CN102871962A - Drug combination of mezlocillin sodium for injection and preparation method of same - Google Patents
Drug combination of mezlocillin sodium for injection and preparation method of same Download PDFInfo
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- CN102871962A CN102871962A CN 201210300664 CN201210300664A CN102871962A CN 102871962 A CN102871962 A CN 102871962A CN 201210300664 CN201210300664 CN 201210300664 CN 201210300664 A CN201210300664 A CN 201210300664A CN 102871962 A CN102871962 A CN 102871962A
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- mezlocillin
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Abstract
The invention discloses a drug combination of mezlocillin sodium, namely mezlocillin sodium nanoparticle injection which comprises mezlocillin sodium, a carrier material, a stabilizing agent and an excipient. The average effective particlesize of nanoparticle is 10 to 20 nm. The preparation method of the injection comprises the steps of mixing the mezlocillin sodium and the stabilizing agent in water for injection, adjusting pH value, and then adding the carrier material and the excipient into the mezlocillin sodium and the stabilizing agent. The mezlocillin sodium nanoparticle injection has the advantages of good re-solubility, good stability, high drug loading capacity and the like, and the method is suitable for industrial production.
Description
Technical field
The invention belongs to medical technical field, relate to pharmaceutical composition of a kind of mezlocillin for inj and preparation method thereof, relate to a kind of mezlocillin for inj nanoparticle injection and preparation method thereof.
Background technology
These product of mezlocillin (Azlocillin) are the semi-synthetic penicillins antibiotic, to Pseudomonas aeruginosa, escherichia coli, pneumobacillus, Bacillus proteus, Enterobacter, citrobacter, Serratia, acinetobacter and to the gram positive coccus of penicillin sensitivity bacteriostasis is arranged all, heavy dose has bactericidal action.Antibacterial activity to escherichia coli, Enterobacter, pneumobacillus, citrobacter, Serratia and acinetobacter etc. is better than carbenicillin, ampicillin; Antibacterial activity to the positive Bacillus proteus of indole, Pseudomonas aeruginosa is better than carbenicillin and sulbenicillin; Antibacterial activity to gram positive bacteria such as staphylococcus aureus is similar to carbenicillin, and more superior than carbenicillin, sulbenicillin to the antibacterial activity of streptococcus faecalis.Most of anaerobe such as bacteroides fragilis had better antibacterial action.This product in vitro tests show its to antibacterial produce (lactamase is unstable.The aminoglycoside antibiotics use in conjunction such as these product and gentamycin, kanamycin have remarkable synergism.
There is not open Patents about mezlocillin sodium nanoparticle injection and preparation method thereof in Patent Office through the retrieval current national.
Summary of the invention
The invention provides a kind of Novel injection mezlocillin sodium pharmaceutical composition, i.e. it is good that mezlocillin sodium nanoparticle injection, this injection have a solubility, excellent, the drug loading advantages of higher of stability.
The purpose of this invention is to provide a kind of mezlocillin sodium nanoparticle injection.
Another object of the present invention provides the preparation method of above-mentioned injection.
Specifically, the invention provides a kind of mezlocillin sodium injection, this injection is comprised of mezlocillin sodium, nanoparticulate carriers material, surface stability, excipient; Wherein, each composition weight umber is:
1 part of mezlocillin sodium
3～10 parts of carrier materials
0.03～0.1 part of surface stability
2～8 parts of excipient.
In a preferred embodiment of the invention, the invention provides a kind of mezlocillin sodium injection, wherein, each composition weight umber is:
1 part of mezlocillin sodium
4～6 parts of carrier materials
New 0.04～0.06 part of surface-stable
4～6 parts of excipient.
In the most preferred embodiment of the present invention, the invention provides a kind of mezlocillin sodium injection, wherein, each composition weight umber is:
1 part of mezlocillin sodium
5 parts of carrier materials
New 0.05 part of surface-stable
5 parts of excipient.
In the sodium injection of mezlocillin provided by the invention, wherein, carrier material is selected from alpha-cyanoacrylate alkane ester or methyl methacrylate, preferably, be selected from a kind of in methyl 2-cyanoacrylate, cyanacrylate, alpha-cyanoacrylate propyl ester, BCA, the isobutylcyanoacrylate, most preferably, be selected from BCA.
