CN104474595A - Production method of dilayer compounding coated esophageal stent with esophageal cancer treatment assisting function - Google Patents
Production method of dilayer compounding coated esophageal stent with esophageal cancer treatment assisting function Download PDFInfo
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- CN104474595A CN104474595A CN201410640182.9A CN201410640182A CN104474595A CN 104474595 A CN104474595 A CN 104474595A CN 201410640182 A CN201410640182 A CN 201410640182A CN 104474595 A CN104474595 A CN 104474595A
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- 206010030155 Oesophageal carcinoma Diseases 0.000 title claims abstract description 31
- 238000011282 treatment Methods 0.000 title claims abstract description 26
- 238000013329 compounding Methods 0.000 title abstract 6
- 208000000461 Esophageal Neoplasms Diseases 0.000 title abstract 3
- 201000004101 esophageal cancer Diseases 0.000 title abstract 3
- 238000004519 manufacturing process Methods 0.000 title abstract 2
- 229920001610 polycaprolactone Polymers 0.000 claims abstract description 75
- 239000004632 polycaprolactone Substances 0.000 claims abstract description 75
- KHYBPSFKEHXSLX-UHFFFAOYSA-N iminotitanium Chemical compound [Ti]=N KHYBPSFKEHXSLX-UHFFFAOYSA-N 0.000 claims abstract description 53
- 229910001000 nickel titanium Inorganic materials 0.000 claims abstract description 53
- 239000000835 fiber Substances 0.000 claims abstract description 25
- 230000006870 function Effects 0.000 claims abstract description 24
- 239000003814 drug Substances 0.000 claims abstract description 21
- 229940079593 drug Drugs 0.000 claims abstract description 20
- 238000010041 electrostatic spinning Methods 0.000 claims abstract description 17
- 239000003960 organic solvent Substances 0.000 claims abstract description 17
- 150000001875 compounds Chemical class 0.000 claims description 44
- 208000017897 Carcinoma of esophagus Diseases 0.000 claims description 28
- 230000006835 compression Effects 0.000 claims description 28
- 238000007906 compression Methods 0.000 claims description 28
- 201000005619 esophageal carcinoma Diseases 0.000 claims description 28
- 229930012538 Paclitaxel Natural products 0.000 claims description 22
- 229960001592 paclitaxel Drugs 0.000 claims description 22
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 22
- 238000011275 oncology therapy Methods 0.000 claims description 19
- 238000002360 preparation method Methods 0.000 claims description 19
- 238000003756 stirring Methods 0.000 claims description 16
- 108010010803 Gelatin Proteins 0.000 claims description 15
- 229920000159 gelatin Polymers 0.000 claims description 15
- 239000008273 gelatin Substances 0.000 claims description 15
- 235000019322 gelatine Nutrition 0.000 claims description 15
- 235000011852 gelatine desserts Nutrition 0.000 claims description 15
- 229910000831 Steel Inorganic materials 0.000 claims description 14
- 239000010959 steel Substances 0.000 claims description 14
- 239000012528 membrane Substances 0.000 claims description 10
- 239000011368 organic material Substances 0.000 claims description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 7
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 7
- 229960002949 fluorouracil Drugs 0.000 claims description 7
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 claims description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- 238000007599 discharging Methods 0.000 claims description 4
- 238000001523 electrospinning Methods 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- NWXMGUDVXFXRIG-WESIUVDSSA-N (4s,4as,5as,6s,12ar)-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide Chemical compound C1=CC=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]4(O)C(=O)C3=C(O)C2=C1O NWXMGUDVXFXRIG-WESIUVDSSA-N 0.000 claims description 2
- 229930195573 Amycin Natural products 0.000 claims description 2
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 9
- 238000009987 spinning Methods 0.000 abstract description 7
- 239000000463 material Substances 0.000 abstract description 5
- 238000005516 engineering process Methods 0.000 abstract description 3
- 229920000620 organic polymer Polymers 0.000 abstract description 2
- 239000011248 coating agent Substances 0.000 abstract 2
- 238000000576 coating method Methods 0.000 abstract 2
