CN101632671B - Suspensoid powder injection of piperacillin sodium sulbactam sodium medicine composition and novel application thereof - Google Patents
Suspensoid powder injection of piperacillin sodium sulbactam sodium medicine composition and novel application thereof Download PDFInfo
- Publication number
- CN101632671B CN101632671B CN200910018015XA CN200910018015A CN101632671B CN 101632671 B CN101632671 B CN 101632671B CN 200910018015X A CN200910018015X A CN 200910018015XA CN 200910018015 A CN200910018015 A CN 200910018015A CN 101632671 B CN101632671 B CN 101632671B
- Authority
- CN
- China
- Prior art keywords
- sodium
- sulbactam sodium
- piperacillin
- sulbactam
- suspension injection
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to suspensoid powder injection of a piperacillin sodium sulbactam medicine composition prepared by applying an emulsification suspensoid technology and freeze drying. The invention further relates to a novel application of the suspensoid powder injection in preparing a medicine treating the infection of the oral cavity.
Description
Technical field
Suspension injection powder that the present invention relates to piperacillin-sulbactam sodium medicinal composition and preparation method thereof is used with new.
Background technology
The oral cavity is one of approach of pathogenic microorganism intrusion body.Because the suitable microbial growth breeding of temperature, humidity and the food debris in oral cavity.Have a large amount of pathogenic bacterias in the normal person oral cavity, postoperative patient is because resistance descends, and oral cavity drinking-water, feed are lacked, and often can make a large amount of breedings of oral cavity bacterium that oral cavity infection very easily takes place.Under normal circumstances, exist more than ten kind of flora in the oral cavity, mutual restriction between them, interdepend, keeping relative balance state oral cavity acid-base value is 6.6～7.1.The variation of pH value is relevant with the sickness rate of stomatitis in the oral cavity.When pH reduced, fungal infection easily took place.The postoperative patient Abwehrkraft des Koepers reduces, the oral cavity self-cleaning action weakens, and easily causes dysbacteriosis in the oral cavity, and pH value is all 5.0～6.0, bacterial reproduction acts on tissue or blood, and carbohydrate breakdown, fermentation, release metabolite hydrogen sulfide, indole, amino material etc. cause halitosis.
Oral cavity infection makes the clinician feel very thorny, and one of problem is exactly a drug-resistance of bacteria, and the antibiotic of how selecting to have drug susceptibility becomes the key for the treatment of oral cavity infection.
Piperacillin belongs to the penicillins broad ectrum antibiotic, main by disturbing the bactericidal action of having synthesized of bacteria cell wall, be mainly used in the infection due to Pseudomonas aeruginosa and the various gram negative bacilli but easily produced drug resistance by bacteriogenic beta-lactam enzyme hydrolysis; Sulbactam does not have antibiotic activity except that to Neisseriaceae and the acinetobacter calcoaceticus to other antibacterials, but sulbactam has the inhibitory action of irreversibility to the most important beta-lactamase that is produced by the beta-lactam antibiotic Resistant strain.Sulbactam can prevent the destruction of fastbacteria to penicillins and cephalosporins, and sulbactam and penicillins and cephalosporins have the obvious synergistic effect.As far back as 2000, Chinese patent CN10590286C disclosed a kind of anti-beta-lactamase antibiotic composition, by being made up of sulbactam and piperacillin or cefotaxime.
The clinical consumption of piperacillin-sulbactam sodium compound preparation is big, determined curative effect, and market prospect is good, and is the same with most of cephalosporinses, all is to be made by avocin and the aseptic raw material packing of sulbactam sodium or lyophilizing.There is a common defective in it is exactly that preparation stabilization is poor, the prescription that can not satisfy the prescriptive period.
And, avocin and another subject matter of sulbactam sodium preparation are this solution less stables at room temperature, and unsettled solution easily produces granule, especially relax piperazine that solution melts the back again or be prepared into freeze-dried powder of the piperazine of stored frozen relaxes preparation when being mixed with solution again, and the time of placing is long more, and granule generates manyly more.Granule in the solution of used for intravenous injection is deleterious to patient.Studies have shown that the granule content in infusion phlebitis and the transfusion closely related (Mark Publishing, 1990, page 1567 for Remmington ' s Pharmaceutical Science, 18 Edition).
