CN107496351A - A kind of ornidazole injection and preparation method thereof - Google Patents
A kind of ornidazole injection and preparation method thereof Download PDFInfo
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- CN107496351A CN107496351A CN201710707702.7A CN201710707702A CN107496351A CN 107496351 A CN107496351 A CN 107496351A CN 201710707702 A CN201710707702 A CN 201710707702A CN 107496351 A CN107496351 A CN 107496351A
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K9/00—Medicinal preparations characterised by special physical form
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- 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
- A61K31/4164—1,3-Diazoles
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- A—HUMAN NECESSITIES
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- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
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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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Abstract
The invention discloses a kind of ornidazole injection and preparation method thereof.The solvent of described ornidazole injection is the mixed liquor of absolute ethyl alcohol and the hydroxy stearic acid ester of polyethylene glycol 15, the hydroxy stearic acid ester of polyethylene glycol 15 accounts for parenteral solution mass ratio as 6% ~ 14%, propylene glycol solvent can be avoided using, better stability of preparation, clinical safety is good；The invention also discloses the preparation method of the parenteral solution, and preparation is simple for this.
Description
Technical field
The present invention relates to a kind of ornidazole injection and preparation method thereof, belong to pharmaceutical formulating art.
Background technology
Ornidazole（Omidazole）It is nitro imidazole derivatives for anaerobe resistant and the medicine of antigen insect infection, it is unparalleled
Sulphur logical sequence sample acts on.Ornidazole anti-microbial effect is that amino is reduced into oxygen-free environment by the nitro in its molecule or is passed through
Free radical and microbial cell interaction between component, it is former by anaerobic bacteria, amoeba for treating so as to cause the death of microorganism
Various diseases caused by the infection such as worm, giardia lamblia, trichmonad, with curative effect height, better tolerance, tissue permeability is good, divides in vivo
The advantages that cloth is wide, it is metronidazole, the substitute of Tinidazole.The good antioxygen bacterium of Ornidazole and protozoa resisting（Such as trichomonad）Infection
Effect makes its clinical practice increasingly extensive, and Ornidazole biological half-life is very long, and there is good Clinical practice to be worth.
But existing ornidazole injection liquid formulation has following 2 defects：
（1）Former triturate Tiberal contains a large amount of propane diols so that ornidazole injection keeps stable, and the use of propane diols is pacified
Gamut is that dosage is no more than daily 25mg/kg, in Tiberal every containing about 1.4g propane diols, Clinical practice is first
It is 0.5g/ branch that Ornidazole 1g, Tiberal specification, which is administered, it is therefore desirable to two, i.e. propane diols about 2.8g, is come by 70kg people
Calculate, be 40mg/kg, more than human-body safety scope, there is potential safety hazard.
（2）Domestic imitation medicine preparation is but water-soluble under Ornidazole neutrallty condition mostly using water for injection as solvent
Property it is bad, existing process makes ornidazole injection basic during preparation and storage by acid for adjusting pH value to 1.8 ~ 2.3
It is stable, and relevant material is no more than quality standard limit（List is miscellaneous to be no more than 0.5%, always miscellaneous to be no more than 1.0%）, but pH values 1.8 ~
2.3 ornidazole injection is stronger to blood vessel irritation, beyond the tolerance degree of human body, while adds infusion pain and quiet
The scorching incidence of arteries and veins, shows according to statistics, and ornidazole injection causes the patient of pain and various phlebitis to be in various degree about 59%
（Wang Bo, Chinese medical forward position, 2009,4（24）：69）.Document CN201310000708.2 discloses a kind of ornidazole injection,
The pH value of the ornidazole injection reaches 4.0-7.0, and can be kept under conditions of 40 ± 2 DEG C of temperature and humidity 75 ± 5%
The good storage stability of 6 months.But research is found, above-mentioned ornidazole injection is at a lower temperature（- 10 DEG C to 20
℃）Under storage stability it is poor, easily there is the defects of visible particulate matter is exceeded.
The content of the invention
For above-mentioned the shortcomings of the prior art, it is an object of the present invention to provide a kind of ornidazole injection anhydrous formulation,
Solve the security risks of existing ornidazole injection and vascular stimulation sex chromosome mosaicism；It is a further object of the present invention to provide the injection
The preparation method of liquid, Clinical practice security is more preferable, reduces medical-risk, and preparation technology is simple.
