CN105148332A - Degradable blood vessel stent and preparation method and application thereof - Google Patents
Degradable blood vessel stent and preparation method and application thereof Download PDFInfo
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- CN105148332A CN105148332A CN201510604291.XA CN201510604291A CN105148332A CN 105148332 A CN105148332 A CN 105148332A CN 201510604291 A CN201510604291 A CN 201510604291A CN 105148332 A CN105148332 A CN 105148332A
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Abstract
The invention discloses a degradable blood vessel stent. The degradable blood vessel stent is characterized in that the degradable blood vessel stent is of a hollow tubular structure made of acyl amino polysaccharide, the inner surface of the tubular structure is provided with an anticoagulation coating, the outer surface of the tubular structure is provided with a development coating, and the tube wall is provided with or not provided with a transparent hole structure or pattern structure. The degradable blood vessel stent can be applied to treatment of narrowing or embolism of vascular lumen and can be degraded and absorbed in a human body.
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 the narrow or embolotherapy of the vessel lumen that causes for angiopathy, " is strutted " by narrow blood vessel, increases blood flow and prevents the implantable medical devices product of myocardial infarction.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 can cause the hyperplasia of tunica intima, cause 15% ~ 30% restenosis, the biocompatibility issues such as simultaneously can also produce Endothelial Dysfunction, chronic inflammatory disease, blood vessel and rack mechanical performance are not mated.Because nondegradable 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 keeps enough mechanical strengths and radial support effect in time of 6 ~ 12 months in vivo, and along with the reparation of lesion vessels, degradable blood vessel bracket is finally degraded gradually and is absorbed by the body, 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, can degradation in vivo absorb, but its acid degradation thing that degraded produces in tissue can produce certain aseptic inflammation reaction.
The macromolecular material of the biogenetic derivations such as chitin, chitosan, fibroin albumen, alginic acid, biological safety is good, and degradable absorbs, and has 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.Due to deliquescent restriction, there is technical difficulty in it in actual applications.The catabolite of chitin is micromolecular acetylamino oligosaccharide or acetylamino 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 needs.
The time that desirable degradable blood vessel bracket exists in vivo should with vascular repair time consistency, generally need 6 ~ 12 months, vascular function rebuild after, degradable blood vessel bracket is degraded gradually, is finally absorbed completely by human body.Desirable degradable blood vessel bracket should not produce degraded fragment etc. in degradation process, to affect the blood flow patency of blood vessel.
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 the hollow tubular structure made for material with acylated amino polysaccharide; the inner surface of tubular structure has anticoagulant coatings, and the outer surface of tubular structure has development coating, and tube wall is with or without penetrating pore space structure or patterning.
The acylated amino polysaccharide that acylated amino polysaccharide of the present invention is is construction unit with acylated amino glucose.
Acylated amino polysaccharide of the present invention can be that chitosan is modified obtained through acyl groupization, also can be that chitin is modified obtained through acyl groupization.
Acylated amino polysaccharide of the present invention; molecular structure is polyamides base glucosamine polysaccharide; total acyl group degree in the molecular structure of described acylated amino polysaccharide is more than or equal to 70%; described acyl group is one or more in acetyl group, propiono, bytyry, caproyl, caprylyl, certain herbaceous plants with big flowers acyl group, lauroyl, palmityl and other aliphatic or aromatic acyl group, and the molecular structural formula of acylated amino polysaccharide 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
11o), caprylyl (-C
8h
15o) one or more or in certain herbaceous plants with big flowers acyl group, lauroyl, palmityl and other aliphatic or aromatic acyl group, n is greater than 100: the acyl group degree of acylated amino polysaccharide is more than or equal to 70%, namely the acyl group quantity on average in every 100 sugar units is more than or equal to 70, 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, caprylyl, certain herbaceous plants with big flowers acyl group, lauroyl, palmityl and other aliphatic or aromatic acyl group, and described acyl group degree is the summation that acylated amino polysaccharide comprises one or more the acyl group degree in acetyl group, propiono, bytyry, caproyl, caprylyl, certain herbaceous plants with big flowers acyl group, lauroyl, palmityl and other aliphatic or aromatic acyl group.
Above-mentioned anticoagulant coatings is the azido benzoyl aminopolysaccharide coating containing anticoagulant; Above-mentioned development coating is the azido benzoyl aminopolysaccharide coating containing developing agent.
The present invention for material, has prepared degradable blood vessel bracket base material with acylated amino polysaccharide.Described degradable blood vessel bracket base material has that water absorption rate is low, intensity is high, degradable absorbs, the feature of good biocompatibility.
Azido benzoyl aminopolysaccharide of the present invention; comprise hydrazoic benzoyl chitosan, azido benzoyl hydroxyethyl chitosan, azido benzoyl hydroxypropyl chitosan, azido benzoyl carboxymethyl chitosan, azido benzoyl chitin, azido benzoyl ethoxyl chitin, azido benzoyl Chitofilmer, and chitin, chitosan other azido benzoyl derivant.Described azido benzoyl aminopolysaccharide is when absorbing ultraviolet, and active azido benzoyl group photodissociation is carbene, carbene can with the element generation cross-linking reaction such as C, S, O.
The present invention utilizes this characteristic of azido benzoyl aminopolysaccharide, carries out sensitivity to the degradable blood vessel bracket base material of preparation.Prepared the azido benzoyl aminopolysaccharide glue containing anticoagulant, the inner surface anticoagulant coatings carrying out intravascular stent base material is modified; Prepare the azido benzoyl aminopolysaccharide glue containing developing agent, carry out the outer surface development coating modifying of intravascular stent base material, so that the radiography in intravascular stent is observed.Containing the azido benzoyl aminopolysaccharide coating of anticoagulant with containing the azido benzoyl aminopolysaccharide coating of developing agent, occur crosslinked under the action of uv light, make anticoagulant, developing agent is fixed on intravascular stent base material.
