CN104161732B - Injection omeprazole sodium and its production and use - Google Patents
Injection omeprazole sodium and its production and use Download PDFInfo
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- CN104161732B CN104161732B CN201310183302.2A CN201310183302A CN104161732B CN 104161732 B CN104161732 B CN 104161732B CN 201310183302 A CN201310183302 A CN 201310183302A CN 104161732 B CN104161732 B CN 104161732B
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Abstract
The invention discloses a kind of injection omeprazole sodium and its production and use. Injection omeprazole sodium of the present invention is to be prepared from through freeze-drying by Omeprazole sodium water solution, and to prepare 1000, described Omeprazole sodium water solution is formulated by Omeprazole Sodium 30-55g, water for injection 1200ml and active carbon; Wherein, the weight of described Omeprazole Sodium is calculated with Omeprazole; The consumption of described active carbon is 0.01-0.03% (g/ml); The pH of described Omeprazole sodium water solution is 9.5-11.5. It is few that injection omeprazole sodium of the present invention has component kind, and simple feature; Product is stable, is more suitable in being used as medicine.
Description
Technical field
The invention belongs to pharmaceutical technology, specifically, relate to injection omeprazole sodium and system thereofPreparation Method and purposes.
Background technology
Peptic ulcer is the mankind's common disease, becomes worldwide distribution, according to document announcement approximately 10%Population was suffered from this disease in life. In the pathogenic factors of peptic ulcer, the existence of hydrochloric acid in gastric juice is that ulcer is sent outRaw decisive factor, and helicobacter pylori infections is also its Etiological. Clinical treatment eliminate the cause of disease,Remove on the basis of symptom, apply the effective gastric acid secretion inhibiting of related drugs and thoroughly eradicate pylorus spiral shellBacillus is a very important link for the treatment of. Therefore, select comparatively effectively medicine of oneParticularly important. Omeprazole Sodium can reduce gastric acid secretion because of it, promotes ulcer healing and makes pylorus spiralBacterium quantity declines or the effect of turning out cloudy has the treatment of patients with peptic ulcer that should not oral administrationImportant clinical meaning.
Omeprazole Sodium, English name omeprazolesodium, is the research and development of A.B.Astra company of SwitzerlandThe novel PUD curative of one of producing, for artificial synthetic benzimidazole proton pump presses downPreparation, is used for the treatment of peptic ulcer, reflux esophagitis, Zuo-Ai Er Shi (Zollinger-Ellison)Syndrome.
Topaz is bright discloses a kind of stable injection in Chinese patent application CN200610042004.1With omeprazol sodium preparation, contain disodium ethylene diamine tetraacetate and sweet mellow wine.
SHANDONG LUOXIN PHARMACY STOCK Co., LTD. is public in Chinese patent application CN200810001181.4Open a kind of omeprazole sodium freeze-dried powder pin and preparation method thereof, prepared Aomei by adding natrium citricumDraw azoles sodium freeze-drying powder.
Hainan Ruiji Drug Research Co., Ltd. is public in Chinese patent application CN200810062160.3Open a kind of omeprazole freeze-dried powder injection, taking Omeprazole as main active, contained skeletonAgent, complexing of metal ion agent, stabilizing agent, antioxidant, pH value conditioning agent, preparation pH value is adjusted to10.8～11.2。
Hainan Benchuang Pharmaceutical Technology Co., Ltd. discloses in Chinese patent CN200810211501.9A kind of Omeprazole Sodium nanoparticle lyophilized formulations is to be made up of the raw material of following portions by weight: Aomei draws20～40 parts, azoles sodium, 20～200 parts of glucans, 5～60 parts of stabilizing agents, sodium sulfite 5～40Part, 40～400 parts of polymethyl methacrylates, 10～500 parts of freeze-drying skeleton agent.
Beijing Sihuankebao Pharmaceutical Co., Ltd. is public in Chinese patent application CN200910244378.5Opened a kind of omeprazole sodium freeze-dried powder pin, use in conjunction antioxidant and chelating agent.
Hainan Levtec Pharmaceutical Co., Ltd. is public in Chinese patent application CN200910226008.9Opened a kind of omeprazole sodium freeze-dried powder pin, be by Omeprazole sodium-hydrate, mosatil andNaOH composition.
