CN100496489C - Nizofenone fumarate freeze-dried powder and method of preparing the same - Google Patents
Nizofenone fumarate freeze-dried powder and method of preparing the same Download PDFInfo
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- CN100496489C CN100496489C CNB2008100906716A CN200810090671A CN100496489C CN 100496489 C CN100496489 C CN 100496489C CN B2008100906716 A CNB2008100906716 A CN B2008100906716A CN 200810090671 A CN200810090671 A CN 200810090671A CN 100496489 C CN100496489 C CN 100496489C
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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
The invention belongs to medical technical field, the present invention relates to a kind of lyophilized formulations, particularly relate to a kind of Boletic acid buddhist nun azoles phenyl ketone freeze-dried powder and preparation method thereof.
Background technology
Y-9179 (Nizofenone fumarate), CAS:54533-85-6, molecular formula: C
25H
25ClN
4O
7, molecular weight: 528.88, structural formula:
This product is developed by Japanese Welfide company, goes on the market in Japan in 1988.Went on the market in Korea S by Hanall company in 1991.This product is that novel imidazole class ischemic cerebrovascular improves medicine, can improve brain function, suppresses cerebral infarction and forms; Improve the brain wave after the cerebral ischemia and recover the tractus pyramidalis function.Zoopery shows that also this product can prolong the life span of brain cell under ischemia or the anoxia condition significantly, thereby improves a series of symptoms that brain cell causes after anoxia.
Through pharmacological evaluation proof Y-9179 the ischemic disordered brain function is had the improvement effect, in ischemia and anoxybiotic animal model, can prolong life cycle, be applicable to the improvement of cerebral disorders due to subarachnoid hemorrhage acute stage (mild to moderate) ischemia.
Y-9179 is used for the treatment of the disordered brain function due to the ischemia, especially subarachnoid hemorrhage during acute stage, and the acute cerebral ischemia due to the cerebral hemorrhage of other types.
U.S. Pat 3915981 discloses the synthetic method of a kind of nizofenone and salt thereof, and has mentioned it and can be prepared as tablet, injectable powder and injection.Wherein tablet consists of 1 portion of major ingredient, 66.3 parts of lactose, 25 parts of corn starchs, 6 parts of microcrystalline Cellulose, 1 part of methylcellulose and 0.7 part of magnesium stearate composition; The powder pin is 1 portion of major ingredient, 88 parts of lactose, 10 parts of microcrystalline Cellulose and 1 part of methylcellulose; Injection is for being dissolved in 0.1mg or 0.5mg major ingredient the solution that is mixed with 1ml in 5% the G/W.Need when wherein tablet is oral through gastrointestinal tract, be subjected to first pass effect to influence drug effect relatively poor.Injectable powder uses in the microcrystalline Cellulose water dissolubility relatively poor, and dissolubility is also relatively poor in Y-9179 self water, is easy to generate insoluble matter during use, comes with being danger close as injection.And that its injection is stocked is cumbersome, decomposes rotten easily.
The market is sold the Y-9179 preparation and mostly is aqueous injection at present, and inconvenience is in use arranged more: 1, need repeatedly take out in practical operation and use liquid, preparation causes pyrogen defective very easily by germ contamination.2, in the actual clinical, various disease conditions requires to reduce the patient infusion amount, and can't solve with liquid drugs injection.3, in cold season, particularly in the north and the transportation of extremely frigid zones and storage all have an inconvenience.4, liquid preparation breakage very easily pollutes packing.5, range of application is narrower.And the disclosed injectable powder of prior art has adopted unaccommodated adjuvant.In view of this, special proposition the present invention.
Summary of the invention
It is a kind of to stable performances such as light, heat, oxygen, water, pollution-free that one of the object of the invention is to provide, applied range, and be convenient to the Boletic acid buddhist nun azoles phenyl ketone freeze-dried powder operating, transport and preserve.
Another purpose of the present invention is to provide a kind of Boletic acid buddhist nun azoles phenyl ketone freeze-dried powder preparation method of suitable large-scale production.
For achieving the above object, the technical solution used in the present invention is:
A kind of Boletic acid buddhist nun azoles phenyl ketone freeze-dried powder, described lyophilized powder contains Y-9179 and pharmaceutically acceptable auxiliaries, and described pharmaceutic adjuvant is selected from excipient, solubilizing agent, pH regulator agent.
