CN1788725A - Voriconazole freeze-drying powder injection and its preparation process - Google Patents
Voriconazole freeze-drying powder injection and its preparation process Download PDFInfo
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- CN1788725A CN1788725A CN 200410098736 CN200410098736A CN1788725A CN 1788725 A CN1788725 A CN 1788725A CN 200410098736 CN200410098736 CN 200410098736 CN 200410098736 A CN200410098736 A CN 200410098736A CN 1788725 A CN1788725 A CN 1788725A
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- voriconazole
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Abstract
The present invention relates to one kind of freeze dried voriconazole composition including voriconazole in effectively treating amount and hydroxypropyl-beta-cyclodextrin. Each of the preparation unit contains voriconazole in 50-400 mg, pregreably 200 mg and hydroxypropyl-beta-cyclodextrin of 5-40 time, preferably 15-25 times, weight of voriconazole.
Description
Technical field
The present invention relates to a kind of pharmaceutical preparation, specifically is voriconazole freeze-drying powder and preparation method.
Background technology
Voriconazole is a kind of synthetic triazole type medicine, is the synthetic fluconazol derivant of the second filial generation.As novel antifungal agent, it has has a broad antifungal spectrum, characteristics that antibacterial efficacy is strong.Pfizer company has found this product the eighties, can be used for the higher serious fungal infection treatment of mortality rate.The low 0.2mg/ml that is about of the dissolubility of voriconazole in water, pH3) and unstable, facile hydrolysis.Make lyophilized injectable powder good solution beyond doubt, if but its lower dissolubility is difficult to reach the concentration of therapeutic effect without solubilising.Chinese patent CN1261287 discloses a kind of voriconazole and has made the method for lyophilized injectable powder through the cyclodextrin inclusion compound solubilising, but the cyclodextrin that adopts is butyl oxide sulfur-beta-schardinger dextrin-, and this cyclodextrin has certain toxicity to body.
Summary of the invention
The purpose of this invention is to provide a kind of voriconazole and make lyophilized injectable powder through HP-enclose solubilising.Compare with the lyophilized formulations of the disclosed employing butyl oxide of Chinese patent CN1261287 sulfur-beta-cyclodextrin inclusion compound, the toxicity of this product is lower.Because this product is a lyophilized formulations, good stability is easy to the long term store of product in addition.
The present invention makes injectable powder by principal agent voriconazole and HP-through the enclose lyophilizing, also can add proper amount of diluting as mannitol, lactose, dextran, glucose, glycine, gelatin hydrolysate, polyvidone etc.The weight of voriconazole in each unit formulation is that 50～400mg/ props up among the present invention, and preferred 200mg/ props up.The consumption of the HP-among the present invention is 5～40 times of voriconazole weight, preferred 15～25 times.Preparation technology is: gets HP-and is dissolved in the water for injection, and standby; Get voriconazole and join in the above solution stirring and dissolving.Activated carbon adsorption, decarbonization filtering with 0.22 μ m filtering with microporous membrane, adds water to full dose, fill; Vacuum lyophilization.
The vacuum lyophilization condition:
1) pre-freeze: the medicine that branch is installed is put on the freeze drying box internal partition-40 ℃ of following pre-freezes 4 hours;
2) sublimation drying: condenser temperature is dropped to below-45 ℃, start vacuum pump, after treating that vacuum reaches certain numerical value, slowly open butterfly valve, below reaching 13.33Pa (0.1mmHg), the vacuum in the drying baker closes fridge, slowly heat by the heating system under the dividing plate, the temperature of frozen product is increased to gradually-20 ℃.About 24 hours of whole sublimation drying process.
3) dry again: drying is about 10 hours under 10 ℃, and loss on drying is up to specification.
The products appearance that the present invention makes is plentiful, fine and smooth, and quality is loose, and dissolution velocity is fast again, is convenient to clinical use.
Following examples are used for further specifying the present invention, rather than limitation of the scope of the invention.
