CN100358522C - Anti-beta-lactamase antibiotic composite preparation - Google Patents
Anti-beta-lactamase antibiotic composite preparation Download PDFInfo
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- CN100358522C CN100358522C CNB2005100850793A CN200510085079A CN100358522C CN 100358522 C CN100358522 C CN 100358522C CN B2005100850793 A CNB2005100850793 A CN B2005100850793A CN 200510085079 A CN200510085079 A CN 200510085079A CN 100358522 C CN100358522 C CN 100358522C
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Abstract
The present invention discloses an anti-beta-lactamase antibiotic compound preparation, more specifically, a compound preparation composed of ticarcillin and salts thereof, and sulbactam and salts thereof, or tazobactam and salts thereof. In the compound preparation, the weight ratio range of the ticarcillin and the salts thereof to the sulbactam and the salts thereof, or the tazobactam and the salts thereof is from 1:1 to 10:1; the preferable weight ratio range of the ticarcillin and the salts thereof to the sulbactam and the salts thereof is from 2:1 to 6:1, and the optimal weight ratio is 2:1; the preferable weight ratio range of the ticarcillin and the salts thereof to the tazobactam and the salts thereof is from 1:1 to 6:1, and the optimal weight ratio is 4:1. Compared with ticarcillin, the present invention has the advantages of broader antibacterial spectrum and stronger antibacterial action.
Description
Technical field
The present invention relates to a kind of anti-beta-lactamase antibiotic composite preparation, specifically relate to the compound preparation that ticarcillin and salt thereof and sulbactam and salt thereof or Tazobactam Sodium and salt thereof are formed.
Background technology
The penicillins antibacterials have been widely used in clinical, for human beings'health has played positive role.Simultaneously, owing to use clinically for a long time, widely, antibacterial is serious day by day to the drug resistance problem of Penicillin antibiotics.Antibacterial is the specific beta-lactamase of generation (β-lactmases) decompose medicine, comprising the I type cephalosporinase that is mediated by chromosome with by plasmid-mediated extended spectrum to the drug-fast main mechanism of Penicillin antibiotics.
To produce the clinical drug-resistant sexuality that the beta-lactamase antibacterial caused and dye in order to overcome, the compound preparation of development Penicillin antibiotics and beta-lactamase inhibitor has the important clinical meaning.
(Cefuroxime TIC) is semisynthetic anti-pseudomonas penicillin to ticarcillin, infects effective especially for serious gram-negative bacteria.Its common dosage forms ticarcillin disodium is a kind of injection semisynthetic penicillin injection.Ticarcillin is a kind of new thiophene alkene penicillin carboxy, and its antimicrobial spectrum and pharmacological characteristics and carbenicillin are similar.Ticarcillin is a kind of bactericide, influences the synthetic of bacteria cell wall by disturbing the mucopeptide cross link, causes the defective or the weakness of cell wall, and antibacterial presents deformity, and it is dead with rapid dissolving to continue, thereby reaches antibacterial action.Ticarcillin antimicrobial spectrum and carbenicillin are approximate, and the bacteriostasis of gram positive bacteria is lower than benzylpenicillin; To the bacteriostasis of gram-negative bacteria than the strong several times of carbenicillin.In recent years, along with ticarcillin use clinically increasingly extensive, experimental study shows that the original responsive bacterial strain of part has produced the drug resistance phenomenon to ticarcillin, cure rate descends to some extent.
Summary of the invention
At more present bacterial strains ticarcillin has been produced the drug resistance problem, the objective of the invention is to overcome above-mentioned the deficiencies in the prior art, provide a kind of drug resistance that can resist bacterial strain to send out the anti-beta-lactamase antibiotic composite preparation of giving full play to the ticarcillin antibiotic property.
The inventor is by studying for a long period of time and test in a large number, filtered out the beta-lactamase inhibitor that good collaborative, booster action can be arranged with ticarcillin finally, forms compound preparation with ticarcillin.The invention provides a kind of anti-beta-lactamase antibiotic composite preparation, be made up of ticarcillin and salt thereof and sulbactam and salt thereof, the weight ratio of described ticarcillin and salt thereof and sulbactam and salt thereof is 1: 1 to 10: 1.
