CN105534919A - Pharmaceutical composition containing cefoperazone sodium and sulbactam sodium - Google Patents

Pharmaceutical composition containing cefoperazone sodium and sulbactam sodium Download PDF

Info

Publication number
CN105534919A
CN105534919A CN201610125206.6A CN201610125206A CN105534919A CN 105534919 A CN105534919 A CN 105534919A CN 201610125206 A CN201610125206 A CN 201610125206A CN 105534919 A CN105534919 A CN 105534919A
Authority
CN
China
Prior art keywords
sodium
cefoperazone
sulbactam
pharmaceutical composition
cefoperazone sodium
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.)
Pending
Application number
CN201610125206.6A
Other languages
Chinese (zh)
Inventor
阎虎林
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Priority to CN201610125206.6A priority Critical patent/CN105534919A/en
Publication of CN105534919A publication Critical patent/CN105534919A/en
Pending legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/429—Thiazoles condensed with heterocyclic ring systems
    • A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
    • A61K31/546—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine containing further heterocyclic rings, e.g. cephalothin

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention discloses pharmaceutical composition. Raw medicinal materials of the pharmaceutical composition comprise cefoperazone sodium micro-powder and sulbactam sodium micro-powder with d95 in a range from 90 mu m to 60 mu m. An experiment proves that the pharmaceutical composition is high in antibacterial activity, good in re-dissolution performance and high in product safety.