Above-mentioned injection Boletic acid buddhist nun azoles phenyl ketone freeze-dried powder, described excipient be in mannitol, dextran, the glucosan any one, described solubilizing agent be in Tween 80, hydroxypropyl beta cyclodextrin, poloxamer, the Polyethylene Glycol any one, described pH regulator agent is mineral acid or alkali or the two combination.
Above-mentioned injection Boletic acid buddhist nun azoles phenyl ketone freeze-dried powder, described excipient are mannitol; Described solubilizing agent is a Tween 80; Described pH regulator agent is an one or more combination in hydrochloric acid, sulphuric acid, sodium hydroxide, potassium hydroxide, sodium bicarbonate, the potassium bicarbonate.
Above-mentioned injection Boletic acid buddhist nun azoles phenyl ketone freeze-dried powder, described amount of excipient is 0.1～10 times of Y-9179, described solubilizing agent consumption is 0.1～10 times of Y-9179, and described pH regulator agent consumption is for to be adjusted to 3～11 with Y-9179 pH value of solution before the lyophilizing.
Above-mentioned injection Boletic acid buddhist nun azoles phenyl ketone freeze-dried powder, described amount of excipient is 0.1～10 times of Y-9179, described solubilizing agent consumption is 0.1～10 times of Y-9179, and described pH regulator agent consumption is for to be adjusted to 3～11 with Y-9179 pH value of solution before the lyophilizing.
Above-mentioned injection Boletic acid buddhist nun azoles phenyl ketone freeze-dried powder, described amount of excipient is 0.5～3 times of Y-9179, described solubilizing agent consumption is 0.2～1 times of Y-9179, and described pH regulator agent consumption is for to be adjusted to 3～4 with Y-9179 pH value of solution before the lyophilizing.
The present invention is for making that described Boletic acid buddhist nun azoles phenyl ketone freeze-dried powder is stable more, outward appearance is full, dissolubility good, through groping, in prescription, add excipient, to improve the lyophilized powder outward appearance, the excipient that is suitable for the Boletic acid buddhist nun azoles phenyl ketone freeze-dried powder preparation has mannitol, dextran, glucosan, and wherein mannitol is optimum selection.
Y-9179 is different solubility in different solvents, places in 25～27 ℃ of water-baths, and jolting was 30 seconds in per 5 minutes, in 30 minutes, observe, found that this product is indissoluble in water, acetone and ethyl acetate, almost insoluble in chloroform, hexane and diisopropyl ether, easily molten in methanol.Because its dissolubility in water is very little, so need to add cosolvent.When carrying out the solubilising test, find, Tween 80, hydroxypropyl beta cyclodextrin, poloxamer, Polyethylene Glycol have significant solubilization to Y-9179, further investigate and find Tween 80 hydrotropy performance the best, further investigate the solubilising power of different amounts Tween 80 again, solubilizing effect is better when finding that Tween 80 weight is 0.1～10 times of Y-9179, and preferred multiple is 0.2～1 times.
The preparation method of Boletic acid buddhist nun azoles phenyl ketone freeze-dried powder noted earlier, described method is:
(1) dosing: main materials and auxiliary materials is dropped into Agitation Tank, add an amount of water for injection stirring and dissolving, add the pH regulator agent;
(2) decolouring: the solution for preparing is added medicinal active carbon, stir decolouring under the room temperature, filter de-carbon then, add water for injection again to ormal weight after survey pH is qualified, with 0.22 μ m microporous filter membrane fine straining, packing, half tamponade;
(3) lyophilizing:
A, pre-freeze: the drug solution that branch is installed is refrigerated to-60～-30 ℃, is incubated freezing 1～6 hour,
B, distillation: evacuation after the pre-freeze, to 0.1～10mmHg, at the uniform velocity slowly heat up with 2～5 ℃/speed at one hour rating then, to 0～30 ℃,
C, drying: after being warming up to 0～30 ℃, be warming up to 30～50 ℃ by 4～9 ℃/speed at one hour rating, freeze-day with constant temperature is 3～7 hours then.
Above-mentioned Boletic acid buddhist nun azoles phenyl ketone freeze-dried powder preparation method, described method is:
The described an amount of water for injection of step (1) is 240 times of major ingredient;
The described medicinal active carbon of step (2) consumption is 0.05% of step (a 1) obtain solution volume, and described stirring is for stirring 10～30 minutes, and described water for injection ormal weight is 400 times of major ingredient;
Cryogenic temperature is-50～-40 ℃ described in step (3) a pre-freeze process, and cooling time is 2～4 hours;
Vacuum described in the b sublimation process is 0.5～5mmHg, and programming rate is 3 ℃/hour, is warming up to 10～20 ℃;
Be warming up to 40～50 ℃ described in the c dry run, be 5～7 hours drying time.