In the described anti-beta-lactamase antibiotic composite preparation, the preferred weight ratio of described ticarcillin and salt thereof and sulbactam and salt thereof is 2: 1 to 6: 1.
In the described anti-beta-lactamase antibiotic composite preparation, the optimum weight ratio of described ticarcillin and salt thereof and sulbactam and salt thereof is 2: 1.
The equal preferred as alkali salt of the salt of described ticarcillin, sulbactam.
The preparation method of described anti-beta-lactamase antibiotic composite preparation is undertaken making injectable powder or lyophilized injectable powder by known injectable powder or the operation of lyophilized injectable powder process.
Adopt technical scheme provided by the invention, compare with simple employing ticarcillin, owing to adopted sulbactam as beta-lactamase inhibitor, resist and suppressed the Drug resistance of strain generation, and has good synergism with ticarcillin, can bring into play the antibiotic property of ticarcillin, injection anti-beta-lactamase antibiotic composite preparation antimicrobial spectrum is wider, antibacterial action is stronger.
The specific embodiment
Below in conjunction with specific embodiment anti-beta-lactamase antibiotic composite preparation of the present invention is described further.
Embodiment 1: preparation ticarcillin and sulbactam compound preparation
1g ticarcillin aseptic powder and 1g sulbactam aseptic powder are mixed, by known injectable powder or the operation of lyophilized injectable powder process.
Embodiment 2: preparation ticarcillin sodium and sulbactam compound preparation
1g ticarcillin sodium aseptic powder and 0.5g sulbactam aseptic powder are mixed, by known injectable powder or the operation of lyophilized injectable powder process.
Embodiment 3: preparation ticarcillin potassium and sulbactam compound preparation
1g ticarcillin potassium aseptic powder and 0.25g sulbactam aseptic powder are mixed, by known injectable powder or the operation of lyophilized injectable powder process.
Embodiment 4: preparation ticarcillin and sulbactam sodium compound preparation
1g ticarcillin aseptic powder and 0.2g sulbactam sodium aseptic powder are mixed, by known injectable powder or the operation of lyophilized injectable powder process.
Embodiment 5: preparation ticarcillin sodium and sulbactam sodium compound preparation
1g ticarcillin sodium aseptic powder and 0.1g sulbactam sodium aseptic powder are mixed, by known injectable powder or the operation of lyophilized injectable powder process.
Embodiment 6: preparation ticarcillin potassium and sulbactam sodium compound preparation
1g ticarcillin potassium aseptic powder and 0.25g sulbactam sodium aseptic powder are mixed, by known injectable powder or the operation of lyophilized injectable powder process.
Embodiment 7: preparation ticarcillin and Potassium penicillanate 1,1-dioxide. compound preparation
1g ticarcillin aseptic powder and 0.25g Potassium penicillanate 1,1-dioxide. aseptic powder are mixed, by known injectable powder or the operation of lyophilized injectable powder process.
Embodiment 8: preparation ticarcillin sodium and Potassium penicillanate 1,1-dioxide. compound preparation
1g ticarcillin sodium aseptic powder and 0.25g Potassium penicillanate 1,1-dioxide. aseptic powder are mixed, by known injectable powder or the operation of lyophilized injectable powder process.
Embodiment 9: preparation ticarcillin potassium and Potassium penicillanate 1,1-dioxide. compound preparation
1g ticarcillin potassium aseptic powder and 0.25g Potassium penicillanate 1,1-dioxide. aseptic powder are mixed, by known injectable powder or the operation of lyophilized injectable powder process.
Embodiment 10: preparation ticarcillin potassium and sulbactam sodium compound preparation
1.6g ticarcillin potassium aseptic powder and 0.2g sulbactam sodium aseptic powder are mixed, become injectable powder or lyophilized injectable powder by existing injectable powder or lyophilized injectable powder prepared.
