CN103127114B - Medicinal composition including piperacillin sodium and sulbactam sodium - Google Patents
Medicinal composition including piperacillin sodium and sulbactam sodium Download PDFInfo
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- CN103127114B CN103127114B CN201310078165.6A CN201310078165A CN103127114B CN 103127114 B CN103127114 B CN 103127114B CN 201310078165 A CN201310078165 A CN 201310078165A CN 103127114 B CN103127114 B CN 103127114B
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- sulbactam sodium
- avocin
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- sodium
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- NKZMPZCWBSWAOX-IBTYICNHSA-M Sulbactam sodium Chemical compound [Na+].O=S1(=O)C(C)(C)[C@H](C([O-])=O)N2C(=O)C[C@H]21 NKZMPZCWBSWAOX-IBTYICNHSA-M 0.000 title claims abstract description 85
- 229960000614 sulbactam sodium Drugs 0.000 title claims abstract description 85
- 239000000203 mixture Substances 0.000 title abstract description 9
- WCMIIGXFCMNQDS-IDYPWDAWSA-M piperacillin sodium Chemical compound [Na+].O=C1C(=O)N(CC)CCN1C(=O)N[C@H](C=1C=CC=CC=1)C(=O)N[C@@H]1C(=O)N2[C@@H](C([O-])=O)C(C)(C)S[C@@H]21 WCMIIGXFCMNQDS-IDYPWDAWSA-M 0.000 title abstract description 7
- 229960005264 piperacillin sodium Drugs 0.000 title abstract description 6
- 239000007924 injection Substances 0.000 claims abstract description 16
- 238000002347 injection Methods 0.000 claims abstract description 16
- 239000003814 drug Substances 0.000 claims abstract description 10
- 229910017488 Cu K Inorganic materials 0.000 claims abstract description 5
- 229910017541 Cu-K Inorganic materials 0.000 claims abstract description 5
- 230000005260 alpha ray Effects 0.000 claims abstract description 5
- 238000000634 powder X-ray diffraction Methods 0.000 claims abstract description 5
- 239000000243 solution Substances 0.000 claims description 30
- 239000000843 powder Substances 0.000 claims description 25
- 238000002360 preparation method Methods 0.000 claims description 22
- 239000008194 pharmaceutical composition Substances 0.000 claims description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
- 239000012046 mixed solvent Substances 0.000 claims description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 12
- 229940079593 drug Drugs 0.000 claims description 7
- 239000012065 filter cake Substances 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 4
- 238000009413 insulation Methods 0.000 claims description 4
- 239000013081 microcrystal Substances 0.000 claims description 4
- 230000002829 reductive effect Effects 0.000 claims description 4
- 238000010792 warming Methods 0.000 claims description 4
- 238000005406 washing Methods 0.000 claims 1
- 230000000295 complement effect Effects 0.000 abstract description 2
- 238000005259 measurement Methods 0.000 abstract 1
- 230000002195 synergetic effect Effects 0.000 abstract 1
- 239000000047 product Substances 0.000 description 13
- 238000012856 packing Methods 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 239000013078 crystal Substances 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000002994 raw material Substances 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 4
- 108090000204 Dipeptidase 1 Proteins 0.000 description 4
- 102000006635 beta-lactamase Human genes 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 230000002427 irreversible effect Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 241000194033 Enterococcus Species 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 206010022000 influenza Diseases 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 150000002960 penicillins Chemical class 0.000 description 2
- 238000007670 refining Methods 0.000 description 2
- 239000011877 solvent mixture Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- NDIURPSCHWTXDC-UHFFFAOYSA-N 2-(4,5-dimethoxy-2-nitrophenyl)acetohydrazide Chemical compound COC1=CC(CC(=O)NN)=C([N+]([O-])=O)C=C1OC NDIURPSCHWTXDC-UHFFFAOYSA-N 0.000 description 1
- NKBWMBRPILTCRD-UHFFFAOYSA-N 2-Methylheptanoic acid Chemical compound CCCCCC(C)C(O)=O NKBWMBRPILTCRD-UHFFFAOYSA-N 0.000 description 1
- 241000304886 Bacilli Species 0.000 description 1
- 241000606125 Bacteroides Species 0.000 description 1
- 241000606124 Bacteroides fragilis Species 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 description 1
- 241000193403 Clostridium Species 0.000 description 1
- 206010010144 Completed suicide Diseases 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 241000588921 Enterobacteriaceae Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 241000588653 Neisseria Species 0.000 description 1
