CN1965838A - Pharmaceutical composition containing cefpiramide and beta-lactamase inhibitor - Google Patents
Pharmaceutical composition containing cefpiramide and beta-lactamase inhibitor Download PDFInfo
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- CN1965838A CN1965838A CN 200510048556 CN200510048556A CN1965838A CN 1965838 A CN1965838 A CN 1965838A CN 200510048556 CN200510048556 CN 200510048556 CN 200510048556 A CN200510048556 A CN 200510048556A CN 1965838 A CN1965838 A CN 1965838A
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Abstract
The invention relates to a drug composite with cooperate antibiosis function, and relative production, wherein it comprises cephalosporin or its salt, and beta-lactamase restrainer (clavulanic acid, methmazole, etc) at 10:1-1:10 ration. Said composite has better antibiosis effect on single cephalosporin, etc.
Description
Technical field
The present invention relates to the pharmaceutical composition that a kind of cefpiramide and beta-lactamase inhibitor compatibility are formed
Background technology
Cephalosporin antibacterial and clinically be used widely, for human health plays positive role, but owing to use widely for a long time clinically, antibacterial is serious day by day to the antibiotic drug resistance problem of cephalo-type, antibacterial is to produce specific beta-lactamase (β-Lactmases) decomposes medicine to the main cause of cephalo-type antibiotics resistance, comprising the defeated enzyme of the I type cephalo bacterium that the chromosome mediation is arranged with by plasmid-mediated extended spectrum, to produce the clinical drug-resistant sexuality that the beta-lactamase antibacterial caused and dye in order to overcome, the compound preparation of development cephalosporins and beta-lactamase inhibitor has the important clinical meaning.Lactamase restrainer has sulbactam (Subactam SBT), Tazobactam Sodium (Tazobactam TAZ), clavulanic acid (Clavulanic acid) and derivant thereof etc.At present, successively the cephalosporins of listing and the compound preparation of beta-lactamase inhibitor have cefoperazone/sulbactam sodium, ceftriaxone sodium/sulbactam sodium, cefoperazone sodium/tazobactam sodium etc.
Cefpiramide (Cefpiramide) is a third generation cephalosporin by invention in the age, by anti-microbial property belong to the 4th generation cephalosporin.This product has has a broad antifungal spectrum, has good characteristics of pharmacokinetics, to the lactamase good stability, cefpiramide all has good antibacterial activity to the Gram-positive ball, simultaneously gram negative bacilli is had antibacterial activity efficiently, have the antimicrobial spectrum of perfect balance.
Cefpiramide be by with the PBP1A of penicillin-binding protein (PBP), PBP1B and PBP3 have very strong affinity, suppress the synthetic of cell wall, thus the performance bactericidal action.G+, G-bacterium are had broad spectrum antibiotic activity, especially bacillus pyocyaneus is had very strong antimicrbial power.Minimum inhibitory concentration (MIC) to bacillus pyocyaneus is 0.78-3.13 μ g/ml, is 0.39-0.78 μ g/ml to the MIC of golden Portugal Pseudomonas, and colibacillary MIC is 0.39 μ g/ml, is 0.05-6.25 μ g/ml to the MIC of Proteus.MIC80 difference 0.78 μ g/ml and 0.39 μ g/ml to dyspepsiacoccus, peptostreptococcus in the anaerobe.
When quiet notes cefpiramide 0.5g of health adult and 1.0g, blood level reached 163 μ g/ml and 264 μ g/ml respectively after 5 minutes, dropped to 10.7 μ g/ml and 17.7 μ g/ml after 24 hours respectively, and the blood level half-life is 4.5h.When quiet 1g of 1h and 2g, the blood drug level peaking when finishing that instils is respectively 215 μ g/ml and 306 μ g/ml, drops to 14.7 μ g/ml and 30.6 μ g/ml respectively behind the beginning 12h that instils.Blood level is high and lasting, but does not have cumulative bad due to the successive administration.This product distributes good in body fluid, tissue.This product is metabolism hardly in vivo, does not find the antibacterial activity metabolite in urine, the excrement.Elimination factor is the high concentration that still keeps 50 μ g/ml in the urine after 23%, 24 hour in the urine in health adult's intravenous injection 24 hours.This product is a bile excretion type medicine, so dense in the bile.The patient of renal function height obstacle, the half-life also only prolongs 1.3 times in the blood, this be since this product mainly from bile excretion, when renal dysfunction, bile excretion is able to due to the compensatory increase in the body.