Experimental example 1: ticarcillin and sulbactam compound preparation in-vitro antibacterial and bactericidal assay
Dissolve and by active drug content preparation and be diluted to required drug level, the active drug proportioning of ticarcillin/sulbactam is 1: 1,2: 1,4: 1,8: 1,10: 1 with sterilized water or sterile saline.The bacterial strain that experiment is adopted is clinical separation strain, and every strain derives from different patients.
1.1 the mensuration of minimum inhibitory concentration (MIC)
The medicine of drawing the good variable concentrations of an amount of dilution places aseptic plane ware, adds the sterilising medium of constant temperature in about 55 ℃, and the medicine flat board is made in the mixing cooling.Cultured test organisms is diluted to desired concn with sterilized water (is generally 10
7About CFU/ml), adopt multiple spot inoculation instrument to be connected to the medicine flat board of variable concentrations, inoculum concentration is about 10
4～10
5The CFU/ point.Test organisms is in 24 hours observed results of 37 ℃ of constant temperature culture, and record MIC value.It the results are shown in Table 1-1.
1.2 the mensuration of minimum bactericidal concentration (MBC)
Adopt meat soup doubling dilution viable bacteria counting method, promptly in the drug solution of doubling dilution, add certain density bacterium liquid, mix the back in 37 ℃ of constant temperature culture 24 hours, measure the MIC value earlier, to not see the clarifying culture sucking-off 0.1ml respectively that respectively manages of bacterial growth more successively, carry out dull and stereotyped count plate, wherein clump count is less than the MBC value that 5 dull and stereotyped pairing lowest concentration of drug is this medicine.It the results are shown in Table 1-2.
By table 1-1 as can be known, the weight ratio of ticarcillin and sulbactam is 1: 1 to 10: 1 o'clock in ticarcillin and the sulbactam compound preparation, and antibacterial activity in vitro is better, and the preferred weight ratio of ticarcillin and sulbactam is 2: 1 to 6: 1.Ticarcillin and sulbactam compound preparation (TIC/SBT=2: 1) strong than ticarcillin to the antibacterial activity in vitro of producing the enzyme strain, antibacterial activity in vitro to the strain of non-product enzyme is similar to ticarcillin, wherein to the MIC of staphylococcus aureus (product enzyme), staphylococcus epidermidis (product enzyme), streptococcus pneumoniae (product enzyme), colon bacillus (product enzyme), Klebsiella pneumonia (product enzyme), Pseudomonas aeruginosa (product enzyme), acinetobacter calcoaceticus (product enzyme), aerobacteria (product enzyme), shigella flexneri (product enzyme) and enterobacter cloacae (product enzyme)
50Be respectively 16,8,4,8,8,8,2,1,2 and 32 μ g/ml, MIC
90Be respectively 64,32,16,64,64,32,8,8,8 and 256 μ g/ml, ticarcillin is to the MIC of staphylococcus aureus (product enzyme), staphylococcus epidermidis (product enzyme), streptococcus pneumoniae (product enzyme), colon bacillus (product enzyme), Klebsiella pneumonia (product enzyme), Pseudomonas aeruginosa (product enzyme), acinetobacter calcoaceticus (product enzyme), aerobacteria (product enzyme), shigella flexneri (product enzyme) and enterobacter cloacae (product enzyme)
50Be respectively 64,128,32,64,64,128,8,8,8 and 128 μ g/ml, MIC
90Be respectively 256, 〉=256,128, 〉=256, 〉=256, 〉=256,32,32,64 and 〉=256 μ g/ml.
By table 1-2 as can be known, ticarcillin and sulbactam compound preparation (TIC/SBT=2: 1) strong than ticarcillin to the antibacterial activity in vitro of producing the enzyme strain, antibacterial activity in vitro to the strain of non-product enzyme is similar to ticarcillin, wherein staphylococcus aureus (is produced enzyme, S.aures
E), colon bacillus (produces enzyme, E.coli
E) and Pseudomonas aeruginosa (product enzyme, P.aeruginosa
E) MBC/MIC value scope is respectively 4-8,4,4-8; Ticarcillin to staphylococcus aureus (product enzyme), colon bacillus (product enzyme) and Pseudomonas aeruginosa (product enzyme) MBC/MIC value scope be 4-8,4-8 and 〉=4.