- 241000293871 Salmonella enterica subsp. enterica serovar Typhi Species 0.000 description 1
- 241000607768 Shigella Species 0.000 description 1
- 241000191963 Staphylococcus epidermidis Species 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003781 beta lactamase inhibitor Substances 0.000 description 1
- 229940126813 beta-lactamase inhibitor Drugs 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 229960003324 clavulanic acid Drugs 0.000 description 1
- HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- QGBSISYHAICWAH-UHFFFAOYSA-N dicyandiamide Chemical compound NC(N)=NC#N QGBSISYHAICWAH-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- QAXZWHGWYSJAEI-UHFFFAOYSA-N n,n-dimethylformamide;ethanol Chemical compound CCO.CN(C)C=O QAXZWHGWYSJAEI-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- RBKMMJSQKNKNEV-RITPCOANSA-N penicillanic acid Chemical compound OC(=O)[C@H]1C(C)(C)S[C@@H]2CC(=O)N21 RBKMMJSQKNKNEV-RITPCOANSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229960002292 piperacillin Drugs 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 229960000373 tazobactam sodium Drugs 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 229940126085 β‑Lactamase Inhibitor Drugs 0.000 description 1
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Abstract
The invention belongs to the technical field of medicaments, and in particular relates to a medicinal composition including piperacillin sodium and sulbactam sodium. The medicinal composition is an injection, and an X-ray powder diffraction spectrogram, which is obtained through Cu-K alpha-ray measurement, of a sulbactam sodium compound in the medicinal composition is as shown in figure 1. The sulbactam sodium has very good storage stability, and the medicinal composition including the piperacillin sodium and the sulbactam sodium has better storage stability and high use safety; moreover, the medicinal composition including the piperacillin sodium and the sulbactam sodium has better accumulating, synergistic and complementary functions, and is better in bioavailability.
Description
Technical field
The invention belongs to medical technical field, be specifically related to a kind of sulbactam sodium compound and with the pharmaceutical composition of avocin.
Background technology
Sulbactam sodium Chinese another name: (2S, 5R)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo [3.2.0] heptane-2-carboxylic acid sodium-4,4-dioxide; (2S-CIS)-3,3-dimethyl-7-oxo-4-sulfo--1-azabicyclo [3,2,0] heptane-2-carboxylic acid 4,4-dioxide sodium salt; English name Sulbactam Sodium; Molecular formula: C
8h
10nNaO
5s; Molecular weight: 255.22; Molecular structural formula is as follows:
Sulbactam sodium is irreversible competitive beta-lactamase inhibitor, the beta-lactamase that Grain-positive and negative bacterium (except bacillus pyocyaneus) are produced all has inhibitory action, after there is irreversible reaction with enzyme, make enzyme deactivation, inhibitor can not make the activity of enzyme be restored after removing.In such cases, enzyme inhibition itself is inevitably destroyed in the process of enzyme, therefore claim suicide inhibitor; Because the prolongation of inhibitory enzyme effect along with the time strengthens, so also claim carrying out property inhibitor, sulbactam sodium and clavulanic acid all belong to this type of.Sulbactam sodium only has stronger antibacterial activity to gonococcus and meningococcus, and its MIC is respectively 0.1～3.2 μ g/ml and 0.1～0.2 μ g/ml.To the effect of other antibacterials very the MIC of Cha，Dui Jin Portugal bacterium, staphylococcus epidermidis, hemophilus influenza, Shigella, Bacillus typhi etc. be 25～400 μ g/ml, the MIC of other enterobacteriaceae lactobacteriaceaes is surpassed to 50 μ g/ml more.Enterococcus and bacillus pyocyaneus are to this product drug resistance.The beta-lactamase that sulbactam sodium Dui Jin Portugal bacterium and most gram negative bacilli produce has very strong and irreversible inhibitory action.2 μ g/ml concentration are very strong to the inhibitory action of Richmond-Syks II, III, IV and V type beta-lactamase, but to I type beta-lactamase without effect.When penicillins and cephalosporins and sulbactam sodium share, can there is cooperative phenomenon, make within the MIC of golden Portugal bacterium to front two class antibiotics resistances, hemophilus influenza, escherichia coli, bacteroides fragilis etc. drops to sensitive range.
