CN116870261A - Restenosis-resistant shape memory polymer intestinal stent and preparation method thereof - Google Patents
Restenosis-resistant shape memory polymer intestinal stent and preparation method thereof Download PDFInfo
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- CN116870261A CN116870261A CN202310972818.9A CN202310972818A CN116870261A CN 116870261 A CN116870261 A CN 116870261A CN 202310972818 A CN202310972818 A CN 202310972818A CN 116870261 A CN116870261 A CN 116870261A
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- stent
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- intestinal
- shape memory
- restenosis
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Classifications
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- A—HUMAN NECESSITIES
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Abstract
The invention provides an anti-restenosis shape memory polymer intestinal canal stent and a preparation method thereof, wherein the intestinal canal stent comprises a tubular stent and a drug carrying layer embedded in the tubular stent; both the tubular stent and the drug-carrying layer are biodegradable materials; the tubular stent is composed of at least two shape memory materials with different driving conditions; materials of the drug-carrying layer include drugs and hydrogels; the intestinal stent comprises an initial shape, an intermediate shape and a temporary shape; the volume of the initial shape is greater than the volumes of the intermediate shape and the temporary shape; the volume of the intermediate shape is greater than the volume of the temporary shape; wherein, intestinal canal stent becomes different shapes under different driving conditions. The anti-restenosis shape memory polymer intestinal stent provided by the invention not only can solve the problem of damage or infection of intestinal mucosa caused by friction between the intestinal stent and the operation mouth of a patient or even by scar after implantation of the existing intestinal stent, but also has an anti-restenosis function and can prevent the problem of restenosis after operation.
Description
Technical Field
The invention relates to the technical field of medical material manufacturing, in particular to an anti-restenosis shape memory polymer intestinal stent and a preparation method thereof.
Background
Intestinal canal stents are commonly used stents for treating intestinal obstruction, intestinal fistula and other diseases caused by intestinal cancers and the like; patients suffering from intestinal cancer generally need to undergo intestinal and intestinal tissue resections, and intestinal scaffolds as intestinal endoluminal supports provide new options for intestinal cancer patients. However, after the common intestinal canal stent is implanted, the wearing discomfort caused by friction with the operation mouth of a patient, scars and the like can cause damage or infection of intestinal canal mucous membranes; meanwhile, after the intestinal stent is implanted into an affected part, the problem of intestinal restenosis can also occur in part of patients, so that the treatment effect of the intestinal stent is affected, and potential risks are generated for wound healing and life safety of the patients.
Disclosure of Invention
The embodiment of the invention provides an anti-restenosis shape memory polymer intestinal stent and a preparation method thereof, and the provided anti-restenosis shape memory polymer intestinal stent not only can solve the problems of damage or infection of intestinal mucosa even caused by friction with the operation mouth and scars of a patient after the implantation of the existing intestinal stent, but also has an anti-restenosis function so as to better prevent the restenosis problem after the operation of the intestinal stent and ensure the life safety of the patient.
In a first aspect, the present invention provides an anti-restenosis shape memory polymer intestinal stent comprising a tubular stent and a drug-loaded layer embedded in the tubular stent;
the tubular stent and the drug carrying layer are both biodegradable materials; the tubular stent is composed of at least two shape memory materials with different driving conditions; the material of the medicine carrying layer comprises medicine and hydrogel;
the intestinal stent comprises an initial shape, an intermediate shape and a temporary shape; the volume of the initial shape is greater than the volumes of the intermediate shape and the temporary shape; the volume of the intermediate shape is greater than the volume of the temporary shape; wherein the intestinal stent is deformed into different shapes under different driving conditions.
Preferably, the shape memory material is a shape memory polymer or a shape memory polymer comprising a functional filler;
the shape memory polymer is at least one of polyurethane, polyester, polyvinyl alcohol, polyethylene glycol, polycaprolactone, polylactic acid, poly (ethylene glycol) diacrylate, acrylated epoxidized soybean oil or poly (d, l-lactide-co-trimethylene carbonate);
the functional filler is magnetic filler or photo-thermal filler.
Preferably, the intestinal scaffold is deformed into the temporary shape at a material transition temperature;
the intestinal stent is deformed from the temporary shape to the intermediate shape under a first driving condition;
the intestinal stent is deformed from the intermediate shape to the initial shape under a second driving condition; wherein the first driving condition is different from the second driving condition.
Preferably, the tubular stent comprises a mesh structure and a negative poisson's ratio structure; the driving conditions of the mesh structure and the negative poisson ratio structure are different, and the negative poisson ratio structure is positioned on a node of the mesh structure.
Preferably, the shape memory material used in the mesh structure comprises at least one of polyurethane, polyester, polyvinyl alcohol or polyethylene glycol.
Preferably, the negative poisson's ratio structure consists of a shape memory polymer and a functional filler; the functional filler is magnetic filler or photo-thermal filler; the shape memory polymer is at least one of polycaprolactone, polylactic acid, polyurethane, poly (ethylene glycol) diacrylate, acrylated epoxidized soybean oil or poly (d, l-lactide-co-trimethylene carbonate).