Cefpiramide is used for responsive microbial following infection clinically: septicemia, burn, secondary infection such as surgical wound, pharyngolaryngitis (throat abscess) acute bronchitis, tonsillitis (peritonsillitis disease, peritonsillar abscess), chronic bronchitis, bronchiectasis (during infection), the secondary infection of chronic respiratory tract disease, pneumonia, pulmonary abscess, empyema, pyelonephritis, cystitis, prostatitis, epididymis inflammation, cholecystitis, cholangitis, peritonitis (peritonaeum pelvicum inflammation, bladder rectum depression abscess, adnexitis, intrauterine infection, pelvic inflammatory disease, the other inflammation of connective tissue in uterus, bartholinitis, brain (ridge) film inflammation, jaw arthritis, cellulitis around the jawbone.
Detailed Description Of The Invention
The object of the present invention is to provide a kind of antibacterial compound drug that suppresses beta-lactamase, do not destroyed, strengthen its curative effect again, solve antibacterial the drug-fast problem of cefpiramide by bacteriogenic beta-lactamase with the protection cefpiramide.
Another object of the present invention is to antibacterial compound drug and combined by cefpiramide (Cefpiramide) and beta-lactamase inhibitor, cefpiramide and beta-lactamase inhibitor are by active acid, and their weight ratio is 1-10: 10-1.
The antibacterial compound drug of inhibition beta-lactamase of the present invention is characterized in that by proportioning cefpiramide being mixed back administration or administration respectively with beta-lactamase inhibitor again when said combination comprises clinical use.
The antibacterial compound drug of inhibition beta-lactamase of the present invention, the alkali metal salt (comprising its hydrate) that it is characterized in that said cefpiramide, the alkali metal salt of cefpiramide is meant cefpiramide sodium, also can be other alkali metal salt or its hydrate of cefpiramide, preferred cefpiramide sodium.
The antibacterial compound drug of inhibition beta-lactamase of the present invention is characterized in that said cefpiramide can be the form that Cefpiramide Acid adds (comprising its hydrate) cosolvent.
The antibacterial compound drug of inhibition beta-lactamase of the present invention is characterized in that said cosolvent is the L-arginine, or sodium carbonate, or sodium bicarbonate.
Beta-lactamase inhibitor among the present invention is meant sulbactam (Subactam) or derivatives thereof, or clavulanic acid (Clavulanic acid) or derivatives thereof, or Tazobactam Sodium (Tazobactam) or derivatives thereof.
The antibacterial compound drug of inhibition beta-lactamase of the present invention is characterized in that said clavulanic acid derivant is the alkali metal salt of clavulanic acid, preferred clavulanate potassium.
The antibacterial compound drug of inhibition beta-lactamase of the present invention is characterized in that said sulbactam derivant is the alkali metal salt of sulbactam, preferred sulbactam sodium.
The antibacterial compound drug of inhibition beta-lactamase of the present invention is characterized in that said Tazobactam Sodium derivant is the alkali metal salt of Tazobactam Sodium, preferred sodium-tazobactam.
Technical solution of the present invention is as follows:
A kind ofly be used to prevent that cefpiramide from by the enzyme inhibitor of the beta-lactam enzyme hydrolysis deactivation that antibacterial produced, is characterized in that:
Cefpiramide and beta-lactamase inhibitor be 1-10 by a certain percentage: 10-1 fully mixes use.
