CN109464389A - A kind of glycerin and fructose injection production technology - Google Patents
A kind of glycerin and fructose injection production technology Download PDFInfo
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- CN109464389A CN109464389A CN201811609945.8A CN201811609945A CN109464389A CN 109464389 A CN109464389 A CN 109464389A CN 201811609945 A CN201811609945 A CN 201811609945A CN 109464389 A CN109464389 A CN 109464389A
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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
- A61K9/08—Solutions
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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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
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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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
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- 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
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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
- A61K9/0012—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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/10—Antioedematous agents; Diuretics
Abstract
The present invention provides a kind of glycerin and fructose injection production technologies, by being formed with liquid, filling, sterilization process, specifically: water for injection is added in dense preparing tank, glycerol is completely dissolved and is mixed after dense preparing tank is added, fructose is completely dissolved and dense preparing tank mixing is added；Then stirring and adsorbing after activated carbon is added into medical fluid, adds sodium chloride and is completely dissolved, dilute preparing tank will be directed into after medical fluid decarburization and mixed after adding to the full amount of water for injection, adjust PH to intermediate standard, filtering obtains injection, last filling finished product.Water for injection is added into dense preparing tank using first by the present invention, even if then putting into glycerol into dense preparing tank and fructose only needing 5min glycerol, fructose, water for injection to be uniformly mixed, the ingredient time is saved, the 5-HMF that the medical fluid processing condition of high temperature is generated to excess for a long time is avoided.Filter type of the invention is more conducive to save the process time.Glycerol of the invention and fructose dissolution are more preferable；More effectively heat source substance is avoided to enter in finished product.
Description
Technical field
The present invention relates to a kind of medical glycerine fructose injection production technologies.
Background technique
Glycerin and fructose injection, indication are for cerebrovascular disease, brain trauma, brain tumor, intracranial inflammation and other reasons
The diseases such as caused acute and chronic increased intracranial pressure and brain edema.Glycerin and fructose injection is compound injection, wherein containing glycerol, fruit
Sugar, sodium chloride.
Existing glycerin and fructose injection preparation process is as follows:
1, it is weighed in fructose and sodium chloride investment dense preparing tank by recipe quantity, with the water for injection of prescription full dose 50%, heating
Stirring and dissolving is uniform, adds the glycerol dissolution of recipe quantity, 0.2% (W/V) activated carbon is added, stirs it, protects
(about 80 DEG C) of temperature adsorb 10 minutes, and pressure filtration decarburization while hot, in filling, obtains clear solution to dilute.
2, recipe quantity is injected water in dilute preparing tank, is stirred evenly.PH, content are surveyed in sampling.After qualification through 0.45um,
The miillpore filter refined filtration of 0.22um, is sub-packed in soft bag, sterilizes 30 minutes at 115 DEG C, lets cool inspection clarity, packs, full inspection
It is finished product after qualification.
In prior art, there are the following problems for the finished product finally obtained:
1, fructose content is relatively low, feeds intake by 100%, and finished product content declines about 4 percentage points 96.5% or so.
2,5-HMF is generated in finished product, by standard: the 5-HMF upper limit is 0.80, and the finished product 5-HMF obtained by above-mentioned technique
It is exceeded.
Above-mentioned phenomenon is analyzed, predominantly product raw material addition sequence in process for preparation is problematic, and preparation temperature is excessively high, produces
Product sterilization time is longer, affects final product quality.
Meanwhile in existing Glycerin Fructose preparation process, since the dissolubility of glycerol and fructose is not very well, to need
To accelerate stirring in course of dissolution, but existing agitating mode is generally blade stirring, and a blade is protruded into tank body,
Pot liquid is stirred by blade, or by reflux pump, the liquid in tank is pumped up into reflux repeatedly.
Moreover, being also required to carry out blade stirring or return when carried out in dense preparing tank and dilute preparing tank with liquid, active carbon adsorption
Stream stirring.