Preferably, the mass ratio of the shape memory polymer to the functional filler in the negative poisson's ratio structure is (3-5): 1.
More preferably, the magnetic filler is at least one of gamma-ferric oxide, ferroferric oxide, neodymium iron boron, carbonyl iron and nickel zinc ferrite.
More preferably, the photo-thermal filler is at least one of gold nanoparticles, carbon black, graphene oxide or black phosphorus.
Preferably, the intestinal scaffold is deformed into the temporary shape at a material transition temperature;
the mesh structure reverts to a first initial shape under a first driving condition, deforming the intestinal stent from the temporary shape to the intermediate shape;
the negative poisson's ratio structure reverts to a second initial shape under a second driving condition, deforming the intestinal stent from the intermediate shape to the initial shape.
Preferably, the hydrogel is at least one of chitosan, cellulose, hyaluronic acid, heparin, alginate, polyacrylic acid, polyethylene glycol, polymethacrylic acid, polyvinyl alcohol, polyacrylamide or poly (N-isopropylacrylamide) with stress response property;
the drug-loaded layer is responsive to an external stimulus to control the rate of drug release; the external stimulus includes one or more of pH, light, magnetism, temperature, specific ions, or enzymes.
More preferably, the mass ratio of the drug to the hydrogel is 1 (10-20).
In a second aspect, the present invention provides a method for preparing the anti-restenosis shape memory polymer intestinal stent of the first aspect, which comprises the following steps:
(1) Designing a three-dimensional structure model of an intestinal canal stent comprising a tubular stent and a drug carrying layer;
(2) And determining shape memory materials used by the tubular stent and the drug carrying layer, printing a plurality of materials by adopting a 4D printing technology, and obtaining the 4D printed intestinal canal stent with the initial shape after molding.
Preferably, the medicine carrying layer consists of medicine and hydrogel with stress response performance, and the mass ratio of the medicine to the hydrogel is 1 (10-20).
Preferably, the tubular stent comprises a mesh structure and a negative poisson's ratio structure; the driving conditions of the mesh structure and the negative poisson ratio structure are different, and the negative poisson ratio structure is positioned on a node of the mesh structure.
Compared with the prior art, the invention has at least the following beneficial effects:
(1) The anti-restenosis shape memory polymer intestinal canal stent provided by the invention is composed of at least two shape memory materials with different driving conditions, so that the intestinal canal stent can be deformed into different shapes under different driving conditions, the volume of an initial shape is larger than the volume of a middle shape is larger than the volume of a temporary shape, and when the intestinal canal stent is deformed from the temporary shape to the middle shape, the function of supporting intestinal canal of the existing intestinal canal stent is achieved; when the intestinal canal bracket is changed from the temporary shape to the middle shape, the support effect of the intestinal canal bracket is further improved when restenosis occurs on the affected part of the intestinal canal of a patient, so that the effect of resisting the intestinal canal restenosis is achieved, and the intestinal canal bracket is ensured to still play a good treatment effect under the condition of facing the intestinal canal restenosis of the patient.
(2) Compared with other drug carriers, the anti-restenosis shape memory polymer intestinal canal stent provided by the invention has the advantages that the hydrogel has better stability, higher encapsulation effectiveness, better biocompatibility and biodegradability, and can continuously release drugs at an affected part. In addition, for the hydrogel with stress response performance, the drug carrying layer can respond to external stimulus such as pH, light, magnetism, temperature, specific ions or enzymes, and the like, so that the drug release rate is further controlled, and the convenience and the delivery efficiency of drug delivery are remarkably improved.
(3) The preparation method of the restenosis-resistant shape memory polymer intestinal stent provided by the invention utilizes a 4D printing technology to prepare the multi-material shape memory polymer intestinal stent, is not limited by a complex structure, has the characteristic of rapid molding, is suitable for personalized customization of the intestinal stent, and has wider application prospect.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are required in the embodiments or the description of the prior art will be briefly described, and it is obvious that the drawings in the following description are some embodiments of the present invention, and other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a schematic plan view of an anti-restenosis shape memory polymer intestinal stent according to an embodiment of the present invention;
FIG. 2 is a schematic illustration of structural units of an anti-restenosis shape memory polymer intestinal stent according to an embodiment of the present invention;
FIG. 3 is a schematic illustration of the temporary shape of an anti-restenosis shape memory polymer intestinal stent according to an embodiment of the present invention;
FIG. 4 is a schematic illustration of the structure of an intermediate shape of an anti-restenosis shape memory polymer intestinal stent according to an embodiment of the present invention;
FIG. 5 is a schematic illustration of the structure of an initial shape of an anti-restenosis shape memory polymer stent according to an embodiment of the present invention;
FIG. 6 is a schematic representation of a return shape change of an anti-restenosis shape memory polymer stent according to an embodiment of the present invention;
reference numerals:
1-net structure, 2-negative poisson ratio structure, 3-medicine carrying layer.