Table 1-1 ticarcillin (TIC) and ticarcillin/sulbactam (TIC/SBT) antibacterial activity in vitro (MIC≤16 are judged to be sensitivity)
| Antibacterial | The strain number | Medicine | MIC(μg/ml) | |||||||
| ≤6 | 32 | 64 | ≥128 | MIC 50 | MIC 90 | The MIC scope | Responsive rate (%) | |||
| The strain number | ||||||||||
| Staphylococcus aureus (product enzyme) | 30 | TIC TIC/SBT(1∶1) TIC/SBT(2∶1) TIC/SBT(4∶1) TIC/SBT(8∶1) TIC/SBT(10∶1) | 1 14 20 17 11 6 | 6 7 6 4 2 4 | 9 6 3 4 3 4 | 14 3 1 5 14 16 | 64 32 16 16 64 64 | 256 64 64 128 256 256 | 4～≥256 4～≥256 4～256 4～≥256 16～≥256 8～≥256 | 3.3 46.7 66.7 56.7 36.7 20 |
| Staphylococcus aureus | 30 | TIC TIC/SBT(1∶1) TIC/SBT(2∶1) TIC/SBT(4∶1) TIC/SBT(8∶1) TIC/SBT(10∶1) | 23 23 23 24 24 24 | 3 4 5 3 2 4 | 4 2 2 2 3 2 | 0 1 0 1 1 0 | 2 4 2 2 2 2 | 32 32 32 32 64 32 | 1～64 2～128 2～64 0.5～128 1～128 1～64 | 76.7 76.7 76.7 80 80 80 |
| Staphylococcus epidermidis (product enzyme) | 20 | TIC TIC/SBT(1∶1) TIC/SBT(2∶1) TIC/SBT(4∶1) TIC/SBT(8∶1) | 0 9 15 14 3 | 0 4 3 3 5 | 4 5 1 2 4 | 16 2 1 1 8 | 128 32 8 8 64 | ≥256 64 32 64 ≥256 | 64～≥256 4～128 2～128 4～128 16～≥256 | 0 45 75 70 15 |
| TIC/SBT(10∶1) | 0 | 0 | 5 | 15 | 64 | ≥256 | 64～≥256 | 0 | ||
| Staphylococcus epidermidis | 20 | TIC TIC/SBT(1∶1) TIC/SBT(2∶1) TIC/SBT(4∶1) TIC/SBT(8∶ 1) TIC/SBT(10∶1) | 19 14 18 18 19 18 | 0 4 1 1 0 2 | 1 2 1 1 1 0 | 0 0 0 0 0 0 | 2 4 2 2 2 1 | 8 32 16 16 8 8 | 0.5～64 0.5～64 0.25～64 0.5～64 0.5～64 0.5～32 | 95 70 90 90 95 90 |
| Streptococcus pneumoniae (product enzyme) | 10 | TIC TIC/SBT(1∶1) TIC/SBT(2∶1) TIC/SBT(4∶1) TIC/SBT(8∶1) TIC/SBT(10∶1) | 2 5 8 8 5 3 | 4 2 2 1 2 3 | 2 2 0 1 2 2 | 2 1 0 0 1 2 | 32 16 4 4 16 32 | 128 64 16 32 64 128 | 16～256 4～128 0.5～32 1～64 2～128 2～128 | 20 50 80 80 50 30 |
| Streptococcus pneumoniae | 10 | TIC TIC/SBT(1∶1) TIC/SBT(2∶1) TIC/SBT(4∶1) TIC/SBT(8∶1) TIC/SBT(10∶1) | 9 5 7 7 9 9 | 1 2 2 2 0 1 | 0 2 1 1 1 0 | 0 1 0 0 0 0 | 4 8 8 8 4 4 | 16 64 32 32 16 16 | 2～32 2～128 1～64 2～64 2～64 1～32 | 90 50 70 70 90 90 |
