Lyophilized powder injection of rabeprazole sodium medicinal composition and preparation method of lyophilized powder injection

Abstract

The invention relates to a lyophilized powder injection of a rabeprazole sodium medicinal composition and a preparation method of the lyophilized powder injection. The medicinal composition is composed of rabeprazole sodium and pharmaceutically acceptable auxiliary materials, wherein the rabeprazole sodium is a rabeprazole sodium crystal compound. By utilizing a powder X-ray diffraction determination method to determine, characteristic diffraction peaks are displayed at parts of 5.8 degrees, 7.5 degrees, 12.1 degrees, 12.8 degrees, 13.3 degrees, 15.6 degrees, 16.7 degrees, 18.3 degrees, 20.4 degrees, 25.7 degrees, 26.8 degrees and 31.5 degrees by an X-ray powder diffraction pattern which is represented by a 2 theta+ / -0.2 degree diffraction angle; and the pharmaceutically acceptable auxiliary materials comprise mannitol and disodium ethylene diamine tetraacetate and further comprise meglumine and sodium sulfite. The prepared rabeprazole sodium powder injection is full in appearance andgood in redissolving property and has fewer insoluble particles; and a test shows that the lyophilized powder injection has a stronger acid-inhibiting capability.

Description

technical field

[0001] The invention relates to a rabeprazole sodium composition, in particular to a rabeprazole sodium pharmaceutical composition freeze-dried powder injection and a preparation method thereof. Background technique

[0002] Ulcer disease is a common type of disease, and it is prone to recurrent clinically, often accompanied by serious complications, such as gastric and duodenal ulcers, which can be complicated by upper gastrointestinal bleeding and perforation, which seriously threaten people's health. Proton pump inhibitors are powerful weapons in the fight against ulcer disease. Japan's Eisai Company's proton pump inhibitor (Proton Pump Inhibitors, PPI) anti-ulcer drug rabeprazole is following Astra's omeprazole, Takeda's lansorazole (lansorazole) and Byk Gulden's panax The fourth PPI developed after pantoprazole.

[0003] The chemical name of Rabeprazole Sodium is: 2-[[[4-(3-methoxypropoxy)-3-methyl-2-pyridyl]methyl]sulfinyl]- 1H-Benzimidazole Sodium. ...

Examples

Embodiment 1

[0079] [Compound Example 1] Preparation of rabeprazole sodium crystalline compound

[0080] 1) Add 60 g of the raw drug rabeprazole sodium into 300 ml of water, stir and dissolve to obtain an aqueous solution of rabeprazole sodium;

[0081] 2) Add a mixed solution of 480ml tetrahydrofuran and methanol (the volume ratio of tetrahydrofuran and methanol is 3:1) to the above-mentioned rabeprazole sodium aqueous solution under stirring at a speed of 300r / min, decolorize with activated carbon at 25°C, filter, get the filtrate;

[0082] 3) The filtrate was dropped into 1440ml of acetonitrile, cooled to 5°C, crystals were precipitated, filtered, and vacuum-dried to obtain 54.1g of white rabeprazole sodium crystalline compound.

[0083] The melting point of the crystalline compound detected by capillary method is 162-163°C.

[0084] Adopt U.S. Perkin-Elmer company PE2400II elemental analyzer, elemental analysis (%) is: measured value (calculated value), C: 56.68 (56.68), H: 5.29 (5.3...

Embodiment 2-9

[0088]

[0089] The melting point of the crystalline compound obtained in Example 2-9 is detected by capillary method to be 162~163° C., and the crystalline compound obtained in Compound Example 2-9 is analyzed by the PE2400II elemental analyzer of American Perkin-Elmer Company, and the results and implementation Example 1 is similar.

[0090] Simultaneously, the crystalline compounds of compound examples 2-9 were measured by powder X-ray diffraction method, and the X-ray powder diffraction patterns represented by 2θ±0.2° diffraction angle were similar to those of Example 1.

[0091] [composition embodiment 1] rabeprazole sodium pharmaceutical composition

[0092] composition:

[0093]

[0094] Preparation method: Mix 20 g of rabeprazole sodium crystalline compound prepared in compound example 1, 5.0 g of disodium diethylamine tetraacetate and 150 g of mannitol, and divide into 1000 bottles to obtain the product.