In the sodium injection of mezlocillin provided by the invention, wherein, surface stabilizer is selected from anionic surface stabilizing agent, cationic surface stabilizing agent, amphion surface stability and nonionic surface stabilizer.Preferably, described anionic surface stabilizing agent is selected from sodium lauryl sulphate, sodium hexadecyl sulfate, dodecyl sodium sulfate, sodium stearyl sulfate, dihexyl sodium sulfosuccinate, liver sodium cholate, Bile Salts: described cationic surfactant is selected from benzalkonium bromide,, benzalkonium chloride, poly-butylamine, bromination polybutene acid methyl ester trimethyl ammonium bromide, bromination hexyl desyl,a-phenyl phenacyl trimethyl ammonium, methyl tricaprylammonium chloride, dimethylammonium chloride, Tetrabutylammonium bromide; Described amphion surface-stable dosage form is selected from cephalin, phosphatidylcholine, serinephosphatide, lipositol, glycolipid, neutral esters, cholesterol; Described nonionic surface stabilizer is selected from polyvinyl alcohol, Polyethylene Glycol, Arlacel-20, sorbitan palmitate, sorbitan monostearate, Arlacel-80, sorbitan trioleate, dextran, polysorbate 20, polysorbate 40, polysorbate 60, polyoxyethylene sorbitan monoleate, polysorbate 85, Brij30, Brij35, poloxamer; Most preferably, described surface stabilizer selects Polyethylene Glycol, poloxamer.
In the sodium injection of mezlocillin provided by the invention, wherein, excipient is selected from gelatin hydrolysate, and one or more in glycine, glutamic acid, lactose, glucose, sorbitol, mannitol, the xylitol preferably, are selected from lactose glue or mannitol.
Mezlocillin provided by the invention sodium injection, by the light dispersion method measurement, its effective particle mean size is 10～1800nm, 10～1200nm, 10～800nm, 10～400nm, 10～200nm. here, described effective particle mean size represents based on weighing scale, the granularity of at least 50% mezlocillin sodium granule is less than effective meansigma methods, by above-mentioned commercial measurement, be 10～1800nm, 10～1200nm, 10～800nm, 10～400nm, 10～200nm etc. namely.In embodiments of the invention, the granularity of at least 80%, at least 90%, at least 95% mezlocillin sodium is less than effective meansigma methods, i.e. 10～1800nm, 10～1200nm, 10～800nm, 10～400nm, 10～200nm etc.
The invention provides a kind of mezlocillin sodium nanoparticle injection, this injection is comprised of mezlocillin sodium, nanoparticulate carriers material, surface stabilizer, excipient; Wherein, each composition weight mark is:
1 part of mezlocillin sodium
3～10 parts of carrier materials
0.03～0.1 part of surface stabilizer
2～8 parts of excipient.
And, described mezlocillin sodium nanoparticle injection, by the light dispersion method, its effective size of grain is 10～1800nm, 10～1200nm, 10～800nm, 10～400nm, 10～200nm. are here, described effective particle mean size represents based on weighing scale, the granularity of at least 50% mezlocillin sodium granule by above-mentioned commercial measurement, is 10～1800nm, 10～1200nm, 10～800nm, 10～400nm, 10～200nm etc. namely less than effective meansigma methods.In embodiments of the invention, the granularity of at least 80%, at least 90%, at least 95% mezlocillin sodium is less than effective meansigma methods, i.e. 10～1800nm, 10～1200nm, 10～800nm, 10～400nm, 10～200nm etc.
1 part of mezlocillin sodium
4～6 parts of carrier materials
0.04～0.06 part of surface stabilizer
4～6 parts of excipient.
And, described mezlocillin sodium nanoparticle injection, by the light dispersion method, its effective size of grain is 10～1800nm, 10～1200nm, 10～800nm, 10～400nm, 10～200nm. are here, described effective particle mean size represents based on weighing scale, the granularity of at least 50% mezlocillin sodium granule by above-mentioned commercial measurement, is 10～1800nm, 10～1200nm, 10～800nm, 10～400nm, 10～200nm etc. namely less than effective meansigma methods.In embodiments of the invention, the granularity of at least 80%, at least 90%, at least 95% mezlocillin sodium is less than effective meansigma methods, i.e. 10～1800nm, 10～1200nm, 10～800nm, 10～400nm, 10～200nm etc.
In the most preferred embodiment of the present invention, the invention provides a kind of mezlocillin sodium injection, wherein, each composition weight umber is:
1 part of mezlocillin
5 parts of carrier materials
0.05 part of surface stabilizer
5 parts of excipient.
