CN101953805B - Method for preparing antitumor medical preparation - Google Patents
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- CN101953805B CN101953805B CN2010105006190A CN201010500619A CN101953805B CN 101953805 B CN101953805 B CN 101953805B CN 2010105006190 A CN2010105006190 A CN 2010105006190A CN 201010500619 A CN201010500619 A CN 201010500619A CN 101953805 B CN101953805 B CN 101953805B
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Abstract
The invention belongs to the technical field of chemical pharmacy and in particular relates to a method for preparing an antitumor medical preparation. The method comprises the following steps of: (1) preparing solution by taking Lobaplatin as a raw material and adding a proper amount of cooled water for injection; (2) adding a proper amount of active carbon with needle uses and adding the water for injection until full content, stirring while preserving heat and then performing aseptic filtration; (3) bulking filtrate and half pressing the plug, collecting the filtrate to a free-drying plate; putting into a freeze fryer cooling chamber, prefreezing, vacuumizing and heating, performing sublimation drying and desorbtion drying and performing vacuum breaking and free-drying; (4) introducingdried and degermed high-purity nitrogen, taking the obtained product out of the freezer and rolling the cover to obtain Lobaplatin for injection.
Description
Technical field
The invention belongs to the technical field of chemical pharmacy, be specifically related to a kind of method for preparing of injection preparation of antitumor drug lobaplatin.
Background technology
Lobaplatin, chemical name is: 1,2-diaminomethyl-Tetramethylene .-lactic acid closes platinum.Molecular formula is C
9H
18N
2O
3Pt, molecular weight are 397.34, belong to alkylating agent kind anti-cancer drugs thing, are the third generation platinum series antineoplastic medicaments after cisplatin, carboplatin.Multiple animal and human's tumor cell line there is clear and definite cytotoxicity; Sihe is stronger mutually with the tumor-inhibiting action of cisplatin; Cell strain to anti-cisplatin still has certain cytotoxicity, is mainly used in the treatment of breast carcinoma, small cell lung cancer and chronic myelocytic leukemia.
The characteristics of lobaplatin are that active anticancer is strong, and toxicity is less, in dimethyl sulfoxide, are prone to dissolve, and dissolve in the water part omitted.Compare with hydrate, anhydride has hygroscopy, and water absorption is strong especially, becomes sticky easily; And the dissolubility of this product in water is very little, lobaplatin is processed freeze-dried powder with freeze-drying after, product dosage is accurate; Drug content is not had influence, and better stability of preparation is easy to store.In the concrete large-scale production of lobaplatin lyophilized injectable powder, there are two problems always, the one, moisture content of finished products is difficult to reach requirement, stipulates in the standard that its moisture must not surpass 3%, two, and it is bad to freeze type.Moisture high UCL makes the anhydrous dry powder moisture absorption once more easily, influences product stability.Freezing type, bad mainly to show as the dry powder outward appearance that obtains not fully up to expectations; Tend to occur situation such as bubble, layering, surface irregularity and variable color, the dry powder crystal formation is bad, not only influences product appearance; And causing the content heterogeneity of dry powder, rehydration is relatively poor during use waits harmful effect.
Summary of the invention
The object of the present invention is to provide a kind of method for preparing of injection lobaplatin, to solve Moisture high UCL and the bad problem of product crystallization in the existing product.
For this reason, the present invention provides a kind of method for preparing of injection lobaplatin, these method process following steps:
(1) gets the lobaplatin raw material, add an amount of cooling water for injection, be mixed with solution;
(2) add an amount of pin and use activated carbon, add to the full amount of water for injection insulated and stirred, aseptic filtration again;
(3) get filtrating fill half tamponade, be collected into the lyophilizing dish, the freeze dryer household freezer of packing into carries out pre-freeze, evacuation, and heating, sublimation drying, adsorption stripping and dry, vacuum breaker, lyophilizing finishes;
(4) high pure nitrogen of the dry degerming of feeding, outlet rolls lid, promptly gets the injection lobaplatin.
