CN107485563A - Preparing device of naloxone hydrochloride injection and preparation method thereof - Google Patents
Preparing device of naloxone hydrochloride injection and preparation method thereof Download PDFInfo
- Publication number
- CN107485563A CN107485563A CN201710676349.0A CN201710676349A CN107485563A CN 107485563 A CN107485563 A CN 107485563A CN 201710676349 A CN201710676349 A CN 201710676349A CN 107485563 A CN107485563 A CN 107485563A
- Authority
- CN
- China
- Prior art keywords
- naloxone hydrochloride
- tank body
- hydrochloride injection
- injection
- lower tank
- 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.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- 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
- A61K9/08—Solutions
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0053—Details of the reactor
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0053—Details of the reactor
- B01J19/0066—Stirrers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/18—Stationary reactors having moving elements inside
- B01J19/1862—Stationary reactors having moving elements inside placed in series
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dermatology (AREA)
- Emergency Medicine (AREA)
- Inorganic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a kind of preparing device of naloxone hydrochloride injection and preparation method thereof, it is included in the upper tank body of preparing device and adds calibrated shot water, sodium chloride and naloxone hydrochloride, and it is passed through nitrogen, mixing obtains mixed liquor, then natrium adetate regulation pH value is added, through the first membrane filtration in the middle part of preparing device to lower tank；A certain amount of water for injection is added in lower tank, and is stirred in the case where being passed through nitrogen, and pH value is adjusted with hydrochloric acid solution；Visible foreign matters inspection, and the nitrogen charging embedding after qualified are most carried out after the second membrane filtration of lower tank bottom afterwards, sterilizing, produces naloxone hydrochloride injection.It is not added with auxiliary material, the purity and safety in utilization of parenteral solution made of guarantee, and preparation method is simple and easy, effectively reduces preparation cost.A kind of preparing device for preparing naloxone hydrochloride injection is provided simultaneously, the more exchange device in the preparation process of naloxone hydrochloride injection is avoided, improves drug quality, ensure that drug safety.
Description
Technical field
The present invention relates to medical processing technique field, the preparing device and its system of more particularly to a kind of naloxone hydrochloride injection
Preparation Method.
Background technology
The Main Ingredients and Appearance of naloxone hydrochloride injection is naloxone hydrochloride, and its chemical name is：17- pi-allyls -4,5 α-ring
Epoxide -3,14- dihydroxy morphinan-6-ones hydrochloride dihydrate, indication are opioid recdptor antagonistic.Be mainly used in Ah
Opiates combined anesthesia medicine is postoperative, the respiration inhibition of such drug-induced of antagonism, promotes emergence, opioid drug mistake
Amount, respiration inhibition caused by opioid drug, rescue acute alcoholism and acute opioid drug are reversed completely or partially
Excessive diagnosis.For naloxone because liver first-pass effect is big, tablet is orally substantially invalid, clinically has injection using formulation at present
Two kinds of formulations of liquid and sublingual tablet, but medication of the sublingual tablet for critical or stupor patient has certain difficulty, and due to containing change
When saliva loss and influence bioavilability.So exploitation parenteral solution is more beneficial for patient's medication.But although at present for
The preparation method of naloxone hydrochloride injection is a lot, but needs to add auxiliary material mostly, after various auxiliary materials mix with naloxone hydrochloride
Clinically the influence to drug effect is not quite similar, and the use to parenteral solution causes certain risk, thus it is a kind of pure to be badly in need of preparation
Degree is high, and the naloxone hydrochloride injection of steady quality clinically has far-reaching significance.
In addition, at present still without the special equipment prepared for naloxone hydrochloride injection, thus in the preparation of parenteral solution
During need by medicine be transferred to distinct device carry out following process, certain influence be present to the quality of medicine, to medicine
Safety form serious potential safety hazard.
The content of the invention
It is an object of the invention to solve at least the above, and provide the advantages of at least will be described later.
It is a still further object of the present invention to provide a kind of preparing device for preparing naloxone hydrochloride injection, avoid receiving in hydrochloric acid
More exchange device repeatedly in the preparation process of Lip river ketone parenteral solution, improves the quality of medicine, ensure that the safety of medicine.
It is a still further object of the present invention to provide a kind of preparation method of naloxone hydrochloride injection, in manufacturing process not
Auxiliary material, the security that ensure that the purity of manufactured parenteral solution and use are added, and preparation method is simple and easy, effectively reduces
Prepare cost.