Detailed Description
For the purpose of making the objects, technical solutions and advantages of the embodiments of the present invention more apparent, the technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention, and it is apparent that the described embodiments are some embodiments of the present invention, but not all embodiments, and all other embodiments obtained by persons of ordinary skill in the art without making creative efforts based on the embodiments of the present invention are all within the scope of protection of the present invention.
The embodiment of the invention provides an anti-restenosis shape memory polymer intestinal canal stent, which comprises a tubular stent and a drug carrying layer embedded in the tubular stent;
both the tubular stent and the drug-carrying layer are biodegradable materials; the tubular stent is composed of at least two shape memory materials with different driving conditions; materials of the drug-carrying layer include drugs and hydrogels;
the intestinal stent comprises an initial shape, an intermediate shape and a temporary shape; the volume of the initial shape is greater than the volumes of the intermediate shape and the temporary shape; the volume of the intermediate shape is greater than the volume of the temporary shape; wherein, intestinal canal stent becomes different shapes under different driving conditions.
In the invention, the anti-restenosis shape memory polymer intestinal stent is composed of at least two shape memory materials with different driving conditions, so that the intestinal stent can be deformed into different shapes under different driving conditions, the volume of an initial shape is larger than the volume of a middle shape is larger than the volume of a temporary shape, and when the intestinal stent is deformed from the temporary shape to the middle shape, the function of supporting the intestinal tract of the existing intestinal stent is achieved; when the intestinal canal bracket is changed from the temporary shape to the middle shape, the support effect of the intestinal canal bracket is further improved when restenosis occurs on the affected part of the intestinal canal of a patient, so that the effect of resisting the intestinal canal restenosis is achieved, and the intestinal canal bracket is ensured to still play a good treatment effect under the condition of facing the intestinal canal restenosis of the patient.
In the invention, the drug-carrying layer is embedded in the anti-restenosis shape memory polymer intestinal stent, compared with other drug carriers, the hydrogel has better stability, higher encapsulation effectiveness, better biocompatibility and biodegradability, can realize the controlled slow release of the drug at an affected part, achieves the aim of targeted treatment, and obtains better treatment effect.
In the invention, the intestinal canal bracket is prepared from biodegradable materials, and the intestinal canal bracket with biocompatibility can reduce rejection reaction after being implanted into a human body, thereby effectively relieving the pain of a patient; meanwhile, in the time of intestinal healing, the intestinal stent can be gradually biodegraded into non-toxic and non-immune products, and the products are absorbed by a human body or discharged out of the body, so that the safety is higher.
The initial shape, the intermediate shape and the temporary shape of the anti-restenosis shape memory polymer intestinal stent are all three-dimensional net-shaped tubular structures.
According to some preferred embodiments, the shape memory material is a shape memory polymer or a shape memory polymer comprising a functional filler;
the shape memory polymer is at least one of polyurethane, polyester, polyvinyl alcohol, polyethylene glycol, polycaprolactone, polylactic acid, poly (ethylene glycol) diacrylate, acrylated epoxidized soybean oil or poly (d, l-lactide-co-trimethylene carbonate);
the functional filler is magnetic filler or photo-thermal filler.
At least one kind is a mixture of any one or any plurality of kinds mixed in any proportion.
According to some preferred embodiments, the intestinal stent is deformed into a temporary shape at the material transition temperature;
the intestinal canal stent is deformed from a temporary shape to an intermediate shape under a first driving condition;
the intestinal stent is deformed from the intermediate shape to the initial shape under the second driving condition.
The first driving condition is different from the second driving condition. The intestinal canal stent is shaped into a temporary shape at the glass transition temperature of the material, the intestinal canal stent with the temporary shape is implanted into a human body or placed in an environment simulating body fluid of the human body after being compressed into the temporary shape which is small in volume and easy to be implanted in a minimally invasive manner, and the intestinal canal stent can return to the middle shape under the first driving condition, so that the effect of supporting the intestinal canal is achieved; under the second driving condition, the intestinal canal support can continuously return to the initial shape to finally reach the preset three-dimensional space shape, and the intestinal canal is further supported. Thus, in the invention, since the tubular stent is composed of at least two shape memory materials with different driving conditions, the corresponding shape memory materials can be deformed under different driving conditions, and after the driving conditions are carried out twice, the intestinal stent can be deformed twice, and the temporary shape is deformed to the middle shape and then the initial shape is deformed, so that the problem of restenosis after the intestinal stent operation can be solved by deforming again.
According to some preferred embodiments, the tubular stent comprises a mesh structure and a negative poisson's ratio structure; the driving conditions of the mesh structure and the negative poisson ratio structure are different, and the negative poisson ratio structure is positioned on the nodes of the mesh structure.