By above-mentioned blade stirring or return stirring two ways, it is required to be placed in tank body using another equipment,
And make mechanical movement, in mechanical movement, due to mechanical abrasion, it can generate and largely fall bits, fall bits and be mixed into medical fluid,
It will form new heat source substance, heat source substance is the underproof factor of injection, and heat source substance can cause injection to be injected into
Uncomfortable reaction is generated in patient body.Especially in dilute preparing tank, due to having had been subjected to active carbon adsorption, new means will not be taken again
Heat source substance is adsorbed, therefore the bits that fall of the generation in dilute preparing tank will be directly by canned into finished product.
Therefore, it is necessary to study new glycerin and fructose injection production technologies.
Summary of the invention
To solve the above-mentioned problems, it the present invention provides a kind of glycerin and fructose injection production technology, ensure that in finished product
Fructose content, and make 5-HMF in critical field, and more effectively heat source substance is avoided to be mixed into finished product.
A kind of glycerin and fructose injection production technology provided by the invention, by being formed with liquid, filling, sterilization process, specifically
Are as follows: (1) water for injection of recipe quantity 50%-60% is added, in dense preparing tank；Glycerol is completely dissolved and is mixed after dense preparing tank is added
Even formation glycerol medical fluid controls glycerol fluid temperature at 60-73 DEG C.
(2), fructose is completely dissolved to and is added dense preparing tank, forms Glycerin Fructose medical fluid after mixing.
(3), it stirs, is adsorbed after activated carbon being added into Glycerin Fructose medical fluid.
(4), sodium chloride is added and is completely dissolved and mixes, obtains concentrated wiring liquid.
(5), decarburization.
(6), it is directed into dilute preparing tank and is mixed after adding to the full amount of water for injection, adjust PH to intermediate standard, filtering must infuse
Penetrate liquid.
(7), filling and sterilize, obtain finished product.
A kind of glycerin and fructose injection production technology as described above, further explaining is that the adjusting PH is into
Mesosome standard, filtering return filter 20-30 minutes specifically, starting back filter pump and passing through back filter system, and intermediate from sample point sampling progress
Physical examination is surveyed, and after detection is qualified, medical fluid is back to visible foreign matters qualification.
A kind of glycerin and fructose injection production technology as described above, further explains and is, it is described filling specifically,
Total return valve is adjusted, guarantees ultimate filter discharge pressure between 0.3-0.35Mpa, filling temperature control is at 50-60 DEG C；Institute
The sterilizing stated specifically: injection after will be filling carries out water-bath sterilization together with package body, and 121 DEG C of water-bath sterilization temperature, the time 8
Minute, value >=8 F0.
A kind of glycerin and fructose injection production technology as described above, further explains and is, described that glycerol is complete
Dissolution method particularly includes: glycerol and water for injection 70L are added in dissolving tank and are sealed dissolving tank, it is true by being extracted in dissolving tank
It is empty that after the interior whole dissolution to glycerol of sonic oscillation dissolving tank, glycerol lysate is imported into dense preparing tank to -700pa to -900Pa, and
Sonic oscillation cleans dissolving tank, and cleaning solution imports dense preparing tank.
A kind of glycerin and fructose injection production technology as described above, further explains and is, described that fructose is complete
Dissolution method particularly includes: fructose and water for injection 80L are added in dissolving tank and are sealed dissolving tank, it is true by being extracted in dissolving tank
It is empty that fructose lysate is imported into dense preparing tank after the interior whole dissolution to glycerol of sonic oscillation dissolving tank to -500Pa extremely -900pa；And
Vacuum will be extracted in dissolving tank to -100Pa, sonic oscillation cleans dissolving tank, and cleaning solution imports dense preparing tank.
A kind of glycerin and fructose injection production technology as described above, further explains and is, described to Glycerin Fructose
Stirred after activated carbon is added in medical fluid, specifically, by every 1000 milliliters of Glycerin Fructose medical fluids addition 0.2g activated carbon ratio to
Activated carbon is added in dense preparing tank, vacuum will be extracted in dense preparing tank to -65KPa to -75KPa, and using 75-80 DEG C to concentrated compounding tank body
Bottom-heated makes to generate convection current and boiling in dense preparing tank, is stirred and adsorbs 15-25 minutes by convection current and boiling.
