KR102481801B1 - Shape-memory polymer containing supramolecular cross-linkers, preparation method thereof, and Drug-eluting shape-memory polymer using the same - Google Patents

Abstract

The present invention relates to a shape-memory polymer comprising a vegetable oil-based polymer and a crosslinking agent having a molecular necklace structure, wherein the shape-memory polymer improves mechanical strength and elongation at the same time, has drug-eluting characteristics, and is stable in the in vivo environment. and maintain mechanical strength even after dissolution of the drug.

Description

Shape-memory polymer containing supramolecular cross-linkers, preparation method thereof, and Drug-eluting shape-memory polymer using the same}

The present invention includes a supramolecular crosslinking agent, and a copolymer of a vegetable oil and a polymer. It relates to a shape memory polymer having high mechanical strength, elongation, and shape memory recovery rate, a manufacturing method thereof, and a shape memory polymer for drug elution.

The shape memory effect is a phenomenon that remembers a shape stored at a certain temperature, transforms it into a completely different shape by applying force, and immediately returns to its original shape when heated. Materials exhibiting such a shape memory effect are classified into shape memory alloys and shape memory polymers depending on the material.

In general, shape memory polymers have been widely used as polymers that can remember and recover various shapes by combining various materials based on biodegradable polymers such as polycaprolactone and adjusting mechanical properties. It is difficult to simultaneously increase the elongation, resulting in a trade-off problem in practical applications.

The polycaprolactone is generally well known as a biocompatible material and is coated on a material such as a stent or catheter used in the body and has properties for drug elution, but it is difficult to stably coat a metal material in the body environment. There is a problem that it is difficult to have stable drug dissolution characteristics.

Recently, studies on polycaprolactone-based biodegradable polymers and cross-linked vegetable oil-based shape-memory polymers have been reported for the purpose of delivering drugs by being inserted while maintaining a complex shape, but cross-linked vegetable oil-based shape-memory polymers are generally hard. It exhibits mechanical properties, making it difficult to manufacture complex shapes, and, moreover, the increase in flexibility through mixing with polycaprolactone-based biodegradable polymers lowers mechanical strength, resulting in a conflict.

Therefore, there is a need to develop a new crosslinking agent capable of simultaneously improving the flexibility and mechanical properties of vegetable oil-based shape memory polymers and demonstrating stable mechanical properties of the shape memory polymers even after dissolution of the drug.

Republic of Korea Patent No. 10-1906472 (2018.10.10)

The problem to be solved by the present invention is to simultaneously improve the mechanical strength and elongation of a bulk material with only a small amount of a supramolecular crosslinking agent in a shape memory polymer whose main components are vegetable oil and a biocompatible polymer, and have shape memory properties simultaneously with drug elution properties. It is to provide a polymer and a manufacturing method thereof.

The present invention is a copolymer in which vegetable oil and bio-derived polymers are polymerized; and

A supramolecular crosslinking agent comprising a linear polymer, a cyclic polysaccharide, and a spacer substituted for the cyclic polysaccharide;

The spacer is substituted for the cyclic polysaccharide of the supramolecular crosslinking agent to connect the supramolecular crosslinking agent and the copolymer,

The supramolecular crosslinking agent is in the form of inclusion of 10 to 80 cyclic polysaccharides in the main chain of a linear polymer,

The crosslinking density is 5X10 ^-3 to 20X10 ^-3 mol/cm ³ , and the tensile strength is 1.5 MPa or more to provide a shape memory polymer.

In addition, the present invention comprises the steps of preparing a supramolecular crosslinking agent by mixing a linear polymer, a cyclic polysaccharide and a spacer; and

Preparing a shape memory polymer by mixing the prepared supramolecular crosslinking agent and the copolymer; Including,

The copolymer is a polymerized vegetable oil and bio-derived polymer,

The supramolecular crosslinking agent is in the form of inclusion of 10 to 80 cyclic polysaccharides in the main chain of a linear polymer,

The crosslinking density is 5X10 ^-3 to 20X10 ^-3 mol/cm ³ , and the tensile strength is 1.5 MPa or more.

In addition, the present invention provides a shape memory polymer for drug elution using the shape memory polymer described above.

The shape memory polymer according to the present invention improves mechanical strength and elongation at the same time by including a vegetable oil-based polymer and a molecular necklace structure crosslinking agent, has drug elution characteristics, maintains its shape stably even in the in vivo environment, and even after drug elution mechanical strength can be maintained.