In order to realize according to object of the present invention and further advantage, there is provided a kind of system of naloxone hydrochloride injection
Standby device, including：
Upper tank body, it is the double-decker being arranged by internal layer and outer layer, and opening is provided with above the upper tank body,
Lid is provided with the opening, the opening is covered, the top center of the upper tank body, which is provided with, to be protruded from described
The pipeline of tank body upper surface, the pipeline communicate with the gap of the internal layer and outer interlayer, are evenly distributed with the internal layer logical
Hole；Agitating device is provided with the upper tank body, the agitating device includes rotary shaft and the first stirring vane, the rotary shaft
Be vertically installed in inside the upper tank body, and be fixed on the both ends of the upper tank body, the rotary shaft is hollow setting, and with institute
State pipeline to communicate, first stirring vane is the hollow setting that another end opening is closed in one end, first stirring vane
Openend and rotation axis connection, and connected with the inside of the rotary shaft, set on the side of first stirring vane and top surface
It is equipped with the first perforate；
First filter, it includes the first filter cartridge and the first filter membrane, the top of first filter cartridge with it is described on
The lower removable connection of tank body, and it is arranged at first filter cartridge with the upper tank body fluid communication, first filter membrane
Inside, and the inwall at the edge of first filter membrane and first filter cartridge fits；
Lower tank, its upper opening, and be connected with the lower removable of first filter cartridge, the inside of the lower tank is set
Hollow agitating shaft is equipped with, the agitating shaft is vertically installed in the lower tank, and the lower end of the agitating shaft is fixedly connected
In the bottom of the lower tank, the upper end of the agitating shaft is provided with opening, and the opening of the agitating shaft upper end is connected with conduit,
The conduit stretches out the lower tank surface by the side wall of the lower tank, and the second stirring vane is arranged with the agitating shaft,
Second stirring vane is the hollow setting that another end opening is closed in one end, the openend of second stirring vane and stirring
Axis connection, and connected with the inside of the agitating shaft, it is provided with the second perforate on the side of second stirring vane and top surface；
Second filter, it includes the second filter cartridge and the second filter membrane, the top of second filter cartridge with it is described under
The lower removable connection of tank body, and it is arranged at second filter cartridge with the lower tank fluid communication, second filter membrane
Inside, and the inwall at the edge of second filter membrane and second filter cartridge fits；The side-lower of second filter cartridge
It is provided with liquid outlet.
Preferably, in the preparing device of described naloxone hydrochloride injection, in addition to：
Drive mechanism, it is connected respectively with the rotary shaft and agitating shaft, to drive the rotary shaft and agitating shaft to rotate.
Preferably, in the preparing device of described naloxone hydrochloride injection, in the side wall of the upper tank body and lower tank
Air bleeding valve is respectively arranged with, magnetic valve is provided with the air bleeding valve.
Preferably, in the preparing device of described naloxone hydrochloride injection, it is respectively arranged with the pipeline and conduit
Check valve.
Preferably, in the preparing device of described naloxone hydrochloride injection, outside the circular upper tank body and lower tank
Wall is respectively arranged with pH test paper slots, and the upper tank body and lower tank are provided with a diameter of 2-3mm on the position of the slot
Opening, electrically-controlled valve is provided with the opening, with when the electrically-controlled valve is opened so that the slot and the upper tank body and
Lower tank distinguishes fluid communication.
Preferably, in the preparing device of described naloxone hydrochloride injection, first filter and the second filtering
The top of device is provided with baffle plate, and the baffle plate is respectively embedded into the groove of the upper tank body bottom and lower tank top, with
Make the pulling baffle plate, the upper tank body and the first filter, and the lower tank and the second filter fluid communication.
A kind of method that preparing device described in prepares naloxone hydrochloride injection, comprises the following steps：
Step 1, water for injection 500-800 parts by weight, sodium chloride 7.2-9 parts by weight and hydrochloric acid are added in the upper tank body
Naloxone 0.32-0.4 parts by weight, and nitrogen is passed through, sodium chloride and naloxone hydrochloride dissolving are mixed to, obtains the first mixing
Solution；
Step 2, natrium adetate is added in the first mixed solution, to adjust pH value to 3-3.5, obtain rough hydrochloric acid and receive
Lip river ketone parenteral solution；
Step 3, by rough naloxone hydrochloride injection through first membrane filtration to lower tank；
The aperture of wherein described first filter membrane is 0.4-0.5 μm；
Step 4, water for injection 200-300 parts by weight are added in the lower tank, and held in the case where being passed through nitrogen
Continuous stirring 5-10min, obtains prefabricated naloxone hydrochloride injection；
The pH value of step 5, the measurement prefabricated naloxone hydrochloride injection, and the hydrochloric acid solution for being 0.1mol/L with concentration
Its pH value is adjusted to 3-3.3；
Step 6, step 5 is adjusted to second filter membrane mistake of the prefabricated naloxone hydrochloride injection through lower tank bottom after pH value
After filter, semi-finished product naloxone hydrochloride injection is obtained；
Wherein, the aperture of second filter membrane is 0.2-0.25 μm；
Step 7, visible foreign matters inspection is carried out to the semi-finished product naloxone hydrochloride injection, and nitrogen charging fills after qualified
Envelope, through 100 DEG C of flowing steam sterilization 30min, produces the naloxone hydrochloride injection.