Xiuxinchenbang Medical Science and Technology Co., Ltd., Shanghai is at Chinese patent application CN200910056113.2In a kind of omeprazol sodium preparation for injection is disclosed, be by Omeprazole Sodium, ethylenediamine tetra-acetic acid twoSodium and sterile water for injection are made into, and make injection omeprazole sodium through freeze-drying.
Liu Jianhong discloses a kind of injection Aomei in Chinese patent application CN200910115570.4Draw azoles sodium pharmaceutical composition and preparation method thereof, by Omeprazole Sodium, disodium ethylene diamine tetraacetate, sweetReveal the raw materials such as alcohol and sodium sulfite and put into water for injection stirring and dissolving, regulating pH value is 10.5-10.9,And carry out freeze drying and make freeze drying powder injection.
Deng Jujuan discloses a kind of injection Aomei in Chinese patent application CN200910143916.1Draw azoles sodium, by Omeprazole Sodium, filler, complexing of metal ion agent, antioxidant, pH adjusting agent groupBecome.
Wang Ming discloses a kind of Omeprazole Sodium and has frozen in Chinese patent application CN200910019998.9Dry Liposomal formulation, each component and weight portion are: Omeprazole Sodium 10-20 part, phosphatidase 11 0-40 part,Cholesterol 0-10 part, antioxidant 0-10 part, frozen-dried supporting agent 5-20 part.
Shandong Xinshidai Pharmaceutical Industry Co., Ltd. is open in Chinese patent application CN201010123742.5A kind of omeprazole sodium freeze-dried powder pin and preparation method thereof, this powder-injection contains proppant as sweet dewAlcohol, metal-chelator are if mosatil and pH adjusting agent are as sodium carbonate.
Deng Xuefeng discloses a kind of Omeprazole Sodium in Chinese patent application CN201010045826.1Pharmaceutical composition, comprises Omeprazole Sodium, vitamin C and natrium adetate.
Hainan Jinrui Pharmacy stock Co., Ltd is public in Chinese patent application CN201110429043.8Opened a kind of omeprazole sodium freeze-dried powder pin, it is by Omeprazole Sodium dihydrate, sodium chloride, complies withThe compositions such as ground acid disodium, pH adjusting agent.
Jiangsu Aosaikang Pharmaceutical Co., Ltd is open in Chinese patent application CN201110119352.5A kind of Omeprazole composition of sodium of injection, contain Omeprazole Sodium and ethylenediamine tetra-acetic acid twoSodium.
Hubei Neo-Treation Pharmaceutical Co., Ltd. discloses one in Chinese patent CN201210042788.3Containing the Omeprazole sodium injection of sodium tartrate.
Hainan Jinrui Pharmacy stock Co., Ltd is public in Chinese patent application CN201210587183.2Opened a kind of omeprazole sodium medicinal composition, it is by Omeprazole Sodium, sodium chloride, edetic acid(EDTA) twoThe composition such as sodium, pH adjusting agent.
Zhejiang Asia-Pacific Pharmaceutical Co., Ltd is public in Chinese patent application CN201210390823.0Open a kind of Omeprazole freeze-dried powder that comprises mosatil and NaOH, solved Aomei and drawnThe problem of azoles sodium to metal ion-sensitive.
Nanjing Zhengkuan Pharmaceutical Technology Co., Ltd. is public in Chinese patent application CN201310023685.7Opened a kind of injection omeprazole sodium, it is by Omeprazole Sodium, phosphatide, sodium citrate and pHConditioning agent composition.
Above-mentioned disclosed omeprazole sodium freeze-dried preparation all adopts chelating agent or stabilizing agent to prepare.Therefore there are such needs in prior art: a kind of stable and few omeprazole sodium freeze-dried powder of componentPin.
Summary of the invention
The inventor has been surprisingly found out that a kind of stable and without multiple groups through a large amount of researchThe omeprazole sodium freeze-dried preparation of part, without chelating agent or stabilizing agent, and, the injection obtainingOmeprazole stable sodium, meets medicinal requirement.
The object of this invention is to provide a kind of stable injection omeprazole sodium.