Above-mentioned Boletic acid buddhist nun azoles phenyl ketone freeze-dried powder preparation method, described method is:
The described stirring of step (2) is for stirring 15～25 minutes;
Cryogenic temperature is-45 ℃ described in step (3) a pre-freeze process, and cooling time is 3 hours;
Vacuum is 1mmHg described in the b sublimation process, is warming up to 15 ℃;
Be warming up to 45 ℃ described in the c dry run, 6 ℃/hour of programming rates, be 5 hours drying time.
In the Boletic acid buddhist nun azoles phenyl ketone freeze-dried powder preparation method, the present invention further defines the use amount of water for injection, has solved because poor, the inefficient problem of lyophilizing of the improper medicine solubility property that causes of water consumption; The present invention has guaranteed the product final mass to the qualification of activated carbon consumption.
The back freeze-drying process then is the key technology point of preparation lyophilized powder: the present invention is defined as-60～-30 ℃ with the pre-freeze temperature, cooling time 1～6 hour, guaranteed that solution can fully freeze, can not make product subside owing to solution freezes reality, then further the pre-freeze temperature and time is limited again, find out optimum range; Sublimation stage is made clearly regulation to programming rate, and 2～5 ℃/hour, preferred 3 ℃/hour, and solved the problem of the product appearance difference that may occur in conjunction with vacuum; Determining of baking temperature and time guaranteed that moisture can fully evaporate.
Above described Boletic acid buddhist nun azoles phenyl ketone freeze-dried powder preparation method, described method is specially: with 1 part of Y-9179, mannitol, dextran, any one or a few combination in any is 0.5～3 part in the glucosan, Tween 80, hydroxypropyl beta cyclodextrin, poloxamer, any one 0.2～1 part adds the dosing cylinder in the Polyethylene Glycol, with 240 times of water for injection dissolvings of major ingredient, add 0.05% medicinal active carbon and stir decolouring 10～30 minutes, filter de-carbon then, the qualified back adding of filtrate survey pH water for injection to liquor capacity is 400 times of major ingredient, with 0.22 μ m microporous filter membrane fine straining, the filtrate packing, half tamponade, the drug solution that branch is installed is refrigerated to-50～-40 ℃, is incubated freezing 2～4 hours, be evacuated to 0.5～5mmHg then, at the uniform velocity slowly heat up with 3 ℃/speed at one hour rating,, and then be warming up to 40～50 ℃ by 5～7 ℃/speed at one hour rating to 10～20 ℃, freeze-day with constant temperature is 4～6 hours again, gland, the packing warehouse-in.
Above described Boletic acid buddhist nun azoles phenyl ketone freeze-dried powder preparation method, described method is specially again: with 1 part of Y-9179, mannitol, dextran, any one or a few combination in any is 0.6 part in the glucosan, Tween 80, hydroxypropyl beta cyclodextrin, poloxamer, any one 0.4 part adds the dosing cylinder in the Polyethylene Glycol, with 240 times of water for injection dissolvings of major ingredient, add 0.05% medicinal active carbon and stir decolouring 10～30 minutes, filter de-carbon then, the qualified back adding of filtrate survey pH water for injection to liquor capacity is 400 times of major ingredient, with 0.22 μ m microporous filter membrane fine straining, the filtrate packing, half tamponade, the drug solution that branch is installed is refrigerated to-50～-40 ℃, is incubated freezing 2～4 hours, be evacuated to 0.5～5mmHg then, at the uniform velocity slowly heat up with 3 ℃/speed at one hour rating,, and then be warming up to 40～50 ℃ by 5～7 ℃/speed at one hour rating to 10～20 ℃, freeze-day with constant temperature is 4～6 hours again, gland, the packing warehouse-in.