And, described mezlocillin sodium nanoparticle injection, by the light dispersion method, its effective size of grain is 10～1800nm, 10～1200nm, 10～800nm, 10～400nm, 10～200nm. are here, described effective particle mean size represents based on weighing scale, the granularity of at least 50% mezlocillin sodium granule by above-mentioned commercial measurement, is 10～1800nm, 10～1200nm, 10～800nm, 10～400nm, 10～200nm etc. namely less than effective meansigma methods.In embodiments of the invention, the granularity of at least 80%, at least 90%, at least 95% mezlocillin sodium is less than effective meansigma methods, i.e. 10～1800nm, 10～1200nm, 10～800nm, 10～400nm, 10～200nm etc.
On the other hand, the preparation method of above-mentioned mezlocillin provided by the invention sodium injection, mezlocillin sodium, stabilizing agent are mixed in water for injection, regulate pH value, rear adding carrier material and excipient dissolving, get mezlocillin sodium nanoparticle solution, it is sub-packed in the cillin bottle, adopting freeze drying process to be worth the nanoparticle injection.
The preparation method of mezlocillin sodium nano injection provided by the invention agent comprises the steps:
⑴ add mezlocillin sodium, stabilizing agent in the water for injection, stirs and make dissolving, with acid for adjusting pH value to 1.0～3.0;
⑵ make progress and add carrier material in the solution, and stirring at room 4～6h adds excipient and stirs and make dissolving, regulates pH value to 6.0～8.0 with alkali;
⑶ adopt 0.22 μ m filtering with microporous membrane, obtains mezlocillin sodium nanoparticle solution;
⑷ divide mentioned solution in the cillin bottle that is filled to after the sterilization, uses the freezer dryer lyophilizing, with aseptic plug sealing, seals carrying out Zha Gai with aseptic aluminium lid at last, obtains mezlocillin sodium nanoparticle injection.
The preparation method of a kind of mezlocillin sodium nanoparticle injection provided by the invention, wherein, the described acid of step ⑴ is selected from hydrochloric acid, sulphuric acid, carbonic acid, nitric acid, phosphoric acid, formic acid, acetic acid, ethanedioic acid, citric acid; Be preferably hydrochloric acid, sulphuric acid, carbonic acid.
The preparation method of a kind of mezlocillin sodium nanoparticle injection provided by the invention, wherein, the described alkali of step ⑵ is selected from sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, sodium hydrogen phosphate, sodium dihydrogen phosphate; Be preferably sodium bicarbonate, sodium hydroxide.
Compared with the prior art, mezlocillin sodium nano particle preparations provided by the invention and preparation method thereof has the following advantages:
1, good stability: mezlocillin sodium provided by the invention is with its parcel and be adsorbed in the nano carrier material, and its active component is effectively protected, therefore stability is better than commercially available product.Accelerate June and long-time stability investigate the result also show solution colour, pH value, related substance,, content all do not have significant change, envelop rate is little, has greatly improved medicine stability.
2, preparation is simple: nanoparticle solution preparation technology of the present invention is simple, does not need to add any organic solvent, can finish in normal temperature condition hemostasis water, more is adapted to industrialized great production.
3, solubility is good, Save Range is wide, the employing of Freeze Drying Technique has effectively avoided the degraded of polymeric material, medicine to reveal or drug degradation, make the medicine preservation condition wider, and add excipient before the lyophilization and make the solubility of this product good, basic identical before the various physicochemical properties of medicine and the lyophilizing after redissolving.
The specific embodiment
Further specify the present invention by following specific embodiment, but and be not limited by the following examples.
The preparation of embodiment 1 mezlocillin sodium nanoparticle injection
Write out a prescription 100 bottles
Mezlocillin sodium 600g
BCA 700g
Polyethylene Glycol 7g
Lactose 500g.
Preparation technology:
⑴ join 200g mezlocillin sodium, 7g Polyethylene Glycol in the 2.4L water for injection, stirs to make dissolving, with sulfur acid for adjusting pH to 2.0～3.0;
⑵ with mentioned solution under agitation to wherein adding the 700g BCA, behind the stirring at room 6h, add lactose 500g, continuing to be stirred to fully dissolving, regulates pH to 4.0～6.0 with sodium hydroxide;
⑶ adopt 0.22 μ m filtering with microporous membrane with mentioned solution, obtains mezlocillin sodium nanoparticle solution;
⑷ divide mentioned solution in the cillin bottle that is filled to after the sterilization, behind-40 ℃～-50 ℃ pre-freeze 3h, uses the freezer dryer lyophilizing, afterwards with aseptic plug sealing, seals carrying out Zha Gai with aseptic aluminium lid Zha Gai, obtains mezlocillin sodium nanoparticle injection.
