CN103191067A - Freeze-dried powder injection of bromhexine hydrochloride and preparation method thereof - Google Patents
Freeze-dried powder injection of bromhexine hydrochloride and preparation method thereof Download PDFInfo
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- CN103191067A CN103191067A CN2013101187504A CN201310118750A CN103191067A CN 103191067 A CN103191067 A CN 103191067A CN 2013101187504 A CN2013101187504 A CN 2013101187504A CN 201310118750 A CN201310118750 A CN 201310118750A CN 103191067 A CN103191067 A CN 103191067A
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Abstract
The invention relates to the field of pharmaceutical preparations, and in particular relates to freeze-dried powder injection of bromhexine hydrochloride and a preparation method thereof. The freeze-dried powder injection of bromhexine hydrochloride is prepared from bromhexine hydrochloride, acidity regulator, pharmaceutically acceptable accessories and water for injection; and the acidity regulator is one or more than two of benzoic acid, citric acid, acetic acid, malic acid, boric acid, phosphoric acid and lactic acid. According to the invention, the stability of the preparation is improved; the bioavailability is high; oxidative degradation can be effectively prevented; reactions such as nausea and stomach discomfort, caused by oral medicines, are avoided; and the freeze-dried powder injection of bromhexine hydrochloride disclosed by the invention is conveniently used in clinical.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, particularly lyophilized injectable powder of a kind of Bisolvon and preparation method thereof.
Background technology
Bisolvon belongs to mucolytic drugs, and this medicine can change the viscosity composition of sputum, reduces the thick sputum degree, makes expectorant be easy to expectoration, after the nineteen sixty-five listing, uses for many years clinically.China began in 1973 to produce, and existing oneself becomes the expectorant of domestic and international clinical first-selection.All oneself records for Britain, France, Germany, Holland, Switzerland, Italy, Portugal, Chinese Pharmacopoeia, the mucus that mainly acts on trachea, bronchorrhea body of gland produces cell, make it to secrete the lower small molecular protein of viscosity, and therefore make the rheological properties of trachea, bronchus secretion recover normal, sticking expectorant reduces, and the sputum dilution is easy to expectoration.
Bisolvon can promote degeneration and the removing of goblet cell, stimulates ciliated epithelial cell and activates Mucociliary function, helps the discharge of airway secretions; Can also suppress lysosomal acid phosphorus enzyme, promote generation and the secretion of surfactant, stimulate broncho-pulmonary patient's slurry activity, recover the generation of sulfomucin, thereby help generation and the secretion of lung surface mass, listed national basic medical insurance medicine catalogue respiratory system expectorant Class A medicine at this medicine of China, indication is: be used for chronic bronchitis, asthma, bronchiectasis, emphysema, being particularly useful for the sticking productive cough of white goes out difficult person and extensively blocks critical emergency case that bronchia causes etc. because of sputum, its dosage is little, toxicity is low, and prolonged application does not have side effects.
Existing Bisolvon dosage form has tablet, injection, 2% solution, aerosol etc. on the market.Untoward reaction such as that oral tablet draws after the patient uses easily is nauseating, stomach discomfort, can be directly used in the Bisolvon injection of venoclysis, bad reflection after having avoided peroral dosage form to take, clinical easy to use, but exist the defective of dosage form stability difference, and the time and the condition that store all have been subjected to very big restriction, are not easy to long-distance transport and long preservation.Therefore, extensive, easy to use to good stability, clinical practice on the market, the simple Bisolvon sterile preparation of preparation technology has proposed demand.
Summary of the invention
Shortcomings and deficiencies at above-mentioned prior art existence, the object of the present invention is to provide a kind of Bisolvon sterile freeze-drying preparation and preparation method thereof, adopt the Bisolvon sterile freeze-drying preparation of the inventive method preparation to improve stability of formulation, the bioavailability height, can prevent oxidative degradation effectively and avoid that oral medication causes feel sick, reaction such as stomach discomfort, clinical easy to use.
In order to realize the foregoing invention purpose, the invention provides following technical scheme:
The invention provides a kind of Bisolvon lyophilized injectable powder, made by Bisolvon, acidity regulator, acceptable accessories and water for injection;
Wherein, acidity regulator is a kind of or both the above mixture in benzoic acid, citric acid, acetic acid, malic acid, boric acid, phosphoric acid, the lactic acid.