Above described Boletic acid buddhist nun azoles phenyl ketone freeze-dried powder preparation method, described method more specifically is: with 1 part of Y-9179, mannitol, dextran, any one or a few combination in any is 0.6 part in the glucosan, Tween 80, hydroxypropyl beta cyclodextrin, poloxamer, any one 0.4 part adds the dosing cylinder in the Polyethylene Glycol, with 240 times of water for injection dissolvings of major ingredient, add 0.05% medicinal active carbon and stir decolouring 15～25 minutes, filter de-carbon then, the qualified back adding of filtrate survey pH water for injection to liquor capacity is 400 times of major ingredient, with 0.22 μ m microporous filter membrane fine straining, the filtrate packing, half tamponade, the drug solution that branch is installed is refrigerated to-45 ℃, is incubated freezing 3 hours, be evacuated to 1mmHg then, at the uniform velocity slowly heat up with 3 ℃/speed at one hour rating,, and then be warming up to 45 ℃ by 6 ℃/speed at one hour rating to 15 ℃, freeze-day with constant temperature is 5 hours again, gland, the packing warehouse-in.
Injection Boletic acid buddhist nun azoles phenyl ketone freeze-dried powder provided by the present invention and preparation method thereof has following advantages:
(1) injection Boletic acid buddhist nun azoles phenyl ketone freeze-dried powder provided by the present invention is to stable performances such as light, heat, oxygen, water, and is pollution-free, applied range, and be convenient to operation, transportation and storage.
(2) injection Boletic acid buddhist nun azoles phenyl ketone freeze-dried powder provided by the present invention adopts the given dose excipient especially to adopt given dose mannitol, makes product appearance full, does not subside, bad phenomenon such as cavity; Adopt the given dose solubilizing agent especially to adopt the given dose Tween 80, improved the very little problem of Y-9179 dissolubility in water.
(3) injection Boletic acid buddhist nun azoles phenyl ketone freeze-dried powder preparation method provided by the present invention is simple, be easy to large-scale industrial production, key elements such as pre-freeze temperature, freeze-off time, programming rate, vacuum, baking temperature is reasonably combined, obtained the quality height, the freeze-drying prods that outward appearance is good.
Description of drawings
Fig. 1. the Boletic acid buddhist nun azoles phenyl ketone freeze-dried powder preparation flow
The specific embodiment
The following examples will be done to explain more specifically to the present invention, but the present invention is not limited only to these embodiment, and these embodiment do not limit the present invention in any way yet equally.
Embodiment 1
Y-9179 5g
Mannitol 3g
Tween 80 2g
Main ingredient is dropped in the dosing cylinder, add water for injection 1200m dissolving, regulate pH to 3～4 with hydrochloric acid or sodium hydroxide, add 0.05% medicinal active carbon then and stir decolouring 20 minutes, filter de-carbon then, it is 2000ml that filtrate is surveyed the qualified back adding of pH water for injection to liquor capacity, with 0.22 μ m microporous filter membrane fine straining, the filtrate packing, half tamponade, the drug solution that branch is installed is refrigerated to-45 ℃, is incubated freezing 3 hours, be evacuated to 1mmHg then, at the uniform velocity slowly heat up with 3 ℃/speed at one hour rating,, and then be warming up to 45 ℃ by 6 ℃/speed at one hour rating to 15 ℃, freeze-day with constant temperature is 5 hours again, gland, the packing warehouse-in.
Embodiment 2
Y-9179 5g
Dextran 2.5g
Hydroxypropyl beta cyclodextrin 2g
Main ingredient is dropped in the dosing cylinder, add water for injection 1200ml dissolving, regulate pH to 3～11 with hydrochloric acid or sodium hydroxide, add 0.05% medicinal active carbon then and stir decolouring 10 minutes, filter de-carbon then, it is 2000ml that filtrate is surveyed the qualified back adding of pH water for injection to liquor capacity, with 0.22 μ m microporous filter membrane fine straining, the filtrate packing, half tamponade, the drug solution that branch is installed is refrigerated to-60 ℃, is incubated freezing 1 hour, be evacuated to 10mmHg then, at the uniform velocity slowly heat up with 5 ℃/speed at one hour rating,, and then be warming up to 50 ℃ by 9 ℃/speed at one hour rating to 0 ℃, freeze-day with constant temperature is 3 hours again, gland, the packing warehouse-in.