Degradable blood vessel bracket of the present invention; with the hollow tubular structure that acylated amino polysaccharide is made for material; the inner surface of tubular structure has anticoagulant coatings, and the outer surface of tubular structure has development coating, and tube wall is with or without penetrating pore space structure or patterning.The preparation method of a kind of degradable blood vessel bracket of the present invention, is characterized in that:
Acylated amino polysaccharide is dissolved in solvent, preparation concentration expressed in percentage by weight be 1% ~ 20% or w/v be 1% ~ 25% acylated amino polysaccharide glue;
Open the tuber with Pipe making mold, by acylated amino polysaccharide glue coating on Pipe making mold, control glue thickness, room temperature or temperature control heat drying become tubulose;
Pipe making mold is put into dilute alkaline aqueous solution, ethanol water or distilled water together with the tubular material prepared soak, de-pipe, is washed to pH neutrality, and dehydration is dry, obtains the degradable blood vessel bracket base material of hollow tubular;
Preparation concentration expressed in percentage by weight is the azido benzoyl aminopolysaccharide glue of 0.5% ~ 25%, adds anticoagulant, and obtained anticoagulant glue, opens plater, by anticoagulant glue coating at degradable blood vessel bracket base material inner surface, and ultraviolet light cross-linking;
Preparation concentration expressed in percentage by weight is the azido benzoyl aminopolysaccharide glue of 0.5% ~ 25%, adds developing agent, and obtained developing agent glue, opens plater, by developing agent glue coating at degradable blood vessel bracket substrate outer surface, and ultraviolet light cross-linking;
Drying, the degradable blood vessel bracket tubing of obtained band anticoagulant and developing agent;
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.
The preparation method of degradable blood vessel bracket of the present invention, it is characterized in that the molecular structure of described acylated amino polysaccharide is polyamides base glucosamine polysaccharide, the total acyl group degree in molecular structure is more than or equal to 70%; Described acyl group is one or more in acetyl group, propiono, bytyry, caproyl, caprylyl, certain herbaceous plants with big flowers acyl group, lauroyl, palmityl and other aliphatic or aromatic acyl group.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, ethanol, and those skilled in the art other solvent of being familiar with, as trichloroacetic acid, dichloroacetic acid etc.;
Degradable blood vessel bracket of the present invention, is characterized in that described anticoagulant coatings is the azido benzoyl aminopolysaccharide coating containing anticoagulant.
Described anticoagulant is heparin, and the anticoagulation preparation that other anticoagulation preparation of Clinical practice and those skilled in the art predict.
Degradable blood vessel bracket of the present invention, is characterized in that described development coating is the azido benzoyl aminopolysaccharide coating containing developing agent.
Degradable blood vessel bracket of the present invention, is characterized in that described developing agent is barium sulfate, cardiografin, and the developing agent that other developing agent of Clinical practice and those skilled in the art predict, as fluorescein, tantalum powder etc.
Degradable blood vessel bracket of the present invention, it is characterized in that described hollow tubular structure be the interior diameter of tube chamber is 2.0 ~ 10mm, the thickness of tube wall is 0.05mm ~ 2.0mm.
Degradable blood vessel bracket of the present invention 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.
Degradable blood vessel bracket of the present invention has good mechanical strength, and it is good that pressure holds rebound performance; The main raw material(s) preparing degradable blood vessel bracket tubing is acylated amino polysaccharide, and have the feature of good biocompatibility, degradable absorption, coating material azido benzoyl aminopolysaccharide also degradable absorbs.Meanwhile, degradable blood vessel bracket of the present invention has anticoagulant coatings and development coating, significantly increases the result of use of intravascular stent, can possess anticoagulant functions, can by image be undertaken operate and observe when support is implanted in vivo simultaneously.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.
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.
Accompanying drawing explanation
The observation on Growth of Fig. 1: L929 cell on diaphragm
Fig. 2: mtt assay measures the growth of L929 cell on diaphragm
Detailed description of the invention
Embodiment 1
A kind of degradable blood vessel bracket; it is characterized in that the hollow tubular structure made for material with acylated amino polysaccharide; the inner surface of tubular structure has anticoagulant coatings, and the outer surface of tubular structure has development coating, and tube wall is with or without penetrating pore space structure or patterning.
Described acylated amino polysaccharide is polyamides base glucosamine polysaccharide; total acyl group degree in its molecular structure is more than or equal to 70%; described acyl group is one or more in acetyl group, propiono, bytyry, caproyl, caprylyl, certain herbaceous plants with big flowers acyl group, lauroyl, palmityl and other aliphatic or aromatic acyl group, and the molecular structural formula of acylated amino polysaccharide 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
11o), caprylyl (-C
8h
15o) one or more or in certain herbaceous plants with big flowers acyl group, lauroyl, palmityl and other aliphatic or aromatic acyl group, acyl group degree is more than or equal to 70%.
Described anticoagulant coatings is the azido benzoyl aminopolysaccharide coating containing anticoagulant;
Described development coating is the azido benzoyl aminopolysaccharide coating containing developing agent.
Described azido benzoyl aminopolysaccharide is hydrazoic benzoyl chitosan, azido benzoyl hydroxyethyl chitosan, azido benzoyl hydroxypropyl chitosan, azido benzoyl carboxymethyl chitosan, azido benzoyl chitin, azido benzoyl ethoxyl chitin, azido benzoyl Chitofilmer, and chitin, chitosan other azido benzoyl derivant.
Described hollow tubular structure is the interior diameter of tube chamber is 2.0 ~ 10mm, and the thickness of tube wall is 0.05mm ~ 2.0mm.
The screening of embodiment 2 degradable blood vessel bracket base material:
(1) preparation of diaphragm:
The preparation of chitosan diaphragm: take chitosan powder (deacetylation 92.5%) 2g, add aqueous acetic acid (volume fraction) 100ml of 2%, stirring and dissolving, is mixed with the chitosan glue that w/v (w/v) is 2%.Measure 15ml chitosan glue respectively 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 acid-base neutralization in the NaOH aqueous solution (concentration expressed in percentage by weight, lower same) of 2%, is washed to pH neutrality, dry, obtained chitosan diaphragm.
The preparation of chitin diaphragm: take chitin powder 2g, adds hexafluoroisopropanol solution 100ml, stirring and dissolving, is mixed with the chitin glue (w/v) of 2%.Measure 15ml chitin glue respectively and be placed in the rustless steel square plate that the length of side is 50mm × 50mm, standing and drying in ventilating kitchen, obtained chitin diaphragm.
The preparation of acyl group chitin diaphragm: take chitin powder 10g; add in glass reaction container; add acylating reagent solution of acetic anhydride 20mL; add methanol 150ml; stir, control temperature is 0 DEG C ~ 5 DEG C, then adds the perchloric acid solution (concentration expressed in percentage by weight of 70%; down together) 1ml 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) dewaters, and 50 DEG C of heat dryings, obtain acyl group chitin; it is 115% (molar percentage, lower same) that elemental microanalysis method (lower same) records its degree of acetylation.Take the acyl group chitin 2g that degree of acetylation is 115%, add formic acid solution (concentration expressed in percentage by weight, the lower same) 100ml of 80%, stirring and dissolving, is mixed with the acyl group chitin glue that w/v is 2%.Measure 15ml acyl group chitin glue respectively 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 acid medium alkali neutralization of 2%, is washed to pH neutrality, dry, obtained acyl group chitin diaphragm.
(2) physical property of diaphragm compares:
Water absorption rate: get the chitosan diaphragm, chitin diaphragm, each 3 of the acyl group chitin diaphragm that are dried to constant weight respectively, specification is 2cm × 2cm, weighs respectively; be placed in distilled water and soak 24h; take out diaphragm filter paper and suck surface moisture, weigh, calculate water absorption rate.Result shows, and the water absorption rate of chitosan film is 416%, and the diaphragm after water suction has certain dilatancy; The water absorption rate of chitin film is 104%, and the diaphragm after water suction also has certain dilatancy, and degrees of expansion is lower than chitosan diaphragm; The water absorption rate of acyl group chitin film is 58%, and diaphragm expands minimum.The water absorption rate of visible acyl group chitin is minimum, and low water absorption decreases the expansion of diaphragm.
Hot strength: three kinds of diaphragms are under hygrometric state, and the hot strength of acyl group chitin diaphragm is maximum, and the hot strength of chitin diaphragm is taken second place, and the hot strength of chitosan diaphragm is the poorest.
(3) biocompatibility of diaphragm and degradability compare:
Cell compatibility: under aseptic condition, obtaining diameter respectively with trepan is 7mm chitosan diaphragm, chitin diaphragm, acyl group chitin diaphragm, is placed in the bottom of 96 porocyte culture plates respectively, adds 10% new-born calf serum fully infiltrate 24h by DMEM culture medium.Choose the L929 cell of the exponential phase through trypsinization, regulate cell density 4 × 10
4individual/ml, cell is inoculated in respectively the chaffy culture hole in bottom, and without the contrast culture hole of diaphragm, culture medium is that DMEM culture medium adds 10% new-born calf serum, every hole 200 μ l, in 37 DEG C, and 5%CO
2cultivate under condition, regularly change liquid.When cultivating 4d, the growth conditions of observation of cell under inverted microscope, and with mtt assay, the light absorption value at microplate reader mensuration 492nm place, calculates relative appreciation rate (RGR).As shown in Figure 1, the growth conditions of cell on acyl group chitin diaphragm is best, and cell density is high for experimental result, and state stretches, and the Growth of Cells on chitin diaphragm takes second place, and the cell quantity on chitosan diaphragm is minimum, and state is poor.The relative appreciation rate of cell the results are shown in Figure 2; the relative appreciation rate of cell on acyl group chitin film is 90.88 ± 26.35%; relative appreciation rate on chitin film is 50.31 ± 12.42%; relative appreciation rate on chitosan film is 15.08 ± 8.67%; as can be seen here, the cell compatibility of acyl group chitin diaphragm is better.
Degeneration: on cell compatibility experiment basis, chitin film has been screened in this research and acyl group chitin film carries out et al. Ke degradation experiment.Take rat as laboratory animal; chitin diaphragm, the acyl group chitin diaphragm of 5mm × 5mm is implanted respectively in subcutaneous rat and muscle; respectively at postoperative 1 week, 2 weeks, January, February, March, April, May, June, July, August, JIUYUE put to death often organize each 3 rats; observe the response situation of implantation film surrounding tissue; and get diaphragm surrounding tissue; 10% formalin fixative is fixed, and makes HE staining tissue slides, carries out pathologic examination.Experimental result shows, and two kinds of diaphragms implant subcutaneous rat and muscle, and acyl group chitin diaphragm has no the tissue inflammation reactions such as obvious encapsulation, capillary injection at the implantation initial stage, and its compatibility in subcutaneous, muscular tissue is good; Chitin diaphragm has slight tissue inflammation reaction at the implantation initial stage, and the degraded inflammatory reaction with diaphragm fades away, and also shows good biocompatibility; Acyl group chitin diaphragm is complete degraded in subcutaneous 7 months, and in muscle degraded in 8 months completely, chitin diaphragm is subcutaneous complete with muscle degraded in 6 ~ 7 months, and degradation speed is slightly faster than acyl group chitin diaphragm.Shown by et al. Ke degradation experiment, chitin film and acyl group chitin film all have good degeneration and histocompatibility, and wherein acyl group chitin diaphragm shows better histocompatibility.
Chitosan diaphragm, chitin diaphragm, acyl group chitin diaphragm screen through above-mentioned physical property and biocompatibility, degradability; acyl group chitin diaphragm has better physical property and biology performance; show that aminopolysaccharide water absorption rate after acyl group is low, good biocompatibility further, be better than the aminopolysaccharide without acyl group.Chitosan, chitin are aminopolysaccharide, and the C6-O position in both molecular structures, C3-O position, C2-N position all acylation reaction can occur, and make acylated amino polysaccharide.
The preparation of embodiment 3 degradable blood vessel bracket tubing 1:
Take chitosan powder (deacetylation 92%) 20g, add in glass reaction container, add acylating reagent solution of acetic anhydride 50mL; add methanol 100ml; control temperature is 10 DEG C, adds the perchloric acid solution 1ml of 70% as catalyst, stirring reaction 36h under stirring.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, and solid content washing desalination, 95% ethanol dehydration, 60 DEG C of heat dryings, obtain the acylated amino polysaccharide 1 that acyl group degree is 74.5%.Acylated amino polysaccharide 1 has acetyl group structure, and acetyl content is 74.5%.
Take the above-mentioned acylated amino polysaccharide 1 of 2.5g; add hexafluoroisopropanol solution 61ml (proportion 1.60) and make solvent; low temperature dissolves, and is mixed with the acylated amino polysaccharide glue (w/v is 4.1%) that concentration expressed in percentage by weight is 2.5%.Get the stainless steel bar Pipe making mold of length 10cm, diameter 4mm, be connected to the Pipe making mold seam on tuber, open tuber; by acylated amino polysaccharide glue, coating is surperficial at the stainless steel bar rotated equably; control glue thickness at 2mm ~ 3mm, under room temperature, Rotary drying becomes tubulose.After glue drying, take off above-mentioned stainless steel bar, together with the tubular material of preparation, the ethanol water putting into 50% soaks, de-pipe, and tubular material is through washing, and ethanol dehydration, drying at room temperature, obtains the degradable blood vessel bracket base material 1 of hollow tubular.
Take hydrazoic benzoyl chitosan 0.2g, add 10ml distilled water, stirring and dissolving, obtain the azido benzoyl aminopolysaccharide glue that concentration expressed in percentage by weight is 2%, add anticoagulant heparin 5mg, stir, obtain anticoagulant glue.Get the degradable blood vessel bracket base material 1 of above-mentioned hollow tubular, two ends connect and are fixed on the undercoating seam of plater, the built-in moveable playpipe in one end of undercoating interface and injector head, open plater, anticoagulant glue is evenly injected in the inner surface of the degradable blood vessel bracket base material 1 of rotation through built-in moveable playpipe, injector head, make anticoagulant glue uniform coating at the inner surface of degradable blood vessel bracket base material 1, control glue thickness 0.5mm, ultraviolet light cross-linking under room temperature.Take hydrazoic benzoyl chitosan 0.2g again, add 10ml distilled water, stirring and dissolving, obtain the azido benzoyl aminopolysaccharide glue that concentration expressed in percentage by weight is 2%, add developing agent cardiografin 1ml, stir, obtain developing agent glue.Developing agent glue is evenly injected in the outer surface of the degradable blood vessel bracket base material 1 of rotation through the external moveable playpipe of plater, injector head, make developing agent glue uniform coating at the outer surface of degradable blood vessel bracket base material 1, control glue thickness 0.5 ~ 1mm, ultraviolet light cross-linking under room temperature, dry, the degradable blood vessel bracket tubing 1 of obtained band anticoagulant and developing agent, its lumen diameter is 3.8mm, and pipe thickness is 0.08mm.
The preparation of embodiment 4 degradable blood vessel bracket tubing 2:
Take chitosan powder (deacetylation 92%) 20g, add in glass reaction container, add acylating reagent propionic andydride solution 120mL; add methanol 100ml; control temperature is 0 ~ 5 DEG C, adds methanesulfonic acid solution 2.0ml as catalyst, stirring reaction 24h under stirring.Reaction is finished, and filter, solid-liquid separation, solid content adds in the KOH aqueous solution of 2% 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, obtain the acylated amino polysaccharide 2 that acyl group degree is 102.3%.Acylated amino polysaccharide 2 has propiono, acetyl group structure, and wherein acetyl content is about 8%, and propionyl content is about 94.3%.
Take the above-mentioned acylated amino polysaccharide 2 of 14.8g; the formic acid solution 60ml (proportion 1.17) adding 75% makes solvent; stirring and dissolving, is mixed with the acylated amino polysaccharide glue (w/v is 24.7%) that concentration expressed in percentage by weight is 17.4%.Get the ceramic rod Pipe making mold of length 10cm, diameter 8mm; be connected to the Pipe making mold seam on tuber; open tuber; by acylated amino polysaccharide glue equably coating rotate ceramic rod on the surface; control glue thickness at 3mm ~ 5mm; temperature control 40 ~ 50 DEG C, Rotary drying becomes tubulose.After glue drying, take off ceramic 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, dehydrated alcohol dewaters, 50 ~ 60 DEG C of heat dryings, the degradable blood vessel bracket base material 2 of obtained hollow tubular.
Take azido benzoyl hydroxyethyl chitosan 3.0g, add 10ml distilled water, stirring and dissolving, obtain the azido benzoyl aminopolysaccharide glue that concentration expressed in percentage by weight is 23.1%, add anticoagulant heparin 20mg, stir, obtain anticoagulant glue.Get the degradable blood vessel bracket base material 2 of above-mentioned hollow tubular, two ends connect and are fixed on the undercoating seam of plater, the built-in moveable playpipe in one end of undercoating interface and injector head, open plater, anticoagulant glue is evenly injected in the inner surface of the degradable blood vessel bracket base material 2 of rotation through built-in moveable playpipe, injector head, make anticoagulant glue uniform coating at the inner surface of degradable blood vessel bracket base material 2, control glue thickness 0.5 ~ 0.8mm, ultraviolet light cross-linking under room temperature.Take azido benzoyl hydroxyethyl chitosan 2.5g again, add 10ml distilled water, stirring and dissolving, obtain the azido benzoyl aminopolysaccharide glue that concentration expressed in percentage by weight is 20%, add developing agent barium sulfate 20mg, stir, obtain developing agent glue.Developing agent glue is evenly injected in the outer surface of the degradable blood vessel bracket base material 2 of rotation through the external moveable playpipe of plater, injector head, make developing agent glue uniform coating at the outer surface of degradable blood vessel bracket base material 2, control glue thickness 1 ~ 1.5mm, ultraviolet light cross-linking under room temperature, dry, the degradable blood vessel bracket tubing 2 of obtained band anticoagulant and developing agent, its lumen diameter is about 7.8mm, and pipe thickness is 1.6mm.
The preparation of embodiment 5 degradable blood vessel bracket tubing 3:
Take chitosan powder (deacetylation 85%) 20g; add in glass reaction container; add acylating reagent butyryl oxide. solution 200mL; add methanol 100ml; control temperature is 20 DEG C; add under stirring 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 5%, acid-base neutralization, water washing desalination, solid-liquid separation, and dehydrated alcohol dewaters, and natural drying, obtains the acylated amino polysaccharide 3 that acyl group degree is 135%.Acylated amino polysaccharide 3 has bytyry, acetyl group structure, and wherein acetyl content is about 15%, and bytyry content is about 120%.
Take the above-mentioned acylated amino polysaccharide 3 of 6.2g; add concentration expressed in percentage by weight be 80% formic acid solution 60ml (proportion 1.18) make solvent; low temperature dissolves, and is mixed with the acylated amino polysaccharide glue (w/v is 10.3%) that concentration expressed in percentage by weight is 8.1%.Get the PP rod Pipe making mold of length 10cm, diameter 10mm, be connected to the Pipe making mold seam on tuber, open tuber; by acylated amino polysaccharide glue equably coating rotate PP rod surface on; control glue thickness at 2mm ~ 4mm, temperature control 40 ~ 50 DEG C, Rotary drying becomes tubulose.After glue drying, stop operating, take off PP rod, together with the tubular material of preparation, the NaOH aqueous solution putting into 4% soaks, acid-base neutralization, de-pipe, tubular material is neutral to pH through water washing, and dehydrated alcohol dewaters, 50 ~ 60 DEG C of heat dryings, the degradable blood vessel bracket base material 3 of obtained hollow tubular.
Take azido benzoyl hydroxypropyl chitosan 0.5g, add 10ml distilled water, stirring and dissolving, obtain the azido benzoyl aminopolysaccharide glue that concentration expressed in percentage by weight is 5%, add anticoagulant heparin 80mg, stir, obtain anticoagulant glue.Get the degradable blood vessel bracket base material 3 of above-mentioned hollow tubular, two ends connect and are fixed on the undercoating seam of plater, open plater, anticoagulant glue is evenly injected in the inner surface of the degradable blood vessel bracket base material 3 of rotation through built-in moveable playpipe, injector head, make anticoagulant glue uniform coating at the inner surface of degradable blood vessel bracket base material 3, control glue thickness 0.8 ~ 1.2mm, ultraviolet light cross-linking under room temperature.Take azido benzoyl hydroxypropyl chitosan 1.1g again, add 10ml distilled water, stirring and dissolving, obtain the azido benzoyl aminopolysaccharide glue that concentration expressed in percentage by weight is 10%, add developing agent cardiografin 1ml, stir, obtain developing agent glue.Developing agent glue is evenly injected in the outer surface of the degradable blood vessel bracket base material 3 of rotation through the external moveable playpipe of plater, injector head, make developing agent glue uniform coating at the outer surface of degradable blood vessel bracket base material 3, control glue thickness 1 ~ 1.5mm, ultraviolet light cross-linking under room temperature, dry, the degradable blood vessel bracket tubing 3 of obtained band anticoagulant and developing agent, its lumen diameter is 9.8mm, and pipe thickness is 1.0mm.
The preparation of embodiment 6 degradable blood vessel bracket tubing 4:
Take chitosan powder (deacetylation 92%) 10g, add in glass reaction container, add acylating reagent caproic anhydride 200ml, control temperature is 0 DEG C, adds 70% perchloric acid solution 5.0ml as catalyst, stirring reaction 36h under stirring.Reaction is finished, and leach reaction solid content, by the NaOH aqueous solution acid-base neutralization of 2%, water washing desalination, solid-liquid separation, 50 ~ 60 DEG C of heat dryings, obtain the acylated amino polysaccharide 4 that acyl group degree is 108.7%.Acylated amino polysaccharide 4 has caproyl, acetyl group structure, and wherein acetyl content is about 8%, and caproyl content is about 100.7%.
Take the above-mentioned acylated amino polysaccharide 4 of 2g, add dehydrated alcohol 60ml (proportion 0.79) and make solvent, stirring and dissolving, be mixed with the acylated amino polysaccharide glue (w/v is 3.3%) that concentration expressed in percentage by weight is 4%.Get the stainless steel bar Pipe making mold of length 10cm, diameter 3mm; be connected to the Pipe making mold seam on tuber; open tuber; by acylated amino polysaccharide glue equably coating rotate stainless steel bar on the surface; control glue thickness at 2mm ~ 4mm; temperature control 40 ~ 50 DEG C, Rotary drying becomes tubulose.After glue drying, take off stainless steel bar, together with the tubular material of preparation, put into distilled water and soak, de-pipe, 50 ~ 60 DEG C of heat dryings, the degradable blood vessel bracket base material 4 of obtained hollow tubular.
Take azido benzoyl carboxymethyl chitosan 0.1g, add 10ml distilled water, stirring and dissolving, obtain the azido benzoyl aminopolysaccharide glue that concentration expressed in percentage by weight is 1%, add anticoagulant heparin 50mg, stir, obtain anticoagulant glue.Get the degradable blood vessel bracket base material 4 of above-mentioned hollow tubular, two ends connect and are fixed on the undercoating seam of plater, open plater, anticoagulant glue is evenly injected in the inner surface of the degradable blood vessel bracket base material 4 of rotation through built-in moveable playpipe, injector head, make anticoagulant glue uniform coating at the inner surface of degradable blood vessel bracket base material 4, control glue thickness 0.5mm, ultraviolet light cross-linking under room temperature.Take azido benzoyl carboxymethyl chitosan 0.5g again, add 10ml distilled water, stirring and dissolving, obtain the azido benzoyl aminopolysaccharide glue that concentration expressed in percentage by weight is 5%, add developing agent barium sulfate 200mg, stir, obtain developing agent glue.Developing agent glue is evenly injected in the outer surface of the degradable blood vessel bracket base material 4 of rotation through the external moveable playpipe of plater, injector head, make developing agent glue uniform coating at the outer surface of degradable blood vessel bracket base material 4, control glue thickness 0.5 ~ 1mm, ultraviolet light cross-linking under room temperature, dry, the degradable blood vessel bracket tubing 4 of obtained band anticoagulant and developing agent, its lumen diameter is about 3.0mm, and pipe thickness is 0.6mm.
The preparation of embodiment 7 degradable blood vessel bracket tubing 5:
Take chitin powder (acetyl content 85%) 20g; add in glass reaction container; add acylating reagent butyryl oxide. solution 150mL; add methanol 100ml; controlling reaction temperature is 0 ~ 5 DEG C; add under stirring concentration expressed in percentage by weight be the perchloric acid solution 2ml of 70% as catalyst, stirring reaction 48h.Reaction is finished, and filter, solid-liquid separation, puts into the NaOH aqueous solution of 5%, acid-base neutralization, solid-liquid separation by solid content, solid content water washing is to center, and 95% ethanol dehydration, natural drying, obtains the acylated amino polysaccharide 5 of acyl group degree 235%.Acylated amino polysaccharide 5 has bytyry, acetyl group structure, and wherein acetyl content is about 85%, and bytyry content is about 150%.
Take the above-mentioned acylated amino polysaccharide 5 of 1.0g, add tetrahydrofuran solution 60ml (proportion 0.89) and make solvent, stirring and dissolving, preparation concentration expressed in percentage by weight is the acylated amino polysaccharide glue (w/v is 1.7%) of 1.8%.Get the stainless steel bar Pipe making mold of length 10cm, diameter 4mm; be connected to the Pipe making mold seam on tuber, open tuber, by acylated amino polysaccharide glue, coating is surperficial at the stainless steel bar rotated equably; control glue thickness at 2mm ~ 4mm, Rotary drying becomes tubulose.After glue drying, take off stainless steel bar, together with the tubular material of preparation, put into 50% ethanol water and soak, de-pipe, 50 ~ 60 DEG C of heat dryings, the degradable blood vessel bracket base material 5 of obtained hollow tubular.
Take azido benzoyl chitin 0.2g, add 10ml distilled water, stirring and dissolving, obtain the azido benzoyl aminopolysaccharide glue that concentration expressed in percentage by weight is 2%, add anticoagulant heparin 100mg, stir, obtain anticoagulant glue.Get the degradable blood vessel bracket base material 5 of above-mentioned hollow tubular, two ends connect and are fixed on the undercoating seam of plater, open plater, anticoagulant glue is evenly injected in the inner surface of the degradable blood vessel bracket base material 5 of rotation through built-in moveable playpipe, injector head, make anticoagulant glue uniform coating at the inner surface of degradable blood vessel bracket base material 5, control glue thickness 0.5mm, ultraviolet light cross-linking under room temperature.Take azido benzoyl chitin 0.5g again, add 10ml distilled water, stirring and dissolving, obtain the azido benzoyl aminopolysaccharide glue that concentration expressed in percentage by weight is 5%, add developing agent barium sulfate 50mgl, stir, obtain developing agent glue.Developing agent glue is evenly injected in the outer surface of the degradable blood vessel bracket base material 5 of rotation through the external moveable playpipe of plater, injector head, make developing agent glue uniform coating at the outer surface of degradable blood vessel bracket base material 5, control glue thickness 0.5 ~ 1mm, ultraviolet light cross-linking under room temperature, dry, the degradable blood vessel bracket tubing 5 of obtained band anticoagulant and developing agent, its lumen diameter is about 3.9mm, and pipe thickness is 0.25mm.
The preparation of embodiment 8 degradable blood vessel bracket tubing 6:
Take chitin powder (acetyl content 85%) 20g, add in glass reaction container, add acylating reagent solution of acetic anhydride 300mL; add methanol 50ml; control temperature is 10 DEG C, adds the sulfuric acid solution 2ml of 70% as catalyst, stirring reaction 72h under stirring.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, obtains the acylated amino polysaccharide 6 that acyl group degree is 275%.Acylated amino polysaccharide 6 has acetyl group structure, and acetyl content is about 275%.
Take the above-mentioned acylated amino polysaccharide 6 of 3.5g; add concentration expressed in percentage by weight be 80% formic acid solution 60ml (proportion 1.18) make solvent; stirring and dissolving, preparation concentration expressed in percentage by weight is the acylated amino polysaccharide glue (w/v is 5.8%) of 4.7%.Get the Glass rod Pipe making mold of length 10cm, diameter 5mm; be connected to the Pipe making mold seam on tuber; open tuber; by acylated amino polysaccharide glue equably coating rotate Glass rod on the surface; control glue thickness at 2mm ~ 4mm; temperature control 40 ~ 50 DEG C, Rotary drying becomes tubulose.After glue drying, take off Glass rod, together with the tubular material of preparation, put into containing 2%NaOH 50% ethanol water soak, de-pipe, tubular material water washing is neutral to pH, the ethanol dehydration of 95%, dry at 30 ~ 40 DEG C, the degradable blood vessel bracket base material 6 of obtained hollow tubular.
Take azido benzoyl ethoxyl chitin 0.5g, add 10ml distilled water, stirring and dissolving, obtain the azido benzoyl aminopolysaccharide glue that concentration expressed in percentage by weight is 5%, add anticoagulant heparin 5mg, stir, obtain anticoagulant glue.Get the degradable blood vessel bracket base material 6 of above-mentioned hollow tubular, two ends connect and are fixed on the undercoating seam of plater, open plater, anticoagulant glue is evenly injected in the inner surface of the degradable blood vessel bracket base material 6 of rotation through built-in moveable playpipe, injector head, make anticoagulant glue uniform coating at the inner surface of degradable blood vessel bracket base material 6, control glue thickness 0.5mm, ultraviolet light cross-linking under room temperature.Take azido benzoyl ethoxyl chitin 1.1g again, add 10ml distilled water, stirring and dissolving, obtain the azido benzoyl aminopolysaccharide glue that concentration expressed in percentage by weight is 10%, add developing agent barium sulfate 50mg, stir, obtain developing agent glue.Developing agent glue is evenly injected in the outer surface of the degradable blood vessel bracket base material 6 of rotation through the external moveable playpipe of plater, injector head, make developing agent glue uniform coating at the outer surface of degradable blood vessel bracket base material 6, control glue thickness 0.5 ~ 1mm, ultraviolet light cross-linking under room temperature, dry, the degradable blood vessel bracket tubing 6 of obtained band anticoagulant and developing agent, its lumen diameter is about 4.8mm, and pipe thickness is 0.7mm.
The preparation of embodiment 9 degradable blood vessel bracket tubing 7:
Take the acylated amino polysaccharide 2 that the above-mentioned acyl group degree of 1.5g is 102.3%; 2.5g acyl group degree is the acylated amino polysaccharide 6 of 275%; add concentration expressed in percentage by weight be 88% formic acid solution 60ml (proportion 1.20) make solvent; low temperature dissolves, and is mixed with the acylated amino polysaccharide glue (w/v is 2.5%) that concentration expressed in percentage by weight is 4.6%.Get the stainless steel bar Pipe making mold of length 10cm, diameter 8mm; be connected to the Pipe making mold seam on tuber; open tuber; by acylated amino polysaccharide glue equably coating rotate stainless steel bar on the surface; control glue thickness at 2mm ~ 4mm; temperature control 30 ~ 40 DEG C, Rotary drying becomes tubulose.After glue drying, take off stainless steel bar, together with the tubular material of preparation, the aqueous solution put into containing 3%NaOH 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 base material 7 of obtained hollow tubular.
Take azido benzoyl Chitofilmer 0.5g, add 10ml distilled water, stirring and dissolving, obtain the azido benzoyl aminopolysaccharide glue that concentration expressed in percentage by weight is 5%, add anticoagulant heparin 80mg, stir, obtain anticoagulant glue.Get the degradable blood vessel bracket base material 7 of above-mentioned hollow tubular, two ends connect and are fixed on the undercoating seam of plater, open plater, anticoagulant glue is evenly injected in the inner surface of the degradable blood vessel bracket base material 7 of rotation through built-in moveable playpipe, injector head, make anticoagulant glue uniform coating at the inner surface of degradable blood vessel bracket base material 7, control glue thickness 0.5 ~ 0.8mm, ultraviolet light cross-linking under room temperature.Take azido benzoyl Chitofilmer 0.5g again, add 10ml distilled water, stirring and dissolving, obtain the azido benzoyl aminopolysaccharide glue that concentration expressed in percentage by weight is 5%, add developing agent barium sulfate 500mg, stir, obtain developing agent glue.Developing agent glue is evenly injected in the outer surface of the degradable blood vessel bracket base material 7 of rotation through the external moveable playpipe of plater, injector head, make developing agent glue uniform coating at the outer surface of degradable blood vessel bracket base material 7, control glue thickness 0.8 ~ 1.2mm, ultraviolet light cross-linking under room temperature, dry, the degradable blood vessel bracket tubing 7 of obtained band anticoagulant and developing agent, its lumen diameter is about 6.8mm, and pipe thickness is 0.8mm.
The preparation of embodiment 10 degradable blood vessel bracket tubing 8:
Take the acylated amino polysaccharide 2 that the above-mentioned acyl group degree of 1.5g is 102.3%; 2.5g acyl group degree is the acylated amino polysaccharide 6 of 275%; add concentration expressed in percentage by weight be 88% formic acid solution 60ml (proportion 1.20) make solvent; low temperature dissolves, and is mixed with the acylated amino polysaccharide glue (w/v is 2.5%) that concentration expressed in percentage by weight is 4.6%.Get the stainless steel bar Pipe making mold of length 10cm, diameter 8mm; be connected to the Pipe making mold seam on tuber; open tuber; by acylated amino polysaccharide glue equably coating rotate stainless steel bar on the surface; control glue thickness at 2mm ~ 4mm; temperature control 30 ~ 40 DEG C, Rotary drying becomes tubulose.After glue drying, take off stainless steel bar, together with the tubular material of preparation, the aqueous solution put into containing 3%NaOH 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 base material 8 of obtained hollow tubular.
Take azido benzoyl Chitofilmer 0.5g, add 10ml distilled water, stirring and dissolving, obtain the azido benzoyl aminopolysaccharide glue that concentration expressed in percentage by weight is 5%, add anticoagulant 2mg arasaponin R1, stir, obtain anticoagulant glue.Get the degradable blood vessel bracket base material 8 of above-mentioned hollow tubular, two ends connect and are fixed on the undercoating seam of plater, open plater, anticoagulant glue is evenly injected in the inner surface of the degradable blood vessel bracket base material 8 of rotation through built-in moveable playpipe, injector head, make anticoagulant glue uniform coating at the inner surface of degradable blood vessel bracket base material 8, control glue thickness 0.5 ~ 0.8mm, ultraviolet light cross-linking under room temperature.Take azido benzoyl Chitofilmer 0.5g again, add 10ml distilled water, stirring and dissolving, obtain the azido benzoyl aminopolysaccharide glue that concentration expressed in percentage by weight is 5%, add developing agent barium sulfate 500mg, stir, obtain developing agent glue.Developing agent glue is evenly injected in the outer surface of the degradable blood vessel bracket base material 8 of rotation through the external moveable playpipe of plater, injector head, make developing agent glue uniform coating at the outer surface of degradable blood vessel bracket base material 8, control glue thickness 0.8 ~ 1.2mm, ultraviolet light cross-linking under room temperature, dry, the degradable blood vessel bracket tubing 8 of obtained band anticoagulant and developing agent, its lumen diameter is about 6.8mm, and pipe thickness is 0.8mm.
The mechanical experimental results of embodiment 11 intravascular stent tubing
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 mechanical properties of tubular goods is as shown in table 1, shows the better mechanical property of vascular stent material.
The For Measuring Mechanical Properties of table 1. vascular stent material
| Tubing | Hot strength (N) | Elongation at break (%) |
| Intravascular stent tubing 1 | 1.3 | 52.5 |
| Intravascular stent tubing 2 | 3.8 | 75.6 |
| Intravascular stent tubing 3 | 3.2 | 70.3 |
| Intravascular stent tubing 4 | 2.5 | 63.2 |
| Intravascular stent tubing 5 | 1.7 | 52.8 |
| Intravascular stent tubing 6 | 2.6 | 65.9 |
| Intravascular stent tubing 7 | 3.5 | 75.3 |
| Intravascular stent tubing 8 | 3.5 | 76.4 |
The rate of release of the heparin of embodiment 12 intravascular stent tubing
By the degradable blood vessel bracket tubing 3 of the band anticoagulant in above-described embodiment 5 and embodiment 7 and developing agent and intravascular stent tubing 5, clip length is the tubing 2 sections of 2mm respectively, totally 4 sections, the tubing of each section of clip is put into respectively the little triangular flask that 15ml distilled water is housed, 37 DEG C, 60rmp, constant temperature oscillation.Within every 2 days, the tubing soaked is taken out, puts into the little triangular flask that 15ml distilled water is newly housed, continue constant temperature oscillation, measure absorption value with the normal saline of the former immersion of reddish black A Determination Staining at 505nm simultaneously, contrast Heparin Standard curve, calculate heparin slow release amount, slow release result is as table 2.Visible vessels support tubing, after the 1st day prominent is released, enters the slow releasing stage, has good anticoagulation function thus after 2 days.
Table 2. heparin slow release measures
Embodiment 13
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.The degradable blood vessel bracket tubing 1 of above-described embodiment 3, the degradable blood vessel bracket tubing 4 of embodiment 6 are 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 4.Degradable blood vessel bracket 1 pipe range 4cm after processing, lumen diameter 3.8mm, pipe thickness 0.08mm; Degradable blood vessel bracket 4 pipe range 3cm, lumen diameter 3.0mm, pipe thickness 0.6mm; Tube wall all has penetrating rule or irregular pore space structure or patterning.
Embodiment 14
The machine cuts processing of degradable blood vessel bracket: the degradable blood vessel bracket tubing 2 in above-described embodiment 4, embodiment 8, intravascular stent tubing 6 are individually fixed on support process operation platform, machine cuts processing is carried out to intravascular stent tubing.Degradable blood vessel bracket 2 pipe range 2cm after processing, lumen diameter 7.8mm, pipe thickness 1.6mm; Degradable blood vessel bracket 6 pipe range 2cm, lumen diameter 4.8mm, pipe thickness 0.7mm; Tube wall does not have penetrating pore space structure or patterning.
Embodiment 15
Respectively in Example 13 in the degradable blood vessel bracket 4 and embodiment 14 of Laser cutting through the degradable blood vessel bracket 6 of machine cuts processing, respectively get 2, pack separately, ethane via epoxyethane sterilizing, be used as dog femoral artery and implant.Experiment beasle 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.Test the intravascular stent observing to implant with X-ray for latter 1 day, the image of visible implantable intravascular, the unobstructed situation of femoral artery blood flow of postoperative 6 months Doppler observation operative sites, display femoral artery blood flow is unobstructed, have no obvious stenosis, observe obvious vascular pulsation by frequency spectrum.
Claims (10)
1. a degradable blood vessel bracket, is characterized in that:
With the hollow tubular structure that acylated amino polysaccharide is made for material, the inner surface of tubular structure has anticoagulant coatings, and the outer surface of tubular structure has development coating, and tube wall is with or without penetrating pore space structure or patterning.
2. degradable blood vessel bracket as claimed in claim 1, is characterized in that:
The molecular structure of described acylated amino polysaccharide is polyamides base glucosamine polysaccharide; total acyl group degree in the molecular structure of described acylated amino polysaccharide is more than or equal to 70%; described acyl group is one or more in acetyl group, propiono, bytyry, caproyl, caprylyl, certain herbaceous plants with big flowers acyl group, lauroyl, palmityl and other aliphatic or aromatic acyl group, and the molecular structural formula of acylated amino polysaccharide is:
In formula, R
1, R
2or R
3be one or more in H, acetyl group, propiono, bytyry, caproyl, caprylyl or certain herbaceous plants with big flowers acyl group, lauroyl, palmityl and other aliphatic or aromatic acyl group, acyl group degree is more than or equal to 70%.
3. degradable blood vessel bracket as claimed in claim 1, is characterized in that:
Described anticoagulant coatings is the azido benzoyl aminopolysaccharide coating containing anticoagulant;
Described development coating is the azido benzoyl aminopolysaccharide coating containing developing agent.
4. as claim 3 and azido benzoyl aminopolysaccharide according to claim 4; it is characterized in that described azido benzoyl aminopolysaccharide is hydrazoic benzoyl chitosan, azido benzoyl hydroxyethyl chitosan, azido benzoyl hydroxypropyl chitosan, azido benzoyl carboxymethyl chitosan, azido benzoyl chitin, azido benzoyl ethoxyl chitin, azido benzoyl Chitofilmer, and chitin, chitosan other azido benzoyl derivant.
5. degradable blood vessel bracket as claimed in claim 1, is characterized in that:
Described hollow tubular structure is the interior diameter of tube chamber is 2.0 ~ 10mm, and the thickness of tube wall is 0.05mm ~ 2.0mm.
6. the preparation method of a kind of degradable blood vessel bracket according to claim 1, is characterized in that:
Acylated amino polysaccharide is dissolved in solvent, preparation concentration expressed in percentage by weight be 1% ~ 20% or w/v be 1% ~ 25% acylated amino polysaccharide glue; Open the tuber with Pipe making mold, by acylated amino polysaccharide glue coating on Pipe making mold, control glue thickness, room temperature or temperature control heat drying become tubulose;
Pipe making mold is put into dilute alkaline aqueous solution, ethanol water or distilled water together with the tubular material prepared soak, de-pipe, is washed to pH neutrality, and dehydration is dry, obtains the degradable blood vessel bracket base material of hollow tubular;
Preparation concentration expressed in percentage by weight is the azido benzoyl aminopolysaccharide glue of 0.5% ~ 25%, adds anticoagulant, obtained anticoagulant glue, by anticoagulant glue coating at degradable blood vessel bracket base material inner surface, and ultraviolet light cross-linking;
Preparation concentration expressed in percentage by weight is the azido benzoyl aminopolysaccharide glue of 0.5% ~ 25%, adds developing agent, obtained developing agent glue, by developing agent glue coating at degradable blood vessel bracket substrate outer surface, and ultraviolet light cross-linking;
Drying, the degradable blood vessel bracket tubing of obtained band anticoagulant and developing agent;
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.
7. the preparation method of a kind of degradable blood vessel bracket as claimed in claim 7, is characterized in that:
Described solvent is that aqueous formic acid concentration expressed in percentage by weight is more than or equal to 70%, hexafluoroisopropanol, oxolane, ethanol, and those skilled in the art other solvent of being familiar with, as trichloroacetic acid, dichloroacetic acid etc.
8. the preparation method of a kind of degradable blood vessel bracket as claimed in claim 7, is characterized in that:
Described anticoagulant is heparin, and the anticoagulation preparation that other anticoagulation preparation of Clinical practice and those skilled in the art predict.
9. the preparation method of a kind of degradable blood vessel bracket as claimed in claim 7, is characterized in that:
Described developing agent is barium sulfate, cardiografin, and the developing agent that other developing agent of Clinical practice and those skilled in the art predict, as fluorescein, tantalum powder etc.
10. degradable blood vessel bracket as claimed in claim 1, is characterized in that:
By in 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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| CN105944153A (en) * | 2016-05-24 | 2016-09-21 | 德州海利安生物科技股份有限公司 | Development type degradable repair biliary tract stent |
| CN105999434A (en) * | 2016-05-24 | 2016-10-12 | 德州海利安生物科技股份有限公司 | Developing type degradable ureter repairing stent |
| CN105999435A (en) * | 2016-05-24 | 2016-10-12 | 德州海利安生物科技股份有限公司 | Developing type degradable urethra repairing stent |
| CN105999425A (en) * | 2016-05-24 | 2016-10-12 | 德州海利安生物科技股份有限公司 | Developing type degradable repairing stent |
| CN106039426A (en) * | 2016-05-24 | 2016-10-26 | 德州海利安生物科技股份有限公司 | Developing type degradable restoration pancreatic duct bracket |
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| CN105148332B (en) | 2017-11-21 |
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