To achieve the above object, the present invention uses following technical proposals：
A kind of ornidazole injection, it is characterised in that solvent is the mixed of absolute ethyl alcohol and polyethylene glycol -15- hydroxy stearic acid esters
Close liquid.
Preferable technical scheme is as follows：
Polyethylene glycol -15- the hydroxy stearic acid esters account for solution quality ratio as 4% ~ 40%.
The Ornidazole is racemic modification or levo form.
The Ornidazole concentration is 0.15g/ml ~ 0.5g/ml.
Further preferential technical scheme is：
Polyethylene glycol -15- hydroxy stearic acid esters account for solution quality ratio as 6% ~ 14%.
The preparation method of the ornidazole injection, preparation process are：
（1）Equipment processing：High-temperature heat treatment liquid distribution pipe, pipeline and apparatus are to sterilize, depyrogenation and moisture, ensure the anhydrous of decoction
State；
（2）Solvent configures：By polyethylene glycol -15- hydroxy stearic acid esters water-bath to 37 DEG C of thawings, added into the ethanol of formula ratio
Liquid polyethylene glycol -15- the hydroxy stearic acid esters of formula ratio, it is dispersed with stirring uniformly.
（3）Decoction configures：The solvent of 10 ~ 80% formula ratios is first injected into Agitation Tank, under agitation by the nitre difficult to understand of formula ratio
Azoles is added into Agitation Tank, then adds the solvent of remaining formula ratio, and closing, dissolving obtains decoction；
（4）Carbon adsorption：To step（3）In obtained decoction add activated carbon cleaned, depyrogenation, stirring and adsorbing, use micropore
Membrane filtration；
（5）It is degerming：By step（4）Obtained decoction is filtered using 0.22 μm of miillpore filter, obtains head product；
（6）Head product is examined：Checking procedure（5）Obtained head product, detection project include clarity, particulate matter, visible
Foreign matter, content, obtain examining qualified decoction；Wherein test stone reference《Pharmacopoeia of People's Republic of China》Version second in 2015
The standard of Ornidazole is carried out in portion；
（7）Filling, packaging：By step（6）Examine filling qualified decoction, leak detection, lamp inspection and packing.Pouring process is according to preparation
Parenteral solution Ornidazole concentration, select the volume of per unit parenteral solution of preparation, scope is in 1 ~ 2ml, to cause each medication
The content of Ornidazole is 0.5g；Produce.
Step（1）In, by temperature be 150 ~ 250 DEG C of high hot compressed air after filtering by Agitation Tank and pipeline,
Sterilized, depyrogenation and moisture removal, meanwhile, all apparatus load the high heat sterilization of sterilizing cabinet；
Step（3）In, the temperature of heating is 45 ~ 55 DEG C；
Step（4）In, the amount of the activated carbon of addition is addition 0.005g ~ 0.002g in every milliliter of parenteral solution；Stirring and adsorbing
Condition is：Stir speed (S.S.) is 50 ~ 100 revs/min, and mixing time is 25 ~ 35 minutes；The aperture of the miillpore filter be 0.1 ~
0.5μm。
Beneficial effects of the present invention are as follows：Compared with prior art, no matter ornidazole injection of the invention be in preparation
During or the raw material of product in do not contain water, and use pure absolute ethyl alcohol either absolute ethyl alcohol and polyethylene glycol -15-
For the mixture of hydroxy stearic acid ester as solvent, the finished product impurity of the ornidazole injection thus prepared is extremely low, has good stability,
Quality grinds product better than original, extremely stable, term of validity length, and is free of propane diols, and Clinical practice is safer, while preparation method
Simply, suitable for industrial production.
Embodiment
Below by instantiation, the present invention will be further elaborated, it should which explanation, the description below is merely to solution
The present invention is released, its content is not defined.
Embodiment 1
A kind of ornidazole injection, wherein, Ornidazole content is 450g, and surplus solubilizer makes cumulative volume be 3000ml.Solvent is
The quality of the mixed liquor, wherein polyethylene glycol -15- hydroxy stearic acid esters of absolute ethyl alcohol and polyethylene glycol -15- hydroxy stearic acid esters
Than for 4%.
