Boletic acid buddhist nun azoles phenyl ketone freeze-dried powder and method of preparing the same

Abstract

The invention provides nizofenone fumarate lyophilized powder for injection and a preparation method thereof. The lyophilized powder for injection comprises nizofenone fumarate, excipient, solubilizer and pH regulator. The dose of excipient is 0.1-10 times of that of the nizofenone fumarate, the dose of solubilizer is 0.1-10 times of the nizofenone fumarate, and the pH regulator is used for adjusting the pH value of the nizofenone fumarate before lyophilization to 3-11. The preparation method comprises the following steps of dissolving main raw materials and adjuvants in water, adjusting pH value, adding activated carbon for discoloration, filtering to remove carbon, subpackaging, freezing to -60-(-30) DEG C, keeping the temperature for 1-6 hours, vacuuming to 0.1-10mmHg, increasing the temperature to 0-30 DEG C with rate of 2-5 DEG C / hour, increasing the temperature to 30-50 DEG C with rate of 4-9 DEG C, and drying at constant temperature for 3-7 hours. The method of the invention is simple and easy for industrial production, and the obtained lyophilized powder has good quality, good appearance, and is easy for storage and transportation.

Description

technical field

[0001] The invention belongs to the technical field of medicine, and relates to a freeze-dried preparation, in particular to a nizophenone fumarate freeze-dried powder and a preparation method thereof. Background technique

[0002] Nizofenone fumarate, CAS: 54533-85-6, molecular formula: C 25 h 25 ClN 4 o 7 , molecular weight: 528.88, structural formula:

[0003]

[0004] This product was researched and developed by Welfide Company of Japan, and it was launched in Japan in 1988. In 1991, it was listed in Korea by Hanall Company. This product is a new type of imidazole ischemic cerebrovascular disease improving drug, which can improve brain function, inhibit the formation of cerebral infarction, improve brain waves after cerebral ischemia and restore pyramidal tract function. Animal experiments also show that this product can significantly prolong the survival time of brain cells under ischemic or hypoxic conditions, thereby improving a series of symp...

Examples

Embodiment 1

[0051] Nizophenone Fumarate 5g

[0052] Mannitol 3g

[0053] Tween 80 2g

[0054] Put the main and auxiliary materials into the liquid mixing tank, add 1200m water for injection to dissolve, adjust the pH to 3~4 with hydrochloric acid or sodium hydroxide, then add 0.05% medical activated carbon and stir for 20 minutes to decolorize, then filter to remove carbon, and the filtrate is qualified after pH measurement Add water for injection until the volume of the solution is 2000ml, fine filter with a 0.22μm microporous membrane, subpackage the filtrate, and half-tamp the plug, freeze the subpackaged drug solution to -45°C, keep it frozen for 3 hours, and then evacuate to 1mmHg, the temperature was raised slowly at a constant speed of 3°C / hour to 15°C, and then raised to 45°C at a speed of 6°C / hour, then dried at a constant temperature for 5 hours, capped, packed and put into storage.

Embodiment 2

[0056] Nizophenone Fumarate 5g

[0057] Dextran 2.5g

[0058] Hydroxypropyl beta cyclodextrin 2g

[0059] Put the main and auxiliary materials into the liquid mixing tank, add 1200ml of water for injection to dissolve, adjust the pH to 3-11 with hydrochloric acid or sodium hydroxide, then add 0.05% medical activated carbon and stir for 10 minutes to decolorize, then filter to remove carbon, and the filtrate is qualified after pH measurement Add water for injection until the volume of the solution is 2000ml, fine filter with a 0.22μm microporous membrane, subpackage the filtrate, and half-tamp the plug, freeze the subpackaged drug solution to -60°C, insulate and freeze for 1 hour, and then evacuate to 10mmHg, the temperature was raised slowly at a constant speed of 5°C / hour to 0°C, and then the temperature was raised to 50°C at a speed of 9°C / hour, then dried at a constant temperature for 3 hours, capped, packed and put into storage.

