CN102949397B - Cefotaxime sodium and tazobactam sodium preparation for injection and preparing method thereof - Google Patents
Cefotaxime sodium and tazobactam sodium preparation for injection and preparing method thereof Download PDFInfo
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- CN102949397B CN102949397B CN201210471942.9A CN201210471942A CN102949397B CN 102949397 B CN102949397 B CN 102949397B CN 201210471942 A CN201210471942 A CN 201210471942A CN 102949397 B CN102949397 B CN 102949397B
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Abstract
The invention discloses a cefotaxime sodium and tazobactam sodium preparation for injection and a preparing method thereof. The preparing method comprises the step that cefotaxime sodium and tazobactam sodium are mixed uniformly to prepare the cefotaxime sodium and tazobactam sodium preparation for injection, wherein the mass ratio of the cefotaxime sodium to the tazobactam sodium is 1-4:1. A product prepared throughin the preparing method has good uniformity, the operation is simple, no special devices are needed in the production, and the method is suitable for industrial production. The cefotaxime sodium and tazobactam sodium preparation for injection has good content uniformity and stable quality.
Description
Technical field
The present invention relates to medical technical field, be specifically related to a kind of cefotaxime sodium for injection and Tazobactam Sodium preparation of sodium and preparation method thereof.
Background technology
Cefotaxime sodium is (6R, 7R)-3-[(acetoxyl group) methyl]-7-[(2-amino-4-thiazolyl)-(methoxyimino) acetylamino]-8-oxo-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2-formic acid sodium salt.Molecular formula C
16h
16n
5naO
7s
2, molecular weight: 477.45, chemical structural formula is as follows:
Cefotaxime sodium is third generation cephalosporin, have broad-spectrum antibacterial action, this medicine is applicable to pneumonia and other lower respiratory infections, urinary tract infection, meningitis, septicemia, abdominal cavity infection, pelvic infection, skin soft-tissue infection, reproductive tract infection, bone and the infection of joint etc. due to sensitive bacterial.Cefotaxime sodium can be used as the medicine of selecting of infant meninges inflammation.
Cefotaxime sodium has powerful antibacterial activity to enterobacteriaceae lactobacteriaceae, compared with cefuroxime or cefoxitin (cefoxitin), to escherichia coli, clostridium perfringen, Proteus, root fungus does not belong to, the antibacterial actions of Pu Luweideng bacterium and Serratia etc. obviously strengthens.Cefotaxime sodium is generally strong compared with second generation cephalosporins such as cefamandole to the antibacterial action of gram negative bacilli.Cefotaxime sodium is similar to hemophilus influenza and gonococcal minimal inhibitory concentration (MIC) and ampicillin, and the effect of hemophilus influenza is all better than to first and second cephalosporin in generation.Penicillin resistant hemophilus influenza, moraxelle catarrhalis, gonococcus and meningococcus Cefotaxime sodium are also very responsive.
Sodium-tazobactam is [2S-(2 α, 2 β, 5 α)]-3-methyl-7-oxygen-3-(1H-1,2,3-triazole-1-methyl)-4-thia-1-azabicyclo-[3,2,0]-heptane-2-carboxylic acid sodium-4,4-dioxide.Molecular formula C
10h
11n
4naO
5s, molecular weight: 322.28, chemical structural formula is as follows:
Tazobactam Sodium (tazobacam) is the product that Japanese roc (Tai ho) company the eighties is developed, after 1997, and the successively granted production such as domestic Shanghai, Zhejiang, Zhuhai, Hainan.Tazobactam Sodium is the derivant of sulbactam, dividing subclass to typical irreversible beta-lactamase is that the inhibitory action of TEM-1, TEM-2 etc. is strong, enzyme and ClassCP99 enzyme to ClassB metalloenzyme C-also have stronger inhibitory action, and to a little less than S2 enzyme inhibition, can be used for treating the microbial infection of multiple aerobe and anaerobism; Comprise lower respiratory tract, urethra, skin, soft tissue, intraperitoneal and gynecological infection and bacteremia.There is the advantages such as toxicity is low, good stability; can protect antibiotic not to be damaged to the unsettled beta-Lactam antibiotic of enzyme (as penicillins, cephalosporins) use in conjunction; bring into play its original anti-microbial property, its Main Function mechanism is to be combined and to make it inactivation with bacteriogenic beta-lactamase.
