CN102805725A - Azlocillin sodium medicinal composition for injection and preparation method for azlocillin sodium medicinal composition for injection - Google Patents
Azlocillin sodium medicinal composition for injection and preparation method for azlocillin sodium medicinal composition for injection Download PDFInfo
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- CN102805725A CN102805725A CN 201210262214 CN201210262214A CN102805725A CN 102805725 A CN102805725 A CN 102805725A CN 201210262214 CN201210262214 CN 201210262214 CN 201210262214 A CN201210262214 A CN 201210262214A CN 102805725 A CN102805725 A CN 102805725A
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- azlocillin
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Abstract
The invention discloses an azlocillin sodium medicinal composition, namely azlocillin sodium nanoparticle injection. The azlocillin sodium nanoparticle injection consists of azlocillin sodium, a carrier material, stabilizer and excipient, and the effective average particle size of nanoparticles is 10 to 200nm. The invention discloses a preparation method for the injection; and the method comprises the following steps of: mixing the azlocillin sodium and the stabilizer in water for injection, adjusting pH value, and adding the carrier material and the excipient to obtain the azlocillin sodium nanoparticle injection. The injection has the advantages of high redissolution performance, excellent stability, high medicine loading capacity and the like, and the process is suitable for industrial large-scale production.
Description
Technical field
The invention belongs to medical technical field, relate to pharmaceutical composition of a kind of azlocillin sodium for injection and preparation method thereof, relate to a kind of azlocillin sodium for injection nanoparticle injection and preparation method thereof.
Background technology
Azlocillin (Azlocillin) is one of penbritin, and most of gram-positive coccis and negative bacillus are had strong antibacterial activity, especially bacillus pyocyaneus is comprised that the antibacterial action of drug resistance bacillus pyocyaneus is its outstanding advantage by force.Be mainly used in responsive gram positive bacteria and various infection and the charrin disease due to the negative bacterium clinically; Comprise that septicemia, meningitis, endocarditis, purulent pleurisy, peritonitis and lower respiratory tract, gastrointestinal tract, biliary tract, urinary tract, bone and soft tissue and genitals official rank infect; Gynecological, obstetrics infect pernicious external otitis, burn, skin and postoperative infection etc.We can say that the azlocillin is a kind of has a broad antifungal spectrum, antibacterial activity is strong, and safety is big, is prone to the medicine of tolerance.To various antibacterials, especially bacillus pyocyaneus (comprising drug-fast bacillus pyocyaneus) effect is strong, and clinical efficacy is higher, is another alternative medicine in the broad ectrum antibiotic.
The disclosed azlocillin sodium for injection of current Chinese patent mainly contains two kinds of common lyophilizing of production technology (CN102161665A) and raw material direct packaging (CN101265265); Azlocillin sodium for injection high-efficiency antimicrobial pharmaceutical composition (CN1586478), its weight ratio that contains azlocillin sodium and sulbactam is 1: 10-10: 1; Another disclosed azlocillin sodium for injection high-efficient medicament composition (CN1586480), its weight ratio that contains azlocillin sodium and Tazobactam Sodium is 1: 10-10: 1.Above patent is prescription and the production technology of azlocillin sodium for injection in conventional field, and made medicine solubility and stability are all relatively poor, has influenced the safety and the effectiveness of pharmaceutical trial greatly.
Summary of the invention
The invention provides a kind of novel azlocillin sodium for injection pharmaceutical composition, i.e. it is good that azlocillin 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 azlocillin sodium nanoparticle injection.
Another object of the present invention provides the method for preparing of above-mentioned injection.
Specifically, the invention provides a kind of azlocillin sodium injection, this injection is made up of azlocillin sodium, nanoparticulate carriers material, surface stabilizer, excipient; Wherein, each composition weight umber is:
1 part of azlocillin sodium
3～10 parts of carrier materials
0.03～0.1 part of surface stabilizer
2～8 parts of excipient
In a preferred embodiment of the invention, the invention provides a kind of azlocillin sodium injection, wherein, each composition weight umber is:
1 part of azlocillin sodium
4～6 parts of carrier materials
0.04～0.06 part of surface stabilizer
4～6 parts of excipient
In the most preferred embodiment of the present invention, the invention provides a kind of azlocillin sodium injection, wherein, each composition weight umber is:
1 part of azlocillin sodium
5 parts of carrier materials
0.05 part of surface stabilizer
5 parts of excipient
In the sodium injection of azlocillin provided by the invention; Wherein, Carrier material is selected from alpha-cyanoacrylate alkane ester or methyl methacrylate, preferably, is selected from a kind of in methyl 2-cyanoacrylate, cyanacrylate, alpha-cyanoacrylate propyl ester, the positive butyl ester of alpha-cyanoacrylate, the isobutylcyanoacrylate; Most preferably, be selected from cyanacrylate.