It should be noted that, the negative poisson ratio structures are all stepwise on the mesh structure. In the invention, the negative poisson ratio structure is arranged on the nodes of the net structure step by step, so that when the driving condition of the negative poisson ratio structure is reached, the negative poisson ratio structure can enable the intestinal stent to have a negative poisson ratio effect in the radial direction and the axial direction, and has special mechanical properties of the negative poisson ratio structure, namely, when the driving condition is reached after implantation, the intestinal stent is expanded in the radial direction and the axial direction simultaneously.
Specifically, negative poisson's ratio structures include, but are not limited to, rotating quadrilateral structural units, concave hexagonal structural units, star structural units, double-arrow structural units.
According to some preferred embodiments, the shape memory material employed in the mesh structure comprises at least one of polyurethane, polyester, polyvinyl alcohol, or polyethylene glycol.
According to some preferred embodiments, the negative poisson's ratio structure consists of a shape memory polymer and a functional filler; the functional filler is magnetic filler or photo-thermal filler; the shape memory polymer is at least one of polycaprolactone, polylactic acid, polyurethane, poly (ethylene glycol) diacrylate, acrylated epoxidized soybean oil or poly (d, l-lactide-co-trimethylene carbonate).
According to some preferred embodiments, the mass ratio of shape memory polymer to functional filler in the negative poisson's ratio structure is (3-5): 1 (e.g., may be either 3:1, 3.5:1, 4:1, 4.5:1 or 5:1).
In the invention, experiments prove that if the mass ratio of the shape memory polymer to the functional filler in the negative poisson ratio structure is lower than 3:1, the shape memory polymer and the functional filler are difficult to disperse uniformly and even agglomerate, and the negative poisson ratio structure is difficult to prepare; if the mass ratio of the shape memory polymer to the functional filler in the negative poisson ratio structure is higher than 5:1, the prepared negative poisson ratio structure has poor response and small deformation under the corresponding driving condition.
According to some more preferred embodiments, the magnetic filler is at least one of gamma-ferric oxide, neodymium iron boron, carbonyl iron, nickel zinc ferrite.
According to some more preferred embodiments, the photo-thermal filler is at least one of gold nanoparticles, carbon black, graphene oxide, or black phosphorus.
The particle size of the magnetic filler and the photo-thermal filler is smaller than 20nm.
According to some preferred embodiments, the drug-carrying layer is embedded in the mesh structure.
In the invention, the medicine carrying layer is embedded into the main body of the reticular structure of the intestinal canal bracket, and the reticular structure is embedded but not completely replaced, so that the reticular structure is used as the bracket for carrying the medicine carrying layer, and the hydrogel carrying medicine is not easy to fall off when being deformed along with the intestinal canal bracket. The medicine carried on the medicine carrying layer can reduce inflammatory reaction caused by implantation of the intestinal canal bracket, and meanwhile, the medicine can better reach the affected part along with the intestinal canal bracket, so that the medicine effect is improved.
According to some preferred embodiments, the intestinal stent is deformed into a temporary shape at the material transition temperature;
the net structure returns to the first initial shape under the first driving condition, so that the intestinal stent is deformed from the temporary shape to the middle shape;
the negative poisson ratio structure returns to the second initial shape under the second driving condition, so that the intestinal canal bracket is deformed from the middle shape to the initial shape; wherein the first driving condition is different from the second driving condition.
In the invention, under the first driving condition, only the reticular structure is deformed, the negative poisson ratio structure is not deformed, and the intestinal canal bracket is deformed from a temporary shape to an intermediate shape; under the second driving condition, the net structure is not deformed any more, the negative poisson ratio structure is deformed, and the intestinal canal bracket is deformed from the middle shape to the initial shape. The first initial shape is used to represent the initial shape of the mesh structure when the mesh structure returns from the contracted temporary shape to the original shape; the second initial shape is used to represent the initial shape of the negative poisson's ratio structure when the reduced temporary shape is returned to the original shape, respectively.
According to some preferred embodiments, the hydrogel is at least one of chitosan, cellulose, hyaluronic acid, heparin, alginate, polyacrylic acid, polyethylene glycol, polymethacrylic acid, polyvinyl alcohol, polyacrylamide or poly (N-isopropylacrylamide) with stress response properties;
the drug-loaded layer is responsive to an external stimulus to control the rate of drug release; the external stimulus includes one or more of pH, light, magnetism, temperature, specific ions or enzymes.
In the invention, the erosion and degradation of the hydrogel loaded with the drug by the body fluid of the human body causes the drug to be slowly released and dissolved. The degradation rate of the drug-loaded layer is generally determined by its composition, and standard PK animal tests can be used to select one or more polymers to confirm that the polymer has completed degradation 45 to 90 days after implantation.
According to more preferred embodiments, the mass ratio of drug to hydrogel is 1 (10-20) (e.g., may be 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, or 1:20).
In the invention, experiments prove that if the mass ratio of the drug to the hydrogel is higher than 1:10, the hydrogel is too little in dosage, the stress response performance of the drug carrying layer is poor, and the release rate of the drug and the convenience of drug delivery are further affected; if the mass ratio of the drug to the hydrogel is lower than 1:20, the drug dosage is too low, the drug carrying layer carries too little drug, and the treatment effect is reduced.
