CN100496463C - Omeprazole sodium freeze-dried powder injection and preparing method thereof - Google Patents
Omeprazole sodium freeze-dried powder injection and preparing method thereof Download PDFInfo
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- CN100496463C CN100496463C CNB2008100011814A CN200810001181A CN100496463C CN 100496463 C CN100496463 C CN 100496463C CN B2008100011814 A CNB2008100011814 A CN B2008100011814A CN 200810001181 A CN200810001181 A CN 200810001181A CN 100496463 C CN100496463 C CN 100496463C
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- 238000002347 injection Methods 0.000 title claims abstract description 37
- 239000007924 injection Substances 0.000 title claims abstract description 37
- 229940063517 omeprazole sodium Drugs 0.000 title claims abstract description 30
- KNVABRFVZVESIL-UHFFFAOYSA-N sodium;6-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]-1h-benzimidazole Chemical compound [Na+].N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C KNVABRFVZVESIL-UHFFFAOYSA-N 0.000 title claims abstract description 30
- 238000000034 method Methods 0.000 title claims abstract description 26
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides an omeprazole sodium freeze-dried injection and a preparation method which is simple and feasible and the prepared freeze-dried injection is high in drug contents and low in related substances content. The method comprises the following steps: (1) the raw materials of the recipe quantity are stirred with injection water until the omeprazole sodium is completely dissolved to get omeprazole sodium solutions; sodium citrate solutions are put into the solutions got from step (1) and the pH value of the solutions is adjusted to 10.0 to 11.0; the injection water is put into the prepared products got from step (2) to the recipe quantity and then pin activated carbon is put into the prepared products, and filter decarburization is carried out after stirring to get filtrates; the filtrates got from step (3) are fine filling filtered by 0.22Mum removal bacteria microporous membrane, and the filtrates after fine filling filtering are put into a bottle which is partially stoppered, and then the filtrates are freeze-dried to get the freeze-dried injection.
Description
Technical field
The invention belongs to biomedicine field, what relate to is a kind of preparation method of lyophilized injectable powder, and more particularly, what the present invention relates to is a kind of preparation method of omeprazole freeze-dried powder injection.
Background technology
Injection omeprazole sodium (Omeprazole Sodium for Injection, molecular formula: C
17H
18N
3NaO
3SH
2O, molecular weight: 385.41), its chemical name is: 5-methoxyl group-2[[(4-methoxyl group-3,5-dimethyl-2-pyridine radicals)-methyl]-sulfinyl]-1H-benzimidazole sodium-hydrate.Chemical structural formula:
This product adjuvant is in the prior art: mannitol and water for injection.This product is loose block of white or off-white color or powder.As when the alternative medicine of the inapplicable epidemy at present of oral therapy disease: duodenal ulcer, gastric ulcer, reflux esophagitis and Zollinger-Ellison syndrome.
Omeprazole is the racemic mixture of a pair of active optical antimer, reduces the secretion of gastric acid by the mechanism of action of high targeted, is the specific inhibitor of sour pump in the parietal cell.This product effect is rapid, the secretion that dosage once a day can reversible gastric acid inhibitory.Be mainly used in duodenal ulcer and Zollinger-Ellison Syndrome etc. clinically.Omeprazole is a kind of alkalescence material, is concentrated in this peracidity environment of tubule in parietal cell and is converted into active substance, suppresses H+, K+-ATP enzyme (proton pump).This inhibitory action to gastric acid formation final step is dosage correlation, and highly suppresses basal gastric acid secretion and zest gastric acid secretion, but irrelevant with stimulus object.
Human vein gives omeprazole, is the gastric acid inhibitory secretion of dosage correlation, in order to reach rapidly and the repeatedly effect of oral 20 milligrams of identical reduction gastric acidity, advises that intravenous gives 40 milligrams of omeprazoles first.40 milligrams of omeprazoles of quiet notes reduce gastric acidity rapidly, average decline 90% in 24 hours.The gastric acid inhibitory secretory action of omeprazole and medicine area under curve (AUC) for the moment are relevant, and the blood drug level during with administration has nothing to do.