A kind of glycerin and fructose injection production technology as described above, further explaining is the addition sodium chloride
And be completely dissolved, specifically, by vacuum is extracted in dense preparing tank to -65KPa to -81KPa, and using 75-80 DEG C to concentrated compounding tank body
Bottom-heated makes to generate convection current and boiling in dense preparing tank, completes to mix by convection current and boiling, and clean sky is filled with after 2-8 minutes
Gas makes to balance in dense preparing tank with ambient atmosphere, stops convection current and boiling.
A kind of glycerin and fructose injection production technology as described above, further explains and is, the decarburization specifically,
By concentrated compounding liquid precipitate 20 minutes, and 55-65 DEG C is cooled in precipitation process；Supernatant after precipitating is quickly put into clear liquid
Tank slowly filters the bottom liquid after precipitating to Clear liquid tank by pressurization；Dilute match is directed into after liquid filtering decarburization in Clear liquid tank liquid
Tank.
A kind of glycerin and fructose injection production technology as described above, further explaining is that described adds water for injection
It is mixed after to full dose, specifically: it adds to the full amount of water for injection, vacuum will be extracted in dilute preparing tank to -76KPa to -85KPa, and benefit
With 60-70 DEG C to dilute preparing tank bottom-heated, so that generation convection current and boiling in dilute preparing tank is mixed object in tank, be added after 6-14 minutes
PH regulator adjusts 50-60 DEG C of fluid temperature after adjusting PH to intermediate standard 4.2-5.0,1-3 minutes, and is filled with pure air
Make to balance in dilute preparing tank with ambient atmosphere, stops convection current and boiling.
A kind of glycerin and fructose injection production technology as described above, further explaining is that the PH regulator is
The sodium hydroxide solution of dilute hydrochloric acid and 1mol/L.
The utility model has the advantages that
Then the present invention puts into glycerol and fructose, relatively using water for injection is first added into dense preparing tank into dense preparing tank
Needing 20 points in original technology can just be such that glycerol, fructose, water for injection is uniformly mixed, and present invention only requires 5min, contents
Uniformly, the ingredient time is saved, avoids the 5-HMF that the medical fluid processing condition of high temperature is generated to excess for a long time.
Filter type of the invention is more conducive to save the process time.
Glycerol of the invention and fructose dissolution are more preferable.
Due to having used on-bladed, the stirring without mechanical pump progress, mixed process, the present invention more effectively avoids heat
Source substance enters in finished product.
Specific embodiment
Glycerol course of dissolution of the invention are as follows:
Before glycerol dissolution, the water for injection of recipe quantity 60% is first added in dense preparing tank.
Then start to dissolve glycerol: glycerol needed for formula ratio and small part water for injection are added in dissolving tank and close
Dissolving tank is sealed, water for injection is about 50-150L in dissolving tank, and the present invention takes 70L.Vacuum will be extracted in dissolving tank to -700pa
In the case where not improving equipment performance, vacuumizing cost, vacuum degree can be improved as far as possible certainly to -900Pa.It is true extracting
After sky, after all dissolving in sonic oscillation dissolving tank to glycerol, glycerol lysate is imported into dense preparing tank, in dissolving tank also at this time
Remaining glycerol lysate carries out primary cleaning dissolving tank using water for injection, in the process of cleaning, uses sonic oscillation can be with
Obtain better cleaning effect.Cleaning solution is equally imported into dense preparing tank.
Next fructose is completely dissolved: fructose and water for injection is added in dissolving tank and is sealed dissolving tank, injected
80L is taken with water.It does not improving equipment performance certainly to -500Pa to -900pa by vacuum is extracted in dissolving tank, vacuumizing cost
In the case where, vacuum degree can be improved as far as possible.After all being dissolved in sonic oscillation dissolving tank to glycerol, fructose lysate is imported
Dense preparing tank.
Cleaning dissolving tank: being added water for injection into dissolving tank again, and vacuum will be extracted in dissolving tank to -100Pa, surpasses
Dissolving tank is cleaned in sound oscillation, and cleaning solution imports dense preparing tank.It is repeated once cleaning dissolving tank in this way again.