Description

Cefoperazone sodium and sulbactam sodium medicine composition
Technical field
The present invention relates to drug world, relate to a kind of compound antibiotic, be specifically related to a kind of cefoperazone sodium and sulbactam sodium medicine composition.
Background technology
Cefoperazone is national essential drugs, belongs to beta-lactam antibiotic, has a broad antifungal spectrum, can be used for the treatment of the various infection that responsive zymogenic bacteria causes, and also has good curative effect to the brain inner infection that hemophilus influenza, meningococcus cause.But cefoperazone is easily destroyed by beta-lactamase, lose drug effect.At present, in order to suppress this fermentoid to the effect of beta-lactam antibiotic, except exploitation can be resisted except the beta-lactam antibiotic of enzyme hydrolysis, there have been developed the pharmaceutical composition of beta-lactamase inhibitor and beta-lactam antibiotic.The combination of enzyme inhibitor and beta-lactam antibiotic not only enhances antibiotic activity, also increases its antimicrobial spectrum, improves the therapeutic effect to infecting.Sulbactam sodium is irreversibility competitive type beta-lactamase inhibitor, cefoperazone belongs to penicillins medicine, easily by beta-lactam enzyme hydrolysis, in order to strengthen the activity of cefoperazone, clinically there is cefoperazone and beta-lactamase inhibitor united application, reach synergistic curative effect.Adopt cefoperazone and the former powder physical mixed of sulbactam sodium two kinds in production process, dissolution velocity is undesirable, affects the treatment, and have potential safety hazard when Clinical practice.
In addition, clinical research for many years proves, and antibiotic more easily type Ⅰ hypersensitivity reaction occurs.And in the type Ⅰ hypersensitivity reaction caused by the anti-body element of beta-lactam, the high molecular polymer existed in medicine is only the real anaphylactogen causing type Ⅰ hypersensitivity reaction, the content therefore strictly controlling high molecular polymer in antibiotic has great importance.
In antibiotic, high molecular polymer is mainly divided into exogenous and endogenous two kinds, and Adventitious impurities comprises the impurity such as polypeptide, albumen, polysaccharide, or the conjugate of antibiotic and albumen, polypeptide, polysaccharide etc., and it generally derives from fermentation technology.The polymer that endogenous impurity refers to antibiotic medicine self-polymerization and formed, this base polymer from production process, can produce again in storage process, even also can produce during medication.For present production technology, exogenous macromolecule impurity is less generation, and the control of endogenous polymer is only to the emphasis of current antibiotic macromolecule impurity quality control, control high molecular polymer content, safety and the effectiveness of clinical application can be ensured.
CN104650115 discloses a kind of cefoperazone sodium and the extraordinary superfine powder of compound recipe thereof, wherein the particle diameter of cefoperazone sodium superfine powder is 0.5 ~ 3 μm, but because cefoperazone sodium character is unstable, ultra micro efflorescence increases due to specific surface area, add the possibility of cefoperazone sodium polymerization, thus add clinical application risk.
In view of above problem, be badly in need of the preparation technology of a kind of Cefoperazone Sodium and Tazobactam pharmaceutical composition of research, thus in solution prior art, produce the problems such as polymer and other impurity, solubility be bad, improve clinical drug safety and the effectiveness of gained Cefoperazone Sodium and Tazobactam pharmaceutical composition, reduce irritated risk.
Summary of the invention
The object of the present invention is to provide the cefoperazone sodium sulbactam sodium compositions that a kind of Product Safety is high, the present composition comprises the cefoperazone sodium micropowder of particle diameter d95 within the scope of 90 μm ~ 60 μm and sulbactam sodium micropowder.
In some embodiments, cefoperazone sodium micropowder and sulbactam sodium grain size of micropowder d95 are selected within the scope of 90 μm ~ 80 μm, 90 μm ~ 70 μm, 80 μm ~ 70 μm, 80 μm ~ 60 μm, 70 μm ~ 60 μm, 85 μm ~ 80 μm, 85 μm ~ 70 μm, 85 μm ~ 60 μm, 75 μm ~ 70 μm, 75 μm ~ 60 μm, 75 μm ~ 65 μm, 70 μm ~ 65 μm, 70 μm ~ 60 μm or 65 μm ~ 60 μm.
In some embodiments, the weight ratio of cefoperazone sodium micropowder and sulbactam sodium micropowder is at 1 ~ 4:1.In some embodiments, the weight ratio of described cefoperazone sodium micropowder and sulbactam sodium micropowder is selected from 4:1,3:1,2:1 or 1:1.In some embodiments, the weight ratio of described cefoperazone sodium micropowder and sulbactam sodium micropowder is 1:1.In some embodiments, the weight ratio of described cefoperazone sodium micropowder and sulbactam sodium micropowder is 2:1.