What CN1385214 disclosed that a kind of dedicated solvent of omeprazole sodium injection relates to is a kind of dedicated solvent of specializing in the dissolving omeprazole sodium injection and preparation method thereof.The dedicated solvent of Omeprazole Sodium injection is formulated by inorganic salt or organic salt, disodiumedetate, water for injection, and wherein each composition weight per distribution ratio is: inorganic salt or organic salt 0.9%～15%, disodiumedetate 0.01%～0.1%, water for injection surplus; Inorganic salt adopts a kind of in sodium chloride, sodium bicarbonate, sodium dihydrogen phosphate, the calcium chloride, organic salt to adopt a kind of in sodium lactate solution, the calcium lactate.
CN1686124 discloses a kind of omeprazole sodium injection, by the Omeprazole Sodium 42.7g of following ratio, and disodiumedetate 1g, PEG400-1000mL charges into nitrogen, makes 1000 injection.The preparation method of above-mentioned omeprazole sodium injection is indoor in the sterile working, take by weighing Omeprazole Sodium, disodiumedetate by recipe quantity, add the Polyethylene Glycol-400 of recipe quantity, stir and made its dissolving in 30 minutes, the injection active carbon that adds amount of preparation 0.02% then, fully stir, after the coarse filtration, the microporous filter membrane fine straining of reuse 0.22 μ m, measure the content of Omeprazole Sodium in the solution, determine accurate loading amount, packing is sealed after charging into nitrogen.The present invention compares with the injection powder pin, and injection need not dissolve, and has saved the cost of packing and transportation; Use more conveniently, and avoided the possibility of secondary pollution, can save time, improve medical personnel's work efficiency
CN100998593 discloses a kind of stable omeprazol sodium preparation for injection, comprise Omeprazole Sodium, disodiumedetate, mannitol, the prescription composition of making 1000 doses of units is preferably: Omeprazole Sodium (in omeprazole) 20-80g, disodiumedetate 0.5-5g, mannitol 50-500g.
Prior art shows, omeprazole freeze-dried powder injection exists clarity bad, stability is bad, drug content is low, and the high defective of its related substances, because in the lyophilized injectable powder of Omeprazole Sodium, in order to prevent the catalytic action of metal ion to the medicine autoxidation, add a certain amount of metal ion chelation agent,, also must add the PH regulator simultaneously to reduce the concentration of metal ion, make pH value in scope that human body was fit to, owing to the chelating agen different in the preparation process and the adding of pH value regulator, make the omeprazole freeze-dried powder injection of prior art exist clarity bad, drug content is low, and the problem that preparation process is more loaded down with trivial details, in view of this, the present invention is by selecting suitable metal ion chelation agent, and pH is regulated in agent as pH regulator simultaneously, cooperates suitable step of freeze drying again, prepare the drug content height, and clarity is good, and therefore the lyophilized injectable powder of good stability proposes the present invention.
Summary of the invention
Primary and foremost purpose of the present invention is to provide a kind of omeprazole freeze-dried powder injection, and described lyophilized injectable powder stability is good, the drug content height.
To achieve these goals, the technical solution used in the present invention is:
A kind of omeprazole freeze-dried powder injection, described lyophilized injectable powder is:
Described lyophilizing is: earlier at-45 ℃ of pre-freeze 2-4 hours, dry 24-28 hour of reduced vacuum under-45 ℃～10 ℃ conditions then is at last at 35 ℃ of high temperature drying 6-8 hours.
A kind of omeprazole freeze-dried powder injection, described lyophilized injectable powder is:
Described lyophilizing is: earlier at-45 ℃ of pre-freeze 2-4 hours, dry 24-28 hour of reduced vacuum under-45 ℃～10 ℃ conditions then is at last at 35 ℃ of high temperature drying 6-8 hours.
A kind of omeprazole freeze-dried powder injection, described lyophilized injectable powder is:
Described lyophilizing is: earlier at-45 ℃ of pre-freeze 2-4 hours, dry 24-28 hour of reduced vacuum under-45 ℃～10 ℃ conditions then is at last at 35 ℃ of high temperature drying 6-8 hours.