Its preparation method uses following steps：
（1）Equipment processing：By 180 DEG C of high hot compressed air after filtering by Agitation Tank and pipeline, sterilized, except heat
Former, water removal, apparatus load sterilizing cabinet and carry out high heat sterilization；
（2）Solvent configures：By polyethylene glycol -15- hydroxy stearic acid esters water-bath to 37 DEG C of thawings, added into the ethanol of formula ratio
Liquid polyethylene glycol -15- the hydroxy stearic acid esters of formula ratio, it is dispersed with stirring uniformly.
（3）Configure decoction：80% solvent is first injected into batch tank, the Ornidazole of formula ratio is added under stirring and matches somebody with somebody liquid
In tank, the solvent of surplus is added, closes, is suitably heated to 45 ~ 55 DEG C, the decoction 3000ml of dissolving；
（4）Carbon adsorption：6g activated carbons, 60 revs/min of stirring and adsorbings 30 minutes, with 0.45 μm of miillpore filter mistake are added into decoction
Filter, obtains containing drug solns.
（5）It is degerming：By step（4）What is obtained contains drug solns, through the micropore filter element filtering of 0.22 μm of twice aperture.Obtain primiparity
Product
（6）Head product is examined：Checking procedure（5）Obtained head product, project is examined to include clarity, particulate matter, visible
Foreign matter, content, obtain examining qualified decoction；
（7）Filling, packaging：By step（6）Examine qualified decoction, filling, leak detection, lamp inspection and packaging.Pouring process is according to matching somebody with somebody
The concentration of the Ornidazole of the parenteral solution of system, select the volume of per unit parenteral solution of preparation, 1 ~ 2ml of scope, to cause single medication
The content of Ornidazole is produced in 1g.
Step（1）In, by temperature be 150 ~ 250 DEG C of high hot compressed air after filtering by Agitation Tank and pipeline,
Sterilized, depyrogenation and moisture removal, meanwhile, all apparatus load the high heat sterilization of sterilizing cabinet；
Step（3）In, the temperature of heating is 45 ~ 55 DEG C；
Step（4）In, the amount of the activated carbon of addition is addition 0.005g ~ 0.002g in every milliliter of parenteral solution；Stirring and adsorbing
Condition is：Stir speed (S.S.) is 50 ~ 100 revs/min, and mixing time is 25 ~ 35 minutes；The aperture of the miillpore filter be 0.1 ~
0.5μm。
Embodiment 2
A kind of ornidazole injection, wherein, Ornidazole content is 600g, and surplus solubilizer makes cumulative volume be 3000ml.Solvent is
The quality of the mixed liquor, wherein polyethylene glycol -15- hydroxy stearic acid esters of absolute ethyl alcohol and polyethylene glycol -15- hydroxy stearic acid esters
Than for 6%.
Preparation method is the same as embodiment 1.
Embodiment 3
A kind of ornidazole injection, wherein, Ornidazole content is 750g, and surplus solubilizer makes cumulative volume be 3000ml.Solvent is
The quality of the mixed liquor, wherein polyethylene glycol -15- hydroxy stearic acid esters of absolute ethyl alcohol and polyethylene glycol -15- hydroxy stearic acid esters
Than for 8%.
Preparation method is the same as embodiment 1.
Embodiment 4
A kind of ornidazole injection, wherein, Ornidazole content is 900g, and surplus solubilizer makes cumulative volume be 3000ml.Solvent is
The quality of the mixed liquor, wherein polyethylene glycol -15- hydroxy stearic acid esters of absolute ethyl alcohol and polyethylene glycol -15- hydroxy stearic acid esters
Than for 10%.
Preparation method is the same as embodiment 1.
Embodiment 5
A kind of ornidazole injection, wherein, Ornidazole content is 1050g, and surplus solubilizer makes cumulative volume be 3000ml.Solvent is
The quality of the mixed liquor, wherein polyethylene glycol -15- hydroxy stearic acid esters of absolute ethyl alcohol and polyethylene glycol -15- hydroxy stearic acid esters
Than for 14%.
Preparation method is the same as embodiment 1.
