CN104353128A - Degradable intravascular stent and preparation method and application thereof - Google Patents
Degradable intravascular stent and preparation method and application thereof Download PDFInfo
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- CN104353128A CN104353128A CN201410442884.6A CN201410442884A CN104353128A CN 104353128 A CN104353128 A CN 104353128A CN 201410442884 A CN201410442884 A CN 201410442884A CN 104353128 A CN104353128 A CN 104353128A
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Abstract
The invention relates to a degradable intravascular stent which adopts a hollow tubular structure formed by integrally embedding an acylated chitin membrane and degradable fibers, wherein the tube wall comprises the acylated chitin membrane and the degradable fibers, which are integrally embedded; the fibers are embedded or inlaid into the membrane; a transparent hole or pattern structure is arranged on the tube wall, or the transparent hole or pattern structure is not arranged on the tube wall.
Description
Technical field
The invention belongs to biomedical materials field, relate to a kind of vascular stent material, particularly relate to a kind of degradable blood vessel bracket material and its preparation method and application.
Background technology
Intravascular stent is applied to the narrow or embolotherapy of vessel lumen that angiopathy causes, thus it is unobstructed with the object reaching improvement or disease therapy to improve blood flow.The intravascular stent mainly metallic blood vessel bracket of current Clinical practice, metallic blood vessel bracket is applied to blood vessel can meet supporting role to lumen of vessels, but metal material can not be degraded, in body, longer-term persistence has the risk of vascular restenosis or thromboembolism, and metallic stent material can not be taken out, bring obstacle to the treatment again of original position.Degradable blood vessel bracket is the important directions of intravascular stent research, desirable degradable blood vessel bracket can keep enough mechanical strengths and radial support effect in certain hour in vivo, and along with the reparation of lesion vessels, degradable blood vessel bracket is finally degraded and absorbed, and avoids longer-term persistence in vivo.Studies have reported that with the degradable blood vessel bracket of the chemical macromolecular material manufactures such as polylactic acid, polylactide, PGA, can degradation in vivo absorb, but its acid degradation thing produced during degraded in organizing can produce certain aseptic inflammation reaction.
The bioabsorbable polymer material source organism such as chitin, chitosan, fibroin albumen, alginic acid, compare with chemical macromolecular material, belong to natural material, have better biological safety, have a wide range of applications in degradable biomaterial research.Chitin is a kind of natural macromolecule amylose, and water insoluble and general soda acid solvent, dissolves in minority organic solvent, as trichloroacetic acid, dichloroacetic acid, hexafluoroisopropanol, dimethyl formamide-LiCl etc., is also dissolvable in water low temperature NaOH-aqueous solution of urea system.Due to deliquescent restriction, there is technical difficulty in it in actual applications.The catabolite of chitin is micromolecular amino-oligosacchride or amino monosaccharide, is easily absorbed by body.These bioabsorbable polymer materials are widely used in degradable biomaterial research, its physicochemical characteristics and its biological degradability etc., all carry out modification by chemical modification, or bioabsorbable polymer material different from other mixes or compound, thus more preferably met the bioabsorbable polymer material of different tissues reparation needs.
Summary of the invention
Degradable blood vessel bracket material that the object of this invention is to provide a kind of natural biologic material and its preparation method and application, to make up the above-mentioned deficiency of prior art.
For achieving the above object, the present invention is achieved by the following technical solutions:
A kind of degradable blood vessel bracket, it is characterized in that embedding by degradable polysaccharide film and biodegradable fiber the hollow tubular structure be integrally formed, the degradable polysaccharide film that tube wall is integrated by embedding and biodegradable fiber form, wherein fiber is embedded in the inside of film, in other words, fiber is embedded in the inside of film, and tube wall has penetrating pore space structure or patterning.
A kind of degradable blood vessel bracket; it is characterized in that embedding by acyl group chitin film and biodegradable fiber the hollow tubular structure be integrally formed; the acyl group chitin film that tube wall is integrated by embedding and biodegradable fiber form; wherein fiber is embedded or is embedded in the inside of film, and tube wall is with or without penetrating pore space structure or patterning.
The preparation method of above-mentioned a kind of degradable blood vessel bracket, it is characterized in that: acyl group chitin is dissolved in solvent, preparation concentration expressed in percentage by weight is the acyl group chitin colloid solution of 1.0% ~ 15.0%, or acyl group chitin is dissolved in solvent, add anticoagulant composition, prepare the acyl group chitin colloid solution that the concentration expressed in percentage by weight containing anticoagulant composition is 1.0% ~ 15.0%; Open the tuber being connected with Pipe making mold, by acyl group chitin colloid solution, coating is surperficial at the Pipe making mold of axial rotation equably, controls glue thickness at 50 μm ~ 1000 μm, room temperature or temperature control heat drying film forming; Biodegradable fiber is arranged in or is wrapped on the film of Pipe making mold, or by the woven sheath of biodegradable fiber on the film of Pipe making mold; Open and rotate, continue by acyl group chitin colloid solution uniform coating on the fiber of the Pipe making mold rotated, control glue thickness at 60 μm ~ 1000 μm, room temperature or temperature control heat drying film forming, fiber is embedded or is embedded in the inside of film; Pipe making mold is put into dilute alkaline aqueous solution or ethanol water soaks together with the tubular material of preparation, de-pipe, washing, dehydration, drying, the intravascular stent tubing that obtained intraluminal diameter is 1.5 ~ 12mm, pipe thickness is the hollow tubular structure of 50 μm ~ 1000 μm; Intravascular stent tubing is through Laser cutting or machine cuts processing, and obtained tube wall is with or without penetrating pore space structure or the degradable blood vessel bracket of patterning.
Above-mentioned degradable blood vessel bracket by Operation body or interventional therapeutic technique implant, the application in the vessel lumen that causes for the treatment of angiopathy in narrow or blood vessel embolism.
Advantage of the present invention and technique effect are: degradable blood vessel bracket of the present invention has good mechanical strength, the raw material preparing degradable blood vessel bracket tubing is all biodegradation materials, the degradable blood vessel bracket prepared thus can by organism degrades, and body does not have long-term foreign body to retain; Do not add the chemical compositions such as plasticizer, cross-linking agent or catalyst in degradable blood vessel bracket preparation, there is good biocompatibility and biological safety; It is better functional that degradable blood vessel bracket is applied to enforcement in animal body, is conducive to keeping the unobstructed of blood flow.Degradable blood vessel bracket of the present invention, can by Operation body or interventional technique implant, be applied to the narrow or embolotherapy of vessel lumen that angiopathy causes, along with the reparation of lesion vessels, degradable blood vessel bracket is finally degraded, and avoids longer-term persistence in vivo.
