CN107080750A - Cefoperazone sodium and sulbactam sodium for injection preparation technology - Google Patents
Cefoperazone sodium and sulbactam sodium for injection preparation technology Download PDFInfo
- Publication number
- CN107080750A CN107080750A CN201710284552.3A CN201710284552A CN107080750A CN 107080750 A CN107080750 A CN 107080750A CN 201710284552 A CN201710284552 A CN 201710284552A CN 107080750 A CN107080750 A CN 107080750A
- Authority
- CN
- China
- Prior art keywords
- injection
- sodium
- sulbactam
- water
- 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
Links
Classifications
-
- 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
-
- 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- 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
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
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)
- Dermatology (AREA)
- Apparatus For Disinfection Or Sterilisation (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a kind of cefoperazone sodium and sulbactam sodium for injection preparation technology, comprise the following steps：Mixed powder preparation section：Weigh cefoperazone sodium and sulbactam raw material fine powder is added to the water progress dissolving and mixed solution is made, mixed solution is added in ultrasonic wave dispersing stirrer and carries out scattered mix；Acetone is added into the mixed solution, proceeds the scattered stirring of ultrasonic wave at low temperature；Mixed solution after decentralized processing is placed in freeze drying box and carries out frozen dried；By freeze-dried material successively through being once dried in vacuo, crushing and screening, secondary vacuum drying process obtain mixed material；Soda-lime glass molding injection agent bottle matting, rubber plug cleaning process, aluminium lid matting and aseptic subpackaged process, obtain cefoperazone sodium and sulbactam sodium for injection powder-injection.The present invention can promote cefoperazone sodium raw materials powder and sulbactam raw material powder fully to mix, and relative amount ratio between the two is stable, ensure that product has higher stability.
Description
Technical field
The present invention, which is related to, belongs to field of medicine and chemical technology, and in particular to cefoperazone sodium and sulbactam sodium for injection preparation technology.
Background technology
Cefoperazone sodium and sulbactam sodium for injection (Cefoperazone Sodium and Sulbactam Sodium for
Injection), cefoperazone sodium：(6R, 7R) -3- [[(1- methyl isophthalic acid H- tetrazolium -5- bases) sulphur] methyl] -7- [(R) -2- (4-
Ethyl -2,3- dioxo -1- piperazines carbon acylamino) -2- p-hydroxybenzenes-acetylamino] -8- oxo -5- thia -1- azepines pair
Ring [4.2.0] oct-2-ene -2- formic acid sodium salts；Sulbactam：(2S, 5R) -3,3- dimethyl -7- oxo -4- thia -1- azepines
Bicyclic [3.2.0] heptane -2- carboxylic acid sodium -4,4- dioxide.Cefoperazone sodium and sulbactam sodium for injection is used to treat by sensitivity
Following infection caused by bacterium：Respiratory tract infection (upper respiratory tract and lower respiratory tract)；Urethral infection (with secrete by upper urinary tract
Urethra)；Infected in peritonitis, cholecystitis, cholangitis and other abdomens；Septicemia, meningitis；Skin and soft tissue infection, eye
Infection, bone and the infection of joint；Pelvic infecton, endometritis, gonorrhoea and other genitals, road infection etc.；Prevention is because of abdominal cavity, woman
Post-operative infection caused by section, angiocarpy, orthopaedics and plastic operation.Cefoperazone sodium sulbactam sodium is a compound formulation, is relaxed
Batan is that wide spectrum enzyme inhibitor has weaker antibacterial activity simultaneously, the beta-lactam produced to S. aureus L-forms and most negative bacillus
Enzyme has powerful irreversible inhibitory action, but to the beta-lactam kinase inactive of some negative bacillus Chromosome-encodeds.Note
Penetrate with cefoperazone sodium sulbactam sodium powder-injection preparation process, in the prior art frequently with simple mechanical mixture, it is impossible to real
Now cefoperazone sodium raw materials powder and sulbactam raw material powder are fully mixed, and cefoperazone sodium raw materials powder and sulbactam
The mixing uniformity of raw material powder has material impact effect to the stability of final finished medicine.
The content of the invention
The technical problems to be solved by the invention are in the prior art frequently with simple mechanical mixture, it is impossible to realized head
Spore piperazine ketone sodium raw materials powder and sulbactam raw material powder are fully mixed, it is therefore intended that provide cefoperazone sodium in injection Sulbactam
Sodium preparation technology, can promote cefoperazone sodium raw materials powder and sulbactam raw material powder fully to mix, and between the two relative contains
Amount ratio is stable, ensures that product has higher stability.