Preferably,, need to also be before the step 1 is carried out in the preparation method of described naloxone hydrochloride injection
Water for injection is passed through in the preparing device to be cleaned and dried, and is passed through nitrogen into the preparing device after the drying.
Preferably, in the preparation method of described naloxone hydrochloride injection, after the step 3, also need on described
Water for injection is passed through in tank body, the upper tank body is rinsed, and makes flushing liquor through the first membrane filtration to lower tank.
The present invention comprises at least following beneficial effect：
The present invention use only naloxone hydrochloride injection and injection in the preparation method of naloxone hydrochloride injection
Water is mixed with, and adds the sodium chloride of quality wherein, meets the demand of physiological saline being consistent with human body requirements, and with fitting
Measure natrium adetate regulation pH value so that manufactured naloxone hydrochloride injection raw material is pure, avoids the addition of auxiliary material, ensures
The drug effect of medicine.
By the way that naloxone hydrochloride and water for injection are mixed, pH value is adjusted, is then filtered, then mixed with water for injection, then
Refined filtration, that is, it is 1ml to have obtained specification：0.4mg or so naloxone hydrochloride injection, preparation method is simple and easy, reduces life
Cost is produced, is produced suitable for large-scale promotion.
Further advantage, target and the feature of the present invention embodies part by following explanation, and part will also be by this
The research and practice of invention and be understood by the person skilled in the art.
Brief description of the drawings
Fig. 1 is the structural representation of the preparing device of naloxone hydrochloride injection of the present invention.
Embodiment
The present invention is described in further detail below in conjunction with the accompanying drawings, to make those skilled in the art with reference to specification text
Word can be implemented according to this.
It should be appreciated that such as " having ", "comprising" and " comprising " term used herein do not allot one or more
The presence or addition of individual other elements or its combination.
As shown in figure 1, the present invention provides a kind of preparing device of naloxone hydrochloride injection, including：Upper tank body 1, it is served as reasons
The double-decker that internal layer and outer layer are arranged, the top of the upper tank body 1 are provided with opening 2, lid are provided with the opening 2
Body 3, by the covering of opening 2, the top center of the upper tank body 1 is provided with the pipe for protruding from the upper surface of upper tank body 1
Road 4, the pipeline 4 are communicated with the gap of the internal layer and outer interlayer, and through hole 5 is evenly distributed with the internal layer；The upper tank
Agitating device is provided with body 1, the agitating device includes the stirring vane 7 of rotary shaft 6 and first, and the rotary shaft 6 is vertically set
Be placed in inside the upper tank body 1, and be fixed on the both ends of the upper tank body 1, the rotary shaft 6 is hollow setting, and with it is described
Pipeline 4 communicates, and first stirring vane 7 is the hollow setting that another end opening is closed in one end, first stirring vane 7
Openend is connected with rotary shaft 6, and is connected with the inside of the rotary shaft 6, on the side and top surface of first stirring vane 7
It is provided with the first perforate 8.
First filter, it includes the first filter cartridge 9 and the first filter membrane, the top of first filter cartridge 9 with it is described
The lower removable connection of upper tank body 1, and it is arranged at first filtering with the fluid communication of upper tank body 1, first filter membrane
The inside of box 9, and the inwall at the edge of first filter membrane and first filter cartridge 9 fits.
Lower tank 10, its upper opening, and be connected with the lower removable of first filter cartridge 9, the lower tank 10
Hollow agitating shaft 11 is internally provided with, the agitating shaft 11 is vertically installed in the lower tank 10, and the agitating shaft 11
Lower end be fixedly connected on the bottom of the lower tank 10, the upper end of the agitating shaft 11 is provided with opening, the agitating shaft 11
The opening of upper end is connected with conduit 12, and the conduit 12 stretches out the surface of lower tank 10, institute by the side wall of the lower tank 10
State and the second stirring vane 13 is arranged with agitating shaft 11, second stirring vane 13 is that the hollow of another end opening is closed in one end
Set, the openend of second stirring vane 13 is connected with agitating shaft 11, and is connected with the inside of the agitating shaft 11, described
The second perforate 14 is provided with the side of second stirring vane 13 and top surface.