A kind of omeprazole freeze-dried powder injection, described lyophilized injectable powder is:
Described lyophilizing is: earlier at-45 ℃ of pre-freeze 2-4 hours, dry 24-28 hour of reduced vacuum under-45 ℃～10 ℃ conditions then is at last at 35 ℃ of high temperature drying 6-8 hours.
Another object of the present invention is to provide a kind of preparation method of omeprazole freeze-dried powder injection, this preparation method simple possible, drug content height in the prepared lyophilized injectable powder, its related substances is low.
To achieve these goals, the technical solution used in the present invention is:
A kind of preparation method of omeprazole freeze-dried powder injection is characterized in that, described method may further comprise the steps:
(1) raw material of recipe quantity and water for injection are stirred to omeprazole and receive dissolving fully, obtain omeprazole and receive solution;
(2) add sodium citrate solution in the solution of gained in step (1), the pH value of regulator solution is to 10.0-11.0;
(3) add water for injection to recipe quantity in step (2) products therefrom, the solution after obtaining diluting adds needle-use activated carbon again, after the stirring, carries out filtering decarbonization, obtains filtrate;
(4) with the filtrate of step (3) gained with 0.22 μ m degerming microporous filter membrane fine straining, the filtrate of gained behind the fine straining is packed in the bottle, the false add plug carries out lyophilization then, obtains described lyophilized injectable powder.
In the preparation method of the present invention, adopt sodium citrate as the pH value regulator, its effect not only is the pH value of regulator solution, simultaneously, it is a kind of metal ion chelation agent, can prevent the catalytic action of metal ion to the medicine autoxidation, drug content height when therefore being prepared into lyophilized injectable powder, the content of related substance is low, and described omeprazole freeze-dried powder injection is stable fine.
The concentration of sodium citrate solution of the present invention is 0.05-0.15mol/L.
In the step of the present invention (3) addition of needle-use activated carbon be after the described dilution solution weight 0.05%.
Lyophilization described in the step among the present invention (4) is: earlier at-45 ℃ of pre-freeze 2-4 hours, dry 24-28 hour of reduced vacuum under-45 ℃～10 ℃ conditions then is at last at 35 ℃ of high temperature drying 6-8 hours.
Mixing time described in the step among the present invention (3) is 10-20 minute.
Freezing described in the present invention may further comprise the steps specifically:
1, pre-freeze
It is freezing medicine to be put into the freeze drying box that is cooled to-45 ℃, and the time is 2-4 hour;
The purpose of pre-freeze is for fixed product, so that distil under vacuum.If do not freeze reality, then product can emit bottle outlet external during evacuation, causes the spray bottle, does not have certain shape; If temperature is low excessively, then wasted the energy and time, in addition, the pre-freeze process has also determined the quality of the speed and the freeze-drying prods of dry run to a great extent.
Because the eutectic point of this product is-22.5 ℃, the design cryogenic temperature is-45 ℃, and why freeze drying box will be cooled in advance-45 ℃, is in order to strengthen the temperature difference of shelf in medicine and the freeze dryer.In practical operation, the medicine of bottling mainly with freeze dryer in shelf finish exchange heat.Shelf temperature is low, and the temperature difference of shelf is big in medicine and the freeze dryer, and rate of temperature fall is fast more, and the degree of supercooling of solution and degree of supersaturation are bigger, and critical crystalline granularity is then little, and nucleation rate is fast more, can form the less thin ice crystal of the more size of granule easily.After these thin ice crystal distillations, the pore-size that forms in the material is less, though dry rate afterwards is low, it is good to do the back solubility.Otherwise, not cooling in advance, rate of temperature fall is slow, forms oarse-grained ice crystal, and the aqueous vapor discharge channel size that ice crystal distillation back forms is bigger, though help improving dry rate, it is poor to do the back solubility.