Glycerol and fructose are not readily dissolved in water (injection), it is therefore necessary to effective dissolving step are carried out, if be directly added into
Into dilute preparing tank, dilute preparing tank can not provide the stirring with intensity, to make glycerol and fructose that cannot sufficiently dissolve.Certainly,
If be added directly into dense preparing tank, dense preparing tank in common process, but still can not be non-although the stirring with some strength
Often effectively complete dissolution.Dense preparing tank is not equipped with stirring blade in this technique, so must will be not easy before entering dense preparing tank
Dissolution article sufficiently dissolves.
Sonic oscillation is carried out in small size vacuum environment, and dissolution is effectively performed.The volume of dissolving tank is less than 150 liters, outside
Connect ultrasonator.
Vacuum in extracting centainly in dissolving tank, expands the molecular gap of injection, facilitates between molecule to dissolve
Therefore come in glycerol and fructose molecule in the case where not improving equipment performance, vacuumizing cost, can improve vacuum as far as possible
Degree, in order to dissolve.In addition, have certain bubble in water for injection, and it, can be by part Bubble after extracting vacuum, benefit
In sonic oscillation, two kinds of holes can be generated in sonic oscillation water for injection.One is the gas vaporizations in water for injection to be formed
Bubble hole；One is the true property holes that the steam of water for injection evaporation is formed.It is small in size due to bubble hole,
The shock wave that it is generated when rupturing is also weaker.And the shock wave that the true property hole of steam generation is generated in rupture is eager to excel 10 times
More than.The gas excluded in these waters for injection that can be deaerated using vacuum environment is just conducive to generate true property hole.And it utilizes
The powerful shock wave in true property hole crushes glycerol and fructose.
Cleaning dissolving tank, available better cleaning effect are carried out using ultrasonic wave.It is appropriate clear after glycerol dissolution
It washes, then dissolves fructose.After dissolving fructose, dissolution work is completed, and needs thoroughly to clean dissolving tank, therefore using under vacuum state
Dissolving tank is cleaned twice.
First dissolved glycerol, fructose, water for injection are mixed well in dense preparing tank to obtain Glycerin Fructose medical fluid, then
Activated carbon is added into dense preparing tank in the ratio that 0.2g activated carbon is added in every 1000 milliliters of Glycerin Fructose medical fluids, will be taken out in dense preparing tank
It takes vacuum to -65KPa to -75KPa, and concentrated compounding tank body bottom-heated is made to generate convection current and boiling in hermetically sealed can, to dense preparing tank
Bottom-heated, by modes such as infrared heating, electromagnetic heatings, selects electromagnetic heating using heating outside tank body here.Due to
Main ingredient in dense preparing tank is still water, and therefore, when vacuum is taken away in dense preparing tank, inside pressure water is less than atmospheric pressure, here
Take -65KPa to -75KPa, preferably -70KPa, according to water boiling point and pressure dependence, in -70KPa, the liquid in dense preparing tank exists
It after 77 DEG C, that is, can reach boiling point, therefore, glycerol fluid temperature controlled at 75-85 DEG C；Concentrated compounding pot bottom is heated to above
80 DEG C, dense preparing tank is interior to produce boiling and convection current.
By convection current and boiling, the mixture in dense preparing tank is adequately stirred, and activated carbon is adequately adsorbed.It is right
Stream and boiling 15-25 minutes, preferably 20 minutes.
Then be added and sodium chloride and be completely dissolved, specifically, will be extracted in dense preparing tank after sodium chloride is added vacuum to-
65KPa is to -81KPa, preferably -75KPa, and using 75-80 DEG C to concentrated compounding tank body bottom-heated, make to generate in dense preparing tank convection current with
Boiling is completed to mix, and pure air is filled with after 2-8 minutes to be made to balance in dilute preparing tank with ambient atmosphere, and stops bottom-heated, stops
Only convection current and boiling.