Avocin Chinese another name: (2S, 5R, 6R)-3,3-dimethyl-6-[(4-ethyl-2,3-dioxo-1-piperazine formamido group) phenylacetylamino]-7-oxo-4-thia-1-azabicyclo [3.2.0] heptane-2-formic acid sodium salt; English name: Piperacillin Sodium; Molecular structural formula is as follows:
Piperacillin is semi-synthetic penicillins antibiotic, similar to ampicillin to the effect of gram positive bacteria, and enterococcus is had to good antibacterial action, for some bacteroid and clostridium, also has certain effect.
CN200910169645.7 discloses a kind of process for purification of sulbactam sodium compound, and the method comprises the following steps: a. is first water-soluble by sulbactam sodium crude product, and the pH value of its aqueous solution is adjusted to acidity, collects the solid of separating out in solution; B. solid step a being obtained is used after the organic solvent dissolution mixing with it, makes and treats refining solution; C. will treat that refining solution is placed in macroporous adsorbent resin, eluant eluting purification, collects eluent; D. the eluent pH value that regulating step c obtains, for neutral, is collected the solid of separating out, and obtains sulbactam sodium highly finished product.The sulbactam sodium compound highly finished product purity that adopts the method to obtain reaches more than 99.8%.Yield surpasses 90%.
CN200810134826.1 provides the preparation method of a kind of piperacillin sodium injection sulbactam sodium and lyophilized injectable powder thereof, and the avocin of injection and the isolation and purification method of sulbactam sodium.The present invention adopts high speed adverse current chromatogram, with chloroform, ethyl acetate, methanol, water preparation, form the dicyandiamide solution of immobile phase, mobile phase, avocin and sulbactam sodium are carried out to separation and purification, obtain avocin and the sulbactam sodium of injection, products obtained therefrom purity is more than 99%.
The storage stability of sulbactam sodium of the prior art is poor, in illumination and moist environment, its related substance can significantly increase, the pharmaceutical composition of itself and avocin stores for a long time, impurity content is higher, safety in utilization is poor, in order to obtain a kind of avocin of more excellent performance and the pharmaceutical composition of sulbactam sodium, special proposition the present invention.
Summary of the invention
The object of the present invention is to provide the pharmaceutical composition of a kind of avocin and sulbactam sodium, the pharmaceutical composition providing has better storage stability, safe to use.
In order to realize foregoing invention object, the present invention takes following technical scheme:
A pharmaceutical composition for avocin and sulbactam sodium, the structural formula of the sulbactam sodium compound in described pharmaceutical composition is:
The X-ray powder diffraction spectrogram that described sulbactam sodium compound use Cu-K alpha ray measures as shown in Figure 1.
Sulbactam sodium compound provided by the invention is crystal, the change of its internal crystal structure has caused its physical property that variation has also correspondingly occurred, inventor finds that by stability experiment the special crystal form of sulbactam sodium compound provided by the present invention compares with the solid form of the sulbactam sodium of prior art, there is stronger storage stability, and then improved the storage stability of the pharmaceutical composition of sulbactam sodium compound crystal and avocin, compare with the avocin of prior art and the pharmaceutical composition of sulbactam sodium, the pharmaceutical composition of avocin provided by the invention and sulbactam sodium has better storage stability, greatly improved patient's drug safety.
The preparation method of described sulbactam sodium compound comprises: by N, dinethylformamide and water are mixed with mixed solvent with the volume ratio of 1～3:1, get sulbactam sodium crude drug, add N, the mixed solvent of dinethylformamide and water, the volume of described mixed solvent is 3～5ml:1g with the ratio of the quality of sulbactam sodium, be warming up to 60～70 ℃, be stirred to whole dissolvings, insulation, the pH of solution is adjusted to 5.0～5.5, solution is carried out to magnetic treatment, in the solution of handling, add decolorizing with activated carbon, filter, obtain settled solution, in settled solution, add ethanol, filter, obtain filter cake, use distilled water wash filter cake, drying under reduced pressure 2～4h again, obtain white micro-crystals powder.
In the present invention, inventor is by experiment repeatedly, constantly change method for crystallising and crystallization condition, finally prepare a kind of sulbactam sodium compound crystal with brand-new crystal formation, this sulbactam sodium compound crystal has very high lattice energy, sulbactam sodium molecule is subject to lattice constraint larger, has good storage stability.