The freeze drying box resulting product solubility of lowering the temperature in advance is good, and product appearance is also qualified substantially, but the slightly atrophy of product of minority bottle is arranged, and this is because the present invention is a freeze drying process that adopts bottle to freeze, and is heated and can not accomplishes fully evenly.In when cooling, the medicinal liquid in the bottle up and down two parts can to produce thermograde poor, in the propulsive from bottom to top process in ice interface, upwards migration of solute causes the solute of upper epidermis often more in the solution, density is higher, and bottom density is less down, short texture.Though because the design cryogenic temperature is lower, shortened crystallization time to a great extent, shorten the solute migration time equally, improved the atrophy situation that causes owing to density variation greatly, but in order to reach better effect, the present invention preferably adopts three-step approach pre-freeze, be about to medicinal liquid and be cooled to eutectic point earlier from room temperature and be about-22.5 ℃, be incubated, the time of insulation is 30-60 minute, make temperature autobalance in the medicinal liquid, eliminate the thermograde in it; Then medicinal liquid is put into the freeze drying box that is cooled to-40 ℃, freezing 2-4 hour, can reduce like this in the bottle medicinal liquid up and down two parts can to produce thermograde poor, and it is supercool to make that easily medicinal liquid forms, when energy accumulation is enough, whole crystallizations of moment, prepared product solubility is splendid, and outward appearance is full, color even, hole densification, and is better than the outward appearance that adopts direct pre-freeze method product, clarity and stability.
2, distillation
After medicine freezes, start the vacuum machine and be evacuated to about 10Pa, close fridge, heat up to make to medicine and freeze the product temperature and rise to-27 to-25 ℃; Be incubated 8-12 hour then, continue to be warming up to 10 ℃ again, the needed altogether time 24-28 of this process hour.The distillation phase can be removed the moisture about 90%.
The choice relation of sublimation temperature is to the speed of distillation, why select-27 to-25 ℃, rather than more near the temperature of eutectic point, be because when distillation, the upper materials drying that will take the lead in, if it is too fast that its temperature rises, might reach the temperature of caving in (or being referred to as the disintegrate temperature), porous skeleton rigidity reduces, and coming off appears in the granule in the drying layer, can seal the micro channel of drying nest, stop the carrying out of distillation, rate of sublimation is slowed down, even make underclad portion atrophy slightly, influence the content of goods residual moisture, cause solubility, stability and clarity is variation simultaneously.
In addition, temperature retention time is unsuitable long, this is because the small crystals that medicinal liquid quick freezing of the present invention produces has very high surface energy, when heating recrystallize might take place; mutually combining between the little ice crystal forms big ice crystal; make its surface to volume ratio reach minimum, and big ice crystal makes the dried frozen aquatic products outward appearance bad, solubility is poor.
Pressure during the distillation is 10Pa, though this is because the low distillation that helps ice in the product of pressure, because pressure is unfavorable to conducting heat when too low, product is difficult for the acquisition heat, and rate of sublimation reduces on the contrary.But when pressure was too high, the rate of sublimation of ice slowed down in the product, and minimizing falls in the product caloric receptivity.So the temperature of product self rises, when being higher than temperature of eutectic point, product will melt, and cause the lyophilizing failure.Therefore, pressure is set at 10-12Pa, not only has been beneficial to the transmission of heat but also has been beneficial to the carrying out of distillation.
3, drying
In case the ice distillation finishes in the product, can enter drying stage.Do not freeze ice though do not exist in this stage product, also have the moisture content about 10% in the product, remaining water content meets the requirements in the product in order to make, must be further dry to product.
Exsiccant process is gradually to 35 ℃ of insulation vacuum drying 6-8h with medicine.
The present invention adopts above-mentioned freeze drying process, makes the lyophilized injectable powder good stability, and water content is low, and the products obtained therefrom quality is loose, adds during use can dissolve rapidly behind the water for injection and recover the primary characteristic of medicinal liquid; The products obtained therefrom dose controlled, good appearance.