Prior art is in order to overcome the stable defective of piperacillin-sulbactam sodium combination preparation, multiple solution is proposed, for example patent documentation CN101269072A discloses pharmaceutical composition that contains sulbactam sodium and avocin and pH value regulator of a kind of stable content and preparation method thereof, owing to added the pH value regulator, the pH value of having avoided compatibility clinically to cause reduces the insoluble or muddy phenomenon of milky that produces, but same unstable in the dilution rear solution, influenced curative effect; Patent documentation CN1927201A discloses the antibiotic compound of being made up of avocin, sulbactam sodium and at least a ion chelating agent that suppresses the granule generation, weak point be ion chelating agent particularly the use of EDTA become sodium in the bone, potassium, calcium ion to run off easily, and, preparation process adopts lyophilization, avocin and sulbactam sodium are in solution state in dosing and dry run thereof, the very fast generation oxydrolysis of meeting causes defective.
Patent documentation CN101322702A discloses the preparation method of a kind of piperacillin sodium injection sulbactam sodium and lyophilized injectable powder thereof, adopt high speed adverse current chromatogram, avocin and sulbactam sodium are carried out separation and purification, obtain the avocin and the sulbactam sodium of injection, lyophilization, aseptic subpackaged, thus make the piperacillin sodium injection sulbactam sodium.Improved the purity of preparation to a certain extent, but, active component avocin and sulbactam sodium have not been carried out corresponding protection, also caused product stability poor, had a strong impact on clinical efficacy just with simple aseptic subpackaged the making of two kinds of compositions.
Summary of the invention
The inventor is through long-term conscientious research, and the suspension injection powder of the piperacillin-sulbactam sodium that using emulsion suspendible technology and lyophilization are made has well solved piperacillin-sulbactam sodium poor stability and compatibility acidity and reduced the muddy problem that produces; And the combination of the avocin of specific proportioning and sulbactam sodium overcome the drug resistance of common oral cavity infection in the prior art, is very suitable for treating oral cavity infection, finished the present invention thus.
The object of the present invention is to provide a kind of pharmaceutical composition of stable piperacillin-sulbactam sodium, specifically, the combination of Tween 80, cholesterol, sodium deoxycholate, frozen-dried supporting agent and active component by certain content, adopt emulsified mixed suspension technology and lyophilization to make piperacillin-sulbactam sodium lyophilizing suspension injection powder of the present invention, particularly by selecting specific frozen-dried supporting agent, relax piperazine that solution melts the back again or be prepared into freeze-dried powder of the piperazine that has overcome stored frozen effectively relaxes preparation when being mixed with solution again, generates the problem of crystalline particle.Not only well solved the problem of its poor stability, dissolving is quick, and does not produce crystallization and muddy phenomenon, has obtained desirable therapeutic.
The technical scheme that the present invention solves is as follows:
The invention provides a kind of piperacillin-sulbactam sodium suspension injection powder, comprise the component of following weight portion meter:
Avocin 2-4 part
1 part of sulbactam sodium
Tween 80 3-40 part
Cholesterol 1-15 part
Sodium deoxycholate 0.5-10 part
Frozen-dried supporting agent 1-40 part.
As the present invention's one preferred embodiment, above-mentioned described piperacillin-sulbactam sodium suspension injection powder, the component that comprises following weight portion meter is made:
Avocin 2-4 part
1 part of sulbactam sodium
Tween 80 6-25 part
Cholesterol 3-10 part
Sodium deoxycholate 1.5-5 part
Frozen-dried supporting agent 3-20 part.
Wherein, frozen-dried supporting agent is selected from one or more in mannitol, lactose, trehalose, glucose, sucrose, sorbitol, sodium chloride, the glycine, preferably sucrose and glucose weight ratio are 1: 3 combination, 2: 1 combination of trehalose and lactose, 5: 1 combination of mannitol and sodium chloride, most preferably trehalose and lactose weight ratio are 2: 1 combination.
Wherein, Tween 80, cholesterol are as emulsifying agent, and sodium deoxycholate is as co-emulsifier, best results when preparing suspensoid by said ratio, little and the steady quality of particle diameter if consumption very little, is reunited between granule easily, can not reach the preparation requirement, if consumption is too many, can not obviously improves the stability of suspensoid, even descend on the contrary, in addition, also to consider the too many caused toxicity problem of consumption.