Second filter, it includes the second filter cartridge 15 and the second filter membrane, the top of second filter cartridge 15 and institute
The lower removable connection of lower tank 10 is stated, and described second is arranged at the fluid communication of lower tank 10, second filter membrane
The inside of filter cartridge 15, and the inwall at the edge of second filter membrane and second filter cartridge 15 fits；Second mistake
The side-lower of filter box 15 is provided with liquid outlet 16.
In such scheme, the opening of upper tank body is opened, a certain amount of sodium chloride and naloxone hydrochloride are put in upper tank body
It is interior, lid is shut, water for injection is then passed through by pipeline, water for injection is via pipeline from the through hole on upper tank body internal layer and rotation
Flowed into rotating shaft in the first perforate of the first stirring vane in the upper tank body, and then nitrogen be passed through into upper tank body from pipeline,
Nitrogen is entered in water for injection by through hole and the first stirring vane, promotes the first stirring vane to start to rotate, while coordinate side wall
On the nitrogen that is passed through so that water for injection and sodium chloride, naloxone hydrochloride dissolve and are well mixed, and are passed through after being stirred for by the first mistake
Enter lower tank after filter device filtering, after the mixed liquor enters lower tank, one is first added at the conduit of the lower tank
Quantitative water for injection, is then passed through nitrogen thereto again, in the presence of nitrogen so that and the second stirring vane starts to rotate,
And then mixed liquor is stirred, finally flowed out after the filtering of the second filter by liquid outlet, it is only necessary to liquid outlet
After the liquid of outflow carries out canned and sterilization, that is, the naloxone hydrochloride injection is made.The setting of preparing device causes hydrochloric acid
The preparation process of Naloxone injection can be completed to prepare via one equipment of preparing device, avoid replacing in preparation process and set
It is standby, caused by secondary pollution caused by parenteral solution semi-finished product ingress of air or external environment, and then ensure that what medicine made
Health and safety.Meanwhile by being respectively provided with perforate in the side of stirring vane and top so that the perforate of sidepiece can be passed through nitrogen
Certain thrust backward is produced during gas, and then promotes the stirring vane to rotate, and then improve mixing effect, and top is opened
Hole so that nitrogen is emerged by stirring vane top, and then causes nitrogen to enable to mixed liquor to form rolling, and then is further carried
The high uniformity of mixing, and accelerate the efficiency of mixing.The through hole set in upper tank body side wall so that when nitrogen is passed through,
Mixed liquor rotates in vortex shape, can also accelerate the efficiency of mixing, and then cause the preparation efficiency of the naloxone hydrochloride injection
Significantly improve, that is, reduce production cost.Fitted by the side wall for limiting filter membrane and filter cartridge so that liquid passes fully through filter
Membrane filtration, that is, it ensure that the quality of finished product.
In one preferred scheme, in addition to：Drive mechanism, it is connected respectively with the rotary shaft 6 and agitating shaft 11, to drive
Move the rotary shaft 6 and agitating shaft 11 rotates.
In such scheme, although what the through hole on stirring vane can be certain to stirring vane when being passed through nitrogen pushes away
Power, but because nitrogen intake is limited, and the difference of nitrogen flow rate so that the rotation of agitating shaft and rotary shaft is not necessarily smooth,
Thus by setting drive mechanism, rotary shaft and agitating shaft can be driven to be rotated, and under the auxiliary of stirring vane, energy
The substantial amounts of energy is enough saved, reduces preparation cost.
In one preferred scheme, air bleeding valve 17, the row are respectively arranged with the side wall of the upper tank body 1 and lower tank 10
Magnetic valve 18 is provided with air valve 17.
In such scheme, by setting air bleeding valve in the side wall of upper tank body and lower tank, can when being passed through nitrogen,
Outwards deflate, and then ensure the balance of air pressure in tank body, and by setting magnetic valve on air bleeding valve, it can be passed through in stirring
Open air bleeding valve during nitrogen, ensure air pressure balance in tank body, and when stirring end and needing filtering, close magnetic valve, and to tank
Nitrogen is passed through in vivo, enables to increasing for nitrogen amount, accelerates the filtering of mixed liquor, and then improves the efficiency of filtering, that is, is contracted
The short preparation time of the parenteral solution.