Accompanying drawing explanation
The growth of accompanying drawing 1.HUVEC cell on acyl group chitin diaphragm
The growth of accompanying drawing 2.HUVEC cell on fibroin albumen diaphragm
The growth of accompanying drawing 3.HUVEC cell on polylactic acid diaphragm
The growth of accompanying drawing 4.HUVEC cell on chitosan diaphragm
Detailed description of the invention
Embodiment 1
A kind of degradable blood vessel bracket, it is characterized in that embedding by degradable polysaccharide film and biodegradable fiber the hollow tubular structure be integrally formed, the degradable polysaccharide film that tube wall is integrated by embedding and biodegradable fiber form, wherein fiber is embedded in the inside of film, in other words, fiber is embedded in the inside of film, and tube wall has penetrating pore space structure or patterning.
Described degradable polysaccharide film, is characterized in that acyl group chitin polysaccharide membrane; The molecular structural formula of described acyl group chitin is:
In formula, R
1, R
2or R
3h, acetyl group (-C
2h
3o), propiono (-C
3h
5o), bytyry (-C
4h
7o), caproyl (-C
6h
11or caprylyl (-C O)
8h
15o) one or more in, n is greater than 50; The acyl group degree of acyl group chitin is more than or equal to 75%, and the acyl group quantity namely on average in every 100 sugar units is more than or equal to 75, and the position of acyl group is C6-O position, C3-O position or C2-N position; Described acyl group is one or more in acetyl group, propiono, bytyry, caproyl or caprylyl, and described acyl group degree is the summation that acyl group chitin comprises one or more the acyl group degree in acetyl group, propiono, bytyry, caproyl or caprylyl.
Described biodegradable fiber, is characterized in that by alginic acid fibre, cellulose acetate fibre or silkworm fibroin fiber; Above-mentioned biodegradable fiber through arrangement, be wound around or braiding, be embedded or be embedded in acyl group chitin polysaccharide membrane inside become be integrated, as the muscles and bones of film, to strengthen mechanical strength and the radial support power of degradable blood vessel bracket.
Described hollow tubular structure, is characterized in that the interior diameter of tube chamber is 1.5 ~ 12mm, and the thickness of tube wall is 50 μm ~ 1000 μm.
The screening of embodiment 2 degradable blood vessel bracket membrane material:
(1) preparation of diaphragm:
The preparation of chitosan diaphragm: take chitosan powder (deacetylation 95%) 3g, adds the acetum 97ml that concentration expressed in percentage by weight is 2%, stirring and dissolving, is mixed with the chitosan gum liquid solution that concentration expressed in percentage by weight is 3%.Take 15g chitosan gum liquid solution and be placed in the PP square plate that the length of side is 50mm × 50mm, standing and drying in ventilating kitchen.The diaphragm of drying is placed in immersion, acid-base neutralization in the NaOH aqueous solution (concentration expressed in percentage by weight, lower same) of 2%, is washed to pH neutrality, pave on glass plate dry, obtained chitosan diaphragm.
The preparation of acyl group chitin diaphragm: take chitin powder 30g; add in glass reaction container; add acylating reagent solution of acetic anhydride 50mL; add methanol 250ml; stir, control temperature is 0 DEG C, then adds the perchloric acid solution (concentration expressed in percentage by weight of 70%; down together) 1.5ml is as catalyst, stirring reaction 48h.Reaction is finished, and filters, solid-liquid separation; solid content is put into the NaOH aqueous solution of 5%; acid-base neutralization, centrifugal, solid-liquid separation; solid content water washing desalination; 95% ethanol (volume fraction, lower same) dehydration, 50 DEG C of heat dryings; obtain acyl group chitin, it is 125% that elemental microanalysis method records its degree of acetylation.Take the acyl group chitin powder 3.05g that degree of acetylation is 125%; add the formic acid solution (concentration expressed in percentage by weight of 80%; lower same) 82ml (proportion 1.18), stirring and dissolving, is mixed with the acyl group chitin colloid solution that concentration expressed in percentage by weight is 3%.Take 15g acyl group chitin colloid solution and be placed in the PP square plate that the length of side is 50mm × 50mm, standing and drying in ventilating kitchen.The diaphragm of drying is placed in the NaOH aqueous solution immersion of 2%, acid-base neutralization, is washed to pH neutrality, pave on glass plate dry, obtained acyl group chitin diaphragm.
The preparation of fibroin protein film: take solubility fibroin albumen 3g, add distilled water 97ml, stirring and dissolving, is mixed with the fibroin albumen glue that concentration expressed in percentage by weight is 3%.Take 15g fibroin albumen glue and be placed in the rustless steel square plate that the length of side is 50mm × 50mm, standing and drying in ventilating kitchen, obtained fibroin albumen diaphragm.
The preparation of polylactic acid diaphragm: take soluble poly lactic acid 3g, adds chloroform soln 65ml (proportion 1.48), stirring and dissolving, is mixed with the polylactic acid glue that concentration expressed in percentage by weight is 3%.Take 15g polylactic acid glue and be placed in the rustless steel square plate that the length of side is 50mm × 50mm, standing and drying in ventilating kitchen.The ethanol water diaphragm of drying being placed in 60% soaks, washing, paves on glass plate dry, obtained polylactic acid diaphragm.
Respectively above-mentioned chitosan diaphragm, acyl group chitin diaphragm, fibroin albumen diaphragm and polylactic acid diaphragm are prepared into the disk that diameter is 6.4mm with the trepan that diameter is 6.4mm; it is soaking disinfection in the ethanol water of 75% in concentration expressed in percentage by weight; sterile distilled water washs; dry under aseptic condition, packaging; for subsequent use, obtained aseptic chitosan disk, acyl group chitin disk, fibroin albumen disk and polylactic acid disk respectively.