Another object of the present invention is to provide the preparation method of above-mentioned injection omeprazole sodium.
The 3rd object of the present invention is to provide the purposes of above-mentioned injection omeprazole sodium.
Specifically, the invention provides a kind of stable injection omeprazole sodium, is to be drawn by AomeiAzoles sodium water solution is prepared from through freeze-drying, and to prepare 1000, described Omeprazole Sodium is water-solubleLiquid is formulated by Omeprazole Sodium 30-55g, water for injection 1200ml and active carbon;
Wherein, the weight of described Omeprazole Sodium is calculated with Omeprazole;
The consumption of described active carbon is 0.01-0.03% (g/ml);
The pH of described Omeprazole sodium water solution is 9.5-11.5.
In a kind of preferred embodiment of the present invention, the invention provides a kind of stable injection AustriaAzoles sodium draws in U.S.A, is to be prepared from through freeze-drying by Omeprazole sodium water solution, and to prepare 1000,Described Omeprazole sodium water solution be by Omeprazole Sodium 35-52g, water for injection 1200ml andActive carbon is formulated;
Wherein, the weight of described Omeprazole Sodium is calculated with Omeprazole;
The consumption of described active carbon is 0.015-0.025% (g/ml);
The pH of described Omeprazole sodium water solution is 10.0-11.5.
In a kind of particularly preferred embodiment of the present invention, the invention provides a kind of stable injectionWith Omeprazole Sodium, be to be prepared from through freeze-drying by Omeprazole sodium water solution, to prepare 1000Meter, described Omeprazole sodium water solution be by Omeprazole Sodium 40g, water for injection 1200ml andActive carbon is formulated;
Wherein, the weight of described Omeprazole Sodium is calculated with Omeprazole;
The consumption of described active carbon is 0.02% (g/ml);
The pH of described Omeprazole sodium water solution is 10.0-11.5.
In embodiments of the invention, injection omeprazole sodium provided by the invention, wherein, AustriaIt is to adopt sodium hydrate aqueous solution or hydrochloric acid to regulate that the pH value of azoles sodium water solution is drawn by U.S.A, preferably,Adopt 5 % by weight NaOH, or 5 % by weight hydrochloric acid.
On the other hand, the invention provides the preparation method of above-mentioned injection omeprazole sodium, comprise asLower step:
1. blending process:
(1) dissolving, decolouring, depyrogenation: take the water for injection of total amount 90 volume % in Agitation TankIn, control water temperature below 35 DEG C, add Omeprazole Sodium, stirring at room temperature makes to dissolve, adjust pHTo 9.5-11.5, benefit adds to the full amount of water for injection, and after stirring evenly, then adds active carbon, and stirring at room temperature is inhaledAttached 15 minutes;
(2) coarse filtration: except carbon filter (preferably adopting 0.65 μ m or 0.8 μ m titanium rod) filtersDe-charcoal;
(3) essence filter: by 0.45 μ m and the series connection of 0.22 μ m miillpore filter, carry out essence filter;
(4) divide and be filled to injection bottle made;
2. freeze-drying:
(1) pre-freeze temperature: control products temperature below-40 DEG C; The pre-freeze time: approximately 4 hours;
(2) sublimation temperature: 3 DEG C ± 1 DEG C (shelf temperature); The distillation time: 12-17 hour;
(3) baking temperature again: 20 DEG C (shelf temperature); Drying time again: 2-6 hour, fills nitrogenTamponade;
(4) lyophilization cycle: 20-27 hour.