The present invention makes injectable powder with omeprazole, solved and to have swallowed clinically and the patient of dysphagia, utilize cryodesiccated method, with Omeprazole Sodium under the condition of extremely low temperature and vacuum, after water sublimed, made a kind of new dosage form, lyophilized injectable powder, specification is 20mg, 40mg.
The invention has the beneficial effects as follows:
1, freeze-dried powder can be mixed with the solution of variable concentrations because of the difference of clinical application, satisfies the needs of different way of administration.
2, freeze-dried powder is more stable.Vacuum state one lyophilization includes moisture Control in minimum scope, and ≦ 2.5%, and make medicine in inner container, be in vacuum state all the time, until use.
3, packaging volume is little, and packaging material require low, have reduced packing cost and cost of transportation.
Fragment and particle contamination medicinal liquid when 4, having avoided injection to cut the saw vial.
5, this product is aseptic filter membrane and the sterilization of refrigerated method, can avoid medicine rotten because of hyperpyrexia decomposes; The products obtained therefrom quality is loose, adds can dissolve rapidly behind the water and recover the primary characteristic of medicinal liquid; The products obtained therefrom dose controlled, good appearance.
Description of drawings
Fig. 1 is the production technology and the flow chart of omeprazole freeze-dried powder injection
The specific embodiment
Embodiment 1
1, prescription is formed
20mg
2, preparation method
The Omeprazole Sodium of recipe quantity is added in the dosing cylinder, add 1500ml water for injection and be stirred to whole dissolvings, reuse concentration is that the sodium citrate solution of 0.05mol/L is regulated pH to 11.0, adds water for injection and obtains mixed solution to 2000mL.The needle-use activated carbon that then adds total amount 0.05% stirred filtering decarbonization 15 minutes.The filtrate that obtains with 0.22 μ m degerming microporous filter membrane fine straining, is measured pH value, content, false add plug.Carry out lyophilization then: earlier medicine is reduced to-22.5 ℃ from room temperature, be incubated after 60 minutes, continued to be cooled under-45 ℃ the temperature conditions pre-freeze then 4 hours; Again medicine is warming up to-27 ℃ from-45 ℃, is incubated 8 hours, reduced vacuum drying under-27 ℃～10 ℃ conditions then, the time is 26 hours to this process altogether; At last 35 ℃ of high temperature dryings 6 hours, last tamponade, roll lid, examine and be packaged into warehouse for finished product after qualified entirely.
Embodiment 2
1, prescription is formed
40mg
2, preparation method (specification: 20mg; 40mg)
The omeprazole sodium raw materials of recipe quantity is added in the dosing cylinder, adds 1500mL water for injection and be stirred to whole dissolvings, reuse 0.05mol/L sodium citrate solution is regulated pH to 10.5, adds water for injection to recipe quantity.Add the needle-use activated carbon of total amount 0.05%, stirred filtering decarbonization 15 minutes.Medicinal liquid with 0.22 μ m degerming microporous filter membrane fine straining, is measured pH value, content, false add plug.Carry out lyophilization at last: earlier medicine is reduced to-22.5 ℃ from room temperature, be incubated after 30 minutes, continued to be cooled under-45 ℃ the temperature conditions pre-freeze then 3 hours; Then medicine is warming up to-25 ℃ from-45 ℃, is incubated 12 hours, reduced vacuum drying under-25 ℃～10 ℃ conditions then, the time is 24 hours to this process altogether; At last 35 ℃ of high temperature dryings 7 hours.Tamponade, roll lid, examine and be packaged into warehouse for finished product after qualified entirely.
Embodiment 3
1, prescription is formed
20mg：
2, preparation method
The Omeprazole Sodium and the mannitol supplementary material of recipe quantity are added in the dosing cylinder, add 1000mL water for injection and be stirred to whole dissolvings, reuse 0.15mol/L sodium citrate solution is regulated pH value to 10.0, add water for injection again to 1500mL, solution after obtaining diluting then adds 0.05% needle-use activated carbon of the solution weight of weight after for dilution, stirs 20 minutes, filtering decarbonization obtains filtrate.Filtrate with 0.22 μ m degerming microporous filter membrane fine straining, is measured pH value, content, false add plug.Carry out lyophilization at last: earlier medicine is reduced to-22.5 ℃ from room temperature, be incubated after 45 minutes, continued to be cooled under-45 ℃ the temperature conditions pre-freeze then 2 hours; Then medicine is warming up to-26 ℃ from-45 ℃, is incubated 10 hours, reduced vacuum drying under-26 ℃～10 ℃ conditions then, the time is 28 hours to this process altogether; At last 35 ℃ of high temperature dryings 8 hours.Tamponade, roll lid, examine and be packaged into warehouse for finished product after qualified entirely.
