CN1182849C - Freeze dried hydroxycamptothecin powder injection and its preparing process - Google Patents
Freeze dried hydroxycamptothecin powder injection and its preparing process Download PDFInfo
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- CN1182849C CN1182849C CNB021389306A CN02138930A CN1182849C CN 1182849 C CN1182849 C CN 1182849C CN B021389306 A CNB021389306 A CN B021389306A CN 02138930 A CN02138930 A CN 02138930A CN 1182849 C CN1182849 C CN 1182849C
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- injection
- hydroxycamptothecin
- hydroxy camptothecin
- injectable powder
- freeze
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Abstract
The present invention discloses a freeze dried hydroxycamptothecin powder injection and a preparation method thereof. The injection of the present invention mainly contains the following medical raw material: hydroxycamptothecin which is active substances, an excipient vehicle of a freeze dried powder injection, which is medically acceptable, cosolvent and water for injection, wherein the excipient vehicle is selected from one kind of mannitol, lactose for injection, glucose for injection, dextran, sodium chloride, sodium glycinate, sodium dihydrogenorthophosphate and glycine, the mannitol is preferably selected as the excipient vehicle, the cosolvent is the glycine, and the active substance is the hydroxycamptothecin. The quality of the freeze dried hydroxycamptothecin powder injection is high, and the stability is high. The storage life is prolonged to be two years from 3 months, and the freeze dried hydroxycamptothecin powder injection is not deteriorated.
Description
Technical field
The invention belongs to hydroxy camptothecin pharmaceutical preparation, be specially hydroxy camptothecin lyophilized injectable powder and preparation method thereof.
Background technology
Hydroxy camptothecin has anticancer wide spectrum, characteristics evident in efficacy.At present domestic have only its injection formulation using, and the injection formulation patent application of compound alkyl camptothecine, 96112301 are arranged.There is the shortcoming of poor stability in the injection of hydroxy camptothecin, and is easy to change, and said preparation is after seeing light, heat and air, and color and luster is deepened two days later, produces trickle precipitation after 3 months, and main content descends, and catabolite increases, and its curative effect descends, and toxic and side effects increases.
Summary of the invention
The object of the present invention is to provide a kind of injection hydroxy camptothecin lyophilized injectable powder and preparation method, said preparation is domestic not to be used as yet.
Preparation of the present invention is: its main medicinal raw material comprises: its main medicinal raw material comprises: the active substance hydroxy camptothecin; Medically acceptable lyophilized injectable powder excipient mannitol; The cosolvent glycine; Water for injection, the weight ratio of its hydroxy camptothecin, mannitol, glycine is: 5: 160～200: 10.0～20.0.
Its preparation method is dissolved in the medicinal solid material and adjusts behind the water for injection between the pH value 8.5-10.0, by the microporous filter membrane filtration, and lyophilization in freezer dryer.
The specific embodiment
In order to make preparation easy to use rationally, formulate the specification of hydroxycamptothecin for injection injectable powder: the 5mg/ bottle, carry out adjuvant screening: the PH that regulates water for injection with sodium hydroxide solution is 9.5 ± 0.5 as solvent, to help the hydroxy-camptothecin alkali dissolution, select cosolvent glycine, beta-schardinger dextrin-, sodium carbonate to help the hydroxy-camptothecin alkali dissolution, selecting to reveal a kind of in alcohol, injection lactose, glucose for injection, dextran, sodium chloride, Glycine sodium, sodium dihydrogen phosphate, the glycine is excipient.
Write out a prescription and design and The selection result such as table 1:
| Mannitol | 160～200g | ?160～200g | |||||
| Glycine | ?10.0g | ?20.0g | |||||
| Lactic acid | ?200g | ||||||
| Glucose | ?200g | ||||||
| Beta-schardinger dextrin- | ?30g | ||||||
| Sodium chloride | ?200g | ||||||
| Sodium carbonate | ?30g | ||||||
| The injection pH value | 9.6 | ?9.6 | ?9.42 | ?9.8 | ?9.3 | ?9.31 | ?9.42 |
| PH after the lyophilizing | 9.55 | ?9.3 | ?9.38 | ?9.6 | ?8.9 | ?9.26 | ?9.03 |
| The lyophilizing shape | Profile is full | The surface color depth | The spray bottle | Atrophy | Profile is imperfect | Profile is full | Profile is not full |
| Dissolubility | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving |
| Clarity | Clear and bright | Clear and bright | Clear and bright | Clear and bright | Clear and bright | Clear and bright | Clear and bright |
| Color and luster | Yellow | Yellow | Yellow | Last Huang Xiabai | Yellow | Yellow | Yellow |
According to above screening, preferably inject its main medicinal raw material of hydroxy camptothecin lyophilized injectable powder: the active substance hydroxy camptothecin; Medically acceptable lyophilized injectable powder excipient is a mannitol; Cosolvent is a glycine; Its weight ratio is: 5: 160～200: 10.0～20.0.
Its preparation process is: add other material dissolution with between the sodium hydroxide adjustment pH value 8.5-10.0 after the medicinal solid raw material is dissolved in water for injection, filter and adopt 0.65 μ m and twice filtering with microporous membrane of 0.22 μ m, lyophilization in freezer dryer.Lyophilization comprises pre-freeze and sublimation drying; Wherein the pre-freeze temperature of the preceding case of freeze dryer is-38--45 ℃ in the pre-freeze process, insulation, and the temperature of the rear cabinet of freeze dryer is reduced to-60---55 ℃ between soak; In the sublimation drying process, again under the evacuation condition, be warming up to-20--8 is ℃ through the row distillation, exists until no longer including crystal, and heat up again and remove residual moisture.