1 is a schematic diagram of the structure of polyrotaxane, which is a crosslinking agent included in a shape memory polymer according to an embodiment of the present invention, and (b) showing the chemical structure of polyethylene glycol (PEG) and α-cyclodextrin constituting the crosslinking agent. It is a picture.
Figure 2 is a schematic diagram showing a method for producing a shape memory polymer according to an embodiment of the present invention.
Figure 3 is a graph showing the mechanical properties according to the type of crosslinking agent of the shape memory polymer according to an embodiment of the present invention.
Figure 4 is a graph of the change in crosslinking density according to the type of crosslinking agent of the shape memory polymer according to an embodiment of the present invention.
Figure 5 is an image of the shape memory recovery process according to the type of supramolecular crosslinking agent of the shape memory polymer according to an embodiment of the present invention (a), a graph showing changes in shape memory recovery speed in an aquatic environment (b) and in the air It is a graph (c) showing the change in shape memory recovery rate.
Figure 6 is a differential scanning calorimetry (DSC) analysis result of a shape memory polymer according to an embodiment of the present invention, the glass transition temperature (a), slope (b), and ΔCp value for each type of supramolecular crosslinking agent It is a graph showing (c).
7 is a drug dissolution test result of a shape memory polymer according to an embodiment of the present invention, a graph (a) of a drug dissolution test for 40 days in Example, and a graph (b) of a drug dissolution test in an environment without caprolactone.
8 is a graph of tensile strength after drug dissolution for 40 days of an example of a shape memory polymer according to an embodiment of the present invention (a) and a graph of tensile elongation (b), after drug dissolution for 40 days in an environment without caprolactone It is a tensile strength graph (c) and a tensile elongation graph (d).

Hereinafter, in order to explain the present invention in more detail, preferred embodiments according to the present invention will be described in more detail with reference to the accompanying drawings. However, the present invention is not limited to the embodiments described herein and may be embodied in other forms.

1 is a schematic diagram of the structure of a supramolecular crosslinking agent included in a shape memory polymer according to an embodiment of the present invention and a view showing the chemical structural formula of components constituting the supramolecular crosslinking agent, and FIG. 2 is a view showing the shape memory according to an embodiment of the present invention. The role of the supramolecular cross-linking agent in the shape-memory polymer can be seen in a schematic diagram showing a method for preparing the polymer.

The present invention is a copolymer in which vegetable oil and bio-derived polymers are polymerized; and

A supramolecular crosslinking agent comprising a linear polymer, a cyclic polysaccharide, and a spacer substituted for the cyclic polysaccharide;

The spacer is substituted for the cyclic polysaccharide of the supramolecular crosslinking agent to connect the supramolecular crosslinking agent and the copolymer,

The supramolecular crosslinking agent is in the form of inclusion of 10 to 80 cyclic polysaccharides in the main chain of a linear polymer,

The crosslinking density is 5X10 ^-3 to 20X10 ^-3 mol/cm ³ , and the tensile strength is 1.5 MPa or more to provide a shape memory polymer.

The vegetable oil may be soybean oil. Specifically, the vegetable oil may be acrylated soybean oil.

The bio-derived polymer is 1 selected from the group consisting of polycaprolactone (PCL), polylactic acid (PLA), poly(D,L-lactic acid-co-glycolic acid) (PLGA) and polyhydroxyalkanoate (PHA). There may be more than one species. By including the bio-derived polymer as described above, the shape memory polymer for drug elution of the present invention can have excellent biocompatibility and can be used as a medical device.

The shape memory polymer of the present invention may exhibit excellent mechanical properties by including a polymer obtained by polymerizing a vegetable oil and a bio-derived polymer as described above.

The supramolecular crosslinking agent may be composed of a linear polymer and a cyclic polysaccharide, and 10 to 80 cyclic polysaccharides may be incorporated in the main chain of the linear polymer. Specifically, the supramolecular crosslinking agent may be in a form in which 10 to 60, 10 to 50, or 10 to 30 cyclic polysaccharides are bound to a linear polymer. More specifically, the crosslinking agent may be polytaxane. At this time, the clathrate form refers to a form in which a clathrate compound is formed, and a plurality of cyclic polysaccharides are threaded through a linear polymer main chain.

The supramolecular crosslinking agent may have a linear polymer backbone inserted into a ring portion of the cyclic polysaccharide, and the cyclic polysaccharide may be reversibly movable within the linear polymer backbone. For example, the supramolecular crosslinking agent may have a molecular necklace structure in which 10 to 80 cyclic polysaccharides are threaded through a linear polymer.