In some embodiments, pharmaceutical composition of the present invention can also be prepared into preparation together with pharmaceutically acceptable adjuvant or complementary composition.Described pharmaceutically adjuvant or complementary composition can be filler, diluent, disintegrating agent, binding agent, slow releasing agent, lubricant etc.One or more in the preferred lactose of described filler, mannitol, glucose, pregelatinized Starch, microcrystalline Cellulose; One or more in the preferred carboxymethyl starch sodium of above-mentioned disintegrating agent, microcrystalline Cellulose, crosslinked carboxymethyl fecula sodium; One or more in the preferred hypromellose of above-mentioned slow-release material, ethyl cellulose, polyvinylpolypyrrolidone; One or more in the preferred polyvidone of above-mentioned binding agent, pregelatinized Starch, sodium carboxymethyl cellulose; One or more in the preferred magnesium stearate of above-mentioned lubricant, Pulvis Talci.
The present composition is moisture absorption not easily, dissolve rapidly, quality stability is fabulous, based on these characteristics, we study discovery under 100 grades of conditions, can carry out by loading amount requirement the pharmaceutical composition that namely subpackage obtains cefoperazone sodium and sulbactam sodium for injection by the present invention in sterilizing room.Loading amount can be but be not only 0.625g, 1.25g, 2.5g, 3.75g.Prepare cefoperazone sodium and sulbactam sodium for injection pharmaceutical composition according to this method all to comply with the national standard requirements at content, aseptic, the indices such as thermal source, bacterial endotoxin.
In some embodiments, the preparation that prepared by pharmaceutical composition of the present invention is injection.Injection of the present invention can comprise pharmaceutically acceptable sterilized water or non-aqueous solution, dispersion liquid, suspension or emulsion, and is again mixed with the sterilized powder of aseptic injectable solution or dispersion liquid before using.Aqueous solution is specially adapted to intravenous, intramuscular, the object of subcutaneous and peritoneal injection.In this respect, aseptic aqueous medium used is all easily obtained by the standard technique of those skilled in the art.Suitable aqueous and non-aqueous supporting agent, diluent, the example of solvent or excipient comprises water, ethanol, polyhydric alcohol (as glycerol, propylene glycol, Polyethylene Glycol etc.), carboxymethyl cellulose and suitable mixture thereof, vegetable oil (as olive oil), and injectable organic ester is as ethyl oleate.Suitable mobility can be kept, such as, by use coating material as lecithin, by maintaining required particle diameter when dispersion liquid, and by use surfactant.Preferably, in some embodiments, preferred lyophilized preparation.
For treating, can give bacterial infection patients medicine of the present invention, dosage is enough to prevention, suppresses, or alleviates neural cell injury.The amount being enough to reach this purpose is defined as treating effective dose.Effective dose for this purposes depends on the order of severity of disease and the general status of patient's self immune system.Dosage regimen also can change according to the state of disease condition and patient, is administered once usual every day or continuous several times administration (such as, every 4-6 hour), or is determined according to the situation of patient by the doctor in charge.But, it should be noted that and the invention is not restricted to any specific dosage.
Compared with prior art, beneficial effect of the present invention is: pharmaceutical composition of the present invention is not known to prior art, and this pharmaceutical composition has that antibacterial activity is high, Product Safety high feature.
Specific embodiments
Following is in conjunction with specific embodiments and experimental example, sets forth the present invention further.But these embodiments are only limitted to the present invention instead of for limiting the scope of the invention is described.The experimental technique of unreceipted specific experiment condition in the following example, usually conveniently condition.
Embodiment 1:
Take cefoperazone sodium 1000.0g, sulbactam sodium 250.0g, put jet mill and be crushed to more than 95% grain diameter≤90 μm, to obtain final product.
Embodiment 2:
Take cefoperazone sodium 1000.0g, sulbactam sodium 333.0g, put jet mill and be crushed to more than 95% grain diameter≤85 μm, to obtain final product.
Embodiment 3:
Take cefoperazone sodium 1000.0g, sulbactam sodium 500.0g, put jet mill and be crushed to more than 95% grain diameter≤80 μm, to obtain final product.
Embodiment 4:
Take cefoperazone sodium 1000.0g, sulbactam sodium 1000.0g, put jet mill and be crushed to more than 95% grain diameter≤75 μm, to obtain final product.
Embodiment 5:
Take cefoperazone sodium 1000.0g, sulbactam sodium 1000.0g, put jet mill and be crushed to more than 95% grain diameter≤60 μm, to obtain final product.
Embodiment 6:
Take cefoperazone sodium 1000.0g, sulbactam sodium 500.0g, put jet mill and be crushed to more than 95% grain diameter≤65 μm, to obtain final product.
Embodiment 7:
Take cefoperazone sodium 1000.0g, sulbactam sodium 333.0g, put jet mill and be crushed to more than 95% grain diameter≤60 μm, to obtain final product.
Embodiment 8:
Take cefoperazone sodium 1000.0g, sulbactam sodium 250.0g, put jet mill and be crushed to more than 95% grain diameter≤60 μm, to obtain final product.
Embodiment 9:
Take cefoperazone sodium 1000.0g, sulbactam sodium 300.0g, put jet mill and be crushed to more than 95% grain diameter≤60 μm, to obtain final product.
The preparation of embodiment 10 cefoperazone sodium and sulbactam sodium for injection pharmaceutical composition