The present invention is achieved through the following technical solutions：
Cefoperazone sodium and sulbactam sodium for injection preparation technology, comprises the following steps：
(1) powder preparation section is mixed：Weigh cefoperazone sodium and sulbactam raw material fine powder is added to the water and fully dissolved
Mixed solution is made, and the mixed solution is added into the scattered mixing of progress in ultrasonic wave dispersing stirrer；Secondly to described mixed
Close in solution and add acetone, proceed the scattered stirring of ultrasonic wave under 0~5 DEG C of temperature conditions；Then by after decentralized processing
Mixed solution, which is placed in freeze drying box, carries out frozen dried；Finally by freeze-dried material successively through being once dried in vacuo, crushing and screening, two
Secondary vacuum drying treatment obtains mixed material；The mixed powder preparation section is operated under laminar flow protection；
(2) soda-lime glass molding injection agent bottle matting：Up-to-standard injection bottle is first being entered into bottleneck using following
Ring water inlet cleaning showers processing, then carries out ultrasonic wave cleaning using recirculated water；Enter main cleaning rail secondly by bottle track is carried
Road, the water for injection that the purified water and hydraulic pressure for using hydraulic pressure to be 0.2Mpa for 0.45Mpa recirculated water, hydraulic pressure successively are 0.1Mpa
The inside and outside wall of injection bottle is rinsed；Then blown using the 0.4Mpa compressed air through 0.22 μm of filter filtration, purification
Drying, feeding sterilizing oven guipure carries out sterilization treatment, finally by the injection bottle feeding packing room after sterilizing；
(3) rubber plug cleaning process：Suction dust removal process is first carried out to butyl rubber plug using vavuum pump, then through Full-automatic glue
Plug cleaning machine cleaned, sterilized, being dried, cool down after it is standby；
(4) aluminium lid matting：Aluminium-plastic combined cover is placed in full-automatic aluminum cover cleaning machine and is cleaned, sterilized, dried
With it is standby after cooling treatment；
(5) aseptic subpackaged process：Mixed material bucket/bag the surface is cleaned using drinking water first, then it is new clean with 0.2%
You go out or 2% lysol carries out spray disinfectant；Then enter sector-style in pass-through box and drench processing 10min, vent wind speed is 35m/s, mistake
Cleansing filter efficiency >=0.6 μm dust >=99.99%；Spray disinfectant is carried out using 1% Peracetic acid into C grades of clean areas；Again
Secondary to enter sector-style in pass-through box and drench processing 10min, vent wind speed is 50m/s, filter depuration efficiency >=0.2 μm dust >=
99.99%, finally enter B grades of clean area material temporary rooms and kept in；It is distributed into according to standard metering into injection bottle mixed
Raw material is closed, cefoperazone sodium and sulbactam sodium for injection powder-injection is obtained through tamponade, gland and packing processes；The temperature of control packing room
Spend for 18 DEG C of temperature~24 DEG C, humidity≤65%.
Preferably, in the mixed powder process, cefoperazone sodium, sulbactam, the quality proportioning of aqueous solvent and acetone are：1:
1:5~10：0.1~0.3.
Preferably, in the mixed powder process, the operating parameter of ultrasonic wave dispersing stirrer is：Whipping temp is 10~15
DEG C, frequency is 25KHz.
Preferably, in the mixed powder process, freeze temperature is -35~-45 DEG C, and freeze-drying time is 3~5h.
Preferably, in the mixed powder process, a vacuum drying temperature is 40~50 DEG C, and drying time is 60~80min；
The secondary vacuum drying temperature is 25~35 DEG C, and drying time is 50~60min.
Preferably, in the process (2), in ultrasonic wave cleaning process, circulating water temperature be 25 DEG C, flow velocity be 1.0~
1.5m/s, ultrasonic frequency is 35kHz.
Preferably, in the process (2), the sterilizing oven mesh belt transmission speed is 20cm/min；Sterilisation process
Include preheating, sterilizing and cooling step successively, the sterilization steps are sterilized using 320 DEG C of circulating air, hot air circulation
Speed is 30m/s, and sterilization time is 8min.
Preferably, in the process (3), Full automatic rubber plug cleaning machine processing control parameter is：Water for injection pressure is
0.2Mpa, compressed air pressure is 0.25Mpa, vacuum -0.02Mpa, and the water for injection, compressed air are through 0.22 μm of mistake
Filter is filtered.
Preferably, in the process (4), full-automatic aluminum cover cleaning machine processing control parameter is：Water for injection pressure is
0.2Mpa, compressed air pressure is 0.2Mpa, vacuum -0.02Mpa, and the water for injection, compressed air are through 0.22 μm of mistake
Filter is filtered；Ultrasonic frequency is 20kHz, and is sprayed in ultrasonic wave cleaning process using water circulation.
The present invention compared with prior art, has the following advantages and advantages：
The invention provides a kind of cefoperazone sodium and sulbactam sodium for injection preparation technology, cefoperazone sodium can be promoted former
Feed powder and sulbactam raw material powder are fully mixed, and relative amount ratio between the two is stable, ensure that product has higher steady
It is qualitative.
Embodiment
For the object, technical solutions and advantages of the present invention are more clearly understood, with reference to embodiment, to present invention work
Further to describe in detail, exemplary embodiment and its explanation of the invention is only used for explaining the present invention, is not intended as to this
The restriction of invention.
Embodiment 1
The invention provides a kind of cefoperazone sodium and sulbactam sodium for injection preparation technology, concretely comprise the following steps：
(1) powder preparation section is mixed：Weigh cefoperazone sodium and sulbactam raw material fine powder is added to the water and fully dissolved
Mixed solution is made, and the mixed solution is added into the scattered mixing of progress in ultrasonic wave dispersing stirrer；Secondly to described mixed
Close in solution and add acetone, proceed the scattered stirring of ultrasonic wave under 0 DEG C of temperature conditions；Then by the mixing after decentralized processing
Solution, which is placed in freeze drying box, carries out frozen dried；Finally by freeze-dried material successively through being once dried in vacuo, crushing and screening, it is secondary true
Empty drying process obtains mixed material；The mixed powder preparation section is operated under laminar flow protection, and a vacuum drying temperature is 45
DEG C, drying time is 70min；The secondary vacuum drying temperature is 30 DEG C, and drying time is 55min.The scattered stirring of ultrasonic wave
The operating parameter of device is：Whipping temp is 10 DEG C, and frequency is 25KHz.The cefoperazone sodium, sulbactam, aqueous solvent and third
The quality proportioning of ketone is：1:1:5:0.1；
(2) soda-lime glass molding injection agent bottle matting：Up-to-standard injection bottle is first being entered into bottleneck using following
Ring water inlet cleaning showers processing, is then carried out in ultrasonic wave cleaning, ultrasonic wave cleaning process, circulating water temperature is using recirculated water
25 DEG C, flow velocity is 1.0~1.5m/s, and ultrasonic frequency is 35kHz；Enter main cleaning track secondly by bottle track is carried, successively
The water for injection that the purified water and hydraulic pressure for using hydraulic pressure to be 0.2Mpa for 0.45Mpa recirculated water, hydraulic pressure are 0.1Mpa is to injection
The inside and outside wall of agent bottle is rinsed；Then dried up using the 0.4Mpa compressed air through 0.22 μm of filter filtration, purification,
Send into sterilizing oven guipure and carry out sterilization treatment, the sterilizing oven mesh belt transmission speed is 20cm/min；Sterilisation process
Include preheating, sterilizing and cooling step successively, the sterilization steps are sterilized using 320 DEG C of circulating air, hot air circulation
Speed is 30m/s, and sterilization time is 8min, finally by the injection bottle feeding packing room after sterilizing；
(3) rubber plug cleaning process：Suction dust removal process is first carried out to butyl rubber plug using vavuum pump, then through Full-automatic glue
Plug cleaning machine cleaned, sterilized, being dried, cool down after it is standby；Full automatic rubber plug cleaning machine handles control parameter：Water for injection
Pressure is 0.2Mpa, and compressed air pressure is 0.25Mpa, vacuum -0.02Mpa, and the water for injection, compressed air are passed through
0.22 μm of filter filtering；
(4) aluminium lid matting：Aluminium-plastic combined cover is placed in full-automatic aluminum cover cleaning machine and is cleaned, sterilized, dried
With it is standby after cooling treatment；Full-automatic aluminum cover cleaning machine handles control parameter：Water for injection pressure is 0.2Mpa, compressed air
Pressure is 0.2Mpa, vacuum -0.02Mpa, and the water for injection, compressed air are filtered through 0.22 μm of filter；Ultrasonic wave
Frequency is 20kHz, and is sprayed in ultrasonic wave cleaning process using water circulation；
(5) aseptic subpackaged process：Mixed material bucket/bag the surface is cleaned using drinking water first, then it is new clean with 0.2%
You go out or 2% lysol carries out spray disinfectant；Then enter sector-style in pass-through box and drench processing 10min, vent wind speed is 35m/s, mistake
Cleansing filter efficiency >=0.6 μm dust >=99.99%；Spray disinfectant is carried out using 1% Peracetic acid into C grades of clean areas；Again
Secondary to enter sector-style in pass-through box and drench processing 10min, vent wind speed is 50m/s, filter depuration efficiency >=0.2 μm dust >=
99.99%, finally enter B grades of clean area material temporary rooms and kept in；It is distributed into according to standard metering into injection bottle mixed
Raw material is closed, cefoperazone sodium and sulbactam sodium for injection powder-injection is obtained through tamponade, gland and packing processes；The temperature of control packing room
Spend for 18 DEG C of temperature~24 DEG C, humidity≤65%.
Embodiment 2
(1) powder preparation section is mixed：Weigh cefoperazone sodium and sulbactam raw material fine powder is added to the water and fully dissolved
Mixed solution is made, and the mixed solution is added into the scattered mixing of progress in ultrasonic wave dispersing stirrer；Secondly to described mixed
Close in solution and add acetone, proceed the scattered stirring of ultrasonic wave under 0 DEG C of temperature conditions；Then by the mixing after decentralized processing
Solution, which is placed in freeze drying box, carries out frozen dried；Finally by freeze-dried material successively through being once dried in vacuo, crushing and screening, it is secondary true
Empty drying process obtains mixed material；The mixed powder preparation section is operated under laminar flow protection, and a vacuum drying temperature is 45
DEG C, drying time is 70min；The secondary vacuum drying temperature is 30 DEG C, and drying time is 55min.The scattered stirring of ultrasonic wave
The operating parameter of device is：Whipping temp is 10 DEG C, and frequency is 25KHz.The cefoperazone sodium, sulbactam, aqueous solvent and third
The quality proportioning of ketone is：1:1:8:0.2；
(2) soda-lime glass molding injection agent bottle matting：Up-to-standard injection bottle is first being entered into bottleneck using following
Ring water inlet cleaning showers processing, is then carried out in ultrasonic wave cleaning, ultrasonic wave cleaning process, circulating water temperature is using recirculated water
25 DEG C, flow velocity is 1.0~1.5m/s, and ultrasonic frequency is 35kHz；Enter main cleaning track secondly by bottle track is carried, successively
The water for injection that the purified water and hydraulic pressure for using hydraulic pressure to be 0.2Mpa for 0.45Mpa recirculated water, hydraulic pressure are 0.1Mpa is to injection
The inside and outside wall of agent bottle is rinsed；Then dried up using the 0.4Mpa compressed air through 0.22 μm of filter filtration, purification,
Send into sterilizing oven guipure and carry out sterilization treatment, the sterilizing oven mesh belt transmission speed is 20cm/min；Sterilisation process
Include preheating, sterilizing and cooling step successively, the sterilization steps are sterilized using 320 DEG C of circulating air, hot air circulation
Speed is 30m/s, and sterilization time is 8min, finally by the injection bottle feeding packing room after sterilizing；
(3) rubber plug cleaning process：Suction dust removal process is first carried out to butyl rubber plug using vavuum pump, then through Full-automatic glue
Plug cleaning machine cleaned, sterilized, being dried, cool down after it is standby；Full automatic rubber plug cleaning machine handles control parameter：Water for injection
Pressure is 0.2Mpa, and compressed air pressure is 0.25Mpa, vacuum -0.02Mpa, and the water for injection, compressed air are passed through
0.22 μm of filter filtering；
(4) aluminium lid matting：Aluminium-plastic combined cover is placed in full-automatic aluminum cover cleaning machine and is cleaned, sterilized, dried
With it is standby after cooling treatment；Full-automatic aluminum cover cleaning machine handles control parameter：Water for injection pressure is 0.2Mpa, compressed air
Pressure is 0.2Mpa, vacuum -0.02Mpa, and the water for injection, compressed air are filtered through 0.22 μm of filter；Ultrasonic wave
Frequency is 20kHz, and is sprayed in ultrasonic wave cleaning process using water circulation；
(5) aseptic subpackaged process：Mixed material bucket/bag the surface is cleaned using drinking water first, then it is new clean with 0.2%
You go out or 2% lysol carries out spray disinfectant；Then enter sector-style in pass-through box and drench processing 10min, vent wind speed is 35m/s, mistake
Cleansing filter efficiency >=0.6 μm dust >=99.99%；Spray disinfectant is carried out using 1% Peracetic acid into C grades of clean areas；Again
Secondary to enter sector-style in pass-through box and drench processing 10min, vent wind speed is 50m/s, filter depuration efficiency >=0.2 μm dust >=
99.99%, finally enter B grades of clean area material temporary rooms and kept in；It is distributed into according to standard metering into injection bottle mixed
Raw material is closed, cefoperazone sodium and sulbactam sodium for injection powder-injection is obtained through tamponade, gland and packing processes；The temperature of control packing room
Spend for 18 DEG C of temperature~24 DEG C, humidity≤65%.
Embodiment 3
(1) powder preparation section is mixed：Weigh cefoperazone sodium and sulbactam raw material fine powder is added to the water and fully dissolved
Mixed solution is made, and the mixed solution is added into the scattered mixing of progress in ultrasonic wave dispersing stirrer；Secondly to described mixed
Close in solution and add acetone, proceed the scattered stirring of ultrasonic wave under 0 DEG C of temperature conditions；Then by the mixing after decentralized processing
Solution, which is placed in freeze drying box, carries out frozen dried；Finally by freeze-dried material successively through being once dried in vacuo, crushing and screening, it is secondary true
Empty drying process obtains mixed material；The mixed powder preparation section is operated under laminar flow protection, and a vacuum drying temperature is 45
DEG C, drying time is 70min；The secondary vacuum drying temperature is 30 DEG C, and drying time is 55min.The scattered stirring of ultrasonic wave
The operating parameter of device is：Whipping temp is 10 DEG C, and frequency is 25KHz.The cefoperazone sodium, sulbactam, aqueous solvent and third
The quality proportioning of ketone is：1:1:10:0.3；
(2) soda-lime glass molding injection agent bottle matting：Up-to-standard injection bottle is first being entered into bottleneck using following
Ring water inlet cleaning showers processing, is then carried out in ultrasonic wave cleaning, ultrasonic wave cleaning process, circulating water temperature is using recirculated water
25 DEG C, flow velocity is 1.0~1.5m/s, and ultrasonic frequency is 35kHz；Enter main cleaning track secondly by bottle track is carried, successively
The water for injection that the purified water and hydraulic pressure for using hydraulic pressure to be 0.2Mpa for 0.45Mpa recirculated water, hydraulic pressure are 0.1Mpa is to injection
The inside and outside wall of agent bottle is rinsed；Then dried up using the 0.4Mpa compressed air through 0.22 μm of filter filtration, purification,
Send into sterilizing oven guipure and carry out sterilization treatment, the sterilizing oven mesh belt transmission speed is 20cm/min；Sterilisation process
Include preheating, sterilizing and cooling step successively, the sterilization steps are sterilized using 320 DEG C of circulating air, hot air circulation
Speed is 30m/s, and sterilization time is 8min, finally by the injection bottle feeding packing room after sterilizing；
(3) rubber plug cleaning process：Suction dust removal process is first carried out to butyl rubber plug using vavuum pump, then through Full-automatic glue
Plug cleaning machine cleaned, sterilized, being dried, cool down after it is standby；Full automatic rubber plug cleaning machine handles control parameter：Water for injection
Pressure is 0.2Mpa, and compressed air pressure is 0.25Mpa, vacuum -0.02Mpa, and the water for injection, compressed air are passed through
0.22 μm of filter filtering；
