CN104013586A - Preparation method of lansoprazole freeze-dried powder injection for injection - Google Patents
Preparation method of lansoprazole freeze-dried powder injection for injection Download PDFInfo
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- CN104013586A CN104013586A CN201410276117.2A CN201410276117A CN104013586A CN 104013586 A CN104013586 A CN 104013586A CN 201410276117 A CN201410276117 A CN 201410276117A CN 104013586 A CN104013586 A CN 104013586A
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- injection
- lansoprazole
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- 229960003174 lansoprazole Drugs 0.000 title claims abstract description 59
- MJIHNNLFOKEZEW-UHFFFAOYSA-N lansoprazole Chemical compound CC1=C(OCC(F)(F)F)C=CN=C1CS(=O)C1=NC2=CC=CC=C2N1 MJIHNNLFOKEZEW-UHFFFAOYSA-N 0.000 title claims abstract description 59
- 239000007924 injection Substances 0.000 title claims abstract description 31
- 238000002347 injection Methods 0.000 title claims abstract description 31
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 239000000843 powder Substances 0.000 title abstract 4
- 239000000243 solution Substances 0.000 claims abstract description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 22
- 238000001914 filtration Methods 0.000 claims abstract description 17
- 238000003756 stirring Methods 0.000 claims abstract description 15
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims abstract description 13
- 229930195725 Mannitol Natural products 0.000 claims abstract description 13
- 239000000594 mannitol Substances 0.000 claims abstract description 13
- 235000010355 mannitol Nutrition 0.000 claims abstract description 13
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 12
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 claims abstract description 11
- 229960003194 meglumine Drugs 0.000 claims abstract description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000000706 filtrate Substances 0.000 claims abstract description 9
- 239000003513 alkali Substances 0.000 claims abstract description 7
- 238000004321 preservation Methods 0.000 claims abstract description 7
- 239000008215 water for injection Substances 0.000 claims description 14
- JGSARLDLIJGVTE-UHFFFAOYSA-N 3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-UHFFFAOYSA-N 0.000 claims description 11
- 239000012982 microporous membrane Substances 0.000 claims description 11
- 238000005516 engineering process Methods 0.000 claims description 9
- 238000001035 drying Methods 0.000 claims description 8
- 238000009413 insulation Methods 0.000 claims description 7
- 230000001186 cumulative effect Effects 0.000 claims description 6
- 238000004821 distillation Methods 0.000 claims description 6
- 230000033228 biological regulation Effects 0.000 claims description 5
- 230000014759 maintenance of location Effects 0.000 claims description 5
- 238000000859 sublimation Methods 0.000 claims description 5
- 230000008022 sublimation Effects 0.000 claims description 5
- 229940090044 injection Drugs 0.000 abstract description 23
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 abstract description 11
- 238000000034 method Methods 0.000 abstract description 9
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 abstract description 7
- 229940093181 glucose injection Drugs 0.000 abstract description 7
- 239000001540 sodium lactate Substances 0.000 abstract description 7
- 229940005581 sodium lactate Drugs 0.000 abstract description 7
- 235000011088 sodium lactate Nutrition 0.000 abstract description 7
- 239000008354 sodium chloride injection Substances 0.000 abstract description 6
- 239000012528 membrane Substances 0.000 abstract description 3
- 238000010438 heat treatment Methods 0.000 abstract description 2
- 239000002904 solvent Substances 0.000 abstract description 2
- 239000011148 porous material Substances 0.000 abstract 4
- 238000001816 cooling Methods 0.000 abstract 1
- 238000007865 diluting Methods 0.000 abstract 1
- 238000011049 filling Methods 0.000 abstract 1
- 238000004108 freeze drying Methods 0.000 abstract 1
- 239000002245 particle Substances 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- 229960001855 mannitol Drugs 0.000 description 11
- 239000013618 particulate matter Substances 0.000 description 8
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 6
- 239000008156 Ringer's lactate solution Substances 0.000 description 6
- BMLSTPRTEKLIPM-UHFFFAOYSA-I calcium;potassium;disodium;hydrogen carbonate;dichloride;dihydroxide;hydrate Chemical compound O.[OH-].[OH-].[Na+].[Na+].[Cl-].[Cl-].[K+].[Ca+2].OC([O-])=O BMLSTPRTEKLIPM-UHFFFAOYSA-I 0.000 description 6
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 6
- 238000012856 packing Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000002671 adjuvant Substances 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 3
- 238000007689 inspection Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 229920001983 poloxamer Polymers 0.000 description 3