In some embodiments of the invention, lyophilized injectable powder pH value provided by the invention is 2.0～3.5.
In some embodiments of the invention, lyophilized injectable powder provided by the invention is made by following raw material in weight portion:
4.0～12.0 parts of Bisolvon
40.0～200.0 parts of acceptable accessories
Acidity regulator adjusting pH value is 2.0～3.5 consumption
1000～3000 parts of waters for injection.
In some embodiments of the invention, lyophilized injectable powder provided by the invention is made by following raw material in mass percent:
4.0 parts of Bisolvon
50.0～150.0 parts of acceptable accessories
Acidity regulator adjusting pH value is 2.0～3.5 consumption
1000～3000 parts of waters for injection.
In some embodiments of the invention, lyophilized injectable powder provided by the invention is made by following raw material in mass percent:
4.0 parts of Bisolvon
50.0～150.0 parts of acceptable accessories
Acidity regulator adjusting pH value is 2.0～3.5 consumption
1500～2000 parts of waters for injection.
As preferably, acceptable accessories is excipient.
The present invention also provides the preparation method of lyophilized injectable powder, comprises the steps:
In weight portion, made by following raw material:
4.0～12.0 parts of Bisolvon
40.0～200.0 parts of acceptable accessories
Acidity regulator adjusting pH value is 2.0～3.5 consumption
1000～3000 parts of waters for injection;
Wherein, acidity regulator is a kind of or both the above mixture in benzoic acid, citric acid, acetic acid, malic acid, boric acid, phosphoric acid, the lactic acid;
Acceptable accessories is excipient;
Get excipient and mix acquisition excipient solution in back with the water for injection of 1.5 times of amounts;
After getting Bisolvon and the water for injection of 0.7～0.8 times of amount mixing, regulating pH value through acidity regulator is 2.0～3.5, obtains Bisolvon solution;
Get the water for injection of surplus, regulating pH value through acidity regulator is 2.0～3.5, and the acquisition pH value is 2.0～3.5 aqueous solution for injection;
Get excipient solution, Bisolvon solution and pH value and be 2.0～3.5 aqueous solution for injection and mix the back and obtain first solution, sterilization after filtration, lyophilization, packing are namely.
In some embodiments of the invention, lyophilization is specially: get first solution under-40 ℃, the condition of normal pressure behind pre-freeze 2～10h, under the condition of temperature-25 ℃～-10 ℃, pressure 1.33～13.33Pa, through first lyophilizing 10～20 hours, then under temperature is 0 ℃～10 ℃, the condition of pressure 0.13～1.33Pa, through second lyophilizing 5～10 hours.
The Bisolvon lyophilized injectable powder that the present invention also provides above-mentioned preparation method to obtain; Preparation method specifically comprises the steps:
In weight portion, made by following raw material:
4.0～12.0 parts of Bisolvon
40.0～200.0 parts of acceptable accessories
Acidity regulator adjusting pH value is 2.0～3.5 consumption
1000～3000 parts of waters for injection;
Wherein, acidity regulator is a kind of or both the above mixture in benzoic acid, citric acid, acetic acid, malic acid, boric acid, phosphoric acid, the lactic acid;
Acceptable accessories is excipient;
Get excipient and mix acquisition excipient solution in back with the water for injection of 1.5 times of amounts;
After getting Bisolvon and the water for injection of 0.7～0.8 times of amount mixing, regulating pH value through acidity regulator is 2.0～3.5, obtains Bisolvon solution;
Get the water for injection of surplus, regulating pH value through acidity regulator is 2.0～3.5, and the acquisition pH value is 2.0～3.5 aqueous solution for injection;
Get excipient solution, Bisolvon solution and pH value and be 2.0～3.5 aqueous solution for injection and mix the back and obtain first solution, sterilization after filtration, lyophilization, packing are namely.
In some embodiments of the invention, lyophilization is specially in the preparation method: get first solution under-40 ℃, the condition of normal pressure behind pre-freeze 2～10h, under the condition of temperature-25 ℃～-10 ℃, pressure 1.33～13.33Pa, through first lyophilizing 10～20 hours, then under temperature is 0 ℃～10 ℃, the condition of pressure 0.13～1.33Pa, through second lyophilizing 5～10 hours.
