CN102512378B - Stable and safe oxiracetam pharmaceutical composition for injection - Google Patents
Stable and safe oxiracetam pharmaceutical composition for injection Download PDFInfo
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- CN102512378B CN102512378B CN201110408363.5A CN201110408363A CN102512378B CN 102512378 B CN102512378 B CN 102512378B CN 201110408363 A CN201110408363 A CN 201110408363A CN 102512378 B CN102512378 B CN 102512378B
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Abstract
The invention relates to a stable and safe oxiracetam pharmaceutical composition for injection and a preparation method thereof, especially to an oxiracetam pharmaceutical composition for treating brain damage and neurological deficit caused by the brain damage as well as impediment of anamnesis and aptitude. Preferred are injections and lyophilized powders. The oxiracetam pharmaceutical composition provided by the invention mainly contains active components of oxiracetam, sodium chloride and citric acid. The oxiracetam pharmaceutical composition for injection has stable pH values and low impurity content. By the adoption of the preparation method, curative effects of the product are effectively raised, side effects are minimized, and simultaneously the yield is raised, cost is reduced, and higher benefits are created.
Description
Technical field
The invention belongs to medical technical field, be specifically related to injection oxiracetam pharmaceutical composition of stability and safety and preparation method thereof.
Background technology
Common name: oxiracetam;
English name: Esomeprazole Sodium;
Chemical name: Esomeprazole;
Its structural formula is as follows:
Molecular formula: C
6h
10n
2o
3;
Molecular weight: 158.16;
Indication: for the treatment of the diseases such as brain injury and the neurological deficit causing, memory and disturbance of intelligence.
Pharmacological action type: oxiracetam is to act on the cancellated Cholinergic activity nootropics of maincenter.
Pharmacological mechanism: oxiracetam can promote Phosphorylcholine and phosphatidyl ethanolamine synthetic, improves the ratio of ATP/ADP in brain, makes the synthetic increase of protein and nucleic acid in brain.
Oxiracetam is first in Italy's listing, and by SmithKline, Bi Qiemu company develops, subsequently in Portugal and Japan's listing.
Patent 02114302.1 discloses a kind of oxiracetam injection and manufacture method thereof, and it is made by oxiracetam, mannitol and water for injection, and its percentage by weight is: oxiracetam 20%～40%, mannitol 5%～45%, water for injection 25%～65%.During manufacture, by proportioning, accurately take each component, inject 85% preparation of water, with needle-use activated carbon, decolour, at 40～60 ℃ of temperature, stir 10～20 minutes, coarse filtration, adds into residue water for injection, stirs, and surveys pH value, oxiracetam content, after qualified, fine straining to clear and bright, is sub-packed in bottle, lyophilizing and get final product.Formulation and technology reasonable of the present invention, steady quality is reliable, and drug action is definite, and local application's toxicity research shows that clinical drug safety is reliable, has met the demand of people to different dosage form, is mainly used in cerebral anoxia first aid.
Patent 02135957.1 provides a kind of preparation method and goods of oxiracetam injection, and it is oxiracetam that the prescription of the method forms (weight portion): glucose for injection: water for injection=1: (4～6): (50～100) or oxiracetam: sodium chloride for injection: water for injection=1: (0.8～1.0): (90～110); Preparation method a. takes glucose for injection or the sodium chloride of recipe quantity, add part water for injection and be stirred to dissolving, then technique adds needle-use activated carbon in solution routinely, through the de-charcoal of heating → insulation → filtration; B. in filtrate, add oxiracetam to be stirred to dissolving, then add water for injection → adjust pH → fine straining in solution; C. press 50～500 milliliters of/bottle of fills, gland; D. through 105～126.5 ℃ of heat sterilizations.
Patent 200710151608.4 relates to a kind of oxiracetam injection, comprises 1 weight portion oxiracetam, 1.5-5.5 weight portion glucose, 50-100 weight portion water for injection, and wherein the pH value of injection is 3.8～4.5.The present invention also provides a kind of preparation method of oxiracetam injection, comprise the steps: A) by described oxiracetam crude drug, glucose or sodium chloride are also dissolved in water for injection, solution temperature is 40～70 ℃, obtain lysate, B) by described lysate cool to room temperature, add activated carbon decolorizing, remove by filter active carbon, add suitable quantity of water, add described citric acid and sodium citrate to adjust pH value to 3.8～4.5, the lysate of adjusted pH value, C) carries out sterilizing by the intermediate products after embedding.D) to the packing of product after sterilizing.The oxiracetam injection making according to formula of the present invention and preparation method has good storage stability.
