CN104013586B - Lansoprazole freeze-dried powder injection for injection and preparation method thereof - Google Patents
Lansoprazole freeze-dried powder injection for injection and preparation method thereof Download PDFInfo
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- CN104013586B CN104013586B CN201410276117.2A CN201410276117A CN104013586B CN 104013586 B CN104013586 B CN 104013586B CN 201410276117 A CN201410276117 A CN 201410276117A CN 104013586 B CN104013586 B CN 104013586B
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- 229960003174 lansoprazole Drugs 0.000 title claims abstract description 81
- 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 81
- 239000007924 injection Substances 0.000 title claims abstract description 37
- 238000002347 injection Methods 0.000 title claims abstract description 37
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- 239000000843 powder Substances 0.000 title claims abstract 7
- 239000000243 solution Substances 0.000 claims abstract description 44
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 40
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 34
- 238000001914 filtration Methods 0.000 claims abstract description 27
- 238000003756 stirring Methods 0.000 claims abstract description 25
- 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 21
- 229930195725 Mannitol Natural products 0.000 claims abstract description 21
- 239000000594 mannitol Substances 0.000 claims abstract description 21
- 235000010355 mannitol Nutrition 0.000 claims abstract description 21
- 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 19
- 229960003194 meglumine Drugs 0.000 claims abstract description 19
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000000706 filtrate Substances 0.000 claims abstract description 14
- 238000004321 preservation Methods 0.000 claims abstract description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 42
- 239000008215 water for injection Substances 0.000 claims description 27
- 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 21
- 239000012982 microporous membrane Substances 0.000 claims description 21
- 238000001035 drying Methods 0.000 claims description 12
- 238000007689 inspection Methods 0.000 claims description 12
- 230000001186 cumulative effect Effects 0.000 claims description 11
- 238000004821 distillation Methods 0.000 claims description 11
- 238000004806 packaging method and process Methods 0.000 claims description 11
- 230000033228 biological regulation Effects 0.000 claims description 10
- 238000005516 engineering process Methods 0.000 claims description 10
- 238000009413 insulation Methods 0.000 claims description 10
- 230000014759 maintenance of location Effects 0.000 claims description 10
- 238000000859 sublimation Methods 0.000 claims description 10
- 230000008022 sublimation Effects 0.000 claims description 10
- 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
- 239000003513 alkali Substances 0.000 abstract description 6
- 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
- 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
- 239000000203 mixture Substances 0.000 description 6
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 6
- 239000003814 drug Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000002671 adjuvant Substances 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 3
- 229940079593 drug Drugs 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
- 239000012535 impurity Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 229920001983 poloxamer Polymers 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- CTKXFMQHOOWWEB-UHFFFAOYSA-N Ethylene oxide/propylene oxide copolymer Chemical compound CCCOC(C)COCCO CTKXFMQHOOWWEB-UHFFFAOYSA-N 0.000 description 1
- 206010068052 Mosaicism Diseases 0.000 description 1
- 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
- 239000003795 chemical substances by application Substances 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
- 238000004519 manufacturing process Methods 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
- 229920001993 poloxamer 188 Polymers 0.000 description 1
- 229940044519 poloxamer 188 Drugs 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
- 210000003765 sex chromosome Anatomy 0.000 description 1
- 229940083608 sodium hydroxide Drugs 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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 lansoprazole freeze-dried injection for injection and preparation technology thereof, belong to drug world.
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 composition of existing Lansoprazole for injecting, mainly comprise main constituent lansoprazole, freeze-dried excipient, pH value regulator etc., the prescription composition of most main flow is containing lansoprazole, mannitol, meglumine and sodium hydroxide, and wherein mannitol is freeze-dried excipient, meglumine is stabilizing agent, sodium hydroxide is pH value regulator.After storage a period of time uses, easily there is the problem that clarity of solution declines, particulate matter increases, cause product quality defective, bring drug safety sex chromosome mosaicism in Lansoprazole for injecting.