The volume of described ethanol and the volume ratio of mixed solvent are 5-10:1.
Described magnetic treatment is: solution is flowed through to the D.C. magnetic field of 0.5T with the speed of 5～10m/s, magnetic direction is vertical with flow of solution direction.
The described activated carbon degerming that adds is this area common technology means, can process referring to any decolouring, those skilled in the art are without paying any creative work, and the prior art that can grasp according to himself is carried out suitable selection, and realizes the object of the invention.
In order further to improve formulation products quality, the present invention also can be preferably filtered into use ultrafiltration membrance filter after decolouring.
Preferably, described pharmaceutical composition is injection.
Preferred, described injection is sterile powder injection.
In described sterile powder injection, the mass ratio of avocin and sulbactam sodium is 1:0.25～1.5.
Preferably, in described sterile powder injection, the mass ratio of avocin and sulbactam sodium is 1:0.25～1.
Preferred, in described sterile powder injection, the mass ratio of avocin and sulbactam sodium is 1:0.25～0.5.
The preparation method of described sterile powder injection is: under aseptic condition, take the avocin of recipe quantity and described sulbactam sodium, be placed in solid powder mixer and evenly mix, gained raw material proceeds to sterile preparation workshop, delicate metering packing, and gland, obtains.
Compared with prior art, avocin provided by the invention and tazobactam sodium drug composition tool have the following advantages:
(1) the pharmaceutical composition storage stability of avocin of the present invention and sulbactam sodium is good, and security performance is higher.
(2) pharmaceutical composition of avocin of the present invention and sulbactam sodium has better cumulative, collaborative, complementary action, and its bioavailability is better.
Accompanying drawing explanation
The X-powder diagram of the sulbactam sodium that Fig. 1 provides for the embodiment of the present invention 1.
The specific embodiment
Below by specific embodiment, summary of the invention of the present invention is described further, but does not therefore limit content of the present invention.
Embodiment 1
The preparation of sulbactam sodium compound
By N, dinethylformamide and water are mixed with mixed solvent with the volume ratio of 3:1, get sulbactam sodium crude drug, add N, the mixed solvent of dinethylformamide and water, the volume of described mixed solvent is 5ml:1g with the ratio of the quality of sulbactam sodium, be warming up to 70 ℃, be stirred to whole dissolvings, insulation, the pH of solution is adjusted to 5.5, solution is flowed through to the D.C. magnetic field of 0.5T with the speed of 5m/s, magnetic direction is vertical with flow of solution direction, in the complete solution of magnetic treatment, add decolorizing with activated carbon, the consumption of active carbon is the 0.3%(g/ml of the solvent mixture volume), stir 30min, filter, obtain settled solution, in settled solution, add ethanol, the volume of described ethanol and the volume ratio of mixed solvent are 5:1, filter, obtain filter cake, with distilled water wash filter cake 3 times, drying under reduced pressure 4h again, obtain white micro-crystals powder.Yield 72.4%, HPLC content 99.78%.
Use X-ray powder diffraction spectrogram that Cu-K alpha ray measures for Fig. 1 shown.
Embodiment 2
The preparation of sulbactam sodium compound
By N, dinethylformamide and water are mixed with mixed solvent with the volume ratio of 1:1, get sulbactam sodium crude drug, add N, the mixed solvent of dinethylformamide and water, the volume of described mixed solvent is 3ml:1g with the ratio of the quality of sulbactam sodium, be warming up to 60 ℃, be stirred to whole dissolvings, insulation, the pH of solution is adjusted to 5.0, solution is flowed through to the D.C. magnetic field of 0.5T with the speed of 10m/s, magnetic direction is vertical with flow of solution direction, in the complete solution of magnetic treatment, add decolorizing with activated carbon, the consumption of active carbon is the 0.3%(g/ml of the solvent mixture volume), stir 30min, filter, obtain settled solution, in settled solution, add ethanol, the volume of described ethanol and the volume ratio of mixed solvent are 10:1, filter, obtain filter cake, with distilled water wash filter cake 3 times, drying under reduced pressure 2h again, obtain white micro-crystals powder.Yield 72.4%, HPLC content 99.78%.
The X-ray powder diffraction figure that uses Cu-K alpha ray to measure is consistent with the result of embodiment 1.