Embodiment 1
Prescription: voriconazole 10g
HP-200g
Water for injection is an amount of
Make 1000ml altogether
Method for making:
1, with standby after plug, aluminium lid, the cillin bottle processing;
2, take by weighing HP-and be dissolved in about 700ml water for injection, standby;
3, take by weighing voriconazole and join in the above solution stirring and dissolving.(about 5 hours)
4, with 0.1% active carbon 80 ℃ of absorption 15 minutes down, decarbonization filtering with 0.22 μ m filtering with microporous membrane, is tested to the clear and bright filtrate of gained.
5, the medicinal liquid that is up to the standards is diluted to full dose, and every 20ml fill is in the cillin bottle of 30ml;
6, vacuum drying:
1) pre-freeze: the medicine that branch is installed is put on the freeze drying box internal partition-40 ℃ of following pre-freezes 4 hours;
2) sublimation drying: condenser temperature is dropped to below-45 ℃, start vacuum pump, after treating that vacuum reaches certain numerical value, slowly open butterfly valve, below reaching 13.33Pa (0.1mmHg), the vacuum in the drying baker closes fridge, slowly heat by the heating system under the dividing plate, the temperature of frozen product is increased to gradually-20 ℃.About 24 hours of whole sublimation drying process.
3) dry again: drying is about 10 hours under 10 ℃, and loss on drying is up to specification.
7, under vacuum drying condition, gland seal;
8, packing is put in storage after product inspection is qualified.
Embodiment 2
Prescription: voriconazole 10g
HP-50g
Mannitol 100g
Water for injection is an amount of
Make 1000ml altogether
Method for making:
1, with standby after plug, aluminium lid, the cillin bottle processing;
2, take by weighing HP-and be dissolved in the water for injection of about 700ml, standby;
3, take by weighing voriconazole and join in the above solution, stirring and dissolving (about 5 hours) adds the mannitol dissolving.
4, with 0.1% active carbon 80 ℃ of absorption 15 minutes down, decarbonization filtering with 0.22 μ m filtering with microporous membrane, is tested to the clear and bright filtrate of gained.
5, the medicinal liquid that is up to the standards is diluted to full dose, and every 20ml fill is in the cillin bottle of 30ml;
6, vacuum drying:
1) pre-freeze: the medicine that branch is installed is put on the freeze drying box internal partition-40 ℃ of following pre-freezes 4 hours;
2) sublimation drying: condenser temperature is dropped to below-45 ℃, start vacuum pump, after treating that vacuum reaches certain numerical value, slowly open butterfly valve, below reaching 13.33Pa (0.1mmHg), the vacuum in the drying baker closes fridge, slowly heat by the heating system under the dividing plate, the temperature of frozen product is increased to gradually-20 ℃.About 24 hours of whole sublimation drying process.
3) dry again: drying is about 10 hours under 10 ℃, and loss on drying is up to specification.
7, under vacuum drying condition, gland seal;
8, packing is put in storage after product inspection is qualified.
Embodiment 3
Prescription: voriconazole 10g
HP-400g
Water for injection is an amount of
Make 1000ml altogether
Method for making:
1, with standby after plug, aluminium lid, the cillin bottle processing;
2, take by weighing HP-and be dissolved in the water for injection of about 700ml, standby;
3, take by weighing voriconazole and join in the above solution stirring and dissolving.(about 5 hours)
4, with 0.1% active carbon 80 ℃ of absorption 15 minutes down, decarbonization filtering with 0.22 μ m filtering with microporous membrane, is tested to the clear and bright filtrate of gained.