As one of most preferred embodiment of the present invention, make 100 bottles of piperacillin-sulbactam sodium suspension injection powders: avocin 100g, sulbactam sodium 25g by following component, Tween 80 150g, cholesterol 75g, sodium deoxycholate 37.5g, trehalose 50g and lactose 25g.
As two of most preferred embodiment of the present invention, make 100 bottles of piperacillin-sulbactam sodium suspension injection powders: avocin 200g, sulbactam sodium 50g by following component, Tween 80 1250g, cholesterol 500g, sodium deoxycholate 250g, sucrose 250g and glucose 750g.
As three of most preferred embodiment of the present invention, make 100 bottles of piperacillin-sulbactam sodium suspension injection powders: avocin 200g, sulbactam sodium 100g by following component, Tween 80 2500g, cholesterol 300g, sodium deoxycholate 500g, mannitol 250g and sodium chloride 50g.
As four of most preferred embodiment of the present invention, make 100 bottles of piperacillin-sulbactam sodium suspension injection powders: avocin 100g, sulbactam sodium 50g by following component, Tween 80 300g, cholesterol 500g, sodium deoxycholate 75g, trehalose 666.7g and lactose 333.3g.
The present invention also aims to provide a kind of method for preparing the piperacillin-sulbactam sodium suspension injection powder, comprise the steps:
(1) Tween 80, cholesterol and sodium deoxycholate are added in the water for injection, add avocin and sulbactam sodium mix homogeneously again, 70-90 ℃ of heating in water bath is stirred to molten condition;
(2) aforesaid liquid is incubated employing tissue mincer shear agitation under the 70-90 ℃ of condition, gets colostric fluid,, get emulsion again through high pressure dispersing emulsification machine circulating emulsion;
(3) in emulsion, add frozen-dried supporting agent, the packing of dissolving after-filtration, lyophilization gets the piperacillin-sulbactam sodium suspension injection powder.
Wherein, the selection of the amount of water for injection is the ordinary skill in the art, dissolves above material and gets final product, and is preferably 3-5 times of all whole composition weight summations.
Tissue mincer is a JJ-2B type high-speed tissue mashing machine, and rotating speed is 10000-15000r/min, shear agitation 10-20 minute; High pressure dispersing emulsification machine model is NS1001L, by the import of Italian GEAN Niro Soavi company, maximum working pressure (MWP) 1500bar, output 10L/hr, circulating emulsion 4-5 time.Above tissue mincer and high pressure dispersing emulsification machine and operation thereof are to enumerate explanation not limit, and this area has the equipment of identical function and operation well known in the art can be made and be used for finishing the present invention.
Though patent documentation CN101385715A discloses a kind of preparation method of novel hard-soluble medicine liposome, it is characterized in that comprising the following steps: that A is with insoluble drug dissolving or suspendible or be blended among the water soluble surfactant active; B will be used to form lipid material, water-soluble diluent and dissolving or the suspendible of liposome or be mixed with water soluble surfactant active's mix homogeneously of insoluble drug; C adds suitable quantity of water or aqueous solution in the mixture of step B gained, mix homogeneously, and high pressure homogenize or high pressure breast are even, promptly get the liposome turbid liquor that contains insoluble drug; Other liposome component of D can be according to its physicochemical properties in steps A, B, and any step among the C adopts suitable method to add, and does not then add.The present invention and its difference are not add phospholipid substance, are not the formation liposome, but form Emulsion, and the problem of solution is that drug release process is non-targeting drug release, has improved bioavailability.
Patent documentation CN101283982A discloses a kind of nano suspension of slightly solubility active component fenofibrate, and poloxamer 188 and PVP are dissolved in the distilled water, adds the fenofibrate crude drug again; The heating in water bath fusion; The pre-emulsifying of high shear; High pressure homogenizer circular treatment again; Add the lyophilized preparation lyophilizing.Those skilled in the art are to be understood that, the process of the composition of the surfactant that different active component is selected for use is not apparently, must pay performing creative labour in order to obtain good stable, following embodiment has also proved creative place of the present invention.
The present invention also provides the application in the oral cavity infection after iatrotechnics of a kind of piperacillin-sulbactam sodium suspension injection powder, adopts intravenous drip, each 2.5g, every day 2 times.