Address this problem, a kind of thinking is the composition changing prescription, as Chinese patent CN102151265, do not use mannitol and meglumine wherein, add chelating agen disodiumedetate, for another example Chinese patent CN102600088, in prescription, eliminate meglumine, add surface agent poloxamer 188, also have Chinese patent CN103040737, also be eliminate mannitol, and add disodium edetate, sodium sulfite and sodium citrate.Lansoprazole for injecting is prepared by changing prescription composition, its maximum shortcoming is other adjuvants will introduced outside conventional adjuvant, no matter be disodiumedetate, PLURONICS F87 or disodium edetate, sodium sulfite, sodium citrate, although the production of injection also can be applied to, but all unavoidably produce some side effect, thus reduce the safety of product.
The another kind of thinking addressed this problem changes preparation technology.As Chinese patent CN102920703, have employed micronized for lansoprazole bulk drug method, the mode that Chinese patent CN101313895 then 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 prepared is still good not, can only use with 0.9% sodium chloride injection compatibility clinically, cannot be with the use of with the conventional retarder thinner such as 5% glucose injection, sodium lactate ringer's injection, limit Clinical practice scope and the ease for use of this product.
Chinese patent CN102961344 provides a kind of scheme solving this problem, add glucose as cosolvent, the mode of at high temperature remove impurity with active carbon matter after adding alkali dissolution is adopted to prepare Lansoprazole for injecting, Lansoprazole for injecting prepared by this mode, because the compatibility stability adding glucose and 5% glucose injection is better, but still can not meet the problem that compatibility is stable 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 need to changing the routine prescription of Lansoprazole for injecting, without the need to adding unconventional adjuvant, clarity, the particulate matter of the Lansoprazole for injecting prepared 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. uses, and has wider Clinical practice scope.
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, add the water for injection of cumulative volume 80%-90%, it is heat regulation water temperature to 105 DEG C-110 DEG C under the condition of 0.06-0.07MPa at relative pressure, stir 0.5-1 hour, obtain lansoprazole solution, then the active carbon adding solution gross mass 2%-3% stirs 1.5-2.5 hour, with 0.45 μm of filtering with microporous membrane under heat-retaining condition, the filtrate obtained adds alkali adjust ph to 11.0-11.5 under the condition of insulation 75 DEG C-85 DEG C, be down to room temperature, add mannitol and the meglumine of recipe quantity, and be settled to full dose with water for injection, aseptically, after 0.22 μm of 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, freeze to flaggy, conduction oil inlet oil temperature is set and is-40 DEG C, and keep 1-3 hour, pre-freeze is terminated, freeze to cold-trap, treat that condenser temperature reaches less than-45 DEG C, open vacuum pump, open case trap valve, when casing vacuum is down to below 30Pa, start the sublimation drying that heats up, first stage distillation inlet oil temperature is set to 0 DEG C, retention time is 9 ± 2 hours, second stage heat preservation and dryness, conduction oil inlet oil temperature is made to rise to 25 ~ 30 DEG C, be incubated more than 3 hours, close case trap valve, to closing case trap valve more than 120 seconds and after vacuum rises to and is no more than 10Pa in case, shutdown terminates 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, compared with prior art in CN102961344, alkali add opportunity be decarburization filter after but not before, decarburization filtration stage mainly rely on heating and the principle of non-power alkali salify to ensure the dissolving of lansoprazole, the target impurity removed in this stage and CN102961344 have remarkable difference.Adopt and process in such a way, without the need to 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:
Present invention employs unique dissolution process, its lansoprazole freeze-dried injection for injection prepared, without the need to adding unconventional adjuvant, as disodiumedetate, PLURONICS F87, disodium edetate, sodium sulfite, sodium citrate etc., the clarity of the Lansoprazole for injecting prepared, particulate matter is better, the clarity of solution occurred after storing a period of time can be avoided to decline, 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 uses, there is wider Clinical practice scope.
