CN101584659A - A kind of docetaxel medicament composition injection and preparation method thereof - Google Patents
A kind of docetaxel medicament composition injection and preparation method thereof Download PDFInfo
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- CN101584659A CN101584659A CNA2009103044532A CN200910304453A CN101584659A CN 101584659 A CN101584659 A CN 101584659A CN A2009103044532 A CNA2009103044532 A CN A2009103044532A CN 200910304453 A CN200910304453 A CN 200910304453A CN 101584659 A CN101584659 A CN 101584659A
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Abstract
The invention provides a kind of docetaxel medicament composition injection, be by docetaxel, dehydrated alcohol and Polyoxyethylene Sorbitan Monooleate are formed, docetaxel wherein, the weight ratio of dehydrated alcohol and Polyoxyethylene Sorbitan Monooleate is: 15-25: 10-15: the 550-700 weight portion, said composition adopts following method preparation: docetaxel under agitation slowly joins in the Polyoxyethylene Sorbitan Monooleate of recipe quantity, after stirring, the dehydrated alcohol that adds recipe quantity, obtain mixed solution after the stirring and pass through filtering with microporous membrane, the packing of gained filtrate gets final product, this docetaxel compositions is used the mixed liquor of retarder thinner as ethanol and water for injection, and the volume ratio of 95% ethanol and water for injection is 1: 6.4-8.5.The prescription of this docetaxel compositions is simple, has good stability, and is fit to Long-term Storage; Compositions is diluted among the special diluting agent, and then is diluted to after the injection infusion solutions solution, does not have docetaxel and separate out in long-time.
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 docetaxel medicament composition injection and preparation method thereof, also relate to a kind of docetaxel compositions diluent.
Background technology
At present, both at home and abroad the mortality rate by the initiation of cancer rises year by year, and China accounts for 20% of death toll because of the cancer mortality number.Breast carcinoma, pulmonary carcinoma, carcinoma of prostate and colorectal carcinoma etc. are the most common, and cancer therapy drug commonly used has paclitaxel, Docetaxel, capecitabine etc.
Docetaxel (have another name called: Docetaxel) be a kind of from Ramulus et folium taxi cuspidatae bark or needle extract and carry out semi-synthetic and taxane anti-tumor medicament that obtain.Be widely used in treating the esophageal carcinoma, ovarian cancer, cervical cancer clinically, late period nonsmall-cell lung cancer, gastric cancer, nasopharyngeal carcinoma, advanced breast cancer.It has the effect of blocking-up cell mitogen, its to the retardation of tumour cell cycle to gain public acceptance.Can make most of cell block back death in the G2-M phase, dead mode has necrosis and apoptosis.Can destroy the integrity of microtubule, cause the bcl-2 phosphorylation, impel apoptosis.Present studies show that, can also regulate cellular immune function, act on tumor necrosis factor (INF) receptor of macrophage, impel INF-α 1, interleukin-11 (IL-1), IL-2, IL-6, interferon-alpha (INF-α), and the release of INF-β, thereby tumor cell is produced growth inhibited and lethal effect.
Docetaxel (Docetaxel) structural formula is:
Its chemical name is: [2 α R-[2a α, 4 β, 4a β, 6 β, 9 α (α R*, β S*), 11 α, 12 α, 12a α, 12b α]]-β-[[(1,1-dimethyl ethyoxyl) carbonyl] amino]-Alpha-hydroxy benzenpropanoic acid [12b-acetyl oxygen-12-benzoyl oxygen-2a, 3,4,4a, 5,6,9,10,11,12,12a, 12b-ten dihydros-4,6,11-trihydroxy-4a, 8,13,13-tetramethyl-5-oxo-7,11-methylene-1H-ring pentaene in the last of the ten Heavenly stems is [3,4] benzo [1,2-b] oxa-fourth ring-9-yl also] ester.