Embodiment 6
A kind of ornidazole injection, wherein, Ornidazole content is 1200g, and surplus solubilizer makes cumulative volume be 3000ml.Solvent is
The quality of the mixed liquor, wherein polyethylene glycol -15- hydroxy stearic acid esters of absolute ethyl alcohol and polyethylene glycol -15- hydroxy stearic acid esters
Than for 18%.
Preparation method is the same as embodiment 1.
Embodiment 7
A kind of ornidazole injection, wherein, Ornidazole content is 1500g, and surplus solubilizer makes cumulative volume be 3000ml.Solvent is
The quality of the mixed liquor, wherein polyethylene glycol -15- hydroxy stearic acid esters of absolute ethyl alcohol and polyethylene glycol -15- hydroxy stearic acid esters
Than for 30%.
Preparation method is the same as embodiment 1.
Embodiment 8
A kind of ornidazole injection, wherein, Ornidazole content is 1500g, and surplus solubilizer makes cumulative volume be 3000ml.Solvent is
The quality of the mixed liquor, wherein polyethylene glycol -15- hydroxy stearic acid esters of absolute ethyl alcohol and polyethylene glycol -15- hydroxy stearic acid esters
Than for 40%.
Preparation method is the same as embodiment 1.
The stability test of embodiment 9
Accelerated test, reference are carried out to the sample of 1 ~ embodiment of embodiment 8《Pharmacopoeia of People's Republic of China》2015 editions two are entered
OK.Each sample is put 40 ± 2 DEG C, study on the stability is carried out under conditions of humidity 75% ± 5% 6 months, respectively with after filtration sterilization,
1 month after filtration sterilization, 2 months after filtration sterilization, 3 months after filtration sterilization, sample within 6 months after filtration sterilization, and and SERB
The ornidazole injection of production（Reference preparation）Contrast, Testing index is character, relevant material, particulate matter, visible different
Thing, as a result as shown in table 1.
Table 1
Influence factor experiment, reference are carried out to the sample of 1 ~ embodiment of embodiment 8《Chemicals stability study technological guidance is former
Then》Carry out, by each sample put 60 ± 5 DEG C, 40 ± 5 DEG C, carry out stability under 4500 ± 500lx of illumination and Freezing-Melting Condition and examine
Examine, respectively with after filtration sterilization, each Frozen-thawed cycled terminates, high temperature 10 days, illumination sample for 10 days, and with the nitre difficult to understand of SERB productions
Azoles parenteral solution（Reference preparation）Contrast, Testing index is character, relevant material, particulate matter, visible foreign matters, as a result such as table
Shown in 2：
Table 2
Understand from the above, the use of the invention by preventing water completely during ornidazole injection, ensure poly- second
Glycol -15- hydroxy stearic acid esters proportion is 6% ~ 14%, using absolute ethyl alcohol and polyethylene glycol -15- hydroxy stearic acid esters
For mixture as solvent, the finished product impurity of the ornidazole injection thus prepared is extremely low, has good stability, and quality is better than SERB's
Original grinds product, and quality is extremely stable, term of validity length.
The hemolytic of embodiment 10 is tested
Sample and reference preparation to 1 ~ embodiment of embodiment 8 carry out hemolytic experiment.
（1）The preparation of 2% red cell suspension：10 ~ 20ml of fresh mouse blood is taken, is put into the conical flask for filling bead
Shaking 10 minutes, or blood is stirred with glass bar, celloglobulin is removed, makes into defibrinated blood.Physiological saline 100ml is added,
Shake up, 1000 ~ 1500r/min is centrifuged 15 minutes, removes supernatant, and the red blood cell of precipitation is washed as stated above with physiological saline again
Wash 2 ~ 3 times, untill the not aobvious red of supernatant.By gained red blood cell with physiological saline be made into 2% suspension (red blood cell 2ml,
Add physiological saline to 100ml), it is for experiment.