Embodiment 3
The preparation of avocin and sulbactam sodium powder pin
Under aseptic condition, take the sulbactam sodium of avocin and embodiment 1 preparation, wherein the mass ratio of avocin and sulbactam sodium is 6:1, being placed in solid powder mixer evenly mixes, gained raw material proceeds to sterile preparation workshop, delicate metering packing, every bottle contains sulbactam sodium 0.5g, jumps a queue, rolls lid, finished product packing warehouse-in censorship.
Embodiment 4
The preparation of avocin and sulbactam sodium powder pin
Under aseptic condition, take the sulbactam sodium of avocin and embodiment 1 preparation, wherein the mass ratio of avocin and sulbactam sodium is 1:1, being placed in solid powder mixer evenly mixes, gained raw material proceeds to sterile preparation workshop, delicate metering packing, every bottle contains sulbactam sodium 3.0g, jumps a queue, rolls lid, finished product packing warehouse-in censorship.
Embodiment 5
The preparation of avocin and sulbactam sodium powder pin
Under aseptic condition, take the sulbactam sodium of avocin and embodiment 1 preparation, wherein the mass ratio of avocin and sulbactam sodium is 2:1, being placed in solid powder mixer evenly mixes, gained raw material proceeds to sterile preparation workshop, delicate metering packing, every bottle contains sulbactam sodium 1.5g, jumps a queue, rolls lid, finished product packing warehouse-in censorship.
Embodiment 6
The preparation of avocin and sulbactam sodium powder pin
Under aseptic condition, take the sulbactam sodium of avocin and embodiment 1 preparation, wherein the mass ratio of avocin and sulbactam sodium is 4:1, being placed in solid powder mixer evenly mixes, gained raw material proceeds to sterile preparation workshop, delicate metering packing, every bottle contains sulbactam sodium 2.0g, jumps a queue, rolls lid, finished product packing warehouse-in censorship.
Experimental example 1
This test example detects related substance in the prepared sulbactam sodium of embodiment 1～2, and this test is carried out according to 2010 editions second appendix VIII P residual solvent algoscopy of Chinese Pharmacopoeia, appendix XIXF medicine impurity analysis guideline, and it the results are shown in Table 1:
The assay of table 1 related substance
| Preparation | DMF | Ethanol | Other related substance |
| Embodiment 1 product | Up to specification | Up to specification | Up to specification |
| Embodiment 2 products | Up to specification | Up to specification | Up to specification |
Experimental example 2
This experimental example has been investigated the stability of sulbactam sodium provided by the invention
This test is carried out according to 2005 editions second appendix XIXC medicine stability test guideline of Chinese Pharmacopoeia, and result is as follows:
Table 2, accelerated test assay result
| ? | 0 month | 1 month | 3 months | 6 months | 9 months |
| 1 | 99.95% | 99.94% | 99.93% | 99.91% | 99.73% |
| 2 | 99.71% | 99.70% | 99.68% | 99.65% | 99.45% |
| 3 | 99.74% | 99.72% | 99.61% | 99.05% | 98.35% |
| 4 | 99.85% | 99.78% | 99.45% | 99.15% | 98.52% |
Table 3, long term test assay result
| ? | 0 month | 3 months | 6 months | 9 months | 15 months | 24 months |
| 1 | 99.95% | 99.93% | 99.90% | 99.85% | 99.70% | 99.58% |
| 2 | 99.71% | 99.69% | 99.65% | 99.60% | 99.41% | 99.21% |
| 3 | 99.74% | 99.70% | 99.65% | 99.30% | 98.64% | 97.80% |
| 4 | 99.85% | 99.75% | 99.40% | 99.11% | 98.50% | 97.74% |
Sample 1 is the product of the embodiment of the present invention 1;
Sample 2 is the product of the embodiment of the present invention 2;
Sample 3 is that HPLC is 99.74% with reference to the sulbactam sodium of CN200910169645.7 embodiment 1 preparation;
Sample 4 is commercially available sulbactam sodium crude drug, uses ethanol/water recrystallization, and HPLC is 99.85%;
Accelerated test and long term test by this experimental example are known, and compared with prior art, the stability of sulbactam sodium provided by the invention is better.