In the sodium injection of azlocillin 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, gather 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, said surface stabilizer selects Polyethylene Glycol, poloxamer.
In the sodium injection of azlocillin 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 gelatin hydrolysate or glycine.
Azlocillin provided by the invention sodium injection is measured through the light dispersion method, and its effective particle mean size is 10～1800nm; 10～1200nm, 10～800nm, 10～400nm; 10～200nm. here, said effective particle mean size representes that based on the weight meter the particulate granularity of at least 50% azlocillin sodium is less than effective meansigma methods;, be 10～1800nm, 10～1200nm, 10～800nm, 10～400nm, 10～200nm etc. promptly through above-mentioned commercial measurement.In embodiments of the invention, the granularity of at least 80%, at least 90%, at least 95% azlocillin 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 azlocillin sodium nanoparticle injection, this injection is made up of azlocillin sodium, nanoparticulate carriers material, surface stabilizer, excipient; Wherein, each composition weight mark is:
1 part of azlocillin sodium
3～10 parts of carrier materials
0.03～0.1 part of surface stabilizer
2～8 parts of excipient
And described azlocillin sodium nanoparticle injection is through the light dispersion method; Its effective size of grain is 10～1800nm, 10～1200nm, 10～800nm; 10～400nm, 10～200nm. here, said effective particle mean size is represented based on the weight meter; The particulate granularity of at least 50% azlocillin sodium through above-mentioned commercial measurement, is 10～1800nm, 10～1200nm, 10～800nm, 10～400nm, 10～200nm etc. promptly less than effective meansigma methods.In embodiments of the invention, the granularity of at least 80%, at least 90%, at least 95% azlocillin sodium is less than effective meansigma methods, i.e. 10～1800nm, 10～1200nm, 10～800nm, 10～400nm, 10～200nm etc.
1 part of azlocillin sodium
4～6 parts of carrier materials
0.04～0.06 part of surface stabilizer
4～6 parts of excipient
And described azlocillin sodium nanoparticle injection is through the light dispersion method; Its effective size of grain is 10～1800nm, 10～1200nm, 10～800nm; 10～400nm, 10～200nm. here, said effective particle mean size is represented based on the weight meter; The particulate granularity of at least 50% azlocillin sodium through above-mentioned commercial measurement, is 10～1800nm, 10～1200nm, 10～800nm, 10～400nm, 10～200nm etc. promptly less than effective meansigma methods.In embodiments of the invention, the granularity of at least 80%, at least 90%, at least 95% azlocillin sodium is less than effective meansigma methods, i.e. 10～1800nm, 10～1200nm, 10～800nm, 10～400nm, 10～200nm etc.
In most preferred embodiment of the present invention, the invention provides a kind of azlocillin sodium injection, wherein, each composition weight umber is:
1 part of azlocillin
5 parts of carrier materials
0.05 part of surface stabilizer
5 parts of excipient.
And described azlocillin sodium nanoparticle injection is through the light dispersion method; Its effective size of grain is 10～1800nm, 10～1200nm, 10～800nm; 10～400nm, 10～200nm. here, said effective particle mean size is represented based on the weight meter; The particulate granularity of at least 50% azlocillin sodium through above-mentioned commercial measurement, is 10～1800nm, 10～1200nm, 10～800nm, 10～400nm, 10～200nm etc. promptly less than effective meansigma methods.In embodiments of the invention, the granularity of at least 80%, at least 90%, at least 95% azlocillin 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 method for preparing of above-mentioned azlocillin provided by the invention sodium injection is mixed azlocillin sodium, stabilizing agent in water for injection, regulate pH value; The back adds carrier material and excipient dissolving; Get azlocillin sodium nanoparticle solution, it is sub-packed in the cillin bottle, adopting freeze drying process to be worth the nanoparticle injection.
The method for preparing of azlocillin sodium nano injection provided by the invention agent comprises the steps
⑴ add azlocillin 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 azlocillin sodium nanoparticle solution.