5, the medicinal liquid that is up to the standards is diluted to full dose, and every 20ml fill is in the cillin bottle of 30ml;
6, vacuum drying:
1) pre-freeze: the medicine that branch is installed is put on the freeze drying box internal partition-40 ℃ of following pre-freezes 4 hours;
2) sublimation drying: condenser temperature is dropped to below-45 ℃, start vacuum pump, after treating that vacuum reaches certain numerical value, slowly open butterfly valve, below reaching 13.33Pa (0.1mmHg), the vacuum in the drying baker closes fridge, slowly heat by the heating system under the dividing plate, the temperature of frozen product is increased to gradually-20 ℃.About 24 hours of whole sublimation drying process.
3) dry again: drying is about 10 hours under 10 ℃, and loss on drying is up to specification.
7, under vacuum drying condition, gland seal;
8, packing is put in storage after product inspection is qualified.
Embodiment 4
Prescription: voriconazole 10g
HP-300g
Water for injection is an amount of
Make 1000ml altogether
Method for making:
1, with standby after plug, aluminium lid, the cillin bottle processing;
2, take by weighing HP-and be dissolved in the water for injection of about 700ml, standby;
3, take by weighing voriconazole and join in the above solution stirring and dissolving.(about 5 hours)
4, with 0.1% active carbon 80 ℃ of absorption 15 minutes down, decarbonization filtering with 0.22 μ m filtering with microporous membrane, is tested to the clear and bright filtrate of gained.
5, the medicinal liquid that is up to the standards is diluted to full dose, and every 20ml fill is in the cillin bottle of 30ml;
6, vacuum drying:
1) pre-freeze: the medicine that branch is installed is put on the freeze drying box internal partition-40 ℃ of following pre-freezes 4 hours;
2) sublimation drying: condenser temperature is dropped to below-45 ℃, start vacuum pump, after treating that vacuum reaches certain numerical value, slowly open butterfly valve, below reaching 13.33Pa (0.1mmHg), the vacuum in the drying baker closes fridge, slowly heat by the heating system under the dividing plate, the temperature of frozen product is increased to gradually-20 ℃.About 24 hours of whole sublimation drying process.
3) dry again: drying is about 10 hours under 10 ℃, and loss on drying is up to specification.
7, under vacuum drying condition, gland seal;
8, packing is put in storage after product inspection is qualified.
Embodiment 5
Prescription: voriconazole 10g
HP-100g
Water for injection is an amount of
Make 1000ml altogether
Method for making:
1, with standby after plug, aluminium lid, the cillin bottle processing;
2, take by weighing HP-and be dissolved in the water for injection of about 700ml, standby;
3, take by weighing voriconazole and join in the above solution stirring and dissolving.(about 5 hours)
4, with 0.1% active carbon 80 ℃ of absorption 15 minutes down, decarbonization filtering with 0.22 μ m filtering with microporous membrane, is tested to the clear and bright filtrate of gained.
5, the medicinal liquid that is up to the standards is diluted to full dose, and every 20ml fill is in the cillin bottle of 30ml;
6, vacuum drying:
1) pre-freeze: the medicine that branch is installed is put on the freeze drying box internal partition-40 ℃ of following pre-freezes 4 hours;
2) sublimation drying: condenser temperature is dropped to below-45 ℃, start vacuum pump, after treating that vacuum reaches certain numerical value, slowly open butterfly valve, below reaching 13.33Pa (0.1mmHg), the vacuum in the drying baker closes fridge, slowly heat by the heating system under the dividing plate, the temperature of frozen product is increased to gradually-20 ℃.About 24 hours of whole sublimation drying process.
3) dry again: drying is about 10 hours under 10 ℃, and loss on drying is up to specification.
7, under vacuum drying condition, gland seal;
8, packing is put in storage after product inspection is qualified.
Embodiment 6
Prescription: voriconazole 10g
HP-200g
Water for injection is an amount of
Make 1000ml altogether
Method for making:
1, with standby after plug, aluminium lid, the cillin bottle processing;
2, take by weighing HP-and be dissolved in the water for injection of about 700ml, standby;
3, take by weighing voriconazole and join in the above solution stirring and dissolving.(about 5 hours)
4, with 0.1% active carbon 80 ℃ of absorption 15 minutes down, decarbonization filtering with 0.22 μ m filtering with microporous membrane, is tested to the clear and bright filtrate of gained.