Detailed description of the invention
Below in conjunction with specific embodiment, set forth the present invention further.Should be understood that these embodiments are only not used in for illustration of the present invention to limit the scope of the invention.In addition should be understood that those skilled in the art can make various changes or modifications the present invention, and these equivalent form of values fall within the application's appended claims limited range equally after the content of having read the present invention's instruction.
Embodiment 1
Prescription
Getting recipe quantity lansoprazole puts in pressure vessel, add the water for injection of cumulative volume 80%, be under the condition of 0.06MPa at relative pressure, heat regulation water temperature to 105 DEG C, stir 0.5 hour, obtain lansoprazole solution, then the active carbon adding solution gross mass 2% stirs 2.5 hours, with 0.45 μm of filtering with microporous membrane under heat-retaining condition, the filtrate obtained adds 5% sodium hydroxide solution adjust ph to 11.5 under the condition of insulation 85 DEG C, be down to room temperature, add mannitol and the meglumine of recipe quantity, and be settled to full dose with water for injection, aseptically, after 0.22 μm of 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, freeze to flaggy, conduction oil inlet oil temperature is set and is-40 DEG C, and keep 2 hours, pre-freeze is terminated, freeze to cold-trap, treat that condenser temperature reaches-45 DEG C, 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 set to 0 DEG C, retention time is 9 hours, second stage heat preservation and dryness, conduction oil inlet oil temperature is made to rise to 25 DEG C, be incubated 3 hours, close case trap valve, to closing case trap valve after 120 seconds, after in case, vacuum rises above 10Pa, shutdown terminates lyophilizing, inspection, packaging, obtain Lansoprazole for injecting.
Embodiment 2
Prescription
Getting recipe quantity lansoprazole puts in pressure vessel, add the water for injection of cumulative volume 90%, it is heat regulation water temperature to 110 DEG C under the condition of 0.07MPa at relative pressure, stir 0.5 hour, obtain lansoprazole solution, then the active carbon adding solution gross mass 3% stirs 1.5 hours, with 0.45 μm of filtering with microporous membrane under heat-retaining condition, the filtrate obtained adds 1% sodium hydroxide solution adjust ph to 11.0 under the condition of insulation 85 DEG C, be down to room temperature, add mannitol and the meglumine of recipe quantity, and be settled to full dose with water for injection, aseptically, after 0.22 μm of 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, freeze to flaggy, conduction oil inlet oil temperature is set and is-40 DEG C, and keep 2 hours, pre-freeze is terminated, freeze to cold-trap, treat that condenser temperature reaches-45 DEG C, 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 set to 0 DEG C, retention time is 9 hours, second stage heat preservation and dryness, conduction oil inlet oil temperature is made to rise to 25 DEG C, be incubated 3 hours, close case trap valve, to closing case trap valve after 120 seconds, after in case, vacuum rises above 10Pa, shutdown terminates lyophilizing, inspection, packaging, obtain Lansoprazole for injecting.
Embodiment 3
Prescription
Getting recipe quantity lansoprazole puts in pressure vessel, add the water for injection of cumulative volume 84%, it is heat regulation water temperature to 108 DEG C under the condition of 0.065MPa at relative pressure, stir 0.5 hour, obtain lansoprazole solution, then the active carbon adding solution gross mass 2.6% stirs 2.0 hours, with 0.45 μm of filtering with microporous membrane under heat-retaining condition, the filtrate obtained adds 0.5% sodium hydroxide solution adjust ph to 11.3 under the condition of insulation 79 DEG C, be down to room temperature, add mannitol and the meglumine of recipe quantity, and be settled to full dose with water for injection, aseptically, after 0.22 μm of 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, freeze to flaggy, conduction oil inlet oil temperature is set and is-40 DEG C, and keep 2 hours, pre-freeze is terminated, freeze to cold-trap, treat that condenser temperature reaches-45 DEG C, 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 set to 0 DEG C, retention time is 9 hours, second stage heat preservation and dryness, conduction oil inlet oil temperature is made to rise to 25 DEG C, be incubated 3 hours, close case trap valve, to closing case trap valve after 120 seconds, after in case, vacuum rises above 10Pa, shutdown terminates lyophilizing, inspection, packaging, obtain Lansoprazole for injecting.