- 239000002246 antineoplastic agent Substances 0.000 abstract 1
- 229940041181 antineoplastic drug Drugs 0.000 abstract 1
- 238000013270 controlled release Methods 0.000 abstract 1
- 239000007788 liquid Substances 0.000 abstract 1
- 238000002156 mixing Methods 0.000 abstract 1
- 239000002861 polymer material Substances 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 46
- 238000001035 drying Methods 0.000 description 13
- 239000000203 mixture Substances 0.000 description 11
- 208000027418 Wounds and injury Diseases 0.000 description 7
- 230000006378 damage Effects 0.000 description 4
- 208000014674 injury Diseases 0.000 description 4
- 230000000694 effects Effects 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 239000003005 anticarcinogenic agent Substances 0.000 description 2
- 239000002657 fibrous material Substances 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 208000019505 Deglutition disease Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000033240 Progressive symmetric erythrokeratodermia Diseases 0.000 description 1
- 238000009098 adjuvant therapy Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000002390 hyperplastic effect Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000010030 laminating Methods 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000002362 mulch Substances 0.000 description 1
- 238000002638 palliative care Methods 0.000 description 1
- 239000002985 plastic film Substances 0.000 description 1
- 229920006255 plastic film Polymers 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
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- Medicinal Preparation (AREA)
- Materials For Medical Uses (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a production method of a dilayer compounding coated esophageal stent with an esophageal cancer treatment assisting function. The method comprises the following steps: making an inner layer polycaprolactone compact surface on the surface of a Ni-Ti memory esophageal stent through a solution film paving technology; spinning a fiber film obtained by using a solution of an outer fiber film to the inner layer polycaprolactone compact film through an electrostatic spinning technology by using a rotary receiver with the Ni-Ti memory esophageal stent with the surface provided with the inner layer polycaprolactone compact film as an electrostatic spinning device with a mixed liquid obtained through blending and dissolving an organic polymer material and an anticancer drug in an organic solvent as the solution for making the outer layer fiber film to obtain a dilayer compounding coating with an esophageal cancer treatment function. The dilayer compounding coating is obtained through compounding the outer layer fiber film with the inner layer polycaprolactone compact film when the organic solvent does not volatilize completely, and two layers are tightly adhered to each other. The dilayer compounding coated esophageal stent improves the cell compatibility of film materials, and also realizes the controlled release of drugs; and the method has the advantages of simplicity, easy operation and low cost.
Description
Technical field
The present invention relates to the preparation of Multi-functional food pipe holder overlay film, be specifically related to the preparation method of the Esophageal Stent of the two-layer compound overlay film with auxiliary treatment esophageal carcinoma function.
Background technology
The esophageal carcinoma is a kind of common digestive tract tumor, and the whole world about has 310,000 people to die from the esophageal carcinoma every year, wherein 160,000 betides China.The classical symptom of the esophageal carcinoma is Progressive symmetric erythrokeratodermia dysphagia, and this can cause patient to become thin gradually, directly reduces the quality of life of patient, even dead.Because the early symptom of the esophageal carcinoma is not obvious, when making a definite diagnosis, cancerous cell may be in middle and late stage or spread, and in addition, the lesion volume scope of some patient is comparatively large, so, approximately only have 50% patient to be applicable to excision.So in order to feed, the dysdipsia of reduction of patient, implanting Esophageal Stent is a kind of very important palliative treatment.