Patent 200910131292.1 relates to a kind of injection preparation that levo-oxiracetam is active component of take.It is that to take levo-oxiracetam or its salt or its purified hydrate be medicinal active ingredient, with pharmaceutically acceptable adjuvant make can injection compositions.Dosage form comprises injectable powder, bulk capacity injection (more than 50ml), small-volume injection (20ml is following).Take levo-oxiracetam or its salt or its purified hydrate is raw material, adds the adjuvant of some specific kinds and ratio, according to the illustrated technological means of this patent, is developed into the preparation that injection for intravenous is used.
Patent 200910256416.9 discloses a kind of oxiracetam liposome injection, it is characterized in that comprising following parts by weight of component: 1 part of oxiracetam, 3-18 part phospholipid, 1-12 part cholesterol, 0.5-7 part Tween 80 and appropriate osmotic pressure regulator and buffer solution.Described oxiracetam injection has good stability, envelop rate is high, toxic and side effects is little, prepare simple advantage, is suitable for clinical needs.
Patent 201010536590.1 is a kind of new Pharmaceutical composition.Said composition comprise a kind of optionally calcium ion antagonist, a kind of pyrrolidinone compounds cerebral metabolism and with pharmaceutically suitable adjuvant.Said composition can be made into oral formulations and ejection preparation, for the preparation of affecting cerebrovascular, brain metabolism and nootropics.
Routine is prepared the oxiracetam pharmaceutical composition of injection, maximum deficiency, and sterilising conditions is non-excessive sterilizing, do not reach 121 ℃ of 20 minutes or 115 ℃ 40 minutes, related substance is higher, of poor quality, high to storage condition requirement in storage, need cool dark place to preserve.
The injection oxiracetam pharmaceutical composition that the present invention obtains on the basis of great many of experiments, has advantages of: safe, maximum contaminant is less than 5 ‰; Good stability, though room temperature preservation, reliable in quality.
Summary of the invention
In order to overcome the above-mentioned defect of prior art, a kind of stable oxiracetam injection is provided, and the inventor has passed through further investigation, is surprisingly found out that, select specific adjuvant (citric acid), can obtain the oxiracetam injection of good stability, effective and safe.
Therefore, an object of the present invention is to provide that a kind of formulation and technology is simple, the injection oxiracetam pharmaceutical composition of good stability, effective and safe, this pharmaceutical composition contains oxiracetam, citric acid.Oxiracetam pharmaceutical composition of the present invention, the pharmaceutical preparation that is applicable to drug administration by injection, be preferably injection and lyophilized injectable powder, and when this injection is injection, its by oxiracetam, citric acid, that other pharmaceutic adjuvant (such as sodium chloride etc.) injects water is formulated; When this injection is lyophilized injectable powder, this injection is prepared from after lyophilizing by the aqueous solution of oxiracetam, citric acid, other pharmaceutic adjuvant (such as sodium chloride etc.), other pharmaceutic adjuvant can be sodium hydroxide, mannitol, the pharmaceutically acceptable adjuvant of sorbitol, these adjuvants can be used separately wherein a kind of, also can use by multiple auxiliary materials simultaneously.
Another object of the present invention is to provide a kind of industrialized mass of being convenient to, the preparation method of the simple oxiracetam pharmaceutical composition of technique.
Oxiracetam pharmaceutical composition of the present invention, wherein the prescription of compositions consists of: oxiracetam, sodium chloride, citric acid and water for injection.
Oxiracetam 200-1000g
Sodium chloride 9-45g
Citric acid 1-5g
Water for injection adds to 1L-5L
Make 1000
The prescription of injection is preferably: oxiracetam, sodium chloride, citric acid and water for injection, and the weight ratio of each component is: oxiracetam: sodium chloride: citric acid: water=200-1000:9-45:1-5:1000-5000, preferably aforementioned proportion is: 400-1000:18-45:2-5:2000-5000.