Comparative example 1
Lansoprazole for injecting is prepared according to CN101313895 method
Prescription
Getting recipe quantity lansoprazole puts in container, add the water for injection of cumulative volume 30%, add alkali stir make its dissolve and mix homogeneously obtain lansoprazole concentrated solution, add mannitol again, stirring makes it dissolve and mix homogeneously, acid adding is counter adjusts solution ph to 10.3, leave standstill and make crystallization of solution, with microporous filter membrane, crystallize out is filtered out, measure the content of lansoprazole in solution, regulate filtrate pH value to 11.5 according to measurement result and be settled to full dose with water for injection, aseptically, with 0.22 μm of filtering with microporous membrane to clarification, in filtrate fill and aseptic cillin bottle, partly jump a queue, sabot, cartonning, open freeze dryer, reduce sample temperature to-40 DEG C, keep 4 hours, stop board is cold, open cold condenser, when condenser temperature reaches below-45 DEG C, open vacuum system, start the distillation that heats up, final drying temperature product temperature is 30 DEG C, keep this temperature after 3 hours, tamponade, outlet, gland, quality inspection, packaging, obtain Lansoprazole for injecting.
Comparative example 2
Lansoprazole for injecting is prepared according to CN102961344 method
Prescription
Taking recipe quantity sodium hydroxide is dissolved in the water for injection of brand-new, be mixed with about 2% sodium hydroxide solution for subsequent use; Take the lansoprazole of recipe quantity, glucose, mannitol is dissolved in the brand-new water for injection of full dose 80%, add above-mentioned sodium hydroxide solution and be stirred to entirely molten; , add medicine liquid volume 1 ‰ (m/v) active carbon, constant temperature about 80 DEG C stir 30 minutes; Coarse filtration, filters out active carbon with husky filter stick; Fine straining 0.22 μm of accurate filter filters; Intermediate pick test, according to surveyed content determination fill loading amount; Fill, partly jumps a queue, lyophilizing, tamponade, outlet, Zha Gai, semi-finished product pick test, packaging, the Lansoprazole for injecting arrived.
By the Lansoprazole for injecting that embodiment 1-3 and comparative example 1,2 obtain, store 6 months under normal temperature condition after, check the clarity in three kinds of solvents and particulate matter respectively, as follows:
Lansoprazole for injecting clarity checks
Get Lansoprazole for injecting, use 0.9% sodium chloride injection, 5% glucose injection, sodium lactate ringer's injection 10ml solution respectively, check according to clarity inspection technique.
Lansoprazole for injecting particulate matter checks
Get Lansoprazole for injecting, use 0.9% sodium chloride injection, 5% glucose injection, sodium lactate ringer's injection 10ml solution respectively, check according to particulate matter inspection technique.
The results are shown in Table 1.
Claims (6)
1. a lansoprazole freeze-dried injection for injection, the prescription of its lyophilized injectable powder is:
Lansoprazole 30g
Mannitol 60g
Meglumine 10g
Water for injection adds to 6000ml
Make 1000 bottles altogether
Its preparation technology is: get recipe quantity lansoprazole and put in pressure vessel, add the water for injection of cumulative volume 80%, be under the condition of 0.06MPa at relative pressure, heat regulation water temperature to 105 DEG C, stir 0.5 hour, obtain lansoprazole solution, then the active carbon adding solution gross mass 2% stirs 2.5 hours, with 0.45 μm of filtering with microporous membrane under heat-retaining condition, the filtrate obtained adds 5% sodium hydroxide solution adjust ph to 11.5 under the condition of insulation 85 DEG C, be down to room temperature, add mannitol and the meglumine of recipe quantity, and be settled to full dose with water for injection, aseptically, after 0.22 μm of 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, freeze to flaggy, conduction oil inlet oil temperature is set and is-40 DEG C, and keep 2 hours, pre-freeze is terminated, freeze to cold-trap, treat that condenser temperature reaches-45 DEG C, 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 set to 0 DEG C, retention time is 9 hours, second stage heat preservation and dryness, conduction oil inlet oil temperature is made to rise to 25 DEG C, be incubated 3 hours, close case trap valve, to closing case trap valve after 120 seconds, after in case, vacuum rises above 10Pa, shutdown terminates lyophilizing, inspection, packaging, obtain Lansoprazole for injecting.