Technical solution of the present invention also comprises:
Cefpiramide and a certain proportion of beta-lactamase inhibitor aseptic powder are by the content of measuring, behind the deduction moisture, after in blender, fully mixing, in the toilet, under aseptic condition, pack in the antibiotics bottle of cleaning, dry sterilization butyl rubber plug beyond the Great Wall, gland seal into.
Pharmaceutical composition of the present invention has synergetic antibacterial effect, and said composition can be used for mammiferous bacterial infection.Contained cefpiramide or its pharmaceutical salts are because of share the generation synergism with beta-lactamase inhibitor in the said composition, its activity to gram-positive cocci and gram negative bacilli greatly strengthens, expanded antimicrobial spectrum simultaneously, solve the drug resistance problem of cefpiramide effectively, enlarged clinical application range.
The present invention has following good effect:
(1) in the pharmaceutical composition of the present invention, as antibiotics is cefpiramide, it has high activity to grand coccus of gram and part gram negative bacilli, and act on simultaneously with the different piece of beta-lactamase inhibitor to pathogen, therefore can stop the resistant function of pathogen effectively, slow down drug-fast development greatly.
(2) pharmaceutical composition of the present invention has synergetic antibacterial effect simultaneously, and beta-lactamase inhibitor has strengthened the cefpiramide antibacterial activity effectively, and antibacterial range is expanded simultaneously.
(3) pharmaceutical composition of the present invention has little, the no allergy of blood vessel irritation and haemolysis, safe feature.
Experimental example 1 vivo bacteria corrosion action
Do laboratory animal with white mice, clinical isolating product enzyme antibacterial staphylococcus aureus, dust Xi Shi escherichia coli, bacillus pyocyaneus are strain subject.In quantitative inoculation of bacterial strain and nutrient broth, cultivating temperature for 37 ℃ incubated 6 hours, get bacterium liquid 0.1ml transferred species in the 10ml nutrient broth, 37 ℃ of cultivations were hatched 18 hours, make the zoogenetic infection bacterium, after the test organisms liquid inductance of amount dyes till death with the mouse peritoneal injection, can after infecting 6 hours, give cefpiramide respectively, clavulanate potassium, Tazobactam Sodium is received, sulbactam is received, cefpiramide sodium/crin is tieed up sour potassium, the cefpiramide sodium/tazobactam sodium, cefpiramide sodium/sulbactam sodium is subjected to the reagent product, observed 7 days continuously, write down each treated animal death condition, calculate median effective dose (ED50), the results are shown in Table 1.
Table 1 cefpiramide sodium/clavulanate potassium, cefpiramide sodium/tazobactam and cefpiramide sodium/sulbactam sodium are to the intravital antibacterial action of infecting mouse
| Infectious bacteria MLD (Cfu.mouse -1) | Medicine | ED50/(mgkg -1) |
| Staphylococcus aureus 3.1 * 10 5 | 2: 14: 1 CefPiramide Sodium/sulbactams of 2: 14: 1 cefpiramide sodium/tazobactams of cefpiramide CefPiramide Sodium/potassium clavulanate 2: 14: 1 | 7.7(5.3-10.1) 2.7(1.5-4.1) 3.1(1.8-4.6) 1.9(1.1-3.5) 2.3(1.4-3.8) 1.8(1.2-3.3) 2.4(1.3-3.5) |
| Dust Xi Shi escherichia coli 6.9 * 10 6 | 2: 14: 1 CefPiramide Sodium/sulbactams of 2: 14: 1 cefpiramide sodium/tazobactams of CefPiramide Sodium CefPiramide Sodium/potassium clavulanate 2: 14: 1 | 0.42(0.25-0.59) 0.8(0.53-1.20) 0.92(0.84-1.27) 0.57(0.32-0.85) 0.68(0.49-0.96) 0.59(0.34-0.86) 0.69(0.47-0.98) |
| Bacillus pyocyaneus 5.7 * 10 4 | 2: 14: 1 CefPiramide Sodium/sulbactams of 2: 14: 1 cefpiramide sodium/tazobactams of CefPiramide Sodium CefPiramide Sodium/clavulanic acid 2: 14: 1 | 40.5(32.3-51.8) 11.9(8.8-14.7) 17.2(13.7-22.1) 8.2(6.7-10.0) 10.5(7.8-13.9) 8.1(6.8-10.1) 10.3(7.9-13.89) |
Experimental example 2 animal acute toxicity tests
Test animal is a white mice, and is oral respectively to being received (2: 1) with cefpiramide sodium/clavulanate potassium (2: 1), cefpiramide sodium/tazobactam (4: 1) and cefpiramide sodium/sulbactam, observes and also measures LD
50
The result shows, two medicine LD
50All above 10000mgkg
-1
The test of experimental example 3 hemolytics
Use male rabbit, hemolytic test requirements document and method are carried out the hemolytic test of cefpiramide sodium/clavulanate potassium (2: 1), cefpiramide sodium/tazobactam (4: 1) and cefpiramide sodium/sulbactam sodium (2: 1) routinely.The results are shown in Table 2.