（2）The clean teat glasses of 10ml 11 are taken, are numbered, 1 to No. 8 pipe is test sample, and No. 9 pipe reference preparations, No. 10 are managed
For negative control pipe, No. 11 pipes are positive control pipe (complete hemolysis control),.As shown in table 3, sequentially add 2% red blood cell and hang
Liquid.0.9% sodium chloride solution or distilled water, after mixing, put in the water bath with thermostatic control of (37 ± 0.5) DEG C and incubated immediately, observation is simultaneously
Record the haemolysis situation of each pipe.Observed 1 time, observe 3 hours every 1 hour.When negative control pipe is without haemolysis and cohesion generation, sun
When property control tube has haemolysis generation, if haemolysis and cohesion do not occurred in 3 hours for the solution in tested property management, tested material can be with
Injection uses, if haemolysis or aggregation occurred in 3 hours for the solution in tested material, tested material can not inject use.As a result such as
Shown in table 4：Test sample test tube 1-8 does not have haemolysis without haemolysis, No. 9 pipes yet, therefore, Ornidazole prepared by the present invention
Parenteral solution is as reference preparation without haemolysis risk.
The hemolytic experiment of table 3 designs table
| Test tube is numbered | 2% red blood cell suspension（ml） | Physiological saline（ml） | Distilled water（ml） | 5% decoction（ml） |
| 1 | 2.5 | 2 | 0 | 0.5 |
| 2 | 2.5 | 2 | 0 | 0.5 |
| 3 | 2.5 | 2 | 0 | 0.5 |
| 4 | 2.5 | 2 | 0 | 0.5 |
| 5 | 2.5 | 2 | 0 | 0.5 |
| 6 | 2.5 | 2 | 0 | 0.5 |
| 7 | 2.5 | 2 | 0 | 0.5 |
| 8 | 2.5 | 2 | 0 | 0.5 |
| 9 | 2.5 | 2 | 0 | 0.5 |
| 10 | 2.5 | 2.5 | 0 | 0 |
| 11 | 2.5 | 0 | 2.5 | 0 |
The hemolytic test result of table 4
| Test tube is numbered | Time（1h） | Time（2h） | Time（3h） |
| 1 | - | - | - |
| 2 | - | - | - |
| 3 | - | - | - |
| 4 | - | - | - |
| 5 | - | - | - |
| 6 | - | - | - |
| 7 | - | - | - |
| 8 | - | - | - |
| 9 | - | - | - |
| 10 | - | - | - |
| 11 | + | + | + |
+：Full haemolysis：Solution is clear and bright, red, and ttom of pipe remains without red blood cell
-：Not haemolysis：Red blood cell all sinks, supernatant fluid achromatism and clarity；R-RBC does not condense
The vascular stimulation test of embodiment 11
Sample and reference preparation to 1 ~ embodiment of embodiment 8 carry out vascular stimulation tests.Every group takes rabbit 3, totally 9 groups,
27, right side auricular vein is with sterile working method injection embodiment 1-8 ornidazole injection liquid formulation and reference preparation, left side
Isometric 5% glucose injection of auricular vein injection, 1 time/d, successive administration 5d.96h after last dose, visually observe injection
Position, which whether there is redness, hyperemia etc., stimulates phenomenon.Animal is put to death, with auricular vein injection point to centripetal direction, continuously takes 3 sections of blood vessels
Together with surrounding tissue, every section of 1cm, fixed with 10% formalin, conventional dehydration, FFPE, cut 5um thin slices, HE dyeing, light
Histological examination is done under mirror, opposite side compares blood vessel also same treatment.
8 groups of ornidazole injection group rabbit auricular vein injection sites, which are showed no redness, hyperemia etc., stimulates phenomenon, reference system
The rabbit auricular vein injection site of agent group, which has 1 redness, hyperemia etc. occur, stimulates phenomenon.Light microscopic histopathologic examination：It is difficult to understand
Nitre azoles parenteral solution group and control group rabbit auricular vein injection site blood vessel structure are complete, vascular endothelial cell without swelling, denaturation,
Necrosis, tube wall have 1 blood vessel endothelium swelling, denaturation occur, tube wall has inflammation without cell infiltration in 3 rabbit of reference preparation group
Cellular infiltration.
Understand from the above, ornidazole injection liquid formulation prepared by the present invention, no haemolysis and vascular stimulation implementations are excellent
In reference preparation, available for clinic, while preparation method is simple, suitable for industrial production.