Along with cephalosporins is in clinical extensive use, third generation cephalosporins is on the rise to the drug resistance of some gram negative bacilli, and the antibacterial activity of staphylococcus aureus is declined.And, antibacterial with antibiotic antagonism in produced and can be hydrolyzed antibiotic enzyme.
Therefore one of method that solves Production by Bacteria enzyme drug resistance is by beta-lactamase inhibitor and beta-lactam antibiotic use in conjunction.Enzyme inhibitor sodium-tazobactam has improved the stability of cephalosporins to beta-lactamase that gram negative bacilli produces really, has expanded antimicrobial spectrum, has strengthened antibacterial action.
Many medical institutions adopt drug combinations (being generally a kind of coupling in ceftriaxone sodium and azithromycin, ceftibuten, doxycycline or clarithromycin etc.) to treat for this reason, not still safety, effective and to press Pharmacoeconomics analysis reasonable more economically.And for example the drug combination of ceftriaxone sodium and amikacin not only has synergetic antibacterial effect, and obviously reduces ceftriaxone sodium and discharge endotoxic amount.And being typical irreversible beta-lactamase inhibitor, sodium-tazobactam can protect antibiotic not to be damaged to the unsettled beta-lactam antibiotic of enzyme (as penicillins, cephalosporins) use in conjunction; bring into play its original antibacterial functions, its Main Function mechanism is to be combined and to make it inactivation with bacteriogenic beta-lactam.The third generation cephalo compound preparation of and for example in recent years selling on market: as ceftriaxone sodium is joined sulbactam sodium, cefotaxime sodium is joined the drug combination that sulbactam sodium Deng Xi China Medicine University's new drug development center Xiangbei Weierman Pharmaceutical Co., Ltd produces.
Application number is that the Chinese patent application of 02125821.X discloses a kind of cefotaxime sodium for injection and sodium-tazobactam compound preparation, and this compound preparation is made up of cefotaxime sodium and sodium-tazobactam, and the weight ratio of cefotaxime sodium and sodium-tazobactam is 5:1.This cefotaxime sodium and sodium-tazobactam compound preparation have collaborative and cumulative antibacterial action to Resistant strain, there is clinical, document and animal experiment foundation fully, can strengthen clinical antibacterial effect, and not increase the generation of untoward reaction, will there is great social benefit and economic benefit.While mixing in the preparation method of disclosed compound preparation in this application, sodium-tazobactam is freeze-dried powder, in actual production, directly mixes and there will be layering, causes final products, and uniformity of dosage units is bad, and occurs variable color after storing a period of time.
Summary of the invention
The invention provides a kind of uniformity of dosage units good and stay-in-grade cefotaxime sodium for injection and Tazobactam Sodium preparation of sodium.
The present invention also provides the preparation method of a kind of cefotaxime sodium for injection and Tazobactam Sodium preparation of sodium, can significantly improve uniformity of dosage units and the stability of formulation products, has greatly improved the qualification rate of product.
A preparation method for cefotaxime sodium for injection and Tazobactam Sodium preparation of sodium, comprises step:
Cefotaxime sodium is mixed homogeneously with sodium-tazobactam, make cefotaxime sodium for injection and Tazobactam Sodium preparation of sodium; Wherein, the mass ratio of cefotaxime sodium and sodium-tazobactam is 1-4:1.
Cefotaxime sodium and the ratio of sodium-tazobactam that the present invention limits, can significantly strengthen the drug effect of gained preparation, better brings into play the effect of sterilization and the collaborative bactericidal action that adds up of medicine of medicine, and be conducive to obtain the good and stay-in-grade preparation of uniformity of dosage units.
Described cefotaxime sodium and the mass ratio of sodium-tazobactam are preferably 2-4:1, more preferably 4:1.
Described cefotaxime sodium is preferably selected injection rank, to meet the needs of injection preparation.
Described sodium-tazobactam preferably carries out pretreatment before using, obtain freshly prepd sodium-tazobactam by tazobactam and reaction of sodium bicarbonate, as freshly prepd Tazobactam Sodium sodium freeze dry, carrying out pretreatment is because general sodium-tazobactam hygroscopicity is very strong, can cause mixing inhomogeneous so that the final bad control of the product content uniformity, after pretreatment, can improve resistance to water soak and the stability of sodium-tazobactam, obtain the stable sodium-tazobactam of output and quality.The method that tazobactam and reaction of sodium bicarbonate is obtained to freshly prepd sodium-tazobactam adopts prior art, as: tazobactam is dissolved in to appropriate water for injection and makes suspension, adding excessive reaction of sodium bicarbonate and regulating pH with aqueous hydrochloric acid solution is 4.5 ~ 6.0, obtain Tazobactam Sodium sodium solution, through activated carbon filtration, then through 0.22 μ m filter membrane fine straining, lyophilization, pulverize, make Tazobactam Sodium sodium freeze dry.