In a preferred embodiment of the present invention, above-mentioned injection omeprazole sodium provided by the inventionPreparation method, comprises the steps:
1. blending process:
(1) dissolving, decolouring, depyrogenation: take the water for injection of total amount 90 volume % in Agitation TankIn, control water temperature below 35 DEG C, add Omeprazole Sodium, stirring at room temperature makes to dissolve, and uses 5 weightsAmount %NaOH (or 5 % by weight HCl) adjust pH to 10.5～11.0, benefit adds to the full amount of water for injection,After stirring evenly, then add active carbon, stirring at room temperature absorption 15 minutes;
(2) coarse filtration: be ready to, except carbon filter (0.65 μ m or 0.8 μ m titanium rod), open feedingValve, opens filter pump, and filtering decarbonization, refluxes 10 minutes, and sampling detects just filtrate clarity, orderSurvey should be clarified, and without leaking charcoal phenomenon, the liquid that carbon removal is handled well is sent into receiver;
(3) essence filter: by 0.45 μ m of integrity test passed examination and 0.22 μ m miillpore filterSeries connection, carries out essence filter. After essence filter, sampling detects, qualified rear calculating loading amount;
(4) divide and be filled in injection bottle made, the laggard case of partly jumping a queue;
2. freeze-drying:
(1) pre-freeze temperature: control products temperature below-40 DEG C; The pre-freeze time: approximately 4 hours;
(2) sublimation temperature: 3 DEG C ± 1 DEG C (shelf temperature); The distillation time: about 15h;
(3) baking temperature again: 20 DEG C (shelf temperature); Drying time again: about 4h, fills nitrogen tamponade;
(4) lyophilization cycle: about 23h.
The third aspect, the invention provides the purposes of above-mentioned injection omeprazole sodium, comprises that treatment disappearsPeptic-ulcer, reflux esophagitis and ZE syndrome. Intravenous injection injection of the present invention AustriaAzoles sodium draws in U.S.A, and dosage is 40 milligrams, once a day. Every daily dose can be higher, and dosage should be individualChange. When exceeding 60 milligram hours, odd-numbered day dosage can give for twice.
Stability test proves: not containing chelating agent or stabilizing agent in the situation that, and note provided by the inventionIt is stable penetrating with Omeprazole Sodium.
Compared with prior art, injection omeprazole sodium tool of the present invention has the following advantages:
(1) component kind is few, and auxiliary material is simply easy to obtain. Without chelating agent or stabilizing agentUnder condition, obtain equally stable injection omeprazole sodium.
(2) in the situation that not using skeleton agent containing injection, no matter be dissolubility or appearance character,Obtain equally and met the product that Chinese pharmacopoeia (2010 editions) requires.
Brief description of the drawings
The freeze-drying curve of the embodiment 1 that Fig. 1 represents.
The freeze-drying curve of the embodiment 2 that Fig. 2 represents.
Detailed description of the invention
Further illustrate the present invention below by embodiment, but these embodiment do not form to thisBright protection domain restriction. For a person skilled in the art, under instruction of the present invention, according toThe instruction of prior art, modifies or is equal to replacement following embodiment, still belongs to of the present inventionProtection domain.
Embodiment 1
Technology preparation: (in 10,000 bottles)
2, technique preparation process:
1. washing and the sterilizing of injection bottles made of glass tubes etc.
Injection bottles made of glass tubes, butyl rubber bung are by routine requirement washing, the sterilizing of aseptic injectionFor subsequent use afterwards, aluminium-plastic combined cover is for subsequent use after sterilizing.
2. blending process:
(1) dissolving, decolouring, depyrogenation: the water for injection that takes total amount 90% by production ordering inIn Agitation Tank, control water temperature below 35 DEG C, add command quantity Omeprazole Sodium, stirring at room temperature makes moltenSeparate, with 5%NaOH (or 5%HCl) adjust pH to 10.6, benefit adds to the full amount of water for injection, and stirsAfter even, then add injection-use activated carbon by 0.2 ‰ of liquid weight, stirring at room temperature absorption 15 minutes;
(2) coarse filtration: be ready to, except carbon filter (0.65 μ m or 0.8 μ m titanium rod), open feed valve,Open filter pump, filtering decarbonization, refluxes 10 minutes, and sampling detects just filtrate clarity, and range estimation shouldClarification, without leaking charcoal phenomenon, the liquid that carbon removal is handled well is sent into receiver.
(3) essence filter: by 0.45 μ m of integrity test passed examination and 0.22 μ m miillpore filter stringConnection, carries out essence filter. After essence filter, sampling detects, qualified rear calculating loading amount.
(4) be filled in 5ml injection bottles made of glass tubes respectively half by labelled amount (40mg/ bottle) pointInlet after jumping a queue.
3. freeze-drying:
(1) pre-freeze temperature: control products temperature below-40 DEG C; The pre-freeze time: approximately 4 hours.