In one preferred scheme, check valve is respectively arranged with the pipeline 4 and conduit 12.
In such scheme, by setting check valve in pipeline 4 and conduit so that pipeline and conduit can only be into tank bodies
Gas or liquid are conveyed, and can not outwards be revealed, and then ensure that being smoothed out for preparation process, also ensure that tank body inner ring
The health in border, improve the quality for the parenteral solution being prepared into.
In one preferred scheme, the outer wall around the upper tank body 1 and lower tank 10 is respectively arranged with pH test paper slot 19,
The upper tank body 1 and lower tank 10 are provided with a diameter of 2-3mm opening on the position of the slot 19, are set in the opening
Electrically-controlled valve is equipped with, with when the electrically-controlled valve is opened so that the slot 19 distinguishes liquid with the upper tank body 1 and lower tank 10
Communicate.
In such scheme, by setting the test paper slot around the tank body in the outer wall of upper tank body and lower tank, make
Obtaining can be by controlling electrically-controlled valve to be taken out conveniently the survey that a certain amount of mixed liquor carries out pH value in the configuration process of parenteral solution
It is fixed, and then final product quality is ensure that, and make it that preparing device application is more convenient and strength-saving, meanwhile, it is 2- by setting opening diameter
3mm so that mixed liquor can only have in micro inflow slot, and then ensure that the pure of mixed liquor in tank body, and avoid waste.
In one preferred scheme, the top of first filter and the second filter is provided with baffle plate 20, institute
Baffle plate 20 is stated to be respectively embedded into the groove on the bottom of upper tank body 1 and the top of lower tank 10, so as to the baffle plate 20 is pulled, it is described
The filter of upper tank body 1 and first, and the filter fluid communication of the lower tank 10 and second.
In such scheme, by setting baffle plate between filter and tank body so that mixed liquor ability when needing filtering
Baffle plate is opened, filtering can be realized, so as to avoid mixed liquor is unmixed from uniformly flowing into subsequent processing by filter.
A kind of method that preparing device described in prepares naloxone hydrochloride injection, comprises the following steps：
Step 1, water for injection 500-800 parts by weight, sodium chloride 7.2-9 parts by weight and hydrochloric acid are added in the upper tank body
Naloxone 0.32-0.4 parts by weight, and nitrogen is passed through, sodium chloride and naloxone hydrochloride dissolving are mixed to, obtains the first mixing
Solution；
Step 2, natrium adetate is added in the first mixed solution, to adjust pH value to 3-3.5, obtain rough hydrochloric acid and receive
Lip river ketone parenteral solution；
Step 3, by rough naloxone hydrochloride injection through first membrane filtration to lower tank；
The aperture of wherein described first filter membrane is 0.4-0.5 μm；
Step 4, water for injection 200-300 parts by weight are added in the lower tank, and held in the case where being passed through nitrogen
Continuous stirring 5-10min, obtains prefabricated naloxone hydrochloride injection；
The pH value of step 5, the measurement prefabricated naloxone hydrochloride injection, and the hydrochloric acid solution for being 0.1mol/L with concentration
Its pH value is adjusted to 3-3.3；
Step 6, step 5 is adjusted to second filter membrane mistake of the prefabricated naloxone hydrochloride injection through lower tank bottom after pH value
After filter, semi-finished product naloxone hydrochloride injection is obtained；
Wherein, the aperture of second filter membrane is 0.2-0.25 μm；
Step 7, visible foreign matters inspection is carried out to the semi-finished product naloxone hydrochloride injection, and nitrogen charging fills after qualified
Envelope, through 100 DEG C of flowing steam sterilization 30min, produces the naloxone hydrochloride injection.
In such scheme, by being stirred during logical nitrogen to mixed liquor, naloxone hydrochloride can be effectively avoided
Oxidation, so as to ensure that the drug effect of medicine.By in nitrogen charging embedding after the assay was approved so that air is not contained in medicine bottle and is only contained
There is nitrogen, avoid degraded of the naloxone hydrochloride in placement process so that product stability greatly improves.In addition, using secondary
Filtering, and the decreasing pore size of filter membrane, can further remove the foreign matter in parenteral solution, to improve the quality of finished product so that
Manufactured naloxone hydrochloride injection orange is bright, and is free of foreign matter.Certainly, the present invention can also carry out multiple mistake to mixed solution
Filter, so as to further improve the quality of finished product.