The invention provides lyophilized injectable powder of a kind of Bisolvon and preparation method thereof.Hydrochloride for injection bromhexine lyophilized injectable powder provided by the invention has improved stability of formulation, the bioavailability height, can prevent oxidative degradation effectively and avoid that oral medication causes feel sick, reaction such as stomach discomfort, clinical easy to use.
The specific embodiment
The invention discloses lyophilized injectable powder of a kind of Bisolvon and preparation method thereof, those skilled in the art can use for reference this paper content, suitably improve technological parameter and realize.Special needs to be pointed out is that all similarly replace and change apparent to those skilled in the art, they all are regarded as being included in the present invention.Method of the present invention and application are described by preferred embodiment, the related personnel obviously can change or suitably change and combination methods and applications as herein described in not breaking away from content of the present invention, spirit and scope, realizes and use the technology of the present invention.
The raw materials used medicine of Bisolvon lyophilized injectable powder provided by the invention and acceptable accessories all can be buied by market.
In Bisolvon lyophilized injectable powder provided by the invention, formula for a product has 3 kinds of production specifications, and (4mg/ props up, 8mg/ props up, 12mg/ props up), wherein Bisolvon is principal agent, requires by prescription dispensing respectively according to different size, and mannitol is excipient, phosphoric acid is used for the acidity of regulator solution, makes the pH value of solution in 2.0～3.5 scope; Water for injection according to the concentration of principal agent and the charging quantity of every medicine, adds an amount of as the solvent of dissolving raw material.
Below in conjunction with embodiment, further set forth the present invention:
Embodiment 1: the preparation of Bisolvon lyophilized injectable powder
The specification of 4mg/ bottle, 1000 bottles of hydrochloride for injection bromhexine sterile freeze-drying preparation prescriptions are:
Bisolvon 4g, mannitol 70g, the Fructus Citri Limoniae acid for adjusting pH is to 2.0-3.5, and water for injection adds to 2000ml, makes 1000 bottles altogether.
Preparation method:
1) takes by weighing mannitol 70g by prescription, add proper amount of water for injection (500mL), after the stirring and dissolving, add the injection active carbon of 0.2% (m/v), stir, in hot bath, be incubated 20～30 minutes, take off charcoal with filter filter just then, and with a small amount of injection washing twice, merging filtrate gets the excipient dosing;
2) get Bisolvon 4g, add the water for injection that about 3/4-1.5 doubly measures, make its dissolving, regulate its pH value to 2.0～3.5 with the 0.1mol/L citric acid, get the Bisolvon dosing;
3) merge excipient dosing and Bisolvon dosing, measure intermediate, qualified after, add with the adjusting of 0.1mol/L citric acid afterwards, pH value is 2.0～3.5 water for injection standardize solution, the content that makes Bisolvon is 4mg/2ml;
4) under tight aseptic technique, filter with 0.22 μ m filter membrane degerming;
5) packing is 1000 bottles, and half turunda chlorinated scoline bottle stopper is sent into the freeze dryer lyophilizing;
6) drying finishes, and compresses bottle stopper, slowly bleeds off vacuum, outlet, and gland checks, packing.
The lyophilization condition: below temperature-40 ℃, pre-freeze is 10 hours under normal pressure with this solution; Then under the condition of temperature-25 ℃, pressure 1.33～13.33Pa, through first lyophilizing 20 hours; Be warming up to again under 0 ℃, the condition of pressure 0.13～1.33 handkerchief, through second lyophilizing 10 hours.
Adding solvent for injection (available injection normal saline, glucose injection) during clinical practice is mixed with and meets injection preparation.
Embodiment 2: the preparation of Bisolvon lyophilized injectable powder
4mg/ bottle specification, 1000 bottles of hydrochloride for injection bromhexine sterile freeze-drying preparation prescriptions are:
Hydrochloric acid is smelt oneself new 4.0g, glucose 70g, and mannitol 100g, phosphoric acid is regulated pH to 2.0-3.5, and water for injection adds to 2000ml, makes 1000 bottles altogether.