(2) sublimation temperature: 3 DEG C ± 1 DEG C (shelf temperature); The distillation time: about 15h.
(3) baking temperature again: 20 DEG C (shelf temperature); Drying time again: about 4h, fills nitrogen tamponade.
(4) lyophilization cycle: about 23h. Freeze-drying curve as shown in Figure 1.
Sampling observation conform with the regulations after tamponade, outlet, roll lid, lamp and examine.
5. packaging, Quan Jian, warehouse-in.
Embodiment 2
Technology preparation: (in 10,000 bottles)
2, technique preparation process:
1. washing and the sterilizing of injection bottles made of glass tubes etc.
Injection bottles made of glass tubes, butyl rubber bung are by routine requirement washing, the sterilizing of aseptic injectionFor subsequent use afterwards, aluminium-plastic combined cover is for subsequent use after sterilizing.
2. blending process:
(1) dissolving, decolouring, depyrogenation: the water for injection that takes total amount 90% by production ordering inIn Agitation Tank, control water temperature below 35 DEG C, add command quantity Omeprazole Sodium, stirring at room temperature makes moltenSeparate, with 5%NaOH (or 5%HCl) adjust pH to 10.8, benefit adds to the full amount of water for injection, and stirsAfter even, then add injection-use activated carbon by 0.2 ‰ of liquid weight, stirring at room temperature absorption 15 minutes;
(2) coarse filtration: be ready to, except carbon filter (0.65 μ m or 0.8 μ m titanium rod), open feed valve,Open filter pump, filtering decarbonization, refluxes 10 minutes, and sampling detects just filtrate clarity, and range estimation shouldClarification, without leaking charcoal phenomenon, the liquid that carbon removal is handled well is sent into receiver.
(3) essence filter: by 0.45 μ m of integrity test passed examination and 0.22 μ m miillpore filter stringConnection, carries out essence filter. After essence filter, sampling detects, qualified rear calculating loading amount.
(4) be filled in 5ml injection bottles made of glass tubes respectively half by labelled amount (40mg/ bottle) pointInlet after jumping a queue.
3. freeze-drying:
(1) pre-freeze temperature: control products temperature below-40 DEG C; The pre-freeze time: approximately 4 hours.
(2) sublimation temperature: 3 DEG C ± 1 DEG C (shelf temperature); The distillation time: about 15h.
(3) baking temperature again: 25 DEG C (shelf temperature); Drying time again: about 3h, fills nitrogen tamponade.
(4) lyophilization cycle: about 23h. Freeze-drying curve as shown in Figure 2.
Sampling observation conform with the regulations after tamponade, outlet, roll lid, lamp and examine.
5. packaging, Quan Jian, warehouse-in.
Reference examples 1
Prescription, with embodiment 1 and 2, adds sweet mellow wine 500g, and process for preparation and freeze-drying are with embodiment 1With 2. This product raw material is Omeprazole Sodium, and every contains 40mg, auxiliary material screening following (50 in prescription/ batch)
The screening of table 1 injection omeprazole sodium auxiliary material
From above experiment, after freeze-drying, both outward appearances all show white loose bulk, dissolubility aspect,Embodiment 1 is better than reference examples 1.
Reference examples 2
Prescription is with embodiment 1, and wherein, the addition of active carbon is respectively: 0.1% (w/v), detectsThe content of Omeprazole Sodium. The results are shown in Table 2.
The absorption situation of the needle-use activated carbon of table 2 variable concentrations to main ingredient
Result of the test shows, active carbon has suction-operated to injection omeprazole sodium, adds and adopt0.02% active carbon can solve the problem of preparation clarity and pyrogen as adsorbent, also can be to AustriaU.S.A draws the suction-operated of azoles sodium minimum.
Test example
To the product of 1 three batches of the embodiment of the present invention (20030215,20030216,20030217)Product carry out quality research and stability study thereof, and its result is as follows:
1. quality research
The situation of three batches of quality researches is as table 3, check and detection method referring to inspection below andDetection method of content.
The inspection of three batches of injection omeprazole sodiums of table 3
2. the study on the stability of preparation
(1) influence factor test
A. strong illumination test
Injection omeprazole sodium sample (20030215) is positioned in the lighting box that fluorescent lamp is housed,Under the high light condition that is 4500lx in illumination, place 10 days, take a sample to check respectively at the 5th, 10 days,And with result comparison in 0 day, the results are shown in Table 4.