Esophageal Stent is divided into bare bracket and is coated with the overlay film frame of particularity membrane material.Compared to bare bracket, overlay film frame can effectively stop hyperplastic tissue to grow to internal stent, and after esophagostenosis is alleviated, is convenient to take out, so the covering material on overlay film frame needs to have good mechanical property and biocompatibility.On this basis, anticarcinogen is joined in the overlay film of overlay film frame, both the effect of general overlay film frame can have been played, also can locally to fix a point slow releasing pharmaceutical, reach auxiliary effect of killing cancerous cell more rapidly and effectively, more targeted more than general intravenous injection anticarcinogen, utilization rate is higher.
In conjunction with the medical present situation of China, the overlay film frame with the auxiliary treatment esophageal carcinoma of a kind of implantable focal zone of current urgent need, and require that this overlay film can either well adhere on metal rack, also pulling wound in support taking-up process can be avoided to cause secondary injury, reach the adjuvant treatment effect to the esophageal carcinoma simultaneously.
Summary of the invention
The object of the invention is for the deficiencies in the prior art, a kind of preparation method with the Esophageal Stent of the two-layer compound overlay film of auxiliary treatment esophageal carcinoma function is provided.
First the present invention prepares the solution of preparation inner compact layer film, and obtains inner compact layer film by the surface that the method for solution plastic film mulch remembers Esophageal Stent at Ni-Ti; Then the mixed solution that obtains in organic solvent is dissolved in for preparing the solution of outer layer fiber film with high-molecular organic material and cancer therapy drug blended, the Ni-Ti of inner compact layer film is had to remember the rotating receiver that Esophageal Stent is electrospinning device with surface, utilize electrostatic spinning technique to spin on inner compact layer film by the fibrous membrane that the solution by outer layer fiber film obtains, obtain the two-layer compound overlay film with treatment esophageal carcinoma function thus; This two-layer compound overlay film is not yet evaporated completely full-time being composited by outer layer fiber film and inner compact layer film at organic solvent, and laminating closely.The two-layer compound overlay film with the Esophageal Stent of the two-layer compound overlay film of auxiliary treatment esophageal carcinoma function obtained by this preparation method is made up of inner compact layer film and outer layer fiber film, its inner compact layer film can be good at adhering on metal rack, and outer layer fiber film is by the mixed solution containing organic polymer and cancer therapy drug, employing electrostatic spinning technique is made, the mechanical property of the fibrous material of the softness of this outer layer fiber film is more weak, can avoid causing secondary injury to wound in the taking-up process of support; The release of cancer therapy drug can also be controlled in addition.
The preparation method with the Esophageal Stent of the two-layer compound overlay film of auxiliary treatment esophageal carcinoma function of the present invention comprises the steps:
(1) prepare polycaprolactone (PCL) inner layer film solution: be dissolved in by polycaprolactone in organic solvent, be mixed with the solution that concentration is 10 ~ 20%w/v, stirring at room temperature (general stirring 3 hours) evenly;
(2) internal layer polycaprolactone (PCL) dense film is prepared: solution step (1) obtained falls in culture dish, the Ni-Ti of compression memory Esophageal Stent is placed in this culture dish roll, until the surface uniform that polycaprolactone solution remembers Esophageal Stent at the Ni-Ti of this compression covers; The Ni-Ti discharging this compression remembers Esophageal Stent, and make the Ni-Ti of compression remember Esophageal Stent and return to original length, the surface remembering Esophageal Stent at Ni-Ti obtains internal layer polycaprolactone dense film;
(3) mixed liquor of outer layer fiber film is prepared: be dissolved in by high-molecular organic material in organic solvent, be mixed with the solution that concentration is 9 ~ 15%w/v, add cancer therapy drug, stirring at room temperature (general stirring 12 hours) evenly, obtains mixed liquor;
(4) two-layer compound overlay film is prepared: mixed liquor step (3) obtained injects the syringe of electrospinning device, add that in the front end of syringe diameter is the rustless steel syringe needle of 0.3 ~ 0.7mm, the Ni-Ti returning to original length obtained with step (2) remembers Esophageal Stent for rotating receiver; Be 12 ~ 25kv at voltage, solution flow rate is 3 ~ 8ml/h, rotating receiver distance rustless steel syringe needle is carry out electrostatic spinning under the condition of 10 ~ 25cm, the two-layer compound overlay film that the fibrous membrane that the surface remembering Esophageal Stent at Ni-Ti thus obtains containing high-molecular organic material and cancer therapy drug by internal layer polycaprolactone dense film and skin is formed; Room temperature in vacuo drying (time of general room temperature in vacuo drying is 24 ~ 48 hours), removes residual organic solvent, obtain the Esophageal Stent of the two-layer compound overlay film with auxiliary treatment esophageal carcinoma function.This Esophageal Stent with the two-layer compound overlay film of auxiliary treatment esophageal carcinoma function is preserved in 4 DEG C of drying baker.
