CN110433140A - A kind of production technology of mezlocillin for injection sulbactam powder-injection - Google Patents
A kind of production technology of mezlocillin for injection sulbactam powder-injection Download PDFInfo
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- CN110433140A CN110433140A CN201910563221.2A CN201910563221A CN110433140A CN 110433140 A CN110433140 A CN 110433140A CN 201910563221 A CN201910563221 A CN 201910563221A CN 110433140 A CN110433140 A CN 110433140A
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- mezlocillin
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- 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
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- 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
- A61K31/431—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 containing further heterocyclic rings, e.g. ticarcillin, azlocillin, oxacillin
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- 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
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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Abstract
The present invention discloses a kind of production technology of mezlocillin for injection sulbactam powder-injection, including prepares cillin bottle and rubber plug, mixing, dispense, roll lid, lamp inspection and packaging and other steps.Wherein, it is filled with inert gas into cillin bottle in packing, to replace the air and moisture in bottle, the mezlocillin for injection sulbactam powder-injection degradation in bottle can be blocked；Any auxiliary material is not added, reduces impurity, improves content of drug and purity, reduces adverse reaction；And stable for extended periods of time.Damp-proof treatment is also added after rolling cover process, increased sealing wax and wraps up the technique of tinfoil paper to guarantee the air-tightness of Packaging Bottle, is put into desiccant in packing box, case, is further decreased the risk made moist in the storage in product later period.The stability that Variable Control link even more fundamentally ensure that the quality of product and store for a long time.
Description
Technical field
The present invention relates to a kind of production technologies of mezlocillin for injection sulbactam powder-injection, belong to medical science neck
Domain.
Technical background
Mezlocillin for injection sulbactam is novel wide by one kind that mezlocillin sodium and sulbactam proportion form
Compose compound antibiotic.Wherein, mezlocillin belongs to penicillins broad-spectrum antibiotic, the main synthesis by interference bacteria cell wall
And play bactericidal effect；Although Sulbactam is in addition to having antibacterial activity to Neisseriaceae and acinetobacter calcoaceticus, to other bacteriums without antibacterial
Activity, but have to the important beta-lactamases of majority generated by beta-lactam antibiotic antibody-resistant bacterium can not for Sulbactam
The inhibiting effect of inverse property, therefore Sulbactam can prevent destruction of the drug-fast bacteria to penicillins and cephalosporins, to blueness
Mycin class and cephalosporins have apparent synergistic effect.Domestic mezlocillin for injection Sulbactam at present
Sodium compound preparation is made of mezlocillin sodium and sulbactam according to the proportion packing of 4:1, which belongs to existing country's mark
Quasi- kind, it is external temporarily without listing, it is domestic most to be listed earlier than 2003, it is primarily adapted for use in caused by enzyme-resistant bacteria, under severe
Column infectious diseases, including infection in respiratory system, urogenital infections, abdominal cavity infection, skin and soft tissue infection, pelvic cavity
Infection, severe systemic infection etc..
In the prior art, the production method of mezlocillin sodium includes freeze-drying and solvent crystallization, obtained product
The generally unformed mezlocillin sodium without the crystallization water, but use the mezlocillin sodium hygroscopicity of prior art preparation very
By force, therefore the stability of product is poor.It is easypro that Chinese patent literature CN103012430B discloses a kind of mezlocillin for injection
Batan sodium compound medicament composition includes a kind of mezlocillin sodium entity chemical combination for having two crystallization water forms in the composition
Object makes drug keep high stability it is said that the compound is not easy the moisture absorption.However, in reagent application, due to the technique of production
Be difficult to total number removal packing container in moisture and oxygen, the later period storage in, drug still be easy dampness, cause drug for a long time
After preservation, still can moisture absorption oxidation, destroy the drug effect of drug.Moreover, existing disclosed mezlocillin sodium and sulbactam sodium drug, is
Guarantee its long-term stability, there is addition auxiliary material, such as Chinese patent CN101703506A discloses a kind of mezlocillin sodium
Sulbactam sodium medicine composition suspension injection powder and its application, the suspension powder needle have used 5 kinds of auxiliary materials；Chinese patent
CN105963263B discloses a kind of mezlocillin for injection sulbactam compound medicament composition, and the composition also contains anti-
Rotten agent sodium benzoate, this is not only easy to make between main ingredient and auxiliary material, and there are consistency problems, but also the addition of auxiliary material is easy to cause medicine
Product impurity increases, it is often more important that improves the risk that patient uses.It is therefore desirable to start with improvement from the technique of production, not
In the case where adding any auxiliary material, the stability of drug can be also kept for a long time.