The application of piperacillin-sulbactam sodium suspension injection powder of the present invention in the medicine of preparation treatment oral cavity infection is in particular for the treatment halitosis.
Piperacillin-sulbactam sodium suspension injection powder provided by the invention compared with prior art, has beyond thought effect, and major advantage is as follows:
(1) improved avocin and the sulbactam sodium stability in preparation, guaranteed that product quality is qualified in effect duration;
(2) suspension injection powder dissolving of the present invention does not produce crystallization and muddy phenomenon fast, and slowly administration has for a long time improved bioavailability greatly in vivo;
(3) used Tween 80, cholesterol and sodium deoxycholate degradation in vivo, avirulence and non-immunogenicity, and can improve the Drug therapy index, reduce drug toxicity and reduce drug side effect;
(4) production technology is simple, and cost is low, can industrial-scale production.
The specific embodiment
Further specify the present invention by the following examples, but should not be construed as limitation of the present invention.
Embodiment 1
The preparation of piperacillin-sulbactam sodium suspension injection powder
Prescription (100 bottles):
Avocin 100g
Sulbactam sodium 25g
Tween 80 150g
Cholesterol 75g
Sodium deoxycholate 37.5g
Trehalose 50g
Lactose 25g
Preparation technology
(1) 150g Tween 80,75g cholesterol and 37.5g sodium deoxycholate are added in the 2000ml water for injection, add 100g avocin and 25g sulbactam sodium mix homogeneously again, 90 ℃ of heating in water bath are stirred to molten condition;
(2) aforesaid liquid is incubated under the 70-90 ℃ of condition and adopts the shear agitation 10min of tissue mincer, rotating speed 1 5000r/min, colostric fluid, again through high pressure dispersing emulsification machine circulating emulsion 4 times, emulsion;
(3) in emulsion, add 50g trehalose and 25g lactose, the packing of dissolving after-filtration, lyophilization gets the piperacillin-sulbactam sodium suspension injection powder.
Comparative Examples 1
The preparation of piperacillin-sulbactam sodium suspension injection powder
Prescription (100 bottles):
Avocin 100g
Sulbactam sodium 25g
Poloxamer 188 225g
PVPK30 37.5g
Trehalose 50g
Lactose 25g
Preparation technology chooses the combination of the not preferred component of the present invention with embodiment 1, makes the piperacillin-sulbactam sodium suspension injection powder.
Embodiment 2
The preparation of piperacillin-sulbactam sodium suspension injection powder
Prescription (100 bottles):
Avocin 200g
Sulbactam sodium 50g
Tween 80 1250g
Cholesterol 500g
Sodium deoxycholate 250g
Sucrose 250g
Glucose 750g
Preparation technology
(1) 1250g Tween 80,500g cholesterol and 250g sodium deoxycholate are added in the 10000ml water for injection, add 200g avocin and 50g sulbactam sodium mix homogeneously again, 70 ℃ of heating in water bath are stirred to molten condition;
(2) aforesaid liquid is incubated under the 70-90 ℃ of condition and adopts the shear agitation 20min of tissue mincer, rotating speed 10000r/min, colostric fluid, again through high pressure dispersing emulsification machine circulating emulsion 5 times, emulsion;
(3) in emulsion, add 250g sucrose and 750g glucose, the packing of dissolving after-filtration, lyophilization gets the piperacillin-sulbactam sodium suspension injection powder.
Comparative Examples 2
The preparation of piperacillin-sulbactam sodium suspension injection powder
Prescription (100 bottles):
Avocin 200g
Sulbactam sodium 50g
Tween 80 2200g
Cholesterol 800g
Sodium deoxycholate 520g
Sucrose 1000g
Glucose 1200g
Preparation technology chooses the combination outside the preferred ingredient parts by weight scope of the present invention with embodiment 2, makes the piperacillin-sulbactam sodium suspension injection powder.