Add cancer therapy drug described in step (3), to be the mass values being high-molecular organic material in the solution of 9 ~ 15%w/v according to the quality of cancer therapy drug and concentration be for the addition of its cancer therapy drug 3 ~ 15% to add cancer therapy drug.
The thickness of the outer layer fiber film of described two-layer compound overlay film is 30 ~ 150 μm.
The thickness of the inner compact layer film of described two-layer compound overlay film is 10 ~ 80 μm.
Described high-molecular organic material is selected from one or more in poly lactic coglycolic acid (PLGA), polycaprolactone (PCL), gelatin (GT).The weight average molecular weight of described PCL is 50,000 ~ 200,000.
The weight average molecular weight of described PLGA is 50,000 ~ 200,000.
Described cancer therapy drug is selected from the one in paclitaxel, amycin, 5-fluorouracil etc.
Described organic solvent be selected from DMF, acetone, trifluoroethanol, hexafluoroisopropanol, oxolane, chloroform, dichloromethane, dimethyl sulfoxide one or both.
Described electrospinning device is many spinning heads electrostatic spinning machine.
Beneficial effect of the present invention: the Esophageal Stent of prepared by the present invention the have two-layer compound overlay film of auxiliary treatment esophageal carcinoma function, inner compact layer film can be good at adhering on metal rack, and the mechanical property of the fibrous material of the softness of outer layer fiber film is more weak, secondary injury can not be caused to wound in the taking-up process of Esophageal Stent.In two-layer compound overlay film, load has cancer therapy drug, by regulating and controlling the ratio of high-molecular organic material, also achieves the Co ntrolled release of medicine while the cell compatibility improving membrane material; And make cancer therapy drug in this two-layer compound covering material when maintaining the lasting lethal effect to cancerous cell, less to Normocellular injury.This have the technique of the preparation method of the Esophageal Stent of the two-layer compound overlay film of auxiliary treatment esophageal carcinoma function simple, be easy to operation and cost is low, have wide practical use.
Detailed description of the invention
Below by specific embodiment, the present invention is described in further detail; but should not be understood as limiting the scope of the invention; all based on above-mentioned technological thought, the amendment utilizing ordinary skill knowledge and customary means to make, replacement, change all belong to scope of the present invention.