Summary of the invention
To solve above-mentioned problems of the prior art, the present invention starts with from the technique of production, removes in drug
Air and moisture, and effectively avoid drug in long-term preservation from relaxing without making moist to improve mezlocillin sodium by improving packaging
The stability of Batan sodium drug.Specific technical solution is as follows:
A kind of production technology of mezlocillin for injection sulbactam powder-injection, wherein free mezlocillin and Shu Ba
Smooth mass ratio is 4:1, comprising the following steps:
Cillin bottle prepares: by the packing put in order with cillin bottle after supersonic cleaning machine washs, then successively with purified water and
After water for injection flushing and air blow leaching, it is sent into hot air circulation tunnel, sterilize 5~10min under the conditions of 350 DEG C, is subsequently cooled to
45 DEG C or less spare；
Rubber plug prepares: rubber plug matched with cillin bottle in step (1) being sucked washing in cleaning barrel by vacuum intake valve
90min, be then cooled to after steam sterilizing 15min or more, then vacuum dried 120min at 121 DEG C 45 DEG C or less it is spare；
Sterile mixing: the ratio with mass ratio for 4:1 weighs mezlocillin sodium and sulbactam sodium, sterilizes respectively through ultraviolet lamp
After 30min, then cleanliness be B grades of A grades of parts, 25 DEG C of temperature or less, relative humidity in 50% environment below, successively to
Mezlocillin sodium and sulbactam are added in batch mixer, and with 30r/min revolving speed mixing 120min, obtains Mei Luoxi to be packed
Woods sodium and sulbactam sodium (4:1) middle material；
It is aseptic subpackaged: to be equally B grades of A grades of parts, 25 DEG C of temperature or less, relative humidity in 50% ring below in cleanliness
In border, into cillin bottle described in step (1), it is filled with inert gas, further according to prescription specification with screw rod packing head by step (3)
Mezlocillin sodium and sulbactam sodium (4:1) middle material to be packed of middle preparation is fitted into cillin bottle, as injection mezlocillin
Then sodium and sulbactam sodium powder-injection presses rubber plug described in upper step (2) with corking machine again；
It rolls lid lamp inspection: the cillin bottle of mezlocillin for injection sulbactam powder-injection will be housed described in step (4)
It is sent into capping machine and presses upper sterile aluminium lid, be then fed into visible foreign matters and product appearance that detection workshop carries out range estimation lamp inspection product；
Be packed and stored: the drug that will be finished through lamp inspection, each cillin bottle aluminium cover port apply one layer of sealing wax, and one by one with aluminium foil
It is reloaded into packing box after cillin bottle is wrapped up, and is furnished with cardboard shape desiccant in packing box, with dry in keeping box；Then exist
Loading is placed with packaging and warehousing in drug/food special drying agent packing case.
As of the invention one preferred technical solution, in step (4), the inert gas being filled with is preferably
99.99% nitrogen.
As of the invention one preferred technical solution, in step (5), the aluminium lid is stainless using preceding needing line to be put into
In steel sieve, using 120 DEG C, sterilize 2 hours, and the aluminium lid after disinfection uses no more than 48 hours.
As of the invention one preferred technical solution, in step (6), the sealing wax is preferably edible wax；It is described
Cardboard shape desiccant be the production of upper sea-freight suitable desiccant Co., Ltd silica-gel desiccant.