- 230000000630 rising effect Effects 0.000 description 3
- 239000001509 sodium citrate Substances 0.000 description 3
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 3
- 235000010265 sodium sulphite Nutrition 0.000 description 3
- 238000005261 decarburization Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 208000000718 duodenal ulcer Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 208000000689 peptic esophagitis Diseases 0.000 description 1
- 229940126409 proton pump inhibitor Drugs 0.000 description 1
- 239000000612 proton pump inhibitor Substances 0.000 description 1
- 239000011265 semifinished product Substances 0.000 description 1
- 229940083608 sodium hydroxide Drugs 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
Abstract
The invention provides a preparation method of a lansoprazole freeze-dried powder injection for injection. The preparation method of the lansoprazole freeze-dried powder injection for injection is characterized by comprising the following steps: taking lansoprazole and adding the lansoprazole into a pressure container, adding injection water, heating and adjusting the temperature of the water to 105 DEG C-110 DEG C under pressurized condition, stirring for 0.5-1 hour to obtain a lansoprazole solution, then adding active carbon counting for 2%-3% of the total mass of the solution to stir for 1.5-2.5 hours, filtering by using a micro-pore filtration membrane with a pore diameter being 0.45 microns under the heat preservation condition to obtain a filtrate, adding alkali into the filtrate under the condition of the heat preservation temperature being 75 DEG C-85 DEG C and adjusting pH value to 11.0-11.5, cooling to the room temperature, adding a recipe amount of mannitol and meglumine and dropwise adding the injection water to reach the full dose, filtering by using a micro-pore filtration membrane with a pore diameter being 0.22 microns under the aseptic condition, filling and carrying out freeze-drying to obtain the lansoprazole freeze-dried powder injection for injection. The injection lansoprazole prepared by the method is relatively good in clarity and insoluble particle and can be used in match with common diluting solvents such as 0.9% sodium chloride injection, 5% glucose injection, sodium lactate injection and the like.
Description
Technical field
The present invention relates to a kind of preparation technology of lansoprazole freeze-dried injection for injection, belong to pharmaceutical production technical field.
Background technology
Lansoprazole for injecting is a kind of novel proton pump inhibitor class medicine, is mainly used in clinically treating reflux esophagitis, gastric ulcer, duodenal ulcer.The prescription of existing Lansoprazole for injecting forms, mainly comprise main constituent lansoprazole, freeze-dried excipient, pH value regulator etc., the prescription of main flow forms and contains lansoprazole, mannitol, meglumine and sodium hydroxide, and wherein mannitol is that freeze-dried excipient, meglumine are that stabilizing agent, sodium hydroxide are pH value regulators.After storing a period of time use, easily there is the problem that clarity of solution declines, particulate matter increases in Lansoprazole for injecting, causes product quality defective, brings drug safety problem.
Address this problem, a kind of thinking is the composition that changes prescription, as Chinese patent CN102151265, do not use therein mannitol and meglumine, increased chelating agen disodiumedetate, for another example Chinese patent CN102600088, in prescription, remove meglumine, increased surfactant PLURONICS F87, also had Chinese patent CN103040737, also be to have removed mannitol, and increased disodium edetate, sodium sulfite and sodium citrate.By change, write out a prescription to form and prepare Lansoprazole for injecting, its maximum shortcoming is other adjuvants that will introduce outside conventional adjuvant, no matter be disodiumedetate, PLURONICS F87 or disodium edetate, sodium sulfite, sodium citrate, although also can be applied to the production of injection, but all unavoidably produce some side effect, thereby reduced the safety of product.
The another kind of thinking addressing this problem is to change preparation technology.As Chinese patent CN102920703, adopted by the micronized method of lansoprazole bulk drug the mode that Chinese patent CN101313895 adopts crystallize to filter.These solutions can solve the clarity of Lansoprazole for injecting, the problem of particulate matter to a certain extent, but its product compatibility stability of preparing is still good not, can only use with 0.9% sodium chloride injection compatibility clinically, the retarder thinner conventional with 5% glucose injection, sodium lactate ringer's injection etc. cannot be used in conjunction with, and limited the clinical scope of application and the ease for use of this product.