The assay of the hydroxycamptothecin for injection lyophilized injectable powder of producing with above-mentioned preparation method as
Table 2:
| Numbering | Character | Differentiate | Basicity PH | Related substance | Loss on drying | Content uniformity | Aseptic | Bacterial endotoxin | Clarity | Assay |
| 2551 | Be the loose bulk of yellow | Be positive | 9.2 | Up to specification | 1.3％ | Up to specification | Up to specification | Up to specification | Up to specification | 99.6％ |
| 2552 | Be the loose bulk of yellow | Be positive | 9.2 | Up to specification | 1.3％ | Up to specification | Up to specification | Up to specification | Up to specification | 100. 6％ |
| 2553 | Be the loose bulk of yellow | Be positive | 9.3 | Up to specification | 1.4％ | Up to specification | Up to specification | Up to specification | Up to specification | 100. 4％ |
More than check all meets national WS1-421 (372)-2001 touchstone.
Carry out stability test with reference to " quality standard of Hubei Province medicine inspecting institute authorization ", check structure
As show 3-1,3-2,4:
Table 3-1 lot number 990901
Table 3-2 lot number 990901
Table 4 lot number 990902
By above experiment this product quality height as can be known, good stability, storage life has 3 months and extends to 2 years never degenerates.
Claims (4)
1, injection hydroxy camptothecin lyophilized injectable powder, its medicinal raw material is: the active substance hydroxy camptothecin; Lyophilized injectable powder excipient mannitol; The cosolvent glycine; Water for injection, the weight ratio of its hydroxy camptothecin, mannitol, glycine is: 5: 160～200: 10.0～20.0.
2, a kind of preparation method of injecting the hydroxy camptothecin lyophilized injectable powder according to claim 1, it is characterized in that: add other raw material after described medicinal solid raw material is dissolved in water for injection, adjust then between the pH value 8.5-10.0, by the microporous filter membrane filtration, lyophilization in freezer dryer.
3,, it is characterized in that filtering and adopt 0.65 μ m and twice filtering with microporous membrane of 0.22 μ m as the preparation method of injection hydroxy camptothecin lyophilized injectable powder as described in the claim 2.
4, as the preparation method of injection hydroxy camptothecin lyophilized injectable powder as described in the claim 2, it is characterized in that lyophilization comprises pre-freeze and sublimation drying; Wherein the pre-freeze temperature of the preceding case of freeze dryer is-38--45 ℃ in the pre-freeze process, insulation, and the temperature of the rear cabinet of freeze dryer is reduced to-60---55 ℃ between soak; In the sublimation drying process, again under the evacuation condition, be warming up to-20--8 is ℃ through the row distillation, exists until no longer including crystal, and heat up again and remove residual moisture.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021389306A CN1182849C (en) | 2002-08-15 | 2002-08-15 | Freeze dried hydroxycamptothecin powder injection and its preparing process |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021389306A CN1182849C (en) | 2002-08-15 | 2002-08-15 | Freeze dried hydroxycamptothecin powder injection and its preparing process |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1397280A CN1397280A (en) | 2003-02-19 |
| CN1182849C true CN1182849C (en) | 2005-01-05 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB021389306A Expired - Lifetime CN1182849C (en) | 2002-08-15 | 2002-08-15 | Freeze dried hydroxycamptothecin powder injection and its preparing process |
Country Status (1)
| Country | Link |
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| CN (1) | CN1182849C (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1326525C (en) * | 2004-11-26 | 2007-07-18 | 复旦大学 | 10-hydroxy camptothecin long cyclic liposome and its freeze aried preparation |
| CN102151248A (en) * | 2010-02-12 | 2011-08-17 | 复旦大学 | 9-nitrocamptothecin freeze-dried powder injection and preparation method thereof |
| CN106551910A (en) * | 2015-09-17 | 2017-04-05 | 四川赛诺唯新生物技术有限公司 | A kind of ejection preparation containing camptothecin derivative, its injection, preparation and application |
-
2002
- 2002-08-15 CN CNB021389306A patent/CN1182849C/en not_active Expired - Lifetime
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| Publication number | Publication date |
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| CN1397280A (en) | 2003-02-19 |
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Owner name: FRESENIUS-KABI PHARMACEUTICAL (WUHAN) CO., LTD. Free format text: FORMER OWNER: HUANGSHI LISHIZHEN PHARMACEUTICAL GROUP WUHAN LISHIZHEN PHARMACEUTICAL CO., LTD. Effective date: 20121127 |
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| C41 | Transfer of patent application or patent right or utility model | ||
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Effective date of registration: 20121127 Address after: 430073 Guan Nan Industrial Zone, East Lake New Technology Development Zone, Wuhan, Hubei Patentee after: Fresenius Cabi (Wuhan) Pharmaceutical Co.,Ltd. Address before: 430073 Guan Nan Industrial Park, Hubei, Wuhan Patentee before: HUANGSHI LISHIZHEN PHARMACEUTICAL GROUP WUHAN LISHIZHEN PHARMACEUTICAL CO.,LTD. |
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| CX01 | Expiry of patent term |
Granted publication date: 20050105 |
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| CX01 | Expiry of patent term |