⑷ be filled to above-mentioned solution branch in the cillin bottle after the sterilization, uses the freezer dryer lyophilizing, sealing with aseptic plug, carry out the Zha Gai sealing with aseptic aluminium lid, obtains azlocillin sodium nanoparticle injection at last.
The method for preparing of a kind of azlocillin 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 method for preparing of a kind of azlocillin 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 carbonate, sodium hydroxide.
With the prior art ratio, azlocillin sodium nano particle preparations provided by the invention and preparation method thereof has the following advantages:
1, good stability: azlocillin sodium provided by the invention is with its parcel and be adsorbed in the nano carrier material, and its active component is had
Imitate protection, so stability is superior to commercially available article.Quicken June and long-time stability investigation result and show that also 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 formulations prepared from solutions technology of the present invention is simple, need not add any organic solvent, in normal temperature condition injected water, can accomplish, and 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 the adding excipient make the solubility of these article good before the lyophilization, basic identical before various physicochemical properties of medicine and the lyophilizing after redissolving.
The specific embodiment
Further specify the present invention through following specific embodiment, but do not receive the restriction of following examples
The preparation of embodiment 1 azlocillin sodium nanoparticle injection
Write out a prescription 100 bottles
Azlocillin sodium 600g
The positive butyl ester 700g of alpha-cyanoacrylate
Polyethylene Glycol 7g
Glycine 700g
Preparation technology:
⑴ join 200g azlocillin sodium, 7g Polyethylene Glycol in the 2.4L water for injection, stirs to make dissolving, regulates pH to 2.0～3.0. with sulphuric acid
⑵ with above-mentioned solution under agitation to wherein adding the positive butyl ester of 700g alpha-cyanoacrylate, behind the stirring at room 6h, add glycine 700g, continuing to be stirred to dissolving fully, regulates pH to 6.0～8.0 with sodium hydroxide.
⑶ adopt 0.22 μ m filtering with microporous membrane with above-mentioned solution, obtains azlocillin sodium nanoparticle solution.
⑷ be filled to above-mentioned solution branch in the cillin bottle after the sterilization, behind-40 ℃～-50 ℃ pre-freeze 3h, uses the freezer dryer lyophilizing, and seal with aseptic plug the back, seals carrying out Zha Gai with aseptic aluminium lid Zha Gai, obtains azlocillin sodium nanoparticle injection.
The preparation of embodiment 2 azlocillin sodium nanoparticle injections
Write out a prescription 100 bottles
Azlocillin sodium 200g
Alpha-cyanoacrylate propyl ester 600g
Polyethylene Glycol 6g
Gelatin hydrolysate 600g
Preparation technology:
⑴ join 200g azlocillin sodium, 6g Polyethylene Glycol in the 2L water for injection, stirs to make dissolving, regulates pH to 2.0～3.0 with formic acid.
⑵ with above-mentioned solution under agitation to wherein adding 600g alpha-cyanoacrylate propyl ester, behind the stirring at room 5h, add gelatin hydrolysate 600g, continuing to be stirred to dissolving fully, regulates pH to 6.0～8.0 with sodium bicarbonate.
⑶ adopt 0.22 μ m filtering with microporous membrane with above-mentioned solution, obtains azlocillin sodium nanoparticle solution.
⑷ be filled to above-mentioned solution branch in the cillin bottle after the sterilization, behind-40 ℃～-50 ℃ pre-freeze 3h, uses the freezer dryer lyophilizing, and seal with aseptic plug the back, seals carrying out Zha Gai with aseptic aluminium lid Zha Gai, obtains azlocillin sodium nanoparticle injection.
The preparation of embodiment 3 azlocillin sodium nanoparticle injections
Write out a prescription 100 bottles
Azlocillin sodium 200g
The positive butyl ester 600g of alpha-cyanoacrylate
Poloxamer 6g
Mannitol 600g
Preparation technology:
⑴ join 100g azlocillin sodium, 5g poloxamer in the 2L water for injection, stirs to make dissolving, regulates pH to 1.0～2.0 with hydrochloric acid.
⑵ with above-mentioned solution under agitation to wherein adding the positive butyl ester of 600g alpha-cyanoacrylate, behind the stirring at room 5h, add mannitol 600g, continuing to be stirred to dissolving fully, regulates pH to 6.0～8.0 with sodium bicarbonate.
⑶ adopt 0.22 μ m filtering with microporous membrane with above-mentioned solution, obtains azlocillin sodium nanoparticle solution.