The production technology of the mezlocillin for injection sulbactam powder-injection above-mentioned stated further includes through entire production
The Variable Control link of technique, the Variable Control link includes detecting to cillin bottle and rubber plug cleanliness, after sterile mixing
The quality inspection of mezlocillin sodium and sulbactam sodium (4:1) middle material to be packed, Variable Control during dispensing and to most
Whole mezlocillin for injection sulbactam powder-injection finished product sampling observation.
The cillin bottle cleanliness detection are as follows: sampled in the cillin bottle after cleaning, at interval of 20min sampling 10
Branch is perfused qualified water for injection, observation is carried out in accordance with regulations under lamp inspection instrument, rejects the antibiotic cillin bottle for having visible foreign matters.
The rubber plug cleanliness detection are as follows: the triangular flask having first with three with regard to rubber plug takes rubber plug finally to elute respectively
Each 500ml of water, has seen whether foreign matter under clarity detecting apparatus, then takes rubber plug after sterilization, do respectively particulate matter,
Detection of bacterial endotoxin and sterility test.
The quality inspection of described mezlocillin sodium and sulbactam sodium (4:1) middle material to be packed are as follows: take mixed wait divide
Mezlocillin sodium and sulbactam sodium (4:1) middle material sample of dress, send quality department to chemically examine, and measures content mezlocillin and Sulbactam
The case where content and ratio, moisture, visible foreign matters, clarity and color and bacterial endotoxin.
Variable Control during the packing includes foreign matter control and Packing Unit control, the foreign matter control are as follows: dividing
Every 20min is sampled 1 time during dress, takes 5 every time, and every batch of samples 3 times, amounts to 15, checks respectively for its visible foreign matters；It is described
Packing Unit control are as follows: it is primary every sampling in 30 minutes during packing, 5 are taken every time, every batch of samples 3 times, 15 are amounted to, point
Its loading amount is not measured.
As of the invention one preferred technical solution, the prescription specification of the packing includes 1.25g
(C21H25N5O8S21.0g and C8H11NO5S 0.25g) and 2.5g (C21H25N5O8S22.0g and C8H11NO5S 0.5g), packing
Average loading amount and every bottle of content uniformity control in ± 5% range.
The beneficial effects of the present invention are:
For compared with the prior art, present invention process has following advantage:
Present invention process is filled with inert gas into cillin bottle in packing, can be with to replace the air and moisture in bottle
The mezlocillin for injection sulbactam powder-injection degradation in bottle is blocked, any auxiliary material is not added, reduces impurity, improve drug
Content and purity reduce adverse reaction, reach long-term corrosion-resistant purpose.Damp-proof treatment is also added after rolling cover process, is increased
Sealing wax guarantees the air-tightness of Packaging Bottle with the technique for wrapping up tinfoil paper, is put into desiccant in packing box, case, further decreases production
The risk made moist in the storage in product later period.In addition, the Variable Control link through entire process flow even more fundamentally guarantees
The quality of product and the stability stored for a long time, experimental result also indicate that, the injection mezlocillin of present invention process production
Sodium and sulbactam sodium powder-injection has brilliant stability.
Detailed description of the invention
Fig. 1 is the flow chart of the production technology of mezlocillin for injection sulbactam powder-injection of the present invention.
Specific embodiment
To make the object, technical solutions and advantages of the present invention clearer, below in conjunction with embodiment, to skill of the invention
Art scheme is clearly and completely described, the entire preparation process of mezlocillin for injection sulbactam powder-injection of the present invention
Flow chart, referring to Fig.1.
Embodiment 1: prepare the cillin bottle of packing
Preparation before carrying out wash bottle first: by workspace, cillin bottle cleaning machine and tunnel oven are clear clean and raw
Any material unrelated with operation is not present in the scene of production, and file is used in residue and record this batch of production of verification；It checks filtered
Purified water, water for injection visible foreign matters；Purified water is opened, water for injection compresses air valve, checks whether each pressure meets technique
It is required that: purifying water pressure >=0.2Mpa, water for injection pressure >=0.2Mpa, compressed air pressure is between >=0.3Mpa；Manage bottle
It is washed with stainless steel disc with purified water spare.It opens each blower of tunnel oven and exhaust blower opens heating power supply, make to sterilize
Temperature rises to 250 DEG C or more and starts to walk mesh belt, and wash bottle can be started by rising to 350 DEG C or more to temperature.