(4) aluminium lid matting：Aluminium-plastic combined cover is placed in full-automatic aluminum cover cleaning machine and is cleaned, sterilized, dried
With it is standby after cooling treatment；Full-automatic aluminum cover cleaning machine handles control parameter：Water for injection pressure is 0.2Mpa, compressed air
Pressure is 0.2Mpa, vacuum -0.02Mpa, and the water for injection, compressed air are filtered through 0.22 μm of filter；Ultrasonic wave
Frequency is 20kHz, and is sprayed in ultrasonic wave cleaning process using water circulation；
(5) aseptic subpackaged process：Mixed material bucket/bag the surface is cleaned using drinking water first, then it is new clean with 0.2%
You go out or 2% lysol carries out spray disinfectant；Then enter sector-style in pass-through box and drench processing 10min, vent wind speed is 35m/s, mistake
Cleansing filter efficiency >=0.6 μm dust >=99.99%；Spray disinfectant is carried out using 1% Peracetic acid into C grades of clean areas；Again
Secondary to enter sector-style in pass-through box and drench processing 10min, vent wind speed is 50m/s, filter depuration efficiency >=0.2 μm dust >=
99.99%, finally enter B grades of clean area material temporary rooms and kept in；It is distributed into according to standard metering into injection bottle mixed
Raw material is closed, cefoperazone sodium and sulbactam sodium for injection powder-injection is obtained through tamponade, gland and packing processes；The temperature of control packing room
Spend for 18 DEG C of temperature~24 DEG C, humidity≤65%.
Embodiment 4
(1) powder preparation section is mixed：Weigh cefoperazone sodium and sulbactam raw material fine powder is added to the water and fully dissolved
Mixed solution is made, and the mixed solution is added into the scattered mixing of progress in ultrasonic wave dispersing stirrer；Secondly to described mixed
Close in solution and add acetone, proceed the scattered stirring of ultrasonic wave under 5 DEG C of temperature conditionss；Then by the mixing after decentralized processing
Solution, which is placed in freeze drying box, carries out frozen dried；Finally by freeze-dried material successively through being once dried in vacuo, crushing and screening, it is secondary true
Empty drying process obtains mixed material；The mixed powder preparation section is operated under laminar flow protection, and a vacuum drying temperature is 40
DEG C, drying time is 60min；The secondary vacuum drying temperature is 25 DEG C, and drying time is 50min.The scattered stirring of ultrasonic wave
The operating parameter of device is：Whipping temp is 15 DEG C, and frequency is 25KHz.The cefoperazone sodium, sulbactam, aqueous solvent and third
The quality proportioning of ketone is：1:1:8:0.2；
(2) soda-lime glass molding injection agent bottle matting：Up-to-standard injection bottle is first being entered into bottleneck using following
Ring water inlet cleaning showers processing, is then carried out in ultrasonic wave cleaning, ultrasonic wave cleaning process, circulating water temperature is using recirculated water
25 DEG C, flow velocity is 1.0~1.5m/s, and ultrasonic frequency is 35kHz；Enter main cleaning track secondly by bottle track is carried, successively
The water for injection that the purified water and hydraulic pressure for using hydraulic pressure to be 0.2Mpa for 0.45Mpa recirculated water, hydraulic pressure are 0.1Mpa is to injection
The inside and outside wall of agent bottle is rinsed；Then dried up using the 0.4Mpa compressed air through 0.22 μm of filter filtration, purification,
Send into sterilizing oven guipure and carry out sterilization treatment, the sterilizing oven mesh belt transmission speed is 20cm/min；Sterilisation process
Include preheating, sterilizing and cooling step successively, the sterilization steps are sterilized using 320 DEG C of circulating air, hot air circulation
Speed is 30m/s, and sterilization time is 8min, finally by the injection bottle feeding packing room after sterilizing；
(3) rubber plug cleaning process：Suction dust removal process is first carried out to butyl rubber plug using vavuum pump, then through Full-automatic glue
Plug cleaning machine cleaned, sterilized, being dried, cool down after it is standby；Full automatic rubber plug cleaning machine handles control parameter：Water for injection
Pressure is 0.2Mpa, and compressed air pressure is 0.25Mpa, vacuum -0.02Mpa, and the water for injection, compressed air are passed through
0.22 μm of filter filtering；
(4) aluminium lid matting：Aluminium-plastic combined cover is placed in full-automatic aluminum cover cleaning machine and is cleaned, sterilized, dried
With it is standby after cooling treatment；Full-automatic aluminum cover cleaning machine handles control parameter：Water for injection pressure is 0.2Mpa, compressed air
Pressure is 0.2Mpa, vacuum -0.02Mpa, and the water for injection, compressed air are filtered through 0.22 μm of filter；Ultrasonic wave
Frequency is 20kHz, and is sprayed in ultrasonic wave cleaning process using water circulation；
(5) aseptic subpackaged process：Mixed material bucket/bag the surface is cleaned using drinking water first, then it is new clean with 0.2%
You go out or 2% lysol carries out spray disinfectant；Then enter sector-style in pass-through box and drench processing 10min, vent wind speed is 35m/s, mistake
Cleansing filter efficiency >=0.6 μm dust >=99.99%；Spray disinfectant is carried out using 1% Peracetic acid into C grades of clean areas；Again
Secondary to enter sector-style in pass-through box and drench processing 10min, vent wind speed is 50m/s, filter depuration efficiency >=0.2 μm dust >=
99.99%, finally enter B grades of clean area material temporary rooms and kept in；It is distributed into according to standard metering into injection bottle mixed
Raw material is closed, cefoperazone sodium and sulbactam sodium for injection powder-injection is obtained through tamponade, gland and packing processes；The temperature of control packing room
Spend for 18 DEG C of temperature~24 DEG C, humidity≤65%.