| Colon bacillus (product enzyme) | 20 | TIC TIC/SBT(1∶1) TIC/SBT(2∶1) TIC/SBT(4∶1) TIC/SBT(8∶1) TIC/SBT(10∶1) | 0 11 15 14 8 2 | 3 2 3 2 5 5 | 4 2 1 3 3 3 | 13 1 1 1 4 10 | 64 16 8 16 32 64 | ≥256 64 32 64 128 ≥256 | 2～≥256 2～256 1～128 4～128 8～≥256 4～≥256 | 0 55 75 70 40 10 |
| Colon bacillus | 32 | TIC TIC/SBT(1∶1) TIC/SBT(2∶1) TIC/SBT(4∶1) TIC/SBT(8∶1) TIC/SBT(10∶1) | 29 16 22 22 29 28 | 1 5 6 7 3 3 | 1 9 3 3 0 1 | 1 2 1 0 0 0 | 8 16 16 16 8 8 | 16 64 32 32 16 32 | 0.25～128 2～128 2～128 0.5～64 0.5～32 1～64 | 90.6 50 68.8 68.8 90.6 87.5 |
| Pseudomonas aeruginosa (product enzyme) | 18 | TIC TIC/SBT(1∶1) TIC/SBT(2∶1) TIC/SBT(4∶1) TIC/SBT(8∶1) TIC/SBT(10∶1) | 0 11 13 12 3 0 | 0 3 3 4 4 5 | 1 1 1 1 3 5 | 17 3 1 1 8 8 | 128 16 8 16 64 64 | ≥256 128 32 32 256 ≥256 | 64～≥256 4～≥256 2～128 2～128 16～≥256 32～≥256 | 0 61.1 72.2 66.7 16.7 0 |
| Pseudomonas aeruginosa | 16 | TIC TIC/SBT(1∶1) TIC/SBT(2∶1) TIC/SBT(4∶1) TIC/SBT(8∶1) TIC/SBT(10∶1) | 7 7 7 6 13 12 | 4 4 5 8 3 2 | 4 3 2 1 0 1 | 1 2 2 1 2 1 | 16 32 32 32 16 16 | 64 128 128 64 128 64 | 2～128 4～≥256 4～128 4～≥256 2～≥256 4～128 | 43.8 43.8 43.8 37.5 81.3 75 |
| Klebsiella pneumonia (product enzyme) | 16 | TIC TIC/SBT(1∶1) TIC/SBT(2∶1) TIC/SBT(4∶1) TIC/SBT(8∶1) TIC/SBT(10∶1) | 0 5 12 10 3 2 | 3 4 2 3 4 3 | 5 4 1 2 3 4 | 8 3 1 1 6 7 | 64 32 8 16 64 64 | ≥256 128 64 64 128 256 | 16～≥256 4～≥256 2～128 4～128 4～≥256 16～≥256 | 0 31.3 75 62.5 18.8 12.5 |
| Klebsiella pneumonia | 25 | TIC TIC/SBT(1∶1) TIC/SBT(2∶1) TIC/SBT(4∶1) TIC/SBT(8∶1) TIC/SBT(10∶1) | 22 16 19 23 23 24 | 3 7 6 2 2 1 | 0 1 0 1 1 1 | 0 1 0 0 0 0 | 4 16 8 8 4 4 | 8 32 16 32 32 16 | 1～32 4～128 1～32 2～64 1～64 1～64 | 88 64 72 92 92 96 |
| Acinetobacter calcoaceticus (product enzyme) | 10 | TIC TIC/SBT(1∶1) TIC/SBT(2∶1) TIC/SBT(4∶1) TIC/SBT(8∶1) TIC/SBT(10∶1) | 7 7 9 9 8 6 | 2 2 1 0 1 2 | 1 1 0 1 1 2 | 0 0 0 0 0 0 | 8 4 2 4 8 8 | 32 32 8 16 32 64 | 4～64 1～64 1～32 1～64 2～64 4～64 | 70 70 90 90 80 60 |
| Acinetobacter calcoaceticus | 12 | TIC TIC/SBT(1∶1) TIC/SBT(2∶1) TIC/SBT(4∶1) TIC/SBT(8∶1) TIC/SBT(10∶1) | 12 8 12 10 11 11 | 0 4 0 2 1 1 | 0 0 0 0 0 0 | 0 0 0 0 0 0 | 1 4 2 2 1 1 | 4 32 8 8 8 16 | 0.5～16 1～32 0.5～16 0.5～32 0.25～32 0.5～32 | 100 66.7 100 83.3 91.7 91.7 |