In one preferred scheme, before the step 1 is carried out, water for injection need to be also passed through in the preparing device and is carried out clearly
Wash and dry, and be passed through nitrogen into the preparing device after the drying.
, can by being cleaned and being dried to preparing device before naloxone hydrochloride injection is prepared in such scheme
Ensure the health in preparing device, avoid being mixed with quality prepared by debris influence parenteral solution in preparing device, and by existing after the drying
Inside is passed through nitrogen, can further reduce the content of air and dust in preparing device, i.e., further improve parenteral solution
Quality, ensure that the drug effect and safety of medicine.
In one preferred scheme, after the step 3, also need to be passed through water for injection into the upper tank body, to the upper tank
Body is rinsed, and makes flushing liquor through the first membrane filtration to lower tank.
In such scheme, by being rinsed after step 3 with water for injection to upper tank body, enable on upper tank body
The drug ingedient of residual is rinsed and filtered into lower tank, is wasted so as to avoid medicine, reduce further the hydrochloric acid
The preparation cost of Naloxone injection.
Although embodiment of the present invention is disclosed as above, it is not restricted in specification and embodiment listed
With it can be applied to various suitable the field of the invention completely, can be easily for those skilled in the art
Other modification is realized, therefore under the universal limited without departing substantially from claim and equivalency range, it is of the invention and unlimited
In specific details and shown here as the legend with description.
Claims (9)
1. a kind of preparing device of naloxone hydrochloride injection, wherein, including：
Upper tank body, it is the double-decker being arranged by internal layer and outer layer, and opening is provided with above the upper tank body, described
Lid is provided with opening, the opening is covered, the top center of the upper tank body, which is provided with, protrudes from the upper tank body
The pipeline of upper surface, the pipeline are communicated with the gap of the internal layer and outer interlayer, and through hole is evenly distributed with the internal layer；Institute
State and agitating device is provided with upper tank body, the agitating device includes rotary shaft and the first stirring vane, and the rotary shaft is vertical
Be arranged inside the upper tank body, and be fixed on the both ends of the upper tank body, the rotary shaft is hollow setting, and with the pipe
Road communicates, and first stirring vane closes the hollow setting of another end opening, the opening of first stirring vane for one end
End and rotation axis connection, and connected with the inside of the rotary shaft, it is provided with the side of first stirring vane and top surface
First perforate；
First filter, it includes the first filter cartridge and the first filter membrane, top and the upper tank body of first filter cartridge
Lower removable connection, and be arranged at the inside of first filter cartridge with the upper tank body fluid communication, first filter membrane,
And the inwall at the edge of first filter membrane and first filter cartridge fits；
Lower tank, its upper opening, and be connected with the lower removable of first filter cartridge, the lower tank is internally provided with
Hollow agitating shaft, the agitating shaft are vertically installed in the lower tank, and the lower end of the agitating shaft is fixedly connected on institute
The bottom of lower tank is stated, the upper end of the agitating shaft is provided with opening, and the opening of the agitating shaft upper end is connected with conduit, described
Conduit stretches out the lower tank surface by the side wall of the lower tank, and the second stirring vane is arranged with the agitating shaft, described
Second stirring vane is the hollow setting that another end opening is closed in one end, and openend and the agitating shaft of second stirring vane connect
Connect, and connected with the inside of the agitating shaft, the second perforate is provided with the side of second stirring vane and top surface；
Second filter, it includes the second filter cartridge and the second filter membrane, top and the lower tank of second filter cartridge
Lower removable connection, and be arranged at the inside of second filter cartridge with the lower tank fluid communication, second filter membrane,
And the inwall at the edge of second filter membrane and second filter cartridge fits；The side-lower of second filter cartridge is provided with
Liquid outlet.
2. the preparing device of naloxone hydrochloride injection as claimed in claim 1, wherein, in addition to：
Drive mechanism, it is connected respectively with the rotary shaft and agitating shaft, to drive the rotary shaft and agitating shaft to rotate.
3. the preparing device of naloxone hydrochloride injection as claimed in claim 1, wherein, the side wall of the upper tank body and lower tank
On be respectively arranged with air bleeding valve, be provided with magnetic valve on the air bleeding valve.
4. the preparing device of naloxone hydrochloride injection as claimed in claim 1, wherein, set respectively in the pipeline and conduit
There is check valve.
5. the preparing device of naloxone hydrochloride injection as claimed in claim 1, wherein, the circular upper tank body and lower tank
Outer wall is respectively arranged with pH test paper slots, and the upper tank body and lower tank are provided with a diameter of 2- on the position of the slot
3mm opening, electrically-controlled valve is provided with the opening, with when the electrically-controlled valve is opened so that the slot and the upper tank
Body and lower tank difference fluid communication.
