CN112274481A - Pantoprazole sodium composition for injection and preparation method thereof - Google Patents
Pantoprazole sodium composition for injection and preparation method thereof Download PDFInfo
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- CN112274481A CN112274481A CN202011166949.0A CN202011166949A CN112274481A CN 112274481 A CN112274481 A CN 112274481A CN 202011166949 A CN202011166949 A CN 202011166949A CN 112274481 A CN112274481 A CN 112274481A
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- 238000002347 injection Methods 0.000 title claims abstract description 158
- 239000007924 injection Substances 0.000 title claims abstract description 158
- 229960004048 pantoprazole sodium Drugs 0.000 title claims abstract description 107
- YNWDKZIIWCEDEE-UHFFFAOYSA-N pantoprazole sodium Chemical compound [Na+].COC1=CC=NC(CS(=O)C=2[N-]C3=CC=C(OC(F)F)C=C3N=2)=C1OC YNWDKZIIWCEDEE-UHFFFAOYSA-N 0.000 title claims abstract description 107
- 239000000203 mixture Substances 0.000 title claims abstract description 66
- 238000002360 preparation method Methods 0.000 title claims abstract description 47
- 239000011550 stock solution Substances 0.000 claims abstract description 151
- 238000001914 filtration Methods 0.000 claims abstract description 121
- 239000007788 liquid Substances 0.000 claims abstract description 101
- 238000000034 method Methods 0.000 claims abstract description 12
- 238000004140 cleaning Methods 0.000 claims abstract description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 108
- 238000003860 storage Methods 0.000 claims description 76
- 238000003756 stirring Methods 0.000 claims description 68
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 68
- 239000000243 solution Substances 0.000 claims description 57
- 239000008215 water for injection Substances 0.000 claims description 32
- 239000000706 filtrate Substances 0.000 claims description 31
- 230000007246 mechanism Effects 0.000 claims description 31
- 229940124274 edetate disodium Drugs 0.000 claims description 30
- 230000003139 buffering effect Effects 0.000 claims description 16
- 229930182555 Penicillin Natural products 0.000 claims description 15
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 claims description 15
- 229940049954 penicillin Drugs 0.000 claims description 15
- 239000010865 sewage Substances 0.000 claims description 11
- 238000009777 vacuum freeze-drying Methods 0.000 claims description 9
- 238000005303 weighing Methods 0.000 claims description 9
- 229910052782 aluminium Inorganic materials 0.000 claims description 8
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 8
- 238000009434 installation Methods 0.000 claims description 8
- 239000000463 material Substances 0.000 claims description 8
- 238000001035 drying Methods 0.000 claims description 7
- 238000010438 heat treatment Methods 0.000 claims description 7
- 239000004695 Polyether sulfone Substances 0.000 claims description 6
- 229920006393 polyether sulfone Polymers 0.000 claims description 6
- 230000000903 blocking effect Effects 0.000 claims description 5
- 230000000149 penetrating effect Effects 0.000 claims description 2
- 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 claims 10
- 238000009826 distribution Methods 0.000 claims 5
- 239000003814 drug Substances 0.000 abstract description 18
- 239000012535 impurity Substances 0.000 abstract description 18
- 229940079593 drug Drugs 0.000 abstract description 8
- 239000002994 raw material Substances 0.000 abstract description 7
- 230000002378 acidificating effect Effects 0.000 abstract description 4
- 230000015556 catabolic process Effects 0.000 abstract description 4
- 238000006731 degradation reaction Methods 0.000 abstract description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 33
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- 238000005096 rolling process Methods 0.000 description 6
- 238000000926 separation method Methods 0.000 description 6
- 239000007787 solid Substances 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 3
- 238000007599 discharging Methods 0.000 description 3
- 229960001484 edetic acid Drugs 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- XUKUURHRXDUEBC-SXOMAYOGSA-N (3s,5r)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoic acid Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-SXOMAYOGSA-N 0.000 description 2
- AAEQXEDPVFIFDK-UHFFFAOYSA-N 3-(4-fluorobenzoyl)-2-(2-methylpropanoyl)-n,3-diphenyloxirane-2-carboxamide Chemical compound C=1C=CC=CC=1NC(=O)C1(C(=O)C(C)C)OC1(C=1C=CC=CC=1)C(=O)C1=CC=C(F)C=C1 AAEQXEDPVFIFDK-UHFFFAOYSA-N 0.000 description 2
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 2
- -1 pH value regulators Substances 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- FCJYMBZQIJDMMM-UHFFFAOYSA-N 1H-Benzimidazole, 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl]sulfonyl]- Chemical compound COC1=CC=NC(CS(=O)(=O)C=2NC3=CC(OC(F)F)=CC=C3N=2)=C1OC FCJYMBZQIJDMMM-UHFFFAOYSA-N 0.000 description 1
- NQWYXCHABHQOMJ-UHFFFAOYSA-N 5-(difluoromethoxy)-2-[(3,4-dimethoxypyridin-2-yl)methylsulfinyl]-1-methylbenzimidazole Chemical compound COC1=CC=NC(CS(=O)C=2N(C3=CC=C(OC(F)F)C=C3N=2)C)=C1OC NQWYXCHABHQOMJ-UHFFFAOYSA-N 0.000 description 1
- UKILEIRWOYBGEJ-UHFFFAOYSA-N 6-(difluoromethoxy)-2-[(3,4-dimethoxypyridin-2-yl)methylsulfanyl]-1h-benzimidazole Chemical group COC1=CC=NC(CSC=2NC3=CC(OC(F)F)=CC=C3N=2)=C1OC UKILEIRWOYBGEJ-UHFFFAOYSA-N 0.000 description 1
- FYIXLAGYOWZQJO-UHFFFAOYSA-N 6-(difluoromethoxy)-2-[(3,4-dimethoxypyridin-2-yl)methylsulfinyl]-1-methylbenzimidazole Chemical compound COC1=CC=NC(CS(=O)C=2N(C3=CC(OC(F)F)=CC=C3N=2)C)=C1OC FYIXLAGYOWZQJO-UHFFFAOYSA-N 0.000 description 1
- IQPSEEYGBUAQFF-UHFFFAOYSA-N Pantoprazole Chemical compound COC1=CC=NC(CS(=O)C=2NC3=CC=C(OC(F)F)C=C3N=2)=C1OC IQPSEEYGBUAQFF-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 230000003749 cleanliness Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 229960005019 pantoprazole Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Dermatology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a pantoprazole sodium composition for injection and a preparation method thereof, aiming at the problem that the raw material medicine is possibly degraded under an acidic condition in the prior art, the adding sequence of components in a liquid preparation procedure is adjusted, so that the raw material medicine is in a strong alkaline environment in the liquid preparation process, the risk of acid-catalyzed degradation of the raw material medicine is reduced, the preparation is more stable, and the safety and the effectiveness of the medicine are improved; in the preparation method, the injection stock solution is subjected to fine filtration by using fine filtration equipment, and is subjected to twice filtration by using the primary filter cylinder and the fine filter plate, so that impurities in the injection stock solution are effectively removed, the prepared pantoprazole sodium composition for injection is high in quality, and the safety and the effectiveness of the medicine are further improved; the fine filtration equipment has a self-cleaning function, so that the safety of medicines is further improved, the times of replacing the primary filter cylinder and the fine filter plate are reduced, and the production cost is reduced.