The hemolytic result of the test of table 2 cefpiramide sodium/clavulanic acid (2: 1), cefpiramide sodium/tazobactam (4: 1) and cefpiramide sodium/sulbactam sodium (2: 1)
| Experiment liquid | 1 | 2 | 3 | 4 | 5 | 6 | 7 |
| Cefpiramide sodium/clavulanic acid normal saline red blood cell suspension | 0.1 2.4 2.5 | 0.2 2.3 2.5 | 0.3 2.2 2.5 | 0.4 2.1 2.5 | 0.5 2.0 2.5 | - 2.5 2.5 | -distilled water 2.5 |
| The result | - | - | - | - | - | - | + |
| Cefpiramide sodium/tazobactam normal saline red blood cell suspension | 0.1 2.4 2.5 | 0.2 2.3 2.5 | 0.3 2.2 2.5 | 0.4 2.1 2.5 | 0.5 2.0 2.5 | - 2.5 2.5 | -distilled water 2.5 |
| The result | - | - | - | - | - | - | + |
| Cefpiramide sodium/sulbactam sodium normal saline red blood cell suspension | 0.1 2.4 2.5 | 0.2 2.3 2.5 | 0.3 2.2 2.5 | 0.4 2.1 2.5 | 0.5 2.0 2.5 | - 2.5 2.5 | -distilled water 2.5 |
| The result | - | - | - | - | - | - | + |
Annotate: "-" represents not haemolysis; "+" expression haemolysis.
The test of experimental example 4 local irritations
Laboratory animal is a rabbit, according to a conventional method medicine cefpiramide sodium/clavulanate potassium (2: 1), cefpiramide sodium/tazobactam (4: 1) and cefpiramide sodium/sulbactam sodium (2: 1) is instiled by ear vein respectively and the quadriceps femoris injection.As a result, three medicine intravenous injection 100ml, quadriceps femoris injection 2ml fails to observe the congested and edema phenomenon of injection portion after 24 hours; Tissue slice is not seen obvious change.
The test of experimental example 5 systemic anaphylaxis
Experimental animal is a Cavia porcellus, with medicine cefpiramide sodium/clavulanate potassium (2: 1), cefpiramide sodium/tazobactam (4: 1) and cefpiramide sodium/sulbactam sodium (2: 1), makes positive control with Ovum Gallus domesticus album, respectively through lumbar injection by rectangular method.Experimental result shows that the Cavia porcellus of administration group all do not have obvious anaphylaxis, and the matched group anaphylaxis is obvious after administration is attacked.
From the test the result as can be known, use in conjunction cefpiramide and beta-lactamase inhibitor have synergism to multiple gram positive bacteria and negative infectious bacteria.