The linear polymer may include at least one of polyethylene glycol, polypropylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, poly(meth)acrylic acid, polyacrylamide, and polyvinylmethyl ether. Specifically, the linear polymer may be polyethylene glycol, polypropylene glycol, polyvinyl alcohol or polyvinylpyrrolidone.

The molecular weight of the linear polymer may be 10,000 g/mol to 1,000,000 g/mol. Specifically, the molecular weight of the linear polymer is 10,000 g / mol to 700,000 g / mol, 10,000 g / mol to 500,000 g / mol, 10,000 g / mol to 200,000 g / mol 50,000 g / mol to 500,000 g / mol or 50,000 g/mol to 300,000 g/mol.

The cyclic polysaccharide includes any one or more of α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin. Specifically, the cyclic polysaccharide may be alpha-cyclodextrin.

The amount of the supramolecular linking agent may be 0.5wt% to 5wt% based on the total weight of the shape memory polymer. Specifically, the content of the supramolecular crosslinking agent may be 0.5 wt% to 5 wt%, 0.5 wt% to 3 wt%, or 0.5 wt% to 2 wt% based on the total weight of the shape memory polymer.

By including the above cross-linking agent, the shape-memory polymer of the present invention has excellent mechanical strength and exhibits excellent flexibility due to the structural characteristics of the supramolecular cross-linking agent.

The spacer may be polyethylene glycol having a methacrylic or acrylic derivative; and a polycaprolactone polymerizer having a methacrylic or acrylic derivative. Specifically, the spacer may be an ethylene oxy group.

In addition, the molecular weight of the spacer may be 100 g/mol to 10,000 g/mol, 100 g/mol to 5,000 g/mol, 100 g/mol to 1,000 g/mol, or 100 g/mol to 500 g/mol. By including the spacer having the above molecular weight, appropriate mechanical strength may be obtained by not only connecting the copolymer and the crosslinking agent but also mediating the bonding of different crosslinking agents.

The shape memory polymer according to the present invention may have a crosslinking density of 5X10 ^-3 to 20X10 ^-3 mol/cm ³ , 5X10 ^-3 to 15X10 ^-3 mol/cm ³ or 5X10 ^-3 to 10X10 ^-3 mol/cm ³ . By having the above cross-linking density, the drug can be continuously eluted while maintaining the external appearance, and excellent durability can be exhibited by having appropriate strength.

In addition, the shape memory polymer of the present invention can exhibit excellent mechanical properties even when a small amount of a supramolecular crosslinking agent including a spacer is included. Specifically, the tensile strength of the shape memory polymer may be 1.5 MPa or more or 1.7 MPa or more. In addition, the shape memory polymer may have a tensile elongation of 40X10 ^-2 or more or 50X10 ^-2 or more.

In addition, the shape memory polymer of the present invention includes a crosslinking agent composed of a cyclic polysaccharide in a linear polymer to exhibit excellent shape memory ability and can return to its original form within a short period of time. Specifically, the shape memory polymer may have a recovery time of less than 70 seconds or less than 60 seconds in a state folded in half at a temperature of -30 ℃ to 0 ℃.

In addition, the shape memory polymer of the present invention may be a shape memory polymer for dissolution.

In addition, the shape memory polymer for drug elution can continuously elute the drug during the first elution time. Specifically, the first elution time may be 30 days or more, 35 days or more, or 40 days or more. Accordingly, the drug can be stably eluted for a long period of time compared to conventional polymers for drug elution.

In addition, the shape memory polymer for drug elution of the present invention can exhibit excellent mechanical properties even when a small amount of a supramolecular crosslinking agent including a spacer is included. Specifically, the shape memory polymer for drug elution may have a tensile strength of 0.4 MPa or more or 0.5 MPa or more after 40 days of drug elution. In addition, the shape memory polymer for drug elution may have a tensile elongation of 40X10 ^-2 or more or 50X10 ^-2 or more after 40 days of drug elution.

In addition, the shape memory polymer according to the present invention can be used as a shape memory catheter or a shape memory blood vessel stent.