Embodiment 1
(1) polycaprolactone (PCL, weight average molecular weight is 100,000) inner layer film solution is prepared: be dissolved in by PCL in oxolane, be mixed with the solution that concentration is 10%w/v, stirring at room temperature 3 hours;
(2) internal layer PCL dense film is prepared: solution step (1) obtained falls in culture dish, the Ni-Ti of compression memory Esophageal Stent is placed in this culture dish roll, until the surface uniform that PCL solution remembers Esophageal Stent at the Ni-Ti of this compression covers; To take out and the Ni-Ti discharging this compression remembers Esophageal Stent, make the Ni-Ti of compression remember Esophageal Stent and return to original length, remember the surface of Esophageal Stent at Ni-Ti and obtain the internal layer polycaprolactone dense film that thickness is about 10 μm;
(3) mixed liquor of outer layer fiber film is prepared: by PLGA (weight average molecular weight is 80,000), PCL (weight average molecular weight is 200,000) and GT, the ratio being 10:2.5:5 with the mass ratio of PLGA:PCL:GT is dissolved in hexafluoroisopropanol jointly, be mixed with the solution that concentration is 11%w/v, add paclitaxel, stirring at room temperature 12 hours, obtains the mixed liquor of mix homogeneously; To be the ratio being the gross mass of PLGA, PCL and GT solute in the solution of 11%w/v according to the quality of paclitaxel and concentration be for the addition of its paclitaxel 10% to add paclitaxel;
(4) two-layer compound overlay film is prepared: the mixed liquor of mix homogeneously step (3) obtained injects the syringe of many spinning heads electrostatic spinning machine, add that in the front end of syringe diameter is the rustless steel syringe needle of 0.5mm, the Ni-Ti returning to original length obtained with step (2) remembers Esophageal Stent for rotating receiver; Be 20kv at voltage, solution flow rate is 5ml/h, rotating receiver distance rustless steel syringe needle is carry out electrostatic spinning under the condition of 20cm, the two-layer compound overlay film that the fibrous membrane that the surface remembering Esophageal Stent at Ni-Ti thus obtains containing PLGA, PCL, GT and paclitaxel by internal layer polycaprolactone dense film and skin is formed, and the thickness of outer layer fiber film is about 150 μm; Room temperature in vacuo drying 48 hours, remove residual organic solvent, obtain the Esophageal Stent of the two-layer compound overlay film with auxiliary treatment esophageal carcinoma function.This Esophageal Stent with the two-layer compound overlay film of auxiliary treatment esophageal carcinoma function is preserved in 4 DEG C of drying baker.
Embodiment 2
(1) polycaprolactone (PCL, weight average molecular weight is 100,000) inner layer film solution is prepared: be dissolved in by PCL in oxolane, be mixed with the solution that concentration is 15%w/v, stirring at room temperature 3 hours;
(2) internal layer PCL dense film is prepared: solution step (1) obtained falls in culture dish, the Ni-Ti of compression memory Esophageal Stent is placed in this culture dish roll, until the surface uniform that PCL solution remembers Esophageal Stent at the Ni-Ti of this compression covers; To take out and the Ni-Ti discharging this compression remembers Esophageal Stent, make the Ni-Ti of compression remember Esophageal Stent and return to original length, remember the surface of Esophageal Stent at Ni-Ti and obtain the internal layer polycaprolactone dense film that thickness is about 50 μm;
(3) mixed liquor of outer layer fiber film is prepared: by PLGA (weight average molecular weight is 200,000), PCL (weight average molecular weight is 100,000) and GT, the ratio being 10:2.5:1 with the mass ratio of PLGA:PCL:GT is dissolved in hexafluoroisopropanol jointly, be mixed with the solution that concentration is 9%w/v, add paclitaxel, stirring at room temperature 12 hours, obtains the mixed liquor of mix homogeneously; To be the ratio being the gross mass of PLGA, PCL and GT in the solution of 9%w/v according to the quality of paclitaxel and concentration be for the addition of its paclitaxel 3% to add paclitaxel;
(4) two-layer compound overlay film is prepared: the mixed liquor of mix homogeneously step (3) obtained injects the syringe of many spinning heads electrostatic spinning machine, add that in the front end of syringe diameter is the rustless steel syringe needle of 0.3mm, the Ni-Ti returning to original length obtained with step (2) remembers Esophageal Stent for rotating receiver; Be 12kv at voltage, solution flow rate is 3ml/h, rotating receiver distance rustless steel syringe needle is carry out electrostatic spinning under the condition of 10cm, the two-layer compound overlay film that the fibrous membrane that the surface remembering Esophageal Stent at Ni-Ti thus obtains containing PLGA, PCL, GT and paclitaxel by internal layer polycaprolactone dense film and skin is formed, and the thickness of outer layer fiber film is about 100 μm; Room temperature in vacuo drying 48 hours, remove residual organic solvent, obtain the Esophageal Stent of the two-layer compound overlay film with auxiliary treatment esophageal carcinoma function.This Esophageal Stent with the two-layer compound overlay film of auxiliary treatment esophageal carcinoma function is preserved in 4 DEG C of drying baker.