Specifically, the medicine is one or more of antitumor medicine, antiinfectious medicine, antiviral medicine, antifungal medicine, antiinflammatory and analgesic medicine and immunopotentiator. The intestinal canal bracket added with anticancer drugs, anti-infective drugs, anti-inflammatory and analgesic drugs, immunopotentiators and other drugs releases drugs in the diseased intestinal canal of a patient after the implantation of the intestinal canal bracket and the friction of the operation mouth, scars and the like of the patient can cause wearing discomfort and even skin damage or infection, thereby achieving the effects of inhibiting the growth and diffusion of cancer cells, preventing or treating wound infection, anti-inflammatory and analgesic or improving immunity and the like.
More specifically, the antitumor drug is one or more of oxaliplatin, abnormal spring alkaloid, paclitaxel, docetaxel, gemcitabine, capecitabine, rituximab, hydroxycamptothecin, pirarubicin or epirubicin; the anti-infective drug is one or more of beta-lactam antibiotics, aminoglycoside antibiotics, macrolide antibiotics or quinolones; the antiviral drug is one or more of ribavirin, acyclovir or ganciclovir; the anti-inflammatory analgesic is one or more of aspirin, acetaminophen, indomethacin, naproxen, diclofenac, ibuprofen, nimesulide, rofecoxib or celecoxib; the antifungal medicine is clotrimazole, ketoconazole, etc.; the immunopotentiator is one or more of chemically synthesized drugs (such as levamisole and isoprinosine), human or animal immune products (such as thymosin, transfer factor, interferon and interleukin), microorganism derived drugs (such as BCG vaccine), fungus polysaccharides (such as lentinan, etc.), or Chinese medicinal effective components.
The invention also provides a preparation method of the restenosis-resistant shape memory polymer intestinal stent, which comprises the following steps:
(1) Designing a three-dimensional structure model of an intestinal canal stent comprising a tubular stent and a drug carrying layer;
(2) And determining shape memory materials used for the tubular stent and the drug-carrying layer, printing multiple materials by adopting a 4D printing technology, and obtaining the 4D printed intestinal stent with the initial shape after molding.
In the present invention, the 4D printing technique includes, but is not limited to, a fused deposition modeling fabrication technique, a direct write modeling fabrication technique, a stereolithography fabrication technique, or a polymer jetting technique. The preparation method of the restenosis-resistant shape memory polymer intestinal stent provided by the invention utilizes the 4D printing technology to prepare the intestinal stent, is not limited by a complex structure, is suitable for personalized customization of the intestinal stent, and has wider application prospect; the preparation method has the characteristics of rapid molding, greatly shortens the preparation time of the intestinal stent mold, is low in preparation cost, simple in preparation method, high in practicability, easy to accept by consumers and has remarkable social and economic benefits.
According to some preferred embodiments, the drug-carrying layer is composed of a drug and a hydrogel having stress response properties, the mass ratio of drug to hydrogel being 1 (10-20).
According to some preferred embodiments, the tubular stent comprises a mesh structure and a negative poisson's ratio structure; the driving conditions of the mesh structure and the negative poisson ratio structure are different, and the negative poisson ratio structure is positioned on the nodes of the mesh structure.
In the invention, during practical application, the anti-restenosis shape memory polymer intestinal stent is shaped into a temporary shape with smaller volume at the glass transition temperature, after the temporary shape is implanted into a human body, the net structure of the intestinal stent is restored to the original shape by a first driving condition (for example, water at about 37 ℃), so as to play a role in supporting the intestinal tract, and the intestinal stent is in a middle shape at the moment; when restenosis occurs at the affected part of the intestinal canal in the human body, the negative poisson ratio structure of the intestinal canal bracket is restored to the original shape through the second driving condition (such as driving of a magnetic field or illumination), and the intestinal canal bracket is deformed from the middle shape to the original shape at the moment, so that the supporting effect of the intestinal canal bracket is further improved, and the effect of resisting the restenosis of the intestinal canal is achieved.
It should be noted that, the initial shape and the intermediate shape of the anti-restenosis shape memory polymer intestinal stent are obtained by acquiring medical image data of tumor, intestinal fistula or incision and surrounding tissues of a patient by applying a human body three-dimensional scanner, a Magnetic Resonance Imaging (MRI) technique, a CT scanning technique and the like before operation, and the obtained data are processed, designed and established by software such as medical simulation software, computer aided design and the like, so that the intestinal stent returned to the initial shape can play a better supporting and drug administration function for the intestinal tract of the patient.
In the invention, as the driving conditions of the reticular structure and the negative poisson ratio structure are relatively independent, the negative poisson ratio structure of the intestinal canal bracket can be selected according to the actual condition of a patient to treat the restenosis problem of the patient when the intestinal canal bracket plays a role in supporting the intestinal canal, and the drug release rate can be controlled by matching with the drug-carrying hydrogel epidermis, thereby being beneficial to personalized treatment for different patients and further relieving the pain of the patient.