Preferably, the method for preparing of injection lobaplatin of the present invention, the process following steps:
(1) get the lobaplatin raw material, add the water for injection of preparating liquid total amount 70～90%, water temperature is mixed with solution less than 50 ℃;
(2) add dosing total amount 0.03-0.08% pin and use activated carbon, add to the full amount of water for injection again, insulated and stirred 20-40 minute, aseptic filtration;
(3) get filtrating fill half tamponade, be collected into the lyophilizing dish, the freeze dryer household freezer of packing into carries out pre-freeze, and the pre-freeze temperature is-50～-40 ℃, keeps 2-4 hour; Evacuation, vacuum is: 10-30Pa, heating, temperature rises to-20～-10 ℃, keeps 8-12 hour; Rise to-10-0 ℃ kept 1-3 hour, was warming up to 0-10 ℃, kept 1-3 hour, and the pressure that raises simultaneously, pressure rising number is less than 3Pa; Temperature rises to 10-20 ℃ again, keeps 1-2 hour, rises to 20-30 ℃, is incubated 1-2 hour, rises to 30-40 ℃; Be incubated 1 hour, rise to 35-45 ℃ at last, do pressure rising test after vacuum is stable, per minute pressure rising≤3pa, lyophilizing finishes;
(4) feeding flow velocity is the dry degerming high pure nitrogen of 0.10-0.15L/s, and the time is: 15-25 minute, outlet rolled lid, promptly got the injection lobaplatin.
Preferred, the method for preparing of injection lobaplatin of the present invention, the process following steps:
(1) get the lobaplatin raw material, add the water for injection of preparating liquid total amount 80%, water temperature is mixed with solution less than 50 ℃;
(2) add dosing total amount 0.05% pin and use activated carbon, add to the full amount of water for injection insulated and stirred 30 minutes, aseptic filtration again;
(3) get filtrating fill half tamponade, be collected into the lyophilizing dish, the freeze dryer household freezer of packing into carries out pre-freeze, and the solution with room temperature is chilled to-10 ℃ earlier, keeps 30 minutes; In 10 minutes, be cooled to-40 ℃, kept 2.5 hours, evacuation, vacuum is: 10-30Pa, heating, temperature rises to-20 ℃; Kept 10 hours, and rose to-10 ℃ and kept 2 hours, be warming up to 0 ℃, kept 2 hours, the pressure that raises simultaneously, pressure rising number is less than 3Pa; Temperature rises to 10 ℃ again, keeps 1 hour, rises to 20 ℃, is incubated 1 hour, rises to 30 ℃; Be incubated 1 hour, rise to 40 ℃ at last, do pressure rising test after vacuum is stable, per minute pressure rising≤3pa, lyophilizing finishes;
(4) feeding flow velocity is the dry degerming high pure nitrogen of 0.12-0.15L/s, and the time is: 20 minutes, outlet rolled lid.Promptly get the injection lobaplatin.
The inventor has taked following technical measures to defective of the prior art:
Unstable for product, be prone to the moisture absorption, the Moisture high UCL problem; The inventor is after the lyophilization of injection lobaplatin production process finishes; Adopt nitrogen protection, feed exsiccant high pure nitrogen after aseptic filtration, gets into before case press again, moisture content in goods and the pure air and the thorough isolation of oxygen are got up; Avoid the product moisture absorption and eremacausis, increase the stability of medicine.The 2nd, the adsorption stripping and dry time of prolongation freeze-drying process, make the product intensive drying, remove residual moisture.
Not high for product degree of crystallinity; The problem that crystal habit is bad; The inventor has carried out a large amount of explorations repeatedly to the freeze-dry process of lobaplatin; Find unique lobaplatin lyophilizing that is used for to produce only temperature-time parameter in pre-freeze, distillation and these three processes of parsing-desiccation, greatly degree avoided in the freeze-drying process moisture content to remove not reaching the bad harmful effect of temperature control only to the product crystal formation, with the moisture Control of product at minimum state; Make that finished product dry powder small particles microlite is more, uniform particles.