Embodiment 3
(1) polycaprolactone (PCL, weight average molecular weight is 50,000) inner layer film solution is prepared: be dissolved in by PCL in dichloromethane, be mixed with the solution that concentration is 20%w/v, stirring at room temperature 3 hours;
(2) internal layer PCL dense film is prepared: solution step (1) obtained falls in culture dish, the Ni-Ti of compression memory Esophageal Stent is placed in this culture dish roll, until the surface uniform that PCL solution remembers Esophageal Stent at the Ni-Ti of this compression covers, take out and discharge this compression Ni-Ti remember Esophageal Stent, make the Ni-Ti of compression remember Esophageal Stent and return to original length, the surface remembering Esophageal Stent at Ni-Ti obtains the internal layer polycaprolactone dense film that thickness is about 80 μm;
(3) mixed liquor of outer layer fiber film is prepared: by PLGA (weight average molecular weight is 50,000), PCL (weight average molecular weight is 200,000) and GT, the ratio being 10:2.5:1 with the mass ratio of PLGA:PCL:GT is dissolved in hexafluoroisopropanol jointly, be mixed with the solution that concentration is 15%w/v, add paclitaxel, stirring at room temperature 12 hours, obtains the mixed liquor of mix homogeneously; To be the ratio being the gross mass of PLGA, PCL and GT solute in the solution of 15%w/v according to the quality of paclitaxel and concentration be for the addition of its paclitaxel 3% to add paclitaxel;
(4) two-layer compound overlay film is prepared: the mixed liquor of mix homogeneously step (3) obtained injects the syringe of many spinning heads electrostatic spinning machine (specification is 5ml), add that in the front end of syringe diameter is the rustless steel syringe needle of 0.7mm, the Ni-Ti returning to original length obtained with step (2) remembers Esophageal Stent for rotating receiver; Be 25kv at voltage, solution flow rate is 8ml/h, rotating receiver distance rustless steel syringe needle is carry out electrostatic spinning under the condition of 25cm, the two-layer compound overlay film that the fibrous membrane that the surface remembering Esophageal Stent at Ni-Ti thus obtains containing PLGA, PCL, GT and paclitaxel by internal layer polycaprolactone dense film and skin is formed, and the thickness of outer layer fiber film is about 50 μm; Room temperature in vacuo drying 48 hours, remove residual organic solvent, obtain the Esophageal Stent of the two-layer compound overlay film with auxiliary treatment esophageal carcinoma function.This Esophageal Stent with the two-layer compound overlay film of auxiliary treatment esophageal carcinoma function is preserved in 4 DEG C of drying baker.