Preparation method:
1) weighs up glucose 70g, mannitol 100g by prescription, add proper amount of water for injection, after the stirring and dissolving, adding 0.2%(m/v) injection active carbon stirs, and is incubated 20～30 minutes in the hot bath, just filter decarburization with filter, and with a small amount of injection washing twice, merging filtrate gets the excipient dosing;
2) get Bisolvon 4.0g by prescription, add the water for injection of about 3/4 amount, make its dissolving, regulate its pH value to 2.0～3.5 with 0.1mol/L phosphoric acid, get the Bisolvon dosing;
3) merge excipient dosing and Bisolvon dosing, measure intermediate, qualified after, add with the adjusting of 0.1mol/L phosphoric acid afterwards, pH value is 2.0～3.5 water for injection standardize solution, making Bisolvon content is 4mg/2ml;
4) under tight aseptic technique, with 0.22 μ m filter membrane aseptic filtration;
5) packing is 1000 bottles, and half turunda chlorinated scoline bottle stopper is sent into freeze dryer and frozen;
6) drying finishes, and compresses bottle stopper, slowly bleeds off vacuum, outlet, and gland checks, packing.
The lyophilization condition: with this solution in-40 ℃ of temperature to foretell, pre-freeze is 10 hours under normal pressure; Under the condition of temperature-25 ℃, pressure 1.33～13.33 handkerchiefs, through first lyophilizing 20 hours; Be warming up to again under 0 ℃, the condition of pressure 0.13～1.33 handkerchief, through second lyophilizing 10 hours.
Adding solvent for injection (available injection normal saline, glucose injection) during clinical practice is mixed with and meets injection preparation.
Embodiment 3: the preparation of Bisolvon lyophilized injectable powder
Hydrochloric acid is smelt oneself new 8.0g, mannitol 70g, and phosphoric acid is regulated pH to 2.0-3.5, and water for injection adds to 1000ml.
Preparation method:
1) take by weighing mannitol 70g by prescription, add proper amount of water for injection, after the stirring and dissolving, add 0.2%(m/v) the injection active carbon, stir, be incubated 20～30 minutes in the hot bath, just filter decarburization with filter, and with a small amount of injection washing twice, merging filtrate gets the excipient dosing;
2) get Bisolvon 8.0g by prescription, add the water for injection of about 3/4 amount, make its dissolving, regulate its pH value to 2.0～3.5 with 0.1mol/L phosphoric acid, get the Bisolvon dosing;
3) merge excipient dosing and Bisolvon dosing, measure intermediate, qualified after, with the adjusting of 0.1mol/L phosphoric acid afterwards, pH value is 2.0～3.5 water for injection standardize solution, making Bisolvon content is 4mg/2ml;
4) under tight aseptic technique, with 0.22 μ m filter membrane aseptic filtration;
5) packing, half turunda chlorinated scoline bottle stopper is sent into freeze dryer and is frozen;
6) drying finishes, and compresses bottle stopper, slowly bleeds off vacuum, outlet, and gland checks, packing.
The lyophilization condition: with this solution in-40 ℃ of temperature to foretell, pre-freeze is 2 hours under normal pressure; Under the condition of temperature-18 ℃, pressure 1.33Pa, through first lyophilizing 12 hours; Be warming up under 10 ℃, the condition of pressure 1.1Pa the second stage of lyophilizing 10 hours again.
Adding solvent for injection (available injection normal saline, glucose injection) during clinical practice is mixed with and meets injection preparation.
Embodiment 4: the preparation of Bisolvon lyophilized injectable powder
Hydrochloric acid is smelt oneself new 8.0g, glucose 70g, and mannitol 100g, the Fructus Citri Limoniae acid for adjusting pH is to 2.0-3.5, and water for injection adds to 2000ml.
Preparation method:
1) takes by weighing glucose 70g, mannitol 100g by prescription, add proper amount of water for injection, after the stirring and dissolving, adding 0.2%(m/v) injection active carbon stirs, and is incubated 20～30 minutes in the hot bath, just filter decarburization with filter, and with a small amount of injection washing twice, merging filtrate gets the excipient dosing;
2) get Bisolvon 8.0g by prescription, add the water for injection of about 3/4 amount, make its dissolving, regulate its pH value to 2.0～3.5 with the 0.1mol/L citric acid, get the Bisolvon dosing;
3) merge excipient dosing and Bisolvon dosing, measure intermediate, qualified after, with the adjusting of 0.1mol/L citric acid afterwards, pH value is 2.0～3.5 water for injection standardize solution, making Bisolvon content is 4mg/2ml;
4) under tight aseptic technique, with 0.22 μ m filter membrane aseptic filtration;
5) packing, half turunda chlorinated scoline bottle stopper is sent into freeze dryer and is frozen;
6) drying finishes, and compresses bottle stopper, slowly bleeds off vacuum, outlet, and gland checks, packing.