Embodiment 3
The preparation of piperacillin-sulbactam sodium suspension injection powder
Prescription (100 bottles):
Avocin 200g
Sulbactam sodium 100g
Tween 80 2500g
Cholesterol 300g
Sodium deoxycholate 500g
Mannitol 250g
Sodium chloride 50g
Preparation technology
(1) 2500g Tween 80,300g cholesterol and 500g sodium deoxycholate are added in the 16000ml water for injection, add 200g avocin and 100g sulbactam sodium mix homogeneously again, 80 ℃ of heating in water bath are stirred to molten condition;
(2) aforesaid liquid is incubated under the 70-90 ℃ of condition and adopts the shear agitation 10min of tissue mincer, rotating speed 12000r/min, colostric fluid, again through high pressure dispersing emulsification machine circulating emulsion 5 times, emulsion;
(3) in emulsion, add 250g mannitol and 50g sodium chloride, the packing of dissolving after-filtration, lyophilization gets the piperacillin-sulbactam sodium suspension injection powder.
Comparative Examples 3
The preparation of piperacillin-sulbactam sodium suspension injection powder (preparation technology's difference)
Prescription (100 bottles):
Avocin 200g
Sulbactam sodium 100g
Tween 80 2500g
Cholesterol 300g
Sodium deoxycholate 500g
Mannitol 250g
Sodium chloride 50g
Preparation technology
(1) 2500g Tween 80,300g cholesterol, 500g sodium deoxycholate, 200g avocin and 100g sulbactam sodium are added in the 16000ml water for injection, be uniformly dispersed stirring at room 30min;
(2) the aforesaid liquid room temperature condition is adopted the shear agitation 10min of tissue mincer down, rotating speed 5000r/min gets emulsion;
(3) in emulsion, add 250g mannitol and 50g sodium chloride, the packing of dissolving after-filtration, lyophilization gets the piperacillin-sulbactam sodium suspension injection powder.
Embodiment 4
The preparation of piperacillin-sulbactam sodium suspension injection powder
Prescription (100 bottles):
Avocin 100g
Sulbactam sodium 50g
Tween 80 300g
Cholesterol 500g
Sodium deoxycholate 75g
Trehalose 666.7g
Lactose 333.3g
Preparation technology
(1) 300g Tween 80,500g cholesterol and 75g sodium deoxycholate are added in the 8000ml water for injection, add 100g avocin and 50g sulbactam sodium mix homogeneously again, 80 ℃ of heating in water bath are stirred to molten condition;
(2) aforesaid liquid is incubated under the 70-90 ℃ of condition and adopts the shear agitation 20min of tissue mincer, rotating speed 13000r/min, colostric fluid, again through high pressure dispersing emulsification machine circulating emulsion 5 times, emulsion;
(3) in emulsion, add 666.7g trehalose and 333.3g lactose, the packing of dissolving after-filtration, lyophilization gets the piperacillin-sulbactam sodium suspension injection powder.
Test example 1
The distribution of particle diameter
Suspension injection powder water for injection dissolved dilution with embodiment of the invention 1-4 and Comparative Examples 1-3 preparation, with the suspension injection powder granular size homogeneous of JSM-5900 sem observation to embodiment of the invention 1-4 preparation, be irregular spherical or oval spherical, and the suspension injection powder granular size heterogeneity of Comparative Examples 1-3 preparation, present different shape, disorderly and unsystematic.
Test example 2
The size of particle diameter
Suspension injection powder water for injection dissolved dilution with embodiment of the invention 1-4 and Comparative Examples 1-3 preparation, measure size with the zetasizer3000HS laser particle size analyzer, embodiment 1-4 sample is about 210nm, and Comparative Examples 1-3 sample size heterogeneity does not have stable scope.The results are shown in Table 1:
Table 1 particle size determination result
Test example 3
Study on the stability
With above each embodiment and the sample of Comparative Examples preparation and piperacillin sodium injection sulbactam sodium (the HARBIN PHARMACEUTICAL GROUP CO., LTD. General Pharm. Factory production of listing, lot number 20071017-2) under 40 ℃ of high temperature, relative humidity 75% ± 5% condition 6 month, carry out accelerated test and investigate, the results are shown in Table 2; Under 25 ℃ of high temperature, relative humidity 60% ± 10% condition 12 months, carry out long term test and investigate, detect the variation of every quality index, wherein can well embody in " clarity " quicken and long term test after, the situation of generation crystalline particle.The results are shown in Table 3.
Table 2 accelerated test result
Table 3 long-term test results
Quickened March, June by above found that, the piperacillin-sulbactam sodium injectable powder clarity of Comparative Examples and listing is against regulation during long-term December, and pH value descends bigger, and content reduces obviously, and related substance raises; And sample appearance character, clarity, pH value, content and the related substance of the preparation of supplementary material proportioning all do not have obvious variation in the scope of the invention.The sample stable quality after long time storage that the present invention's preparation is described is better.