Description
Technical Field
The invention relates to the field of medicines, and in particular relates to a pantoprazole sodium composition for injection and a preparation method thereof.
Background
The pantoprazole sodium for injection can be prepared into a pantoprazole sodium compound for injection after adding different metal chelating agents, pH value regulators, excipients and adsorbents, and can be directly applied to clinical treatment in a dosage form of sterile powder for injection.
Patent application No. CN201110119354.4 discloses a pantoprazole sodium composition for injection, which contains pantoprazole sodium and ethylene diamine tetraacetic acid, wherein the weight ratio of the pantoprazole sodium to the ethylene diamine tetraacetic acid is 1:0.02-0.1, and the composition is prepared by the following method: 1. preparing a liquid medicine: putting pantoprazole sodium and ethylene diamine tetraacetic acid into a preparation tank, adding water for injection, stirring to dissolve and uniformly mix, and adjusting the pH value to 10.5-12.5; 2. rubber plug treatment; 3. sterile filtering, and packaging; 4. vacuum freeze drying to obtain the final product.
The pantoprazole sodium composition for injection does not consider the condition that the raw material medicine is easy to generate degradation impurities under an acidic condition in the production process, so that the raw material medicine is likely to degrade to influence related substances in the preparation.
Disclosure of Invention
In order to overcome the technical problems, the invention aims to provide a pantoprazole sodium composition for injection and a preparation method thereof, wherein the pantoprazole sodium composition comprises the following components in parts by weight: dissolving sodium hydroxide in water for injection to prepare a sodium hydroxide solution, adding the water for injection into a concentrated preparation tank, adding the edetate disodium into the water for injection according to the formula amount, and stirring at the stirring speed of 50Hz for 5-10min to dissolve the edetate disodium to obtain an edetate disodium solution; adjusting the pH value of an edetate disodium solution to 10.5-11.0 by using a sodium hydroxide solution, adding pantoprazole sodium with a formula amount into a concentrated preparation tank, stirring to dissolve the pantoprazole sodium, adding injection water until the total weight of the solution is 2kg to obtain an injection stock solution, taking a rubber plug, adding the rubber plug and the injection stock solution in a weight ratio of 1:10, heating to 41-47 ℃, preserving heat for 30 minutes, taking out the rubber plug, rinsing for 15 minutes by using the injection water, drying at 121 ℃ in a rubber plug cleaning machine, filtering the injection stock solution by a fine filter, conveying the injection stock solution into a sterile chamber, subpackaging the injection solution into a penicillin bottle, semi-tamponade, conveying the injection stock solution into a vacuum freeze dryer, performing vacuum freeze drying, tamponade, taking out of a box, rolling an aluminum cover to obtain the pantoprazole sodium composition for injection, and solving the problem that the existing pantoprazole sodium composition for injection does not consider that raw material medicines are easy to generate degradation impurities under an acidic condition in the production process, so that the raw material medicine is possibly degraded to influence related substances in the preparation.
The purpose of the invention can be realized by the following technical scheme:
a pantoprazole sodium composition for injection comprises pantoprazole sodium and disodium edetate, wherein the weight ratio of the pantoprazole sodium to the disodium edetate is 40: 1;
the pantoprazole sodium composition for injection is prepared by the following steps:
the method comprises the following steps: weighing 40g of pantoprazole sodium and 1g of edetate disodium according to the formula for later use:
step two: dissolving sodium hydroxide in water for injection to prepare a sodium hydroxide solution;
step three: adding injection water into a concentrated preparation tank, adding edetate disodium of formula amount into the injection water, and stirring at 50Hz for 5-10min to dissolve to obtain edetate disodium solution;
step four: adjusting the pH value of the edetate disodium solution to 10.5-11.0 by using a sodium hydroxide solution, adding pantoprazole sodium in a formula amount into a concentrated preparation tank, stirring to dissolve the pantoprazole sodium, and adding water for injection until the total weight of the solution is 2kg to obtain an injection stock solution;
step five: adding a rubber plug into the injection stock solution according to the weight ratio of the rubber plug to the injection stock solution of 1:10, heating to 41-47 ℃, preserving heat for 30 minutes, taking out the rubber plug, rinsing with injection water for 15 minutes, and drying at 121 ℃ in a rubber plug cleaning machine for later use;
step six: conveying the injection stock solution from an input pipe of the fine filtration equipment to an inner cavity of a stock solution storage tank, starting a stirring motor to operate and drive a stirring blade to rotate so as to stir the injection stock solution, starting a first conveying liquid pump, operating the first conveying liquid pump to pump out the injection stock solution in the stock solution storage tank through a liquid inlet pipe, and conveying the injection stock solution to a fine filtration mechanism through a liquid conveying pipe;
conveying the injection stock solution into a fine filtration bin from an input port, reducing the speed of the injection stock solution by the blockage of a buffering splitter disc, storing the injection stock solution in a buffer area, conveying the injection stock solution to a primary filtration component through a liquid separation hole, filtering the injection stock solution into an inner cavity from the outside of a primary filtration cylinder due to the blockage of an installation disc to obtain primary filtrate, discharging the primary filtrate through a connecting pipe and conveying the primary filtrate to a fine filtration plate, and filtering the primary filtrate from the fine filtration plate to obtain pantoprazole sodium composition stock solution;
step eight: and (3) storing the pantoprazole sodium composition stock solution in a storage area, conveying the pantoprazole sodium composition stock solution to a connecting pipe through a conveying pipe for storage, conveying the pantoprazole sodium composition stock solution into an aseptic chamber, subpackaging the pantoprazole sodium composition stock solution into penicillin bottles, semi-corking the penicillin bottles, conveying the pantoprazole sodium composition stock solution into a vacuum freeze dryer, carrying out vacuum freeze drying, corking the penicillin bottles out of a box, and rolling an aluminum cover to obtain the pantoprazole sodium composition for injection.