Prescription: (specification: 0.625g)
Cefoperazone sodium compound 500g
Sulbactam sodium 125g
Make 1000
Technique:
1, by the cefoperazone sodium compound of recipe quantity and sulbactam sodium, put jet mill and be crushed to more than 95% grain diameter≤90 μm, in sterilizing room, under 100 grades of conditions, 170 mesh sieves are crossed, mix homogeneously by sterile working, stand-by.
2, calculate content, get product by the fill of specification loading amount.
The preparation of embodiment 11 cefoperazone sodium and sulbactam sodium for injection pharmaceutical composition
Prescription: (specification: 1.25g)
Cefoperazone sodium compound 1000g
Sulbactam sodium 250g
Make 1000
Technique:
By the cefoperazone sodium compound of recipe quantity and sulbactam sodium, put jet mill and be crushed to more than 95% grain diameter≤80 μm, in sterilizing room, under 100 grades of conditions, 170 mesh sieves are crossed, mix homogeneously by sterile working, stand-by.
2, calculate content, get product by the fill of specification loading amount.
The preparation of embodiment 12 cefoperazone sodium and sulbactam sodium for injection pharmaceutical composition
Prescription: (specification: 2.5g)
Cefoperazone sodium compound 1250g
Sulbactam sodium 1250g
Make 1000
Technique:
1, by the cefoperazone sodium compound of recipe quantity and sulbactam sodium, put jet mill and be crushed to more than 95% grain diameter≤70 μm, in sterilizing room, under 100 grades of conditions, 170 mesh sieves are crossed, mix homogeneously by sterile working, stand-by
2, calculate content, get product by the fill of specification loading amount.
The preparation of embodiment 13 cefoperazone sodium and sulbactam sodium for injection pharmaceutical composition
Prescription: (specification: 3.75g)
Cefoperazone sodium 2500g
Sulbactam sodium 1250g
Make 1000
Technique:
1, by the cefoperazone sodium compound of recipe quantity and sulbactam sodium, put jet mill and be crushed to more than 95% grain diameter≤60 μm, in sterilizing room, under 100 grades of conditions, 170 mesh sieves are crossed, mix homogeneously by sterile working, stand-by
2, content is calculated, by the fill of specification loading amount and get final product.
The preparation of embodiment 14 Cefoperazone Sodium and Tazobactam pharmaceutical composition
Prescription: (specification: 0.725g)
Cefoperazone sodium 500g
Sulbactam sodium 250g
Make 1000
Technique:
By the cefoperazone sodium compound of recipe quantity and sulbactam sodium, put jet mill and be crushed to more than 95% grain diameter≤70 μm, in sterilizing room, under 100 grades of conditions, 170 mesh sieves are crossed, mix homogeneously by sterile working, stand-by
2, calculate content, get product by the fill of specification loading amount.
The preparation of embodiment 15 Cefoperazone Sodium and Tazobactam pharmaceutical composition
Prescription: (specification: 1.25g)
Cefoperazone sodium 1000g
Sulbactam sodium 250g
Make 1000
Technique:
By the cefoperazone sodium compound of recipe quantity and sulbactam sodium, put jet mill and be crushed to more than 95% grain diameter≤60 μm, in sterilizing room, under 100 grades of conditions, 170 mesh sieves are crossed, mix homogeneously by sterile working, stand-by
2, calculate content, get product by the fill of specification loading amount.
Comparative example 1:
Take cefoperazone sodium 1000.0g, sulbactam sodium 250.0g, put jet mill and be crushed to more than 95% grain diameter≤200 μm, to obtain final product.
Comparative example 2:
Take cefoperazone sodium 1000.0g, sulbactam sodium 333.0g, put jet mill and be crushed to more than 95% grain diameter≤150 μm, to obtain final product.
Comparative example 3:
Take cefoperazone sodium 1000.0g, sulbactam sodium 500.0g, put jet mill and be crushed to more than 95% grain diameter≤200 μm, to obtain final product.
Comparative example 4:
Take cefoperazone sodium 1000.0g, sulbactam sodium 1000.0g, put jet mill and be crushed to more than 95% grain diameter≤150 μm, to obtain final product.
Comparative example 5:
Take cefoperazone sodium 1000.0g, sulbactam sodium 250.0g, put jet mill and be crushed to more than 95% grain diameter≤50 μm, to obtain final product.
Comparative example 6:
Take cefoperazone sodium 1000.0g, sulbactam sodium 333.0g, put jet mill and be crushed to more than 95% grain diameter≤30 μm, to obtain final product.
Comparative example 7:
Take cefoperazone sodium 1000.0g, sulbactam sodium 500.0g, put jet mill and be crushed to more than 95% grain diameter≤20 μm, to obtain final product.
Comparative example 8:
Take cefoperazone sodium 1000.0g, sulbactam sodium 1000.0g, put jet mill and be crushed to more than 95% grain diameter≤50 μm, to obtain final product.
The preparation of comparative example 9 cefoperazone sodium and sulbactam sodium for injection pharmaceutical composition
Prescription: (specification: 0.625g)
Cefoperazone sodium compound 500g
Sulbactam sodium 125g
Make 1000
Technique:
1, by the cefoperazone sodium compound of recipe quantity and sulbactam sodium, put jet mill and be crushed to more than 95% grain diameter≤200 μm, in sterilizing room, under 100 grades of conditions, 70 mesh sieves are crossed, mix homogeneously by sterile working, stand-by.
2, calculate content, get product by the fill of specification loading amount.
The preparation of comparative example 10 cefoperazone sodium and sulbactam sodium for injection pharmaceutical composition