Preferred preparation method is:
In clean area, first the citric acid of recipe quantity, sodium chloride are added in appropriate water for injection to stirring and dissolving, the oxiracetam that adds again recipe quantity, is stirred to dissolve complete, regulates pH value to 3.0-4.0, get the 0.1%-0.5%(W/V that accounts for solution total amount) active carbon add appropriate water for injection and stir evenly, benefit injects water to entirely bright, and agitation cycle is more than 15 minutes, and first coarse filtration takes off charcoal, for example, by microporous filter membrane (0.22um filter membrane) fine straining, embedding, more than 121 ℃ pressure sterilizing is 15 minutes, obtains.
In above preparation technology, after microporous filter membrane fine straining, can get fine straining liquid and carry out the project detections such as content, pH value, endotoxin, visible foreign matters, qualified rear inflated with nitrogen, embedding, sterilizing, lamp inspection, obtain.
In oxiracetam lyophilized injectable powder of the present invention, except containing active component oxiracetam and adjuvant sodium chloride, citric acid, optionally can also contain other adjuvant for example mannitol and/or sorbitol.
The prescription of oxiracetam lyophilized injectable powder of the present invention is:
Oxiracetam 200-1000g
Sodium chloride 9-45g
Citric acid 1-5g
Mannitol 0-500g
Water for injection adds to 1L-5L
Make 1000
The prescription of lyophilized injectable powder is preferably: oxiracetam, sodium chloride, citric acid, manna are worn and water for injection, and the weight ratio of each component is: oxiracetam: sodium chloride: citric acid: mannitol: water=200-1000:9-45:1-5:0-500:1000-5000, preferably aforementioned proportion is: 400-1000:18-45:2-5:0-500:2000-5000.
Preferred preparation method is:
In clean area, first the citric acid of recipe quantity, sodium chloride are added in appropriate water for injection to stirring and dissolving, the oxiracetam that adds again recipe quantity, is stirred to dissolve complete, regulates pH value to 3.0-4.0, get the 0.1%-0.5%(W/V that accounts for solution total amount) active carbon add appropriate water for injection and stir evenly, benefit injects water to entirely bright, and agitation cycle is more than 15 minutes, and first coarse filtration takes off charcoal, for example, by microporous filter membrane (0.22um filter membrane) fine straining, fill, lyophilizing, obtains.
In above preparation technology, after microporous filter membrane fine straining, can get fine straining liquid and carry out the project detections such as content, pH value, endotoxin, visible foreign matters, qualified rear fill, lyophilizing, obtains.
In above-mentioned preparation technology, wherein freeze-dry process is: pre-freeze is carried out in establish-35--50 of shelf temperature ℃, during product Wen Dayue-25 ℃, is incubated evacuation after at least 2 hours.In 30 minutes, evacuation makes more than front case vacuum value reaches 10Pa, dividing plate is not less than 5 ℃ and heats up for the first time, product temperature reaches after 1-3 ℃, dividing plate is established 20 ℃ and is heated up for the second time, product temperature reaches 25-30 ℃, vacuum tamponade, enters outlet after pure air negative pressure, and lyophilizing overall process running time is approximately more than 15 hours.
Oxiracetam pharmaceutical composition dosage range of the present invention is: 200-1000mg/ props up, and is preferably 400-1000mg/ and props up.
Active component oxiracetam in prescription is easily molten in water, so while making injection, in research process, find, in neutral solution, oxiracetam is unstable, in put procedure, easily related substance increases, the easy flavescence of solution colour, the quality of medicine and the safety of clinical practice have been affected, through lot of experiments research, find, add citric acid available buffer pH value to play Stabilization to medicinal liquid, not only having solved related substance in the storage of injection exceeds standard, the problem of solution changes color, also solved freeze-dried powder related substance in storage increases simultaneously, guaranteed the quality of medicine and stablized.
the specific embodiment:
Below in conjunction with embodiment, the present invention is described further, makes professional and technical personnel in the field better understand the present invention.Embodiment is only indicative, never means that it limits the scope of the invention by any way.
