Table 4, the MIC value to escherichia coli, streptococcus pneumoniae, staphylococcus aureus of four kinds of proportioning cefamandole nafate+Tazobactam Sodiums does not have obviously influence in pH5.0～pH8.5 scope.
(3) human albumin's content in the culture medium, the appreciable impact (table 5) that the outer antibacterial action of the cefamandole nafate+sodium-tazobactam of four kinds of proportionings is not had.
Table 5. cefamandole nafate+sodium-tazobactam human albumin's content is to the influence of MIC
Description of drawings
Fig. 1 is the killing curve figure of cefamandole nafate+sodium-tazobactam to the No.157 escherichia coli
Fig. 2 is the killing curve figure of cefamandole nafate+sodium-tazobactam to the No.198 escherichia coli
Fig. 3 is the killing curve figure of cefamandole nafate+sodium-tazobactam to MSSA No.188
Fig. 4 is the killing curve figure of cefamandole nafate+sodium-tazobactam to MSSA No.164.
Claims (3)
1. the compositions and the proportioning thereof of cefamandole nafate and sodium-tazobactam is characterized in that said composition is the combination and the proportioning of cefamandole nafate and sodium-tazobactam.
2. the compositions and the proportioning thereof of a kind of cefamandole nafate according to claim 1 and sodium-tazobactam is characterized in that the combination weight ratio of described cefamandole nafate and sodium-tazobactam is 1: 1～8: 1.
3. the compositions and the proportioning thereof of a kind of cefamandole nafate according to claim 2 and sodium-tazobactam is characterized in that the preferable weight ratio of combination of the compositions of described cefamandole nafate and sodium-tazobactam is 1: 1～2: 1.
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Citations (3)
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| CN1850047A (en) * | 2006-06-01 | 2006-10-25 | 济南帅华医药科技有限公司 | Slow-release preparation containing beta-lactamase inhibitor and cephalosporin and its use |
| CN101129382A (en) * | 2006-08-25 | 2008-02-27 | 天津和美生物技术有限公司 | Antibiotic compound containing beta-lactam antibiotic and buffering component |
| CN101129381A (en) * | 2006-08-25 | 2008-02-27 | 天津和美生物技术有限公司 | Antibiotic compound containing beta-lactam antibiotic and ion chelating agent |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1850047A (en) * | 2006-06-01 | 2006-10-25 | 济南帅华医药科技有限公司 | Slow-release preparation containing beta-lactamase inhibitor and cephalosporin and its use |
| CN101129382A (en) * | 2006-08-25 | 2008-02-27 | 天津和美生物技术有限公司 | Antibiotic compound containing beta-lactam antibiotic and buffering component |
| CN101129381A (en) * | 2006-08-25 | 2008-02-27 | 天津和美生物技术有限公司 | Antibiotic compound containing beta-lactam antibiotic and ion chelating agent |
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