Embodiment 3

[0061] Nizophenone Fumarate 5g

[0062] Dextran 50g

[0063] Poloxamer 2g

[0064] Put the main and auxiliary materials into the liquid mixing tank, add 1200ml of water for injection to dissolve, adjust the pH to 5-7 with hydrochloric acid or sodium hydroxide, then add 0.05% medical activated carbon and stir for 30 minutes to decolorize, then filter to remove carbon, and the filtrate is qualified after pH measurement Add water for injection until the volume of the solution is 2000ml, fine filter with a 0.22μm microporous membrane, subpackage the filtrate, and half-tamp the plug, freeze the subpackaged drug solution to -30°C, keep it frozen for 6 hours, and then evacuate to 0.5mmHg, the temperature was raised slowly at a constant speed of 2°C / hour to 0°C, and then raised to 40°C at a speed of 7°C / hour, and then dried at a constant temperature for 7 hours, capped, packed and put into storage.

technical field

[0001] The invention belongs to the technical field of medicine, and relates to a freeze-dried preparation, in particular to a nizophenone fumarate freeze-dried powder and a preparation method thereof. Background technique

[0002] Nizofenone fumarate, CAS: 54533-85-6, molecular formula: C 25 h 25 ClN 4 o 7 , molecular weight: 528.88, structural formula:

[0003]

[0004] This product was researched and developed by Welfide Company of Japan, and it was launched in Japan in 1988. In 1991, it was listed in Korea by Hanall Company. This product is a new type of imidazole ischemic cerebrovascular disease improving drug, which can improve brain function, inhibit the formation of cerebral infarction, improve brain waves after cerebral ischemia and restore pyramidal tract function. Animal experiments also show that this product can significantly prolong the survival time of brain cells under ischemic or hypoxic conditions, thereby improving a series of symp...

Examples

Embodiment 1

[0051] Nizophenone Fumarate 5g

[0052] Mannitol 3g

[0053] Tween 80 2g

[0054] Put the main and auxiliary materials into the liquid mixing tank, add 1200m water for injection to dissolve, adjust the pH to 3~4 with hydrochloric acid or sodium hydroxide, then add 0.05% medical activated carbon and stir for 20 minutes to decolorize, then filter to remove carbon, and the filtrate is qualified after pH measurement Add water for injection until the volume of the solution is 2000ml, fine filter with a 0.22μm microporous membrane, subpackage the filtrate, and half-tamp the plug, freeze the subpackaged drug solution to -45°C, keep it frozen for 3 hours, and then evacuate to 1mmHg, the temperature was raised slowly at a constant speed of 3°C / hour to 15°C, and then raised to 45°C at a speed of 6°C / hour, then dried at a constant temperature for 5 hours, capped, packed and put into storage.

Embodiment 2

[0056] Nizophenone Fumarate 5g

[0057] Dextran 2.5g

[0058] Hydroxypropyl beta cyclodextrin 2g

[0059] Put the main and auxiliary materials into the liquid mixing tank, add 1200ml of water for injection to dissolve, adjust the pH to 3-11 with hydrochloric acid or sodium hydroxide, then add 0.05% medical activated carbon and stir for 10 minutes to decolorize, then filter to remove carbon, and the filtrate is qualified after pH measurement Add water for injection until the volume of the solution is 2000ml, fine filter with a 0.22μm microporous membrane, subpackage the filtrate, and half-tamp the plug, freeze the subpackaged drug solution to -60°C, insulate and freeze for 1 hour, and then evacuate to 10mmHg, the temperature was raised slowly at a constant speed of 5°C / hour to 0°C, and then the temperature was raised to 50°C at a speed of 9°C / hour, then dried at a constant temperature for 3 hours, capped, packed and put into storage.

Embodiment 3

[0061] Nizophenone Fumarate 5g

[0062] Dextran 50g

[0063] Poloxamer 2g

[0064] Put the main and auxiliary materials into the liquid mixing tank, add 1200ml of water for injection to dissolve, adjust the pH to 5-7 with hydrochloric acid or sodium hydroxide, then add 0.05% medical activated carbon and stir for 30 minutes to decolorize, then filter to remove carbon, and the filtrate is qualified after pH measurement Add water for injection until the volume of the solution is 2000ml, fine filter with a 0.22μm microporous membrane, subpackage the filtrate, and half-tamp the plug, freeze the subpackaged drug solution to -30°C, keep it frozen for 6 hours, and then evacuate to 0.5mmHg, the temperature was raised slowly at a constant speed of 2°C / hour to 0°C, and then raised to 40°C at a speed of 7°C / hour, and then dried at a constant temperature for 7 hours, capped, packed and put into storage.

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