Prescription: (specification: 1.25g)
Cefoperazone sodium compound 1000g
Sulbactam sodium 250g
Make 1000
Technique:
By the cefoperazone sodium compound of recipe quantity and sulbactam sodium, put jet mill and be crushed to more than 95% grain diameter≤150 μm, in sterilizing room, under 100 grades of conditions, 70 mesh sieves are crossed, mix homogeneously by sterile working, stand-by.
2, calculate content, get product by the fill of specification loading amount.
The preparation of comparative example 11 cefoperazone sodium and sulbactam sodium for injection pharmaceutical composition
Prescription: (specification: 2.5g)
Cefoperazone sodium compound 1250g
Sulbactam sodium 1250g
Make 1000
Technique:
1, by the cefoperazone sodium compound of recipe quantity and sulbactam sodium, put jet mill and be crushed to more than 95% grain diameter≤200 μm, in sterilizing room, under 100 grades of conditions, 70 mesh sieves are crossed, mix homogeneously by sterile working, stand-by
2, calculate content, get product by the fill of specification loading amount.
The preparation of comparative example 12 cefoperazone sodium and sulbactam sodium for injection pharmaceutical composition
Prescription: (specification: 3.75g)
Cefoperazone sodium 2500g
Sulbactam sodium 1250g
Make 1000
Technique:
1, by the cefoperazone sodium compound of recipe quantity and sulbactam sodium, put jet mill and be crushed to more than 95% grain diameter≤150 μm, in sterilizing room, under 100 grades of conditions, 70 mesh sieves are crossed, mix homogeneously by sterile working, stand-by
2, content is calculated, by the fill of specification loading amount and get final product.
The preparation of comparative example 13 cefoperazone sodium and sulbactam sodium for injection pharmaceutical composition
Prescription: (specification: 0.625g)
Cefoperazone sodium compound 500g
Sulbactam sodium 125g
Make 1000
Technique:
1, by the cefoperazone sodium compound of recipe quantity and sulbactam sodium, put jet mill and be crushed to more than 95% grain diameter≤50 μm, in sterilizing room, under 100 grades of conditions, 270 mesh sieves are crossed, mix homogeneously by sterile working, stand-by.
2, calculate content, get product by the fill of specification loading amount.
The preparation of comparative example 14 cefoperazone sodium and sulbactam sodium for injection pharmaceutical composition
Prescription: (specification: 1.25g)
Cefoperazone sodium compound 1000g
Sulbactam sodium 250g
Make 1000
Technique:
By the cefoperazone sodium compound of recipe quantity and sulbactam sodium, put jet mill and be crushed to more than 95% grain diameter≤20 μm, in sterilizing room, under 100 grades of conditions, 270 mesh sieves are crossed, mix homogeneously by sterile working, stand-by.
2, calculate content, get product by the fill of specification loading amount.
The preparation of comparative example 15 cefoperazone sodium and sulbactam sodium for injection pharmaceutical composition
Prescription: (specification: 2.5g)
Cefoperazone sodium compound 1250g
Sulbactam sodium 1250g
Make 1000
Technique:
1, by the cefoperazone sodium compound of recipe quantity and sulbactam sodium, put jet mill and be crushed to more than 95% grain diameter≤30 μm, in sterilizing room, under 100 grades of conditions, 270 mesh sieves are crossed, mix homogeneously by sterile working, stand-by
2, calculate content, get product by the fill of specification loading amount.
The preparation of comparative example 16 cefoperazone sodium and sulbactam sodium for injection pharmaceutical composition
Prescription: (specification: 3.75g)
Cefoperazone sodium 2500g
Sulbactam sodium 1250g
Make 1000
Technique:
1, by the cefoperazone sodium compound of recipe quantity and sulbactam sodium, put jet mill and be crushed to more than 95% grain diameter≤50 μm, in sterilizing room, under 100 grades of conditions, 270 mesh sieves are crossed, mix homogeneously by sterile working, stand-by
2, content is calculated, by the fill of specification loading amount and get final product.
Test example 1: different-grain diameter compositions Related substances separation
1, method:
Present composition its related substances is detected according to document " the Quality situation research of cefoperazone sodium and sulbactam sodium for injection " (" Asia-Pacific traditional medicine ", volume the 2nd phase February the 6th in 2010,20th ~ 21 pages) method
3, results contrast
Table 1 present composition related substance comparative result
As can be seen from Table 1, when cefoperazone sodium and sulbactam sodium grain size of micropowder d95 are within the scope of 90 μm ~ 60 μm, related substance increases to some extent, and increasing degree is not obvious, quality controllable.But when cefoperazone sodium and sulbactam sodium grain size of micropowder d95 are within the scope of 50 μm ~ 20 μm, related substance to some extent increasing degree increases, and illustrates that cefoperazone sodium and the excessive micronization of sulbactam sodium can cause cefoperazone sodium and sulbactam sodium degradation reaction.
Test example 2: present composition polymer content is investigated
1, method:
According to the document assay of macromolecule impurity " in the cefoperazone sodium sulbactam sodium " (" Heilungkiang medicine " the 18th volume the 1st phase in 2005,168 ~ 169 pages)
2, the investigation result of polymer
Polymer content the results are shown in Table 2.