Table 4 injection omeprazole sodium intense light irradiation result of the test
Table 4 result shows: this product is placed after 10 days under high light 4500lx illumination condition, sampling inspectionLook into, related substance increases slightly to some extent, and other every detection indexs have no significant change, and this product palpus is describedShading is preserved.
B. hot test
Get injection omeprazole sodium sample (20030215), open external packing, be placed in 60 DEG C of insulating boxsMiddle placement 10 days, took a sample to check respectively at the 5th, 10 days, and with result comparison in 0 day, the results are shown inTable 5.
60 DEG C of hot test results of table 5 injection omeprazole sodium
Table 5 result shows: this product is placed after 10 days under 60 DEG C of conditions, takes a sample to check, relevant thingMatter increases, and other every detection indexs have no significant change, therefore this product is preserved under cryogenic conditions.
C. hot test
Get injection omeprazole sodium sample (20030215), open external packing, be placed in 25 DEG C relatively wetDegree is placed 10 days under 90% ± 5% condition, take a sample to check respectively at the 5th, 10 days, and with 0 day knotFruit relatively, the results are shown in Table 6.
Table 6 injection omeprazole sodium high humidity result of the test
Table 6 result shows: this product is placed after 10 days under hot conditions, take a sample to check, and Ge XiangjianSurvey index has no significant change, therefore this product is stable under hot conditions.
(2) accelerated test
Get this product quality research sample (lot number: 20030215,20030216,20,030,217 3 batches,Put 40 DEG C ± 2 DEG C of temperature, in RH75% temperature and humidity regulator, respectively at 0,1,2,3,6, DecemberSampling, measures indices, the results are shown in Table 7.
(3) room temperature keep sample for a long time investigate test
Get three batch samples of quality research, be placed on 25 DEG C ± 2 DEG C, under RH60% ± 10% condition,Respectively at sampling in 0,3,6,9,12 month, measure relevant indices, the results are shown in Table 8.
Table 7 injection omeprazole sodium accelerated test result
Table 8 injection omeprazole sodium long term test is investigated result
Conclusion: show injection of the present invention Austria by the accelerated test to three batch samples and long term testU.S.A draws azoles sodium indices to have no significant change.
3. check and content assaying method
1. check
1.1 basicity
Get the solution under clarity and the color item of solution, measure (Chinese pharmacopoeia version in 2010 in accordance with the lawTwo annex VIH) pH value.
The clarity of 1.2 solution and color
Get 5 bottles of this product, add water or appended dedicated solvent makes in right amount to dissolve and makes every 1ml and draws containing AomeiThe solution of azoles 4.0mg, solution should be clarified, as aobvious muddy, with No. 1 turbidity standard (Chinese pharmacopoeia2010 editions two annex IXB) relatively, must not be denseer; Get solution, according to UV-VIS spectrophotometry(2010 editions two annex IVA of Chinese pharmacopoeia), measure at 440nm wavelength place, and absorbance must not mistake0.1。
1.3 moisture
Get this product, according to aquametry (two annex VIIIM first methods of Chinese pharmacopoeia version in 2010)Measure, moisture content must not cross 7.0%.
1.4 visible foreign matters
Get this product, check in accordance with the law and should conform with the regulations (two annex IXH of Chinese pharmacopoeia version in 2010).
1.5 particulate matter
Get this product, check in accordance with the law and should conform with the regulations (two annex IXC of Chinese pharmacopoeia version in 2010).
1.6 aseptic
Get this product, add respectively sterilized water for injection (or peptone water solution of 0.1%) and make every 1mlMiddle approximately containing the solution of Omeprazole 8mg, after processing with membrane-filter procedure, check (Chinese pharmacopoeia in accordance with the lawTwo annex XIH of version in 2010), should conform with the regulations.
1.7 bacterial endotoxin
Get this product, check (two annex XIE of Chinese pharmacopoeia version in 2010), every 1mg Aomei in accordance with the lawDraw in azoles and should be less than 2.0EU containing endotoxic amount.