The lyophilization condition: with this solution in-40 ℃ of temperature to foretell, pre-freeze is 5 hours under normal pressure; Under the condition of temperature-22 ℃, pressure 10Pa, through first lyophilizing 18 hours; Be warming up under 5 ℃, the condition of pressure 0.8Pa the second stage of lyophilizing 8 hours again.
Adding solvent for injection (available injection normal saline, glucose injection) during clinical practice is mixed with and meets injection preparation.
Embodiment 5: the preparation of Bisolvon lyophilized injectable powder
Hydrochloric acid is smelt oneself new 8.0g, sucrose 60g, and mannitol 100g, phosphoric acid is regulated pH to 2.0-3.5, and water for injection adds to 3000ml.
Preparation method:
1) weighs up sucrose 60g, mannitol 100g by prescription, add proper amount of water for injection, after the stirring and dissolving, adding 0.2%(m/v) injection active carbon stirs, and is incubated 20～30 minutes in the hot bath, just filter decarburization with filter, and with a small amount of injection washing twice, merging filtrate gets the excipient dosing;
2) get Bisolvon 8.0g by prescription, add the water for injection of about 3/4 amount, make its dissolving, regulate its pH value to 2.0～3.5 with 0.1mol/L phosphoric acid, get the Bisolvon dosing;
3) merge excipient dosing and Bisolvon dosing, measure intermediate, qualified after, with the adjusting of 0.1mol/L phosphoric acid afterwards, pH value is 2.0～3.5 water for injection standardize solution, making Bisolvon content is 4mg/2ml;
4) under tight aseptic technique, with 0.22 μ m filter membrane aseptic filtration;
5) packing, half turunda chlorinated scoline bottle stopper is sent into freeze dryer and is frozen;
6) drying finishes, and compresses bottle stopper, slowly bleeds off vacuum, outlet, and gland checks, packing.
The lyophilization condition: with this solution in-40 ℃ of temperature to foretell, pre-freeze is 8 hours under normal pressure; Under the condition of temperature-20 ℃, pressure 13.33Pa, through first lyophilizing 15 hours; Be warming up under 8 ℃, the condition of pressure 0.5Pa the second stage of lyophilizing 9 hours again.
Adding solvent for injection (available injection normal saline, glucose injection) during clinical practice is mixed with and meets injection preparation.
Embodiment 6: the preparation of Bisolvon lyophilized injectable powder
Hydrochloric acid is smelt oneself new 4.0g, glucose 70g, and mannitol 100g, phosphoric acid, Fructus Citri Limoniae acid for adjusting pH are to 2.0-3.5, and water for injection adds to 2000ml.
Preparation method:
1) takes by weighing glucose 70g, mannitol 100g by prescription, add proper amount of water for injection, after the stirring and dissolving, adding 0.2%(m/v) injection active carbon stirs, and is incubated 20～30 minutes in the hot bath, just filter decarburization with filter, and with a small amount of injection washing twice, merging filtrate gets the excipient dosing;
2) get Bisolvon 4.0g by prescription, add the water for injection of about 3/4 amount, make its dissolving, regulate its pH value to 2.0～3.5 with 0.1mol/L phosphoric acid, citric acid, get the Bisolvon dosing;
3) merge excipient dosing and Bisolvon dosing, measure intermediate, qualified after, with 0.1mol/L phosphoric acid, citric acid adjusting afterwards, pH value is 2.0～3.5 water for injection standardize solution, making Bisolvon content is 4mg/2ml;
4) under tight aseptic technique, with 0.22 μ m filter membrane aseptic filtration;
5) packing, half turunda chlorinated scoline bottle stopper is sent into freeze dryer and is frozen;
6) drying finishes, and compresses bottle stopper, slowly bleeds off vacuum, outlet, and gland checks, packing.