Table 2, the present composition and comparative example compositions polymer determination result
Cefoperazone sodium is penicillins beta-lactam antibiotic, and clinical and experimentation proves, the anaphylaxis that such medicine causes is caused by high molecular polymer wherein, and therefore controlling polymer in product is the key factor controlling drug quality.As can be seen from polymer determination result, compositions polymer content of the present invention is significantly less than d95≤50 μm and following compositions, little with the composition levels difference of d95≤200 μm or d95≤100 μm, d95≤100 μm.Illustrate that cefoperazone sodium and the excessive micronization of sulbactam sodium can cause compound polymerization.
Test example 4: solubility is tested
This experimental example has investigated the impact of micronization on the solubility of cefoperazone sodium and sulbactam sodium for injection compositions.The results are shown in Table 3, table 4.
Table 3, the present composition and comparative example composition product redissolution performance (dissolution velocity) result
Table 4, the present composition and comparative example composition product redissolution performance (solid precipitation) result
As can be seen from the above table, after placement a period of time, the redissolution speed of the present composition is greater than the comparative example compositions redissolution speed of d95 within the scope of 200 μm ~ 150 μm, and the redissolution performance of composition for injection of the present invention is significantly better than d95 comparative example composition product within the scope of 200 μm ~ 150 μm.Therefore, the product dissolubility adopting preparation method of the present invention to prepare is more stable, not easily separates out solid matter, thus substantially increases the drug safety of patient.
Test example 4: cefoperazone sodium sulbactam sodium micronization compositions is to the protective effect of escherichia coli, staphylococcus aureus and bacillus pyocyaneus In vivo infection mice.
Animal ICR mice, body weight 18-22g, male and female half and half.
Experimental strain produces the strain of enzyme antibacterial 3, and escherichia coli (97115), staphylococcus aureus (981901) and bacillus pyocyaneus (00080840), above bacterial strain is Clinical isolation.
Protective agent high activity dried yeast, commercial goods.
Experimental technique: press the tested bacterium of mouse infection in trial test, after finding out 100% dead mouse and not occurring dead each drug dose concentration, treating excess syndrome is tested front 18h fasting and be can't help water, body weight 18-22g mice, male and female half and half, random packet, often organize 5 drug level, often organize 10 animals, and establish 10 animals to make blank (giving isopyknic sterilized water for injection), every Mus equal lumbar injection 1MLD(causes the minimum bacterium amount of mice 100% death) bacterium liquid 0.5ml, cause infection model, at once the tested medicinal liquid 0.2ml/ Mus of subcutaneous injection variable concentrations is distinguished with 6h after infecting, Continuous Observation 7 days, record each treated animal death condition.Inspection is cutd open to dead mice, does perusal.Calculate respectively by the ED of reagent by Bliss method 50and 95% fiducial limit, and carry out t inspection, compare the significance of its difference between group.
Experimental result calculates: experimental drug is to institute experimental strain infecting mouse ED 50value and ED 5095% fiducial limit, ED 95and ED 50(each medicine) t inspection all use Bliss method, use NDST software program counting statistics.
Common-used formula:
A）ED 50＝log -1[X m-I(∑p-0.5)+i/4(1-p m-p n)]
B）L 95＝log -1(logED 50±1.96Sx 50)
C）Sx 50＝I[(∑p-∑p 2)/(n-1)] 0.5
D）t＝ED 50-ED 50/(Sx 2 50+Sx 50) 0.5
Result judges: statistics specifies significance level traditionally often as following several:
A) P≤0.01, " two groups of difference have highly significant meaning "
B) P≤0.05, (0.01 < P < 0.05) " two groups of difference significances "
C) P > 0.05, " though having difference between two groups, nonsignificance "
D) P≤0.1, (0.05 < P≤0.1) is screened valuable being worth and is studied further.
Experimental result in table 5 ~
Table 5 present composition and comparative example compositions are to infecting mouse Protective effect
Applicant finds unexpectedly, and micronization d95 has better effect 90 μm ~ 60 μm scope cefoperazone sodium sulbactam sodium compositionss in antibacterial activity.From table 3 data, d95 is better than the activity of d95≤200 μm, d95≤150 μm at the antibacterial activity of 90 μm ~ 60 μm scope cefoperazone sodium sulbactam sodium compositions micropowders, may be because the micronization reason that causes medicine bioavailability in vivo to improve.D95 is better than the activity of d95≤50 μm, d95≤30 μm at the antibacterial activity of 90 μm ~ 60 μm scope cefoperazone sodium sulbactam sodium compositions micropowders, may be because excessive micronization to cause active constituents of medicine that degraded occurs relevant.
Should be understood that those skilled in the art can make various changes or modifications the present invention after having read above-mentioned teachings of the present invention, these equivalent form of values fall within the application's appended claims limited range equally.