Embodiment 4
(1) polycaprolactone (PCL, weight average molecular weight is 200,000) inner layer film solution is prepared: be dissolved in by PCL in oxolane, be mixed with the solution that concentration is 10%w/v, stirring at room temperature 3 hours;
(2) internal layer PCL dense film is prepared: solution step (1) obtained falls in culture dish, the Ni-Ti of compression memory Esophageal Stent is placed in this culture dish roll, until the surface uniform that PCL solution remembers Esophageal Stent at the Ni-Ti of this compression covers, take out and discharge this compression Ni-Ti remember Esophageal Stent, make the Ni-Ti of compression remember Esophageal Stent and return to original length, the surface remembering Esophageal Stent at Ni-Ti obtains the internal layer polycaprolactone dense film that thickness is about 30 μm;
(3) mixed liquor of outer layer fiber film is prepared: by PLGA (weight average molecular weight is 100,000) and PCL (weight average molecular weight is 100,000), the ratio being 4:1 with the mass ratio of PLGA:PCL to be dissolved in the mixed solvent of oxolane, chloroform and DMF composition in (volume ratio is 2:1:2) jointly, be mixed with the solution that concentration is 15%w/v, add 5-fluorouracil, stirring at room temperature 12 hours, obtains the mixed liquor of mix homogeneously; To be the ratio being the gross mass of PLGA and PCL solute in the solution of 15%w/v according to the quality of 5-fluorouracil and concentration be for the addition of its 5-fluorouracil 5% to add 5-fluorouracil;
(4) two-layer compound overlay film is prepared: the mixed liquor of mix homogeneously step (3) obtained injects the syringe of many spinning heads electrostatic spinning machine, add that in the front end of syringe diameter is the rustless steel syringe needle of 0.5mm, the Ni-Ti returning to original length obtained with step (2) remembers Esophageal Stent for rotating receiver; Be 20kv at voltage, solution flow rate is 5ml/h, rotating receiver distance rustless steel syringe needle is carry out electrostatic spinning under the condition of 25cm, the two-layer compound overlay film that the fibrous membrane that the surface remembering Esophageal Stent at Ni-Ti thus obtains containing PLGA, PCL and 5-fluorouracil by internal layer polycaprolactone dense film and skin is formed, and the thickness of outer layer fiber film is about 100 μm; Room temperature in vacuo drying 48 hours, remove residual organic solvent, obtain the Esophageal Stent of the two-layer compound overlay film with auxiliary treatment esophageal carcinoma function.This Esophageal Stent with the two-layer compound overlay film of auxiliary treatment esophageal carcinoma function is preserved in 4 DEG C of drying baker.
Embodiment 5
(1) polycaprolactone (PCL, weight average molecular weight is 200,000) inner layer film solution is prepared: be dissolved in by PCL in oxolane, be mixed with the solution that concentration is 12%w/v, stirring at room temperature 3 hours;
(2) internal layer PCL dense film is prepared: solution step (1) obtained falls in culture dish, the Ni-Ti of compression memory Esophageal Stent is placed in this culture dish roll, until the surface uniform that PCL solution remembers Esophageal Stent at the Ni-Ti of this compression covers, take out and discharge this compression Ni-Ti remember Esophageal Stent, make the Ni-Ti of compression remember Esophageal Stent and return to original length, the surface remembering Esophageal Stent at Ni-Ti obtains the internal layer polycaprolactone dense film that thickness is about 30 μm;
(3) mixed liquor of outer layer fiber film is prepared: be dissolved in hexafluoroisopropanol by PLGA (weight average molecular weight is 150,000), be mixed with the solution that concentration is 12%w/v, add paclitaxel, stirring at room temperature 12 hours, obtains the mixed liquor of mix homogeneously; To be the ratio being the quality of PLGA solute in the solution of 12%w/v according to the quality of paclitaxel and concentration be for the addition of its paclitaxel 10% to add paclitaxel;
(4) two-layer compound overlay film is prepared: the mixed liquor of mix homogeneously step (3) obtained injects the syringe of many spinning heads electrostatic spinning machine, add that in the front end of syringe diameter is the rustless steel syringe needle of 0.5mm, the Ni-Ti returning to original length obtained with step (2) remembers Esophageal Stent for rotating receiver; Be 20kv at voltage, solution flow rate is 5ml/h, rotating receiver distance rustless steel syringe needle is carry out electrostatic spinning under the condition of 20cm, the two-layer compound overlay film that the fibrous membrane that the surface remembering Esophageal Stent at Ni-Ti thus obtains containing PLGA and paclitaxel by internal layer PCL dense film and skin is formed, and the thickness of outer layer fiber film is about 150 μm; Room temperature in vacuo drying 26 hours, remove residual organic solvent, obtain the Esophageal Stent of the two-layer compound overlay film with auxiliary treatment esophageal carcinoma function.This Esophageal Stent with the two-layer compound overlay film of auxiliary treatment esophageal carcinoma function is preserved in 4 DEG C of drying baker.
Claims (10)
1. have a preparation method for the Esophageal Stent of the two-layer compound overlay film of auxiliary treatment esophageal carcinoma function, it is characterized in that, described preparation method comprises the steps:
(1) prepare polycaprolactone inner layer film solution: be dissolved in by polycaprolactone in organic solvent, be mixed with the solution that concentration is 10 ~ 20%w/v, stirring at room temperature is even;
(2) internal layer polycaprolactone dense film is prepared: solution step (1) obtained falls in culture dish, the Ni-Ti of compression memory Esophageal Stent is placed in this culture dish roll, until the surface uniform that polycaprolactone solution remembers Esophageal Stent at the Ni-Ti of this compression covers; The Ni-Ti discharging this compression remembers Esophageal Stent, and make the Ni-Ti of compression remember Esophageal Stent and return to original length, the surface remembering Esophageal Stent at Ni-Ti obtains internal layer polycaprolactone dense film;
(3) prepare the mixed liquor of outer layer fiber film: be dissolved in by high-molecular organic material in organic solvent, be mixed with the solution that concentration is 9 ~ 15%w/v, add cancer therapy drug, stirring at room temperature is even, obtains mixed liquor;
(4) two-layer compound overlay film is prepared: mixed liquor step (3) obtained injects the syringe of electrospinning device, add that in the front end of syringe diameter is the rustless steel syringe needle of 0.3 ~ 0.7mm, the Ni-Ti returning to original length obtained with step (2) remembers Esophageal Stent for rotating receiver; Be 12 ~ 25kv at voltage, solution flow rate is 3 ~ 8ml/h, rotating receiver distance rustless steel syringe needle is carry out electrostatic spinning under the condition of 10 ~ 25cm, the two-layer compound overlay film that the fibrous membrane obtaining containing high-molecular organic material and cancer therapy drug by internal layer polycaprolactone dense film and skin on the surface that Ni-Ti remembers Esophageal Stent is formed; Dry at room temperature in vacuo, remove residual organic solvent, obtain the Esophageal Stent of the two-layer compound overlay film with auxiliary treatment esophageal carcinoma function.
2. preparation method according to claim 1, it is characterized in that: add cancer therapy drug described in step (3), to be the mass values being high-molecular organic material in the solution of 9 ~ 15%w/v according to the quality of cancer therapy drug and concentration be for the addition of its cancer therapy drug 3 ~ 15% to add cancer therapy drug.
3. preparation method according to claim 1, is characterized in that: the thickness of the outer layer fiber film of described two-layer compound overlay film is 30 ~ 150 μm.
4. preparation method according to claim 1, is characterized in that: the thickness of the inner compact layer film of described two-layer compound overlay film is 10 ~ 80 μm.
5. preparation method according to claim 1 and 2, is characterized in that: described high-molecular organic material is selected from one or more in poly lactic coglycolic acid, polycaprolactone, gelatin.
6. preparation method according to claim 1, is characterized in that: the weight average molecular weight of described polycaprolactone is 50,000 ~ 200,000.
7. preparation method according to claim 5, is characterized in that: the weight average molecular weight of described polycaprolactone is 50,000 ~ 200,000.
8. preparation method according to claim 5, is characterized in that: the weight average molecular weight of described poly lactic coglycolic acid is 50,000 ~ 200,000.
9. preparation method according to claim 1 and 2, is characterized in that: described cancer therapy drug is selected from the one in paclitaxel, amycin, 5-fluorouracil.
10. preparation method according to claim 1, is characterized in that: described organic solvent be selected from DMF, acetone, trifluoroethanol, hexafluoroisopropanol, oxolane, chloroform, dichloromethane, dimethyl sulfoxide one or both.
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