CN103083233B - Pharmaceutical composition of paclitaxel compound - Google Patents
Pharmaceutical composition of paclitaxel compound Download PDFInfo
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- CN103083233B CN103083233B CN201310035406.9A CN201310035406A CN103083233B CN 103083233 B CN103083233 B CN 103083233B CN 201310035406 A CN201310035406 A CN 201310035406A CN 103083233 B CN103083233 B CN 103083233B
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Abstract
The invention discloses a pharmaceutical composition of a paclitaxel compound. The composition comprises the following components: 1 part by weight of paclitaxel, 30-35 parts by weight of polyoxyethylene castor oil, 5-10 parts by weight of sodium dodecyl sulfate, 40-70 parts by weight of 95% ethanol solvent and an appropriate amount of citric acid-sodium citrate. The composition is simple in component, little in auxiliary material dosage and good in drug stability; no crystallization phenomenon occurs when the pharmaceutical composition is placed for a long time, so that the pharmaceutical composition meets the quality requirement of an injection to insoluble particles.
Description
Technical field
The present invention relates to a kind of compositions that is used for the treatment of cancer, more specifically, relate to a kind of taxol drug composition injection and preparation method thereof.
Background technology
At present, risen year by year by the mortality rate of the initiation of cancer both at home and abroad, China accounts for 20% of death toll because of cancer mortality number.Breast carcinoma, pulmonary carcinoma, carcinoma of prostate and colorectal carcinoma etc. are the most common, and conventional cancer therapy drug has paclitaxel, Docetaxel, capecitabine etc.
Paclitaxel is from taxaceae Chinese yew genus plants Ramulus et folium taxi cuspidatae, to extract to separate a kind of antineoplastic agent obtaining, it has unique mechanism of action, tubulin polymerization, assembling and stable microcosmic effect stoping the growth of tumor cell by inducing and promoting, is spectrum cancer therapy drug.Its structure is complicated diterpene-kind compound, and its chemical name is 5 β, 20-epoxy-1,2 α, 4,7 β, 10 β, 13 α-hexahydroxy taxane-11-alkene-9-ketone-4,10-diacetate esters-2-benzoate-13-(2 ' R, 3 ' S)-N-benzoyl-3-phenylisoserine ester, molecular formula C
47h
51nO
14, its skeleton symbol is as follows:
The water solublity of paclitaxel is very poor, approximately dissolves 0.006mg paclitaxel in 1ml water, and water-soluble hardly, the effective bioavailability in human body is low.The paclitaxel injection of current clinical use dissolves paclitaxel with polyoxyethylene castor oil and dehydrated alcohol with the ratio mixed solvent of 1:1, makes the medicinal liquid of 5ml containing 30mg paclitaxel.Polyoxyethylene castor oil can cause histamine release in human body, and anaphylaxis occurs, and part patient just there will be Drug as anaphylaxiss such as erythra, rapid breathing, bronchospasm, hypotension in several minutes after instillation.
Chinese patent application CN200910009286.9 discloses a kind of composite injection that contains paclitaxel and phenylalanine, the weight ratio of paclitaxel and phenylalanine is 1:0.01-0.8, solubilizing agent in injection is polyoxyethylene castor oil, solvent is dehydrated alcohol, the volume ratio 1:2 of polyoxyethylene castor oil and ethanol, although the consumption of the polyoxyethylene castor oil in this injection also has suitable minimizing,, or the degree reducing is outstanding not enough.Chinese patent application CN200710026746.X discloses a kind of injection of paclitaxel, comprise paclitaxel 0.6-3g, dehydrated alcohol 200-400ml, PEG400 150-400ml, tween 80 20-40g, needle-use activated carbon 0.2-0.5g and normal saline 200-400ml, this injection adds in part infusion solutions solution, has a small amount of paclitaxel solid and separates out.In prior art, also have multiple paclitaxel injection, all exist defect more or less, still, when applying a kind of medicine, consider its performance.For this reason, paclitaxel compositions of the present invention is proposed.
Summary of the invention
The object of this invention is to provide a kind of pharmaceutical composition of taxol compound, the component of said composition is simple, and medicine stability is good, and long-term placement does not have crystallization, meets the quality regulation of injection to particulate matter.
Another object of the present invention is to provide a kind of preparation method of paclitaxel composite injection, and because adjuvant used is fairly simple, the method operation sequence is also corresponding simple, and is easy to control.
For realizing object of the present invention, a kind of pharmaceutical composition of taxol compound, said composition comprises following component:
Preferably, paclitaxel compositions comprises following component:
Described 95% ethanol refers to that the volume content of dehydrated alcohol is 95%(v/v)).
A kind of paclitaxel composite injection that contains aforementioned pharmaceutical compositions.
In taxol drug compositions provided by the invention, the water solublity of active component paclitaxel is very poor, add a small amount of polyoxyethylene castor oil, dodecyl sodium sulfate and ethanol, increase the dissolubility of paclitaxel, the good stability of the paclitaxel injection obtaining, compared with the disclosed paclitaxel injections such as patent application CN200910203243.4, the kind that the adjuvant using uses is few, and the consumption of polyoxyethylene castor oil and ethanol greatly reduces, example 1 is relatively analyzed by experiment, and the stability of paclitaxel compositions of the present invention is basic identical.
A preparation method for above-mentioned taxol drug composition injection, comprises the steps:
(1) under the condition of temperature 45-50 DEG C, the dodecyl sodium sulfate of recipe quantity is joined in the alcohol solvent of 1/4-1/395% and dissolve, then the paclitaxel of recipe quantity is under agitation slowly joined in the alcoholic solution of middle dodecyl sodium sulfate, stir, obtain mixed solution A;
(2) recipe quantity polyoxyethylene castor oil is dissolved in to remaining 95% ethanol, stirs, obtain mixed solution B;
(3) mixed solution A is joined to mixed solution B and mix, then add citric acid, sodium citrate, the PH of the solution making is controlled between 5.1-5.4, by micro-pore-film filtration, obtains filtrate subpackage, obtains paclitaxel composite injection.
The present invention is in the time of preparation taxol drug composition injection, first dodecyl sodium sulfate is dissolved in 95% alcohol solvent, then add paclitaxel, make that paclitaxel is well-proportioned to be scattered in dodecyl sodium sulfate, and then mixed solution A joins in mixed solution B, the paclitaxel composition stable obtaining is like this good.When in use, above-mentioned injection is diluted in infusion solutions liquid injection solution sodium chloride, glucose solution etc., long-time placement does not have paclitaxel solid and separates out.Prior art is dissolved in infusion solutions solution in order to increase paclitaxel, need to add a large amount of polyoxyethylene castor oils, in paclitaxel injection of the present invention, add a small amount of dodecyl sodium sulfate, can significantly reduce the consumption of polyoxyethylene castor oil, the dissolubility of the paclitaxel injection obtaining in infusion solutions solution is significantly improved.Especially adopt above-mentioned preparation method to obtain paclitaxel solvent, paclitaxel is placed for a long time in infusion solutions solution, does not have solid and separates out.
Compared with prior art, the supplementary product consumption of paclitaxel injection of the present invention is few, especially has the supplementary product consumption of side effect to reduce in a large number, the paclitaxel injection good stability obtaining, and in infusion solutions solution, do not have for a long time solid and separate out.
Detailed description of the invention
With embodiment, technical scheme of the present invention is further described below; by the advantage contributing to technical scheme of the present invention; effect has further to be understood, and embodiment does not limit protection scope of the present invention, and protection scope of the present invention is decided by claim.
Embodiment 1
Prescription:
Preparation method:
Under the condition of temperature 50 C, the dodecyl sodium sulfate of recipe quantity is joined in 1/495% alcohol solvent and dissolve, then the paclitaxel of recipe quantity is under agitation slowly joined in the alcoholic solution of middle dodecyl sodium sulfate, stir, obtain mixed solution A; Recipe quantity polyoxyethylene castor oil is dissolved in to remaining 95% ethanol, stirs, obtain mixed solution B; Mixed solution A is joined to mixed solution B and mix, then add citric acid, sodium citrate, the PH of the solution making is controlled between 5.1, by micro-pore-film filtration, obtains filtrate subpackage, obtains paclitaxel composite injection.
Embodiment 2
Prescription:
Preparation method:
Under the condition of 48 DEG C of temperature, the dodecyl sodium sulfate of recipe quantity is joined in 1/395% alcohol solvent and dissolve, then the paclitaxel of recipe quantity is under agitation slowly joined in the alcoholic solution of middle dodecyl sodium sulfate, stir, obtain mixed solution A; Recipe quantity polyoxyethylene castor oil is dissolved in to remaining 95% ethanol, stirs, obtain mixed solution B; Mixed solution A is joined to mixed solution B and mix, then add citric acid, sodium citrate, the PH of the solution making is controlled between 5.3, by micro-pore-film filtration, obtains filtrate subpackage, obtains paclitaxel composite injection.
Embodiment 3
Prescription:
Preparation method:
Under the condition of temperature 45 C, the dodecyl sodium sulfate of recipe quantity is joined in 1/395% alcohol solvent and dissolve, then the paclitaxel of recipe quantity is under agitation slowly joined in the alcoholic solution of middle dodecyl sodium sulfate, stir, obtain mixed solution A; Recipe quantity polyoxyethylene castor oil is dissolved in to remaining 95% ethanol, stirs, obtain mixed solution B; Mixed solution A is joined to mixed solution B and mix, then add citric acid, sodium citrate, the PH of the solution making is controlled between 5.4, by micro-pore-film filtration, obtains filtrate subpackage, obtains paclitaxel composite injection.
Embodiment 4
Prescription:
Preparation method:
Under the condition of temperature 45 C, the dodecyl sodium sulfate of recipe quantity is joined in 1/495% alcohol solvent and dissolve, then the paclitaxel of recipe quantity is under agitation slowly joined in the alcoholic solution of middle dodecyl sodium sulfate, stir, obtain mixed solution A; Recipe quantity polyoxyethylene castor oil is dissolved in to remaining 95% ethanol, stirs, obtain mixed solution B; Mixed solution A is joined to mixed solution B and mix, then add citric acid, sodium citrate, the PH of the solution making is controlled between 5.2, by micro-pore-film filtration, obtains filtrate subpackage, obtains paclitaxel composite injection.
Experimental example 1
This experimental example is that the taxol drug composition injection of embodiment 1 joins in different infusion liquid, the time that insoluble matter occurs, refers to table 1:
Table 2 paclitaxel compositions crystal in infusion liquid is separated out the comparison of time
As can be seen from the table, paclitaxel compositions of the present invention all just has crystal in the long time and separates out in conventional infusion liquid.
Table 2, table 3 are respectively the investigations that the paclitaxel compositions of embodiment 1 joins 0.9% sodium chloride solution, 0.5% glucose solution Chinese medicine stability.
Table 2 paclitaxel is stability in 0.9% sodium chloride solution
Table 3 paclitaxel is stability in 0.5% glucose solution
Can draw from the experimental result of table 2, table 3, paclitaxel compositions of the present invention can stable existence in 10 hours in infusion liquid, and relative amount is stable.
The present invention carries out above-mentioned experiment to the paclitaxel compositions of other embodiment except embodiment 1, obtains the result similar to experimental example.
Experimental example 2
This experimental example is the stability experiment that the paclitaxel compositions of embodiment 1 is carried out at ambient temperature, in table 4.
The experiment of table 4 paclitaxel composition stable
From table 4 stability experiment data, the paclitaxel compositions of embodiment 1 can effectively be preserved 2 years at room temperature condition.
The present invention carries out aforementioned stable experiment to the paclitaxel compositions of other embodiment except embodiment 1, obtains the result similar to experimental example.
Claims (4)
1. a pharmaceutical composition for taxol compound, the component of said composition is:
2. compositions according to claim 1, is characterized in that, the component of described paclitaxel compositions is:
3. the paclitaxel composite injection of a pharmaceutical composition that contains claim 1 or 2.
4. a preparation method for taxol drug composite injection claimed in claim 3, comprises the steps:
(1) under the condition of temperature 45-50 DEG C, the dodecyl sodium sulfate of recipe quantity is joined in the ethanol of 1/4-1/395% and dissolve, then the paclitaxel of recipe quantity is under agitation slowly joined in the alcoholic solution of middle dodecyl sodium sulfate, stir, obtain mixed solution A;
(2) recipe quantity polyoxyethylene castor oil is dissolved in to remaining 95% ethanol, stirs, then add citric acid, sodium citrate, the PH of the solution making is controlled between 5.1-5.4, obtains mixed solution B;
(3) mixed solution A is mixed with mixed solution B, after stirring, by micro-pore-film filtration, obtain filtrate subpackage, obtain paclitaxel composite injection.
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| CN201310035406.9A CN103083233B (en) | 2013-01-29 | 2013-01-29 | Pharmaceutical composition of paclitaxel compound |
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| CN201310035406.9A CN103083233B (en) | 2013-01-29 | 2013-01-29 | Pharmaceutical composition of paclitaxel compound |
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| CN103083233B true CN103083233B (en) | 2014-11-19 |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1602854A (en) * | 2003-09-29 | 2005-04-06 | 北京华京五方实用纳米科技开发有限公司 | Taxel preparation for intravenous injection |
| CN101658516A (en) * | 2008-08-26 | 2010-03-03 | 齐鲁制药有限公司 | Taxol medicinal compositions and preparation method thereof |
-
2013
- 2013-01-29 CN CN201310035406.9A patent/CN103083233B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1602854A (en) * | 2003-09-29 | 2005-04-06 | 北京华京五方实用纳米科技开发有限公司 | Taxel preparation for intravenous injection |
| CN101658516A (en) * | 2008-08-26 | 2010-03-03 | 齐鲁制药有限公司 | Taxol medicinal compositions and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| Let He 等.An alternative paclitaxel microemulsion formulation:hypersensitivity evaluation and pharmacokinetic profile.《International Journal of Pharmaceutics》.2003,第250卷45-50. * |
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Application publication date: 20130508 Assignee: NORTH CHINA PHARMACEUTICAL Co.,Ltd. Assignor: Luo Cheng Contract record no.: 2016990000460 Denomination of invention: Pharmaceutical composition of paclitaxel compound Granted publication date: 20141119 License type: Common License Record date: 20161107 |
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Effective date of registration: 20230626 Address after: 350108 Medical Engineering Technology Building, Haixi Park, High tech Zone, Minhou County, Fuzhou City, Fujian Province Patentee after: Fujian Yiyi Xinghua Biotechnology Development Co.,Ltd. Address before: 366200 Floor 2, No. Y13, Hongxin Food Processing Park, Jiangfang Village, Lianfeng Town, Liancheng County, Longyan, Fujian Province Patentee before: Luo Cheng |
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