Claims (6)

1. a pharmaceutical composition, comprises the cefoperazone sodium micropowder of particle diameter d95 within the scope of 90 μm ~ 60 μm and sulbactam sodium micropowder.
2., as weighed a pharmaceutical composition as described in 1, it is characterized in that described cefoperazone sodium micropowder and sulbactam sodium micropowder footpath d95 are selected within the scope of 90 μm ~ 80 μm, 90 μm ~ 70 μm, 80 μm ~ 70 μm, 80 μm ~ 60 μm, 70 μm ~ 60 μm, 85 μm ~ 80 μm, 85 μm ~ 70 μm, 85 μm ~ 60 μm, 75 μm ~ 70 μm, 75 μm ~ 60 μm, 75 μm ~ 65 μm, 70 μm ~ 65 μm, 70 μm ~ 60 μm or 65 μm ~ 60 μm.
3., as weighed a pharmaceutical composition as described in 2, it is characterized in that the weight ratio of described cefoperazone sodium micropowder and sulbactam sodium micropowder is at 1 ~ 4:1.
4., as weighed a pharmaceutical composition as described in 3, it is characterized in that the weight ratio of described cefoperazone sodium micropowder and sulbactam sodium micropowder is selected from 4:1,3:1,2:1 or 1:1.
5., as weighed a pharmaceutical composition as described in 4, it is characterized in that the weight ratio of described cefoperazone sodium micropowder and sulbactam sodium micropowder is 1:1.
6., as weighed a pharmaceutical composition as described in 4, it is characterized in that the weight ratio of described cefoperazone sodium micropowder and sulbactam sodium micropowder is 2:1.
CN201610125206.6A 2016-03-07 2016-03-07 Pharmaceutical composition containing cefoperazone sodium and sulbactam sodium Pending CN105534919A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201610125206.6A CN105534919A (en) 2016-03-07 2016-03-07 Pharmaceutical composition containing cefoperazone sodium and sulbactam sodium