Therefore, bactericidal composition of the present invention not only can be used for preventing or treating the infection that various infectious bacterias cause separately, and can be used for prevention or treatment has a plurality of microbial infection, especially the infection that gram positive bacteria and above-mentioned other Pseudomonas are caused.
The present invention will describe preparation of drug combination in detail below with embodiment, but the present invention is not by these
Embodiment limits.
Embodiments of the invention are as follows:
Embodiment 1 mixes cefpiramide sodium 250mg (by cefpiramide) with clavulanate potassium 250mg (by active acid), get final product by the preparation of injection procedure operation.
Embodiment 2 mixes cefpiramide sodium 250mg (by cefpiramide) with clavulanate potassium 62.5mg (by active acid), get final product by the preparation of injection procedure operation.
Embodiment 3 mixes cefpiramide sodium 250mg (by cefpiramide) with clavulanate potassium 31.25mg (by active acid), get final product by the preparation of injection procedure operation.
Embodiment 4 mixes cefpiramide sodium 500mg (by cefpiramide) with clavulanate potassium 500mg (by active acid), get final product by the preparation of injection procedure operation.
Embodiment 5 mixes cefpiramide sodium 500mg (by cefpiramide) with clavulanate potassium 250mg (by active acid), get final product by the preparation of injection procedure operation.
Embodiment 6 mixes cefpiramide sodium 500mg (by cefpiramide) with clavulanate potassium 100mg (by active acid), get final product by the preparation of injection procedure operation.
Embodiment 7 mixes cefpiramide potassium 500mg (by cefpiramide) with sodium-tazobactam 1000mg (by active acid), get final product by the preparation of injection procedure operation.
Embodiment 8 mixes cefpiramide sodium 500mg (by cefpiramide) with Tazobactam Sodium 62.5mg, get final product by the preparation of injection procedure operation.
Embodiment 9 mixes cefpiramide hydrate 500mg (by cefpiramide) with sulbactam sodium 1000mg (by active acid) and L-arginine 500mg, get final product by the preparation of injection procedure operation.
Embodiment 10 mixes cefpiramide sodium 600mg (by cefpiramide) with sulbactam sodium 100mg (by active acid), get final product by the preparation of injection procedure operation.
Embodiment 11 mixes Cefpiramide sodium hydrate 700mg (by cefpiramide) with sulbactam sodium 200mg (by active acid), get final product by the operation of preparation of injection journey.
Embodiment 12 mixes cefpiramide potassium 800mg (by cefpiramide) with clavulanate potassium 100mg (by active acid), get final product by the preparation of injection procedure operation.
Embodiment 13 mixes cefpiramide potassium 800mg (by cefpiramide) with sodium-tazobactam 100mg (by active acid), get final product by the preparation of injection procedure operation.
Embodiment 14 mixes cefpiramide potassium (by cefpiramide) 900mg with clavulanate potassium 300mg (by active acid), get final product by the preparation of injection procedure operation.
Embodiment 15 mixes Cefpiramide Acid (by cefpiramide) 900mg with sulbactam sodium 100mg (by active acid) and L-arginine 500mg, get final product by the preparation of injection procedure operation.
Embodiment 16 mixes cefpiramide potassium 1000mg (by cefpiramide) with clavulanate potassium 2000mg (by active acid), get final product by the preparation of injection procedure operation.
Embodiment 17 mixes cefpiramide sodium 1000mg with clavulanate potassium 1000mg (by active acid), get final product by the preparation of injection procedure operation.
Embodiment 18 mixes cefpiramide potassium 1000mg (by cefpiramide) with clavulanate potassium 200mg (by active acid), get final product by the preparation of injection procedure operation.
Embodiment 19 mixes Cefpiramide sodium hydrate 1000mg (by cefpiramide) with clavulanate potassium 100mg (by active acid), get final product by the preparation of injection procedure operation.
Embodiment 20 mixes cefpiramide potassium hydrate 1000mg (by cefpiramide) with sodium-tazobactam 1000mg (by active acid), get final product by the preparation of injection procedure operation.