Described mixing comprises: will account for the cefotaxime sodium premixing 10 minutes-15 minutes of cefotaxime sodium gross mass 1/3 amount, add again the sodium-tazobactam that accounts for sodium-tazobactam gross mass 1/2 amount, mixing limit, limit ventilation 5 minutes-10 minutes, add again remaining cefotaxime sodium to mix 10 minutes-15 minutes, then add remaining sodium-tazobactam, mixing limit, limit ventilation 5 minutes-10 minutes, makes cefotaxime sodium for injection and Tazobactam Sodium preparation of sodium.Due to cefotaxime sodium and the easy moisture absorption of sodium-tazobactam, under common environment,, in mixed process, can there is the phenomenon of sticky equipment inner surface in all moisture absorptions, adopt common mixed method, there will be and mix inhomogeneous phenomenon, moreover in the case of the proportion of cefotaxime sodium and sodium-tazobactam is different, can avoid sodium-tazobactam to mix with cefotaxime sodium by the method mixing of gradation and ventilation time, occur lamination, improve the uniformity of mixing, and cost-saving and shortening incorporation time.
The gas passing in described aeration step is preferably compressed air, not only economical and practical but also can reach good mixed effect, while avoiding sodium-tazobactam to mix with cefotaxime sodium, occurs lamination, makes the mixing homogeneity of sodium-tazobactam and cefotaxime sodium good.
A kind of cefotaxime sodium for injection and Tazobactam Sodium preparation of sodium, adopt described cefotaxime sodium for injection and the preparation method of Tazobactam Sodium preparation of sodium to prepare.
The usage and dosage of cefotaxime sodium for injection of the present invention and Tazobactam Sodium preparation of sodium:
Every daily dose 2 ~ 6g that is grown up, point 2 ~ 3 intravenous injections or intravenous drip; Treat uncomplicated streptococcus pneumoniae property pneumonia or acute urinary tract infection, every 12 hours 1g; Do prophylactic in operation process time, perform the operation intramuscular injection in first 0.5 ~ 1.5 hour or intravenous injection 1g, postoperative every 6 ~ 8 hours repeat once, till performing the operation latter 24 hours.
Tool of the present invention has the following advantages:
1), by cefotaxime sodium and the sodium-tazobactam of special ratios, reduce the toleration of medicine and reduce clinical dosage.
2) while mixing, adopt the way of gradation and ventilation, avoided the inhomogeneous phenomenon of mixing that occurs while mixing, improved the degree of mixing of compound preparation of the present invention, guarantee final product content good evenness, steady quality.
3) in preparation method of the present invention, operating procedure is simple, and cost is low, need not any equipment, be applicable to suitability for industrialized production.
The specific embodiment
Further explain by the following examples or explanation content of the present invention, but the embodiment providing should not be understood to protection domain of the present invention to be construed as limiting.
Tazobactam is dissolved in to appropriate water for injection and makes suspension, adding excessive reaction of sodium bicarbonate and regulating pH with aqueous hydrochloric acid solution is 5.0, obtains Tazobactam Sodium sodium solution, through activated carbon filtration, then through 0.22 μ m filter membrane fine straining, lyophilization, pulverize, make Tazobactam Sodium sodium freeze dry.
Embodiment 1
The preparation of cefotaxime sodium for injection and Tazobactam Sodium preparation of sodium
The mass ratio of cefotaxime sodium and sodium-tazobactam is 3.9:1.
279.5g cefotaxime sodium is placed in mixer and is mixed 10 minutes, add the freshly prepd Tazobactam Sodium sodium freeze dry of 107.3g, mix 5 minutes on logical compressed air limit, limit, add again 559g cefotaxime sodium to mix 10 minutes, add the freshly prepd Tazobactam Sodium sodium freeze dry of 107.3g, mix 5 minutes on logical compressed air limit, limit, discharging, subpackage, makes cefotaxime sodium for injection and Tazobactam Sodium preparation of sodium.