The oxiracetam injection of the present invention and prior art contrasts, and according to oxiracetam injection pertinent literature and the disclosed prescription of package insert, prepares corresponding oxiracetam injection, as a comparison case.
embodiment 1
Oxiracetam 1000g
Sodium chloride 45g
Citric acid 5g
Water for injection adds to 5L
Make 1000
Preparation method is:
In clean area, first by the citric acid of recipe quantity, sodium chloride adds in appropriate water for injection, stirring and dissolving, the oxiracetam that adds again recipe quantity, be stirred to dissolve complete, regulate pH value to 3.0-4.0, get the 0.1%-0.5%(W/V that accounts for solution total amount) active carbon add appropriate water for injection and stir evenly, benefit injects water to entirely bright, agitation cycle is more than 15 minutes, the de-charcoal of first coarse filtration, for example, by microporous filter membrane (0.22um filter membrane) fine straining, after microporous filter membrane fine straining, can get fine straining liquid and carry out content, pH value, endotoxin, the projects such as visible foreign matters detect, qualified rear inflated with nitrogen, embedding, it is more than 121 ℃ that pressure sterilizing is 15 minutes, lamp inspection, obtain.
embodiment 2
Oxiracetam 400g
Sodium chloride 18g
Citric acid 2g
Water for injection adds to 2L
Make 1000
Preparation method is:
In clean area, first by the citric acid of recipe quantity, sodium chloride adds in appropriate water for injection, stirring and dissolving, the oxiracetam that adds again recipe quantity, be stirred to dissolve complete, regulate pH value to 3.0-4.0, get the 0.1%-0.5%(W/V that accounts for solution total amount) active carbon add appropriate water for injection and stir evenly, benefit injects water to entirely bright, agitation cycle is more than 15 minutes, the de-charcoal of first coarse filtration, for example, by microporous filter membrane (0.22um filter membrane) fine straining, after microporous filter membrane fine straining, can get fine straining liquid and carry out content, pH value, endotoxin, the projects such as visible foreign matters detect, qualified rear inflated with nitrogen, embedding, it is more than 121 ℃ that pressure sterilizing is 15 minutes, lamp inspection, obtain.
embodiment 3
Oxiracetam 200g
Sodium chloride 9g
Citric acid 1g
Water for injection adds to 1L
Make 1000
Preparation method is:
In clean area, first by the citric acid of recipe quantity, sodium chloride adds in appropriate water for injection, stirring and dissolving, the oxiracetam that adds again recipe quantity, be stirred to dissolve complete, regulate pH value to 3.0-4.0, get the 0.1%-0.5%(W/V that accounts for solution total amount) active carbon add appropriate water for injection and stir evenly, benefit injects water to entirely bright, agitation cycle is more than 15 minutes, the de-charcoal of first coarse filtration, for example, by microporous filter membrane (0.22um filter membrane) fine straining, after microporous filter membrane fine straining, can get fine straining liquid and carry out content, pH value, endotoxin, the projects such as visible foreign matters detect, qualified rear inflated with nitrogen, embedding, it is more than 121 ℃ that pressure sterilizing is 15 minutes, lamp inspection, obtain.
embodiment 4
Oxiracetam 1000g
Sodium chloride 45g
Citric acid 5g
Water for injection adds to 5L
Make 1000
Preparation method is:
In clean area, first by the citric acid of recipe quantity, sodium chloride adds in appropriate water for injection, stirring and dissolving, the oxiracetam that adds again recipe quantity, be stirred to dissolve complete, regulate pH value to 3.0-4.0, get the 0.1%-0.5%(W/V that accounts for solution total amount) active carbon add appropriate water for injection and stir evenly, benefit injects water to entirely bright, agitation cycle is more than 15 minutes, the de-charcoal of first coarse filtration, for example, by microporous filter membrane (0.22um filter membrane) fine straining, after microporous filter membrane fine straining, can get fine straining liquid and carry out content, pH value, endotoxin, the projects such as visible foreign matters detect, qualified rear fill, lyophilizing, wherein freeze-dry process is: pre-freeze is carried out in establish-35--50 of shelf temperature ℃, during product Wen Dayue-25 ℃, be incubated evacuation after at least 2 hours.In 30 minutes, evacuation makes more than front case vacuum value reaches 10Pa, dividing plate is not less than 5 ℃ and heats up for the first time, product temperature reaches after 1-3 ℃, dividing plate is established 20 ℃ and is heated up for the second time, product temperature reaches 25-30 ℃, vacuum tamponade, enters outlet after pure air negative pressure, and lyophilizing overall process running time is approximately more than 15 hours.
embodiment 5
Oxiracetam 400g
Sodium chloride 18g
Citric acid 2g
Mannitol 200g
Water for injection adds to 2L
Make 1000
Preparation method is:
In clean area, first by the citric acid of recipe quantity, sodium chloride, mannitol adds in appropriate water for injection, stirring and dissolving, the oxiracetam that adds again recipe quantity, be stirred to dissolve complete, regulate pH value to 3.0-4.0, get the 0.1%-0.5%(W/V that accounts for solution total amount) active carbon add appropriate water for injection and stir evenly, benefit injects water to entirely bright, agitation cycle is more than 15 minutes, the de-charcoal of first coarse filtration, for example, by microporous filter membrane (0.22um filter membrane) fine straining, after microporous filter membrane fine straining, can get fine straining liquid and carry out content, pH value, endotoxin, the projects such as visible foreign matters detect, qualified rear fill, lyophilizing, wherein freeze-dry process is: pre-freeze is carried out in establish-35--50 of shelf temperature ℃, during product Wen Dayue-25 ℃, be incubated evacuation after at least 2 hours.In 30 minutes, evacuation makes more than front case vacuum value reaches 10Pa, dividing plate is not less than 5 ℃ and heats up for the first time, product temperature reaches after 1-3 ℃, dividing plate is established 20 ℃ and is heated up for the second time, product temperature reaches 25-30 ℃, vacuum tamponade, enters outlet after pure air negative pressure, and lyophilizing overall process running time is approximately more than 15 hours.
embodiment 6
Oxiracetam 200g
Sodium chloride 9g
Citric acid 1g
Mannitol 500g
Water for injection adds to 1L
Make 1000
Preparation method is:
In clean area, first by the citric acid of recipe quantity, sodium chloride, mannitol adds in appropriate water for injection, stirring and dissolving, the oxiracetam that adds again recipe quantity, be stirred to dissolve complete, regulate pH value to 3.0-4.0, get the 0.1%-0.5%(W/V that accounts for solution total amount) active carbon add appropriate water for injection and stir evenly, benefit injects water to entirely bright, agitation cycle is more than 15 minutes, the de-charcoal of first coarse filtration, for example, by microporous filter membrane (0.22um filter membrane) fine straining, after microporous filter membrane fine straining, can get fine straining liquid and carry out content, pH value, endotoxin, the projects such as visible foreign matters detect, qualified rear fill, lyophilizing, wherein freeze-dry process is: pre-freeze is carried out in establish-35--50 of shelf temperature ℃, during product Wen Dayue-25 ℃, be incubated evacuation after at least 2 hours.In 30 minutes, evacuation makes more than front case vacuum value reaches 10Pa, dividing plate is not less than 5 ℃ and heats up for the first time, product temperature reaches after 1-3 ℃, dividing plate is established 20 ℃ and is heated up for the second time, product temperature reaches 25-30 ℃, vacuum tamponade, enters outlet after pure air negative pressure, and lyophilizing overall process running time is approximately more than 15 hours.
comparative example 1
0313899.8 embodiment 1
Take that to make 100 bottles of oxiracetam lyophilized injectable powder goods be example, concrete preparation method is take 1000g oxiracetam and 250g sorbitol and insert in sterile chamber in aseptic proportioning room, inject water 4000ml, after dissolving, in lysate, add 0.02%(W/V again) needle-use activated carbon 1g, be heated to 60 ℃, stir 15 minutes, filtering decarbonization, obtains filtrate, then in filtrate, add water for injection to 5000ml, adjust pH to 4.8, use again 0.22um microporous filter membrane fine straining, obtain filtrate, check the clarity of filtrate, pH, measure oxiracetam content, after qualified, be sub-packed in 12ml control antibiotic glass bottle, every bottle of 5ml, put in freezer dryer dry, first freeze drying box temperature is down to-40 ℃ (this product eutectic point is-3.5 ℃), again goods are put into freeze drying box and carry out pre-freeze, the pre-freeze time be 3.5 hours to guarantee goods fully charge, when being cooled to-60 ℃, opens by condenser vacuum pump, carry out sublimation drying, temperature maintains-10 ℃ once, after the drying layer and the disappearance of condensed layer demarcation line of goods, be incubated again 3 hours, being that first stage life is dry finishes, and then rise to 35 ℃ of insulations 6 hours with 5 ℃ of temperature per hour, as far as possible residual moisture is removed, freeze-drying process finishes, and finally with covering, determines machine plug and plastic-aluminum combined lid packs.
comparative example 2
Weigh oxiracetam 100g, glucose 150g, 500ml water for injection is dissolved in dilute preparing tank, be controlled at 40-50 ℃, and stir, know and be dissolved in completely in 500ml water for injection, lysate is cooled to 20 ℃, in the above-mentioned lysate preparing, add activated carbon decolorizing, again activated carbon filtration is wherein removed, add the citric acid and the sodium citrate buffer solution that have prepared that the pH value of this lysate has been regulated to 4.0, add again water for injection to 5000ml, fill envelope, at 105 ℃, to the intermediate products sterilizing of fill envelope 30 minutes, obtain oxiracetam injection, the concentration of metal ions that detects oxiracetam injection is 0.5PPM.
test example 1
Oxiracetam injection key index prepared by the embodiment of the present invention and comparative example: character, acidity (pH value), visible foreign matters, clarity, related substance and content etc. are tested, and the results are shown in Table 1.
Result of the test shows that oxiracetam pharmaceutical composition quality of the present invention is better than comparative example.
test example 2
According to 2010 editions two appendix XIXC stability tests of Chinese Pharmacopoeia, know that principle tests, key index to embodiment and comparative example: character, acidity (pH), visible foreign matters, clarity, related substance and content are tested, and testing result is in Table 2,3.
Influence factor's high temperature (temperature 60 C ± 2 ℃) illumination (illumination 4500 ± 500LX) result of the test is in Table 2.
Sample thief, by paid packing, accelerate (temperature is under 40 ℃ ± 2 ℃, the relative humidity condition that is 75% ± 5%) 6 months and long-term (temperature is under 25 ℃ ± 2 ℃, the relative humidity condition that is 60% ± 10%) experimental study in 24 months, according to table 3 point in time sampling, detect, result is as follows.
Every key index is without significant change in influence factor, acceleration, long term test for product prepared by the present invention, and especially clarity and visible foreign matters item are better than comparative example, quality assurance, good stability.
test example 3
The specific safety test of the oxiracetam injection that preparation method of the present invention obtains
Hemolytic test
Oxiracetam injection 0.4mg/ml of the present invention, without obvious haemolysis, meets the requirement of intravenous injection medication security inspection.Show that concentration is that the oxiracetam injection of 0.4mg/ml has no haemolysis and agglutination, its result intravenous injection medication vascular stimulation tests meets security requirement.
The injection oxiracetam pharmaceutical composition pH value that the present invention obtains is stable, and impurity content is low, has effectively improved the therapeutic effect of product, has reduced side reaction; Improve yield simultaneously, reduced cost, created higher benefit.
Claims (4)
1. the oxiracetam pharmaceutical composition of an injection, it is characterized in that this injection is injection, wherein in injection, each components by weight is: oxiracetam: sodium chloride: citric acid: water=200-1000:9-45:1-5:1000-5000, pH value scope is in 3.0-4.0 scope, prepare 1000, composed as follows:
Oxiracetam 200-1000g
Sodium chloride 9-45g
Citric acid 1-5g
Water for injection adds to 1L-5L
Comprise the following steps:
In clean area, first by the citric acid of recipe quantity, sodium chloride adds in appropriate water for injection, stirring and dissolving, the oxiracetam that adds again recipe quantity, be stirred to dissolve complete, regulate pH value to 3.0-4.0, get the 0.1%-0.5%(W/V that accounts for solution total amount) active carbon add appropriate water for injection and stir evenly, benefit adds to the full amount of water for injection, agitation cycle is more than 15 minutes, the de-charcoal of first coarse filtration, by 0.22um microporous filter membrane fine straining, after microporous filter membrane fine straining, can get fine straining liquid and carry out content, pH value, endotoxin, the project of visible foreign matters detects, qualified rear inflated with nitrogen, embedding, it is more than 121 ℃ that pressure sterilizing is 15 minutes, lamp inspection, obtain.