In order to more clearly illustrate the technical scheme and advantages of the present invention, the following describes an anti-restenosis shape memory polymer intestinal stent and a preparation method thereof in detail through several examples.
Example 1
The preparation method of the anti-restenosis shape memory polymer intestinal stent comprises the following steps:
s1, diagnosing the size and shape of intestinal obstruction or fistula, and designing a three-dimensional structural model of a tubular bracket, as shown in fig. 1 and 2; the tubular support comprises a net structure 1 and a negative poisson ratio structure 2, the negative poisson ratio structure 2 is positioned on a node of the net structure 1, and the medicine carrying layer 3 is embedded into the net structure 1;
s2, determining a material with a net structure and a negative Poisson ratio structure (wherein the mass ratio of the shape memory polymer to the functional filler is 3:1); the medicine carrying layer consists of medicine and hydrogel with stress response performance, wherein the mass ratio of the medicine to the hydrogel is 1:10;
and (3) performing multi-material printing on the model designed according to the step (S1) by adopting a fused deposition or direct writing printing method, and obtaining the 4D printed tubular stent embedded in the drug-carrying layer after molding, namely obtaining the intestinal canal stent with the initial shape.
Application of intestinal stents: shaping the intestinal canal bracket into a temporary shape at the glass transition temperature, and restoring the net structure of the intestinal canal bracket into an initial shape through the driving action of water after the intestinal canal bracket is implanted into a human body, so as to play a supporting role for the intestinal canal of a patient, wherein the intestinal canal bracket is in a middle shape; when the patient generates intestinal restenosis in the postoperative recovery process, the negative poisson ratio structure of the intestinal stent is recovered to the initial shape through the driving action of the magnetic field or illumination, and the intestinal stent is in the initial shape at the moment, so that the effect of resisting the intestinal restenosis is achieved.
Specifically, for the application of the intestinal stent, as shown in fig. 3 to 6, after the initial shape of the intestinal stent as shown in fig. 5 is obtained, the intestinal stent is warmed up to the glass transition temperature and shaped, an external force is applied to keep the intestinal stent for 5-10s to cool down to room temperature, and the intestinal stent is given a temporary shape as shown in fig. 3. The temporary shape of the intestinal canal bracket can be set into a shape which is small in volume and easy to be implanted in a minimally invasive way, the intestinal canal bracket deforms after being implanted into a human body, and the temporary shape returns to a preset three-dimensional space shape, thereby providing possibility for realizing implantation of the intestinal canal bracket in a minimally invasive operation. The anti-restenosis shape memory polymer intestinal stent is deformed into a temporary shape shown in fig. 3 at the material transition temperature, is cooled to room temperature after being compressed and reduced, is implanted into a human body or placed in an environment simulating body fluid of the human body, and the net structure of the intestinal stent can be restored to an original shape at about 37 ℃ under the driving action of water, so that the effect of supporting the intestinal tract is achieved, and the intestinal stent is in an intermediate shape shown in fig. 4. When the patient produces intestinal restenosis in the postoperative recovery process, the negative poisson ratio structure in the intestinal stent can be recovered to the initial shape at about 45 ℃ through the driving effect of a magnetic field or illumination, and the intestinal stent is in the initial shape shown in fig. 5 at the moment, so that the supporting effect of the intestinal stent is further improved, the effect of resisting the intestinal restenosis is achieved, and the intestinal stent is ensured to still play a good treatment effect under the condition of facing the intestinal restenosis of the patient. Wherein, fig. 6 is a temporary shape, a middle shape and an initial shape of the intestinal stent from left to right, and fig. 6 shows a recovery shape change of the intestinal stent.
Example 2
The preparation method of the anti-restenosis shape memory polymer intestinal stent comprises the following steps:
s1, diagnosing the size and shape of intestinal obstruction or fistula site, and designing a three-dimensional structural model of a tubular stent; the tubular support comprises a reticular structure and a negative poisson ratio structure, the negative poisson ratio structure is positioned on nodes of the reticular structure, and the medicine carrying layer is embedded into the reticular structure;
s2, determining a material with a net structure and a negative Poisson ratio structure (wherein the mass ratio of the shape memory polymer to the functional filler is 4:1); the medicine carrying layer consists of medicine and hydrogel with stress response performance, wherein the mass ratio of the medicine to the hydrogel is 1:10;
and (3) performing multi-material printing on the model designed according to the step (S1) by adopting a fused deposition or direct writing printing method, and obtaining the 4D printed tubular stent embedded in the drug-carrying layer after molding, namely obtaining the intestinal canal stent with the initial shape.