Then carry out the processing work of cillin bottle: the cillin bottle managed passes through sub-bottle area, is slightly washed by ultrasound, circulating water to flush
Wash, compressed air function blows leaching, purified water rinse, compressed air function blow leaching, water for injection rinse, compressed air blow leaching, be admitted to
Tunnel, using 350 DEG C, 5 minutes or more, bottle outlet after sterilizing, it is desirable that bottle outlet temperature≤45 DEG C.The bottle to have sterilized is from tunnel
Track under 100 grades of outlet is sent into bottle placer track, and standard is that bottle is inverted to residual water in 15 seconds to be no more than 1 drop.It checks: wash bottle
It takes clean empty bottled water to check visible foreign matters in the process, starts, it is intermediate, it is respectively checked before terminating primary.The measurement of wash bottle cleanliness:
It is sampled in antibiotic cillin bottle after cleaning, sampled 10 at interval of 20 minutes, qualified water for injection is perfused, in lamp inspection
Observation is carried out in accordance with regulations under instrument, rejects the antibiotic cillin bottle for there are visible foreign matters.Work of clearing out a gathering place finally also is carried out, removing is washed
Broken glass in bottle machine removes clean, cleaning ground and other sundries.
Embodiment 2: prepare rubber plug
Preparation before rubber plug washing: verification production file, production status mark and record are removed unrelated with production
Article, check that slurry is normal, and replace overdue filter；Check rubber plug model, quantity, lot number, manufacturer with
And whether there is inspection certificate, while checking whether rubber plug has phenomena such as breakage, became uneven；Check the cleaning and drying of equipment
Degree, the projects such as water for injection visible foreign matters；Check whether rubber plug machine feeding gate and discharge door shut；Open water for injection, true
Empty pump, steam valve, compressed air valve, check whether each pressure and vacuum degree meet technique requirement.It is required that injection hydraulic pressure
Power >=0.2Mpa.
Rubber plug washing: charging vacuum intake valve is opened, is controlled by photoelectricity stream controller, rubber plug is sucked in cleaning barrel, so
Charging lid is closed afterwards；Rubber plug passes through spray 3 minutes, steam mixing rinses 12 minutes, rinsing 5 minutes 1 time, steam sterilizing F0
>=15, it is dried in vacuo 2.5 hours, is cooled to 45 DEG C hereinafter, taking out from automatic discharging mouth.Unused plug had been cleaned by spray 3
Minute, mixing rinsing 12 minutes, rinsing 5 minutes 1 time, silication 10 minutes (3~5ml/ ten thousand), vacuum drying 2.5 hours, it is cold
But to 45 DEG C hereinafter, being taken out from automatic discharging mouth.After rinsing, three tool plugs three of final washing water after rubber plug has rinsed
Angle bottle, takes rubber plug each 500ml of final washing water respectively, observes under clarity detecting apparatus.Pure steam sterilizing uses F0Value >=15
It controls or 121 DEG C sterilizes 30 minutes；When box temperature degree up to 45 DEG C with bottom discharge.Rubber plug sterilizing after, sampling do respectively particulate matter,
Detection of bacterial endotoxin and sterility test.Rubber plug is stored under 100 grades after sterilizing, and Ying is used in 24 hours.If ahead of time prepare,
It is then placed in machine, is taken out to the used time, and carry out the state mark of content in equipment.
Embodiment 3: mezlocillin for injection sulbactam powder-injection is prepared, steps are as follows:
Water processed first, including water for injection, purified water, sterilized water for injection and water for pharmaceutical purposes.Drinking water is through quartz sand mistake
Filter and active carbon be filtered to remove organic matter and particle in water, through two-pass reverse osmosis remove 90%~95% monovalent ion and
98%~99% divalent ion, while the obtained purified water such as remove organic fine particles, colloidal substance and microbial virus, with purifying
Water is raw material by the obtained water for injection of multi-effect water distillator distillation, is made pure by pure steam generator using purified water as raw material
Steam.Purified water is water of the drinking water through hyoscine made from ion exchange, reverse osmosis or other proper methods, without any attached
Add agent；Water for injection is purified water through distilling resulting water；Sterilized water for injection is the sterilized gained of water for injection.