The preparation of embodiment 2 mezlocillin sodium nanoparticle injections
Write out a prescription 100 bottles
Mezlocillin sodium 200g
Alpha-cyanoacrylate propyl ester 600g
Polyethylene Glycol 6g
Mannitol 600g.
Preparation technology:
⑴ join 200g mezlocillin sodium, 6g Polyethylene Glycol in the 2L water for injection, stirs to make dissolving, with first acid for adjusting pH to 2.0～3.0;
⑵ with mentioned solution under agitation to wherein adding 600g alpha-cyanoacrylate propyl ester, behind the stirring at room 5h, add mannitol 600g, continuing to be stirred to fully dissolving, regulates pH to 4.0～7.0 with sodium bicarbonate;
⑶ adopt 0.22 μ m filtering with microporous membrane with mentioned solution, obtains mezlocillin sodium nanoparticle solution;
⑷ divide mentioned solution in the cillin bottle that is filled to after the sterilization, behind-40 ℃～-50 ℃ pre-freeze 3h, uses the freezer dryer lyophilizing, afterwards with aseptic plug sealing, seals carrying out Zha Gai with aseptic aluminium lid Zha Gai, obtains mezlocillin sodium nanoparticle injection.
The preparation of embodiment 3 mezlocillin sodium nanoparticle injections
Write out a prescription 100 bottles
Mezlocillin sodium 200g
BCA 600g
Poloxamer 6g
Glucose 600g.
Preparation technology:
⑴ join 100g mezlocillin sodium, 5g poloxamer in the 2L water for injection, stirs to make dissolving, with salt acid for adjusting pH to 1.0～2.0;
⑵ with mentioned solution under agitation to wherein adding the 600g BCA, behind the stirring at room 5h, add glucose 600g, continuing to be stirred to fully dissolving, regulates pH to 4.0～7.0 with sodium bicarbonate;
⑶ adopt 0.22 μ m filtering with microporous membrane with mentioned solution, obtains mezlocillin sodium nanoparticle solution;
⑷ divide mentioned solution in the cillin bottle that is filled to after the sterilization, behind-40 ℃～-50 ℃ pre-freeze 3h, uses the freezer dryer lyophilizing, afterwards with aseptic plug sealing, seals carrying out Zha Gai with aseptic aluminium lid Zha Gai, obtains mezlocillin sodium nanoparticle injection.
The preparation of embodiment 4 mezlocillin sodium nanoparticle injections
Write out a prescription 100 bottles
Mezlocillin sodium 200g
Methyl 2-cyanoacrylate 600g
Polyethylene Glycol 6g
Mannitol 600g.
Preparation technology:
⑴ join 200g mezlocillin sodium, 5g Polyethylene Glycol in the 2L water for injection, stirs to make dissolving, with salt acid for adjusting pH to 1.0～2.0;
⑵ with mentioned solution under agitation to wherein adding the 600g methyl 2-cyanoacrylate, behind the stirring at room 4h, add mannitol 600g, continuing to be stirred to fully dissolving, regulates pH to 4.0～7.0 with sodium hydroxide;
⑶ adopt 0.22 μ m filtering with microporous membrane with mentioned solution, obtains mezlocillin sodium nanoparticle solution;
⑷ divide mentioned solution in the cillin bottle that is filled to after the sterilization, behind-40 ℃～-50 ℃ pre-freeze 3h, uses the freezer dryer lyophilizing, afterwards with aseptic plug sealing, seals carrying out Zha Gai with aseptic aluminium lid Zha Gai, obtains mezlocillin sodium nanoparticle injection.
The preparation of embodiment 5 mezlocillin sodium nanoparticle injections
Write out a prescription 100 bottles
Mezlocillin sodium 200g
Isobutylcyanoacrylate 500g
Polyethylene Glycol 5g
Glucose 500g.