Freeze lamination problem for bottle, the inventor finds in the lobaplatin freeze-drying process, the freeze drying process that lobaplatin adopts bottle to freeze in actual production, and it is inhomogeneous to occur easily being heated; Stratified phenomenon, according to the research to bottled goods shelf pre-freeze process, the sample initial temperature is high more; The thermograde of material medicine top and the bottom is big more, and ice-crystal growth speed is slow more, and the from bottom to top propulsive speed in ice interface is slower; Solute migration time abundance in the solution, gathering of solution surface frozen crust solute is also just intensive relatively, thereby causes the solute of upper epidermis often more; Density is higher, and bottom density is less down, short texture.Pre-freeze speed is not high, and influences that crystal in this process of follow-up sublimation drying is shaped and the uniformity of dosage units of finished product.The present invention has adopted the pre-freeze method, solves bottle and freezes stratified problem, the sample solution for preparing is cooled to the initial solidification point of sample earlier from room temperature; Stop temperature-fall period then; Make temperature autobalance in the sample, eliminate thermograde wherein, at last cooling rapidly again.Because this moment, the temperature of sample top and the bottom was all nearer from crystallization temperature, so thermograde is just less relatively in freezing process, therefore ice-crystal growth speed accelerated, and improves pre-freeze speed.
The invention reside in, through to selection of technical parameter, found the method that solves the prior art problem, therefore, the injection lobaplatin that adopts the inventive method to make has following beneficial effect:
1, after lyophilization finishes, adopts nitrogen protection, avoid the product moisture absorption and eremacausis, increase the stability of medicine.
2, in freeze-drying process, adopt only technological parameter, product moisture is controlled at floor level.Temperature transfer is even, bottle can not occur and freeze stratified phenomenon, and the product dry powder small particles microlite that makes is more, uniform particles.
In order to make those of ordinary skills better understand the present invention, the applicant has carried out series of experiment research, to prove effect of the present invention:
1, technological parameter is selected experiment
In freezing dry process, the technological parameter in each stage is very important, directly influences the moisture of finished product and the color size of crystal formation; Pre-freeze temperature, pre-freeze time, pre-freeze speed and this Several Parameters of adsorption stripping and dry time that the inventor is bigger to influence; With the finished product moisture, powder particle size, uniform particles degree; Sedimentation has carried out a series of selection test for investigating index.
Method A: pre-freeze, the solution with room temperature is chilled to-10 ℃ earlier, keeps 30 minutes, in 10 minutes, is cooled to-40 ℃, keeps 2.5 hours; Evacuation, vacuum is: 10-30Pa, heating, temperature rises to-20 ℃, keeps 10 hours; Rise to-10 ℃ and kept 2 hours, be warming up to 0 ℃, kept 2 hours, temperature rises to 10 ℃ again, keeps 1 hour; Rise to 20 ℃, be incubated 1 hour, rise to 30 ℃, be incubated 1 hour, rise to 40 ℃ at last; Be incubated 2 hours, do pressure rising test after vacuum is stable, per minute pressure rising≤3pa, lyophilizing finishes.
Method B: pre-freeze, pre-freeze temperature are-30 ℃, kept 4 hours, and evacuation, vacuum is: 10-30Pa; Heating, temperature rises to-20 ℃, keeps 10 hours, rises to-10 ℃ and keeps 2 hours, is warming up to 0 ℃; Kept 2 hours, and rose to 20 ℃, be incubated 2 hours, rise to 40 ℃; Be incubated 2 hours, do pressure rising test after vacuum is stable, per minute pressure rising≤3pa, lyophilizing finishes.