(2) the attaching growth fraction of vascular endothelial cell on diaphragm is comparatively:
Experiment is divided into 4 groups: chitosan diaphragm group, acyl group chitin diaphragm group, fibroin albumen diaphragm group and polylactic acid diaphragm group.Immersed in D-Hank ' s liquid by above-mentioned 4 kinds of aseptic disks respectively and soak 12h, 5 aseptic chitosan disks are aseptically laid in the bottom in 5 holes of 96 porocyte culture plates by chitosan diaphragm group respectively, obtain 5 hole chitosan diaphragm groups; Same method obtains 5 hole acyl group chitin diaphragm groups, 5 hole fibroin albumen diaphragm groups and 5 hole polylactic acid diaphragm groups.The Human umbilical vein endothelial cells (HUVEC cell) of exponential phase is adjusted cell density to 2 × 10 through trypsinization, the cleaning of D-Hank ' s liquid, DMEM culture medium (10% serum)
4individual/mL, obtains HUVEC cell suspension.By in the culture hole of the chitosan diaphragm group of cell suspension inoculation on 96 porocyte culture plates, acyl group chitin diaphragm group, fibroin albumen diaphragm group and polylactic acid diaphragm group, every hole adds cell suspension 200uL, at 37 DEG C, and 5%CO
2quiescent culture 72h in incubator, observes the attaching growing state of each group of cell, and takes pictures.
Experimental result is shown by Figure of description, HUVEC cell through the cultivation of 72h, the attaching growing state of cell on acyl group chitin diaphragm best (Fig. 1), cell attachment stretches, and form is normal, sharpness of border, in normal growth state, cell quantity is many; The attaching growing state of cell on fibroin albumen diaphragm takes second place (Fig. 2), the adherent stretching, extension of most cells, and form is normal, and have a few cell spherical in shape, do not stretch, cell quantity is many; The attaching growing state of cell on polylactic acid diaphragm not good (Fig. 3), about half cell attachment stretches, and normal under form, about one semicell is spherical in shape, not adherent; The attaching growing state of cell on chitosan diaphragm poor (Fig. 4), cell is spherical in shape not adherent, and on diaphragm, cell quantity is few.The attaching growth result display of cell on 4 kinds of diaphragms, the growth result of HUVEC cell on acyl group chitin diaphragm is best, and fibroin albumen diaphragm effect is taken second place, and again, chitosan diaphragm effect is poor for polylactic acid diaphragm effect.
Intravascular stent is the key solving vascular restenosis at the endothelialization of blood vessel patient part; what grow from above-mentioned 4 kinds of diaphragms the attaching of vascular endothelial cell affects result; acyl group chitin diaphragm effect in 4 kinds of diaphragms is best, and vascular endothelial cell can attach growth preferably on acyl group chitin diaphragm.Therefore select acyl group chitin diaphragm as the membrane material of degradable blood vessel bracket, vascular endothelial cell can be made to attach growth preferably.
The preparation of embodiment 3 degradable blood vessel bracket tubing 1:
Take chitosan powder 30g; add in glass reaction container; add acylating reagent solution of acetic anhydride 60mL; add methanol 120ml; the solid-to-liquid ratio (w/v) making reaction system is 1: 6, stirs, and controlling reaction temperature is 10 DEG C; add the perchloric acid solution 1.5ml of 70% as catalyst, stirring reaction 24h.Reaction is finished, and filter, solid-liquid separation, puts into the NaOH aqueous solution of 5%, acid-base neutralization by solid content, centrifugal, solid-liquid separation, solid content water washing desalination, 95% ethanol dehydration, 50 DEG C of heat dryings, and obtaining degree of acetylation is 78% acyl group chitin powder.
Take the acyl group chitin powder 3.05g that degree of acetylation is 78%; add hexafluoroisopropanol solution 62ml (proportion 1.60) and make solvent; low temperature dissolves, and is mixed with the acyl group chitin colloid solution (w/v is 4.9%) that concentration expressed in percentage by weight is 3.0%.Get the stainless steel bar Pipe making mold of length 10cm, diameter 10mm; end holds the Pipe making mold seam be connected on tuber; open tuber; stainless steel bar is rotated vertically; by acyl group chitin colloid solution, coating is surperficial at the stainless steel bar rotated equably; control glue thickness at 600 μm ~ 1000 μm, under room temperature, Rotary drying becomes acyl group chitin polysaccharide membrane.When glue drying and forming-film, stop the rotation, biodegradable fiber alginic acid fibre is axially arranged on the polysaccharide membrane of stainless steel bar equably along stainless steel bar, anchoring fiber two ends, open and rotate, continue acyl group chitin colloid solution uniform coating on the fiber of the stainless steel bar rotated, glue is by the infiltration of interfibrous gap ecto-entad, colloid solution and polysaccharide membrane are combined together, control glue thickness at 600 μm ~ 1000 μm, under room temperature, Rotary drying film forming, fiber is embedded or is embedded in the inside of acyl group chitin film, become to be integrated with film.After glue drying and forming-film, stop operating, take off above-mentioned stainless steel bar, together with the tubular material of preparation, the ethanol water putting into 40% soaks, de-pipe, tubular material through washing, ethanol dehydration, drying at room temperature, the degradable blood vessel bracket tubing 1 of obtained hollow tubular structure, its lumen diameter is 10mm, and pipe thickness is 810 μm.
Alginic acid fibre described in embodiment 3, can be but be not limited only to calcium alginate fibre, alginic acid zinc fiber and braided tube thereof.
The preparation of embodiment 4 degradable blood vessel bracket tubing 2:
Take chitosan powder 30g; add in glass reaction container; add acylating reagent propionic andydride solution 130mL; add methanol 110ml; the solid-to-liquid ratio (w/v) making reaction system is 1: 8, stirs, and controlling reaction temperature is 30 DEG C; add methanesulfonic acid solution 2.5ml as catalyst, stirring reaction 10h.Reaction is finished, and filter, solid-liquid separation, solid content adds in the KOH aqueous solution of 5% of ice bath, acid-base neutralization, and water washing is neutral to pH, and solid-liquid separation, 95% ethanol dehydration, 50 DEG C of heat dryings, obtaining propionating degree is 87% acyl group chitin powder.