Embodiment 3
Y-9179 5g
Glucosan 50g
Poloxamer 2g
Main ingredient is dropped in the dosing cylinder, add water for injection 1200ml dissolving, regulate pH to 5～7 with hydrochloric acid or sodium hydroxide, add 0.05% medicinal active carbon then and stir decolouring 30 minutes, filter de-carbon then, it is 2000ml that filtrate is surveyed the qualified back adding of pH water for injection to liquor capacity, with 0.22 μ m microporous filter membrane fine straining, the filtrate packing, half tamponade, the drug solution that branch is installed is refrigerated to-30 ℃, is incubated freezing 6 hours, be evacuated to 0.5mmHg then, at the uniform velocity slowly heat up with 2 ℃/speed at one hour rating,, and then be warming up to 40 ℃ by 7 ℃/speed at one hour rating to 0 ℃, freeze-day with constant temperature is 7 hours again, gland, the packing warehouse-in.
Embodiment 4
Y-9179 5g
Mannitol 5g
Polyethylene Glycol 5g
Main ingredient is dropped in the dosing cylinder, add water for injection 1200ml dissolving, regulate pH to 7～9 with hydrochloric acid or sodium hydroxide, add 0.05% medicinal active carbon then and stir decolouring 15 minutes, filter de-carbon then, it is 2000ml that filtrate is surveyed the qualified back adding of pH water for injection to liquor capacity, with 0.22 μ m microporous filter membrane fine straining, the filtrate packing, half tamponade, the drug solution that branch is installed is refrigerated to-50 ℃, is incubated freezing 2 hours, be evacuated to 5mmHg then, at the uniform velocity slowly heat up with 5 ℃/speed at one hour rating,, and then be warming up to 30 ℃ by 4 ℃/speed at one hour rating to 10 ℃, freeze-day with constant temperature is 7 hours again, gland, the packing warehouse-in.
Embodiment 5
Y-9179 5g
Dextran 10 g
Tween 80 10g
Main ingredient is dropped in the dosing cylinder, add water for injection 1200ml dissolving, regulate pH to 9～11 with hydrochloric acid or sodium hydroxide, add 0.05% medicinal active carbon then and stir decolouring 25 minutes, filter de-carbon then, it is 2000ml that filtrate is surveyed the qualified back adding of pH water for injection to liquor capacity, with 0.22 μ m microporous filter membrane fine straining, the filtrate packing, half tamponade, the drug solution that branch is installed is refrigerated to-40 ℃, is incubated freezing 4 hours, be evacuated to 2mmHg then, at the uniform velocity slowly heat up with 4 ℃/speed at one hour rating,, and then be warming up to 45 ℃ by 7 ℃/speed at one hour rating to 20 ℃, freeze-day with constant temperature is 6 hours again, gland, the packing warehouse-in.
Embodiment 6
Y-9179 5g
Dextran 15 g
Hydroxypropyl beta cyclodextrin 30g
Main ingredient is dropped in the dosing cylinder, add water for injection 1200ml dissolving, regulate pH to 9～11 with hydrochloric acid or sodium hydroxide, add 0.05% medicinal active carbon then and stir decolouring 20 minutes, filter de-carbon then, it is 2000ml that filtrate is surveyed the qualified back adding of pH water for injection to liquor capacity, with 0.22 μ m microporous filter membrane fine straining, the filtrate packing, half tamponade, the drug solution that branch is installed is refrigerated to-45 ℃, is incubated freezing 3 hours, be evacuated to 8mmHg then, at the uniform velocity slowly heat up with 5 ℃/speed at one hour rating,, and then be warming up to 40 ℃ by 5 ℃/speed at one hour rating to 15 ℃, freeze-day with constant temperature is 4 hours again, gland, the packing warehouse-in.
Embodiment 7
Y-9179 5g
Arbitrarily than glucosan+dextran 30g
Poloxamer 30g
Main ingredient is dropped in the dosing cylinder, add water for injection 1200ml dissolving, regulate pH to 9～11 with hydrochloric acid or sodium hydroxide, add 0.05% medicinal active carbon then and stir decolouring 25 minutes, filter de-carbon then, it is 2000ml that filtrate is surveyed the qualified back adding of pH water for injection to liquor capacity, with 0.22 μ m microporous filter membrane fine straining, the filtrate packing, half tamponade, the drug solution that branch is installed is refrigerated to-35 ℃, is incubated freezing 5 hours, be evacuated to 3mmHg then, at the uniform velocity slowly heat up with 5 ℃/speed at one hour rating,, and then be warming up to 50 ℃ by 4 ℃/speed at one hour rating to 30 ℃, freeze-day with constant temperature is 3.5 hours again, gland, the packing warehouse-in.