Test example 4
Clinical trial is prepared
1, case selection
Oral cavity infection 240 examples, wherein male 188 examples, women 52 examples; 17～49 years old age, average 34.2 years old.The sick kind comprises after pericoronitis of the wisdom tooth, alveolar abscess, all kinds of fascial space infection, dry socket, the facial wound of jaw, the extraction etc.All do not use antibiotic before the prescription on individual diagnosis.Be divided into treatment group, matched group and listing sample matched group at random, three groups all have comparability at aspects such as age, sex, disease type and the state of an illness.
2, Therapeutic Method
Matched group gives metronidazole injection 250ml intravenous drip, every day 1 time; The treatment group gives embodiment the piperacillin-sulbactam sodium suspension injection powder 2.5g of 2 preparations, with an amount of 5% glucose injection dissolving, and then is diluted to 50～100ml for intravenous drip, every day 2 times.The piperacillin sodium injection sulbactam sodium 2.5g (lot number 20071017-2) that the HARBIN PHARMACEUTICAL GROUP CO., LTD. General Pharm. Factory that the listing sample sets gives to have gone on the market is produced with an amount of 5% glucose injection dissolving, and then is diluted to 50～100ml for intravenous drip, every day 2 times.7 days is a course of treatment, observes the clinical efficacy of each group after 7 days.
3, curative effect determinate standard
Three groups of cases are all in medication further consultation after 7 days.(1) produce effects: pain, swelling and General Symptoms obviously alleviate or disappear, and need not continue treatment or postoperative and not have infection, and wound healing is good; (2) take a turn for the better: sx, but must continue to treat or do not have obviously and infect, wound begins healing; (3) invalid: no change before and after the treatment.
4, statistical procedures
Adopt SPSS 8.0 software kits to carry out statistical procedures.
Test example 5
Clinical test results
Clinical trial the results are shown in Table 4, treatment group produce effects 63 examples, obvious effective rate is 78.75%, total effective rate reaches 97.5%, matched group and listing sample sets obvious effective rate and total effective rate are respectively 66.25%, 81.25% and 73.75%, 91.25%.The treatment group is compared with matched group and listing sample sets has tangible significance, P＜0.05.
Table 4 clinical test results
Annotate: compare with matched group: ★ P＜0.05; Compare with the listing sample: △ P＜0.05.
In sum, the piperacillin-sulbactam sodium suspension injection powder determined curative effect of the present invention's preparation can be used for treating oral cavity infection.
Claims (10)
1. suspensoid powder injection of piperacillin sodium sulbactam sodium medicine composition is characterized in that comprising the component of following weight portion meter:
Avocin 2-4 part
1 part of sulbactam sodium
Tween 80 3-40 part
Cholesterol 1-15 part
Sodium deoxycholate 0.5-10 part
Frozen-dried supporting agent 1-40 part;
Described frozen-dried supporting agent is selected from one or more in mannitol, lactose, trehalose, glucose, sucrose, sorbitol, sodium chloride, the glycine;
The employing following steps are made:
(1) Tween 80, cholesterol and sodium deoxycholate are added in the water for injection, add avocin and sulbactam sodium mix homogeneously again, 70-90 ℃ of heating in water bath is stirred to molten condition;
(2) aforesaid liquid is incubated employing tissue mincer shear agitation under the 70-90 ℃ of condition, gets colostric fluid,, get emulsion again through high pressure dispersing emulsification machine circulating emulsion;
(3) in emulsion, add frozen-dried supporting agent, the packing of dissolving after-filtration, lyophilization gets piperacillin-sulbactam sodium lyophilizing suspension injection powder.
2. suspension injection powder according to claim 1 is characterized in that the component that comprises following weight portion meter makes:
Avocin 2-4 part
1 part of sulbactam sodium
Tween 80 6-25 part
Cholesterol 3-10 part
Sodium deoxycholate 1.5-5 part
Frozen-dried supporting agent 3-20 part.
3. according to the described suspension injection powder of claim 1-2, it is characterized in that it is 1: 3 combination, trehalose and 2: 1 combination of lactose or mannitol and 5: 1 combination of sodium chloride that frozen-dried supporting agent is selected from sucrose and glucose weight ratio.