6. the preparing device of naloxone hydrochloride injection as claimed in claim 1, wherein, first filter and the second mistake
The top of filter device is provided with baffle plate, and the baffle plate is respectively embedded into the groove of the upper tank body bottom and lower tank top,
So as to the baffle plate is pulled, the upper tank body and the first filter, and the lower tank and the second filter liquid phase
It is logical.
7. a kind of method that naloxone hydrochloride injection is prepared with preparing device as claimed in claim 1, wherein, including following step
Suddenly：
Step 1, add in the upper tank body water for injection 500-800 parts by weight, sodium chloride 7.2-9 parts by weight and hydrochloric acid and receive Lip river
Ketone 0.32-0.4 parts by weight, and nitrogen is passed through, sodium chloride and naloxone hydrochloride dissolving are mixed to, it is molten to obtain the first mixing
Liquid；
Step 2, natrium adetate is added in the first mixed solution, to adjust pH value to 3-3.5, obtain rough naloxone hydrochloride
Parenteral solution；
Step 3, by rough naloxone hydrochloride injection through first membrane filtration to lower tank；
The aperture of wherein described first filter membrane is 0.4-0.5 μm；
Step 4, water for injection 200-300 parts by weight are added in the lower tank, and persistently stirred in the case where being passed through nitrogen
5-10min is mixed, obtains prefabricated naloxone hydrochloride injection；
The pH value of step 5, the measurement prefabricated naloxone hydrochloride injection, and the hydrochloric acid solution for being 0.1mol/L with concentration adjusts
Its pH value is to 3-3.3；
Step 6, step 5 is adjusted to second membrane filtration of the prefabricated naloxone hydrochloride injection through lower tank bottom after pH value
Afterwards, semi-finished product naloxone hydrochloride injection is obtained；
Wherein, the aperture of second filter membrane is 0.2-0.25 μm；
Step 7, visible foreign matters inspection, and the nitrogen charging embedding after qualified, warp are carried out to the semi-finished product naloxone hydrochloride injection
100 DEG C of flowing steam sterilization 30min, produces the naloxone hydrochloride injection.
8. the preparation method of naloxone hydrochloride injection as claimed in claim 7, wherein, before the step 1 is carried out, also need
Water for injection is passed through in the preparing device to be cleaned and dried, and is passed through nitrogen into the preparing device after the drying.
9. the preparation method of naloxone hydrochloride injection as claimed in claim 7, wherein, after the step 3, also need to described
Water for injection is passed through in upper tank body, the upper tank body is rinsed, and makes flushing liquor through the first membrane filtration to lower tank.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710676349.0A CN107485563B (en) | 2017-08-09 | 2017-08-09 | Preparation device and preparation method of naloxone hydrochloride injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710676349.0A CN107485563B (en) | 2017-08-09 | 2017-08-09 | Preparation device and preparation method of naloxone hydrochloride injection |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107485563A true CN107485563A (en) | 2017-12-19 |
| CN107485563B CN107485563B (en) | 2020-07-28 |
Family
ID=60645140
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710676349.0A Active CN107485563B (en) | 2017-08-09 | 2017-08-09 | Preparation device and preparation method of naloxone hydrochloride injection |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107485563B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110269837A (en) * | 2019-07-19 | 2019-09-24 | 广东奇方药业有限公司 | Naloxone hydrochloride injection and preparation method thereof |
| CN111729634A (en) * | 2020-07-01 | 2020-10-02 | 汪长春 | Ligand-modified myricetin liposome particle size control device |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN87217494U (en) * | 1987-12-29 | 1988-09-07 | 张洪林 | Filter-type utensil for decocting medicinal herbs |
| CN102836665A (en) * | 2012-09-19 | 2012-12-26 | 常州大学 | Mixing stirrer with paddle with airflow driven by air pressure |
| CN103271882A (en) * | 2013-05-30 | 2013-09-04 | 瑞阳制药有限公司 | Small-volume pantoprazole sodium freeze-dried powder injection and preparation method and production device thereof |
| CN103304570A (en) * | 2013-07-12 | 2013-09-18 | 四川省惠达药业有限公司 | Naloxone hydrochloride compound as well as preparation method and pharmaceutical composition of naloxone hydrochloride compound |