Embodiment 21 mixes cefpiramide hydrate 1000mg (by cefpiramide) with sodium-tazobactam 500mg (by active acid) and sodium bicarbonate 500mg, get final product by the preparation of injection procedure operation.
Embodiment 22 mixes cephalo ammonium potassium hydrate (by a cefpiramide) 1000mg with sodium-tazobactam 250mg (by active acid) and L-arginine 500mg, get final product by the preparation of injection procedure operation.
Embodiment 23 mixes cefpiramide potassium (by cefpiramide) 1000mg with sodium-tazobactam 100mg (by active acid), get final product by the preparation of injection procedure operation.
Embodiment 24 mixes cefpiramide 1000mg with sulbactam sodium 1000mg (by active acid) and L-arginine 500mg, get final product by the preparation of injection procedure operation.
Embodiment 25 mixes cefpiramide sodium 1500mg (by cefpiramide) with clavulanic acid 750mg, get final product by the preparation of injection procedure operation.
Embodiment 26 mixes cefpiramide potassium 2000mg (by cefpiramide) with sulbactam sodium 1000mg (by active acid), get final product by the preparation of injection procedure operation.
Embodiment 27 is dissolved in 1 of cefpiramide sodium for injection (1.0g/ props up) and injection clavulanate potassium (0.5g/ props up) in same 100 milliliters of glucose infusion liquids, gives quiet of sensitive organism infected patient.
Embodiment 28 is dissolved in 1 of cefpiramide sodium for injection (1.0g/ props up) and injection clavulanate potassium (0.25g/ props up) in same 100 milliliters of glucose infusion liquids, gives quiet of sensitive organism infected patient.
Embodiment 29 is dissolved in 1 of cefpiramide sodium for injection (1.0g/ props up) and injection sodium-tazobactam (0.5g/ props up) in same 100 milliliters of glucose infusion liquids, gives quiet of sensitive organism infected patient.
Embodiment 30 is dissolved in 1 of cefpiramide sodium for injection (1.0g/ props up) and injection sodium-tazobactam (0.25g/ props up) in same 100 milliliters of glucose infusion liquids, gives quiet of sensitive organism infected patient.
Embodiment 31 is dissolved in 1 of cefpiramide sodium for injection (1.0g/ props up) and injection sulbactam sodium (0.5g/ props up) in same 250 milliliters of glucose infusion liquids, gives quiet of sensitive organism infected patient.
Embodiment 32 is dissolved in 2 of cefpiramide sodium for injection (0.5g/ props up) and injection sulbactam sodium (1.0g/ props up) in same 250 milliliters of glucose infusion liquids, gives quiet of sensitive organism infected patient.
Embodiment 33 mixes cefpiramide 250mg with clavulanic acid 125mg (by active acid), get final product by the preparation of injection procedure operation, and its prescription and technology are as follows:
Prescription: cefpiramide 250mg
Sodium bicarbonate 250mg
Clavulanate potassium 125mg
Mannitol 150mg
Water for injection 5ml
Preparation technology: under aseptic technique, get the cefpiramide, sodium bicarbonate of recipe quantity and clavulanate potassium and add water for injection to be stirred to medicinal liquid clear and bright; Add mannitol, the dissolving back adds the medical active carbon decoloring, filter, and again through the filtering with microporous membrane degerming, bottling, lyophilizing, promptly.
Embodiment 34 mixes cefpiramide sodium 500mg with sodium-tazobactam 125mg, get final product by the preparation of injection procedure operation, and its prescription and technology are as follows:
Prescription: cefpiramide sodium 500mg
Sodium-tazobactam 125mg
Mannitol 150mg
Water for injection 5ml
Preparation technology: under aseptic technique, get the cefpiramide sodium of recipe quantity and sodium-tazobactam and add water for injection to be stirred to medicinal liquid clear and bright; Add mannitol, the dissolving back adds the medical active carbon decoloring, filter, and again through the filtering with microporous membrane degerming, bottling, lyophilizing, promptly.