Get the acyl group chitin powder 14g that propionating degree is 87%; the formic acid solution 70ml (proportion 1.17) adding 75% makes solvent; stirring and dissolving, is mixed with the acyl group chitin colloid solution (w/v is 20%) that concentration expressed in percentage by weight is 14.6%.Get the ceramic rod Pipe making mold of length 10cm, diameter 5mm; end holds the Pipe making mold seam be connected on tuber; open tuber; ceramic rod is rotated vertically; by acyl group chitin colloid solution equably coating rotate ceramic rod on the surface; control glue thickness at 200 μm ~ 400 μm, temperature control 40 ~ 50 DEG C, Rotary drying becomes acyl group chitin polysaccharide membrane.When glue drying and forming-film, stop the rotation, biodegradable fiber cellulose acetate fibre braided tube is enclosed within the polysaccharide membrane of ceramic rod equably along ceramic rod, fixing braided tube two ends, open and rotate, continue acyl group chitin colloid solution uniform coating in the cellulose acetate fibre braided tube of ceramic rod, glue is by the gap ecto-entad infiltration of fiber, colloid solution and polysaccharide membrane are combined together, control colloid thickness at 200 μm ~ 300 μm, temperature control 40 ~ 50 DEG C, Rotary drying film forming, fiber braided tube is embedded or is embedded in the inside of acyl group chitin film, become to be integrated with film.After glue drying and forming-film, stop operating, take off ceramic rod, together with the tubular material of preparation, the NaOH aqueous solution putting into 2% soaks, acid-base neutralization, de-pipe, tubular material is neutral to pH through water washing, ethanol dehydration, 50 ~ 60 DEG C of heat dryings, the degradable blood vessel bracket tubing 2 of obtained hollow tubular structure, its lumen diameter is 5mm, and pipe thickness is 350 μm.
The preparation of embodiment 5 degradable blood vessel bracket tubing 3:
Take chitosan powder 30g; add in glass reaction container; add acylating reagent butyryl oxide. solution 200mL; add methanol 100ml; the solid-to-liquid ratio (w/v) making reaction system is 1: 10, stirs, and controlling reaction temperature is 10 DEG C; add concentration expressed in percentage by weight be the sulfuric acid solution 2ml of 70% as catalyst, stirring reaction 48h.Reaction is finished, and filter, solid-liquid separation, solid content puts into the NaOH aqueous solution of 8%, acid-base neutralization, water washing desalination, solid-liquid separation, 95% ethanol dehydration, natural drying, and obtaining Butyrylation degree is 135% acyl group chitin powder.
Take the acyl group chitin powder 6.75g that Butyrylation degree is 135%; add concentration expressed in percentage by weight be 80% formic acid solution 82ml (proportion 1.18) make solvent; low temperature dissolves, and is mixed with the acyl group chitin colloid solution (w/v is 8.2%) that concentration expressed in percentage by weight is 6.5%.Get the PP rod Pipe making mold of length 10cm, diameter 4mm; end holds the Pipe making mold seam be connected on tuber; open tuber; PP rod is rotated vertically; by acyl group chitin colloid solution equably coating rotate PP rod surface on; control glue thickness at 600 μm ~ 800 μm, under room temperature, Rotary drying becomes acyl group chitin polysaccharide membrane.When glue drying and forming-film; stop the rotation; biodegradable fiber cellulose acetate fibre is axially arranged on the polysaccharide membrane of PP rod along PP rod equably; anchoring fiber two ends; open and rotate; continue acyl group chitin colloid solution uniform coating on the fiber of PP rod; glue is by the gap ecto-entad infiltration of fiber; colloid solution and polysaccharide membrane are combined together; control colloid thickness at 600 μm ~ 800 μm, under room temperature, Rotary drying film forming; fiber be embedded or be embedded in the inside of acyl group chitin film, becoming to be integrated with film.After glue drying and forming-film, stop operating, take off PP rod, together with the tubular material of preparation, the NaOH aqueous solution putting into 5% soaks, acid-base neutralization, de-pipe, tubular material is neutral to pH through water washing, ethanol dehydration, drying at room temperature, the degradable blood vessel bracket tubing 3 of obtained hollow tubular structure, its lumen diameter is 4mm, and pipe thickness is 520 μm.
At the cellulose acetate fibre described in embodiment 4 and embodiment 5, can be but be not limited to a cellulose acetate fibre, cellulose diacetate fibers or cellulose triacetate fiber.
The preparation of embodiment 6 degradable blood vessel bracket tubing 4:
Take chitin powder (degree of acetylation 86%) 30g that acetyl content is 86%; add in glass reaction container; add acylating reagent butyryl oxide. solution 200mL; add methanol 100ml; the solid-to-liquid ratio (w/v) making reaction system is 1: 10, stirs, and controlling reaction temperature is 0 DEG C; add concentration expressed in percentage by weight be the perchloric acid solution 2.5ml of 70% as catalyst, stirring reaction 72h.Reaction is finished, and filter, solid-liquid separation, puts into the NaOH aqueous solution of 8% by solid content; acid-base neutralization, solid-liquid separation, solid content water washing to center, 95% ethanol dehydration; natural drying, obtain the acyl group chitin powder of acyl group degree 205%, wherein degree of acetylation 86%, Butyrylation degree is 119%.
Get the acyl group chitin powder 1.2g that acylation degree is 205%, add tetrahydrofuran solution 80ml (proportion 0.89) and make solvent, stirring and dissolving, preparation concentration expressed in percentage by weight is the acyl group chitin colloid solution (w/v is 1.5%) of 1.6%.Get the stainless steel bar Pipe making mold of length 10cm, diameter 3mm; end holds the Pipe making mold seam be connected on tuber; open tuber; stainless steel bar is rotated vertically; by acyl group chitin colloid solution, coating is surperficial at the stainless steel bar rotated equably; control glue thickness at 200 μm ~ 300 μm, temperature control 30 ~ 40 DEG C, Rotary drying becomes acyl group chitin polysaccharide membrane.When glue drying and forming-film; stop operating; biodegradable fiber fibroin fiber is wrapped on the polysaccharide membrane of stainless steel bar equably; anchoring fiber two ends; open and rotate; continue acyl group chitin colloid solution uniform coating on the fiber of stainless steel bar; glue is by the gap ecto-entad infiltration of fiber; colloid solution and polysaccharide membrane are combined together; control colloid thickness at 100 μm ~ 200 μm, temperature control 30 ~ 40 DEG C, Rotary drying film forming; fiber be embedded or be embedded in the inside of acyl group chitin film, becoming to be integrated with film.After glue drying and forming-film, stop operating, take off above-mentioned stainless steel bar, together with the tubular material of preparation, put into 50% ethanol water and soak, de-pipe, tubular material is through water washing, and 50 ~ 60 DEG C of heat dryings, obtain the degradable blood vessel bracket tubing 4 of hollow tubular structure, its lumen diameter is 3mm, and pipe thickness is 150 μm.
The preparation of embodiment 7 degradable blood vessel bracket tubing 5:
Take chitin powder (acetyl content 86%) 30g; add in glass reaction container; add acylating reagent solution of acetic anhydride 300mL; the solid-to-liquid ratio (w/v) of reaction system is 1: 10; stir; controlling reaction temperature is 10 DEG C, adds the sulfuric acid solution 2.5ml of 70% as catalyst, stirring reaction 72h.Reaction is finished, and filter, solid-liquid separation, solid content puts into the NaOH aqueous solution of 5% of ice bath, acid-base neutralization, water washing desalination, solid-liquid separation, 95% ethanol dehydration, natural drying, and obtaining degree of acetylation is 270% acyl group chitin powder.
Get the acyl group chitin powder 5.5g that degree of acetylation is 270%; add concentration expressed in percentage by weight be 80% formic acid solution 80ml (proportion 1.18) make solvent; stirring and dissolving, preparation concentration expressed in percentage by weight is the acyl group chitin colloid solution (w/v is 6.9%) of 5.5%.Get the Glass rod Pipe making mold of length 10cm, diameter 2.0mm; end holds the Pipe making mold seam be connected on tuber; open tuber; Glass rod is rotated vertically; by acyl group chitin colloid solution equably coating rotate Glass rod on the surface; control glue thickness at 60 μm ~ 200 μm, temperature control 30 ~ 40 DEG C, Rotary drying becomes acyl group chitin polysaccharide membrane.When glue drying and forming-film, stop operating, biodegradable fiber fibroin fiber braided tube is enclosed within the polysaccharide membrane of Glass rod equably along Glass rod, fixing braided tube two ends, open and rotate, continue acyl group chitin colloid solution uniform coating in the fibroin fiber braided tube of Glass rod, glue is by the gap ecto-entad infiltration of fiber, colloid solution and polysaccharide membrane are combined together, control colloid thickness at 100 μm ~ 200 μm, temperature control 30 ~ 40 DEG C, Rotary drying film forming, fiber braided tube is embedded or is embedded in the inside of acyl group chitin film, become to be integrated with film.After glue drying and forming-film, stop operating, take off Glass rod, together with the tubular material of preparation, put into containing 2%NaOH 50% ethanol water soak, acid-base neutralization, de-pipe, tubular material is neutral to pH through water washing, the ethanol dehydration of 95%, dry at 30 ~ 40 DEG C, the degradable blood vessel bracket tubing 5 of obtained hollow tubular structure, its lumen diameter is 2mm, and pipe thickness is 85 μm.
The preparation of embodiment 8 degradable blood vessel bracket tubing 6:
Take chitin powder (acetyl content 86%) 30g; add in glass reaction container; add acylating reagent caproic anhydride solution 200mL; add methanol 100ml; the solid-to-liquid ratio (w/v) making reaction system is 1: 10, stirs, and controlling reaction temperature is 30 DEG C; add the perchloric acid solution 2.5ml of 70% as catalyst, stirring reaction 36h.Reaction is finished, and filter, solid-liquid separation, solid content puts into the NaOH aqueous solution of 8% of ice bath; acid-base neutralization, solid-liquid separation, 95% ethanol dehydration, natural drying; obtain the acyl group chitin powder of acyl group degree 147%, wherein degree of acetylation 86%, own acylation degree is 61%.
Acylation degree prepared by Example 8 is the acyl group chitin powder 8.0g of 147%; add concentration expressed in percentage by weight be 88% formic acid solution 60ml (proportion 1.20) make solvent; low temperature dissolves; add the sulfonated chitin of anticoagulant composition 0.2g; stirring and dissolving, is mixed with the acyl group chitin colloid solution (w/v of acyl group chitin solution is 13.3%) of the interpolation anticoagulant composition containing acyl group chitin 10% (concentration expressed in percentage by weight).Get the PP rod Pipe making mold of length 10cm, diameter 4mm; end holds the Pipe making mold seam be connected on tuber; open tuber; PP rod is rotated vertically; by acyl group chitin colloid solution equably coating rotate PP rod surface on; control glue thickness at 300 μm ~ 500 μm, under room temperature, Rotary drying becomes acyl group chitin polysaccharide membrane.When glue drying and forming-film; stop the rotation; biodegradable fiber fibroin fiber braided tube is enclosed within the polysaccharide membrane of PP rod equably; fixing braided tube two ends; open and rotate; continue acyl group chitin colloid solution uniform coating on the braided tube fiber of PP rod; glue is by the gap ecto-entad infiltration of fiber; colloid solution and polysaccharide membrane are combined together; control colloid thickness at 300 μm ~ 500 μm, under room temperature, Rotary drying film forming; fiber be embedded or be embedded in the inside of acyl group chitin film, becoming to be integrated with film.After glue drying and forming-film, stop operating, take off PP rod, together with the tubular material of preparation, the NaOH aqueous solution putting into 5% soaks, acid-base neutralization, de-pipe, tubular material is neutral to pH through water washing, ethanol dehydration, drying at room temperature, the degradable blood vessel bracket tubing 6 of obtained hollow tubular structure, its lumen diameter is 4mm, and pipe thickness is 420 μm.
At the fibroin fiber described in embodiment 6 ~ 8, can be but be not limited to fibroin fiber or fibroin albumen derivant fiber and braided tube thereof.
The preparation of embodiment 9 degradable blood vessel bracket tubing 7:
Take chitin powder (acetyl content 86%) 30g; add in glass reaction container; add acylating reagent caprylic anhydride solution 300mL; add methanol 60ml; the solid-to-liquid ratio (w/v) making reaction system is 1: 12, stirs, and controlling reaction temperature is 50 DEG C; add methanesulfonic acid solution 2.5ml as catalyst, stirring reaction 36h.Reaction is finished, and filter, solid-liquid separation, solid content puts into the NaOH aqueous solution of 8% of ice bath; acid-base neutralization, solid-liquid separation, 95% ethanol dehydration, natural drying; obtain the acyl group chitin powder of acyl group degree 135%, wherein degree of acetylation 86%, octanylated degree is 49%.
The acylation degree taking embodiment 9 preparation is the acyl group chitin powder 6.3g of 135%; add concentration expressed in percentage by weight be 88% formic acid solution 60ml (proportion 1.20) make solvent; stirring and dissolving; add the sulfonated fibroin albumen of anticoagulant composition 100mg, be mixed with the acyl group chitin colloid solution (w/v of acyl group chitin solution is 10.5%) of the interpolation anticoagulant composition containing acyl group chitin 8.0% (concentration expressed in percentage by weight).Get the Glass rod Pipe making mold of length 10cm, diameter 2.0mm; end holds the Pipe making mold seam be connected on tuber; open tuber; Glass rod is rotated vertically; by acyl group chitin colloid solution equably coating rotate Glass rod on the surface; control glue thickness at 60 μm ~ 200 μm, temperature control 30 ~ 40 DEG C, Rotary drying becomes acyl group chitin film.When glue drying and forming-film; stop operating; cellulose acetate fibre braided tube is enclosed within the film of Glass rod equably along Glass rod; fixing two ends; open and rotate; continue acyl group chitin colloid solution uniform coating on the fiber of Glass rod; glue is by the gap ecto-entad infiltration of fiber; colloid solution and film are combined together; control colloid thickness at 60 μm ~ 200 μm, temperature control 30 ~ 40 DEG C, Rotary drying film forming; fiber be embedded or be embedded in the inside of acyl group chitin film, becoming to be integrated with film.After glue drying and forming-film, stop operating, take off Glass rod, together with the tubular material of preparation, the NaOH aqueous solution putting into 8% soaks, acid-base neutralization, de-pipe, tubular material is neutral to pH through water washing, ethanol dehydration, dry at 30 ~ 40 DEG C, the degradable blood vessel bracket tubing 7 of obtained hollow tubular structure, its lumen diameter is 2mm, and pipe thickness is 83 μm.
Embodiment 8 and the anticoagulant composition described in embodiment 9, can be but be not limited to sulfonated chitin, sulfonated chitosan, sulfonated fibroin albumen, unfractionated heparin, low molecular weight heparin or Calciparine/sodium salt, heparin calcium salt and heparin analog derivative.
Embodiment 10
Degradable blood vessel bracket tubing in above-described embodiment all has good mechanical strength, and it is better that pressure holds rebound performance.Carried out the test of mechanical property by electronic universal puller system to above-mentioned intravascular stent tubing, intravascular stent tubing mechanical property, as table 1, shows the better mechanical property of vascular stent material.
The mechanical experimental results of table 1. intravascular stent tubing
| Tubing | Hot strength (MPa) | Elongation at break (%) |
| Intravascular stent tubing 1 | 88.6 | 8.2 |
| Intravascular stent tubing 2 | 72.9 | 12.8 |
| Intravascular stent tubing 3 | 85.2 | 9.8 |
| Intravascular stent tubing 4 | 55.8 | 7.4 |
| Intravascular stent tubing 5 | 56.9 | 6.6 |
| Intravascular stent tubing 6 | 65.9 | 6.5 |
| Intravascular stent tubing 7 | 55.8 | 6.2 |
Intravascular stent tubing 1-7 derives from embodiment 3-9 respectively.
Embodiment 11
The Laser cutting of degradable blood vessel bracket: be erected at by femto-second laser on operation control platform, connects to form intravascular stent process operation system with computer for controlling, pneumatic motor, the first-class auxiliary facilities of cutting.Degradable blood vessel bracket tubing 1 to degradable blood vessel bracket tubing 4 in above-described embodiment 3 ~ embodiment 6 is individually fixed on the rotatable chuck in support process operation system, computer is according to the cutting pattern programming preset, control support process operation system works, by the movement of the focal beam spot of femto-second laser, laser pulse carries out cutting processing to intravascular stent tubing, carries out Laser cutting respectively to degradable blood vessel bracket tubing 1, tubing 2, tubing 3, tubing 4.Degradable blood vessel bracket 1 pipe range 4cm after processing, lumen diameter 10mm, pipe thickness 810 μm; Degradable blood vessel bracket 2 pipe range 3cm, lumen diameter 5mm, pipe thickness 350 μm; Degradable blood vessel bracket 3 pipe range 3cm, lumen diameter 4mm, pipe thickness 520 μm; Degradable blood vessel bracket 4 pipe range 2.5cm, lumen diameter 3mm, pipe thickness 150 μm; Tube wall all has penetrating rule or irregular pore space structure or patterning.
Embodiment 12
The machine cuts processing of degradable blood vessel bracket: the degradable blood vessel bracket tubing 5 in above-described embodiment 7 ~ embodiment 9, intravascular stent tubing 6 and intravascular stent tubing 7 are individually fixed on support process operation platform, machine cuts processing is carried out to intravascular stent tubing.Degradable blood vessel bracket 5 pipe range 2cm after processing, lumen diameter 2mm, pipe thickness 85 μm; Degradable blood vessel bracket 6 pipe range 2cm, lumen diameter 4mm, pipe thickness 420 μm; Degradable blood vessel bracket 7 pipe range 3cm, lumen diameter 2mm, pipe thickness 83 μm; Tube wall does not have penetrating pore space structure or patterning.
Embodiment 13
Respectively in Example 11 in the degradable blood vessel bracket 3 and embodiment 12 of Laser cutting through the degradable blood vessel bracket 5 of machine cuts processing, respectively get 2, pack separately, ethane via epoxyethane sterilizing, be used as dog femoral artery and implant.Experiment experimental dog 4, water 12h is prohibited in fasting, sleep peaceful II by after 0.05ml/kg dosage intramuscular injection anesthesia with land, dog dorsal position is fixed on operating-table, remove right inboard leg near abdominal part place hair, with iodophor disinfection, aseptic hole-towel is covered in operative site, cut skin and muscular tissue successively, ligation thin vessels, separate dog femoral artery blood vessel, intravenous injection heparin (1mg/Kg body weight), proximal part and the distal end blocking blood flow of femoral artery is clamped respectively with vascular clamp, longitudinally 1cm otch is cut at the femoral artery place of blocking blood flow, the intravascular stent of sterilizing is cut along femoral artery and puts into femoral artery, 4 dogs respectively put an intravascular stent, with 6-0 blood vessel suture blood vessel otch, unclamp near, after distal end vascular clamp, examine anastomotic stoma with or without oozing of blood, determine without layer-by-layer suture muscular tissue and skin after oozing of blood, skin surface smears povidone iodine, and wrap up with sterile gauze.Postoperative animal gives penicillin 800,000 U intramuscular injection 3d, and prevention infection, normally raises, and observes the ordinary circumstance of animal, and in experiment latter 3 months and 6 months unobstructed situations of femoral artery blood flow with ultrasonic examination by Doppler's method operative site.
Ultrasonic examination by Doppler's method result shows, and 4 dog intravascular stents are implanted latter 3 months, and the flowing of femoral artery inner blood is normal, beats obviously in intravascular stent position.Implant latter 6 months, femoral artery blood flow is well unobstructed, has no obvious stenosis, observes obvious vascular pulsation by frequency spectrum.
Degradable blood vessel bracket in the above-described embodiments; it is characterized in that embedding by degradable acyl group chitin film and biodegradable fiber the hollow tubular structure be integrally formed; the acyl group chitin film that tube wall is integrated by embedding and biodegradable fiber form; wherein fiber is embedded or is embedded in the inside of film, and tube wall is with or without penetrating pore space structure or patterning.Described acyl group chitin film; it is characterized in that the total acyl group degree in described acyl group chitin molecule structure is more than or equal to 75%; described acyl group is one or more in acetyl group, propiono, bytyry, caproyl or caprylyl, and the molecular structural formula of acyl group chitin is:
In formula, R
1, R
2or R
3h, acetyl group (-C
2h
3o), propiono (-C
3h
5o), bytyry (-C
4h
7o), caproyl (-C
6h
11or caprylyl (-C O)
8h
15o) one or more in, n is greater than 50; The acyl group degree of acyl group chitin is more than or equal to 75%, and the acyl group quantity namely on average in every 100 sugar units is more than or equal to 75, and the position of acyl group is C6-O position, C3-O position or C2-N position; Described acyl group is one or more in acetyl group, propiono, bytyry, caproyl or caprylyl, and described acyl group degree is the summation that acyl group chitin comprises one or more the acyl group degree in acetyl group, propiono, bytyry, caproyl or caprylyl.
Described biodegradable fiber, it is characterized in that including but not limited to calcium alginate fibre and calcium alginate fibre braided tube, alginic acid zinc fiber and alginic acid zinc fiber braided tube, a cellulose acetate fibre and a cellulose acetate fibre braided tube, cellulose diacetate fibers and cellulose diacetate braided tube, cellulose triacetate fiber and Triafol T braided tube, fibroin fiber and fibroin fiber braided tube, or fibroin albumen derivant fiber and fibroin albumen derivant fiber braided tube.Above-mentioned biodegradable fiber be embedded or be embedded in acyl group chitin film inside become be integrated, as the muscles and bones of film, to strengthen mechanical strength and the radial support power of degradable blood vessel bracket.
Described hollow tubular structure, is characterized in that the interior diameter of tube chamber is 1.5 ~ 12mm, and the thickness of tube wall is 50 μm ~ 1000 μm.
The preparation method of the degradable blood vessel bracket in above-described embodiment, it is characterized in that: acyl group chitin is dissolved in solvent, preparation concentration expressed in percentage by weight is the acyl group chitin colloid solution of 1.0% ~ 15.0%, or acyl group chitin is dissolved in solvent, add anticoagulant composition, prepare the acyl group chitin colloid solution (or the w/v of acyl group chitin solution is 1% ~ 20%) that the concentration expressed in percentage by weight containing anticoagulant composition is 1.0% ~ 15.0%; Open the tuber being connected with Pipe making mold, by acyl group chitin colloid solution, coating is on the Pipe making mold surface of axial rotation equably, and control glue thickness at 50 μm ~ 1000 μm, room temperature or temperature control heat drying become acyl group chitin film; Biodegradable fiber is arranged in equably or is wrapped on the film of Pipe making mold, or the braided tube of biodegradable fiber is evenly enclosed within the film of Pipe making mold; Open and rotate, continue by acyl group chitin colloid solution uniform coating on the fiber of the Pipe making mold of axial rotation, control glue thickness at 50 μm ~ 1000 μm, room temperature or temperature control heat drying film forming, fiber be embedded or be embedded in the inside of acyl group chitin film, becoming to be integrated with film; Pipe making mold is put into dilute alkaline aqueous solution or ethanol water soaks together with the tubular material of preparation, de-pipe, washing, dehydration, drying, the degradable blood vessel bracket tubing that obtained intraluminal diameter is 1.5 ~ 12mm, pipe thickness is the hollow tubular structure of 50 μm ~ 1000 μm; Degradable blood vessel bracket tubing is through Laser cutting or machine cuts processing, and obtained tube wall is with or without penetrating pore space structure or the degradable blood vessel bracket of patterning.Described acyl group chitin is the acyl group chitin of one or more comprised in acetyl group, propiono, bytyry, caproyl or caprylyl, the acyl group degree of acyl group chitin is more than or equal to 75%, and the acyl group quantity namely on average in every 100 sugar units is more than or equal to 75; Described solvent includes but not limited to aqueous formic acid (concentration expressed in percentage by weight is more than or equal to 70%), hexafluoroisopropanol, oxolane, and those skilled in the art other solvent of being familiar with, as trichloroacetic acid, dichloroacetic acid etc.; Described anticoagulant composition is heparin, sulfonated chitosan, sulfonated chitin or sulfonated fibroin albumen; Described Pipe making mold includes but not limited to Glass rod, stainless steel bar, ceramic rod or PP rod; Described biodegradable fiber includes but not limited to calcium alginate fibre and calcium alginate fibre braided tube, alginic acid zinc fiber and alginic acid zinc fiber braided tube, a cellulose acetate fibre and a cellulose acetate fibre braided tube, cellulose diacetate fibers and cellulose diacetate braided tube, cellulose triacetate fiber and Triafol T braided tube, fibroin fiber and fibroin fiber braided tube or fibroin albumen derivant fiber and fibroin albumen derivant fiber braided tube.
Above-mentioned degradable blood vessel bracket has good mechanical strength, and it is good that pressure holds rebound performance; Raw material acyl group chitin and the biodegradable fiber of preparing degradable blood vessel bracket tubing are all biodegradation materials, the degradable blood vessel bracket prepared thus can by organism degrades, micromolecule oligose fragment or unimolecule product is become by organism degrades gradually after et al. Ke, part is absorbed by organism, part excretes, and after intravascular stent degraded, body does not have foreign body to retain; The chemical compositions such as plasticizer, cross-linking agent or catalyst are not added in degradable blood vessel bracket preparation method, as the formic acid, hexafluoroisopropanol, oxolane etc. of solvent, all can be removed by washing in the washing after tubulation, the degradable blood vessel bracket therefore prepared has good biocompatibility and biological safety; After degradable blood vessel bracket implants the femoral artery of dog, femoral artery blood flow is well unobstructed, has no angiostenosis, and vascular pulsation is obvious, shows that the degradable blood vessel bracket prepared is applied to enforcement in animal body better functional.
Water insoluble and the general soda acid solvent of chitin, dissolve in minority organic solvent, it is poorly soluble.Acyl group chitin is water insoluble; but formic acid and part organic solvent can be dissolved in; due in its molecule, the decreased number of intermolecular hydrogen bond association point, its dissolubility is better than chitin, therefore prepares acyl group chitin film than to prepare chitin film easier in practical operation to realize.Described acyl group chitin film, due to the existence of acyl group in its molecular structure, the degree of order of molecule reduces, and degree of crystallinity declines, and than chitin, chitosan is easier is hydrolyzed, and its cell compatibility is better than chitosan.Particularly; the attaching growth of vascular endothelial cell on acyl group chitin film is better than fibroin protein film, polylactic acid membrane; be much better than chitosan film; this makes acyl group chitin film play important function preparing in degradable blood vessel bracket; vascular endothelial cell attaches growth preferably on acyl group chitin film; endothelialization reparation for sufferer vascular site has important effect, can preventing restenosis of blood vessel in advance.For the degradable blood vessel bracket being embedded the hollow tubular structure be integrally formed by acyl group chitin film and biodegradable fiber, biodegradable fiber be embedded or be embedded in acyl group chitin film inside become be integrated, as the muscles and bones of film, enhance mechanical strength and the radial support power of intravascular stent, its mechanical strength is better than and does not embed all-in-one-piece tubing, the surfaces externally and internally of the hollow tubular product simultaneously formed by acyl group chitin film is smooth, be conducive to keeping the unobstructed of blood flow, also the attaching growth of vascular endothelial cell is conducive to, the effect of this support blood vessels and the unobstructed effect of blood flow are all embodied in embodiment 13.
Degradable blood vessel bracket of the present invention, can by Operation body or interventional technique implant, be applied to the narrow or embolotherapy of vessel lumen that angiopathy causes, along with the reparation of lesion vessels, degradable blood vessel bracket is finally degraded, avoid longer-term persistence in vivo, there is wide market prospect.
Claims (9)
1. a degradable blood vessel bracket, it is characterized in that embedding by degradable polysaccharide film and biodegradable fiber the hollow tubular structure be integrally formed, the degradable polysaccharide film that tube wall is integrated by embedding and biodegradable fiber form, wherein fiber is embedded in the inside of film, and tube wall has penetrating pore space structure or patterning.
2. a kind of degradable blood vessel bracket as claimed in claim 1; it is characterized in that embedding by acyl group chitin film and biodegradable fiber the hollow tubular structure be integrally formed; the acyl group chitin film that tube wall is integrated by embedding and biodegradable fiber form; wherein fiber is embedded or is embedded in the inside of film, and tube wall is with or without penetrating pore space structure or patterning.
3. acyl group chitin film as claimed in claim 1; it is characterized in that the total acyl group degree in described acyl group chitin molecule structure is more than or equal to 75%; described acyl group is one or more in acetyl group, propiono, bytyry, caproyl or caprylyl, and the molecular structural formula of acyl group chitin is:
In formula, R
1, R
2or R
3h, acetyl group (-C
2h
3o), propiono (-C
3h
5o), bytyry (-C
4h
7o), caproyl (-C
6h
11or caprylyl (-C O)
8h
15o) one or more in, acyl group degree is more than or equal to 75%.
4. biodegradable fiber as claimed in claim 1, is characterized in that calcium alginate fibre and calcium alginate fibre braided tube, alginic acid zinc fiber and alginic acid zinc fiber braided tube, a cellulose acetate fibre and a cellulose acetate fibre braided tube, cellulose diacetate fibers and cellulose diacetate braided tube, cellulose triacetate fiber and Triafol T braided tube, fibroin fiber and fibroin fiber braided tube or fibroin albumen derivant fiber and fibroin albumen derivant fiber braided tube.
5. hollow tubular structure as claimed in claim 1, it is characterized in that the interior diameter of tube chamber is 1.5 ~ 12mm, the thickness of tube wall is 50 μm ~ 1000 μm.
6. the preparation method of a kind of degradable blood vessel bracket according to claim 1, it is characterized in that: acyl group chitin is dissolved in solvent, preparation concentration expressed in percentage by weight is the acyl group chitin colloid solution of 1.0% ~ 15.0%, or acyl group chitin is dissolved in solvent, add anticoagulant composition, prepare the acyl group chitin colloid solution (or the w/v of acyl group chitin solution is 1% ~ 20%) that the concentration expressed in percentage by weight containing anticoagulant composition is 1.0% ~ 15.0%; Open the tuber being connected with Pipe making mold, by acyl group chitin colloid solution, coating is surperficial at the Pipe making mold of axial rotation equably, controls glue thickness at 50 μm ~ 1000 μm, room temperature or temperature control heat drying film forming; Biodegradable fiber is arranged in or is wrapped on the film of Pipe making mold, or by the woven sheath of biodegradable fiber on the film of Pipe making mold; Open and rotate, continue by acyl group chitin colloid solution uniform coating on the fiber of the Pipe making mold rotated, control glue thickness at 60 μm ~ 1000 μm, room temperature or temperature control heat drying film forming, fiber is embedded or is embedded in the inside of film; Pipe making mold is put into dilute alkaline aqueous solution or ethanol water soaks together with the tubular material of preparation, de-pipe, washing, dehydration, drying, the intravascular stent tubing that obtained intraluminal diameter is 1.5 ~ 12mm, pipe thickness is the hollow tubular structure of 50 μm ~ 1000 μm; Intravascular stent tubing is through Laser cutting or machine cuts processing, and obtained tube wall is with or without penetrating pore space structure or the degradable blood vessel bracket of patterning.
7. the preparation method of a kind of degradable blood vessel bracket as claimed in claim 5, is characterized in that described solvent is aqueous formic acid, hexafluoroisopropanol or the oxolane that concentration expressed in percentage by weight is greater than 70%.
8. the preparation method of a kind of degradable blood vessel bracket as claimed in claim 5, is characterized in that described anticoagulant composition is heparin, sulfonated chitosan, sulfonated chitin or sulfonated fibroin albumen.
9. degradable blood vessel bracket according to claim 1 by Operation body or interventional therapeutic technique implant, the application in the vessel lumen that causes for the treatment of angiopathy in narrow or blood vessel embolism.
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