A kind of injection containing docetaxel and preparation method thereofTechnical field
The present invention relates to field of pharmaceutical preparations, specifically a kind of injection containing docetaxel and preparation method thereof.
Background technology
Docetaxel is a kind of semi-synthetic paclitaxel derivatives, is now used for Several Kinds of Malignancy, is identified as making so farOne of more significant cancer therapy drug of modern curative effect.Its anticancer mechanism is by promoting new report microtubule polymerization, preventing micro-pipe normalPhysiology depolymerization, influenceing cell has private fission process, there is good growth inhibition and apoptosis-induced to kinds of tumors, butThe antitumous effect and toxic side effect of docetaxel will be substantially better than taxol.Docetaxel is now used clinically for treating mammary glandThe malignant tumours such as cancer, oophoroma and non-small cell lung cancer have obtained the effect of preferable, and its antitumor field is more and more wider in recent years.The dosage form of its application clinically is ejection preparation.
Prepared by the preparation technology that the used docetaxel injection preparation of in the market employs lyophilized formulations, but shouldKind has difference again with general lyophilized formulations.In general lyophilized formulations to be powdered, and the products application form be will be moreXi Tasai is dissolved in inside absolute ethyl alcohol and Tween 80, liquid preparation obtained from removing absolute ethyl alcohol by lyophilized technique.ShouldPreparation method has the following disadvantages：1) product stability is general, and it is unqualified relevant material easily occur；2) lyophilized acc power is big, consumesEnergy is more and freeze-drying time is grown, and seriously constrains the production efficiency of the injection of docetaxel.
The content of the invention
The technical assignment of the present invention is to be directed to above-mentioned the deficiencies in the prior art, there is provided a kind of stability is good, and production efficiency is highThe injection containing docetaxel.
Further technical assignment of the invention is to provide the preparation method of above-mentioned injection.
The technical assignment of the present invention is realized in the following manner：Injection containing docetaxel, is characterized in, in its systemDuring standby, the absolute ethyl alcohol that is added when removing dispensing using the method for revolving.
It is preferred that the absolute ethyl alcohol added when removing dispensing using Rotary Evaporators.
The preparation method of above-mentioned injection comprises the following steps：
1) carbonization treatment is carried out to Tween 80 and absolute ethyl alcohol with mass ratio 0.01%-0.05% activated carbons respectively, it is standby；
2) Tween 80 of 30~40 times of docetaxel amounts is accurately weighed, is divided into two parts of a, b, the quality of two parts of Tween 80s of a, bThan for 1: 5~1: 15；
3) absolute ethyl alcohol of 2~6 times of a part Tween 80 amounts is accurately weighed, and it is uniformly mixed with a parts Tween 80；
4) a certain amount of docetaxel is added into mixed liquor obtained by step 3), stirs to docetaxel and be completely dissolved；
5) b parts Tween 80 is added in mixed liquor obtained by step 4), regulation pH value obtains admixing medical solutions to 5.0~7.0；
6) admixing medical solutions obtained by step 5) are transferred in Rotary Evaporators, 20 DEG C -40 DEG C of bath temperature of control, rotation speed60~120 revs/min of degree, vacuumizes backspin and absolute ethyl alcohol is evaporated off, obtain injection liquid；
7) injection liquid obtained by step 6) is detected into pH value, absolute ethyl alcohol residual quantity, qualified rear filling, tamponade, rolls lidProduce targeted injection agent.
Injection containing docetaxel of the present invention and preparation method thereof has with following prominent compared with prior artBeneficial effect：
(1) by stability contrast test, in the case where any stabilizer need not be added, the more west of the present invention heThe stability of match injection is still improved largely；
(2) production time is short, production efficiency is high, can effectively reduce labour cost and energy cost；
(3) 90% absolute ethyl alcohol can be recovered and reuse, and Material Cost is greatly reduced.
Embodiment
It is following to injection containing docetaxel of the present invention and preparation method thereof work detailed to prepare embodiment and test exampleCarefully illustrate.
【Prepare embodiment】
Preparation process：
1) carbonization treatment is carried out to Tween 80 and absolute ethyl alcohol with mass ratio 0.01%-0.05% activated carbons respectively, it is standby；
2) 2.977Kg Tween 80s accurately are weighed, is divided into two parts of a, b, a parts tween is 0.37Kg, and b part Tween 80s are2.607Kg；
3) 1.8Kg absolute ethyl alcohols accurately are weighed, and it is uniformly mixed with a parts Tween 80；
4) 0.0944Kg docetaxels are added into mixed liquor obtained by step 3), stirs to docetaxel and is completely dissolved；
5) b parts Tween 80 is added in mixed liquor obtained by step 4), with 0.1mol/L hydrochloric acid or 0.1mol/L sodium hydroxidesSolution adjusts pH value to 5.0~7.0, obtains admixing medical solutions；
6) admixing medical solutions obtained by step 5) are transferred in Rotary Evaporators, 20 DEG C -40 DEG C of bath temperature of control, rotation speed60~120 revs/min of degree, vacuumizes backspin and absolute ethyl alcohol is evaporated off, obtain injection liquid；
7) injection liquid obtained by step 6) is detected into pH value, absolute ethyl alcohol residual quantity, qualified rear filling, tamponade, rolls lidProduce targeted injection agent.
【Test example one】
Target product：Amount of preparation is 10L, and injection specification is 2ml: 80mg；
Production method：Preparation method of the present invention, traditional lyophilized technique.
Condition of production contrast see the table below：
It may determine that the inventive method is significantly better than prior art from production time, equipment power consumption and Material Cost.
【Test example two】
Test products：Prepare embodiment products obtained therefrom；Commercially available prod；
Experimental condition：40 DEG C ± 2 DEG C of temperature, humidity 75% ± 5%.
Contrast on effect situation is investigated to see the table below：
It was found from experimental data, by product produced by the invention, because the production technology cycle is short compared with lyophilized technique, it is given birth toOutput carrys out product stability and is better than commercialized product, and its stability is especially prominent in terms of relevant material.