The water solublity of docetaxel is very poor, approximately dissolve 4 He docetaxels in the 1ml water, water-soluble hardly, the oral absorption rate only is 2%-4%, docetaxel dissolves in organic solvent, as dehydrated alcohol etc., but after adding normal saline, the drug solution of organic solvent preparation separates out medicine immediately, and can't intravenous drip.The paclitaxel ejection preparation of using clinically uses the solubilizing agent polyoxyethylene castor oil now, taxol drug solution is the colourless thick concentrated solution that double solvent is made with polyoxyethylene castor oil and dehydrated alcohol (50: 50 volume ratios), because the existence of solubilizing agent adds the normal saline Chinese medicine with it during medication and just can not separate out immediately.But this ejection preparation is shorter stabilization time, need during intravenous injection to drip off in the short time, otherwise medicine still can be separated out, in addition, solubilizing agent polyoxyethylene castor oil toxic and side effects is big, patient is prone to anaphylaxiss such as dyspnea, flushing, palpitating speed, erythra after the medication, and before administration, needs of patients is taken antianaphylactic medicine and prevented usually.
For solving the water solublity problem of docetaxel, prior art also has the Polyoxyethylene Sorbitan Monooleate of use to do solubilizing agent, for example patent application CN200710049357.9 discloses a kind of docetaxel injection, component by following weight ratio proportioning is made: docetaxel 0.7-1.3, polysorbate 20-35, lewis acid 0.1-0.3, ethanol 250-450 and water 0-20, this docetaxel injection adds the molecular structure of lewis acid enhanced activity composition, but under this acid condition, inject human body and can produce discomfort, increased patient's misery, simultaneously because the existence of water in the preparation also can cause the easy crystallize of active component.Patent application CN200610032942.3 discloses a kind of injection docetaxel, it comprises following component: active substance docetaxel, solvent Tween-80 and antioxidant, described antioxidant is selected from any mixture of sodium sulfite, sodium sulfite, ascorbic acid, sodium pyrosulfite, thioglycerol, disodium edetate or citric acid etc.
In the prior art in order to improve the water solublity of docetaxel, in injection, add materials such as cosolvent, ethanol, composition more complicated in the injection, the injection docetaxel that perhaps obtains is joining at the less stable in when storage or injection docetaxel has insoluble matter defective such as to separate out in very short time in the infusion solutions solution, above-mentioned defective at the injection docetaxel of prior art proposes docetaxel compositions of the present invention.
Summary of the invention
An object of the present invention is to provide a kind of docetaxel medicament composition injection, the component of said composition is simple, and medicine stability is good, and long-term placement does not have the crystallize phenomenon, meets the quality regulation of injection to particulate matter.
Another object of the present invention provides a kind of docetaxel medicament composition injection diluent.
Last purpose of the present invention provides a kind of preparation method of docetaxel medicament composition injection, because used adjuvant is fairly simple, this method operation sequence is also corresponding simple, and is easy to control.
For realizing first purpose of the present invention, a kind of docetaxel medicament composition injection is provided, said composition is made up of docetaxel, dehydrated alcohol and Polyoxyethylene Sorbitan Monooleate.
This docetaxel compositions is used as injection.
The constituent content of described docetaxel medicament composition injection is:
Docetaxel 15-25 weight portion
Dehydrated alcohol 10-15 weight portion
Polyoxyethylene Sorbitan Monooleate 550-700 weight portion.
The constituent content of described docetaxel medicament composition injection is preferably as follows:
Docetaxel 18-23 weight portion
Dehydrated alcohol 11-13 weight portion
Polyoxyethylene Sorbitan Monooleate 560-630 weight portion.
In the docetaxel medicament composition provided by the invention, the water solublity of active component docetaxel is very poor, add the solubilizing agent Polyoxyethylene Sorbitan Monooleate and the ethanol that are fit to ratio, increase the dissolubility of docetaxel, the good stability of the docetaxel injection that obtains, compare with patent application CN200710049357.9, the disclosed docetaxel injection of patent application CN200610032942.3, the kind that adjuvant uses is few, and consumption of ethanol significantly reduces, example 1 is relatively analyzed by experiment, docetaxel compositions of the present invention stable basic identical.
In the docetaxel compositions of the present invention, the weight ratio of preferred dehydrated alcohol and Polyoxyethylene Sorbitan Monooleate is 10～15: 550～700, consumption of ethanol in the prior art in the injection docetaxel is bigger, though docetaxel well can be dissolved, but the concentration of docetaxel is lower comparatively speaking, and consumption of ethanol of the present invention seldom.
For realizing another object of the present invention, a kind of docetaxel medicament composition injection diluent is provided, described docetaxel medicament composition uses the mixed liquor of retarder thinner as ethanol and water for injection, described ethanol is that mass percent is 95% ethanol, wherein the volume ratio of 95% ethanol and water for injection is 1: 6.4～8.5, and the volume ratio of its preferred 95% ethanol and water for injection is 1: 7.0～8.0.