⑷ be filled to above-mentioned solution branch in the cillin bottle after the sterilization, behind-40 ℃～-50 ℃ pre-freeze 3h, uses the freezer dryer lyophilizing, and seal with aseptic plug the back, seals carrying out Zha Gai with aseptic aluminium lid Zha Gai, obtains azlocillin sodium nanoparticle injection.
The preparation of embodiment 4 azlocillin sodium nanoparticle injections
Write out a prescription 100 bottles
Azlocillin sodium 200g
Methyl 2-cyanoacrylate 600g
Polyethylene Glycol 6g
Gelatin hydrolysate 600g
Preparation technology:
⑴ join 200g azlocillin sodium, 5g Polyethylene Glycol in the 2L water for injection, stirs to make dissolving, regulates pH to 1.0～2.0 with hydrochloric acid.
⑵ with above-mentioned solution under agitation to wherein adding the 600g methyl 2-cyanoacrylate, behind the stirring at room 4h, add gelatin hydrolysate 600g, continuing to be stirred to dissolving fully, regulates pH to 6.0～8.0 with sodium hydroxide.
⑶ adopt 0.22 μ m filtering with microporous membrane with above-mentioned solution, obtains azlocillin sodium nanoparticle solution.
⑷ be filled to above-mentioned solution branch in the cillin bottle after the sterilization, behind-40 ℃～-50 ℃ pre-freeze 3h, uses the freezer dryer lyophilizing, and seal with aseptic plug the back, seals carrying out Zha Gai with aseptic aluminium lid Zha Gai, obtains azlocillin sodium nanoparticle injection.
The preparation of embodiment 5 azlocillin sodium nanoparticle injections
Write out a prescription 100 bottles
Azlocillin sodium 200g
Isobutylcyanoacrylate 500g
Polyethylene Glycol 5g
Glycine 500g
Preparation technology:
⑴ join 200g azlocillin sodium, 5g Polyethylene Glycol in the 2L water for injection, stirs to make dissolving, regulates pH to 2.0～3.0 with hydrochloric acid.
⑵ with above-mentioned solution under agitation to wherein adding the 500g isobutylcyanoacrylate, behind the stirring at room 5h, add glycine 500g, continuing to be stirred to dissolving fully, regulates pH to 6.0～8.0 with sodium bicarbonate.
⑶ adopt 0.22 μ m filtering with microporous membrane with above-mentioned solution, obtains azlocillin sodium nanoparticle solution.
⑷ be filled to above-mentioned solution branch in the cillin bottle after the sterilization, behind-40 ℃～-50 ℃ pre-freeze 3h, uses the freezer dryer lyophilizing, and seal with aseptic plug the back, seals carrying out Zha Gai with aseptic aluminium lid Zha Gai, obtains azlocillin sodium nanoparticle injection.
Embodiment 6 azlocillin 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 azlocillin sodium nano particle preparations of acetonideexample 1～5 preparation is a spherical shape, and particle size distribution is even, and the result sees table 1:
Table 1, azlocillin sodium nanoparticle injection particle diameter detect
| ? | Embodiment 1 | Embodiment 2 | Embodiment 3 | Embodiment 4 | Embodiment 5 |
| d（0.1） | 35nm | 35nm | 55nm | 75nm | 35nm |
| d（0.5） | 85nm | 105nm | 115nm | 135nm | 85nm |
| d（0.9） | 135nm | 155nm | 155nm | 185nm | 145nm |
The result shows that all between 10～200nm, particle size distribution is even for gained azlocillin sodium nanoparticle particle size distribution range of the present invention.
Embodiment 7 azlocillin sodium nanoparticle injection envelop rates and drug loading detect
Method: azlocillin sodium nanoparticle injection is dissolved in water or is diluted to the solution that every 1ml contains azlocillin 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 azlocillin sodium, confirm entrapped content M
1, the azlocillin 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 azlocillin sodium nano particle preparations of acetonideexample 1～5 preparation is that envelop rate and drug loading result see table 2:
The envelop rate of table 2, azlocillin sodium nano particle preparations and drug loading detect
| ? | Embodiment 1 | Embodiment 2 | Embodiment 3 | Embodiment 4 | Embodiment 5 |
| Envelop rate | 87.3% | 87.8% | 91.2% | 93.2% | 87.1% |
| Drug loading | 18.1% | 18.5% | 18.8% | 16.3% | 20.9% |
The result shows that the azlocillin 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 azlocillin sodium for injection wait quality to get 5 bottles respectively, 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 10ml water for injection respectively, and it is jolted on eddy mixer; Clarifying fully with dissolving is index, calculates dissolution velocity (seeing shown in the table 3)
The rate of dissolution of table 3, azlocillin sodium nanoparticle injection and direct packaging gained injection is investigated
The result shows that the rate of dissolution of azlocillin sodium nanoparticle injection provided by the invention obviously is superior to the injection of direct packaging gained.