Then it carries out original powder transmitting: after original powder bucket outer wall is first cleaned with water for injection, then being wiped clean with 75% alcohol, be put into
Self-cleaning passing cabinet ultraviolet radiator is irradiated 30 minutes, and blower blows leaching 30 minutes, and incoming outer disinfection room is put with 75% wipes of alcohol outer wall
Enter self-cleaning passing cabinet ultraviolet radiator to irradiate 30 minutes, blower blows leaching 30 minutes, is passed to desinfection chamber.Desinfection chamber cleanliness is B grades of offices
Portion A grades, 25 DEG C of temperature or less, relative humidity 50% hereinafter, press recipe quantity weighing, weighing pronucleus to the raw material name of an article, specification, batch
Number, the information such as factory and quantity.Raw material weighing calculates, weighs and feed intake and answer double review, and balance, platform scale use every time should school
Just, the load weighted material of every batch of moves to spare between mixing.
Finally enter sterile compounding process: by the quantity calculated cleanliness be B grades of A grades of parts, 25 DEG C of temperature or less,
Mezlocillin sodium and sulbactam is successively added in 50% environment below in relative humidity into batch mixer, pays attention to every time mixed
Doses is no more than the 1/3 of batch mixer volume, 5~70Kg of mixing range.Batch mixer is opened to divide by the revolving speed mixing 120 set
Clock takes out mixed powder barrelling sealing, weighing, and samples and quality department is sent to chemically examine after shutdown, measure content mezlocillin and Sulbactam
The case where content and ratio, moisture, visible foreign matters, clarity and color and bacterial endotoxin, as shown in table 1.
1. mixing quality result of laboratory test of table
Embodiment 4: mezlocillin for injection sulbactam powder-injection is aseptic subpackaged
Notice computer room first opens liquid nitrogen pump, and the rubber plug that embodiment 2 is prepared is added into racking machine oscillator to be made to vibrate
Rubber plug is no more than 1/3 height in device, should at least be paved with bottom, adjusts contact voltage regulator, rubber plug is made to be arranged in correct position, enters
In rubber plug feeder channel.Vial after the sterilizing that embodiment 1 is prepared is through visually inspecting, after dirty bottle, broken bottle are picked, transmission
Then mini-roundabout before to racking machine is separated by packing disk to screw rod packing head, be equally B grades of A grades of parts, temperature in cleanliness
25 DEG C of degree or less, relative humidity after being filled with 99.99% nitrogen into bottle, are reloaded into embodiment 3 in 50% environment below
Prepared mezlocillin sodium and sulbactam sodium mixed powder.Glass bottle after dress powder is sent by packing disk to tamponade head again, pressure
Top cement plug.Pay attention to needing to carry out Variable Control, including foreign matter control and Packing Unit control, the foreign matter control during packing are as follows:
It samples 1 time within every 20 minutes during packing, takes 5 every time, every batch of samples 3 times, amounts to 15, it is visible different to check respectively for its
Object；The Packing Unit control are as follows: it is primary every sampling in 30 minutes during packing, 5 are taken every time, and every batch of samples 3 times, amounts to
15, its loading amount is measured respectively.The prescription specification of the packing includes 1.25g (C21H25N5O8S21.0g and C8H11NO5S
0.25g) and 2.5g (C21H25N5O8S22.0g and C8H11NO5S 0.5g), the average loading amount and every bottle of content uniformity of packing
Control is in ± 5% range.
Embodiment 5: lamp inspection packaging
The mezlocillin for injection sulbactam powder-injection dispensed in embodiment 4 feeding is rolled into lid process, passes through pressure
Lid machine compresses aluminium lid, and the aluminium lid using 120 DEG C, is sterilized 2 hours, and after disinfection using preceding needing line to be put into stainless steel sieve
Aluminium lid use no more than 48 hours.Then lamp inspection, the color and appearance of visual inspection product, stringent control gate of the quality monitoring are carried out respectively.