5, the medicinal liquid that is up to the standards is diluted to full dose, and every 10ml fill is in the cillin bottle of 15ml;
6, vacuum drying:
1) pre-freeze: the medicine that branch is installed is put on the freeze drying box internal partition-40 ℃ of following pre-freezes 4 hours;
2) sublimation drying: condenser temperature is dropped to below-45 ℃, start vacuum pump, after treating that vacuum reaches certain numerical value, slowly open butterfly valve, below reaching 13.33Pa (0.1mmHg), the vacuum in the drying baker closes fridge, slowly heat by the heating system under the dividing plate, the temperature of frozen product is increased to gradually-20 ℃.About 24 hours of whole sublimation drying process.
3) dry again: drying is about 10 hours under 10 ℃, and loss on drying is up to specification.
7, under vacuum drying condition, gland seal;
8, packing is put in storage after product inspection is qualified.
Claims (7)
1, a kind of freeze-dried composition of voriconazole is comprising the voriconazole and the HP-of treatment effective dose.
2, pharmaceutical composition as claimed in claim 1, wherein the weight of voriconazole in each unit formulation is that 50～400mg/ props up.
3, pharmaceutical composition as claimed in claim 1, wherein the weight of voriconazole in each unit formulation is that 200mg/ props up.
4, pharmaceutical composition as claimed in claim 1, wherein the HP-consumption is 5～40 times of voriconazole weight.
5, pharmaceutical composition as claimed in claim 1, wherein the HP-consumption is 15～25 times of voriconazole weight.
6, as the described pharmaceutical composition of claim 1～5, wherein can also contain diluent.
7, pharmaceutical composition as claimed in claim 6, wherein diluent is selected from a kind of or mixture of mannitol, lactose, dextran, glucose, glycine, gelatin hydrolysate, polyvidone etc.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410098736 CN1788725A (en) | 2004-12-15 | 2004-12-15 | Voriconazole freeze-drying powder injection and its preparation process |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410098736 CN1788725A (en) | 2004-12-15 | 2004-12-15 | Voriconazole freeze-drying powder injection and its preparation process |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1788725A true CN1788725A (en) | 2006-06-21 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410098736 Pending CN1788725A (en) | 2004-12-15 | 2004-12-15 | Voriconazole freeze-drying powder injection and its preparation process |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1788725A (en) |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101744778A (en) * | 2010-02-01 | 2010-06-23 | 陕西合成药业有限公司 | Voriconazole phosphate ester for injection and preparation method thereof |
| EP2409699A1 (en) | 2010-07-23 | 2012-01-25 | Combino Pharm, S.L. | Stable compositions of voriconazole |
| WO2012171561A1 (en) | 2011-06-15 | 2012-12-20 | Synthon Bv | Stabilized voriconazole composition |
| CN103251565A (en) * | 2013-04-09 | 2013-08-21 | 珠海亿邦制药股份有限公司 | Voriconazole freeze-dried powder injection for injection and preparation method thereof |
| WO2014108474A1 (en) * | 2013-01-11 | 2014-07-17 | Xellia Pharmaceuticals Aps | Voriconazole inclusion complexes |
| WO2014108918A2 (en) * | 2013-01-08 | 2014-07-17 | Mylan Laboratories Limited | An injectable antifungal formulation |
| CN104840431A (en) * | 2014-02-13 | 2015-08-19 | 长春海悦药业有限公司 | Pharmaceutical composition containing voriconazole |