The lyophilization condition: with this solution in-40 ℃ of temperature to foretell, pre-freeze is 10 hours under normal pressure; Under the condition of temperature-15 ℃, pressure 5.0Pa, through first lyophilizing 20 hours; Be warming up under 3 ℃, the condition of pressure 0.13Pa the second stage of lyophilizing 5 hours again.
Adding solvent for injection (available injection normal saline, glucose injection) during clinical practice is mixed with and meets injection preparation.
Embodiment 7: the preparation of Bisolvon lyophilized injectable powder
Hydrochloric acid is smelt oneself new 12.0g, lactose 100g, and benzoic acid is regulated pH to 2.0-3.5, and water for injection adds to 3000ml.
Preparation method:
1) take by weighing lactose 100g by prescription, add proper amount of water for injection, after the stirring and dissolving, add 0.2%(m/v) the injection active carbon, stir, be incubated 20～30 minutes in the hot bath, just filter decarburization with filter, and with a small amount of injection washing twice, merging filtrate gets the excipient dosing;
2) get Bisolvon 12.0g by prescription, add the water for injection of about 3/4 amount, make its dissolving, regulate its pH value to 2.0～3.5 with the 0.1mol/L benzoic acid, get the Bisolvon dosing;
3) merge excipient dosing and Bisolvon dosing, measure intermediate, qualified after, with the adjusting of 0.1mol/L benzoic acid afterwards, pH value is 2.0～3.5 water for injection standardize solution, making Bisolvon content is 4mg/2ml;
4) under tight aseptic technique, with 0.22 μ m filter membrane aseptic filtration;
5) packing, half turunda chlorinated scoline bottle stopper is sent into freeze dryer and is frozen;
6) drying finishes, and compresses bottle stopper, slowly bleeds off vacuum, outlet, and gland checks, packing.
The lyophilization condition: with this solution in-40 ℃ of temperature to foretell, pre-freeze is 4 hours under normal pressure; Under the condition of temperature-10 ℃, pressure 8.0Pa, through first lyophilizing 10 hours; Be warming up under 0 ℃, the condition of pressure 1.33Pa the second stage of lyophilizing 6 hours again.
Adding solvent for injection (available injection normal saline, glucose injection) during clinical practice is mixed with and meets injection preparation.
Embodiment 8: stability experiment
Touchstone: National Drug Administration's standard (trying).
Sample survey: Bisolvon lyophilized injectable powder provided by the invention
Pilot project: strong illumination test, hot test
1, strong illumination test
Test method: the strong illumination proof box that will adopt the sample of the embodiment of the invention 1 preparation to place tunable optical intensity is to handle 10 days under the condition of 4500lx ± 500lx in light intensity, detects respectively 0 day, 5 days and the emphasis quality index of 10 days samples.Assay (seeing Table 1).
Table 1 strong illumination result of the test
The result shows that under strong illumination, sample is with the prolongation of irradiation time, and the main quality index of sample has no significant change, and product is qualified, illustrates that this product is stable to auroral poles.
2, hot test result
Test method: the sample of the embodiment of the invention 1 preparation is carried out hot test under 60 ℃ of conditions, respectively to handling 0 day, 5 days and the emphasis quality index of 10 days samples detects.Testing result sees Table 2.
Table 2 hot test result
The result shows, deposits under 60 ℃ of conditions, and the steady quality of the Bisolvon lyophilized injectable powder of the embodiment of the invention 1 preparation, content and related substance all do not have significant change.
Bisolvon lyophilized injectable powder to the embodiment of the invention 2 to 7 preparations carries out the aforementioned stable test, the result shows Bisolvon lyophilized injectable powder stability provided by the invention better with the stability test of the Bisolvon lyophilized injectable powder of embodiment 1 preparation unanimity as a result.
The above only is preferred implementation of the present invention; should be pointed out that for those skilled in the art, under the prerequisite that does not break away from the principle of the invention; can also make some improvements and modifications, these improvements and modifications also should be considered as protection scope of the present invention.
Claims (9)
1. a Bisolvon lyophilized injectable powder is characterized in that, is made by Bisolvon, acidity regulator, acceptable accessories and water for injection;
Described acidity regulator is a kind of or both the above mixture in benzoic acid, citric acid, acetic acid, malic acid, boric acid, phosphoric acid, the lactic acid.