4. suspension injection powder according to claim 3 is characterized in that it is 2: 1 combination that frozen-dried supporting agent is selected from trehalose and lactose weight ratio.
5. the preparation method of the described suspension injection powder of claim 1-4 is characterized in that comprising the steps:
(1) Tween 80, cholesterol and sodium deoxycholate are added in the water for injection, add avocin and sulbactam sodium mix homogeneously again, 70-90 ℃ of heating in water bath is stirred to molten condition;
(2) aforesaid liquid is incubated employing tissue mincer shear agitation under the 70-90 ℃ of condition, gets colostric fluid,, get emulsion again through high pressure dispersing emulsification machine circulating emulsion;
(3) in emulsion, add frozen-dried supporting agent, the packing of dissolving after-filtration, lyophilization gets piperacillin-sulbactam sodium lyophilizing suspension injection powder.
6. suspension injection powder according to claim 1 is characterized in that making 100 bottles of piperacillin-sulbactam sodium lyophilizing suspension injection powders by following component: avocin 100g, sulbactam sodium 25g, Tween 80 150g, cholesterol 75g, sodium deoxycholate 37.5g, trehalose 50g and lactose 25g.
7. suspension injection powder according to claim 1 is characterized in that making 100 bottles of piperacillin-sulbactam sodium lyophilizing suspension injection powders by following component: avocin 200g, sulbactam sodium 50g, Tween 80 1250g, cholesterol 500g, sodium deoxycholate 250g, sucrose 250g and glucose 750g.
8. suspension injection powder according to claim 1 is characterized in that making 100 bottles of piperacillin-sulbactam sodium lyophilizing suspension injection powders by following component: avocin 200g, sulbactam sodium 100g, Tween 80 2500g, cholesterol 300g, sodium deoxycholate 500g, mannitol 250g and sodium chloride 50g.
9. suspension injection powder according to claim 1 is characterized in that making 100 bottles of piperacillin-sulbactam sodium lyophilizing suspension injection powders by following component: avocin 100g, sulbactam sodium 50g, Tween 80 300g, cholesterol 500g, sodium deoxycholate 75g, trehalose 666.7g and lactose 333.3g.
10. the application of suspensoid powder injection of piperacillin sodium sulbactam sodium medicine composition according to claim 1 in the medicine of preparation treatment oral cavity infection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910018015XA CN101632671B (en) | 2009-08-18 | 2009-08-18 | Suspensoid powder injection of piperacillin sodium sulbactam sodium medicine composition and novel application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910018015XA CN101632671B (en) | 2009-08-18 | 2009-08-18 | Suspensoid powder injection of piperacillin sodium sulbactam sodium medicine composition and novel application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101632671A CN101632671A (en) | 2010-01-27 |
| CN101632671B true CN101632671B (en) | 2010-12-29 |
Family
ID=41592113
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200910018015XA Expired - Fee Related CN101632671B (en) | 2009-08-18 | 2009-08-18 | Suspensoid powder injection of piperacillin sodium sulbactam sodium medicine composition and novel application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101632671B (en) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101890014B (en) * | 2010-07-29 | 2012-05-23 | 胡建荣 | Piperacillin-sulbactam sodium medicinal composition liposome injection |
| CN101983629B (en) * | 2010-08-06 | 2012-01-11 | 胡建荣 | Piperacillin sodium and sulbactam sodium drug composite microsphere injection |
| US9499565B2 (en) * | 2012-09-14 | 2016-11-22 | Beijing Xintianyu Technology Development Co., Ltd. | Cocrystal of piperacillin sodium and sulbactam sodium and preparation method thereof, as well as pharmaceutical compositions containing same and uses thereof |
| CN102940607B (en) * | 2012-11-01 | 2014-12-24 | 哈药集团制药总厂 | Injection of piperacillin-sulbactum sodium medicine composition injection and preparation method thereof |
| CN102940636A (en) * | 2012-11-01 | 2013-02-27 | 哈药集团制药总厂 | Injection of piperacillin-sulbactum sodium medicine composition and preparation method thereof |
| CN105560243B (en) * | 2016-01-10 | 2018-09-18 | 苏州二叶制药有限公司 | A kind of preparation method of piperacillin sodium injection sulbactam sodium composition |