2. a lansoprazole freeze-dried injection for injection, the prescription of its lyophilized injectable powder is:
Lansoprazole 30g
Mannitol 50g
Meglumine 8g
Water for injection adds to 6000ml
Make 1000 bottles altogether
Its preparation technology is: get recipe quantity lansoprazole and put in pressure vessel, add the water for injection of cumulative volume 90%, it is heat regulation water temperature to 110 DEG C under the condition of 0.07MPa at relative pressure, stir 0.5 hour, obtain lansoprazole solution, then the active carbon adding solution gross mass 3% stirs 1.5 hours, with 0.45 μm of filtering with microporous membrane under heat-retaining condition, the filtrate obtained adds 1% sodium hydroxide solution adjust ph to 11.0 under the condition of insulation 85 DEG C, be down to room temperature, add mannitol and the meglumine of recipe quantity, and be settled to full dose with water for injection, aseptically, after 0.22 μm of 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, freeze to flaggy, conduction oil inlet oil temperature is set and is-40 DEG C, and keep 2 hours, pre-freeze is terminated, freeze to cold-trap, treat that condenser temperature reaches-45 DEG C, 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 set to 0 DEG C, retention time is 9 hours, second stage heat preservation and dryness, conduction oil inlet oil temperature is made to rise to 25 DEG C, be incubated 3 hours, close case trap valve, to closing case trap valve after 120 seconds, after in case, vacuum rises above 10Pa, shutdown terminates lyophilizing, inspection, packaging, obtain Lansoprazole for injecting.
3. a lansoprazole freeze-dried injection for injection, the prescription of its lyophilized injectable powder is:
Lansoprazole 30g
Mannitol 75g
Meglumine 5g
Water for injection adds to 6000ml
Make 1000 bottles altogether
Its preparation technology is: get recipe quantity lansoprazole and put in pressure vessel, add the water for injection of cumulative volume 84%, it is heat regulation water temperature to 108 DEG C under the condition of 0.065MPa at relative pressure, stir 0.5 hour, obtain lansoprazole solution, then the active carbon adding solution gross mass 2.6% stirs 2.0 hours, with 0.45 μm of filtering with microporous membrane under heat-retaining condition, the filtrate obtained adds 0.5% sodium hydroxide solution adjust ph to 11.3 under the condition of insulation 79 DEG C, be down to room temperature, add mannitol and the meglumine of recipe quantity, and be settled to full dose with water for injection, aseptically, after 0.22 μm of 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, freeze to flaggy, conduction oil inlet oil temperature is set and is-40 DEG C, and keep 2 hours, pre-freeze is terminated, freeze to cold-trap, treat that condenser temperature reaches-45 DEG C, 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 set to 0 DEG C, retention time is 9 hours, second stage heat preservation and dryness, conduction oil inlet oil temperature is made to rise to 25 DEG C, be incubated 3 hours, close case trap valve, to closing case trap valve after 120 seconds, after in case, vacuum rises above 10Pa, shutdown terminates lyophilizing, inspection, packaging, obtain Lansoprazole for injecting.