Chinese patent CN102961344 provides a kind of scheme that solves this problem, add glucose as cosolvent, employing adds after alkali dissolution the at high temperature mode of remove impurity with active carbon matter and prepares Lansoprazole for injecting, Lansoprazole for injecting prepared by this mode, because added the compatibility stability of glucose and 5% glucose injection better, but still can not meet the stable problem of compatibility in sodium lactate ringer's injection.
Summary of the invention
The object of the invention is for above deficiency, a kind of preparation technology of lansoprazole freeze-dried injection for injection is provided, this preparation technology is without the routine prescription that changes Lansoprazole for injecting, without adding unconventional adjuvant, clarity, the particulate matter of the Lansoprazole for injecting preparing are better, and retarder thinner compatibility that can be conventional with 0.9% sodium chloride injection, 5% glucose injection, sodium lactate ringer's injection etc. is used, and has the wider clinical scope of application.
To achieve these goals, the invention provides a kind of preparation technology of lansoprazole freeze-dried injection for injection, it is characterized in that, concrete steps comprise: get lansoprazole and be placed in pressure vessel, the water for injection that adds cumulative volume 80%-90%, under the condition that is 0.06-0.07MPa at relative pressure, heat regulation water temperature to 105 is ℃-110 ℃, stir 0.5-1 hour, obtain lansoprazole solution, then add the active carbon of solution gross mass 2%-3% to stir 1.5-2.5 hour, under heat-retaining condition with 0.45 μ m filtering with microporous membrane, the filtrate obtaining adds alkali and regulates pH value to 11.0-11.5 under the condition of 75 ℃-85 ℃ of insulations, be down to room temperature, the mannitol and the meglumine that add recipe quantity, and be settled to full dose with water for injection, under aseptic condition, with after 0.22 μ m filtering with microporous membrane, fill is in cillin bottle, lyophilizing, obtain lansoprazole freeze-dried injection for injection.
Preferably, described freeze-dry process is: by cillin bottle false add plug, sabot is placed in freeze dryer, open freeze dryer, start compressor, to flaggy, freeze, conduction oil inlet oil temperature is set and is-40 ℃, and keep 1-3 hour, pre-freeze is finished, to cold-trap, freeze, treat that condenser temperature reaches below-45 ℃, open vacuum pump, open case trap valve, until casing vacuum, be down to 30Pa when following, start the sublimation drying that heats up, first stage distillation inlet oil temperature is made as 0 ℃, retention time is 9 ± 2 hours, second stage heat preservation and dryness, make conduction oil inlet oil temperature rise to 25～30 ℃, insulation is more than 3 hours, close case trap valve, to close case trap valve more than 120 seconds and in case vacuum rise to and be no more than after 10Pa, shutdown finishes lyophilizing.
In lansoprazole solution after described standardize solution, the concentration of lansoprazole, mannitol and meglumine is respectively 25-35g/6000ml, 50-75g/6000ml and 5-10g/6000ml.
The method that the technical program is taked, compare with prior art in CN102961344, alkali add opportunity be after decarburization is filtered but not before, at decarburization filtration stage, mainly rely on heating but not the principle that adds alkali salify guarantees the dissolving of lansoprazole, the target impurity of removing in this stage and CN102961344 have remarkable difference.Adopt in such a way and process, without adding glucose as stabilizing agent in prescription, and the compatibility stability after long-term placement has remarkable enhancing.
Compared with prior art, the invention has the beneficial effects as follows:
The present invention has adopted unique dissolution process, the lansoprazole freeze-dried injection for injection that it prepares, without adding unconventional adjuvant, as disodiumedetate, PLURONICS F87, disodium edetate, sodium sulfite, sodium citrate etc., the clarity of the Lansoprazole for injecting preparing, particulate matter is better, can avoid the clarity of solution decline occurring after a period of time storing, the problem that particulate matter increases, and can with 0.9% sodium chloride injection, 5% glucose injection, the retarder thinner compatibility that sodium lactate ringer's injection etc. are conventional is used, there is the wider clinical scope of application.
The specific embodiment
Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiment are only not used in and limit the scope of the invention for the present invention is described.In addition should be understood that those skilled in the art can make various changes or modifications the present invention after having read the content of the present invention's instruction, these equivalent form of values fall within the application's appended claims limited range equally.