Claims (5)
1. a pharmaceutical composition for avocin and sulbactam sodium, is characterized in that, described pharmaceutical composition is sterile powder injection, and in described sterile powder injection, the mass ratio of avocin and sulbactam sodium is 1-6:1; The structural formula of described sulbactam sodium compound is:
The X-ray powder diffraction spectrogram that described sulbactam sodium compound use Cu-K alpha ray measures as shown in Figure 1.
2. pharmaceutical composition according to claim 1, it is characterized in that, the preparation method of described sulbactam sodium compound comprises: by N, dinethylformamide and water are mixed with mixed solvent with the volume ratio of 1～3:1, get sulbactam sodium crude drug, add N, the mixed solvent of dinethylformamide and water, the volume of described mixed solvent is 3～5ml:1g with the ratio of the quality of sulbactam sodium, be warming up to 60～70 ℃, be stirred to whole dissolvings, insulation, the pH of solution is adjusted to 5.0～5.5, solution is carried out to magnetic treatment, described magnetic treatment is: solution is flowed through to the D.C. magnetic field of 0.5T with the speed of 5～10m/s, magnetic direction is vertical with flow of solution direction, in the solution of handling, add decolorizing with activated carbon, filter, obtain settled solution, in settled solution, add ethanol, the volume of described ethanol and the volume ratio of mixed solvent are 5-10:1, filter, obtain filter cake, washing, drying under reduced pressure 2～4h again, obtain white micro-crystals powder.
3. pharmaceutical composition according to claim 1, is characterized in that, in described sterile powder injection, the mass ratio of avocin and sulbactam sodium is 2-4:1.
4. pharmaceutical composition according to claim 3, is characterized in that, in described sterile powder injection, the mass ratio of avocin and sulbactam sodium is 2:1.
5. pharmaceutical composition according to claim 3, is characterized in that, in described sterile powder injection, the mass ratio of avocin and sulbactam sodium is 4:1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310078165.6A CN103127114B (en) | 2013-03-12 | 2013-03-12 | Medicinal composition including piperacillin sodium and sulbactam sodium |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310078165.6A CN103127114B (en) | 2013-03-12 | 2013-03-12 | Medicinal composition including piperacillin sodium and sulbactam sodium |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103127114A CN103127114A (en) | 2013-06-05 |
| CN103127114B true CN103127114B (en) | 2014-02-26 |
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| CN104876946A (en) * | 2015-04-30 | 2015-09-02 | 王雪雁 | Sulbactam compound for treating infectious diseases, and preparation method therefor |
| CN106432277A (en) * | 2016-09-21 | 2017-02-22 | 陕西顿斯制药有限公司 | Cefoperazone sodium compound and sulbactam sodium compound prepared with strong-field coupling crystallization technology as well as prepared composition |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009053256A2 (en) * | 2007-10-22 | 2009-04-30 | Sandoz Ag | Process for the production of beta lactam crystals |
| CN102898438A (en) * | 2012-09-14 | 2013-01-30 | 北京新天宇科技开发有限公司 | Eutectic of Piperacillin sodium and Sulbactam sodium, preparation method thereof, pharmaceutical composition containing eutectic and application of pharmaceutical composition |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009053256A2 (en) * | 2007-10-22 | 2009-04-30 | Sandoz Ag | Process for the production of beta lactam crystals |
| CN102898438A (en) * | 2012-09-14 | 2013-01-30 | 北京新天宇科技开发有限公司 | Eutectic of Piperacillin sodium and Sulbactam sodium, preparation method thereof, pharmaceutical composition containing eutectic and application of pharmaceutical composition |
Non-Patent Citations (4)
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| 反应溶媒对舒巴坦钠晶态的影响;周福富等;《淮海医药》;20050930;第23卷(第5期);423 * |
| 周福富等.反应溶媒对舒巴坦钠晶态的影响.《淮海医药》.2005,第23卷(第5期),423. |
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| 舒巴坦钠结晶工艺的改进;姜浩伟;《中国药业》;20111231;第20卷(第8期);48 * |
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Application publication date: 20130605 Assignee: Hainan general Kang Li pharmaceutical Co. Ltd Assignor: Sichuan Province Huida Pharmaceutical Co., Ltd. Contract record no.: 2015460000016 Denomination of invention: Medicinal composition including piperacillin sodium and sulbactam sodium Granted publication date: 20140226 License type: Exclusive License Record date: 20151127 |
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