4. the preparation method of lansoprazole freeze-dried injection for injection according to claim 1, it is characterized in that, step is: get recipe quantity lansoprazole and put in pressure vessel, add the water for injection of cumulative volume 80%, be under the condition of 0.06MPa at relative pressure, heat regulation water temperature to 105 DEG C, stir 0.5 hour, obtain lansoprazole solution, then the active carbon adding solution gross mass 2% stirs 2.5 hours, with 0.45 μm of filtering with microporous membrane under heat-retaining condition, the filtrate obtained adds 5% sodium hydroxide solution adjust ph to 11.5 under the condition of insulation 85 DEG C, be down to room temperature, add mannitol and the meglumine of recipe quantity, and be settled to full dose with water for injection, aseptically, after 0.22 μm of 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, freeze to flaggy, conduction oil inlet oil temperature is set and is-40 DEG C, and keep 2 hours, pre-freeze is terminated, freeze to cold-trap, treat that condenser temperature reaches-45 DEG C, 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 set to 0 DEG C, retention time is 9 hours, second stage heat preservation and dryness, conduction oil inlet oil temperature is made to rise to 25 DEG C, be incubated 3 hours, close case trap valve, to closing case trap valve after 120 seconds, after in case, vacuum rises above 10Pa, shutdown terminates lyophilizing, inspection, packaging, obtain Lansoprazole for injecting.
5. the preparation method of lansoprazole freeze-dried injection for injection according to claim 2, it is characterized in that, step is: get recipe quantity lansoprazole and put in pressure vessel, add the water for injection of cumulative volume 90%, it is heat regulation water temperature to 110 DEG C under the condition of 0.07MPa at relative pressure, stir 0.5 hour, obtain lansoprazole solution, then the active carbon adding solution gross mass 3% stirs 1.5 hours, with 0.45 μm of filtering with microporous membrane under heat-retaining condition, the filtrate obtained adds 1% sodium hydroxide solution adjust ph to 11.0 under the condition of insulation 85 DEG C, be down to room temperature, add mannitol and the meglumine of recipe quantity, and be settled to full dose with water for injection, aseptically, after 0.22 μm of 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, freeze to flaggy, conduction oil inlet oil temperature is set and is-40 DEG C, and keep 2 hours, pre-freeze is terminated, freeze to cold-trap, treat that condenser temperature reaches-45 DEG C, 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 set to 0 DEG C, retention time is 9 hours, second stage heat preservation and dryness, conduction oil inlet oil temperature is made to rise to 25 DEG C, be incubated 3 hours, close case trap valve, to closing case trap valve after 120 seconds, after in case, vacuum rises above 10Pa, shutdown terminates lyophilizing, inspection, packaging, obtain Lansoprazole for injecting.
6. the preparation method of lansoprazole freeze-dried injection for injection according to claim 3, it is characterized in that, step is: get recipe quantity lansoprazole and put in pressure vessel, add the water for injection of cumulative volume 84%, it is heat regulation water temperature to 108 DEG C under the condition of 0.065MPa at relative pressure, stir 0.5 hour, obtain lansoprazole solution, then the active carbon adding solution gross mass 2.6% stirs 2.0 hours, with 0.45 μm of filtering with microporous membrane under heat-retaining condition, the filtrate obtained adds 0.5% sodium hydroxide solution adjust ph to 11.3 under the condition of insulation 79 DEG C, be down to room temperature, add mannitol and the meglumine of recipe quantity, and be settled to full dose with water for injection, aseptically, after 0.22 μm of 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, freeze to flaggy, conduction oil inlet oil temperature is set and is-40 DEG C, and keep 2 hours, pre-freeze is terminated, freeze to cold-trap, treat that condenser temperature reaches-45 DEG C, 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 set to 0 DEG C, retention time is 9 hours, second stage heat preservation and dryness, conduction oil inlet oil temperature is made to rise to 25 DEG C, be incubated 3 hours, close case trap valve, to closing case trap valve after 120 seconds, after in case, vacuum rises above 10Pa, shutdown terminates lyophilizing, inspection, packaging, obtain Lansoprazole for injecting.
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| 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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| 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 |
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| 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 |
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