Application of intestinal stents: shaping the intestinal canal bracket into a temporary shape at the glass transition temperature, and restoring the net structure of the intestinal canal bracket into an initial shape through the driving action of water after the intestinal canal bracket is implanted into a human body, so as to play a supporting role for the intestinal canal of a patient, wherein the intestinal canal bracket is in a middle shape; when the patient generates intestinal restenosis in the postoperative recovery process, the negative poisson ratio structure of the intestinal stent is recovered to the initial shape through the driving action of the magnetic field or illumination, and the intestinal stent is in the initial shape at the moment, so that the effect of resisting the intestinal restenosis is achieved.
Example 3
The preparation method of the anti-restenosis shape memory polymer intestinal stent comprises the following steps:
s1, diagnosing the size and shape of intestinal obstruction or fistula site, and designing a three-dimensional structural model of a tubular stent; the tubular support comprises a reticular structure and a negative poisson ratio structure, the negative poisson ratio structure is positioned on nodes of the reticular structure, and the medicine carrying layer is embedded into the reticular structure;
s2, determining a material of a net structure and a negative Poisson ratio structure, (wherein the mass ratio of the shape memory polymer to the functional filler is 5:1); the medicine carrying layer consists of medicine and hydrogel with stress response performance, wherein the mass ratio of the medicine to the hydrogel is 1:10;
and (3) performing multi-material printing on the model designed according to the step (S1) by adopting a fused deposition or direct writing printing method, and obtaining the 4D printed tubular stent embedded in the drug-carrying layer after molding, namely obtaining the intestinal canal stent with the initial shape.
Application of intestinal stents: shaping the intestinal canal bracket into a temporary shape at the glass transition temperature, and restoring the net structure of the intestinal canal bracket into an initial shape through the driving action of water after the intestinal canal bracket is implanted into a human body, so as to play a supporting role for the intestinal canal of a patient, wherein the intestinal canal bracket is in a middle shape; when the patient generates intestinal restenosis in the postoperative recovery process, the negative poisson ratio structure of the intestinal stent is recovered to the initial shape through the driving action of the magnetic field or illumination, and the intestinal stent is in the initial shape at the moment, so that the effect of resisting the intestinal restenosis is achieved.
Example 4
The preparation method of the anti-restenosis shape memory polymer intestinal stent comprises the following steps:
s1, diagnosing the size and shape of intestinal obstruction or fistula site, and designing a three-dimensional structural model of a tubular stent; the tubular support comprises a reticular structure and a negative poisson ratio structure, the negative poisson ratio structure is positioned on nodes of the reticular structure, and the medicine carrying layer is embedded into the reticular structure;
s2, determining a material with a net structure and a negative Poisson ratio structure (wherein the mass ratio of the shape memory polymer to the functional filler is 5:1); the medicine carrying layer consists of medicine and hydrogel with stress response performance, wherein the mass ratio of the medicine to the hydrogel is 1:15;
and (3) performing multi-material printing on the model designed according to the step (S1) by adopting a fused deposition or direct writing printing method, and obtaining the 4D printed tubular stent embedded in the drug-carrying layer after molding, namely obtaining the intestinal canal stent with the initial shape.
Application of intestinal stents: shaping the intestinal canal bracket into a temporary shape at the glass transition temperature, and restoring the net structure of the intestinal canal bracket into an initial shape through the driving action of water after the intestinal canal bracket is implanted into a human body, so as to play a supporting role for the intestinal canal of a patient, wherein the intestinal canal bracket is in a middle shape; when the patient generates intestinal restenosis in the postoperative recovery process, the negative poisson ratio structure of the intestinal stent is recovered to the initial shape through the driving action of the magnetic field or illumination, and the intestinal stent is in the initial shape at the moment, so that the effect of resisting the intestinal restenosis is achieved.
Example 5
The preparation method of the anti-restenosis shape memory polymer intestinal stent comprises the following steps:
s1, diagnosing the size and shape of intestinal obstruction or fistula site, and designing a three-dimensional structural model of a tubular stent; the tubular support comprises a reticular structure and a negative poisson ratio structure, the negative poisson ratio structure is positioned on nodes of the reticular structure, and the medicine carrying layer is embedded into the reticular structure;
s2, determining a material with a net structure and a negative Poisson ratio structure (wherein the mass ratio of the shape memory polymer to the functional filler is 5:1); the medicine carrying layer consists of medicine and hydrogel with stress response performance, wherein the mass ratio of the medicine to the hydrogel is 1:20, a step of;
and (3) performing multi-material printing on the model designed according to the step (S1) by adopting a fused deposition or direct writing printing method, and obtaining the 4D printed tubular stent embedded in the drug-carrying layer after molding, namely obtaining the intestinal canal stent with the initial shape.
Application of intestinal stents: shaping the intestinal canal bracket into a temporary shape at the glass transition temperature, and restoring the net structure of the intestinal canal bracket into an initial shape through the driving action of water after the intestinal canal bracket is implanted into a human body, so as to play a supporting role for the intestinal canal of a patient, wherein the intestinal canal bracket is in a middle shape; when the patient generates intestinal restenosis in the postoperative recovery process, the negative poisson ratio structure of the intestinal stent is recovered to the initial shape through the driving action of the magnetic field or illumination, and the intestinal stent is in the initial shape at the moment, so that the effect of resisting the intestinal restenosis is achieved.