Embodiment 35 mixes cefpiramide hydrate 500mg with sulbactam sodium 250mg (by active acid), get final product by the preparation of injection procedure operation, and its prescription and technology are as follows:
Prescription: cefpiramide 500mg
Sulbactam sodium 250mg
Sodium bicarbonate 500mg
Mannitol 150mg
Water for injection 5ml
Preparation technology: under aseptic technique, get the cefpiramide, sodium bicarbonate of recipe quantity and sulbactam sodium and add water for injection to be stirred to medicinal liquid clear and bright; Add mannitol, the dissolving back adds the medical active carbon decoloring, filter, and again through the filtering with microporous membrane degerming, bottling, lyophilizing, promptly.
In an embodiment of the present invention, cefpiramide and beta-lactamase inhibitor can provide the suitable amount of effective dose to exist, and described effective dose depends on the reactive compound of given treatment and the pharmaceutical properties of preparation.
Claims (7)
1. bactericidal composition that suppresses beta-lactamase, it is characterized in that by cefpiramide (Cefpiramide) and beta-lactamase inhibitor respectively by active acid weight ratio 1-10: 10-1 combines.
2. according to the antibacterial compound drug of the described inhibition beta-lactamase of claim 1, it is characterized in that by proportioning cefpiramide being mixed back administration or administration respectively with beta-lactamase inhibitor again when said combination comprises clinical use.
3. according to the antibacterial compound drug of claim 1 or 2 described inhibition beta-lactamases, it is characterized in that the alkali metal salt (comprising its hydrate) of said cefpiramide or the form that its free acid adds (comprising its hydrate) cosolvent.
4. according to the antibacterial compound drug of the described inhibition beta-lactamase of claim 3, the alkali metal salt that it is characterized in that said cefpiramide is cefpiramide sodium (Cefpiramide sodium).
5. according to the antibacterial compound drug of the described inhibition beta-lactamase of claim 3, it is characterized in that said cosolvent is the L-arginine, or sodium carbonate, or sodium bicarbonate.
6. according to the antibacterial compound drug of claim 1 or 2 described inhibition beta-lactamases, it is characterized in that said beta-lactamase inhibitor is the clavulanic acid or derivatives thereof, or the sulbactam or derivatives thereof, or the Tazobactam Sodium or derivatives thereof.
7. according to the antibacterial compound drug of the described inhibition beta-lactamase of claim 6, it is characterized in that said clavulanic acid derivant is the alkali metal salt of clavulanic acid, said sulbactam derivant is the alkali metal salt of sulbactam, and said Tazobactam Sodium derivant is the alkali metal salt of Tazobactam Sodium.
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| CN101838276A (en) * | 2010-05-17 | 2010-09-22 | 胡梨芳 | Cefpiramide sodium hydrate and preparation method and application thereof |
| CN101966152A (en) * | 2010-10-29 | 2011-02-09 | 广州白云山天心制药股份有限公司 | Cefpiramide composite |
| CN101849947B (en) * | 2010-02-25 | 2012-07-04 | 深圳市新泰医药有限公司 | Composition of cefazedone sodium and tazobactam sodium and ratio of cefazedone sodium to tazobactam sodium |
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2005
- 2005-11-17 CN CN 200510048556 patent/CN1965838A/en active Pending
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| CN101849947B (en) * | 2010-02-25 | 2012-07-04 | 深圳市新泰医药有限公司 | Composition of cefazedone sodium and tazobactam sodium and ratio of cefazedone sodium to tazobactam sodium |
| CN101838276A (en) * | 2010-05-17 | 2010-09-22 | 胡梨芳 | Cefpiramide sodium hydrate and preparation method and application thereof |
| WO2011144021A1 (en) * | 2010-05-17 | 2011-11-24 | 胡梨芳 | Cefpiramide sodium hydrate, preparation method and uses thereof |
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