1.8 related substance
Lucifuge operation. Get 5 bottles of this product, add respectively mobile phase and make in right amount contents melting, quantitatively shiftTo in same 200ml measuring bottle and be diluted to scale, shake up, precision measures in right amount, adds mobile phase and makesIn every 1ml, approximately contain the solution of Omeprazole 0.5mg, as need testing solution; Precision measures in right amount,Add mobile phase and make the solution that approximately contains Omeprazole 2.5 μ g in every 1ml, solution in contrast. According to containingChromatographic condition under quantitative determination item, detection wavelength is 280nm, gets contrast solution 20 μ l, injects liquid phaseChromatograph, regulates detection sensitivity, makes the high 20%-25% that is about full scale of main peak, more accurate amountGet the each 20 μ l of contrast solution and need testing solution, injection liquid chromatography respectively, records chromatogram to supplying3 times of test product main peak retention time. Need testing solution chromatogram is as aobvious impurity peaks, the peak face of impurity DMust not amass 0.5 times (0.5%) of contrast solution main peak area. It is molten that other single impurity must not be crossed contrast0.5 times (0.5%) of liquid main peak area. Total impurities peak area and must not cross contrast liquid main peak area1.0 times (1.0%).
2. the detection of content
With octyl group silane group silica gel be filler; (use 1% phosphorus with 1.4g/L disodium phosphate solnAcid solution regulates pH value to 7.6)-acetonitrile (73: 27) is mobile phase; Detection wavelength is 305nm;40 DEG C of column temperatures; Precision takes Omeprazole reference substance respectively, impurity D is appropriate to same measuring bottle, addsMobile phase is appropriate, shakes up and makes the solution containing the each 0.1mg of above composition in every ml, and precision measuresState solution 20ul, injection liquid chromatography, theoretical cam curve is calculated and should be not less than by Omeprazole peak3000, the separating degree of Omeprazole peak and impurity D should be not less than 3.0.
Determination method: lucifuge operation. Get 5 bottles of this product, add respectively mobile phase and make in right amount contents melting,Quantitatively be transferred in same 200ml measuring bottle and be diluted to scale, shaking up, precision measures in right amount, adds streamThe moving solution that approximately contains Omeprazole 0.1mg in every 1ml of making mutually, precision measures 20 μ l and injects liquid phasesChromatograph, records chromatogram; Separately get Omeprazole Sodium reference substance appropriate, accurately weighed, use mobile phaseMake the solution that approximately contains Omeprazole 0.1mg in every 1ml, be measured in the same method, with external standard method calculating,.
Claims (4)
1. an injection omeprazole sodium, is to be prepared from through freeze-drying by Omeprazole sodium water solution,To prepare 1000, described Omeprazole sodium water solution is by Omeprazole Sodium 35-52g, notePenetrate water 1200ml, active carbon and pH value conditioning agent formulated;
Wherein, the weight of described Omeprazole Sodium is calculated with Omeprazole;
The consumption of described active carbon is 0.015-0.025% (g/ml);
The pH of described Omeprazole sodium water solution is 10.0-11.5;
The pH value conditioning agent of described Omeprazole sodium water solution is to adopt sodium hydrate aqueous solution or hydrochloric acid;
Here, the preparation method of described injection omeprazole sodium, comprises the steps:
(1). blending process:
(1.1) dissolving, decolouring, depyrogenation: take the water for injection of total amount 90 volume % in dosingIn tank, control water temperature below 35 DEG C, add Omeprazole Sodium, stirring at room temperature makes to dissolve, and adjusts pHBe worth to 10.0-11.5, benefit adds to the full amount of water for injection, and after stirring evenly, then adds active carbon, stirring at room temperatureAdsorb 15 minutes;
(1.2) coarse filtration: adopt 0.65 μ m or 0.8 μ m titanium rod except carbon filter filtering decarbonization;
(1.3) essence filter: by 0.45 μ m and the series connection of 0.22 μ m miillpore filter, carry out essence filter;
(1.4) divide and be filled to injection bottle made;
(2). freeze-drying:
(2.1) pre-freeze temperature: control products temperature below-40 DEG C; The pre-freeze time: approximately 4 hours;
(2.2) sublimation temperature: 3 DEG C ± 1 DEG C of shelf temperature; The distillation time: 12-17 hour;
(2.3) baking temperature again: 20 DEG C-25 DEG C of shelf temperatures; Drying time again: 2-6 hour, fillsNitrogen tamponade;
(2.4) lyophilization cycle: 20-27 hour.