| CN105497032B (en) * | 2016-01-10 | 2018-09-18 | 苏州二叶制药有限公司 | A kind of piperacillin sodium injection sulbactam sodium composition |
| CN107625772A (en) * | 2017-09-30 | 2018-01-26 | 苏州二叶制药有限公司 | A kind of pharmaceutical composition of piperacillin sodium and tazobactam sodium compound |
| CN107638394B (en) * | 2017-09-30 | 2020-07-07 | 苏州二叶制药有限公司 | Pharmaceutical composition of piperacillin sodium and sulbactam sodium compound |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101322702A (en) * | 2008-08-01 | 2008-12-17 | 海南百那医药发展有限公司 | Piperacillin sodium and sulbactam sodium for injection and preparation of freeze-dried injection thereof |
-
2009
- 2009-08-18 CN CN200910018015XA patent/CN101632671B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101322702A (en) * | 2008-08-01 | 2008-12-17 | 海南百那医药发展有限公司 | Piperacillin sodium and sulbactam sodium for injection and preparation of freeze-dried injection thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101632671A (en) | 2010-01-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101632671B (en) | Suspensoid powder injection of piperacillin sodium sulbactam sodium medicine composition and novel application thereof | |
| US6007843A (en) | Sustained release delivery system | |
| US8323643B2 (en) | Methods for treating adhesive capsulitis | |
| CN101703506B (en) | Medicinal-composition suspension powder injection with mezlocillin sodium and sulbactam sodium, and novel application thereof | |
| MX2014004792A (en) | Method of treating or reducing efp. | |
| CN101632677B (en) | Suspension powder injection of cefoperazone sodium and tazobactam sodium pharmaceutical composition and new application thereof | |
| CN101632670B (en) | Suspension powder injection of piperacillin sodium and tazobactam sodium pharmaceutical composition and new application thereof | |
| CN102481288B (en) | Pharmaceutical composition of temozolomide comprising amino acid stabilizer and preparation method thereof | |
| KR101503111B1 (en) | Plasma-adapted full electrolyte solution | |
| CN103110640B (en) | Pharmaceutical composition of injection ceftizoxime sodium and compound amino acid injection | |
| CN100356921C (en) | New combination of Cefpirome Sulfate and preparation method | |
| WO1997011681A1 (en) | Sustained release delivery system and long acting narcotic analgesics and antagonists | |
| CN101637456B (en) | Suspension powder injection of cefamandole nafate and new application thereof | |
| US20230405063A1 (en) | Use of probiotic component and pharmaceutical composition containing probiotic component | |
| CN101721371B (en) | Cefetamet pivoxil hydrochloride submicron emulsion solid preparation and new application thereof | |
| CN101700234B (en) | Flucloxacillin sodium suspension and new application thereof | |
| CN106309473A (en) | Polymer matrix compositions comprising a high concentration of bio-fermented sodium hyaluronate and uses thereof | |
| CN103142587A (en) | Amoxicillin sodium-potassium clavulanate pharmaceutical composition and preparation method thereof | |
| CN103127129A (en) | Cefuroxime sodium pharmaceutical composition and preparation method thereof | |
| CN102716107B (en) | water-soluble ibuprofen pharmaceutical composition | |
| CN102008461A (en) | Ibuprofen drug composite for injection | |
| CN103919779A (en) | Medicinal composition containing moxifloxacin | |
| CN109172600B (en) | A kind of medical composition and its use | |
| CN1820749A (en) | Formula of amoxycillin sodium/ambroxo/ hydrochloride powder injection and its preparing method | |
| CN104706579A (en) | Fusidic acid eye drop and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C57 | Notification of unclear or unknown address | ||
| DD01 | Delivery of document by public notice |
Addressee: Wang Ming Document name: Notification of Passing Preliminary Examination of the Application for Invention |
|
| C06 | Publication | ||
| PB01 | Publication | ||
| C57 | Notification of unclear or unknown address | ||
| DD01 | Delivery of document by public notice |
Addressee: Wang Ming Document name: Notification that Application Deemed not to be Proposed |
|
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| DD01 | Delivery of document by public notice |
Addressee: Wang Ming Document name: Notification of Publication and of Entering the Substantive Examination Stage of the Application for Invention |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20101229 Termination date: 20160818 |