[0095] The following are composition examples 2-9, the...

preparation Embodiment 1

[0099] [Formulation Example 1] Rabeprazole Sodium Freeze-dried Powder Injection

[0100] Prescription: 20mg / bottle (based on rabeprazole sodium)

[0101]

[0102] Preparation:

[0103] 1) Dissolve the disodium diethylamine tetraacetate of prescription quantity in 2500ml water for injection first, then add the rabeprazole sodium crystalline compound prepared by the compound embodiment 1 of prescription quantity under the condition of 30 ℃ of temperature, stir Make it dissolve, then add 150g of mannitol, stir and dissolve, then cool to room temperature, then add the prescribed amount of meglumine and sodium sulfite, adjust the pH of the solution to 11.5, and add water for injection to the full amount;

[0104] 2) Add 0.1% g / ml activated carbon to the above-prepared solution, stir for 15 minutes, and filter to decarbonize;

[0105] 3) Rapidly cool the filtrate obtained in step 2) from room temperature to -22°C, maintain -22°C for 2.5 hours, then drop to -40°C, pre-freeze for...

technical field

[0001] The invention relates to a rabeprazole sodium composition, in particular to a rabeprazole sodium pharmaceutical composition freeze-dried powder injection and a preparation method thereof. Background technique

[0002] Ulcer disease is a common type of disease, and it is prone to recurrent clinically, often accompanied by serious complications, such as gastric and duodenal ulcers, which can be complicated by upper gastrointestinal bleeding and perforation, which seriously threaten people's health. Proton pump inhibitors are powerful weapons in the fight against ulcer disease. Japan's Eisai Company's proton pump inhibitor (Proton Pump Inhibitors, PPI) anti-ulcer drug rabeprazole is following Astra's omeprazole, Takeda's lansorazole (lansorazole) and Byk Gulden's panax The fourth PPI developed after pantoprazole.

[0003] The chemical name of Rabeprazole Sodium is: 2-[[[4-(3-methoxypropoxy)-3-methyl-2-pyridyl]methyl]sulfinyl]- 1H-Benzimidazole Sodium. ...

Examples

Embodiment 1

[0079] [Compound Example 1] Preparation of rabeprazole sodium crystalline compound

[0080] 1) Add 60 g of the raw drug rabeprazole sodium into 300 ml of water, stir and dissolve to obtain an aqueous solution of rabeprazole sodium;

[0081] 2) Add a mixed solution of 480ml tetrahydrofuran and methanol (the volume ratio of tetrahydrofuran and methanol is 3:1) to the above-mentioned rabeprazole sodium aqueous solution under stirring at a speed of 300r / min, decolorize with activated carbon at 25°C, filter, get the filtrate;

[0082] 3) The filtrate was dropped into 1440ml of acetonitrile, cooled to 5°C, crystals were precipitated, filtered, and vacuum-dried to obtain 54.1g of white rabeprazole sodium crystalline compound.

[0083] The melting point of the crystalline compound detected by capillary method is 162-163°C.

[0084] Adopt U.S. Perkin-Elmer company PE2400II elemental analyzer, elemental analysis (%) is: measured value (calculated value), C: 56.68 (56.68), H: 5.29 (5.3...

Embodiment 2-9

[0088]

[0089] The melting point of the crystalline compound obtained in Example 2-9 is detected by capillary method to be 162~163° C., and the crystalline compound obtained in Compound Example 2-9 is analyzed by the PE2400II elemental analyzer of American Perkin-Elmer Company, and the results and implementation Example 1 is similar.

[0090] Simultaneously, the crystalline compounds of compound examples 2-9 were measured by powder X-ray diffraction method, and the X-ray powder diffraction patterns represented by 2θ±0.2° diffraction angle were similar to those of Example 1.

[0091] [composition embodiment 1] rabeprazole sodium pharmaceutical composition

[0092] composition:

[0093]

[0094] Preparation method: Mix 20 g of rabeprazole sodium crystalline compound prepared in compound example 1, 5.0 g of disodium diethylamine tetraacetate and 150 g of mannitol, and divide into 1000 bottles to obtain the product.

[0095] The following are composition examples 2-9, the...

preparation Embodiment 1

[0099] [Formulation Example 1] Rabeprazole Sodium Freeze-dried Powder Injection

[0100] Prescription: 20mg / bottle (based on rabeprazole sodium)

[0101]

[0102] Preparation:

[0103] 1) Dissolve the disodium diethylamine tetraacetate of prescription quantity in 2500ml water for injection first, then add the rabeprazole sodium crystalline compound prepared by the compound embodiment 1 of prescription quantity under the condition of 30 ℃ of temperature, stir Make it dissolve, then add 150g of mannitol, stir and dissolve, then cool to room temperature, then add the prescribed amount of meglumine and sodium sulfite, adjust the pH of the solution to 11.5, and add water for injection to the full amount;

[0104] 2) Add 0.1% g / ml activated carbon to the above-prepared solution, stir for 15 minutes, and filter to decarbonize;

[0105] 3) Rapidly cool the filtrate obtained in step 2) from room temperature to -22°C, maintain -22°C for 2.5 hours, then drop to -40°C, pre-freeze for...

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