As a further scheme of the invention: a preparation method of pantoprazole sodium composition for injection comprises the following steps:
the method comprises the following steps: weighing 40g of pantoprazole sodium and 1g of edetate disodium according to the formula for later use:
step two: dissolving sodium hydroxide in water for injection to prepare a sodium hydroxide solution;
step three: adding injection water into a concentrated preparation tank, adding edetate disodium of formula amount into the injection water, and stirring at 50Hz for 5-10min to dissolve to obtain edetate disodium solution;
step four: adjusting the pH value of the edetate disodium solution to 10.5-11.0 by using a sodium hydroxide solution, adding pantoprazole sodium in a formula amount into a concentrated preparation tank, stirring to dissolve the pantoprazole sodium, and adding water for injection until the total weight of the solution is 2kg to obtain an injection stock solution;
step five: adding a rubber plug into the injection stock solution according to the weight ratio of the rubber plug to the injection stock solution of 1:10, heating to 41-47 ℃, preserving heat for 30 minutes, taking out the rubber plug, rinsing with injection water for 15 minutes, and drying at 121 ℃ in a rubber plug cleaning machine for later use;
step six: conveying the injection stock solution from an input pipe of the fine filtration equipment to an inner cavity of a stock solution storage tank, starting a stirring motor to operate and drive a stirring blade to rotate so as to stir the injection stock solution, starting a first conveying liquid pump, operating the first conveying liquid pump to pump out the injection stock solution in the stock solution storage tank through a liquid inlet pipe, and conveying the injection stock solution to a fine filtration mechanism through a liquid conveying pipe;
conveying the injection stock solution into a fine filtration bin from an input port, reducing the speed of the injection stock solution by the blockage of a buffering splitter disc, storing the injection stock solution in a buffer area, conveying the injection stock solution to a primary filtration component through a liquid separation hole, filtering the injection stock solution into an inner cavity from the outside of a primary filtration cylinder due to the blockage of an installation disc to obtain primary filtrate, discharging the primary filtrate through a connecting pipe and conveying the primary filtrate to a fine filtration plate, and filtering the primary filtrate from the fine filtration plate to obtain pantoprazole sodium composition stock solution;
step eight: and (3) storing the pantoprazole sodium composition stock solution in a storage area, conveying the pantoprazole sodium composition stock solution to a connecting pipe through a conveying pipe for storage, conveying the pantoprazole sodium composition stock solution into an aseptic chamber, subpackaging the pantoprazole sodium composition stock solution into penicillin bottles, semi-corking the penicillin bottles, conveying the pantoprazole sodium composition stock solution into a vacuum freeze dryer, carrying out vacuum freeze drying, corking the penicillin bottles out of a box, and rolling an aluminum cover to obtain the pantoprazole sodium composition for injection.
As a further scheme of the invention: the essence is strained equipment and is included the installation frame, is supported chassis, essence and strain mechanism, stoste holding vessel, first delivery liquid pump, filtrating holding vessel, second delivery liquid pump, clear water holding vessel, agitator motor, stirring leaf, the internally mounted of installation frame has a plurality of essence to strain the mechanism, a plurality of the essence is strained the mechanism and is set up side by side, the support chassis is installed to bottom one side of installation frame, first delivery liquid pump and filtrating holding vessel are installed respectively to the top both ends of support chassis, the stoste holding vessel is installed to the top intermediate position of installation frame, one side that the installation frame is close the filtrating holding vessel is provided with the second delivery liquid pump, one side that the filtrating holding vessel was kept away from to the second delivery liquid pump is provided with the clear water holding vessel.
As a further scheme of the invention: agitator motor is installed at the top of stoste holding vessel, agitator motor's output shaft runs through the top of stoste holding vessel and extends to in the inner chamber of stoste holding vessel, the stirring leaf is installed to agitator motor's output shaft bottom, install the input tube on the lateral wall that the stoste holding vessel is close to the top, the stoste holding vessel is close to and installs the feed liquor pipe on the lateral wall of bottom.
As a further scheme of the invention: one end of the liquid inlet pipe, which is far away from the stock solution storage tank, is communicated to a liquid inlet of the first liquid conveying pump, a conveying pipe is installed at a liquid outlet of the first liquid conveying pump, and one end of the conveying pipe, which is far away from the first liquid conveying pump, is respectively communicated to one end side walls of the fine filtering mechanisms through a plurality of branch pipes.
As a further scheme of the invention: the side wall of the other end of each of the fine filtering mechanisms is connected to a conveying pipe through a plurality of branch pipes, one end, far away from the fine filtering mechanism, of the conveying pipe is communicated to a liquid outlet of a second liquid conveying pump, and a liquid inlet of the second liquid conveying pump is communicated to the side wall, close to the bottom end, of the clear water storage tank through a pipeline.
As a further scheme of the invention: the filter liquor storage tank is close to and installs the output tube on one side on the top, the filter liquor storage tank is close to on the opposite side on top communicates to one side of conveyer pipe through the branch pipe on, the conveyer pipe is provided with the three way valve below the junction of conveyer pipe and filter liquor storage tank.
As a further scheme of the invention: the fine filtration mechanism comprises a fine filtration bin, an input port, an output port, a sewage draining port, a buffering split-flow disc, a buffer area, a primary filtration component, a fine filtration plate and a storage area, wherein the input port and the output port are both arranged at two ends of one side of the fine filtration bin, one end of the fine filtration bin close to the input port is provided with the sewage draining port, and a valve is arranged on the sewage draining port.
As a further scheme of the invention: the inner chamber of the fine filtration bin is close to input port one end and is installed buffering diverter plate, a plurality of liquid separating holes have been seted up on the buffering diverter plate, the fine filtration bin inner chamber forms the buffer with the combination between the buffering diverter plate, the buffer communicates to the input port, the input port communicates to the transfer line, the fine filtration bin inner chamber is close to the one end of delivery outlet and is installed fine filter plate, the combination forms the storage area between fine filtration bin inner chamber and the fine filter plate, the storage area communicates to the delivery outlet, the delivery outlet communicates to the transfer line, install the preliminary filtration subassembly in the inner chamber of the fine filtration bin, the preliminary filtration subassembly is located between buffering diverter plate and the fine filter plate.
As a further scheme of the invention: the primary filter assembly comprises a mounting ring, a mounting plate, positioning discs, a primary filter cylinder, connecting pipes and a mounting disc, wherein the mounting ring and the mounting disc are both mounted on the inner wall of the fine filter bin; the fine filter plate is made of a polyether sulfone material with the aperture of 0.22 mu m, and the primary filter cylinder is made of a polyether sulfone material with the aperture of 0.45 mu m.