2. an injection omeprazole sodium, is to be prepared from through freeze-drying by Omeprazole sodium water solution,To prepare 1000, described Omeprazole sodium water solution is by Omeprazole Sodium 40g, injectionWater 1200ml, active carbon and pH value conditioning agent are formulated;
Wherein, the weight of described Omeprazole Sodium is calculated with Omeprazole;
The consumption of described active carbon is 0.02% (g/ml);
The pH of described Omeprazole sodium water solution is 10.0-11.5;
The pH value conditioning agent of described Omeprazole sodium water solution is to adopt 5 % by weight NaOH or 5% by weight hydrochloric acid;
Here, the preparation method of described injection omeprazole sodium, comprises the steps:
(1). blending process:
(1.1) dissolving, decolouring, depyrogenation: take the water for injection of total amount 90 volume % in dosingIn tank, control water temperature below 35 DEG C, add Omeprazole Sodium, stirring at room temperature makes to dissolve, and uses 5 weightsAmount %NaOH or 5 % by weight HCl adjust pH to 10.5～11.0, benefit adds to the full amount of water for injection,After stirring evenly, then add active carbon, stirring at room temperature absorption 15 minutes;
(1.2) coarse filtration: be ready to the carbon filter that removes of 0.65 μ m or 0.8 μ m titanium rod, open and sendMaterial valve, opens filter pump, and filtering decarbonization, refluxes 10 minutes, and sampling detects just filtrate clarity,Range estimation should be clarified, and without leaking charcoal phenomenon, the liquid that carbon removal is handled well is sent into receiver;
(1.3) essence filter: by 0.45 μ m of integrity test passed examination and 0.22 μ m miillpore filterSeries connection, carries out essence filter, and after essence filter, sampling detects, qualified rear calculating loading amount;
(1.4) divide and be filled in injection bottle made, the laggard case of partly jumping a queue;
(2). freeze-drying:
(2.1) pre-freeze temperature: control products temperature below-40 DEG C; The pre-freeze time: approximately 4 hours;
(2.2) sublimation temperature: 3 DEG C ± 1 DEG C of shelf temperature; The distillation time: about 15h;
(2.3) baking temperature again: 20 DEG C of shelf temperatures; Drying time again: about 4h, fills nitrogen tamponade;
(2.4) lyophilization cycle: about 23h.
3. described in claim 1, injection omeprazole sodium is treated peptic ulcer, anti-fluidity in preparationApplication in esophagitis or ZE syndrome medicine.
4. described in claim 2, injection omeprazole sodium is treated peptic ulcer, anti-fluidity in preparationApplication in esophagitis or ZE syndrome medicine.
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| CN105919953A (en) * | 2016-06-27 | 2016-09-07 | 峨眉山通惠制药有限公司 | Omeprazole sodium composition for injection and production process of omeprazole sodium composition |
| CN111973562A (en) * | 2020-09-04 | 2020-11-24 | 四川制药制剂有限公司 | Esomeprazole sodium for injection 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 |
| CN114191396B (en) * | 2021-11-30 | 2023-05-05 | 海南全星制药有限公司 | Omeprazole sodium for injection and preparation method thereof |
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| CN101229133A (en) * | 2007-08-14 | 2008-07-30 | 山东罗欣药业股份有限公司 | Omeprazole sodium freeze-dried powder injection and preparing method thereof |
| CN102525965A (en) * | 2012-02-24 | 2012-07-04 | 湖北济生医药有限公司 | Omeprazole sodium drug composition and preparation method thereof |
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| CN101229133A (en) * | 2007-08-14 | 2008-07-30 | 山东罗欣药业股份有限公司 | Omeprazole sodium freeze-dried powder injection and preparing method thereof |
| CN102525965A (en) * | 2012-02-24 | 2012-07-04 | 湖北济生医药有限公司 | Omeprazole sodium drug composition and preparation method thereof |
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