By concentrated compounding liquid precipitate 20 minutes, and 55-65 DEG C is cooled in precipitation process；In the process, the object in dense preparing tank
Body generates layering, is above supernatant layer, has a small amount of activated carbon, and bottom is muddy liquid activity carbon deposition.
It utilizes the pipe compared with Large Diameter Pipeline to be quickly put into Clear liquid tank the supernatant after precipitating, is then begun through by Clear liquid tank
Decarbonization device enters dilute preparing tank after carrying out decarburization.Decarbonization device can use stud decarbonization device, can also use ultrafiltration membrane mistake
Filter is filtered using stud here.
After supernatant discharges, muddy liquid activity carbon deposition is started to process, first muddy liquid activity carbon deposition is carried out using stud
Primary filtering is slowly filtered by pressurizeing to Clear liquid tank.Since supernatant activated carbon content is low, filter to the mistake of dilute preparing tank
Cheng Feichang is fast, can save the process the time, and during supernatant is filtered from Clear liquid tank to dilute preparing tank, muddy liquid activity carbon deposition is same
When filter to Clear liquid tank, thus than more saving the time to dilute preparing tank from dense preparing tank by object whole disposable filtering in tank.
After being transferred to dilute preparing tank, temperature fluid temperature is 55-65 DEG C in dilute preparing tank at this time, is closed according to pressure and water boiling point
System reaches boiling point in dilute preparing tank when -76KPa is to -85KPa, and taking temperature is 60 DEG C, and vacuum degree is -81KPa.Using electromagnetism to dilute
Distribution tank bottom-heated makes generation convection current and boiling in dilute preparing tank mix object in tank, and PH regulator (dilute salt is added after 6-14 minutes
The sodium hydroxide solution of acid or 1mol/L).Fluid temperature 50- is adjusted after adjusting PH to intermediate standard 4.2-5.0,1-3 minutes
60 DEG C, and being filled with pure air keeps dilute preparing tank interior and ambient atmosphere balance, stops convection current and boils.
It filters again, starts back filter pump and pass through back filter system time filter 20-30 minutes, and sampled from sample point and carry out intermediate physical examination
It surveys, after detection is qualified, medical fluid is back to visible foreign matters qualification.
When filling, total return valve is adjusted, guarantee ultimate filter discharge pressure is between 0.3-0.35Mpa, filling temperature
At 50-60 DEG C, the temperature of pouring process is not less than 50 DEG C for control.After tank band packaging sterilizing, will be filling after injection together with packet
Dress body progress water-bath sterilization, 121 DEG C of water-bath sterilization temperature, the time 8 minutes, value >=8 F0.
Dense preparing tank of the invention, dissolving tank, dilute preparing tank extract vacuum shape in tank body during dissolving, stirring and evenly mixing
State should first be filled in clean gas air to tank body and balance with atmospheric pressure, then can opening when tank body to be opened.Therefore, to tank
Internal dosing plus active carbon；Or when from a tank body being directed into another tank body, should first be filled in clean gas air to tank body with
Atmospheric pressure balances, then can opening.
The present invention using water for injection is first added, add glycerol, fructose, be eventually adding sodium chloride mode carry out it is dense
Match, obtains mixing more evenly.By experiment, it is as follows: with contrast groups comparison
Conclusion: by first fructose, sodium chloride being added to add water for injection to feed intake again, after agitated 20min, content is just substantially uniform,
And by first filling jetting, again plus fructose, sodium chloride lysate feed intake, and cooperate and boil under vacuum condition, it is only necessary to 5min, content
It is highly uniform.
Consider that glycerol viscosity is big, easily cause content uneven, therefore manufacture experimently and first put into glycerol in water, then throw fructose, finally
Throw sodium chloride.
Following table is the content Homogeneity of different feeding sequences
Conclusion: by first adding water, adding fructose, sodium chloride again, last glycerol adding feeds intake, and after 60min, content is uniform not enough,
And by first plus water, again glycerol adding, finally plus fructose, sodium chloride feed intake, and after 45min, content is substantially uniform, thus select first plus water,
Glycerol adding again, finally plus fructose, sodium chloride feed intake.