2. lyophilized injectable powder according to claim 1 is characterized in that, its pH value is 2.0～3.5.
3. lyophilized injectable powder according to claim 1 is characterized in that, in weight portion, is made by following raw material:
4.0～12.0 parts of Bisolvon
40.0～200.0 parts of acceptable accessories
Acidity regulator adjusting pH value is 2.0～3.5 consumption
1000～3000 parts of waters for injection.
4. lyophilized injectable powder according to claim 1 is characterized in that, in mass percent, is made by following raw material:
4.0 parts of Bisolvon
50.0～150.0 parts of acceptable accessories
Acidity regulator adjusting pH value is 2.0～3.5 consumption
1000～3000 parts of waters for injection.
5. lyophilized injectable powder according to claim 1 is characterized in that, in mass percent, is made by following raw material:
4.0 parts of Bisolvon
50.0～150.0 parts of acceptable accessories
Acidity regulator adjusting pH value is 2.0～3.5 consumption
1500～2000 parts of waters for injection.
6. lyophilized injectable powder according to claim 1 is characterized in that, described acceptable accessories is excipient.
7. according to the preparation method of each described lyophilized injectable powder of claim 1 to 6, it is characterized in that, comprise the steps:
In weight portion, made by following raw material:
4.0～12.0 parts of Bisolvon
40.0～200.0 parts of acceptable accessories
Acidity regulator adjusting pH value is 2.0～3.5 consumption
1000～3000 parts of waters for injection;
Described acidity regulator is a kind of or both the above mixture in benzoic acid, citric acid, acetic acid, malic acid, boric acid, phosphoric acid, the lactic acid;
Described acceptable accessories is excipient;
Get described excipient and mix acquisition excipient solution in back with the water for injection of 1.5 times of amounts;
After getting Bisolvon and the water for injection of 0.7～0.8 times of amount mixing, regulating pH value through described acidity regulator is 2.0～3.5, obtains Bisolvon solution;
Get the water for injection of surplus, regulating pH value through described acidity regulator is 2.0～3.5, and the acquisition pH value is 2.0～3.5 aqueous solution for injection;
Get described excipient solution, described Bisolvon solution and described pH value and be 2.0～3.5 aqueous solution for injection and mix the back and obtain first solution, sterilization after filtration, lyophilization, packing are namely.
8. preparation method according to claim 7, it is characterized in that, described lyophilization is specially: get described first solution under-40 ℃, the condition of normal pressure behind pre-freeze 2～10h, under the condition of temperature-25 ℃～-10 ℃, pressure 1.33～13.33Pa, through first lyophilizing 10～20 hours, then under temperature is 0 ℃～10 ℃, the condition of pressure 0.13～1.33Pa, through second lyophilizing 5～10 hours.
9. the Bisolvon lyophilized injectable powder that obtains according to claim 7 or 8 described preparation methoies.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103505423A (en) * | 2013-09-10 | 2014-01-15 | 蚌埠丰原涂山制药有限公司 | Bromhexine hydrochloride freeze-dried powder injection and preparation method thereof |
| CN112546001A (en) * | 2021-01-05 | 2021-03-26 | 河北智同生物制药股份有限公司 | Bromhexine hydrochloride freeze-dried powder injection for injection and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1557285A (en) * | 2004-02-05 | 2004-12-29 | 马小歧 | Bromhexine Hydrochloride aseptic freeze-drying formulation for injection and its preparation method |
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2013
- 2013-04-08 CN CN2013101187504A patent/CN103191067A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1557285A (en) * | 2004-02-05 | 2004-12-29 | 马小歧 | Bromhexine Hydrochloride aseptic freeze-drying formulation for injection and its preparation method |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103505423A (en) * | 2013-09-10 | 2014-01-15 | 蚌埠丰原涂山制药有限公司 | Bromhexine hydrochloride freeze-dried powder injection and preparation method thereof |
| CN103505423B (en) * | 2013-09-10 | 2016-01-20 | 马鞍山丰原制药有限公司 | Bisolvon lyophilized injectable powder and preparation method thereof |
| CN112546001A (en) * | 2021-01-05 | 2021-03-26 | 河北智同生物制药股份有限公司 | Bromhexine hydrochloride freeze-dried powder injection for injection and preparation method thereof |
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Application publication date: 20130710 |