In addition, the present invention comprises the steps of preparing a supramolecular crosslinking agent by mixing a linear polymer, a cyclic polysaccharide and a spacer; and

Preparing a shape memory polymer by mixing the prepared supramolecular crosslinking agent and the copolymer; Including,

The copolymer is a polymerized vegetable oil and bio-derived polymer,

The supramolecular crosslinking agent is in the form of inclusion of 10 to 80 cyclic polysaccharides in the main chain of a linear polymer,

The crosslinking density is 5X10 ^-3 to 20X10 ^-3 mol/cm ³ , and the tensile strength is 1.5 MPa or more.

In the step of preparing the supramolecular crosslinking agent, a linear polymer and a cyclic polysaccharide may be mixed to prepare a supramolecular crosslinking agent in which 10 to 80 cyclic polysaccharides are incorporated in the main chain of the linear polymer. Specifically, a supramolecular crosslinking agent in which 10 to 60, 10 to 50, or 10 to 30 cyclic polysaccharides are bonded to a linear polymer may be prepared. The prepared supramolecular cross-linking agent may be polytaxane.

In the step of preparing the supramolecular crosslinking agent, the linear polymer is polyethylene glycol, polypropylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, poly(meth)acrylic acid, polyacrylamide, and polyvinylmethyl ether. can include Specifically, the linear polymer may be polyethylene glycol, polypropylene glycol, polyvinyl alcohol or polyvinylpyrrolidone.

The molecular weight of the linear polymer may be 10,000 g/mol to 1,000,000 g/mol. Specifically, the molecular weight of the linear polymer is 10,000 g / mol to 700,000 g / mol, 10,000 g / mol to 500,000 g / mol, 10,000 g / mol to 200,000 g / mol 50,000 g / mol to 500,000 g / mol or 50,000 g/mol to 300,000 g/mol.

The linear polymer may include at least one of polyethylene glycol, polypropylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, poly(meth)acrylic acid, polyacrylamide, and polyvinylmethyl ether. Specifically, the linear polymer may be polyethylene glycol, polypropylene glycol, polyvinyl alcohol or polyvinylpyrrolidone.

The cyclic polysaccharide includes any one or more of α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin. Specifically, the cyclic polysaccharide may be alpha-cyclodextrin.

In addition, in the step of preparing the crosslinking agent, the spacer is an ethyleneoxy group, a hexyloxy group, a hexylate ester group, a butylene carbamoyl group, a substituent having a phenylene derivative, a dimethylsilyl polymerizer, a polyethylene oxide polymerizer, and polycapro It includes any one or more of lactone polymerizers. Specifically, the spacer may be an ethylene oxy group.

In addition, the molecular weight of the spacer may be 100 g/mol to 10,000 g/mol, 100 g/mol to 5,000 g/mol, 100 g/mol to 1,000 g/mol, or 100 g/mol to 500 g/mol. Including the spacer having the above molecular weight, appropriate mechanical strength may be obtained without interfering with the connection of the copolymer and the crosslinking agent or between the crosslinking agent and the crosslinking agent.

In the step of preparing the shape memory polymer, the shape memory polymer may be prepared by mixing 0.5wt% to 5wt% of the prepared crosslinking agent, a copolymer, and a spacer based on the total weight of the shape memory polymer, and the annular shape of the crosslinking agent A shape memory polymer can be prepared by connecting a polysaccharide and a copolymer with a spacer.

Specifically, the step of preparing the shape memory polymer may be performed by mixing 0.5wt% to 5wt%, 0.5wt% to 3wt%, or 0.5wt% to 2wt% of a crosslinking agent.

In addition, in the step of preparing the shape memory polymer, a mixture of the supramolecular crosslinking agent, the copolymer, and the spacer may be poured into a molding and then crosslinked by irradiation with ultraviolet rays.

In the step of preparing the shape memory polymer, the copolymer may be obtained by polymerizing vegetable oil and bio-derived polymer. In this case, the copolymer may be copolymerized by mixing 15wt% to 35wt% or 20wt% to 30wt% of a vegetable oil and 60wt% to 85wt% or 70wt% to 80wt% of a bio-derived polymer.

In addition, in the step of preparing the shape memory polymer, acetone may be used as a solvent, and the solvent may be mixed in an amount of 10 to 40 parts by weight, 10 to 30 parts by weight, or 15 to 30 parts by weight based on 100 parts by weight of the total solid. .

Specifically, the vegetable oil may be soybean oil. For example, the vegetable oil may be acrylated soybean oil.