Embodiment 2
The preparation of cefotaxime sodium for injection and Tazobactam Sodium preparation of sodium
The mass ratio of cefotaxime sodium and sodium-tazobactam is 3.95:1.
279.5g cefotaxime sodium is placed in mixer and is mixed 10 minutes, add the freshly prepd Tazobactam Sodium sodium freeze dry of 106.2g, mix 5 minutes on logical compressed air limit, limit, add again 559g cefotaxime sodium to mix 10 minutes, add the freshly prepd Tazobactam Sodium sodium freeze dry of 106.2g, mix 5 minutes on logical compressed air limit, limit, discharging, subpackage, makes cefotaxime sodium for injection and Tazobactam Sodium preparation of sodium.
Embodiment 3
The preparation of cefotaxime sodium for injection and Tazobactam Sodium preparation of sodium
The mass ratio of cefotaxime sodium and sodium-tazobactam is 3.98:1.
279.5g cefotaxime sodium is placed in mixer and is mixed 10 minutes, add the freshly prepd Tazobactam Sodium sodium freeze dry of 105.3g, mix 5 minutes on logical compressed air limit, limit, add again 559g cefotaxime sodium to mix 10 minutes, add the freshly prepd Tazobactam Sodium sodium freeze dry of 105.3g, mix 5 minutes on logical compressed air limit, limit, discharging, subpackage, makes cefotaxime sodium for injection and Tazobactam Sodium preparation of sodium.
Embodiment 4
The preparation of cefotaxime sodium for injection and Tazobactam Sodium preparation of sodium
The mass ratio of cefotaxime sodium and sodium-tazobactam is 4:1.
279.5g cefotaxime sodium is placed in mixer and is mixed 10 minutes, add the freshly prepd Tazobactam Sodium sodium freeze dry of 104.8125g, mix 5 minutes on logical compressed air limit, limit, add again 559g cefotaxime sodium to mix 10 minutes, add the freshly prepd Tazobactam Sodium sodium freeze dry of 104.8125g, mix 5 minutes on logical compressed air limit, limit, discharging, subpackage, makes cefotaxime sodium for injection and Tazobactam Sodium preparation of sodium.
Embodiment 5
The preparation of cefotaxime sodium for injection and Tazobactam Sodium preparation of sodium
The mass ratio of cefotaxime sodium and sodium-tazobactam is 2:1.
279.5g cefotaxime sodium is placed in mixer and is mixed 10 minutes, add the freshly prepd Tazobactam Sodium sodium freeze dry of 209.625g, mix 5 minutes on logical compressed air limit, limit, add again 559g cefotaxime sodium to mix 10 minutes, add the freshly prepd Tazobactam Sodium sodium freeze dry of 209.625g, mix 5 minutes on logical compressed air limit, limit, discharging, subpackage, makes cefotaxime sodium for injection and Tazobactam Sodium preparation of sodium.
Embodiment 6
The preparation of cefotaxime sodium for injection and Tazobactam Sodium preparation of sodium
The mass ratio of cefotaxime sodium and sodium-tazobactam is 1:1.
279.5g cefotaxime sodium is placed in mixer and is mixed 10 minutes, add the freshly prepd Tazobactam Sodium sodium freeze dry of 419.25g, mix 5 minutes on logical compressed air limit, limit, add again 559g cefotaxime sodium to mix 10 minutes, add the freshly prepd Tazobactam Sodium sodium freeze dry of 419.25g, mix 5 minutes on logical compressed air limit, limit, discharging, subpackage, makes cefotaxime sodium for injection and Tazobactam Sodium preparation of sodium.
Comparative example 1
The preparation of cefotaxime sodium for injection and Tazobactam Sodium preparation of sodium
The mass ratio of cefotaxime sodium and sodium-tazobactam is 5:1.
279.5g cefotaxime sodium is placed in mixer and is mixed 10 minutes, add the freshly prepd Tazobactam Sodium sodium freeze dry of 83.85g, mix 5 minutes on logical compressed air limit, limit, add again 559g cefotaxime sodium to mix 10 minutes, add the freshly prepd Tazobactam Sodium sodium freeze dry of 83.85g, mix 5 minutes on logical compressed air limit, limit, discharging, subpackage, makes cefotaxime sodium for injection and Tazobactam Sodium preparation of sodium.
Comparative example 2
The preparation of cefotaxime sodium for injection and Tazobactam Sodium preparation of sodium
The mass ratio of cefotaxime sodium and sodium-tazobactam is 8:1.