Docetaxel medicament composition of the present invention in use, survival dose according to patient, earlier the docetaxel compositions of this survival dose is diluted with proper amount of diluting and obtain mixed liquor, this mixed liquor joins in the injection infusion solutions solution more then, for example the glucose injection of 0.9% sodium chloride injection, variable concentrations or fructose injection etc.The consumption of preferred many Ta Tasai drug combination injection of the present invention and diluent is as follows:
Docetaxel medicament composition injection is:
Docetaxel 15～25g
Dehydrated alcohol 10～15g
Polyoxyethylene Sorbitan Monooleate 550～700g,
The docetaxel medicament composition injection diluent is:
95% ethanol, 200～250mL
Water for injection 1600～1700mL.
It is more preferably:
Docetaxel medicament composition injection is:
Docetaxel 18～23g
Dehydrated alcohol 11～13g
Polyoxyethylene Sorbitan Monooleate 560～630g,
The docetaxel medicament composition injection diluent is:
95% ethanol, 210～240mL
Water for injection 1650～1700mL.
Docetaxel medicament composition injection of the present invention dilutes in the solution of special diluting agent Zhao ethanol and water for injection earlier, after the docetaxel compositions joins in the diluent, in diluent, Polyoxyethylene Sorbitan Monooleate forms the micelle with core-shell structure in this diluent, docetaxel utilizes hydrophobic interaction, electrostatic interactions etc. are encapsulated in the micelle kernel, small part is not sealed into, and the docetaxel of micelle kernel can be good at being dissolved in the diluent, mixture after will diluting then joins in the injection infusion solutions solution, the micelle of this core-shell structure still can stable existence, the docetaxel that small part is un-encapsulated in the micelle kernel also can better dissolve in infusion solutions solution, so docetaxel compositions of the present invention can be good at existing in injection, does not have particulate matter and separate out in long-time.Respectively the time that the docetaxel of mixed liquor in different injection infusion solutions solution after the dilution of docetaxel compositions separated out is studied at experimental example 2, experimental result shows, docetaxel compositions diluent of the present invention is all separated out just having docetaxel more than 10 hours in used injection infusion solutions solution commonly used.If instead docetaxel compositions of the present invention is directly joined in the injection infusion solutions solution, because the concentration of Polyoxyethylene Sorbitan Monooleate is very low, does not reach critical micelle concentration, can not form the micelle with shell-core structure, adding soon, just have docetaxel and separate out.
A kind of paclitaxel intravenous injection liquid formulation is disclosed in patent application CN200510115531.6, said preparation is by paclitaxel, cosolvent and diluent, cosolvent is polyoxyethylene castor oil or tween 80, diluent is an ethanol, wherein polyoxyethylene castor oil and alcoholic acid volume are 1: 1, said preparation is only selected the injection infusion solutions solution of glucose, fructose, dextran, glycerol for use, and there is very big influence the time of paclitaxel being separated out for the different concentration of above-mentioned solution, has brought inconvenience to use.Docetaxel compositions diluted mixture thing of the present invention is not subjected to the kind of injection infusion solutions solution and the restriction of concentration thereof, all can be for a long time, very stable being dissolved in the infusion solutions solution, and promptly do not have docetaxel and separate out.
The disclosed injection docetaxel of patent application CN200710049357.9, and point out, this injection docetaxel is by two kinds of administrations, one, draw the patient's dosage calculate with syringe, be injected in the diluent, behind the mixing admixing medical solutions be diluted in 5% glucose injection or 0.9% sodium chloride injection, slow drop behind the mix homogeneously, two, injection docetaxel directly joins 5% glucose injection or 0.9% sodium chloride injection of 250ml, slow drop behind the mix homogeneously.No matter this injection docetaxel is by which kind of administration, in aqueous solution, may be because lewis acidic existence, polysorbate hydrolysis under this acid condition, reduced the solubilizing effect of polysorbate, had a spot of docetaxel crystal grain to separate out, the dissolubility of polysorbate hydrolyzed product self also reduces simultaneously, particulate matter can occur, occur so in injection, have particulate matter.
It is 1: 6.4～8.5 that docetaxel medication medication composition injection of the present invention adopts the volume ratio of 95% ethanol and water for injection with diluent, the mixed liquor of diluent under this proportioning and docetaxel compositions can form the stable polysorbate micelle of sealing docetaxel of result, alcoholic acid content is too big, influence this micellar formation, and containing a large amount of ethanol injections, to go into human body also be ill-considered, if alcoholic acid content very little, non-encapsulated docetaxel can be separated out.
For realizing last purpose of the present invention, a kind of preparation method of docetaxel medicament composition injection is provided, adopt following technical scheme:
The docetaxel of recipe quantity is under agitation slowly joined in the Polyoxyethylene Sorbitan Monooleate of recipe quantity, after stirring, add the dehydrated alcohol of recipe quantity, obtain mixed solution after the stirring, by filtering with microporous membrane, the packing of gained filtrate is the docetaxel compositions with mixed solution.
The present invention is when the preparation docetaxel medicament composition injection, earlier docetaxel is joined in the Polyoxyethylene Sorbitan Monooleate, make that docetaxel is well-proportioned to be scattered in the Polyoxyethylene Sorbitan Monooleate, and then adding dehydrated alcohol, the docetaxel composition stable that obtains like this is good, it can be good at docetaxel is encapsulated in the poly-pears alcohol that looses in being diluted in the solution process of ethanol and water for injection.In the prior art, when preparation docetaxel compositions, earlier docetaxel is dissolved in the ethanol, and then adds cosolvent, after docetaxel is dissolved in ethanol, because factors such as hydrogen bonds, the docetaxel molecule is surrounded by ethanol molecule, in use, said composition is diluted in the aqueous solution, can not well docetaxel be encapsulated in micelle inside, promptly cosolvent can not be given full play to its solubilization, has docetaxel for a long time and separates out.
For docetaxel can well be scattered in the Polyoxyethylene Sorbitan Monooleate, before adding, can earlier docetaxel be pulverized, cross 200～500 mesh sieves, it preferably crosses 200～300 mesh sieves.Simultaneously, the speed that docetaxel adds also is vital for solubility property, if adding speed influences the dispersion effect of docetaxel at polysorbate too soon, add and reduce production efficiency too slowly again, the speed that the preferred docetaxel of the present invention adds polysorbate-80 is: for the docetaxel of 1kg, it is 1/15～1/17 of itself quality that per minute adds the medicated powder quality.
In the above-mentioned preparation method, it is 100～160 commentaries on classics/min that described stirring is rotating speed, and preferred rotating speed is 120～140 commentaries on classics/min.
Above-mentioned docetaxel medicament composition injection comprises the steps: to get 95% ethanol and the water for injection of recipe quantity with the preparation method of diluent, and behind the mix homogeneously, mixed solution is through 0.22 μ m degerming membrane filtration, and the filtrate packing gets final product.
The present invention has following advantage with respect to prior art:
The prescription of docetaxel medicament composition injection provided by the invention is simple, has good stability, and is fit to Long-term Storage, and effect duration can reach more than 2 years.
Docetaxel medicament composition injection of the present invention is diluted to after the special diluting agent that provides of the present invention, and then be diluted to after the injection infusion solutions solution, not having docetaxel in long-time separates out, be not subjected to the kind of injection infusion solutions solution and the restriction of concentration, injection infusion solutions solution 0.9% sodium chloride injection commonly used, the glucose injection of variable concentrations or fructose injection etc. all can.
The specific embodiment
Embodiment 1
Prescription:
The constituent content of described docetaxel medicament composition injection is:
Docetaxel 20g
Dehydrated alcohol 11.8g
Polyoxyethylene Sorbitan Monooleate 586.6g
1000 bottles
Preparation method:
The docetaxel of recipe quantity is under agitation slowly joined in the Polyoxyethylene Sorbitan Monooleate of recipe quantity, after stirring, add the dehydrated alcohol of recipe quantity, obtain mixed solution after the stirring, by filtering with microporous membrane, the packing of gained filtrate is the docetaxel compositions with mixed solution.Said composition is used as injection.
Embodiment 2
Prescription:
The constituent content of described docetaxel medicament composition injection is:
Docetaxel 23g
Dehydrated alcohol 11g
Polyoxyethylene Sorbitan Monooleate 656g
1000 bottles
Preparation method:
The docetaxel of recipe quantity is under agitation slowly joined in the Polyoxyethylene Sorbitan Monooleate of recipe quantity, after stirring, add the dehydrated alcohol of recipe quantity, obtain mixed solution after the stirring, by filtering with microporous membrane, the packing of gained filtrate is the docetaxel compositions with mixed solution.Said composition is used as injection.
Embodiment 3
Prescription:
The constituent content of described docetaxel medicament composition injection is:
Docetaxel 18g
Dehydrated alcohol 12.5g
Polyoxyethylene Sorbitan Monooleate 560g
1000 bottles
Preparation method:
The docetaxel of recipe quantity was pulverized 300 mesh sieves, docetaxel after sieving with per minute add its gross mass 1/17 speed, under agitation slowly join in the Polyoxyethylene Sorbitan Monooleate of recipe quantity, rotating speed is controlled at after 130 commentaries on classics/min stir, the dehydrated alcohol that adds recipe quantity, obtain mixed solution after the stirring, by filtering with microporous membrane, the packing of gained filtrate is the docetaxel compositions with mixed solution.
Embodiment 4
Prescription:
The constituent content of described docetaxel medicament composition injection is:
Docetaxel 20g
Dehydrated alcohol 13g
Polyoxyethylene Sorbitan Monooleate 612.6g
1000 bottles
Preparation method:
The docetaxel of recipe quantity was pulverized 300 mesh sieves, docetaxel after sieving with per minute add its gross mass 1/17 speed, under agitation slowly join in the Polyoxyethylene Sorbitan Monooleate of recipe quantity, rotating speed is controlled at after 130 commentaries on classics/min stir, the dehydrated alcohol that adds recipe quantity, obtain mixed solution after the stirring, by filtering with microporous membrane, the packing of gained filtrate is the docetaxel compositions with mixed solution.Said composition is used as injection.
Embodiment 5
Prescription:
The constituent content of described docetaxel medicament composition injection is:
Docetaxel 20g
Dehydrated alcohol 15g
Polyoxyethylene Sorbitan Monooleate 550g
1000 bottles
Preparation method:
The docetaxel of recipe quantity was pulverized 200 mesh sieves, docetaxel after sieving with per minute add its gross mass 1/15 speed, under agitation slowly join in the Polyoxyethylene Sorbitan Monooleate of recipe quantity, rotating speed is controlled at after 120 commentaries on classics/min stir, the dehydrated alcohol that adds recipe quantity, obtain mixed solution after the stirring, by filtering with microporous membrane, the packing of gained filtrate is the docetaxel compositions with mixed solution.
Embodiment 6
Docetaxel medicament composition injection is:
Docetaxel 20g
Dehydrated alcohol 11.8g
Polyoxyethylene Sorbitan Monooleate 560mL
1000 bottles
The docetaxel medicament composition injection diluent is:
95% ethanol 225.8mL
Water for injection 1650mL
1000 bottles
Preparation method:
The docetaxel of recipe quantity was pulverized 300 mesh sieves, docetaxel after sieving with per minute add its gross mass 1/16 speed, under agitation slowly join in the Polyoxyethylene Sorbitan Monooleate of recipe quantity, rotating speed is controlled at after 140 commentaries on classics/min stir, the dehydrated alcohol that adds recipe quantity, obtain mixed solution after the stirring, by filtering with microporous membrane, the packing of gained filtrate is the docetaxel compositions with mixed solution.Said composition is used as injection.
Get 95% ethanol and the water for injection of recipe quantity, behind the mix homogeneously, mixed solution is through 0.22 μ m degerming membrane filtration, and the filtrate packing gets final product.
Embodiment 7
Docetaxel medicament composition injection is:
Docetaxel 20g
Dehydrated alcohol 11.8g
Polyoxyethylene Sorbitan Monooleate 593.6g
1000 bottles
The docetaxel medicament composition injection diluent is:
95% ethanol 225.8mL
Water for injection 1650mL
1000 bottles
Preparation method:
The docetaxel of recipe quantity is under agitation slowly joined in the Polyoxyethylene Sorbitan Monooleate of recipe quantity, after stirring, add the dehydrated alcohol of recipe quantity, obtain mixed solution after the stirring, by filtering with microporous membrane, the packing of gained filtrate is the docetaxel compositions with mixed solution.
Get 95% ethanol and the water for injection of recipe quantity, behind the mix homogeneously, mixed solution is through 0.22 μ m degerming membrane filtration, and the filtrate packing gets final product.
Embodiment 8
Docetaxel medicament composition injection is:
Docetaxel 80g
Dehydrated alcohol 47.2g
Polyoxyethylene Sorbitan Monooleate 2441.6g
1000 bottles
The docetaxel medicament composition injection diluent is:
95% ethanol 920mL
Water for injection 6400mL
1000 bottles
Preparation method:
The docetaxel of recipe quantity was pulverized 300 mesh sieves, docetaxel after sieving with per minute add its gross mass 1/17 speed, under agitation slowly join in the Polyoxyethylene Sorbitan Monooleate of recipe quantity, rotating speed is controlled at after 130 commentaries on classics/min stir, the dehydrated alcohol that adds recipe quantity, obtain mixed solution after the stirring, by filtering with microporous membrane, the packing of gained filtrate is the docetaxel compositions with mixed solution.
Get 95% ethanol and the water for injection of recipe quantity, behind the mix homogeneously, mixed solution is through 0.22 μ m degerming membrane filtration, and the filtrate packing gets final product.
Experimental example 1
This experimental example is the comparison of the stability of the docetaxel medicament composition injection of embodiment 1 gained and the injection docetaxel described in patent application CN200710049357.9, the patent application CN200610032942.3, and three kinds of injection docetaxels are carried out stability comparison according to the method for 2005 editions second one of Chinese Pharmacopoeia simultaneously.Concrete data see Table 1:
Table 1 docetaxel compositions of the present invention and CN200710049357.9, CN200610032942.3 stability are relatively
| The injection docetaxel kind | Embodiment 1 | CN200710049357.9 | CN200610032942.3 |
| Stability | 24 months | 21 months | 19 months |
Find out three kinds of injection docetaxels stable basic identical from the result of table 1.The present invention carries out above-mentioned experiment to the docetaxel compositions of other embodiment except that embodiment 1, obtains the result similar to experimental example.
Experimental example 2
This experimental example is that the docetaxel medicament composition injection of embodiment 6 dilutes later mixture with diluent, and this mixture joins in the different infusion liquid, the time that insoluble matter occurs, sees table 2 for details:
Table 2 docetaxel compositions dilution back crystal in infusion liquid is separated out the comparison of time
Data after the docetaxel compositions process diluent of the present invention dilution, all just have crystal in the long time and separate out as can be seen in infusion liquid commonly used from table.
Table 3, table 4 are respectively that the docetaxel compositions of embodiment 6 is diluted later mixture with diluent, and this mixture joins the investigation of 0.9% sodium chloride solution, 0.5% glucose solution Chinese medicine stability.
Table 3 docetaxel is stable in 0.9% sodium chloride solution
Table 4 docetaxel is stability in 0.5% glucose solution
Can draw from the experimental result of table 3, table 4, docetaxel 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 docetaxel compositions of other embodiment except that embodiment 6, obtains the result similar to experimental example.
Experimental example 3
This experimental example adds speed when being adding embodiment 6 docetaxel composition powders and mixing speed is separated out time effects to this docetaxel compositions crystal in infusion liquid, the prescription of described docetaxel compositions and preparation method reference example 6, except adding speed and the mixing speed, it is the 1/n of gross mass that adding speed adds the medicated powder quality with per minute, mixing speed is m commentaries on classics/min, crystal separate out the time in hour, be example with 5% glucose infusion liquid:
Table 5 docetaxel adds speed, mixing speed to docetaxel compositions crystallize time effects in infusion liquid
Analysis of experimental data from table 5, docetaxel group compositions of the present invention, is 1/15-1/17, the mixing speed of gross mass when being controlled at 100-160 commentariess on classics/min in the adding speed controlling of many Xi Tasai add the medicated powder quality with per minute, the docetaxel compositions that makes can stable existence in infusion liquid after diluting for more time.
Experimental example 4
The stability experiment that this experimental example carries out at ambient temperature for the docetaxel compositions of embodiment 1 sees Table 4, table 6.
The experiment of table 6 docetaxel composition stable
From table 6 stability experiment data as can be known, the docetaxel compositions of embodiment 1 can effectively be preserved 2 years at room temperature condition.
The present invention carries out the aforementioned stable experiment to the docetaxel compositions of other embodiment except that embodiment 1, obtains the result similar to experimental example.
Claims (10)
1. docetaxel medicament composition injection, said composition is made up of docetaxel, dehydrated alcohol and Polyoxyethylene Sorbitan Monooleate.
2. docetaxel medicament composition injection according to claim 1 is characterized in that, the constituent content of described docetaxel compositions is:
Docetaxel 15-25 weight portion
Dehydrated alcohol 10-15 weight portion
Polyoxyethylene Sorbitan Monooleate 550-700 weight portion.
3. docetaxel medicament composition injection according to claim 2 is characterized in that, the constituent content of described docetaxel compositions is as follows:
Docetaxel 18-23 weight portion
Dehydrated alcohol 11-13 weight portion
Polyoxyethylene Sorbitan Monooleate 560-630 weight portion.
4. according to each described docetaxel medicament composition injection of claim 1-3, it is characterized in that, described docetaxel compositions is used the mixed liquor of retarder thinner as ethanol and water for injection, described ethanol is that mass percent is 95% ethanol, wherein the volume ratio of 95% ethanol and water for injection is 1: 6.4-8.5, the volume ratio of its preferred 95% ethanol and water for injection is 1: 7.0-8.0.
5. docetaxel medicament composition injection according to claim 4 is characterized in that, the docetaxel compositions is:
Docetaxel 15-25g
Dehydrated alcohol 10-15g
Polyoxyethylene Sorbitan Monooleate 550-700g,
Docetaxel compositions diluent is:
95% ethanol 200-250mL
Water for injection 1600-1700mL.
6. according to claim 4 or 5 described docetaxel medicament composition injections, it is characterized in that,
The docetaxel compositions is:
Docetaxel 18-23g
Dehydrated alcohol 11-13g
Polyoxyethylene Sorbitan Monooleate 560-630g,
Docetaxel compositions diluent is:
95% ethanol 210-240mL
Water for injection 1650-1700mL.
7. the preparation method of each described docetaxel medicament composition injection of claim 1-6, comprise the steps: under agitation slowly to join the docetaxel of recipe quantity in the Polyoxyethylene Sorbitan Monooleate of recipe quantity, after stirring, the dehydrated alcohol that adds recipe quantity, obtain mixed solution after the stirring, by filtering with microporous membrane, the packing of gained filtrate is the docetaxel compositions with mixed solution.
8. preparation method according to claim 7 is characterized in that, docetaxel was pulverized docetaxel before adding Polyoxyethylene Sorbitan Monooleate, crossed the 200-500 mesh sieve, and it preferably crosses the 200-300 mesh sieve.
9. preparation method according to claim 7 is characterized in that, the speed that docetaxel adds polysorbate-80 is: for the docetaxel of 1kg, it is the 1/15-1/17 of itself quality that per minute adds the medicated powder quality.
10. preparation method according to claim 7 is characterized in that, it is 100-160 commentaries on classics/min that described stirring is rotating speed, and preferred rotating speed is 120-140 commentaries on classics/min.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101829078A (en) * | 2010-03-19 | 2010-09-15 | 福建医科大学附属协和医院 | Absolute ethyl alcohol injection containing docetaxel and application thereof in preparing medicaments for treating tumors under ultrasonic guidance |
| CN107260747A (en) * | 2017-05-25 | 2017-10-20 | 广东工业大学 | A kind of pharmaceutical composition of collaboration anti-prostate cancer |
| CN107260747B (en) * | 2017-05-25 | 2020-07-21 | 广东工业大学 | Pharmaceutical composition for synergistically resisting prostate cancer |
| CN107157926A (en) * | 2017-07-20 | 2017-09-15 | 四川汇宇制药有限公司 | A kind of preparation method of injection docetaxel |
| CN107157926B (en) * | 2017-07-20 | 2020-08-21 | 四川汇宇制药股份有限公司 | Preparation method of docetaxel injection |
| CN110755371A (en) * | 2018-07-25 | 2020-02-07 | 比卡生物科技（广州）有限公司 | Docetaxel composition for injection and preparation method thereof |
| CN112402371A (en) * | 2020-11-19 | 2021-02-26 | 南京正济医药研究有限公司 | Rudesiwei injection and preparation method thereof |
| CN112402371B (en) * | 2020-11-19 | 2023-01-17 | 南京正济医药研究有限公司 | Rudesiwei injection and preparation method thereof |
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| CN101584659B (en) | 2011-08-31 |
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