Embodiment 1
Prescription
Getting recipe quantity lansoprazole puts in pressure vessel, the water for injection that adds cumulative volume 80%, under the condition that is 0.06MPa at relative pressure, heat regulation water temperature to 105 ℃, stir 0.5 hour, obtain lansoprazole solution, then add the active carbon of solution gross mass 2% to stir 2.5 hours, under heat-retaining condition with 0.45 μ m filtering with microporous membrane, the filtrate obtaining adds 5% sodium hydroxide solution and regulates pH value to 11.5 under the condition of 85 ℃ of insulations, be down to room temperature, the mannitol and the meglumine that add recipe quantity, and be settled to full dose with water for injection, under aseptic condition, with after 0.22 μ m filtering with microporous membrane, fill is in cillin bottle, by cillin bottle false add plug, sabot is placed in freeze dryer, open freeze dryer, start compressor, to flaggy, freeze, conduction oil inlet oil temperature is set and is-40 ℃, and keep 2 hours, pre-freeze is finished, to cold-trap, freeze, treat that condenser temperature reaches-45 ℃, open vacuum pump, open case trap valve, when casing vacuum is down to 30Pa, start the sublimation drying that heats up, totally two stages, first stage distillation inlet oil temperature is made as 0 ℃, retention time is 9 hours, second stage heat preservation and dryness, make conduction oil inlet oil temperature rise to 25 ℃, be incubated 3 hours, close case trap valve, to closing case trap valve after 120 seconds, in case, vacuum rising is no more than after 10Pa, shutdown finishes lyophilizing, check, packing, obtain Lansoprazole for injecting.
Embodiment 2
Prescription
Getting recipe quantity lansoprazole puts in pressure vessel, the water for injection that adds cumulative volume 90%, heat regulation water temperature to 110 ℃ under the condition that is 0.07MPa at relative pressure, stir 0.5 hour, obtain lansoprazole solution, then add the active carbon of solution gross mass 3% to stir 1.5 hours, under heat-retaining condition with 0.45 μ m filtering with microporous membrane, the filtrate obtaining adds 1% sodium hydroxide solution and regulates pH value to 11.0 under the condition of 85 ℃ of insulations, be down to room temperature, the mannitol and the meglumine that add recipe quantity, and be settled to full dose with water for injection, under aseptic condition, with after 0.22 μ m filtering with microporous membrane, fill is in cillin bottle, by cillin bottle false add plug, sabot is placed in freeze dryer, open freeze dryer, start compressor, to flaggy, freeze, conduction oil inlet oil temperature is set and is-40 ℃, and keep 2 hours, pre-freeze is finished, to cold-trap, freeze, treat that condenser temperature reaches-45 ℃, open vacuum pump, open case trap valve, when casing vacuum is down to 30Pa, start the sublimation drying that heats up, totally two stages, first stage distillation inlet oil temperature is made as 0 ℃, retention time is 9 hours, second stage heat preservation and dryness, make conduction oil inlet oil temperature rise to 25 ℃, be incubated 3 hours, close case trap valve, to closing case trap valve after 120 seconds, in case, vacuum rising is no more than after 10Pa, shutdown finishes lyophilizing, check, packing, obtain Lansoprazole for injecting.
Embodiment 3
Prescription
Getting recipe quantity lansoprazole puts in pressure vessel, the water for injection that adds cumulative volume 84%, heat regulation water temperature to 108 ℃ under the condition that is 0.065MPa at relative pressure, stir 0.5 hour, obtain lansoprazole solution, then add the active carbon of solution gross mass 2.6% to stir 2.0 hours, under heat-retaining condition with 0.45 μ m filtering with microporous membrane, the filtrate obtaining adds 0.5% sodium hydroxide solution and regulates pH value to 11.3 under the condition of 79 ℃ of insulations, be down to room temperature, the mannitol and the meglumine that add recipe quantity, and be settled to full dose with water for injection, under aseptic condition, with after 0.22 μ m filtering with microporous membrane, fill is in cillin bottle, by cillin bottle false add plug, sabot is placed in freeze dryer, open freeze dryer, start compressor, to flaggy, freeze, conduction oil inlet oil temperature is set and is-40 ℃, and keep 2 hours, pre-freeze is finished, to cold-trap, freeze, treat that condenser temperature reaches-45 ℃, open vacuum pump, open case trap valve, when casing vacuum is down to 30Pa, start the sublimation drying that heats up, totally two stages, first stage distillation inlet oil temperature is made as 0 ℃, retention time is 9 hours, second stage heat preservation and dryness, make conduction oil inlet oil temperature rise to 25 ℃, be incubated 3 hours, close case trap valve, to closing case trap valve after 120 seconds, in case, vacuum rising is no more than after 10Pa, shutdown finishes lyophilizing, check, packing, obtain Lansoprazole for injecting.