Then one layer of edible wax is coated to guarantee the leakproofness of cillin bottle in aluminium lid sealing part, and labelled, then one by one with tinfoil paper packet
It includes cillin bottle to be fitted into packing box, while being equipped with corresponding specification and exterior and interior packing box, and date of manufacture and phase are indicated in coding
Mark is closed, is provided with the dedicated desiccant of drug in packing box, case, is wherein the upper suitable desiccant Co., Ltd of sea-freight in packing case
The cardboard shape silica-gel desiccant of production.Last sampling observation is finally also carried out to finished product, could be put in storage after qualified, it is entire raw
It is as shown in Figure 1 to produce process.
Embodiment 6: mezlocillin for injection sulbactam powder-injection Detection of Stability
The mezlocillin for injection sulbactam powder-injection of Example 1-5 preparation is placed in merging 25 ± 2 DEG C of room temperature, phase
It under the conditions of humidity RH60% ± 10%, places 24 months, with 3rd month, 6 months, 9 months, 12 months, 18 during this
The moon, 24 the end of month samplings are primary, are detected by stability high spot reviews project, compared with 0 month.As a result as follows:
2. mezlocillin for injection sulbactam powder-injection Detection of Stability of table
As can be seen from Table 2, the mezlocillin for injection sulbactam powder-injection of present invention process production is normal
Under storage condition, have good stability.
It is obvious to a person skilled in the art that invention is not limited to the details of the above exemplary embodiments, Er Qie
In the case where without departing substantially from spirit or essential attributes of the invention, the present invention can be realized in other specific forms.Therefore, no matter
From the point of view of which point, the present embodiments are to be considered as illustrative and not restrictive.Although in addition, it should be understood that originally
Specification is described in terms of embodiments, but only includes not one technical solution, and this narrating mode of specification is only
It is only for clarity that the skilled in the art should refer to the specification as a whole, the technical solution in embodiment can also
To be properly combined, form other embodiments that can be understood by those skilled in the art.
Claims (10)
1. a kind of production technology of mezlocillin for injection sulbactam powder-injection, wherein free mezlocillin and Sulbactam
Mass ratio is 4:1, it is characterised in that: the following steps are included:
Cillin bottle prepares: by the packing put in order with cillin bottle after supersonic cleaning machine washs, then successively using purified water and injection
It is rinsed with water after blowing leaching with air, is sent into hot air circulation tunnel, sterilize 5~10min under the conditions of 350 DEG C, is subsequently cooled to 45 DEG C
It is spare below；
Rubber plug prepares: rubber plug matched with cillin bottle in step (1) being sucked washing in cleaning barrel by vacuum intake valve
90min, be then cooled to after steam sterilizing 15min or more, then vacuum dried 120min at 121 DEG C 45 DEG C or less it is spare；
Sterile mixing: the ratio with mass ratio for 4:1 weighs mezlocillin sodium and sulbactam, sterilizes respectively through ultraviolet lamp
After 30min, then cleanliness be B grades of A grades of parts, 25 DEG C of temperature or less, relative humidity in 50% environment below, successively to
Mezlocillin sodium and sulbactam are added in batch mixer, and with 30r/min revolving speed mixing 120min, obtains Mei Luoxi to be packed
Woods sodium and sulbactam sodium (4:1) middle material；
It is aseptic subpackaged: it is equally B grades of A grades of parts, 25 DEG C of temperature or less, relative humidity in 50% environment below in cleanliness,
Into cillin bottle described in step (1), it is filled with inert gas, will be made in step (3) further according to prescription specification screw rod packing head
Standby mezlocillin sodium and sulbactam sodium (4:1) middle material to be packed is fitted into cillin bottle, and as mezlocillin for injection relaxes
Then Batan sodium injection presses rubber plug described in upper step (2) with corking machine again；
It rolls lid lamp inspection: the cillin bottle that mezlocillin for injection sulbactam powder-injection is housed described in step (4) is sent into
Capping machine presses upper sterile aluminium lid, is then fed into visible foreign matters and product appearance that detection workshop carries out range estimation lamp inspection product；
Be packed and stored: the drug that will be finished through lamp inspection, each cillin bottle aluminium cover port apply one layer of sealing wax, and one by one will be western with aluminium foil
It is reloaded into packing box after woods bottle package, and is furnished with cardboard shape desiccant in packing box, with dry in keeping box；Then it is being packed into
It is placed with packaging and warehousing in drug/food special drying agent packing case.