Method C: pre-freeze, the solution with room temperature is chilled to 0 ℃ earlier, keeps 30 minutes, in 20 minutes, is cooled to-50 ℃, keeps 2 hours; Evacuation, vacuum are 10-30Pa, heating, and temperature rises to-20 ℃; Kept 10 hours, and rose to-10 ℃ and kept 2 hours, be warming up to 0 ℃, kept 2 hours; Rise to 20 ℃, be incubated 2 hours, rise to 40 ℃, be incubated 2 hours.Do pressure rising test after vacuum is stable, per minute pressure rising≤3pa, lyophilizing finishes;
The finished product result of three kinds of methods sees table 1.
Table 1 technological parameter method is selected experimental result
Above data show, the freeze-dried powder moisture that three kinds of methods make all＜3% satisfies imperial requirement.Granular size, the uniformity and sedimentation method A and method C are better, mainly are to select reason preferably owing to pre-freeze phase temperature and cool-down method.The product moisture content of method A gained is minimum, possibly adopt the method that progressively heats up relevant with parsing-desiccation.So the pre-freeze stage, preferred final pre-freeze temperature was set in-50～-40 ℃, adopted the segmentation cool-down method, the preferred method that progressively heats up of parsing-desiccation stage.
2, product quality detects
The parameter that adopts method A is prepared the product of gained, carry out quality standard according to the method for State Food and Drug Administration's standard (YBH06222008) regulation and detect, test item is character, moisture, related substance, content, and the result sees table 2.
Table 2 quality control result
3, stability
3.1 accelerated stability test: totally two parts in the sample that picked at random method 1 makes; Numbering A and B; At 30 ℃ ± 2 ℃, relative air humidity is 80% condition held, once investigates in 1st month, 2 months, 3 months, 6 samplings at the end of month of duration of test respectively.
3.2 long-term stable experiment: totally two parts in the sample that picked at random method 1 makes, numbering C and D 4 ℃, room temperature condition storage down, take a sample when 3,6 and 12 the end of month and once investigate respectively.
Above-mentioned investigation is an index with the clarity of active constituent content, impurity, moisture and solution, the stability of inspection product.The result is following:
Table 3, accelerated stability test be table as a result
Table 4,4 ℃ of long-term stable experiments be table as a result
Long-term stable experiment table as a result under table 5, the room temperature condition
Can find out from above-mentioned result of the test; The injection lobaplatin of the present invention preparation is being stored down with 4 ℃, room temperature condition under the accelerated test condition, and from acceleration and long-term investigation result, each investigation project all loses unusually; Significant change does not take place in active constituent content yet, all meets the quality standard requirement.
Below, enumerate embodiment the present invention is further described, but the present invention is not limited to following embodiment.
The specific embodiment
Embodiment 1
(1) get 50g lobaplatin anhydride, add 2100ml water for injection, 40 ℃ of water temperatures are mixed with solution;
(2) add the 1.5g pin and use activated carbon, add the injection water again to 3000ml, insulated and stirred 30 minutes, aseptic filtration;
(3) get filtrating fill half tamponade, be collected into the lyophilizing dish, the freeze dryer household freezer of packing into carries out pre-freeze, and design temperature is-10 ℃, keeps 30 minutes; In 10 minutes, be cooled to-40 ℃, kept 2.5 hours, evacuation, vacuum is: 15Pa, heating, adjustment silicone oil temperature is to-20 ℃; Kept 10 hours, and rose to-10 ℃, kept 2 hours, be warming up to 0 ℃, kept 2 hours, temperature rises to 10 ℃ again; Kept 1 hour, and be warming up to 20 ℃, kept 1 hour, rise to 30 ℃, be incubated 1 hour, rise to 40 ℃; Be incubated 1 hour, rise to 43 ℃ at last, do pressure rising test after vacuum is stable, per minute pressure rising≤3pa, lyophilizing finishes;
(4) feeding flow velocity is the dry degerming high pure nitrogen of 0.12-0.15L/s, and the time is 20 minutes, returns to normal pressure, and outlet rolls lid, visual inspection, and packing promptly gets the injection lobaplatin.
Embodiment 2
(1) get 10g lobaplatin anhydride, add 1800ml water for injection, 30 ℃ of water temperatures are mixed with solution;
(2) add the 1.6g pin and use activated carbon, add the injection water again to 2000ml, insulated and stirred 40 minutes, aseptic filtration;
(3) get filtrating fill half tamponade, be collected into the lyophilizing dish, the freeze dryer household freezer of packing into carries out pre-freeze, and design temperature is-10 ℃, keeps 30 minutes; In 10 minutes, be cooled to-50 ℃, kept 2 hours, evacuation, vacuum is: 20Pa, heating; Temperature rises to-20 ℃, keeps 8 hours, rises to-10 ℃ and keeps 3 hours, is warming up to 0 ℃, keeps 3 hours; Temperature rises to 20 ℃ again, keeps 2 hours, rises to 30 ℃, is incubated 2 hours, rises to 40 ℃; Be incubated 1 hour, rise to 45 ℃ at last, do pressure rising test after vacuum is stable, per minute pressure rising≤3pa, lyophilizing finishes;
(4) feeding flow velocity is the dry degerming high pure nitrogen of 0.10-0.15L/s, and the time is 15 minutes, returns to normal pressure, and outlet rolls lid, visual inspection, and packing promptly gets the injection lobaplatin.
Embodiment 3
(1) get 10g lobaplatin anhydride, add 1400ml water for injection, 35 ℃ of water temperatures are mixed with solution;
(2) add the 0.6g pin and use activated carbon, add the injection water again to 2000ml, insulated and stirred 25 minutes, aseptic filtration;
(3) get filtrating fill half tamponade, be collected into the lyophilizing dish, the freeze dryer household freezer of packing into carries out pre-freeze, and design temperature is-10 ℃, keeps 30 minutes; In 10 minutes, be cooled to-40 ℃, kept 4 hours, evacuation, vacuum is: 25Pa, heating, temperature rises to-10 ℃; Kept 10 hours, and rose to-10 ℃ and kept 3 hours, be warming up to 0 ℃, kept 3 hours, temperature rises to 20 ℃ again; Kept 2 hours, and rose to 30 ℃, be incubated 2 hours, rise to 35 ℃, be incubated 1 hour; Rise to 40 ℃ at last, rise to 44 ℃ at last, do pressure rising test after vacuum is stable, per minute pressure rising≤3pa, lyophilizing finishes;
(4) feeding flow velocity is the dry degerming high pure nitrogen of 0.10-0.15L/s, and the time is 25 minutes, returns to normal pressure, and outlet rolls lid, visual inspection, and packing promptly gets the injection lobaplatin.
Claims (2)
1. the method for preparing of an injection lobaplatin is characterized in that, the process following steps:
(1) get the lobaplatin raw material, add the water for injection of preparating liquid total amount 70～90%, water temperature is mixed with solution less than 50 ℃;
(2) add dosing total amount 0.03-0.08% pin and use activated carbon, add to the full amount of water for injection again, insulated and stirred 20-40 minute, aseptic filtration;
(3) get the filtrating fill, half tamponade is collected into the lyophilizing dish, and the freeze dryer household freezer of packing into carries out pre-freeze, and the pre-freeze temperature is-50～-40 ℃; Kept 2-4 hour, evacuation, vacuum is: 10-30Pa, heating, temperature rises to-20～-10 ℃, keeps 8-12 hour; Rise to-10-0 ℃ kept 1-3 hour, was warming up to 0-10 ℃, kept 1-3 hour, and the pressure that raises simultaneously, pressure rising number is less than 3Pa; Temperature rises to 10-20 ℃ again, keeps 1-2 hour, rises to 20-30 ℃, is incubated 1-2 hour, rises to 30-40 ℃; Be incubated 1 hour, rise to 35-45 ℃ at last, do pressure rising test after vacuum is stable, per minute pressure rising≤3Pa, lyophilizing finishes;
(4) feeding flow velocity is the dry degerming high pure nitrogen of 0.10-0.15L/s, and the time is: 15-25 minute, outlet rolled lid, promptly gets.
2. the method for preparing of an injection lobaplatin is characterized in that, the process following steps:
(1) get the lobaplatin raw material, add the water for injection of preparating liquid total amount 80%, water temperature is mixed with solution less than 50 ℃;
(2) add dosing total amount 0.05% pin and use activated carbon, add to the full amount of water for injection insulated and stirred 30 minutes, aseptic filtration again;
(3) get the filtrating fill, half tamponade is collected into the lyophilizing dish, and the freeze dryer household freezer of packing into carries out pre-freeze, and the solution with room temperature is chilled to-10 ℃ earlier; Kept 30 minutes, and in 10 minutes, be cooled to-40 ℃, kept 2.5 hours, evacuation, vacuum is: 10-30Pa, heating; Temperature rises to-20 ℃, keeps 10 hours, rises to-10 ℃ and keeps 2 hours, is warming up to 0 ℃, keeps 2 hours, and pressure simultaneously raises; Pressure rising number is less than 3Pa, and temperature rises to 10 ℃ again, keeps 1 hour, rises to 20 ℃, is incubated 1 hour, rises to 30 ℃; Be incubated 1 hour, rise to 40 ℃ at last, do pressure rising test after vacuum is stable, per minute pressure rising≤3Pa, lyophilizing finishes;
(4) feeding flow velocity is the dry degerming high pure nitrogen of 0.12-0.15L/s, and the time is: 20 minutes, outlet rolled lid, promptly gets.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102415949A (en) * | 2011-07-20 | 2012-04-18 | 北京莱瑞森医药科技有限公司 | Novel liquid medicine filling and freezing process and liquid medicine filling and freezing device |
| CN104154722A (en) * | 2014-08-25 | 2014-11-19 | 济南康众医药科技开发有限公司 | Application of freeze-drying technology in lamiophlomis rotata drying |
| CN104154713A (en) * | 2014-08-25 | 2014-11-19 | 济南康众医药科技开发有限公司 | Lamiophlomis freeze-drying method |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0216362A2 (en) * | 1985-09-25 | 1987-04-01 | Shionogi & Co., Ltd. | Stable freeze-dried preparation of an anticancer platinum complex |
| WO2000003718A1 (en) * | 1997-01-14 | 2000-01-27 | Toray Industries, Inc. | Freeze-dried preparations and process for producing the same |
| CN1785217A (en) * | 2005-11-08 | 2006-06-14 | 贵州益佰制药股份有限公司 | Ginkgo Damo freeze-drying prepn. and its prepn. method |
| CN101475596A (en) * | 2007-12-13 | 2009-07-08 | 北京嘉事联博医药科技有限公司 | Platinum complexes of quercetin and derivatives thereof, as well as preparation and use thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101185649B (en) * | 2007-03-22 | 2011-03-02 | 上海汇伦生命科技有限公司 | Levoleucovorin freeze-dried injection agent and preparation method and pharmaceutical use thereof |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0216362A2 (en) * | 1985-09-25 | 1987-04-01 | Shionogi & Co., Ltd. | Stable freeze-dried preparation of an anticancer platinum complex |
| WO2000003718A1 (en) * | 1997-01-14 | 2000-01-27 | Toray Industries, Inc. | Freeze-dried preparations and process for producing the same |
| CN1785217A (en) * | 2005-11-08 | 2006-06-14 | 贵州益佰制药股份有限公司 | Ginkgo Damo freeze-drying prepn. and its prepn. method |
| CN101475596A (en) * | 2007-12-13 | 2009-07-08 | 北京嘉事联博医药科技有限公司 | Platinum complexes of quercetin and derivatives thereof, as well as preparation and use thereof |
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