Embodiment 4
1, prescription is formed
40mg：
2, preparation method
The Omeprazole Sodium and the mannitol supplementary material of recipe quantity are added in the dosing cylinder, add 2500mL water for injection and be stirred to whole dissolvings, reuse 0.1mol/L sodium citrate solution is regulated pH value to 10.3, adds water for injection to 3000mL, the solution after obtaining diluting.Add 0.05% the needle-use activated carbon account for dilution back solution weight in the described again solution, stirred 20 minutes, filtering decarbonization obtains filtrate, again with filtrate with 0.22 μ m degerming microporous filter membrane fine straining, mensuration pH value, content, false add plug.Lyophilization: earlier medicine is reduced to-22.5 ℃ from room temperature, be incubated after 45 minutes, continued to be cooled under-45 ℃ the temperature conditions pre-freeze then 2 hours; Then medicine is warming up to-26 ℃ from-45 ℃, is incubated 10 hours, reduced vacuum drying under-26 ℃～10 ℃ conditions then, the time is 28 hours to this process altogether; At last 35 ℃ of high temperature dryings 8 hours.Tamponade, roll lid, examine and be packaged into warehouse for finished product after qualified entirely.
Test example 1
This test example relates to the investigation of pH value, color and clarity
Get the prepared injection omeprazole sodium lyophilized injectable powder of 1 embodiment 2, add water by labelled amount and be mixed with per 1 milliliter of aqueous solution that contains Omeprazole Sodium 0.02g, investigate its pH value, color and clarity respectively.
PH value is measured: sample thief is measured (2000 editions two appendix VI H of Chinese Pharmacopoeia) pH value in accordance with the law.
Colour measurement: sample thief and yellow standard color solution (two appendix IX of Chinese Pharmacopoeia version in 2000 A, first method) are relatively.
Clarity is measured: sample thief compares with No. 1 turbidity standard (two appendix IX of Chinese Pharmacopoeia version in 2000 B) as showing muddy.
Result of the test such as following table 1:
Table 1
Test example 2
This test example relates to study on the stability
(1) influence factor's test
Get 1 embodiment, 2 prepared injection gatifloxacin freeze-dried powder injections and carry out illumination (airtight vial, illumination 4000lx), high temperature (60 ℃), low temperature (4 ℃) test respectively, placed 10 days, in the 0th, 5, the every index of sampling and measuring in the time of 10 days.The results are shown in Table 2:
Table 2. influence factor result of the test
(2) accelerated test
It is 75% thermostatic container that A, B, three groups of samples of C are placed relative humidity (RH), and constant temperature was placed 6 months in 40 ℃ of baking ovens, takes a sample respectively at the 0th, 1,2,3, during June, measures every index.Each batch sample character is white powder, odorless as a result, and sterility test is all qualified, and other indexs see Table 3.
Table 3. accelerated test is investigated the result
(3) the room temperature investigation that keeps sample
Three groups of sample room temperatures of A, B, C are placed, respectively at the 0th, 3,6,9, the December sampling, measure every index.Each batch sample character is white powder, odorless as a result, and sterility test is all qualified, and other indexs see Table 4.
The table 4. room temperature investigation result that keeps sample
The above results shows, the having good stability of product injection Gatifloxacin of the present invention, and pH value can maintain about 10.5-10.9 for a long time.
Claims (9)
1, a kind of preparation method of omeprazole freeze-dried powder injection is characterized in that, described method may further comprise the steps:
(1) raw material of recipe quantity and water for injection are stirred to Omeprazole Sodium and dissolve fully, obtain the omeprazole sodium solution;
(2) add sodium citrate solution in the solution of gained in step (1), the pH value of regulator solution is to 10.0-11.0;
(3) in step (2) products therefrom, add water for injection to recipe quantity, add needle-use activated carbon again, after the stirring, carry out filtering decarbonization, obtain filtrate;
(4) with the filtrate of step (3) gained with 0.22 μ m degerming microporous filter membrane fine straining, the filtrate of gained behind the fine straining is packed in the bottle, the false add plug carries out lyophilization then, obtains described lyophilized injectable powder.
2, method according to claim 1 is characterized in that, the concentration of described sodium citrate solution is 0.05-0.15mol/L.
3, method according to claim 1 is characterized in that, in the described step (3) addition of needle-use activated carbon be after the described dilution solution weight 0.05%.
4, method according to claim 1 is characterized in that, the lyophilization described in the step (4) is: earlier-45 ℃ of pre-freezes 2 hours, dry 24-28 hour of reduced vacuum under-45 ℃～10 ℃ conditions then is at last at 35 ℃ of high temperature drying 6-8 hours.
5, method according to claim 1 is characterized in that, the mixing time described in the step (3) is 10-20 minute.
6, method according to claim 1 is characterized in that, the raw material of the recipe quantity described in the step (1) be Omeprazole Sodium in omeprazole 20g, the water for injection described in the step (1) is that water for injection adds to 2000ml.
7, method according to claim 1 is characterized in that, the raw material of the recipe quantity described in the step (1) be Omeprazole Sodium in omeprazole 40g, the water for injection described in the step (1) is that water for injection adds to 2000ml.
8, method according to claim 1 is characterized in that, the raw material of the recipe quantity described in the step (1) be Omeprazole Sodium in omeprazole 22.31g and mannitol 100g, the water for injection described in the step (1) is that water for injection adds to 1500ml.
9, method according to claim 1 is characterized in that, the raw material of the recipe quantity described in the step (1) be Omeprazole Sodium in omeprazole 44.63g and mannitol 200g, the water for injection described in the step (1) is that water for injection adds to 3000ml.
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| CNB2008100011814A CN100496463C (en) | 2007-08-14 | 2008-01-18 | Omeprazole sodium freeze-dried powder injection and preparing method thereof |
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| CN200710016396.9 | 2007-08-14 | ||
| CN200710016396 | 2007-08-14 | ||
| CNB2008100011814A CN100496463C (en) | 2007-08-14 | 2008-01-18 | Omeprazole sodium freeze-dried powder injection and preparing method thereof |
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| CN100496463C true CN100496463C (en) | 2009-06-10 |
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| CN101744777B (en) * | 2009-12-30 | 2012-09-26 | 北京四环科宝制药有限公司 | Omeprazole sodium freeze-dried powder injection, as well as preparation method and quality control method thereof |
| CN101744815B (en) * | 2010-01-12 | 2011-06-29 | 邓学峰 | Combination drugs with omeprazole sodium |
| CN101791295B (en) * | 2010-02-24 | 2012-07-11 | 王保明 | Compound monoammonium glycyrrhizinate S pharmaceutical composition and method for preparing frozen powder injection |
| CN103006588A (en) * | 2013-01-22 | 2013-04-03 | 南京正宽医药科技有限公司 | Omeprazole sodium for injection and preparation method thereof |
| CN104161732B (en) * | 2013-05-17 | 2016-05-18 | 福建省闽东力捷迅药业有限公司 | Injection omeprazole sodium and its production and use |
| CN104127387A (en) * | 2014-02-21 | 2014-11-05 | 杭州长典医药科技有限公司 | Special ultrafine omeprazole sodium powder freeze-dried preparation and preparation method thereof |
| CN112807282A (en) * | 2021-01-13 | 2021-05-18 | 海南葫芦娃药业集团股份有限公司 | Omeprazole sodium freeze-dried powder injection and preparation method thereof |
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