Embodiment 8
Y-9179 5g
Arbitrarily than glucosan+mannitol 40g
Poloxamer 10g
Main ingredient is dropped in the dosing cylinder, add water for injection 1200ml dissolving, regulate pH to 9～11 with hydrochloric acid or sodium hydroxide, add 0.05% medicinal active carbon then and stir decolouring 30 minutes, filter de-carbon then, it is 2000ml that filtrate is surveyed the qualified back adding of pH water for injection to liquor capacity, with 0.22 μ m microporous filter membrane fine straining, the filtrate packing, half tamponade, the drug solution that branch is installed is refrigerated to-50 ℃, is incubated freezing 2 hours, be evacuated to 7mmHg then, at the uniform velocity slowly heat up with 4 ℃/speed at one hour rating,, and then be warming up to 35 ℃ by 6 ℃/speed at one hour rating to 10 ℃, freeze-day with constant temperature is 5 hours again, gland, the packing warehouse-in.
Claims (4)
1. an injection Boletic acid buddhist nun azoles phenyl ketone freeze-dried powder is characterized in that being made up of Y-9179 and pharmaceutically acceptable auxiliaries, and described pharmaceutic adjuvant is selected from excipient, solubilizing agent, pH regulator agent; Described amount of excipient is 0.6 times of Y-9179, and described solubilizing agent consumption is 0.4 times of Y-9179, and described pH regulator agent consumption is for to be adjusted to 3～4 with Y-9179 pH value of solution before the lyophilizing; Described excipient is a mannitol, and described solubilizing agent is a Tween 80, and described pH regulator agent is hydrochloric acid or sodium hydroxide.
2. a method for preparing the described Boletic acid buddhist nun azoles phenyl ketone freeze-dried powder of claim 1 is characterized in that, described method is:
(1) dosing: main materials and auxiliary materials is dropped into Agitation Tank, add an amount of water for injection stirring and dissolving, add the pH regulator agent;
(2) decolouring: the solution for preparing is added medicinal active carbon, stir decolouring under the room temperature, filter de-carbon then, add water for injection again to ormal weight after survey pH is qualified, with 0.22 μ m microporous filter membrane fine straining, packing, half tamponade;
(3) lyophilizing:
A, pre-freeze: the drug solution that branch is installed is refrigerated to-60～-30 ℃, is incubated freezing 1～6 hour,
B, distillation: evacuation after the pre-freeze, to 0.1～10mmHg, at the uniform velocity slowly heat up with 2～5 ℃/speed at one hour rating then, to 0～30 ℃,
C, drying: after being warming up to 0～30 ℃, be warming up to 30～50 ℃ by 4～9 ℃/speed at one hour rating, freeze-day with constant temperature is 3～7 hours then.
3. Boletic acid buddhist nun azoles phenyl ketone freeze-dried powder preparation method according to claim 2 is characterized in that, described method is:
The described an amount of water for injection of step (1) is 240 times of major ingredient;
The described medicinal active carbon of step (2) consumption is 0.05% of step (a 1) obtain solution volume, and described stirring is for stirring 10～30 minutes, and described water for injection ormal weight is 400 times of major ingredient;
Cryogenic temperature is-50～-40 ℃ described in step (3) a pre-freeze process, and cooling time is 2～4 hours;
Vacuum described in the b sublimation process is 0.5～5mmHg, and programming rate is 3 ℃/hour, is warming up to 10～20 ℃;
Be warming up to 40～50 ℃ described in the c dry run, programming rate is 5～7 ℃/hour, and be 4～6 hours drying time.
4. Boletic acid buddhist nun azoles phenyl ketone freeze-dried powder preparation method according to claim 3 is characterized in that, described method is:
The described stirring of step (2) is for stirring 15～25 minutes;
Cryogenic temperature is-45 ℃ described in step (3) a pre-freeze process, and cooling time is 3 hours;
Vacuum is 1mmHg described in the b sublimation process, is warming up to 15 ℃;
Be warming up to 45 ℃ described in the c dry run, 6 ℃/hour of programming rates, be 5 hours drying time.
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| Application Number | Priority Date | Filing Date | Title |
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| CNB2008100906716A CN100496489C (en) | 2007-08-14 | 2008-04-09 | Nizofenone fumarate freeze-dried powder and method of preparing the same |
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| CN200710016386.5 | 2007-08-14 | ||
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| CNB2008100906716A CN100496489C (en) | 2007-08-14 | 2008-04-09 | Nizofenone fumarate freeze-dried powder and method of preparing the same |
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