Temperature control in process for preparation: temperature is excessively high, fructolysis can be made to generate 5-HMF, but consider product simultaneously
Micro organism quantity.The inspection result of different filtration temperatures is as follows:
Conclusion: by first plus water, again glycerol adding, finally plus fructose, sodium chloride, it is obvious to make product 5-HMF for filtering while hot
Higher than by first plus water, again glycerol adding, finally plus fructose, sodium chloride, it is cooled to 60 ± 5 DEG C of filterings and prepares products, therefore select and cool down
It is filtered to 60 ± 5 DEG C.
Sterilization process: the test of different sterilising temps and time see the table below:
The product testing result obtained using the present invention is as follows:
PH value: it using vertical imperial 868 type pH meters difficult to understand, is measured according to " Chinese Pharmacopoeia " two annex pH measurements.
5-HMF: taking this product 25ml, be diluted with water to 100ml, shake up, and according to spectrophotometry, measures at 284nm, extinction
Degree is not greater than 0.80.
Heavy metal: taking this product 10ml, adds acetate buffer (PH3.5) 2ml and appropriate amount of water to make into 25ml, checks in accordance with the law
(SOP-CZ-12-01-015), 25/10000000ths must not be crossed containing heavy metal.
Arsenic: taking this product 4ml, adds hydrochloric acid 5ml and water 19ml, checks (SOP-CZ-12-028) in accordance with the law, should meet regulation
(0.00005%).
It is sterile: to take 15 bags of this product, according to " Chinese Pharmacopoeia " two Sterility Test inspections, as a result meet regulation.
Content is as follows:
Filler is sulfonic acid polystyrene and divinylbenzene copolymer cation exchange resin H-type.
Mobile phase is 0.04mol/l phosphoric acid solution.
Detection wavelength is 200nm.
Column temperature is 50 DEG C.
The preparation of internal standard compound: taking 1,2-PD 15ml, is diluted to 100ml with mobile phase, shakes up to obtain the final product.
Measuring method: precision weighs sodium chloride 0.9g, fructose 5.0g, glycerol control product 10.0g in 100ml measuring bottle, adds water
It to scale, shakes up, precision measures 5ml and inner mark solution 10.0ml, sets in 100ml measuring bottle, is diluted to scale with mobile phase, shakes
It is even, it takes 20ul to inject liquid chromatograph, records chromatogram；This product 5ml separately is taken, with inner mark solution 10.0ml, sets 100ml measuring bottle
In, it is diluted to scale with mobile phase, is shaken up, is measured in the same method.By internal standard method with calculated by peak area to get.
According to standard detection, separating degree, precision, linear regression, reproducibility, the rate of recovery etc. are missed in the detection of permission
In poor range, meet detection needs.
Using the product testing that obtains of the present invention the result is as follows:
Claims (10)
1. a kind of glycerin and fructose injection production technology, by being formed with liquid, filling, sterilization process, which is characterized in that specifically:
(1), the water for injection of recipe quantity 50%-60% is added in dense preparing tank；After glycerol is completely dissolved and dense preparing tank is added
Mixing forms glycerol medical fluid, and glycerol fluid temperature is controlled at 60-73 DEG C；
(2), fructose is completely dissolved to and is added dense preparing tank, forms Glycerin Fructose medical fluid after mixing；
(3), it stirs, is adsorbed after activated carbon being added into Glycerin Fructose medical fluid；
(4), sodium chloride is added and is completely dissolved and mixes, obtains concentrated wiring liquid；
(5), decarburization；
(6), it is directed into dilute preparing tank and is mixed after adding to the full amount of water for injection, adjust PH to intermediate standard, filtering must inject
Liquid；
(7), filling and sterilize, obtain finished product.
2. a kind of glycerin and fructose injection production technology as described in claim 1, which is characterized in that the adjusting PH is into
Mesosome standard, filtering return filter 20-30 minutes specifically, starting back filter pump and passing through back filter system, and intermediate from sample point sampling progress
Physical examination is surveyed, and after detection is qualified, medical fluid is back to visible foreign matters qualification.