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201610125206.6A CN105534919A (en) 2016-03-07 2016-03-07 Pharmaceutical composition containing cefoperazone sodium and sulbactam sodium

Publications (1)

Publication Number Publication Date
CN105534919A true CN105534919A (en) 2016-05-04

Family

ID=55814853

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201610125206.6A Pending CN105534919A (en) 2016-03-07 2016-03-07 Pharmaceutical composition containing cefoperazone sodium and sulbactam sodium

Country Status (1)

Country Link
CN (1) CN105534919A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110393719A (en) * 2018-08-28 2019-11-01 广东金城金素制药有限公司 The new indication of cefoperazone sodium sulbactam sodium pharmaceutical preparation treatment infectious endocarditis

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102688244A (en) * 2012-06-25 2012-09-26 北京新天宇科技开发有限公司 Compound preparation of cefotaxime sodium and sulbactam sodium as well as preparation method and application thereof
CN103655578A (en) * 2013-12-26 2014-03-26 湖南天圣药业有限公司 Powder mixing method for cefoperazone sodium and sulbactam sodium

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102688244A (en) * 2012-06-25 2012-09-26 北京新天宇科技开发有限公司 Compound preparation of cefotaxime sodium and sulbactam sodium as well as preparation method and application thereof
CN103655578A (en) * 2013-12-26 2014-03-26 湖南天圣药业有限公司 Powder mixing method for cefoperazone sodium and sulbactam sodium

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
王艳等: "注射用头孢哌酮钠-舒巴坦钠与四种输液的配伍稳定性", 《大连医科大学学报》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110393719A (en) * 2018-08-28 2019-11-01 广东金城金素制药有限公司 The new indication of cefoperazone sodium sulbactam sodium pharmaceutical preparation treatment infectious endocarditis
CN110393719B (en) * 2018-08-28 2021-09-28 广东金城金素制药有限公司 Cefoperazone sodium and sulbactam sodium composition pharmaceutical preparation and new indications for treating infectious endocarditis

Similar Documents

Publication Publication Date Title
CN110087632B (en) Calcium Lactate Compositions and Methods of Use
EP2448563A2 (en) 3-cyanoquinoline tablet formulations and uses thereof
CN108125921B (en) Posaconazole solid dispersion composition capable of inhibiting crystallization and preparation method thereof
EP2694037A1 (en) Formulations comprising 2 -amino- 2- [2- (4 - octylphenyl) ethyl]propane -1, 3 - diol
CN110869023B (en) In situ gel forming pharmaceutical composition and its use in sinus disease
WO2021042777A1 (en) Multi-component gel sustained-release pharmaceutical composition for treatment of tumors
US20110207764A1 (en) Cyclopolysaccharide compositions
CN105534919A (en) Pharmaceutical composition containing cefoperazone sodium and sulbactam sodium
CN1921839A (en) Stable sustained-release oral dosage forms of gabapentin and process for preparation thereof
US20210379083A1 (en) Pharmaceutical composition and use
CN107028931A (en) A kind of taxol drug composition and its pharmaceutical preparation, preparation method and purposes
CN105640963A (en) Cefoperazone sodium and tazobactam sodium medicine composition
CN106265526A (en) The solid dispersion of a kind of antifungal drug posaconazole and preparation method and application
JP2847866B2 (en) Peptic ulcer treatment
EP1069914B1 (en) Controlled release tablet produced from linear water-insoluble polysaccharides
CN105476994A (en) Piperacillin sodium and sulbactam sodium medicine composition
CN105640959B (en) Avocin and tazobactam sodium drug composition
US20070099996A1 (en) Pharmaceutical compositions of acitretin
WO2007141806A1 (en) Pharmaceutical formulations comprising oxcarbazepine and methods thereof
US3174899A (en) Composition for the management of post antibiotic enteritis
CN105663128A (en) Pharmaceutical composition of mezlocillin sodium and sulbactam sodium
CN106880598A (en) A kind of Ezetimibe tablet
CN114681406A (en) Carilazine long-acting slow-release microsphere and preparation method thereof
TW202024058A (en) Compounds and methods for treating fungal infections
CN107789355B (en) Compound pharmaceutical composition containing piperacillin and application thereof

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
RJ01 Rejection of invention patent application after publication

Application publication date: 20160504

RJ01 Rejection of invention patent application after publication