2. the production technology of mezlocillin for injection sulbactam powder-injection according to claim 1, it is characterised in that:
In step (4), the inert gas being filled with is nitrogen.
3. the production technology of mezlocillin for injection sulbactam powder-injection according to claim 1, it is characterised in that:
In step (5), the aluminium lid using 120 DEG C, is sterilized 2 hours, and the aluminium lid after disinfection using preceding needing line to be put into stainless steel sieve
It uses no more than 48 hours.
4. the production technology of mezlocillin for injection sulbactam powder-injection according to claim 1, it is characterised in that:
In step (6), the sealing wax is edible wax, and the cardboard shape desiccant is the silica gel of the suitable desiccant Co., Ltd production of upper sea-freight
Desiccant.
5. the production technology of mezlocillin for injection sulbactam powder-injection according to claim 1, it is characterised in that:
It further include the Variable Control link through entire production technology, the Variable Control link includes to cillin bottle and rubber plug cleanliness
It detects, the quality inspection of mezlocillin sodium and sulbactam sodium (4:1) middle material to be packed after sterile mixing, during dispensing
Variable Control and final mezlocillin for injection sulbactam powder-injection finished product is inspected by random samples.
6. the production technology of mezlocillin for injection sulbactam powder-injection according to claim 6, it is characterised in that:
The cillin bottle cleanliness detection are as follows: sampled in the cillin bottle after cleaning, sample 10 at interval of 20min, qualified note is perfused
It penetrates and uses water, observation is carried out in accordance with regulations under lamp inspection instrument, reject the antibiotic cillin bottle for having visible foreign matters.
7. the production technology of mezlocillin for injection sulbactam powder-injection according to claim 6, it is characterised in that:
The rubber plug cleanliness detection are as follows: first with three triangular flasks with rubber plug, rubber plug each 500ml of final washing water is taken respectively,
Foreign matter is seen whether under clarity detecting apparatus, the rubber plug after then taking sterilizing again does particulate matter, bacterium endogenous toxic material respectively
Element detection and sterility test.
8. the production technology of mezlocillin for injection sulbactam powder-injection according to claim 6, it is characterised in that:
The quality inspection of described mezlocillin sodium and sulbactam sodium (4:1) middle material to be packed are as follows: take mixed Mei Luo to be packed
XiLin sodium and sulbactam sodium (4:1) middle material sample, send quality department to chemically examine, and measures the content and ratio of content mezlocillin and Sulbactam
The case where example, moisture, visible foreign matters, clarity and color and bacterial endotoxin.
9. the production technology of mezlocillin for injection sulbactam powder-injection according to claim 6, it is characterised in that:
Variable Control during the packing includes foreign matter control and Packing Unit control, the foreign matter control are as follows: during packing
Every 20min is sampled 1 time, takes 5 every time, and every batch of samples 3 times, amounts to 15, checks respectively for its visible foreign matters；The Packing Unit control
It is made as: it is primary every 30min sampling during packing, 5 are taken every time, and every batch of samples 3 times, amounts to 15, measures it respectively
Loading amount.
10. according to claim 1 or the production technology of mezlocillin for injection sulbactam powder-injection described in 9, feature
Be: the prescription specification includes 1.25g (C21H25N5O8S21.0g and C8H11NO5S 0.25g) and 2.5g(C21H25N5O8S2
2.0g and C8H11NO5S 0.5g), the content difference is in ± 5% range.
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Application publication date: 20191112 |