Embodiment 9 azlocillin sodium nanoparticle injection study on the stability
Accelerated test is investigated
The sample of the embodiment of the invention 1～5 preparation and the azlocillin sodium injection of raw material direct packaging preparation are placed 40 ℃ of high temperature, following 6 months of relative humidity 75% ± 5% condition respectively, quicken to investigate, the result sees table 4:
The study on the stability of table 4, azlocillin sodium nanoparticle injection and direct packaging gained injection
Experiment shows that the injection character of azlocillin sodium raw materials direct packaging preparation becomes micro-yellow powder when quickening June, and pH descends bigger, and content reduces obviously, 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%; Prove that fully product of the present invention is superior to the listing article aspect stable, have gratifying technique effect.
Claims (9)
1. azlocillin pharmaceutical composition, it is an azlocillin nanoparticle injection, wherein, described injection by azlocillin, nanoparticulate carriers material, surface stabilizer, excipient form,, wherein, each composition weight mark is:
1 part of azlocillin
Carrier material 3-10 part
Surface stabilizer 0.03-0.1 part
Excipient 2-8 part
Carrier material described here is an alpha-cyanoacrylate alkane ester: described cyanic acid propylene is calculated the alkane ester and is selected from methyl 2-cyanoacrylate, cyanacrylate, alpha-cyanoacrylate propyl ester, a kind of in the positive butyl ester of alpha-cyanoacrylate, the isobutylcyanoacrylate;
Said surface stabilizer is the nonionic surface stabilizer; Described nonionic surface stabilizer is selected from Polyethylene Glycol, poloxamer.
2. azlocillin according to claim 1 pharmaceutical composition, wherein each composition weight mark is:
1 part of azlocillin
Carrier material 4-6 part
Surface stabilizer 0.04-0.06 part
Excipient 4-6 part.
3. azlocillin according to claim 2 pharmaceutical composition, wherein each composition weight mark is:
1 part of azlocillin
5 parts of carrier materials
0.05 part of surface stabilizer
5 parts of excipient.
4. according to the described azlocillin of arbitrary claim pharmaceutical composition in the claim 1 to 3, wherein said excipient selects gelatin hydrolysate, one or more in glycine, glutamic acid, lactose, glucose, sorbitol, mannitol, the xylitol.
5. azlocillin according to claim 4 pharmaceutical composition, wherein said excipient is selected from gelatin hydrolysate or glycine.
6. according to the described azlocillin of arbitrary claim pharmaceutical composition in the claim 1 to 3, wherein measure through the light dispersion method, its effective particle mean size is 10-200nm.
7. azlocillin according to claim 6 pharmaceutical composition, wherein the granularity of at least 80% azlocillin is less than effective meansigma methods.
8. azlocillin according to claim 7 pharmaceutical composition, wherein the granularity of at least 95% azlocillin is less than effective meansigma methods.
9. the said azlocillin of arbitrary claim preparation of drug combination method in the claim 1 to 8 comprises the steps:
(1) azlocillin 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) in above-mentioned solution, add carrier material, 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 azlocillin sodium nanoparticle solution;
(4) above-mentioned solution branch is filled in the cillin bottle after the sterilization, uses the freezer dryer lyophilizing, aseptic plug seals, and carry out the Zha Gai sealing with aseptic aluminium lid, obtains azlocillin nanoparticle injection at last.
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|---|---|---|---|
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|---|---|---|---|
| CN 201210262214 CN102805725A (en) | 2012-07-27 | 2012-07-27 | Azlocillin sodium medicinal composition for injection and preparation method for azlocillin sodium medicinal composition for injection |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103265561A (en) * | 2013-06-09 | 2013-08-28 | 四川省惠达药业有限公司 | Azlocillin sodium compound, preparation method and medicine composition thereof |
| 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 |
-
2012
- 2012-07-27 CN CN 201210262214 patent/CN102805725A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103265561A (en) * | 2013-06-09 | 2013-08-28 | 四川省惠达药业有限公司 | Azlocillin sodium compound, preparation method and medicine composition thereof |
| 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: 20121205 |