Finally, it should be noted that: the above embodiments are only for illustrating the technical solution of the present invention, and are not limiting; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit and scope of the technical solutions of the embodiments of the present invention.
Claims (10)
1. An anti-restenosis shape memory polymer intestinal stent, characterized in that the intestinal stent comprises a tubular stent and a drug-carrying layer embedded in the tubular stent;
the tubular stent and the drug carrying layer are both biodegradable materials; the tubular stent is composed of at least two shape memory materials with different driving conditions; the material of the medicine carrying layer comprises medicine and hydrogel;
the intestinal stent comprises an initial shape, an intermediate shape and a temporary shape; the volume of the initial shape is greater than the volumes of the intermediate shape and the temporary shape; the volume of the intermediate shape is greater than the volume of the temporary shape; wherein the intestinal stent is deformed into different shapes under different driving conditions.
2. The anti-restenosis shape memory polymer intestinal stent of claim 1, wherein the shape memory material is a shape memory polymer or a shape memory polymer comprising a functional filler;
the shape memory polymer is at least one of polyurethane, polyester, polyvinyl alcohol, polyethylene glycol, polycaprolactone, polylactic acid, poly (ethylene glycol) diacrylate, acrylated epoxidized soybean oil or poly (d, l-lactide-co-trimethylene carbonate);
the functional filler is magnetic filler or photo-thermal filler.
3. The anti-restenosis shape memory polymer intestinal stent of claim 1, wherein the intestinal stent deforms to the temporary shape at a material transition temperature;
the intestinal stent is deformed from the temporary shape to the intermediate shape under a first driving condition;
the intestinal stent is deformed from the intermediate shape to the initial shape under a second driving condition.
4. The anti-restenosis shape memory polymer intestinal stent of claim 1, wherein the tubular stent comprises a mesh structure and a negative poisson's ratio structure; the driving conditions of the mesh structure and the negative poisson ratio structure are different, and the negative poisson ratio structure is positioned on a node of the mesh structure.
5. The anti-restenosis shape memory polymer intestinal stent of claim 4,
the shape memory material adopted by the reticular structure comprises at least one of polyurethane, polyester, polyvinyl alcohol or polyethylene glycol; and/or
The negative poisson ratio structure consists of a shape memory polymer and a functional filler; the functional filler is magnetic filler or photo-thermal filler; the shape memory polymer is at least one of polycaprolactone, polylactic acid, polyurethane, poly (ethylene glycol) diacrylate, acrylated epoxidized soybean oil or poly (d, l-lactide-co-trimethylene carbonate).
6. The anti-restenosis shape memory polymer stent of claim 5, wherein the mass ratio of said shape memory polymer to said functional filler in said negative poisson's ratio structure is (3-5): 1;
preferably, the magnetic filler is at least one of gamma-ferric oxide, ferroferric oxide, neodymium iron boron, carbonyl iron and nickel zinc ferrite;
preferably, the photo-thermal filler is at least one of gold nanoparticles, carbon black, graphene oxide or black phosphorus.
7. The anti-restenosis shape memory polymer stent of claim 4, wherein said stent deforms to said temporary shape at a material transition temperature;
the mesh structure reverts to a first initial shape under a first driving condition, deforming the intestinal stent from the temporary shape to the intermediate shape;
the negative poisson's ratio structure reverts to a second initial shape under a second driving condition, deforming the intestinal stent from the intermediate shape to the initial shape.
8. The anti-restenosis shape memory polymer intestinal stent of any one of claim 1 to 7,
the hydrogel is at least one of chitosan, cellulose, hyaluronic acid, heparin, alginate, polyacrylic acid, polyethylene glycol, polymethacrylic acid, polyvinyl alcohol, polyacrylamide or poly (N-isopropyl acrylamide) with stress response performance;
the drug-loaded layer is responsive to an external stimulus to control the rate of drug release; the external stimulus includes one or more of pH, light, magnetism, temperature, specific ions, or enzymes;
preferably, the mass ratio of the drug to the hydrogel is 1 (10-20).
9. A method of preparing an anti-restenosis shape memory polymer intestinal stent according to any one of claims 1 to 8, comprising:
(1) Designing a three-dimensional structure model of an intestinal canal stent comprising a tubular stent and a drug carrying layer;
(2) And determining shape memory materials used by the tubular stent and the drug carrying layer, printing a plurality of materials by adopting a 4D printing technology, and obtaining the 4D printed intestinal canal stent with the initial shape after molding.
10. The method according to claim 9, wherein,
the medicine carrying layer consists of medicine and hydrogel with stress response performance, and the mass ratio of the medicine to the hydrogel is 1 (10-20); and/or
The tubular stent comprises a mesh structure and a negative poisson ratio structure; the driving conditions of the mesh structure and the negative poisson ratio structure are different, and the negative poisson ratio structure is positioned on a node of the mesh structure.
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