279.5g cefotaxime sodium is placed in mixer and is mixed 10 minutes, add the freshly prepd Tazobactam Sodium sodium freeze dry of 52.4g, mix 5 minutes on logical compressed air limit, limit, add again 559g cefotaxime sodium to mix 10 minutes, add the freshly prepd Tazobactam Sodium sodium freeze dry of 52.4g, mix 5 minutes on logical compressed air limit, limit, discharging, subpackage, makes cefotaxime sodium for injection and Tazobactam Sodium preparation of sodium.
Cefotaxime sodium for injection and Tazobactam Sodium preparation of sodium that the embodiment of the present invention 4,5,6 and comparative example 1 are made carry out stability test, adopt the method for accelerated test to carry out study on the stability to it, 28 ℃～32 ℃ of temperature, relative humidity 55%～65% condition is accelerated to place 6 months, the results are shown in Table 1, wherein, the meansigma methods of difference=| (meansigma methods of the content-content at every turn recording) | summation/5.
Table 1
Visible, the stability of cefotaxime sodium for injection prepared by preparation method of the present invention and Tazobactam Sodium preparation of sodium is better than cefotaxime sodium for injection sodium-tazobactam prepared by prior art.
Prescription screening
The present invention has carried out antibacterial tests in the test of in-vitro antibacterial (seeing attached list 2) antibacterial action and body to cefotaxime sodium for injection and Tazobactam Sodium preparation of sodium, draw Mlc MIC50, MIC measures: concentrate the MIC value to cefotaxime sodium for injection and Tazobactam Sodium preparation of sodium, cefotaxime sodium, cefotaxime sodium and sulbactam sodium preparation (newly controlling monarch, new monarch Bi Zhi) by agar mensuration clinical isolates; Result is as follows:
In Vitro Bacteriostasis tables of data (MIC50 (μ g/ml))
Table 2
Experiment in vitro result shows: 5 kinds of pairings such as cefotaxime sodium for injection and Tazobactam Sodium preparation of sodium 1:1,2:1,4:1,5:1,8:1 all have enhancing in various degree to the vigor of zymogenic bacteria, wherein, take the potentiation of the proportioning of 1:1,2:1,4:1 as good, antibacterial activity is better than and newly controls monarch (the graceful pharmacy Gu Men of North of Hunan Weir company limited).
In body, antibacterial tests shows: this product 1:1,2:1, the different proportioning compound formulations of 4:1; the curative effect of the In vivo infection mices such as staphylococcus aureus, escherichia coli, excrement Pseudomonas alcaligenes and the Pseudomonas stutzeri to clinical separation product enzyme is 8 ~ 64 times of alone cefotaxime sodium; wherein the mice protective effect of escherichia coli In vivo infection is newly controlled to monarch slightly strong; bacillus pyocyaneus (that is: pseudomonas aeruginosa, be called for short: Pseudomonas aeruginosa) is with newly to control monarch suitable.
His azoles of cefotaxime sodium bar sodium (4:1) has bactericidal action, minimum bactericidal concentration (MBC value) is its MIC value 5.3 ~ 21.3 times.
Dead animal is cutd open to inspection result: dead mice is cutd open to inspection perusal, and each treatment group and control group mice all see above limb oxter and submandibular lymph nodes enlargement, and duodenum and adjacent jejunum have the necrosis of 3-6cm unequal length.Other organs no abnormality seen.Inspection result no significant difference is cutd open in the death for the treatment of group and matched group.Test shows, he clings to sodium (4:1 by azoles cefotaxime sodium for injection, embodiment 4) staphylococcus aureus that clinical separation produced to enzyme, the curative effect of escherichia coli and bacillus pyocyaneus In vivo infection mice is 2.4 of alone cefotaxime sodium, 12.5 and 2.4 times (P<0.01), result shows: cefotaxime sodium for injection sodium-tazobactam to clinical common pathogenic bacteria as staphylococcus aureus, escherichia coli, the Protective effect curative effect of charrin's disease mice is obviously better than cefotaxime one pack system, the preparation of comparative example 1, the preparation of comparative example 2 and monarch Xin Zhi.
Comprehensive above showing:
1, experiment in vitro result shows: it is alone to the antibacterial activity of bacterium producing multi enzyme preparation more than 2 ~ 133 times that the compound preparation of this product (4:1) proportioning can effectively strengthen cefotaxime sodium.