| Aerobacteria (product enzyme) | 10 | TIC TIC/SBT(1∶1) TIC/SBT(2∶1) TIC/SBT(4∶1) TIC/SBT(8∶1) TIC/SBT(10∶1) | 6 9 9 9 8 9 | 3 0 1 1 1 0 | 0 1 0 0 1 1 | 1 0 0 0 0 0 | 8 2 1 2 8 8 | 32 16 8 8 32 16 | 2～128 0.5～64 0.25～32 0.5～32 2～64 0.5～64 | 60 90 90 90 80 90 |
| Aerobacteria | 10 | TIC TIC/SBT(1∶1) TIC/SBT(2∶1) TIC/SBT(4∶1) TIC/SBT(8∶1) TIC/SBT(10∶1) | 8 8 9 9 8 9 | 2 1 1 0 1 0 | 0 1 0 1 1 1 | 0 0 0 0 0 0 | 2 8 4 4 4 2 | 8 32 16 16 32 16 | 1～32 2～64 0.5～32 0.5～64 1～64 1～64 | 80 80 90 90 80 90 |
| Shigella flexneri (product enzyme) | 10 | TIC TIC/SBT(1∶1) TIC/SBT(2∶1) TIC/SBT(4∶1) TIC/SBT(8∶1) TIC/SBT(10∶1) | 6 6 10 9 7 5 | 3 1 0 0 2 4 | 1 2 0 1 0 0 | 1 1 0 0 1 1 | 8 16 2 2 8 4 | 64 64 8 16 32 32 | 4～128 2～128 0.5～16 0.25～64 4～128 1～128 | 60 60 100 90 70 50 |
| Shigella flexneri | 10 | TIC TIC/SBT(1∶1) TIC/SBT(2∶1) TIC/SBT(4∶1) TIC/SBT(8∶1) TIC/SBT(10∶1) | 10 7 9 9 8 9 | 0 2 0 0 2 1 | 0 1 1 1 0 0 | 0 0 0 0 0 0 | 2 8 4 4 4 2 | 8 32 16 16 32 16 | 0.25～16 2～64 1～64 1～64 0.5～32 0.5～32 | 100 70 90 90 80 90 |
| Enterobacter cloacae (product enzyme) | 16 | TIC TIC/SBT(1∶1) TIC/SBT(2∶1) TIC/SBT(4∶1) TIC/SBT(8∶1) TIC/SBT(10∶1) | 0 4 8 6 0 0 | 0 3 2 2 5 3 | 4 4 3 5 3 5 | 12 5 3 4 8 8 | 128 64 32 64 64 64 | ≥256 ≥256 256 256 ≥256 ≥256 | 64～≥256 16～≥256 16～≥256 16～≥256 32～≥256 32～≥256 | 0 25 50 37.5 0 0 |
| Enterobacter cloacae | 20 | TIC TIC/SBT(1∶1) TIC/SBT(2∶1) TIC/SBT(4∶1) TIC/SBT(8∶1) TIC/SBT(10∶1) | 14 10 13 14 16 16 | 3 4 5 3 3 3 | 2 4 1 2 0 0 | 1 2 1 1 1 1 | 16 32 16 16 32 16 | 64 64 32 64 32 32 | 4～128 8～128 2～128 2～128 2～128 4～128 | 70 50 65 70 80 80 |
| Typhoid fever Sha Shi door Salmonella | 10 | TIC TIC/SBT(1∶1) TIC/SBT(2∶1) TIC/SBT(4∶1) TIC/SBT(8∶1) TIC/SBT(10∶1) | 8 9 9 8 9 9 | 2 0 1 2 1 1 | 0 1 0 0 0 0 | 0 0 0 0 0 0 | 2 4 4 4 2 2 | 16 16 16 32 16 8 | 0.5～32 2～64 1～32 1～32 0.5～32 1～32 | 80 90 90 80 90 90 |
| The gold ATCC259 of Portugal 23 | 1 | TIC TIC/SBT(1∶1) TIC/SBT(2∶1) TIC/SBT(4∶1) TIC/SBT(8∶1) TIC/SBT(10∶1) | 0.25 1 0.5 1 0.5 0.5 | |||||||
| Escherichia coli ATCC259 22 | 1 | TIC TIC/SBT(1∶1) TIC/SBT(2∶1) TIC/SBT(4∶1) TIC/SBT(8∶1) TIC/SBT(10∶1) | 4 8 4 4 4 2 | |||||||