Preparation technology:
⑴ join 200g mezlocillin sodium, 5g Polyethylene Glycol in the 2L water for injection, stirs to make dissolving, with salt acid for adjusting pH to 2.0～3.0;
⑵ with mentioned solution under agitation to wherein adding the 500g isobutylcyanoacrylate, behind the stirring at room 5h, add glucose 500g, continuing to be stirred to fully dissolving, regulates pH to 4.0～7.0 with sodium bicarbonate;
⑶ adopt 0.22 μ m filtering with microporous membrane with mentioned solution, obtains mezlocillin sodium nanoparticle solution;
⑷ divide mentioned solution in the cillin bottle that is filled to after the sterilization, behind-40 ℃～-50 ℃ pre-freeze 3h, uses the freezer dryer lyophilizing, afterwards with aseptic plug sealing, seals carrying out Zha Gai with aseptic aluminium lid Zha Gai, obtains mezlocillin sodium nanoparticle injection.
Embodiment 6 mezlocillin sodium nanoparticle injection particle diameters detect
Method: get the nano particle preparations of the present invention's preparation, be dissolved in water into the solution that every 1ml contains 1mg, use the laser light scattering particle size analyzer determination.The mezlocillin sodium nano particle preparations of acetonideexample 1～5 preparation is spherical shape, and particle size distribution is even, the results are shown in Table 1:
Table 1, mezlocillin sodium nanoparticle injection particle diameter detect
| ? | Embodiment 1 | Embodiment 2 | Embodiment 3 | Embodiment 4 | Embodiment 5 |
| d（0.1） | 33nm | 34nm | 51nm | 73nm | 31nm |
| d（0.5） | 85nm | 103nm | 114nm | 132nm | 83nm |
| d（0.9） | 131nm | 157nm | 157nm | 187nm | 140nm |
The result shows, all between 10～200nm, particle size distribution is even for gained mezlocillin sodium nanoparticle particle size distribution range of the present invention.
Embodiment 7 mezlocillin sodium nanoparticle injection envelop rates and drug loading detect
Method: mezlocillin sodium nanoparticle injection is dissolved in water or is diluted to the solution that every 1ml contains mezlocillin sodium 1mg, high speed centrifugation, 5000r/min, centrifugal 30min gets supernatant 1ml, uses dissolve with methanol, with the content of high effective liquid chromatography for measuring mezlocillin sodium, determine entrapped content M
1, the mezlocillin sodium total amount is M in the nano particle preparations
0, nano particle preparations gross weight M
2
Envelop rate=M
1/ M
0* 100%
Drug loading=M
1/ M
2* 100%.
The mezlocillin sodium nano particle preparations of acetonideexample 1～5 preparation is that envelop rate and drug loading the results are shown in Table 2:
The envelop rate of table 2, mezlocillin sodium nano particle preparations and drug loading detect
| ? | Embodiment 1 | Embodiment 2 | Embodiment 3 | Embodiment 4 | Embodiment 5 |
| Envelop rate | 85.2% | 86.4% | 89.2% | 91.2% | 86.1% |
| Drug loading | 18.3% | 17.2% | 18.1% | 16.0% | 19.6% |
The result shows, the mezlocillin sodium nanoparticle injection of gained of the present invention is sealed rate all more than 85%, and the limit that also meets 2010 editions guidelines of Chinese Pharmacopoeia requires (envelop rate must not be lower than 80%).
The dissolution velocity of embodiment 8 products is investigated
Embodiment 2, embodiment 3 and physical mixed are obtained mezlocillin for inj wait respectively quality to get 5 bottles, be designated as No. 1, No. 2, No. 3, No. 4, No. 5 with embodiment 2 gained samples; Be designated as No. 6, No. 7, No. 8, No. 9, No. 10 with embodiment 3 gained samples; Be designated as No. 11, No. 12, No. 13, No. 14, No. 15 with direct mixing gained sample, dissolving method by clinical application injects respectively 10ml water for injection, and it is jolted at eddy mixer, take the dissolve complete clarification as index, calculate dissolution velocity (being shown in Table 3)
The rate of dissolution of table 3, mezlocillin sodium nanoparticle injection and direct packaging gained injection is investigated
The result shows, the rate of dissolution of mezlocillin sodium nanoparticle injection provided by the invention obviously is better than the injection of direct packaging gained.