3. a kind of glycerin and fructose injection production technology as described in claim 1, which is characterized in that described is filling specific
To adjust total return valve, guaranteeing ultimate filter discharge pressure between 0.3-0.35Mpa, filling temperature control is in 50-60
℃；The sterilizing specifically: injection after will be filling carries out water-bath sterilization together with package body, and 121 DEG C of water-bath sterilization temperature,
Time 8 minutes, value >=8 F0.
4. a kind of glycerin and fructose injection production technology as described in claim 1, which is characterized in that described that glycerol is complete
Dissolution method particularly includes: glycerol and water for injection 70L are added in dissolving tank and are sealed dissolving tank, it is true by being extracted in dissolving tank
It is empty that after the interior whole dissolution to glycerol of sonic oscillation dissolving tank, glycerol lysate is imported into dense preparing tank to -700pa to -900Pa, and
Sonic oscillation cleans dissolving tank, and cleaning solution imports dense preparing tank.
5. a kind of glycerin and fructose injection production technology as described in claim 1, which is characterized in that described that fructose is complete
Dissolution method particularly includes: fructose and water for injection 80L are added in dissolving tank and are sealed dissolving tank, it is true by being extracted in dissolving tank
It is empty that fructose lysate is imported into dense preparing tank after the interior whole dissolution to glycerol of sonic oscillation dissolving tank to -500Pa extremely -900pa；And
Vacuum will be extracted in dissolving tank to -100Pa, sonic oscillation cleans dissolving tank, and cleaning solution imports dense preparing tank.
6. a kind of glycerin and fructose injection production technology as described in claim 1, which is characterized in that described to Glycerin Fructose
Stirred after activated carbon is added in medical fluid, specifically, by every 1000 milliliters of Glycerin Fructose medical fluids addition 0.2g activated carbon ratio to
Activated carbon is added in dense preparing tank, vacuum will be extracted in dense preparing tank to -65KPa to -75KPa, and using 75-80 DEG C to concentrated compounding tank body
Bottom-heated makes to generate convection current and boiling in dense preparing tank, is stirred and adsorbs 15-25 minutes by convection current and boiling.
7. a kind of glycerin and fructose injection production technology as described in claim 1, which is characterized in that the addition sodium chloride
And be completely dissolved, specifically, by vacuum is extracted in dense preparing tank to -65KPa to -81KPa, and using 75-80 DEG C to concentrated compounding tank body
Bottom-heated makes to generate convection current and boiling in dense preparing tank, completes to mix by convection current and boiling, and clean sky is filled with after 2-8 minutes
Gas makes to balance in dense preparing tank with ambient atmosphere, stops convection current and boiling.
8. a kind of glycerin and fructose injection production technology as described in claim 1, which is characterized in that the decarburization is specific
By concentrated compounding liquid precipitate 20 minutes, and to be cooled to 55-65 DEG C in precipitation process；Supernatant after precipitating is quickly put into clearly
Flow container slowly filters the bottom liquid after precipitating to Clear liquid tank by pressurization；It is directed into after liquid filtering decarburization in Clear liquid tank liquid dilute
Distribution tank.
9. a kind of glycerin and fructose injection production technology as described in claim 1, which is characterized in that described adds water for injection
It is mixed after to full dose, specifically: it adds to the full amount of water for injection, vacuum will be extracted in dilute preparing tank to -76KPa to -85KPa, and benefit
With 60-70 DEG C to dilute preparing tank bottom-heated, so that generation convection current and boiling in dilute preparing tank is mixed object in tank, be added after 6-14 minutes
PH regulator adjusts 50-60 DEG C of fluid temperature after adjusting PH to intermediate standard 4.2-5.0,1-3 minutes, and is filled with pure air
Make to balance in dilute preparing tank with ambient atmosphere, stops convection current and boiling.
10. a kind of glycerin and fructose injection production technology as claimed in claim 10, which is characterized in that the PH regulator
For the sodium hydroxide solution of dilute hydrochloric acid and 1mol/L.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811609945.8A CN109464389A (en) | 2018-12-27 | 2018-12-27 | A kind of glycerin and fructose injection production technology |
Applications Claiming Priority (1)
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