Comparative example 1
According to CN101313895 method, prepare Lansoprazole for injecting
Prescription
Getting recipe quantity lansoprazole puts in container, the water for injection that adds cumulative volume 30%, adding alkali stirring makes its dissolving mix homogeneously make lansoprazole concentrated solution, add again mannitol, stirring is dissolved and mix homogeneously it, the anti-pH to 10.3 of adjusting of acid adding, the standing crystallization of solution that makes, with microporous filter membrane, crystallize out is filtered out, measure the content of lansoprazole in solution, according to measurement result, regulate filtrate pH value to 11.5 and be settled to full dose with water for injection, under aseptic condition, with the extremely clarification of 0.22 μ m filtering with microporous membrane, in filtrate fill and aseptic cillin bottle, partly jump a queue, sabot, cartonning, open freeze dryer, reduce sample temperature to-40 ℃, keep 4 hours, stop board is cold, open cold condenser, when condenser temperature reaches below-45 ℃, open vacuum system, start the distillation that heats up, final drying temperature product temperature is 30 ℃, keep this temperature after 3 hours, tamponade, outlet, gland, quality inspection, packing, obtain Lansoprazole for injecting.
Comparative example 2
According to CN102961344 method, prepare Lansoprazole for injecting
Prescription
Take in the water for injection that recipe quantity sodium hydroxide is dissolved in new system, the sodium hydroxide solution that is mixed with 2% left and right is standby; The lansoprazole, glucose, the mannitol that take recipe quantity are dissolved in the new system water for injection of full dose 80%, add above-mentioned sodium hydroxide solution to be stirred to entirely molten; , add medicine liquid volume 1 ‰ (m/v) active carbon, about 80 ℃ of constant temperature stir 30 minutes: coarse filtration, filters out active carbon with husky filter stick; Fine straining filters with 0.22 μ m accurate filter; Intermediate pick test, determines fill loading amount according to surveyed content; Fill, partly jumps a queue, lyophilizing, tamponade, outlet, Zha Gai, semi-finished product pick test, packing, the Lansoprazole for injecting arriving.
By embodiment 1-3 and comparative example 1,2 resulting Lansoprazole for injecting, under normal temperature condition, store after 6 months, check respectively clarity and particulate matter in three kinds of solvents, as follows:
Lansoprazole for injecting clarity checks
Get Lansoprazole for injecting, use respectively 0.9% sodium chloride injection, 5% glucose injection, sodium lactate ringer's injection 10ml solution, according to clarity inspection technique, check.
Lansoprazole for injecting particulate matter checks
Get Lansoprazole for injecting, use respectively 0.9% sodium chloride injection, 5% glucose injection, sodium lactate ringer's injection 10ml solution, according to particulate matter inspection technique, check.
The results are shown in Table 1.
Claims (2)
1. the preparation technology of a lansoprazole freeze-dried injection for injection, it is characterized in that, concrete steps comprise: get lansoprazole and be placed in pressure vessel, the water for injection that adds cumulative volume 80%-90%, under the condition that is 0.06-0.07MPa at relative pressure, heat regulation water temperature to 105 is ℃-110 ℃, stir 0.5-1 hour, obtain lansoprazole solution, then add the active carbon of solution gross mass 2%-3% to stir 1.5-2.5 hour, under heat-retaining condition with 0.45 μ m filtering with microporous membrane, the filtrate obtaining adds alkali and regulates pH value to 11.0-11.5 under the condition of 75 ℃-85 ℃ of insulations, be down to room temperature, the mannitol and the meglumine that add recipe quantity, and be settled to full dose with water for injection, under aseptic condition, with after 0.22 μ m filtering with microporous membrane, fill is in cillin bottle, lyophilizing, obtain lansoprazole freeze-dried injection for injection.