Embodiment 9 mezlocillin sodium nanoparticle injection study on the stability
Accelerated test is investigated
The sample of the embodiment of the invention 1～5 preparation and the mezlocillin sodium injection of raw material direct packaging preparation are placed respectively 40 ℃ of high temperature, lower 6 months of relative humidity 75% ± 5% condition, accelerate to investigate, the results are shown in Table 4:
The study on the stability of table 4, mezlocillin sodium nanoparticle injection and direct packaging gained injection
Experiment shows, the injection character of mezlocillin sodium raw materials direct packaging preparation becomes micro-yellow powder when accelerating June, and pH descends larger, and content is obvious, and related substance significantly raises; Sample appearance character, visible foreign matters, pH value, content and the related substance of the embodiment of the invention 1～5 preparation have no significant change, and solubility is very fast, and envelop rate descends all in 3%; Sufficient proof product of the present invention is better than the listing product aspect stable, have gratifying technique effect.
Claims (9)
1. mezlocillin pharmaceutical composition, it is mezlocillin nanoparticle injection, and wherein, described injection is comprised of mezlocillin, nanoparticulate carriers material, surface stabilizer, excipient, and wherein, each composition weight umber is:
1 part of mezlocillin
Carrier material 3-10 part
Surface stabilizer 0.03-0.1 part
Excipient 2-8 part
Carrier material described here is alpha-cyanoacrylate alkane ester: described cyano group propylene is calculated the alkane ester and is selected from methyl 2-cyanoacrylate, cyanacrylate, alpha-cyanoacrylate propyl ester, a kind of in BCA, the isobutylcyanoacrylate; Described surface stabilizer is the nonionic surface stabilizer; Described nonionic surface stabilizer is selected from Polyethylene Glycol, poloxamer.
2. mezlocillin according to claim 1 pharmaceutical composition, wherein each composition weight umber is:
1 part of mezlocillin
Carrier material 4-6 part
Surface stabilizer 0.04-0.06 part
Excipient 4-6 part.
3. mezlocillin according to claim 2 pharmaceutical composition, wherein each composition weight umber is:
1 part of mezlocillin
5 parts of carrier materials
0.05 part of surface stabilizer
5 parts of excipient.
4. the described mezlocillin of arbitrary claim pharmaceutical composition in 3 according to claim 1, wherein said excipient selects one or more in gelatin hydrolysate, glycine, glutamic acid, lactose, glucose, sorbitol, mannitol, the xylitol.
5. mezlocillin according to claim 4 pharmaceutical composition, wherein said excipient is selected from lactose or sorbitol.
6. the described mezlocillin of arbitrary claim pharmaceutical composition in 3 according to claim 1, wherein by the light dispersion method measurement, its effective particle mean size is 10-200nm.
7. mezlocillin according to claim 6 pharmaceutical composition, wherein the granularity of at least 80% mezlocillin is less than effective meansigma methods.
8. mezlocillin according to claim 7 pharmaceutical composition, wherein the granularity of at least 95% mezlocillin is less than effective meansigma methods.
9. the preparation method of the described mezlocillin of arbitrary claim pharmaceutical composition in the claim 1 to 8 comprises the steps:
(1) mezlocillin sodium, stabilizing agent are added in the water for injection, stir and make dissolving, regulate pH value to 1.0-3.0 with acid;
(2) add carrier material in mentioned solution, stirring at room 4-6h adds the excipient stirring and makes dissolving, regulates pH value to 6.0-8.0 with alkali;
(3) adopt 0.22 μ m filtering with microporous membrane, obtain mezlocillin sodium nanoparticle solution;
(4) mentioned solution is divided in the cillin bottle that is filled to after the sterilization, use the freezer dryer lyophilizing, aseptic plug sealing seals carrying out Zha Gai with aseptic aluminium lid at last, obtains mezlocillin nanoparticle injection.
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|---|---|---|---|
| CN 201210300664 CN102871962A (en) | 2012-08-23 | 2012-08-23 | Drug combination of mezlocillin sodium for injection and preparation method of same |
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|---|---|---|---|
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106176625A (en) * | 2015-04-29 | 2016-12-07 | 重庆福安药业(集团)股份有限公司 | The pharmaceutical composition of latamoxef sodium for injection |
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2012
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106176625A (en) * | 2015-04-29 | 2016-12-07 | 重庆福安药业(集团)股份有限公司 | The pharmaceutical composition of latamoxef sodium for injection |
| CN106176625B (en) * | 2015-04-29 | 2019-05-31 | 重庆福安药业(集团)股份有限公司 | The pharmaceutical composition of latamoxef sodium for injection |
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Application publication date: 20130116 |