The foregoing is only a preferred embodiment of the present invention, but protection scope of the present invention be not limited thereto,
It is any to be familiar with those skilled in the art in the technical scope that the present invention discloses, technique according to the invention scheme and its invention
Design is subject to equivalent substitution or change, should all be included within the scope of the present invention.
Claims (7)
1. a kind of ornidazole injection, it is characterised in that solvent is absolute ethyl alcohol and polyethylene glycol -15- hydroxy stearic acid esters
Mixed liquor.
2. ornidazole injection as claimed in claim 1, it is characterised in that polyethylene glycol -15- hydroxy stearic acid esters account for injection
Liquid mass ratio is 4% ~ 40%.
3. ornidazole injection as claimed in claim 1, it is characterised in that polyethylene glycol -15- hydroxy stearic acid esters account for injection
Liquid mass ratio is 6% ~ 14%.
4. ornidazole injection as claimed in claim 1, it is characterised in that Ornidazole is racemic modification or levo form.
5. ornidazole injection as claimed in claim 1, it is characterised in that Ornidazole concentration is 0.15g/ml ~ 0.5g/ml.
6. the preparation method of the ornidazole injection described in claim 1-5 any claims, it is characterised in that per 3000ml
The preparation process of parenteral solution be：
（1）Equipment processing：High-temperature heat treatment liquid distribution pipe, pipeline and apparatus are to sterilize, depyrogenation and moisture, ensure the anhydrous of decoction
State；
（2）Solvent configures：By polyethylene glycol -15- hydroxy stearic acid esters water-bath to 37 DEG C of thawings, added into the ethanol of formula ratio
Liquid polyethylene glycol -15- the hydroxy stearic acid esters of formula ratio, it is dispersed with stirring uniformly.
（3）Decoction configures：The solvent of 10 ~ 80% formula ratios is first injected into Agitation Tank, under agitation adds the Ornidazole of formula ratio
Enter into Agitation Tank, then add the solvent of remaining formula ratio, close, dissolving obtains decoction；
（4）Carbon adsorption：To step（3）In obtained decoction add activated carbon cleaned, depyrogenation, stirring and adsorbing, use micropore
Membrane filtration；
（5）It is degerming：By step（4）Obtained decoction is filtered using 0.22 μm of miillpore filter, obtains head product；
（6）Head product is examined：Checking procedure（5）Obtained head product, detection project include clarity, particulate matter, visible
Foreign matter, content, obtain examining qualified decoction；Wherein test stone reference《Pharmacopoeia of People's Republic of China》Version second in 2015
The standard of Ornidazole is carried out in portion；
（7）Filling, packaging：By step（6）Examine filling qualified decoction, leak detection, lamp inspection and packing.
Pouring process selects the volume of per unit parenteral solution of preparation, scope is 1 according to the concentration of the Ornidazole of the parenteral solution of preparation
~ 2ml, to cause the content of each medication Ornidazole as 1g；Produce.
7. preparation method as claimed in claim 6, it is characterised in that step（1）In, by the high fever that temperature is 150 ~ 250 DEG C
Compressed air by Agitation Tank and pipeline, is sterilized after filtering, depyrogenation and moisture removal, meanwhile, all apparatus are equal
Load the high heat sterilization of sterilizing cabinet；Step（3）In, the temperature of heating is 45 ~ 55 DEG C；Step（4）In, the amount of the activated carbon of addition is
0.005g ~ 0.002g is added in every milliliter of parenteral solution；The condition of stirring and adsorbing is：Stir speed (S.S.) is 50 ~ 100 revs/min, is stirred
The time is mixed as 25 ~ 35 minutes；The aperture of the miillpore filter is 0.1 ~ 0.5 μm.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110917135A (en) * | 2019-12-30 | 2020-03-27 | 西南大学 | Solvent system capable of effectively dissolving ornidazole or levoornidazole and injection thereof |
| CN111888328A (en) * | 2020-08-21 | 2020-11-06 | 山东致泰医药技术有限公司 | Ornidazole injection with rapid and stable performance and preparation method thereof |
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| CN111888328B (en) * | 2020-08-21 | 2022-12-30 | 山东致泰医药技术有限公司 | Ornidazole injection with rapid and stable performance and preparation method thereof |
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