Embodiment 5
(1) powder preparation section is mixed：Weigh cefoperazone sodium and sulbactam raw material fine powder is added to the water and fully dissolved
Mixed solution is made, and the mixed solution is added into the scattered mixing of progress in ultrasonic wave dispersing stirrer；Secondly to described mixed
Close in solution and add acetone, proceed the scattered stirring of ultrasonic wave under 0 DEG C of temperature conditions；Then by the mixing after decentralized processing
Solution, which is placed in freeze drying box, carries out frozen dried；Finally by freeze-dried material successively through being once dried in vacuo, crushing and screening, it is secondary true
Empty drying process obtains mixed material；The mixed powder preparation section is operated under laminar flow protection, and a vacuum drying temperature is 50
DEG C, drying time is 80min；The secondary vacuum drying temperature is 35 DEG C, and drying time is 60min.The scattered stirring of ultrasonic wave
The operating parameter of device is：Whipping temp is 10 DEG C, and frequency is 25KHz.The cefoperazone sodium, sulbactam, aqueous solvent and third
The quality proportioning of ketone is：1:1:5~10：0.1~0.3；
(2) soda-lime glass molding injection agent bottle matting：Up-to-standard injection bottle is first being entered into bottleneck using following
Ring water inlet cleaning showers processing, is then carried out in ultrasonic wave cleaning, ultrasonic wave cleaning process, circulating water temperature is using recirculated water
25 DEG C, flow velocity is 1.0~1.5m/s, and ultrasonic frequency is 35kHz；Enter main cleaning track secondly by bottle track is carried, successively
The water for injection that the purified water and hydraulic pressure for using hydraulic pressure to be 0.2Mpa for 0.45Mpa recirculated water, hydraulic pressure are 0.1Mpa is to injection
The inside and outside wall of agent bottle is rinsed；Then dried up using the 0.4Mpa compressed air through 0.22 μm of filter filtration, purification,
Send into sterilizing oven guipure and carry out sterilization treatment, the sterilizing oven mesh belt transmission speed is 20cm/min；Sterilisation process
Include preheating, sterilizing and cooling step successively, the sterilization steps are sterilized using 320 DEG C of circulating air, hot air circulation
Speed is 30m/s, and sterilization time is 8min, finally by the injection bottle feeding packing room after sterilizing；
(3) rubber plug cleaning process：Suction dust removal process is first carried out to butyl rubber plug using vavuum pump, then through Full-automatic glue
Plug cleaning machine cleaned, sterilized, being dried, cool down after it is standby；Full automatic rubber plug cleaning machine handles control parameter：Water for injection
Pressure is 0.2Mpa, and compressed air pressure is 0.25Mpa, vacuum -0.02Mpa, and the water for injection, compressed air are passed through
0.22 μm of filter filtering；
(4) aluminium lid matting：Aluminium-plastic combined cover is placed in full-automatic aluminum cover cleaning machine and is cleaned, sterilized, dried
With it is standby after cooling treatment；Full-automatic aluminum cover cleaning machine handles control parameter：Water for injection pressure is 0.2Mpa, compressed air
Pressure is 0.2Mpa, vacuum -0.02Mpa, and the water for injection, compressed air are filtered through 0.22 μm of filter；Ultrasonic wave
Frequency is 20kHz, and is sprayed in ultrasonic wave cleaning process using water circulation；
(5) aseptic subpackaged process：Mixed material bucket/bag the surface is cleaned using drinking water first, then it is new clean with 0.2%
You go out or 2% lysol carries out spray disinfectant；Then enter sector-style in pass-through box and drench processing 10min, vent wind speed is 35m/s, mistake
Cleansing filter efficiency >=0.6 μm dust >=99.99%；Spray disinfectant is carried out using 1% Peracetic acid into C grades of clean areas；Again
Secondary to enter sector-style in pass-through box and drench processing 10min, vent wind speed is 50m/s, filter depuration efficiency >=0.2 μm dust >=
99.99%, finally enter B grades of clean area material temporary rooms and kept in；It is distributed into according to standard metering into injection bottle mixed
Raw material is closed, cefoperazone sodium and sulbactam sodium for injection powder-injection is obtained through tamponade, gland and packing processes；The temperature of control packing room
Spend for 18 DEG C of temperature~24 DEG C, humidity≤65%.
Performance test：
According to Chinese Pharmacopoeia, investigate performance test is directly carried out after prepared by cefoperazone sodium sulbactam sodium powder, 25 respectively
DEG C, under conditions of relative humidity 60% after test 18 months, and under conditions of 40 DEG C of high temperature, relative humidity 75% test 6
Performance test is carried out after individual month, test index includes content1Refer to cefoperazone sodium content, content2Refer to sulbactam content, it is relevant
Material refers to total impurities content.