| CN103736289A (en) * | 2013-12-31 | 2014-04-23 | 陈富强 | Crystallizer |
| CN105582851A (en) * | 2016-01-19 | 2016-05-18 | 王晓晓 | Novel automatic production line |
| CN205683943U (en) * | 2016-06-16 | 2016-11-16 | 南京青龙线缆材料有限公司 | A kind of blender |
-
2017
- 2017-08-09 CN CN201710676349.0A patent/CN107485563B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN87217494U (en) * | 1987-12-29 | 1988-09-07 | 张洪林 | Filter-type utensil for decocting medicinal herbs |
| CN102836665A (en) * | 2012-09-19 | 2012-12-26 | 常州大学 | Mixing stirrer with paddle with airflow driven by air pressure |
| CN103271882A (en) * | 2013-05-30 | 2013-09-04 | 瑞阳制药有限公司 | Small-volume pantoprazole sodium freeze-dried powder injection and preparation method and production device thereof |
| CN103304570A (en) * | 2013-07-12 | 2013-09-18 | 四川省惠达药业有限公司 | Naloxone hydrochloride compound as well as preparation method and pharmaceutical composition of naloxone hydrochloride compound |
| CN103736289A (en) * | 2013-12-31 | 2014-04-23 | 陈富强 | Crystallizer |
| CN105582851A (en) * | 2016-01-19 | 2016-05-18 | 王晓晓 | Novel automatic production line |
| CN205683943U (en) * | 2016-06-16 | 2016-11-16 | 南京青龙线缆材料有限公司 | A kind of blender |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110269837A (en) * | 2019-07-19 | 2019-09-24 | 广东奇方药业有限公司 | Naloxone hydrochloride injection and preparation method thereof |
| CN110269837B (en) * | 2019-07-19 | 2020-04-10 | 广东奇方药业有限公司 | Naloxone hydrochloride injection and preparation method thereof |
| WO2021012686A1 (en) * | 2019-07-19 | 2021-01-28 | 广东奇方药业有限公司 | Naloxone hydrochloride injection and preparation method therefor |
| CN111729634A (en) * | 2020-07-01 | 2020-10-02 | 汪长春 | Ligand-modified myricetin liposome particle size control device |
| CN111729634B (en) * | 2020-07-01 | 2022-01-28 | 中义(北京)健康研究院 | Ligand-modified myricetin liposome particle size control device |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107485563B (en) | 2020-07-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN205398649U (en) | 3D prints perfusion culture apparatus who contains cell aquogel support | |
| CN107485563A (en) | Preparing device of naloxone hydrochloride injection and preparation method thereof | |
| CN205412914U (en) | Western medicine ratio ware | |
| CN206285269U (en) | A kind of Intensive Care Therapy medicine-feeding device | |
| CN206482860U (en) | Prepare the water dropper and multilayer pill equipment and vibrating device of multilayer pill | |
| CN103399129B (en) | A kind of measure bioadhesive preparations vitro release and stick time/method of erosion time | |
| CN107375207A (en) | A kind of sodium bromophenolate eye drops and its preparation technology | |
| CN207137779U (en) | A kind of veterinary drug processes mixer | |
| CN107898315A (en) | A kind of traditional Chinese medical science conditioning medicinal herb tea brewing device and method | |
| CN105616164B (en) | The preparation process of multilayer pill equipment and its component and multilayer pill | |
| CN106333860A (en) | Method for improving multilayer dropping pill structure and device using in method | |
| CN206295948U (en) | A kind of resin glue processing unit (plant) of copper-clad plate | |
| CN208927995U (en) | A kind of medicinal water numerical control agitating device | |
| CN213569574U (en) | Water environment is administered with high-efficient device of puting in of biological agent | |
| CN213347877U (en) | Heparin sodium production is with removing albumen device | |
| CN108838002A (en) | A kind of convenience is separated the environmentally friendly medicament flusher of preparation to environmentally friendly medicament | |
| CN208097453U (en) | A kind of crystallization kettle being used to prepare methylene blue | |
| CN207756015U (en) | A kind of dept. of radiology is with barium meal without deposition mixer | |
| CN208287846U (en) | A kind of oncology medication dispensation apparatus | |
| CN207785565U (en) | Closed dialysis powder container | |
| CN212328142U (en) | Pneumatic stirring formula traditional chinese medicine powder's dissolution configuration device | |
| CN206328397U (en) | Fermentation tank | |
| CN205679458U (en) | A kind of internal medicine sputum assay device | |
| CN220634032U (en) | Microgravity culture nutrient solution preparing device | |
| CN114602339B (en) | Glue dissolving method and equipment for soft capsule preparation |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |