CN105232182A - Paclitaxel-loaded ethylene-vinyl acetate esophageal stent and preparation method thereof - Google Patents
Paclitaxel-loaded ethylene-vinyl acetate esophageal stent and preparation method thereof Download PDFInfo
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- CN105232182A CN105232182A CN201510695548.7A CN201510695548A CN105232182A CN 105232182 A CN105232182 A CN 105232182A CN 201510695548 A CN201510695548 A CN 201510695548A CN 105232182 A CN105232182 A CN 105232182A
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Abstract
The invention pertains to the field of medical instruments and discloses a paclitaxel-loaded ethylene-vinyl acetate esophageal stent and a preparation method thereof. The stent is composed of a bare metal stent and a covering film covering the bare metal stent. The covering film comprises an ethylene-vinyl acetate esophageal backing layer and a paclitaxel medicine film layer. The inside of the ethylene-vinyl acetate esophageal backing layer is closely adhered to the bare metal stent. The outside of the ethylene-vinyl acetate esophageal backing layer is adhered to the paclitaxel medicine film layer. The stent is 50% in the theoretical drug-loading amount ranges from 48.26% -50.81% in the measured drug-loading amount. Within 80d, paclitaxel ranges from 615.274-1101.368 [mu]m/cm2 in the accumulative releasing amount and ranges from 57.93-108359 [mu]m/cm2 and also ranges from 57.93-108359 [mu]m/cm2 in the infiltration amount from the backing layer. The paclitaxel-loaded ethylene-vinyl acetate esophageal stent and the preparation method thereof have following beneficial effects: the preparation method is easily and conveniently applied; the good mechanical property is obtained; the slow release function can be fulfilled for a long time; and the stent has good functions of mechanical support and prevention against growth inside of tumors.
Description
Technical field
The present invention relates to the medicine-carrying polymer overlay film frame of medical instruments field, be specifically related to ethene-vinyl acetate Esophageal Stent of a kind of year paclitaxel and preparation method thereof, be applied to treatment esophagus tract narrow.
Background technology
Support is a kind of desirable delivery system.Conventional stent does not possess active treatment effect, only play mechanical support and short-term maintain tract open appease effect.Carried stent is compared with common bare mental stents, adds two parts, and one is medicine, can suppress the medicine of neointimal hyperplasia, control restenosis; Two is pharmaceutical carriers, is often the synthetic polymer of good biocompatibility.The release of drug-loaded layer Chinese medicine must be controlled and predictable.Realize this purpose just to need to select suitable medicine carrying material.In non-vascular field, carried stent there is no the significant launch of antitumor curative effect, therefore analyzes and researches carried stent drug-supplying system highly significant.
Find through carrying out retrieval to the document of prior art: China Patent Publication No. is CN2638761Y, publication date is JIUYUE in 2004 8 days, patent name is esophagus medicine stent, this patent is a kind of esophagus medicine stent by carrier patients with implantation esophageal tumor narrow section, its weak point is that the drug loading of medicine is inadequate, and two is that the release of 5-fluorouracil in silicon rubber medicinal film is slow.Guo Shengrong seminar of Shanghai Communications University creates the support/drug regimen body for the esophageal carcinoma, the serial article delivered has LeiL, LiuX, GuoS, TangM, ChengL, TianL.5-fluorouracilloadedmultilayeredfilmsfordrugcontro lledreleasingstentapplication:drugrelease, microstructure, andexvivopermeationbehaviors.JControlRelease.2010; 146 (1): 45 – 53.doi:10.1016/j.jconrel.2010.05.017.GuoQH, GuoSR, WangZM.Estimationof5-fluorouracil-loadedethylenevinylace tatestentcoatingbasedonpercolationthresholds.IntJPharm20 07; 333:95e102. is just that the antineoplastic agent membrane support of carrier carries out relevant research with ethylene-vinyl acetate copolymer, obtains good effect.The weak point of current research is that the model of EVA used is single, and the selection of backing layer lacks foundation, and in film material, taxol release is comparatively slow, can not the release of effective regulation and control medicine.
Summary of the invention
For defect of the prior art, the object of this invention is to provide ethene-vinyl acetate Esophageal Stent of a kind of year paclitaxel and preparation method thereof, improve medicine film layer and the backing layer of support, make support reach better mechanic properties and adjustable medicine-releasing performance.
The object of the invention is to be achieved through the following technical solutions:
First aspect, the invention provides the ethene-vinyl acetate Esophageal Stent of a kind of year paclitaxel, described support is made up of bare mental stents and the overlay film be overlying on described bare mental stents, described overlay film comprises ethene-vinyl acetate backing layer and paclitaxel medicine film layer, the inner side of wherein said ethene-vinyl acetate backing layer and described bare mental stents are close to, and outside and the described paclitaxel medicine film layer of described ethene-vinyl acetate backing layer bond.
Preferably, described bare mental stents is selected from works out support or commercial support voluntarily, and the material of support comprises Ni-Ti alloy, and the model of support is selected from long 3.5cm, diameter 0.9cm.
Preferably, in ethene-vinyl acetate backing layer, the model of described ethene-vinyl acetate comprises one or more in EVA42/60, EVA32/43, EVA30/10.The amount of paclitaxel saturated solution through the film material of three kinds of model same thickness and model different-thickness of the same race is investigated.Wherein EVA30/10 film material ultimate tensile strength is better, and drug permeability is poor.
More preferably, in ethene-vinyl acetate backing layer, the model of described ethene-vinyl acetate is EVA30/10, and thickness is 50 ~ 150 μm.
Preferably, the component of described paclitaxel medicine film layer comprises ethene-vinyl acetate, paclitaxel.Further, in described ethene-vinyl acetate Esophageal Stent, the dosage range of paclitaxel is 48.26 ~ 50.81%.The present invention, in implementation process, if the dosage of paclitaxel is too low, reduces drug loading, if dosage is too high, affects the mechanical property of medicament transport and support.
Preferably, the model of described ethene-vinyl acetate comprises EVA42/60, EVA32/43 or EVA30/10.
More preferably, the thickness of described paclitaxel medicine film layer is 170 ~ 180 μm.
Support provided by the invention is the Esophageal Stent with unidirectional Release Performance.In 80d, the cumulative release amount of paclitaxel is 615.274 ~ 1101.368 μ g/cm
2, be 57.93 ~ 108.59 μ g/cm from the infiltration capacity of backing layer
2.Support of the present invention improves the standby serial Esophageal Stent of my place project team system, preparation method is simple and easy to do, the mechanical property of support medicine film of the present invention is better, can play long-term sustained release effect, and support has good mechanical support and prevents the effect of growth in tumor.
Second aspect, the invention provides a kind of described preparation method of carrying the ethene-vinyl acetate Esophageal Stent of paclitaxel, be included in bare mental stents appearance and cover the step that the preparation of ethene-vinyl acetate backing layer is covered with the metal rack of backing layer, and in the described step being covered with the metal support surface bonding paclitaxel medicine film layer of backing layer.
Preferably, covering the preparation of ethene-vinyl acetate backing layer in bare mental stents appearance is covered with in the step of the metal rack of backing layer, described covering mainly adopts infusion process, impregnated in impregnated in by described bare mental stents the dichloromethane solution being dissolved with ethene-vinyl acetate by described bare mental stents.
Further, the described preparation being dissolved with the dichloromethane solution of ethene-vinyl acetate comprises: dissolve 4.0gEVA in every 30ml dichloromethane, spends the night in 37 DEG C of (experiment is exactly carry out at this temperature, the temperature of simulation human body esophageal site) shaking baths, vortex, to obtain final product; The time of described dipping is 2 ~ 10s.
Preferably, in the step of the described metal support surface bonding paclitaxel medicine film layer being covered with backing layer, the preparation method of described paclitaxel medicine film layer mainly adopts the mixed rear orientation of heat or hot pressing.
Further, the mode of described bonding mainly adopts heating, pressurization.
The third aspect, the invention provides the quantitative analysis method of paclitaxel in a kind of paclitaxel medicine film layer, comprising: be fully dissolved in dichloromethane by described medicine film layer, then add methanol, precipitation macromolecule, finally analyzes with HPLC and measures.
Establish a kind of new method that in EVA medicine film, dose of paclitaxel measures in the present invention, after all dissolving by medicine film, precipitate macromolecule again, then measure the content of paclitaxel in solvent by HPLC analytical method.Result drug loading is about 50%, and the dosage of medicine film and the RSD value of uniformity of dosage units are all in 5%, and after heat is mixed, the medicine film of orientation and compacting is more homogeneous.
The mechanical property of the present invention to different prescription drugs film is studied.The mechanical property difference to some extent of different prescription drugs film, VA content is lower, and ultimate tensile strength and the elastic modelling quantity of support medicine film all present ascendant trend, and maximum elongation rate then reduces.Orientation medicine film than direct pressing medicine film ultimate tensile strength more greatly, there is better mechanical property.
The present invention investigates the release performance of paclitaxel in different prescription drugs film.As can be seen from drug release patterns, all drug release patterns are rendered as two feature stage, the quick medicament release stage at initial stage (1-10 days) and the drug release phase at a slow speed in later stage (10-80 days).Paclitaxel is 1101.368 μ g/cm from the cumulative release amount the EVA42/60 medicine film of orientation
2, be 721.799 μ g/cm from the cumulative release amount the EVA32/43 medicine film of orientation
2, be 615.274 μ g/cm from the cumulative release amount the EVA30/10 medicine film of orientation
2, be 783.441 μ g/cm from the cumulative release amount the EVA32/43 medicine film of direct hot pressing
2.Visible, the difference of EVA film material and medicine film orientation make the burst size difference to some extent of medicine.
The present invention have recorded the surperficial macroscopic form before and after the support overlay film release of medicine carrying.The support film preparing gained is smooth, but slow releasing is after 80 days in the phosphate buffer of the pH6.5 containing 1% Tween 80, and the configuration of surface of film also there occurs change.Film obviously there occurs swelling, and there are a lot of minute bubbles on some film surfaces, some visible slight crack in film surface.
The present invention uses scanning electron microscopic observation to before and after drug release, can see a lot of granule of release experiment cephacoria surface distributed from photo clearly.Discharge after tens days, still can see the granule that film distributes, but aperture has appearred in indivedual place, discharge 80 days and find that the granule being originally present in film surface disappears many afterwards, surface forms more larger holes, even surface the coming off of tablet as seen.
Compared with prior art, the present invention has following beneficial effect:
(1) by with hot pressing and method for alignment, making ethene-vinyl acetate support add medicine to the thickness of film can be very thin, reaches 170 μm ~ 180 μm.
(2) by infusion process, control infiltrating time, the backing layer of different-thickness can be prepared, reach 50 μm ~ 150 μm.
(3) by improving the assay method of paclitaxel skill amount in medicine film, make the measured value of dose of paclitaxel in medicine film more accurate.
(4) by comparing paclitaxel saturated solution through different substrates EVA, same thickness (100 μm) film material and through EVA30/10, the permeance property of different-thickness film material, makes to determine that EVA30/10 is film material, and thickness is 100 μm is preferably backing layer condition.
(5) by paclitaxel from the release experiment the medicine film layer of different EVA film material and the EVA32/43 medicine film layer of orientation and non-orientation, find to change macromolecular material or to medicine film orientation, can the release of regulating drug in various degree.
Accompanying drawing explanation
By reading the detailed description done non-limiting example with reference to the following drawings, other features, objects and advantages of the present invention will become more obvious:
Fig. 1 paclitaxel saturated solution through different substrates EVA, the time m-dose curve of same thickness (100 μm) film material;
Fig. 2 paclitaxel saturated solution through EVA30/10, the time m-dose curve of different-thickness film material;
Fig. 3 medicine is from the medicine film layer release of different EVA film material and the time m-dose curve (n=3) through backing layer;
Fig. 4 medicine is from the EVA32/43 medicine film layer release of orientation and non-orientation and the time m-dose curve (n=3) through backing layer;
Before macroscopical picture of Fig. 5 support overlay film: Film4 tests in PBS release medium and release (a and f) after 80 days;
Fig. 6 medicine carrying overlay film at release 0d, the scanning electron microscope (SEM) photograph on the film surface of 10d, 30d, 80d: Film2 release 0d, 10d, 30d and 80d (a, b, c and d).
Detailed description of the invention
Below in conjunction with specific embodiment, the present invention is described in detail.Following examples will contribute to those skilled in the art and understand the present invention further, but not limit the present invention in any form.It should be pointed out that to those skilled in the art, without departing from the inventive concept of the premise, some distortion and improvement can also be made.These all belong to protection scope of the present invention.
embodiment 1
The present embodiment relates to the preparation of backing layer, and concrete operations are as follows:
Taking about 4.0gEVA is dissolved in the dichloromethane solution of 30ml, and be placed in 37 DEG C of shaking baths and spend the night, then take out, vortex is about 10min to EVA and dissolves completely, obtains backing layer solution.
The Ni-Ti alloying metal bare bracket of woven 3.5cm length, diameter 0.9cm, two ends expansion hatch diameter 1.1cm is enclosed within the glass rod that diameter is 0.9cm, the slow backing layer macromolecular solution 2s ~ 10s immersing preparation, volatilize after taking-up 24h in fume hood, take off from glass rod for subsequent use, the metal rack of backing layer must be covered with.
embodiment 2
The present embodiment relates to the preparation of medicine film, and concrete operations are as follows:
The prescription being 1:1 in macromolecular material and paclitaxel ratio feeds intake and carries out Haake machine and mix, and concrete operation step is: the reinforced cavity temperature of Haake machine KAAKEMiniLabII is raised to 85 DEG C, adds EVA, starts Haake machine, rotates to clean reinforced chamber.Above step repeatedly, can ensure the clean of reinforced chamber.After fully cleaning Haake machine, add the formulation ingredients that in table, each prescription numbering is corresponding, mixing 30min, after mixing, a certain size polyester film pad below reinforced chamber, then opens reinforced chamber, scrapes clean mixture while hot.
embodiment 3
The present embodiment relates to compacting and the orientation of medicine film, and concrete operations are as follows:
(1) be EVA42/60 by carrier material, drug loading be 50% medicine film press down restriction 340 μm and 320 μm at 100 DEG C of film laminators, first long 2.5cm, under 80 DEG C of constant temperatures, stretch on orientation machine with 2.5min/r speed, stretch orientation 2.4 times and 2.35 times, about long 6.0cm and 5.8cm.Reach about 180 μm, room temperature cooling 30min, takes off from orientation machine, cuts out rear for subsequent use.
(2) be EVA32/43 by carrier material, drug loading be 50% medicine film press down restriction 1.5h at 100 DEG C of film laminators, to about 350 μm, first long 2.5cm.Be cut into two parts, portion, at 100 DEG C, is suppressed about 2h, is reached about 180 μm, and room temperature cooling 30min, cuts out rear for subsequent use.
(3) the medicine film of another part of EVA32/43 measures just long is 2.1cm, under 80 DEG C of conditions, and 2.5min/r speed tensile orientation.During orientation 2 times, there is crack, cut off crack, orientation at 90 DEG C, about long 4.7cm.Reach about 180 μm, room temperature cooling 30min, takes off from orientation machine, cuts out rear for subsequent use.
(4) be EVA30/10 by carrier material, drug loading be 50% medicine film press down restriction 4h at 120 DEG C of film laminators, to about 350 μm, first long 2.5cm.Under 80 DEG C of conditions, 2.5min/r speed tensile orientation 2.5 times, about long 5.5cm, reaches about 180 μm, and room temperature cooling 30min, takes off from orientation machine, cut out rear for subsequent use.
embodiment 4
The present embodiment relates to the preparation of carried stent, and concrete operations are as follows:
By the medicine film (prepared by embodiment 3) cut out, heated by blower fan and the mode of pressurizeing with tweezers, medicine film is bonded to and is covered with (prepared by embodiment 1) on the metal rack of backing layer.10min is placed, good seal under uviol lamp, stand-by.
embodiment 5
The present embodiment relates to the mensuration of medicine film thickness, and concrete operations are as follows:
Prepare all kinds of medicine films (prepared by embodiment 3) of gained, Film1, Film2, Film3 are the EVA42/60 that orientation obtains respectively, EVA32/43, EVA30/10 medicine film, and Film4 is the EVA32/43 medicine film obtained after hot pressing.The centre of film and surrounding random get 5 points, measure the thickness at each point place with calibrator, write down thickness number, calculate average thickness and the thickness uniformity of membrane.The results are shown in subordinate list 1, as shown in Table 1, the thickness of the medicine film after orientation and hot pressing, on average at 170 μm ~ 180 μm, changes medicine film prepared by method more homogeneous.
Table 1 support cover the thickness of medicine film
| Macromolecule model in medicine film | Preparation method | Drug loading (%) | Thickness (μm scholar SD%) |
| EVA42/60 | Orientation | 50 | 178 scholars 3.87 |
| EVA32/43 | Orientation | 50 | 172 scholars 2.86 |
| EVA30/10 | Orientation | 50 | 176 scholars 3.13 |
| EVA30/10 | Hot pressing | 50 | 180 scholars 1.19 |
embodiment 6
The present embodiment relates to year drug dose of PTX medicine film and the mensuration of uniformity of dosage units, and concrete operations are as follows:
The paclitaxel medicine film (embodiment 3 prepares) that carries of preparation is cut roundlet membrane sample at random, often organizes 4 (n=4), and use electronic balance precision weighing.After weighing, be fully dissolved in 5ml dichloromethane, slowly in instillation 20ml methanol.Vortex 1min, centrifugal 10min under 10000r.With dichloromethane: methanol is that 1:4 dilutes 5 times and measures with HPLC sample introduction afterwards.The ratio of the value that the drug loading (%) in roundlet membrane sample records for HPLC and roundlet membrane sample quality represents.The results are shown in subordinate list 2, assay value and theoretical value are relatively as shown in Table 2, and uniformity of dosage units is good, and medicine is uniformly distributed in film, and the method is prepared medicine film and facilitated feasible.
The medicament contg (n=3) of table 2 paclitaxel carried medicine overlay film
embodiment 7
The present invention relates to the mechanical property research of overlay film frame (embodiment 4 prepares), concrete operations are as follows:
According to GB1039-1992, (corresponding ISO527-1995, universal tensile test machine (Instron4465, InstronCorp., USA) carries out, and membrane sample is of a size of 50mm × 5mm to the mechanical test of sample, and scale translational speed is 50mmmin
-1, at the uniform velocity apply pulling force until sample breakage.Measure hot strength respectively, elastic modelling quantity, percentage elongation.Hot strength is in process of the test, the peak load (kg/cm that the live part original cross-sectional unit are of sample is born
2); Elongation at break is in process of the test, owing to stretching, during sample fracture, the live part distance between bench marks of sample from the percentage rate of increment and the ratio of initial gage; Material is elastic deformation stage, and its stress and strain direct proportionality (namely meeting Hooke's law), its proportionality coefficient is elastic modelling quantity.Each sample repeats 3 times.The results are shown in subordinate list 3, as shown in Table 3, the medicine film that the medicine film that in three kinds of EVA material, VA content is high is low compared to VA content, elasticity is better, but resistance external force is poor.Medicine film tensile resistance prepared by EVA30/10 is comparatively strong, has better mechanical performance, can reduce the damage of medicine film in related experiment.Orientation medicine film is compared to direct pressing medicine film, and elasticity is poor, but resistance external force is stronger.
The mechanical property parameters of table 3 support medicine film
| Medicine film component | Ultimate tensile strength (Mpa) | Maximum elongation rate (%) | Elastic modelling quantity (Mpa) |
| EVA42/60 (orientation) | 1.56 scholar 2.64 | 546.87 scholars 2.45 | 72.82 scholar 1.87 |
| EVA32/43 (orientation) | 2.96 scholar 1.76 | 210.02 scholars 1.36 | 196.24 scholars 2.89 |
| EVA30/10 (orientation) | 6.52 scholar 1.57 | 200.80 scholars 2.57 | 358.63 scholars 3.42 |
| EVA32/43 (hot pressing) | 1.87 scholar 2.89 | 404.54 scholars 3.09 | 255.97 scholars 2.21 |
embodiment 8
The present embodiment relates to the infiltrative mensuration of paclitaxel in different prescription EVA blank film, and concrete operations are as follows:
(1) paclitaxel saturated solution is measured by the flux V-C horizontal proliferation pond of backing layer and medicine membrane matrix material.Effective diffusion area in horizontal proliferation pond is 0.64cm
2.Adopt casting method to prepare the EVA blank film of 100 μm, the blank film of EVA42/60, EVA32/43, EVA30/10 is cut into the disk that diameter is 1.0cm, to clip with sealing ring and between the supply pool being fixed on V-C horizontal proliferation instrument and reception tank.In each supply pool, add water-ethanol (40:60) saturated solution of 3ml paclitaxel, in each reception tank, add 3ml water-ethanol (40:60) solution.Sealed by the opening of supply pool and reception tank, whole device connects thermostatical circulating water, keeps its temperature 37 DEG C.All put into magneton in supply pool and reception tank and carry out magnetic agitation.At set intervals, the solution in reception tank is all taken out, measure the concentration of wherein paclitaxel with HPLC.Meanwhile, in reception tank, the fresh water-ethanol of 3ml (40:60) solution is added.Often kind of sample film carries out 3 parallel laboratory tests.The results are shown in accompanying drawing 1, as shown in Figure 1, in the EVA film that VA content is higher, the permeance property of paclitaxel is better, and the amount through medicine is more.
(2) obtain the EVA30/10 blank film of different-thickness with casting method, obtain the blank film that thickness is 50,100,150 μm respectively.To clip with sealing ring and between the supply pool being fixed on V-C horizontal proliferation instrument and reception tank.Measure the concentration of paclitaxel in reception tank according to the method described above, often kind of sample film carries out 3 parallel laboratory tests.The results are shown in accompanying drawing 2, as shown in Figure 2, the film material of different-thickness is different through the amount of medicine, and film material is thinner, medicine easier through.
embodiment 9
According to embodiment 8 related experiment result, the preparation of the present embodiment determination release experiment backing layer, concrete operations are:
Taking EVA30/10 is 1g, is dissolved in the dichloromethane of 30ml, and the shaking bath at 37 DEG C spends the night, and casting prepares blank medicine film.As the backing layer of release experiment, thickness is about 100 μm.
embodiment 10
The present embodiment relates to the investigation of medicine film release behavior, and concrete operations are as follows:
According to the prescription of subordinate list 4, four kinds of medicine films (often organizing each three parts) are attached blank backing layer (embodiment 9 prepares), put into the V-C horizontal proliferation pond of 37 DEG C of recirculated waters, add the release medium (containing the phosphate buffer of the pH6.5 of 1% Tween 80, the simulation pH value of esophagus position physiological environment) of 3ml.In following point in time sampling 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 2d, 4d, 6d, 8d, 10d, 15d, 21d, 27d, 32d, 45d, 60d, 80d.And supplement fresh medium in time.In sample, the concentration of paclitaxel measures by above-mentioned HPLC method.After mensuration, calculate preparation and the rate of release of each group of medicine film.The results are shown in accompanying drawing 3 and accompanying drawing 4, from upper figure, paclitaxel is larger from the dose of the cumulative release the high medicine film of VA content.Medicine film orientation makes the burst size difference to some extent of medicine, and the amount of paclitaxel cumulative release from compacting medicine film is a bit larger tham alignment films.By changing macromolecular material or to medicine film orientation, can the release of regulating drug in various degree.
The composition of film material in table 4 release experiment
embodiment 11
The macroscopic view that the present embodiment relates to before and after the release of support overlay film is taken pictures, specific as follows:
Take the photo before and after the loss of each support compound film quality respectively with digital camera (Canon), the time point of shooting is 0 day and 80 days, observes the change of film surface macro morphology.The results are shown in accompanying drawing 5, as shown in Figure 5, the stripping of the paclitaxel in medicine film in release medium makes film configuration of surface change to some extent.
embodiment 12
The present embodiment relates to the SEM research after the release of medicine film, and concrete operations are as follows:
Before release, in, the configuration of surface of the medicine carrying overlay film in later stage adopts scanning electron microscope (scanningelectronmicroscope, SEM) observe, sample preparation methods is as follows: cut the copper sheet that small pieces have conducting function, with double faced adhesive tape on sample stage, then get a fritter support film sample tiling and be affixed on (carried stent overlay film drug-loaded layer is affixed on double faced adhesive tape by lining) on double faced adhesive tape upward, with the electric current of 15mA spraying gold-palladium reagent powder 30s, blow the reagent powder of non-fixation off, membrane sample release 0d is observed with SEM, 10d, 30d, 80d configuration of surface.The results are shown in accompanying drawing 6, as shown in Figure 6, along with the prolongation of release time, taxol release amount increases gradually, and the granule being originally present in film surface fades away, and forms more larger holes to surface.
Above specific embodiments of the invention are described.It is to be appreciated that the present invention is not limited to above-mentioned particular implementation, those skilled in the art can make various distortion or amendment within the scope of the claims, and this does not affect flesh and blood of the present invention.
Claims (10)
1. carry an ethene-vinyl acetate Esophageal Stent for paclitaxel, it is characterized in that, described support is made up of bare mental stents and the overlay film be overlying on described bare mental stents, and described overlay film comprises ethene-vinyl acetate backing layer and paclitaxel medicine film layer; Wherein, the inner side of described ethene-vinyl acetate backing layer and described bare mental stents are close to, outside and the described paclitaxel medicine film layer of described ethene-vinyl acetate backing layer bond.
2. the ethene-vinyl acetate Esophageal Stent of according to claim 1 year paclitaxel, is characterized in that, in ethene-vinyl acetate backing layer, the model of described ethene-vinyl acetate comprises one or more in EVA42/60, EVA32/43, EVA30/10.
3. the ethene-vinyl acetate Esophageal Stent of according to claim 1 year paclitaxel, is characterized in that, the component of described paclitaxel medicine film layer comprises ethene-vinyl acetate, paclitaxel.
4. the ethene-vinyl acetate Esophageal Stent of according to claim 3 year paclitaxel, is characterized in that, the model of described ethene-vinyl acetate comprises EVA42/60, EVA32/43 or EVA30/10.
5. one kind carries the preparation method of the ethene-vinyl acetate Esophageal Stent of paclitaxel according to any one of Claims 1-4, it is characterized in that, be included in bare mental stents appearance and cover the step that the preparation of ethene-vinyl acetate backing layer is covered with the metal rack of backing layer, and in the described step being covered with the metal support surface bonding paclitaxel medicine film layer of backing layer.
6. carry the preparation method of the ethene-vinyl acetate Esophageal Stent of paclitaxel according to claim 5, it is characterized in that, covering the preparation of ethene-vinyl acetate backing layer in bare mental stents appearance is covered with in the step of the metal rack of backing layer, described covering mainly adopts infusion process, impregnated in the dichloromethane solution being dissolved with ethene-vinyl acetate by described bare mental stents.
7. carry the preparation method of the ethene-vinyl acetate Esophageal Stent of paclitaxel according to claim 6, it is characterized in that, described in be dissolved with being prepared as of the dichloromethane solution of ethene-vinyl acetate: dissolve 4.0gEVA in every 30ml dichloromethane, spend the night in 37 DEG C of shaking baths, vortex, to obtain final product; The time of described dipping is 2 ~ 10s.
8. carry the preparation method of the ethene-vinyl acetate Esophageal Stent of paclitaxel according to claim 5, it is characterized in that, in the step of the described metal support surface bonding paclitaxel medicine film layer being covered with backing layer, the preparation method of described paclitaxel medicine film layer mainly adopts the mixed rear orientation of heat or hot pressing.
9. according to claim 5 or 8, carry the preparation method of the ethene-vinyl acetate Esophageal Stent of paclitaxel, it is characterized in that, the mode of described bonding mainly adopts heating, pressurization.
10. the quantitative analysis method of paclitaxel in paclitaxel medicine film layer, is characterized in that, comprising: be fully dissolved in dichloromethane by described medicine film layer, then add methanol, precipitation macromolecule, finally analyzes with HPLC and measures.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN106073942A (en) * | 2015-04-30 | 2016-11-09 | 微创心脉医疗科技（上海）有限公司 | A kind of support and delivery device |
| CN113041407A (en) * | 2021-03-15 | 2021-06-29 | 广州健康元呼吸药物工程技术有限公司 | Multilayer film-covered drug-loaded stent and preparation method and application thereof |
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| CN113041407A (en) * | 2021-03-15 | 2021-06-29 | 广州健康元呼吸药物工程技术有限公司 | Multilayer film-covered drug-loaded stent and preparation method and application thereof |
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