The invention has the beneficial effects that:
(1) the pantoprazole sodium composition for injection and the preparation method thereof are characterized in that pantoprazole sodium and disodium edetate are weighed according to a formula for standby, sodium hydroxide is dissolved in water for injection to prepare a sodium hydroxide solution, the water for injection is added into a concentration preparation tank, the disodium edetate with the formula amount is added into the water for injection, and the disodium edetate is stirred and dissolved under the conditions that the stirring speed is 50Hz and the stirring time is 5-10min to obtain a disodium edetate solution; adjusting the pH value of an edetate disodium solution to 10.5-11.0 by using a sodium hydroxide solution, adding pantoprazole sodium in a formula amount into a concentrated preparation tank, stirring to dissolve the pantoprazole sodium, adding injection water until the total weight of the solution is 2kg to obtain an injection stock solution, taking a rubber plug, adding the rubber plug and the injection stock solution in a weight ratio of 1:10 into the injection stock solution, heating to 41-47 ℃ and preserving heat for 30 minutes, then taking out the rubber plug, rinsing for 15 minutes by using the injection water, drying at 121 ℃ in a rubber plug cleaning machine, filtering the injection stock solution, conveying the injection stock solution into an aseptic chamber, subpackaging the injection stock solution into a penicillin bottle, semi-tamponading the penicillin bottle, conveying the penicillin bottle into a vacuum freeze dryer, performing vacuum freeze drying, tamponad discharging the box, and rolling an aluminum cover to obtain the pantoprazole sodium composition for injection; aiming at the problem that the acidic condition is not considered in the prior art, which possibly degrades the bulk drugs, the invention adjusts the adding sequence of each component in the liquid preparation process, so that the bulk drugs are in the strong alkaline environment in the liquid preparation process, thereby reducing the risk of acid catalytic degradation of the bulk drugs, enabling the preparation to be more stable, and further improving the safety and effectiveness of the drugs;
(2) the invention relates to a pantoprazole sodium composition for injection and a preparation method thereof, wherein injection stock solution is subjected to fine filtration by using fine filtration equipment, the injection stock solution is conveyed into an inner cavity of a stock solution storage tank from an input pipe, a stirring motor is started to operate to drive a stirring blade to rotate so as to stir the injection stock solution, a first conveying liquid pump is started, the first conveying liquid pump operates to pump the injection stock solution in the stock solution storage tank out through a liquid inlet pipe and convey the injection stock solution to a fine filtration mechanism through a liquid conveying pipe, the injection stock solution is conveyed into a fine filtration bin from the input port, the injection stock solution is blocked by a buffering splitter disc, the speed of the injection stock solution is reduced and is stored in a buffer area, the injection stock solution is conveyed to a primary filtration component through a liquid separation hole, the injection stock solution is filtered into the inner cavity from the outside of a primary filtration cylinder due to the blocking of a mounting disc to obtain primary filtrate, the primary filtrate is discharged through a connecting pipe and conveyed to a fine filtration plate, obtaining a pantoprazole sodium composition stock solution; the fine filtering device filters the injection stock solution twice through the primary filter cylinder and the fine filter plate, so that impurities in the injection stock solution are effectively removed, the prepared pantoprazole sodium composition for injection has high quality, and the safety and the effectiveness of the medicine are further improved;
(3) according to the fine filtration equipment, the second liquid conveying pump is started, runs to pump out clean water in the clean water storage tank, conveys the clean water into the fine filtration bin through the conveying pipe, carries impurities attached to the fine filtration plate to convey forwards, then carries the impurities attached to the inner cavity of the primary filter cylinder to convey forwards, and discharges the impurities through the sewage discharge outlet; the fine filtration equipment has a self-cleaning function, so that the cleanliness of the fine filtration equipment is high, the safety of medicines is further improved, the times of replacing a primary filter cylinder and a fine filter plate are reduced, and the production cost is reduced.
Drawings
The invention will be further described with reference to the accompanying drawings.
FIG. 1 is a schematic view of a fine filtration apparatus according to the present invention;
FIG. 2 is a view showing the connection between the stirring motor and the stirring blade in the present invention;
FIG. 3 is a schematic diagram of the fine filter mechanism of the present invention;
FIG. 4 is a schematic view showing the internal structure of the fine filter mechanism of the present invention;
FIG. 5 is a schematic view of the structure of the buffering diverter tray in the invention;
FIG. 6 is a schematic view of the primary filter assembly of the present invention;
FIG. 7 is a side view of the primary filter assembly of the present invention.
In the figure: 101. a mounting frame; 102. a support chassis; 103. a fine filtering mechanism; 104. a stock solution storage tank; 105. a first liquid delivery pump; 106. a liquid inlet pipe; 107. a transfusion tube; 108. a delivery pipe; 109. a filtrate storage tank; 110. a second feed liquid pump; 111. a clear water storage tank; 112. an input tube; 113. a stirring motor; 114. stirring blades; 115. an output pipe; 1030. a fine filtration bin; 116. an input port; 117. an output port; 118. a sewage draining outlet; 119. a buffer diverter disc; 120. a buffer area; 121. a primary filter assembly; 122. fine filtering the plate; 123. a storage area; 124. a liquid separation hole; 125. a mounting ring; 126. mounting a plate; 127. positioning a plate; 128. primary filtering the cylinder; 129. a connecting pipe; 130. and (7) mounting a disc.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Referring to fig. 1-7, a pantoprazole sodium composition for injection comprises pantoprazole sodium and disodium edetate, wherein the weight ratio of pantoprazole sodium to disodium edetate is 40: 1;
the pantoprazole sodium composition for injection is prepared by the following steps:
the method comprises the following steps: weighing 40g of pantoprazole sodium and 1g of edetate disodium according to the formula for later use:
step two: dissolving sodium hydroxide in water for injection to prepare a sodium hydroxide solution;
step three: adding injection water into a concentrated preparation tank, adding edetate disodium of formula amount into the injection water, and stirring at 50Hz for 5-10min to dissolve to obtain edetate disodium solution;
step four: adjusting the pH value of the edetate disodium solution to 10.5-11.0 by using a sodium hydroxide solution, adding pantoprazole sodium in a formula amount into a concentrated preparation tank, stirring to dissolve the pantoprazole sodium, and adding water for injection until the total weight of the solution is 2kg to obtain an injection stock solution;
step five: adding a rubber plug into the injection stock solution according to the weight ratio of the rubber plug to the injection stock solution of 1:10, heating to 41-47 ℃, preserving heat for 30 minutes, taking out the rubber plug, rinsing with injection water for 15 minutes, and drying at 121 ℃ in a rubber plug cleaning machine for later use;
step six: conveying the injection stock solution from an input pipe 112 of the fine filtration device to an inner cavity of the stock solution storage tank 104, starting a stirring motor 113 to operate and drive a stirring blade 114 to rotate so as to stir the injection stock solution, starting a first conveying liquid pump 105, operating the first conveying liquid pump 105 to pump the injection stock solution in the stock solution storage tank 104 through a liquid inlet pipe 106, and conveying the injection stock solution to the fine filtration mechanism 103 through a liquid conveying pipe 107;
seventhly, conveying the injection stock solution from the input port 116 to the fine filter bin 1030, wherein the injection stock solution is blocked by the buffer diverter disc 119, the injection stock solution is reduced in speed and stored in the buffer area 120, the injection stock solution is conveyed to the primary filter assembly 121 through the liquid separation hole 124, the injection stock solution is filtered from the outer part of the primary filter cylinder 128 to the inner cavity due to the blocking of the mounting disc 130 to obtain primary filter solution, the primary filter solution is discharged through the connecting pipe 129 and conveyed to the fine filter plate 122, and the primary filter solution is filtered from the fine filter plate 122 to obtain pantoprazole sodium composition stock solution;
step eight: the pantoprazole sodium composition stock solution is stored in a storage area 123, then is conveyed to a connecting pipe 129 through a conveying pipe 108 to be stored, is conveyed into an aseptic chamber, is subpackaged in a penicillin bottle, is conveyed into a vacuum freeze dryer after being half-stoppered, is subjected to vacuum freeze drying, is stoppered out of a box, and is subjected to aluminum cap rolling to obtain the pantoprazole sodium composition for injection.
The pantoprazole sodium composition for injection in each penicillin bottle is prepared by freeze-drying 2g of pantoprazole sodium composition stock solution, and is obtained by experiments, wherein the formula of each 2g of pantoprazole sodium composition stock solution is as follows:
40mg of pantoprazole, 1.0mg of edetate disodium, 0.261mg of sodium hydroxide and 1958.739mg of water for injection.
Example 1:
the preparation method of the invention is used for preparing the pantoprazole sodium composition stock solution:
the method comprises the following steps: preparing liquid: weighing 80.0g of sodium hydroxide solid, dissolving in a proper amount of water for injection, and adding the water for injection to 1000mL to prepare 1000mL of 2mol/L sodium hydroxide solution;
step two: adding 1mg of edetate disodium into a concentrated preparation tank filled with 1200mL of injection water, stirring to dissolve, stirring at 50Hz for 5 min;
step three: and (3) adjusting the pH value to 10.5 by using 2mol/L sodium hydroxide solution, adding 40mg of pantoprazole sodium into a concentrated preparation tank, stirring to dissolve the pantoprazole sodium, and adding water for injection until the total weight of the solution is 2g to obtain a reagent A.
Comparative example 1:
the difference from example 1 is that: changing the first adding amount of the water for injection and the adding sequence of the pantoprazole sodium:
the method comprises the following steps: preparing liquid: weighing 80.0g of sodium hydroxide solid, dissolving in a proper amount of water for injection, and adding the water for injection to 1000mL to prepare 1000mL of 2mol/L sodium hydroxide solution;
step two: adding 1mg of edetate disodium into a concentrated preparation tank filled with 1600mL of injection water, and stirring at 50Hz for 5min to dissolve;
step three: adding 40mg of pantoprazole sodium into a concentrated preparation tank, stirring to dissolve the pantoprazole sodium, adjusting the pH value to 10.5 by using 2mol/L sodium hydroxide solution, and adding water for injection until the total weight of the solution is 2g to obtain a reagent B.
Comparative example 2:
the difference from example 1 is that: changing the concentration of the sodium hydroxide solution, the first adding amount of the water for injection and the adding sequence of the pantoprazole sodium:
the method comprises the following steps: preparing liquid: weighing 40.0g of sodium hydroxide solid, dissolving in a proper amount of water for injection, and adding the water for injection to 1000mL to prepare 1000mL of 1mol/L sodium hydroxide solution;
step two: taking 40mg of pantoprazole sodium and 1mg of edetate disodium, adding into a concentration tank filled with 1600mL of injection water, stirring to dissolve, stirring at the speed of 50Hz, and stirring for 5 min;
step three: and (3) adjusting the pH value to 10.5 by using 1mol/L sodium hydroxide solution, and supplementing water for injection until the total weight of the solution is 2g to obtain a reagent C.
Comparative example 3:
the difference from example 1 is that: changing the first adding amount of the concentration of the sodium hydroxide solution and the adding sequence of the edetate disodium and the pantoprazole sodium:
the method comprises the following steps: preparing liquid: weighing 40.0g of sodium hydroxide solid, dissolving in a proper amount of water for injection, and adding the water for injection to 1000mL to prepare 1000mL of 1mol/L sodium hydroxide solution;
step two: taking 40mg of pantoprazole sodium, adding into a concentration tank filled with 1200mL of injection water, stirring to dissolve the pantoprazole sodium, wherein the stirring speed is 50Hz, and the stirring time is 5 min;
step three: and (3) adjusting the pH value to 10.5 by using 1mol/L sodium hydroxide solution, adding 1mg of pantoprazole sodium into a concentrated preparation tank, stirring to dissolve the pantoprazole sodium, and adding water for injection until the total weight of the solution is 2g to obtain a reagent D.
And (4) analyzing results: and (3) detecting the reagents A-D, wherein the detection results are as follows:
| related substances | Reagent A (%) | Reagent B (%) | Reagent C (%) | Reagent D (%) |
| Impurity B: less than or equal to 0.1 percent | Not detected out | 0.01％ | 0.025％ | 0.02％ |
| Impurity E: less than or equal to 0.1 percent | Not detected out | Not detected out | Not detected out | Not detected out |
| Impurity C: less than or equal to 0.2 percent | 0.001 | 0.05 | 0.08 | 0.03 |
| Impurity A: less than or equal to 0.2 percent | 0.01 | 0.02 | 0.01 | 0.02 |
| Impurity D + F: less than or equal to 1.0 percent | 0.01 | 0.01 | 0.01 | 0.01 |
| The largest unknown single impurity: less than or equal to 0.2 percent | 0.003 | 0.004 | 0.002 | 0.003 |
| Total impurities (%): less than or equal to 1.0 percent | 0.05 | 0.19 | 0.12 | 0.11 |
From this, it can be seen that the acid-degradable impurity content is the lowest and the total impurity content is the lowest in example 1.
Wherein impurity a is 5- (difluoromethoxy) -2{ [ (3, 4-dimethoxy-2 pyridyl) -methyl ] sulfonyl } -1H-benzimidazole;
impurity B is 5- (difluoromethoxy) -2{ [ (3, 4-dimethoxy-2 pyridyl) -methyl ] thio } -1H-benzimidazole;
impurity C is 5- (difluoromethoxy) -2-thio-1H-benzimidazole;
impurity D is 5- (difluoromethoxy) -2- { (RS) - [ (3, 4-dimethoxy-2 pyridyl) -methyl ] sulfinyl } -1-methyl-1H-benzimidazole;
impurity E is 6,6 '-bis (difluoromethoxy) -2, 2' -bis { [ (3, 4-dimethoxy-2 pyridyl) -methyl ] sulfinyl } -1H, 1H '-5, 5' -dibenzoimidazole;
impurity F is 6- (difluoromethoxy) -2{ (RS) - [ (3, 4-dimethoxy-2 pyridyl) -methyl ] sulfinyl } -1-methyl-1H-benzimidazole.
Example 2:
referring to fig. 1-7, the fine filtering apparatus of the present embodiment includes a mounting frame 101, a supporting frame 102, a fine filtering mechanism 103, a raw liquid storage tank 104, a first liquid pump 105, a filtrate storage tank 109, a second liquid pump 110, a clear water storage tank 111, a stirring motor 113, and a stirring blade 114, a plurality of fine filtering mechanisms 103 are arranged in the mounting frame 101, a plurality of fine filtering mechanisms 103 are arranged in parallel, a supporting chassis 102 is installed at one side of the bottom of the mounting frame 101, a first liquid conveying pump 105 and a filtrate storage tank 109 are respectively installed at two ends of the top of the supporting chassis 102, a stock solution storage tank 104 is arranged at the middle position of the top of the mounting frame 101, a second liquid conveying pump 110 is arranged at one side of the mounting frame 101 close to the filtrate storage tank 109, a clear water storage tank 111 is arranged on one side of the second liquid conveying pump 110, which is far away from the filtrate storage tank 109;
the top of the stock solution storage tank 104 is provided with a stirring motor 113, an output shaft of the stirring motor 113 penetrates through the top of the stock solution storage tank 104 and extends into an inner cavity of the stock solution storage tank 104, the bottom end of the output shaft of the stirring motor 113 is provided with a stirring blade 114, the side wall of the stock solution storage tank 104 close to the top end is provided with an input pipe 112, and the side wall of the stock solution storage tank 104 close to the bottom end is provided with a liquid inlet pipe 106;
one end of the liquid inlet pipe 106, which is far away from the stock solution storage tank 104, is communicated to a liquid inlet of the first liquid conveying pump 105, a liquid outlet of the first liquid conveying pump 105 is provided with a conveying pipe 108, and one end of the conveying pipe 108, which is far away from the first liquid conveying pump 105, is respectively communicated to side walls of one ends of the fine filtering mechanisms 103 through a plurality of branch pipes;
the side walls of the other ends of the fine filtering mechanisms 103 are all connected to a delivery pipe 108 through a plurality of branch pipes, one end of the delivery pipe 108 far away from the fine filtering mechanisms 103 is communicated to a liquid outlet of a second liquid delivery pump 110, and a liquid inlet of the second liquid delivery pump 110 is communicated to the side wall of the clear water storage tank 111 close to the bottom end through a pipeline;
an output pipe 115 is arranged on one side of the filtrate storage tank 109 close to the top end, the other side of the filtrate storage tank 109 close to the top end is communicated to one side of the conveying pipe 108 through a branch pipe, and a three-way valve is arranged below the joint of the conveying pipe 108 and the filtrate storage tank 109 in the conveying pipe 108;
the fine filtering mechanism 103 comprises a fine filtering bin 1030, an input port 116, an output port 117, a sewage draining port 118, a buffering diversion disc 119, a buffer area 120, a primary filtering component 121, a fine filtering plate 122 and a storage area 123, wherein the input port 116 and the output port 117 are respectively arranged at two ends of one side of the fine filtering bin 1030, the sewage draining port 118 is arranged at one end, close to the input port 116, of the fine filtering bin 1030, and a valve is arranged on the sewage draining port 118;
a buffer diverter disc 119 is mounted at one end, close to the input port 116, of the inner cavity of the fine filtering bin 1030, a plurality of liquid dividing holes 124 are formed in the buffer diverter disc 119, a buffer area 120 is formed by combining the inner cavity of the fine filtering bin 1030 and the buffer diverter disc 119, the buffer area 120 is communicated with the input port 116, the input port 116 is communicated with the infusion tube 107, a fine filtering plate 122 is mounted at one end, close to the output port 117, of the inner cavity of the fine filtering bin 1030, a storage area 123 is formed by combining the inner cavity of the fine filtering bin 1030 and the fine filtering plate 122, the storage area 123 is communicated with the output port 117, the output port 117 is communicated with the delivery tube 108, a primary filtering assembly 121 is mounted in the inner cavity of the fine filtering bin 1030, and the primary filtering assembly 121 is;
the primary filter assembly 121 comprises a mounting ring 125, a mounting plate 126, positioning discs 127, primary filter cylinders 128, connecting pipes 129 and a mounting plate 130, wherein the mounting ring 125 and the mounting plate 130 are both mounted on the inner wall of the fine filter bin 1030, the mounting ring 125 is provided with a plurality of mounting plates 126, the mounting plate 130 is provided with a plurality of connecting pipes 129 in a penetrating manner, one side of each mounting plate 126 and one end, far away from the mounting plate 130, of each connecting pipe 129 are provided with a plurality of positioning discs 127, the positioning discs 127 on the mounting plates 126 correspond to the positioning discs 127 on the connecting pipes 129 in a one-to-one manner, and the primary filter cylinders 128 are mounted between the corresponding positioning discs 127;
the fine filter plate 122 is made of a polyethersulfone material with the pore diameter of 0.22 μm, and the primary filter cartridge 128 is made of a polyethersulfone material with the pore diameter of 0.45 μm.