2, experimental result shows in body: this product (4:1) can effectively strengthen that cefotaxime sodium is alone more than 1.8 ~ 12.1 times, is better than newly controlling monarch to escherichia coli and bacillus pyocyaneus to the antibacterial activity of bacterium producing multi enzyme preparation staphylococcus aureus, escherichia coli and bacillus pyocyaneus simultaneously.
3, cefotaxime sodium TZB sodium has bactericidal action, MBC value is its MIC value 5.3 ~ 21.3 times.
4, compound recipe (8:1,5:1) proportioning antibacterial action a little less than, (2:1) and (4:1) antibacterial action, can be killing bacteria all in sensitive range.
5, its toxicity of this product (4:1) proportioning is lower, if rat long term toxication is in whole administration process, and the behavioral activity of each treated animal, outward appearance symptom, urine, feces and food ration all do not occur abnormal, administration treated animal is without the symptom such as sialorrhea, vomiting.
6, cefotaxime sodium-tazobactam sodium (1:1) and (4:1) comparison, calculated as 7 days take each course for the treatment of, and from pharmacy cost-effectiveness analysis, 1:1 spends more more than approximately 600 yuan than the preparation of 4:1 proportioning.
7,, because sodium-tazobactam hygroscopicity is strong, its technique ratio of 4:1 proportioning is easier to control, steady quality.
Comprehensive analyze above result, through screening, screened out the compound preparation of 8:1,5:1 proportioning, the compound preparation of this product 1:1 proportioning simultaneously, because sodium-tazobactam is expensive, from Pharmacoeconomics analysis 1:1 than the product of 4:1 with seven days each courses for the treatment of calculate, approximately spend more more than 600 yuan.And this product 4:1 is applicable to the infected patient due to the pathogen of the product beta-lactamase to this product sensitivity.For this reason, the compound preparation of 4:1 most preferably.
Above proportioning all refers to the mass ratio of cefotaxime sodium and sodium-tazobactam.
Claims (6)
1. a preparation method for cefotaxime sodium for injection and Tazobactam Sodium preparation of sodium, is characterized in that, comprises step:
Cefotaxime sodium is mixed homogeneously with sodium-tazobactam, make cefotaxime sodium for injection and Tazobactam Sodium preparation of sodium; Wherein, the mass ratio of cefotaxime sodium and sodium-tazobactam is 1-4:1;
Described mixing comprises: will account for the cefotaxime sodium premixing 10 minutes-15 minutes of cefotaxime sodium gross mass 1/3 amount, add again the sodium-tazobactam that accounts for sodium-tazobactam gross mass 1/2 amount, mixing limit, limit ventilation 5 minutes-10 minutes, add again remaining cefotaxime sodium to mix 10 minutes-15 minutes, then add remaining sodium-tazobactam, mixing limit, limit ventilation 5 minutes-10 minutes, makes cefotaxime sodium for injection and Tazobactam Sodium preparation of sodium;
The gas passing in described aeration step is compressed air.
2. the preparation method of cefotaxime sodium for injection according to claim 1 and Tazobactam Sodium preparation of sodium, is characterized in that, the mass ratio of cefotaxime sodium and sodium-tazobactam is 2-4:1.
3. the preparation method of cefotaxime sodium for injection according to claim 1 and Tazobactam Sodium preparation of sodium, is characterized in that, the mass ratio of cefotaxime sodium and sodium-tazobactam is 4:1.
4. the preparation method of cefotaxime sodium for injection according to claim 1 and Tazobactam Sodium preparation of sodium, is characterized in that, described cefotaxime sodium is injection rank.
5. the preparation method of cefotaxime sodium for injection according to claim 1 and Tazobactam Sodium preparation of sodium, is characterized in that, the preparation method of described sodium-tazobactam comprises: tazobactam and reaction of sodium bicarbonate are obtained to sodium-tazobactam.
6. cefotaxime sodium for injection and a Tazobactam Sodium preparation of sodium, is characterized in that, adopts cefotaxime sodium for injection described in claim 1～5 any one and the preparation method of Tazobactam Sodium preparation of sodium to prepare.
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| 头孢噻肟钠伍用他唑巴坦钠的临床前实验研究;杨立等;《中国热带医学》;20051231;第5卷(第9期);1816-1818 * |
| 杨立等.头孢噻肟钠伍用他唑巴坦钠的临床前实验研究.《中国热带医学》.2005,第5卷(第9期),1816-1818. |
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