2. the preparation technology of lansoprazole freeze-dried injection for injection as claimed in claim 1, it is characterized in that, described freeze-dry process is: by cillin bottle false add plug, sabot is placed in freeze dryer, open freeze dryer, start compressor, to flaggy, freeze, conduction oil inlet oil temperature is set and is-40 ℃, and keep 1-3 hour, pre-freeze is finished, to cold-trap, freeze, treat that condenser temperature reaches below-45 ℃, open vacuum pump, open case trap valve, until casing vacuum, be down to 30Pa when following, start the sublimation drying that heats up, first stage distillation inlet oil temperature is made as 0 ℃, retention time is 9 ± 2 hours, second stage heat preservation and dryness, make conduction oil inlet oil temperature rise to 25～30 ℃, insulation is more than 3 hours, close case trap valve, to close case trap valve more than 120 seconds and in case vacuum rise to and be no more than after 10Pa, shutdown finishes lyophilizing.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201410276117.2A CN104013586B (en) | 2014-06-19 | 2014-06-19 | Lansoprazole freeze-dried powder injection for injection and preparation method thereof |
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| CN201410276117.2A CN104013586B (en) | 2014-06-19 | 2014-06-19 | Lansoprazole freeze-dried powder injection for injection and preparation method thereof |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105267162A (en) * | 2015-11-29 | 2016-01-27 | 南京多宝生物科技有限公司 | Injection ozagrel sodium freeze-dried powder for treating cerebral infarction |
| CN105343017A (en) * | 2015-12-01 | 2016-02-24 | 李正梅 | Freeze-dried powder of antibacterial cefmetazole sodium for injection |
| CN109394706A (en) * | 2018-12-07 | 2019-03-01 | 杭州上禾健康科技有限公司 | A kind of Lansoprazole freeze-dried powder for injection and preparation method thereof |
| CN113069421A (en) * | 2021-03-29 | 2021-07-06 | 海南锦瑞制药有限公司 | Lansoprazole for injection |
| CN115919783A (en) * | 2022-11-24 | 2023-04-07 | 海南锦瑞制药有限公司 | Lansoprazole freeze-dried powder injection for injection and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101229136A (en) * | 2008-01-18 | 2008-07-30 | 山东罗欣药业股份有限公司 | Lansoprazole freeze-dried powder for injection and preparing method thereof |
| CN101502493A (en) * | 2009-03-23 | 2009-08-12 | 悦康药业集团有限公司 | Method for preparing lansoprazole freeze-dried injection for injection |
| CN103705473A (en) * | 2013-12-26 | 2014-04-09 | 山东博迈康药物研究有限公司 | Lansoprazole freeze-dried powder injection and preparation method thereof |
-
2014
- 2014-06-19 CN CN201410276117.2A patent/CN104013586B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101229136A (en) * | 2008-01-18 | 2008-07-30 | 山东罗欣药业股份有限公司 | Lansoprazole freeze-dried powder for injection and preparing method thereof |
| CN101502493A (en) * | 2009-03-23 | 2009-08-12 | 悦康药业集团有限公司 | Method for preparing lansoprazole freeze-dried injection for injection |
| CN103705473A (en) * | 2013-12-26 | 2014-04-09 | 山东博迈康药物研究有限公司 | Lansoprazole freeze-dried powder injection and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 刘昔平等: "注射用兰索拉唑冻干工艺研究", 《科技创业》, no. 11, 31 December 2013 (2013-12-31), pages 187 - 188 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105267162A (en) * | 2015-11-29 | 2016-01-27 | 南京多宝生物科技有限公司 | Injection ozagrel sodium freeze-dried powder for treating cerebral infarction |
| CN105343017A (en) * | 2015-12-01 | 2016-02-24 | 李正梅 | Freeze-dried powder of antibacterial cefmetazole sodium for injection |
| CN109394706A (en) * | 2018-12-07 | 2019-03-01 | 杭州上禾健康科技有限公司 | A kind of Lansoprazole freeze-dried powder for injection and preparation method thereof |
| CN113069421A (en) * | 2021-03-29 | 2021-07-06 | 海南锦瑞制药有限公司 | Lansoprazole for injection |
| CN115919783A (en) * | 2022-11-24 | 2023-04-07 | 海南锦瑞制药有限公司 | Lansoprazole freeze-dried powder injection for injection and preparation method thereof |
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| CN104013586B (en) | 2015-04-22 |
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Denomination of invention: Lansoprazole freeze-dried powder for injection and its preparation process Effective date of registration: 20230530 Granted publication date: 20150422 Pledgee: Bank of China Limited Yixing branch Pledgor: JIANGSU KINGSLEY PHARMACEUTICAL CO.,LTD. Registration number: Y2023980042280 |