Referring to fig. 1-7, the operation of the fine filtering apparatus in this embodiment is as follows:
the method comprises the following steps: conveying the injection stock solution from an input pipe 112 to an inner cavity of the stock solution storage tank 104, starting a stirring motor 113 to operate to drive a stirring blade 114 to rotate so as to stir the injection stock solution, starting a first conveying liquid pump 105, operating the first conveying liquid pump 105 to pump out the injection stock solution in the stock solution storage tank 104 through a liquid inlet pipe 106, and conveying the injection stock solution to a fine filtering mechanism 103 through a liquid conveying pipe 107;
step two, conveying the injection stock solution from the input port 116 to the fine filter bin 1030, wherein the injection stock solution is blocked by the buffer diverter disc 119, the injection stock solution is reduced in speed and stored in the buffer area 120, the injection stock solution is conveyed to the primary filter assembly 121 through the liquid separation hole 124, the injection stock solution is filtered from the outer part of the primary filter cylinder 128 to the inner cavity due to the blocking of the mounting disc 130 to obtain primary filter solution, the primary filter solution is discharged through the connecting pipe 129 and conveyed to the fine filter plate 122, and the primary filter solution is filtered from the fine filter plate 122 to obtain pantoprazole sodium composition stock solution;
step three: the pantoprazole sodium composition stock solution is stored in a storage area 123, then is conveyed to a connecting pipe 129 through a conveying pipe 108 to be stored, is conveyed into an aseptic chamber, is subpackaged in a penicillin bottle, is conveyed into a vacuum freeze dryer after being half-stoppered, is subjected to vacuum freeze drying, is stoppered out of a box, and is subjected to aluminum cap rolling to obtain the pantoprazole sodium composition for injection.
In the description herein, references to the description of "one embodiment," "an example," "a specific example" or the like are intended to mean that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, the schematic representations of the terms used above do not necessarily refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.
The foregoing is illustrative and explanatory only and is not intended to be exhaustive or to limit the invention to the precise embodiments described, and various modifications, additions, and substitutions may be made by those skilled in the art without departing from the scope of the invention or exceeding the scope of the claims.
Claims (10)
1. The pantoprazole sodium composition for injection is characterized by comprising pantoprazole sodium and disodium edetate, wherein the weight ratio of the pantoprazole sodium to the disodium edetate is 40: 1;
the pantoprazole sodium composition for injection is prepared by the following steps:
the method comprises the following steps: weighing 40g of pantoprazole sodium and 1g of edetate disodium according to the formula for later use:
step two: dissolving sodium hydroxide in water for injection to prepare a sodium hydroxide solution;
step three: adding injection water into a concentrated preparation tank, adding edetate disodium of formula amount into the injection water, and stirring at 50Hz for 5-10min to dissolve to obtain edetate disodium solution;
step four: adjusting the pH value of the edetate disodium solution to 10.5-11.0 by using a sodium hydroxide solution, adding pantoprazole sodium in a formula amount into a concentrated preparation tank, stirring to dissolve the pantoprazole sodium, and adding water for injection until the total weight of the solution is 2kg to obtain an injection stock solution;
step five: adding a rubber plug into the injection stock solution according to the weight ratio of the rubber plug to the injection stock solution of 1:10, heating to 41-47 ℃, preserving heat for 30 minutes, taking out the rubber plug, rinsing with injection water for 15 minutes, and drying at 121 ℃ in a rubber plug cleaning machine for later use;
step six: conveying the injection stock solution from an input pipe (112) of the fine filtration equipment to an inner cavity of a stock solution storage tank (104), starting a stirring motor (113) to operate to drive a stirring blade (114) to rotate to stir the injection stock solution, starting a first conveying liquid pump (105), operating the first conveying liquid pump (105) to pump out the injection stock solution in the stock solution storage tank (104) through a liquid inlet pipe (106), and conveying the injection stock solution to a fine filtration mechanism (103) through a liquid conveying pipe (107);
seventhly, conveying the injection stock solution into a fine filtering bin (1030) from an input port (116), wherein the injection stock solution is blocked by a buffering flow distribution disc (119), the injection stock solution is reduced in speed and stored in a buffering area (120), the injection stock solution is conveyed to a primary filtering assembly (121) through a liquid distribution hole (124), the injection stock solution is filtered into an inner cavity from the outside of a primary filtering cylinder (128) due to the blocking of a mounting disc (130), so as to obtain primary filtrate, the primary filtrate is discharged through a connecting pipe (129) and conveyed to a fine filtering plate (122), and the primary filtrate is filtered from the fine filtering plate (122), so as to obtain pantoprazole sodium composition stock solution;
step eight: the pantoprazole sodium composition stock solution is stored in a storage area (123), and then is conveyed to a connecting pipe (129) through a conveying pipe (108) for storage, the pantoprazole sodium composition stock solution is conveyed to an aseptic chamber, is subpackaged in a penicillin bottle, is conveyed into a vacuum freeze dryer after being half-corked, is subjected to vacuum freeze drying, is corked out of a box, and is rolled with an aluminum cover, so that the pantoprazole sodium composition for injection is obtained.
2. The preparation method of pantoprazole sodium composition for injection according to claim 1, comprising the steps of:
the method comprises the following steps: weighing 40g of pantoprazole sodium and 1g of edetate disodium according to the formula for later use:
step two: dissolving sodium hydroxide in water for injection to prepare a sodium hydroxide solution;
step three: adding injection water into a concentrated preparation tank, adding edetate disodium of formula amount into the injection water, and stirring at 50Hz for 5-10min to dissolve to obtain edetate disodium solution;
step four: adjusting the pH value of the edetate disodium solution to 10.5-11.0 by using a sodium hydroxide solution, adding pantoprazole sodium in a formula amount into a concentrated preparation tank, stirring to dissolve the pantoprazole sodium, and adding water for injection until the total weight of the solution is 2kg to obtain an injection stock solution;
step five: adding a rubber plug into the injection stock solution according to the weight ratio of the rubber plug to the injection stock solution of 1:10, heating to 41-47 ℃, preserving heat for 30 minutes, taking out the rubber plug, rinsing with injection water for 15 minutes, and drying at 121 ℃ in a rubber plug cleaning machine for later use;
step six: conveying the injection stock solution from an input pipe (112) of the fine filtration equipment to an inner cavity of a stock solution storage tank (104), starting a stirring motor (113) to operate to drive a stirring blade (114) to rotate to stir the injection stock solution, starting a first conveying liquid pump (105), operating the first conveying liquid pump (105) to pump out the injection stock solution in the stock solution storage tank (104) through a liquid inlet pipe (106), and conveying the injection stock solution to a fine filtration mechanism (103) through a liquid conveying pipe (107);
seventhly, conveying the injection stock solution into a fine filtering bin (1030) from an input port (116), wherein the injection stock solution is blocked by a buffering flow distribution disc (119), the injection stock solution is reduced in speed and stored in a buffering area (120), the injection stock solution is conveyed to a primary filtering assembly (121) through a liquid distribution hole (124), the injection stock solution is filtered into an inner cavity from the outside of a primary filtering cylinder (128) due to the blocking of a mounting disc (130), so as to obtain primary filtrate, the primary filtrate is discharged through a connecting pipe (129) and conveyed to a fine filtering plate (122), and the primary filtrate is filtered from the fine filtering plate (122), so as to obtain pantoprazole sodium composition stock solution;
step eight: the pantoprazole sodium composition stock solution is stored in a storage area (123), and then is conveyed to a connecting pipe (129) through a conveying pipe (108) for storage, the pantoprazole sodium composition stock solution is conveyed to an aseptic chamber, is subpackaged in a penicillin bottle, is conveyed into a vacuum freeze dryer after being half-corked, is subjected to vacuum freeze drying, is corked out of a box, and is rolled with an aluminum cover, so that the pantoprazole sodium composition for injection is obtained.