| CN110812334A (en) * | 2019-12-03 | 2020-02-21 | 珠海亿邦制药有限责任公司 | Voriconazole pharmaceutical composition for injection and preparation method thereof |
| CN110934834A (en) * | 2019-12-30 | 2020-03-31 | 丽珠集团丽珠制药厂 | Voriconazole-containing composition and preparation method thereof |
| CN111700864A (en) * | 2020-06-28 | 2020-09-25 | 海南倍特药业有限公司 | Preparation method of voriconazole for injection |
| CN115998675A (en) * | 2022-12-26 | 2023-04-25 | 沈阳兴齐眼药股份有限公司 | Voriconazole eye drops, preparation method and application thereof |
-
2004
- 2004-12-15 CN CN 200410098736 patent/CN1788725A/en active Pending
Cited By (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101744778B (en) * | 2010-02-01 | 2014-10-29 | 陕西合成药业有限公司 | Voriconazole phosphate ester for injection and preparation method thereof |
| CN101744778A (en) * | 2010-02-01 | 2010-06-23 | 陕西合成药业有限公司 | Voriconazole phosphate ester for injection and preparation method thereof |
| EP2409699A1 (en) | 2010-07-23 | 2012-01-25 | Combino Pharm, S.L. | Stable compositions of voriconazole |
| WO2012171561A1 (en) | 2011-06-15 | 2012-12-20 | Synthon Bv | Stabilized voriconazole composition |
| EP2720723B1 (en) * | 2011-06-15 | 2018-04-11 | Synthon BV | Stabilized voriconazole composition |
| EP2720723A1 (en) | 2011-06-15 | 2014-04-23 | Synthon BV | Stabilized voriconazole composition |
| WO2014108918A3 (en) * | 2013-01-08 | 2014-12-04 | Mylan Laboratories Limited | Injectable antifungal formulation |
| WO2014108918A2 (en) * | 2013-01-08 | 2014-07-17 | Mylan Laboratories Limited | An injectable antifungal formulation |
| WO2014108474A1 (en) * | 2013-01-11 | 2014-07-17 | Xellia Pharmaceuticals Aps | Voriconazole inclusion complexes |
| AU2014204878B2 (en) * | 2013-01-11 | 2018-04-19 | Xellia Pharmaceuticals Aps | Voriconazole inclusion complexes |
| US11141417B2 (en) | 2013-01-11 | 2021-10-12 | Xellia Pharmaceuticals Aps | Voriconazole inclusion complexes |
| CN103251565A (en) * | 2013-04-09 | 2013-08-21 | 珠海亿邦制药股份有限公司 | Voriconazole freeze-dried powder injection for injection and preparation method thereof |
| CN104840431A (en) * | 2014-02-13 | 2015-08-19 | 长春海悦药业有限公司 | Pharmaceutical composition containing voriconazole |
| CN104840431B (en) * | 2014-02-13 | 2017-09-08 | 长春海悦药业股份有限公司 | A kind of pharmaceutical composition containing voriconazole |
| CN110812334A (en) * | 2019-12-03 | 2020-02-21 | 珠海亿邦制药有限责任公司 | Voriconazole pharmaceutical composition for injection and preparation method thereof |
| CN110934834A (en) * | 2019-12-30 | 2020-03-31 | 丽珠集团丽珠制药厂 | Voriconazole-containing composition and preparation method thereof |
| CN111700864A (en) * | 2020-06-28 | 2020-09-25 | 海南倍特药业有限公司 | Preparation method of voriconazole for injection |
| CN115998675A (en) * | 2022-12-26 | 2023-04-25 | 沈阳兴齐眼药股份有限公司 | Voriconazole eye drops, preparation method and application thereof |
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| TA01 | Transfer of patent application right |
Effective date of registration: 20070810 Address after: Room B, building 20C1, building 1, science and Technology Exhibition Center, North Third Ring Road West, Haidian District, Beijing Applicant after: Dadao Longda (Beijing) Medical Technology Development Co.Ltd Address before: Room 1, No. 807, Pure Land Temple, four crossing, Beijing, Haidian District Applicant before: Boerda Biotech Development Co., Ltd., Beijing |
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| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |