CN111110413A - Intracranial degradable biological stent with micropore array and preparation method thereof - Google Patents

Abstract

The invention discloses an intracranial biodegradable stent with a micropore array and a preparation method thereof. After the vascular stent is sent into intracranial blood vessels, the contact area can be increased, and the drug release quantity is increased. Because the intravascular stent has small mass and high degradation rate in the blood vessel of a human body, the recovery of the lesion part can be accelerated. The intracranial biodegradable stent and the preparation method thereof provided by the invention have automation in the whole process, and have the advantages of simplicity and convenience in operation and higher yield.

Description

Intracranial degradable biological stent with micropore array and preparation method thereof

The technical field is as follows:

the invention belongs to the field of medical treatment, and particularly relates to an intracranial degradable biological stent with a micropore array and a preparation method thereof.

Background art:

at present, as a main medical apparatus for treating cerebral infarction, a drug coating stent body is always made of inert metal materials, mainly 316L medical stainless steel and cobalt-chromium alloy, and the metal stent is implanted into blood vessels as a heterologous substance and always remains in a human body, so that the treatment is more troublesome when restenosis occurs. Moreover, the polymer used as the drug carrier at present is also a non-degradable material, and the drug can be always remained in the human body after being released, which can cause fatal subacute embolism or late thrombosis for some patients.

Therefore, the research adopts a biodegradable material as the stent, so that the stent has various mechanical properties of a metal stent, does not change the currently adopted delivery method, and becomes another research hotspot field in the field of minimally invasive interventional medical instruments. The biodegradable stent can realize the supporting function of the metal stent after being implanted into the vascular disease dislocation, and after the therapeutic drug carried by the biodegradable stent is completely released, the body of the biodegradable stent can be gradually degraded into a substance which can be absorbed by a human body and has no toxic or side effect within a period of time until the substance is completely degraded.

At present, in the aspect of biodegradable stents, BVS stents of Abbotium americana and DESlave stents of Elixir Medical americana enter clinical test stages, and the vascular stents cannot completely meet clinical requirements in the aspects of mechanical strength, volume, degradation performance, release rate of loaded drugs and the like. Meanwhile, the stent has larger mass and larger load in the blood vessel. The surface area of the stent is limited, and the insufficient drug loading is also a problem encountered by the current blood vessel stent. In addition, the existing vascular stent has a rough processing surface, low manufacturing precision and low yield, and the popularization and application of the vascular stent are restricted to a great extent. Therefore, the problems need to be solved, and the action effect of the intracranial degradable biological stent is improved.

The invention content is as follows:

in order to solve the problems, the invention provides an intracranial biodegradable stent with a micropore array and a preparation method thereof. The intracranial vascular stent prepared by the preparation method can solve the problems of large mass, large intravascular load, insufficient drug loading, low manufacturing precision and the like of the existing related stent, has moderate strength, good processing plasticity and high mechanical strength and volume which can meet the clinical requirements, can be used as a carrier of a drug by surface treatment of the stent, can target and slow release the drug, and has relatively low cost, high manufacturing precision and high forming efficiency.

In order to achieve the purpose, the technical scheme of the invention is as follows:

the utility model provides an intracranial biodegradable support with micropore array, includes the support body, the support body includes loop configuration a, ripples pole, loop configuration b, loop configuration a and loop configuration b parallel arrangement, the ripples pole is at loop configuration a and loop configuration b of centre intercommunication, and it has the micropore of closest row array to open on the support body, and the shape of micropore is circular, triangle-shaped, hexagon or dodecagon, loop configuration a and loop configuration b are hollow wave pipeline, at the surface of support body and micropore internal coating medicine layer.

A preparation method of an intracranial biodegradable stent with a micropore array specifically comprises the following steps:

(1) a raw pipe preparation step, wherein a raw pipe with preset inner and outer diameters is prepared by utilizing a degradable material;

(2) an expansion step, wherein the original pipe is placed in a mould, and the original pipe is heated and pressurized to expand the original pipe so that the outer diameter of the original pipe reaches the inner diameter of the mould;

(3) a stent body preparation step in which the expanded tube is cooled and prepared into a final degradable stent;

(4) processing the hollow structure of the vascular stent: the hollow structure on the bracket can be processed by laser, and the pipe is cut by a femtosecond or picosecond laser after expansion molding, wherein the laser wavelength is not more than 400nm, the power range is 0.6 mW-6W, and the pulse interval is 60-6000 fs;

(5) perforating the vascular stent: and (3) punching a hole on the degradable bracket by using the micropore manufacturing shielding plate, irradiating laser on the micropore manufacturing shielding sample plate to form micropores with the same pattern on the bracket, and finishing the processing of the micropore close-packed array by using the relative motion of the laser beam and the degradable bracket. The laser wavelength adopted by the laser processing of the micropore is not more than 400nm, the power range is 0.6 mW-1W, and the pulse interval is 60-1000 fs;

(6) coating the medicine: after laser cutting and laser boring obtain fashioned degradable support, at the surface of support and coating medicine layer in the micropore, after implanting the intravascular suitable position with degradable support, slowly release the medicine of surface coating or inside distribution to the vascular wall according to the demand to the intimal hyperplasia of blood vessel has been inhibited, the incidence of restenosis is reduced. The applied medicine is circularly distributed according to gradient, the medicine is released layer by layer, and the goal of reciprocating circular treatment is realized by the circulation.

An intracranial biodegradable stent having a microporous array coated with a drug selected from one or more of an anti-cancer drug, an anticoagulant, a microbial immunosuppressant, and other anti-restenosis drugs.

The anticancer drug is selected from one or more of methotrexate, purine, pyrimidine, plant alkali, epothilone, Tripterygium wilfordii series compounds, antibiotics (especially actinomycin-D), hormone, and antibody anticancer drugs. Preferably, the plant alkaloid anticancer drug is paclitaxel.

The anticoagulant is selected from one or more of heparin, aspirin, hirudin, colchicine and antiplatelet GP IIb/IIIa receptor antagonist.

The microbial immunosuppressant is selected from one or more of cyclosporine A, tacrolimus and homologues, degerming guanamine, enzymatic phenolate, rapamycin and derivatives thereof, a strain FR900520 of streptomyces species, a strain FR900523 of streptomyces species, daclizumab, valeramide, congolycin C, sertraline, prodigiosin 25C, tranilast, myriocin, cyclosporine C, brevicillin, mycophenolic acid, brefeldin A and ketocorticosteroids.

Helium with purity of more than 99.999 percent is used for cooling in the preparation and processing process of the intracranial biodegradable stent with the micropore array, so that the heat effect is reduced.

Compared with the prior art, the invention has the following beneficial effects:

(1) the intracranial vascular stent provided by the invention has the characteristics of preventing injury to vascular walls, good mechanical property, drug loading capability, large drug loading amount and convenience in drug release.

(2) The intracranial vascular stent provided by the invention has the characteristics of light stent weight and small load in blood vessels, and is more suitable for intracranial blood vessels of a human body.

(3) The intracranial vascular stent provided by the invention has a densely-arranged micropore array, can greatly improve the drug-loading area and the contact area of the vascular stent and the vascular wall, prevents the vascular wall from being damaged, and improves the effect of drugs.

(4) The intracranial vascular stent provided by the invention has the characteristic of light weight, needs shorter time when being decomposed in blood vessels, has good degradation characteristic, and can be more suitable for the treatment requirement of a human body.

Description of the drawings:

FIG. 1 unfolding structure of degradable stent of the present invention

FIG. 2 schematic of multilayer drug application

FIG. 3 is a mask for making micro-holes according to the present invention

1. A cyclic structure a; 2. wave crest; 3. micropores; 4. a wave bar; 5. a cyclic structure b; 6. a support base; 7. 1, a drug; 8. 2, a drug; 9. manufacturing a shielding sample plate by micropores; 10. a micropore gap.

The specific implementation mode is as follows:

the present invention is further illustrated by the following description in conjunction with the accompanying drawings and the specific embodiments, it is to be understood that these examples are given solely for the purpose of illustration and are not intended as a definition of the limits of the invention, since various equivalent modifications will occur to those skilled in the art upon reading the present invention and fall within the limits of the appended claims.

As shown in the figure, the intracranial biodegradable stent with the micropore array comprises a stent body, wherein the stent body comprises an annular structure a, a wave rod 4 and an annular structure b, the annular structure a and the annular structure b are arranged in parallel, the wave rod is communicated with the annular structure a and the annular structure b in the middle,micropores 3 in a closest array are formed in the stent body, the shape of each micropore is circular, triangular, hexagonal or dodecagonal, the diameter of each micropore is 5-10 micrometers, the annular structure a and the annular structure b are hollow wavy pipelines and are provided withwave crests 2 and wave troughs, and a medicine layer is coated on the surface of the stent body and in themicropores 3.

The hollow structures of the vascular stent annular structure a and the vascular stent annular structure b are processed by laser, and the tubular product is cut by a femtosecond or picosecond laser after expansion molding, wherein the laser wavelength is not more than 400nm, the power range is 0.6 mW-6W, and the pulse interval is 60-6000 fs.

The perforation of the bloodvessel support micropore 3 uses the micropore manufacturing shielding sample plate 9 to perforate on thedegradable support substrate 6, laser irradiates on the micropore manufacturing shielding sample plate 9, micropores 1 with the same pattern are formed on thesupport substrate 6, and the processing of the micropore close-packed array is completed by using the relative movement of the laser beam and the degradable support. The laser wavelength adopted by the laser processing of the micropore is not more than 400nm, the power range is 0.6 mW-1W, and the pulse interval is 60-1000 fs.

After the shaped degradable stent is obtained by laser cutting and laser drilling, a drug layer is coated on the surface of the vascular stent and in themicropores 3, as shown in fig. 2. The medicine layer adopts a gradient medicine coating layer according to the characteristics of pathological changes. For example, the drug 1 is applied first, then thedrug 2 is applied, and the drug coating is completed in a cyclic reciprocating manner. After the degradable stent is implanted into a proper position in a blood vessel, the medicine coated on the surface or distributed in themicropores 3 is slowly released to the blood vessel wall as required, so that the intimal hyperplasia of the blood vessel is inhibited, and the occurrence rate of restenosis is reduced. The applied medicine is circularly distributed according to gradient, the medicine is released layer by layer, and the goal of reciprocating circular treatment is realized by the circulation.

The technical means disclosed in the invention scheme are not limited to the technical means disclosed in the above embodiments, but also include the technical scheme formed by any combination of the above technical features.

Claims (9)

1. An intracranial degradable biological stent with a micropore array, which comprises a stent body and is characterized in that: the stent body comprises an annular structure a, a wave rod and an annular structure b, wherein the annular structure a and the annular structure b are arranged in parallel, the wave rod is communicated with the annular structure a and the annular structure b in the middle to form a closed annular stent integrally, micropores are densely arranged on the stent body and are circular, triangular, hexagonal or dodecagonal, the annular structure a and the annular structure b are hollow wavy pipelines, and a medicine layer is coated on the surface of the stent body and in the micropores.

2. An intracranial degradable biological stent having a microporous array as defined in claim 1, wherein: the applied drug is selected from one or more of anticancer drugs, anticoagulants, microbial immunosuppressants and other anti-restenosis drugs.

3. An intracranial degradable biological stent having a microporous array as in claim 2, wherein: the anti-cancer drug is selected from one or more of methotrexate, purines, pyrimidines, plant alkalies, epothilones, tripterygium compounds, antibiotics, hormones and antibody cancer treatment drugs.

4. An intracranial degradable biological stent having a microporous array as defined in claim 1, wherein: the anticoagulant is selected from one or more of heparin, aspirin, hirudin, colchicine and antiplatelet GP IIb/IIIa receptor antagonist.

5. An intracranial degradable biological stent having a microporous array as defined in claim 1, wherein: the microbial immunosuppressant is selected from one or more of cyclosporine A, tacrolimus and homologues, degerming guanamine, enzymatic phenolate, rapamycin and derivatives thereof, a strain FR900520 of streptomyces species, a strain FR900523 of streptomyces species, daclizumab, valeramide, congolycin C, sertraline, prodigiosin 25C, tranilast, myriocin, cyclosporine C, brevicillin, mycophenolic acid, brefeldin A and ketocorticosteroids.

6. An intracranial degradable biological stent having a microporous array as defined in claim 1, wherein: the medicine layer adopts a gradient medicine coating layer.

7. An intracranial degradable biological stent having a microporous array as defined in claim 1, wherein: the diameter of the micropores is 5-10 microns.

8. The method for preparing the intracranial degradable biological stent with the micropore array as recited in claim 1, wherein: the method specifically comprises the following steps:

(1) preparing an original pipe: preparing an original pipe with preset inner and outer diameters by using a degradable material;

(2) an expansion step: placing the original pipe into a mould, heating and pressurizing the original pipe, and expanding the original pipe to enable the outer diameter size of the original pipe to reach the inner diameter size of the mould;

(3) the preparation method of the stent main body comprises the following steps: cooling the expanded pipe and preparing a stent body;

(4) processing the hollow structure of the vascular stent: the hollow structure on the bracket is processed by laser, and the pipe is cut by a femtosecond or picosecond laser after expansion molding, wherein the laser wavelength is not more than 400nm, the power range is 0.6 mW-6W, and the pulse interval is 60-6000 fs;

(5) perforating the vascular stent: punching a hole on a bracket body by using a micropore manufacturing shielding plate, irradiating laser on a micropore manufacturing shielding sample plate to form micropores with the same pattern on the bracket, and finishing the processing of a micropore close-packed array by using the relative motion of a laser beam and the bracket body, wherein the laser wavelength adopted for the laser processing of the micropores is not more than 400nm, the power range is 0.6 mW-1W, and the pulse interval is 60-1000 fs;

(6) coating the medicine: after the formed degradable stent is obtained by laser cutting and laser drilling, a medicine layer is coated on the surface and in the micropores of the stent body.

9. The method for preparing the intracranial degradable biological stent with the micropore array as recited in claim 8, wherein: helium with purity of more than 99.999 percent is used for cooling the bracket body in the steps (3) - (6) of the preparation processing process.

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