3. The preparation method of pantoprazole sodium composition for injection according to claim 2, wherein the fine filtration device comprises a mounting frame (101), a supporting chassis (102), a fine filtration mechanism (103), a stock solution storage tank (104), a first liquid delivery pump (105), a filtrate storage tank (109), a second liquid delivery pump (110), a clear water storage tank (111), a stirring motor (113) and stirring blades (114), wherein the mounting frame (101) is internally provided with a plurality of fine filtration mechanisms (103), the fine filtration mechanisms (103) are arranged in parallel, the supporting chassis (102) is arranged on one side of the bottom of the mounting frame (101), the first liquid delivery pump (105) and the filtrate storage tank (109) are respectively arranged at two ends of the top of the supporting chassis (102), the stock solution storage tank (104) is arranged at the middle position of the top of the mounting frame (101), one side that installation frame (101) are close filtrate holding vessel (109) is provided with second conveying liquid pump (110), one side that filtrate holding vessel (109) are kept away from in second conveying liquid pump (110) is provided with clear water holding vessel (111).
4. The preparation method of the pantoprazole sodium composition for injection according to claim 3, wherein a stirring motor (113) is installed at the top of the stock solution storage tank (104), an output shaft of the stirring motor (113) penetrates through the top of the stock solution storage tank (104) and extends into an inner cavity of the stock solution storage tank (104), a stirring blade (114) is installed at the bottom end of the output shaft of the stirring motor (113), an input pipe (112) is installed on the side wall of the stock solution storage tank (104) close to the top end, and a liquid inlet pipe (106) is installed on the side wall of the stock solution storage tank (104) close to the bottom end.
5. The preparation method of the pantoprazole sodium composition for injection according to claim 4, wherein one end of the liquid inlet pipe (106) far away from the stock solution storage tank (104) is communicated to a liquid inlet of the first liquid conveying pump (105), a liquid outlet of the first liquid conveying pump (105) is provided with a conveying pipe (108), and one end of the conveying pipe (108) far away from the first liquid conveying pump (105) is respectively communicated to the side wall of one end of the fine filtering mechanisms (103) through a plurality of branch pipes.
6. The preparation method of pantoprazole sodium composition for injection according to claim 5, wherein a plurality of fine filtering mechanisms (103) are connected to a delivery pipe (108) through a plurality of branch pipes on the side wall of the other end, one end of the delivery pipe (108) far away from the fine filtering mechanism (103) is communicated to a liquid outlet of a second liquid delivery pump (110), and a liquid inlet of the second liquid delivery pump (110) is communicated to the side wall of the clear water storage tank (111) near the bottom end through a pipeline.
7. The preparation method of the pantoprazole sodium composition for injection according to claim 3, wherein an output pipe (115) is arranged on one side of the filtrate storage tank (109) close to the top end, the other side of the filtrate storage tank (109) close to the top end is communicated to one side of the delivery pipe (108) through a branch pipe, and the delivery pipe (108) is provided with a three-way valve below the joint of the delivery pipe (108) and the filtrate storage tank (109).
8. The preparation method of the pantoprazole sodium composition for injection according to claim 3, wherein the fine filtering mechanism (103) comprises a fine filtering bin (1030), an input port (116), an output port (117), a sewage outlet (118), a buffering diverter disc (119), a buffer area (120), a primary filtering component (121), a fine filtering plate (122) and a storage area (123), the input port (116) and the output port (117) are respectively formed at two ends of one side of the fine filtering bin (1030), the sewage outlet (118) is formed in one end, close to the input port (116), of the fine filtering bin (1030), and a valve is arranged on the sewage outlet (118).
9. The preparation method of the pantoprazole sodium composition for injection according to claim 8, wherein a buffer diverter disc (119) is installed at one end of the inner cavity of the fine filtration bin (1030) close to the input port (116), a plurality of liquid separating holes (124) are formed in the buffer diverter disc (119), a buffer area (120) is formed between the inner cavity of the fine filtration bin (1030) and the buffer diverter disc (119), the buffer area (120) is communicated with the input port (116), the input port (116) is communicated with the liquid conveying pipe (107), a fine filtration plate (122) is installed at one end of the inner cavity of the fine filtration bin (1030) close to the output port (117), a storage area (123) is formed between the inner cavity of the fine filtration bin (1030) and the fine filtration plate (122), the storage area (123) is communicated with the output port (117), and the conveying pipe (108) is arranged at the output port (117), install in the inner chamber of fine filtration storehouse (1030) and just strain subassembly (121), just strain subassembly (121) and be located between buffering flow distribution disc (119) and fine filtration board (122).
10. The preparation method of pantoprazole sodium composition for injection according to claim 9, characterized in that the primary filter assembly (121) comprises a mounting ring (125), a mounting plate (126), a positioning disc (127), a primary filter cylinder (128), a connecting pipe (129) and a mounting disc (130), the mounting ring (125) and the mounting disc (130) are both arranged on the inner wall of the fine filtering bin (1030), a plurality of mounting plates (126) are arranged on the mounting ring (125), a plurality of connecting pipes (129) are arranged on the mounting disc (130) in a penetrating way, a plurality of positioning discs (127) are respectively arranged on one side of the mounting plate (126) and one end of the connecting pipe (129) far away from the mounting disc (130), a plurality of positioning discs (127) on the mounting plate (126) correspond to a plurality of positioning discs (127) on the connecting pipe (129) one by one, and primary filter cylinders (128) are arranged between the mutually corresponding positioning discs (127); the fine filter plate (122) is made of a polyether sulfone material with the aperture of 0.22 mu m, and the primary filter cylinder (128) is made of a polyether sulfone material with the aperture of 0.45 mu m.
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| CN202011166949.0A CN112274481A (en) | 2020-10-27 | 2020-10-27 | Pantoprazole sodium composition for injection and preparation method thereof |
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| CN202011166949.0A CN112274481A (en) | 2020-10-27 | 2020-10-27 | Pantoprazole sodium composition for injection and preparation method thereof |
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Application publication date: 20210129 |