The embodiment 1~5 of table 1 prepares the performance test results of sample
Above-described embodiment, has been carried out further to the purpose of the present invention, technical scheme and beneficial effect
Describe in detail, should be understood that the embodiment that the foregoing is only the present invention, be not intended to limit the present invention
Protection domain, within the spirit and principles of the invention, any modification, equivalent substitution and improvements done etc. all should be included
Within protection scope of the present invention.
Claims (9)
1. cefoperazone sodium and sulbactam sodium for injection preparation technology, it is characterised in that comprise the following steps：
(1) powder preparation section is mixed：Weigh cefoperazone sodium and sulbactam raw material fine powder is added to the water progress fully dissolving and is made
Mixed solution, and the mixed solution is added into the scattered mixing of progress in ultrasonic wave dispersing stirrer；Secondly it is molten to the mixing
Acetone is added in liquid, proceeds the scattered stirring of ultrasonic wave under 0~5 DEG C of temperature conditions；Then by the mixing after decentralized processing
Solution, which is placed in freeze drying box, carries out frozen dried；Finally by freeze-dried material successively through being once dried in vacuo, crushing and screening, it is secondary true
Empty drying process obtains mixed material；The mixed powder preparation section is operated under laminar flow protection；
(2) soda-lime glass molding injection agent bottle matting：First by up-to-standard injection bottle enter bottleneck using circulate into
Water spray cleaning treatment, then carries out ultrasonic wave cleaning using recirculated water；Enter main cleaning track secondly by bottle track is carried, according to
The water for injection that the secondary purified water and hydraulic pressure for using hydraulic pressure to be 0.2Mpa for 0.45Mpa recirculated water, hydraulic pressure is 0.1Mpa is to note
The inside and outside wall for penetrating agent bottle is rinsed；Then blown using the 0.4Mpa compressed air through 0.22 μm of filter filtration, purification
Dry, feeding sterilizing oven guipure carries out sterilization treatment, finally by the injection bottle feeding packing room after sterilizing；
(3) rubber plug cleaning process：Suction dust removal process is first carried out to butyl rubber plug using vavuum pump, it is then clear through Full automatic rubber plug
Washing machine cleaned, sterilized, being dried, cool down after it is standby；
(4) aluminium lid matting：Aluminium-plastic combined cover is placed in full-automatic aluminum cover cleaning machine cleaned, sterilized, it is dry and cold
But it is standby after handling；
(5) aseptic subpackaged process：Mixed material bucket/bag the surface is cleaned using drinking water first, then uses 0.2% bromogeramine
Or 2% lysol carry out spray disinfectant；Then enter sector-style in pass-through box and drench processing 10min, vent wind speed is 35m/s, filter
Purification efficiency >=0.6 μm dust >=99.99%；Spray disinfectant is carried out using 1% Peracetic acid into C grades of clean areas；Exist again
Pass-through box enters sector-style and drenches processing 10min, and vent wind speed is 50m/s, filter depuration efficiency >=0.2 μm dust >=99.99%,
B grades of clean area material temporary rooms are finally entered to be kept in；Mixed material is distributed into injection bottle according to standard metering, is passed through
Tamponade, gland and packing processes obtain cefoperazone sodium and sulbactam sodium for injection powder-injection；The temperature for controlling to dispense room is temperature
18 DEG C~24 DEG C, humidity≤65%.
2. cefoperazone sodium and sulbactam sodium for injection preparation technology according to claim 1, it is characterised in that the mixed powder
In process, cefoperazone sodium, sulbactam, the quality proportioning of aqueous solvent and acetone are：1:1:5~10：0.1~0.3.
3. cefoperazone sodium and sulbactam sodium for injection preparation technology according to claim 1, it is characterised in that the mixed powder
In process, the operating parameter of ultrasonic wave dispersing stirrer is：Whipping temp is 10~15 DEG C, and frequency is 25KHz.
4. cefoperazone sodium and sulbactam sodium for injection preparation technology according to claim 1, it is characterised in that the mixed powder
In process, freeze temperature is -35~-45 DEG C, and freeze-drying time is 3~5h.
5. cefoperazone sodium and sulbactam sodium for injection preparation technology according to claim 1, it is characterised in that the mixed powder
In process, a vacuum drying temperature is 40~50 DEG C, and drying time is 60~80min；The secondary vacuum drying temperature is
25~35 DEG C, drying time is 50~60min.
6. cefoperazone sodium and sulbactam sodium for injection preparation technology according to claim 1, it is characterised in that the process
(2) in, in ultrasonic wave cleaning process, circulating water temperature is 25 DEG C, and flow velocity is 1.0~1.5m/s, and ultrasonic frequency is 35kHz.
7. cefoperazone sodium and sulbactam sodium for injection preparation technology according to claim 1, it is characterised in that the process
(2) in, the sterilizing oven mesh belt transmission speed is 20cm/min；Sterilisation process includes preheating, sterilizing and cooled down successively
Step, the sterilization steps are sterilized using 320 DEG C of circulating air, and hot air circulation speed is 30m/s, and sterilization time is
8min。
8. cefoperazone sodium and sulbactam sodium for injection preparation technology according to claim 1, it is characterised in that the process
(3) in, Full automatic rubber plug cleaning machine processing control parameter is：Water for injection pressure is 0.2Mpa, and compressed air pressure is
0.25Mpa, vacuum -0.02Mpa, the water for injection, compressed air are filtered through 0.22 μm of filter.