| Bacillus pyocyaneus ATCC278 53 | 1 | TIC TIC/SBT(1∶1) TIC/SBT(2∶1) TIC/SBT(4∶1) TIC/SBT(8∶1) TIC/SBT(10∶1) | 1 4 2 2 1 2 |
Table 1-2 ticarcillin (TIC) and ticarcillin/sulbactam (TIC/SBT=2: minimum bactericidal concentration 1) (MBC)
| Antibacterial | The strain number | Medicine | MIC(μg/ml) | MBC(μg/ml) | MBC/MIC | ||
| First strain | Second strain | First strain | Second strain | ||||
| S.aures E | 2 | TIC TIC/SBT | 32 4 | 64 4 | 256 16 | ≥256 32 | 4～8 4～8 |
| S.aures | 2 | TIC TIC/SBT | 4 8 | 8 4 | 32 16 | 32 16 | 4～8 2～4 |
| E.coli E | 2 | TIC TIC/SBT | 32 8 | 32 8 | 256 32 | 128 32 | 4～8 4 |
| E.coli | 2 | TIC TIC/SBT | 4 4 | 8 4 | 16 32 | 64 32 | 4～8 8 |
| P.aeruginosa E | 2 | TIC TIC/SBT | 64 16 | 64 16 | ≥256 128 | ≥256 64 | ≥4 4～8 |
| P.aeruginosa | 2 | TIC TIC/SBT | 8 16 | 16 16 | 64 64 | 64 64 | 4～8 4 |
| S.aures (ATCC25923) | 1 | TIC TIC/SBT | 0.25 0.25 | 2 1 | 8 4 | ||
| E.coli (ATCC25922) | 1 | TIC TIC/SBT | 4 4 | 32 16 | 8 4 | ||
| P.aeruginosa (ATCC27853) | 1 | TIC TIC/SBT | 1 2 | 8 16 | 8 8 | ||
Claims (4)
1, a kind of anti-beta-lactamase antibiotic composite preparation is characterized in that: be made up of ticarcillin and salt thereof and sulbactam and salt thereof, the weight ratio of described ticarcillin and salt thereof and sulbactam and salt thereof is 1: 1 to 10: 1.
2, anti-beta-lactamase antibiotic composite preparation as claimed in claim 1 is characterized in that: the weight ratio of described ticarcillin and salt thereof and sulbactam and salt thereof is 2: 1 to 6: 1.
3, anti-beta-lactamase antibiotic composite preparation as claimed in claim 2 is characterized in that: the weight ratio of described ticarcillin and salt thereof and sulbactam and salt thereof is 2: 1.
4, as described anti-beta-lactamase antibiotic composite preparation one of in the claim 1 to 3, it is characterized in that: described salt is alkali metal salt.
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Non-Patent Citations (1)
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| 舒巴坦单剂对鲍曼不动杆菌的体外抑菌活性研究. 褚少朋，邵海枫，李珍大，王卫萍，曹红琴.临床检验杂志，第22卷第5期. 2004 * |
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