2. oxiracetam pharmaceutical composition according to claim 1, is characterized in that each components by weight in injection is oxiracetam: sodium chloride: citric acid: water=400-1000:18-45:2-5:2000-5000.
3. the oxiracetam pharmaceutical composition of an injection, it is characterized in that this injection is lyophilized injectable powder, wherein in lyophilized injectable powder, each components by weight is: oxiracetam, sodium chloride, citric acid, mannitol and water for injection, and the weight ratio of each component is: oxiracetam: sodium chloride: citric acid: mannitol: water=200-1000:9-45:1-5:0-500:1000-5000, pH value scope can be prepared 1000 in 3.0-4.0 scope, composed as follows:
Oxiracetam 200-1000g
Sodium chloride 9-45g
Citric acid 1-5g
Mannitol 0-500g
Water for injection adds to 1L-5L
Comprise the following steps:
In clean area, first by the citric acid of recipe quantity, sodium chloride adds in appropriate water for injection, stirring and dissolving, the oxiracetam that adds again recipe quantity, be stirred to dissolve complete, regulate pH value to 3.0-4.0, get the 0.1%-0.5%(W/V that accounts for solution total amount) active carbon add appropriate water for injection and stir evenly, benefit adds to the full amount of water for injection, agitation cycle is more than 15 minutes, the de-charcoal of first coarse filtration, by 0.22um microporous filter membrane fine straining, after microporous filter membrane fine straining, can get fine straining liquid and carry out content, pH value, endotoxin, the project of visible foreign matters detects, qualified rear fill, lyophilizing, wherein freeze-dry process is: pre-freeze is carried out in establish-35--50 of shelf temperature ℃, during product Wen Da-25 ℃, be incubated evacuation after at least 2 hours, in 30 minutes, evacuation makes more than front case vacuum value reaches 10Pa, dividing plate is not less than 5 ℃ and heats up for the first time, product temperature reaches after 1-3 ℃, dividing plate is established 20 ℃ and is heated up for the second time, product temperature reaches 25-30 ℃, vacuum tamponade, enter outlet after pure air negative pressure, lyophilizing overall process running time is more than 15 hours.
4. oxiracetam pharmaceutical composition according to claim 3, each components by weight that it is characterized in that lyophilized injectable powder is oxiracetam: sodium chloride: citric acid: mannitol: water=400-1000:18-45:2-5:0-500:2000-5000.
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| CN104069074B (en) * | 2013-03-29 | 2018-04-17 | 重庆药友制药有限责任公司 | A kind of injection Oxiracetam and preparation method thereof |
| CN104083363B (en) * | 2014-07-04 | 2016-03-16 | 重庆东泽医药科技发展有限公司 | Oxiracetam or the levo-oxiracetam new opplication in pharmaceutical field |
| CN104739760B (en) * | 2015-04-09 | 2018-03-06 | 山东罗欣药业集团股份有限公司 | A kind of pharmaceutical composition and its preparation for treating encephaledema |
| CN104906585A (en) * | 2015-05-23 | 2015-09-16 | 河北仁合益康药业有限公司 | Oxiracetam high-capacity injection composition and preparing method thereof |
| CN105434373B (en) * | 2016-01-11 | 2018-06-22 | 所秀艳 | A kind of injection Oxiracetam lyophilized preparation and preparation method thereof |
| CN105853473B (en) * | 2016-03-31 | 2019-12-13 | 海南合瑞制药股份有限公司 | oxiracetam pharmaceutical composition and preparation method thereof |
| CN111888338A (en) * | 2020-09-07 | 2020-11-06 | 广东鼎信医药科技有限公司 | Preparation method of piracetam freeze-dried powder injection for injection |
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| CN1287788C (en) * | 2003-08-08 | 2006-12-06 | 诸葛华明 | Prepn and product of oxiracetam powder for injection |
| CN101396358B (en) * | 2007-09-25 | 2011-10-12 | 广东世信药业有限公司 | Oxiracetam injection |
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