9. cefoperazone sodium and sulbactam sodium for injection preparation technology according to claim 1, it is characterised in that the process
(4) in, full-automatic aluminum cover cleaning machine processing control parameter is：Water for injection pressure is 0.2Mpa, and compressed air pressure is
0.2Mpa, vacuum -0.02Mpa, the water for injection, compressed air are filtered through 0.22 μm of filter；Ultrasonic frequency is
20kHz, and sprayed in ultrasonic wave cleaning process using water circulation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710284552.3A CN107080750A (en) | 2017-04-26 | 2017-04-26 | Cefoperazone sodium and sulbactam sodium for injection preparation technology |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710284552.3A CN107080750A (en) | 2017-04-26 | 2017-04-26 | Cefoperazone sodium and sulbactam sodium for injection preparation technology |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107080750A true CN107080750A (en) | 2017-08-22 |
Family
ID=59612537
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710284552.3A Pending CN107080750A (en) | 2017-04-26 | 2017-04-26 | Cefoperazone sodium and sulbactam sodium for injection preparation technology |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107080750A (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102512374A (en) * | 2011-12-16 | 2012-06-27 | 苏州二叶制药有限公司 | Preparation process for cefoperazone sodium and tazobactam sodium for injection |
| CN104644640A (en) * | 2015-01-27 | 2015-05-27 | 华北制药河北华民药业有限责任公司 | Preparation method of cefoperazone sodium and sulbactam sodium powder injection for injection |
| CN104844624A (en) * | 2015-04-14 | 2015-08-19 | 山东罗欣药业集团股份有限公司 | Cefoperazone sodium-sulbactam sodium eutectic crystal and composition, and preparation methods thereof |
| CN106309448A (en) * | 2016-08-24 | 2017-01-11 | 南昌立健药业有限公司 | Novel cefoperazone sodium and sulbactam sodium pharmaceutical composition for injection |
-
2017
- 2017-04-26 CN CN201710284552.3A patent/CN107080750A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102512374A (en) * | 2011-12-16 | 2012-06-27 | 苏州二叶制药有限公司 | Preparation process for cefoperazone sodium and tazobactam sodium for injection |
| CN104644640A (en) * | 2015-01-27 | 2015-05-27 | 华北制药河北华民药业有限责任公司 | Preparation method of cefoperazone sodium and sulbactam sodium powder injection for injection |
| CN104844624A (en) * | 2015-04-14 | 2015-08-19 | 山东罗欣药业集团股份有限公司 | Cefoperazone sodium-sulbactam sodium eutectic crystal and composition, and preparation methods thereof |
| CN106309448A (en) * | 2016-08-24 | 2017-01-11 | 南昌立健药业有限公司 | Novel cefoperazone sodium and sulbactam sodium pharmaceutical composition for injection |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105968489B (en) | A kind of preparation method of polyethylene antibiotic packing film | |
| CN105198021A (en) | Chemical wastewater treatment agent and preparation method thereof | |
| CN104623719B (en) | A kind of aquagel dressing and preparation method thereof | |
| CN107049958A (en) | The preparation technology of cefotaxime sodium for injection powder-injection | |
| CN108059741A (en) | Orthopedic medical gloves and preparation method thereof | |
| CN107080750A (en) | Cefoperazone sodium and sulbactam sodium for injection preparation technology | |
| CN111514340A (en) | Medical instrument is with degassing unit that disinfects | |
| CN102188723A (en) | Cleaning-free medical ultrasonic couplant, and preparation method thereof | |
| CN211884674U (en) | Through type article disinfection device | |
| CN204446611U (en) | Powder screening homogenizing apparatus in a kind of cefixime dispersible tablet preparation technology | |
| CN107858827A (en) | A kind of preparation method of antibacterial haze screen material | |
| CN106390841A (en) | Nutrient solution raw material anti-pollution mixing equipment used for biological medicine | |
| CN208434653U (en) | A kind of bird's nest Electric liquid processing device | |
| CN107095851A (en) | The preparation technology of Ceftezole sodium used for injection sterile powder injection | |
| CN208065489U (en) | A kind of novel bulk pharmaceutical chemicals sterile processing systems | |
| CN103432121A (en) | Preparation method of amoxicillim sodium and sulbactam sodium for injection | |
| CN103191061B (en) | Cefbuperazone sodium composition powder for injection and preparation method thereof | |
| CN207187763U (en) | A kind of manufacturing equipment of injection ceftiofur sodium | |
| CN107875407A (en) | A kind of new bulk drug sterile processing systems | |
| WO2023272765A1 (en) | Three-dimensional electrostatic flocking device for waste poultry feathers | |
| CN210904202U (en) | Sterilizing device for medical instruments | |
| CN107412167A (en) | The production method of ceftriaxone sodium for injection | |
| CN111423726A (en) | Preparation method of high-elasticity medical high polymer material | |
| CN101791415A (en) | Steam sterilizing device of rare precious medicinal material | |
| CN207811753U (en) | A kind of personalized combination probiotics aqueous preparing and packaging device |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20170822 |
|
| RJ01 | Rejection of invention patent application after publication |