The bio-derived polymer is 1 selected from the group consisting of polycaprolactone (PCL), polylactic acid (PLA), poly(D,L-lactic acid-co-glycolic acid) (PLGA) and polyhydroxyalkanoate (PHA). There may be more than one species. By including the bio-derived polymer as described above, the shape memory polymer for drug elution of the present invention can have excellent biocompatibility and can be used as a medical device.

The shape memory polymer prepared in the step of preparing the shape memory polymer has a crosslinking density of 5X10 ^-3 to 20X10 ^-3 mol/cm ³ , 5X10 ^-3 to 15X10 ^-3 mol/cm ³ or 5X10 ^-3 to 10X10 ^-3 mol /cm can be ³ . By having the above cross-linking density, the drug can be continuously eluted while maintaining the external appearance, and excellent durability can be exhibited by having appropriate strength.

Examples of the present invention are described below. However, the following examples are only preferred embodiments of the present invention, and the scope of the present invention is not limited by the following examples.

1. Preparation of crosslinking agent

Manufacturing example (PRX_PEG_0.5k)

Preparation of functional group-introduced polyrotaxane

Methacrylated PEG (M _n =500) and phenylene diisocyanate (1,4-Phenylene diisocyanate) were dissolved in dimethyl sulfoxyoxide (DMSO) and reacted for 4 to 12 hours, followed by hexane After purification to prepare a spacer, the synthesized polyrotaxane and dimethyl sulfoxyoxide (DMSO) are mixed and reacted for 24 hours. Then, the reaction solution was purified with a 3:1 solution of diethyl ether and ethanol, and then the cross-linking agent polyrotaxane (PRX_PEG0.5k) was recovered through a drying process.

2. Manufacturing of shape-memory polymers

Example (SC_PRX_PEG0.5k)

A mixture of 24.5wt% of acrylated soybean oil, 73.4wt% of acrylated polycaprolactone, 0.1wt% of initiator, and 2wt% of the crosslinking agent prepared in the above Preparation Example, 20 parts by weight of the solid, based on 100 parts by weight of the solid. A shape memory polymer for drug elution was prepared by adding parts by weight to acetone (solvent) to prepare a mixture, pouring it into a molding, and then irradiating ultraviolet rays for 10 minutes.

Comparative Example 1 (SC)

A shape memory polymer for drug elution was prepared in the same manner as in Example, except that a crosslinking agent was not added.

Comparative Example 2 (SC_PEG0.5k)

A shape memory polymer for drug elution was prepared in the same manner as in Example, except that polyethylene glycol having a molecular weight of about 500 g/mol was used as a crosslinking agent.

Comparative Example 3 (SC_PEG010k)

A shape memory polymer for drug elution was prepared in the same manner as in Example, except that polyethylene glycol having a molecular weight of 10,000 g/mol was used as a crosslinking agent.

Experimental Example 1

viscosity measurement

Changes in mechanical properties of the shape memory polymer prepared according to the presence or absence of addition of a crosslinking agent and the type of crosslinking agent were measured and are shown in FIG. 3 below.

As shown in Figure 3, the linear crosslinking agent improves the mechanical properties of the shape memory polymer. However, in the case of the shape memory polymer (PRX_PEG0.5k) of Example, it can be seen that the tensile strength and elongation of the shape memory polymer are simultaneously improved by about 2 to 3 times compared to the addition of the linear crosslinking agent of Comparative Example 2 (PEG_10k). .

It can be seen that, due to the structural characteristics of polyrotaxane, tensile strength and elongation can be simultaneously improved compared to the case of containing only polyethylene glycol, which is another crosslinking agent.

Crosslink density evaluation

To evaluate the crosslinking density, a dynamic mechanical analysis (DMA) test was performed on Examples and Comparative Examples 1 to 3, which is shown in FIG. 4 below.

Referring to Figure 4, it can be seen that the physical properties shown in the tensile strength are related to the internal crosslinking density. Comparative Example 3 (SC_PEG10k) and Example (SC_PRX_PEG0.5k), which previously showed excellent physical properties, showed higher crosslinking density and glass transition temperature than other materials.

In the case of Example (SC_PRX_PEF0.5k), in addition to internally forming high crosslinking density, the elongation rate was higher than that of Comparative Example 3 (SC_PEG10k) in the tensile test, while α-CD moved along the PEG axis while tensile force was applied. It can be seen that it is a structural characteristic shown.

shape memory recovery rate

In order to measure the recovery rate for improving the shape memory properties of the shape memory polymers according to Examples and Comparative Examples 1 to 3, each sample was bent at a low temperature (below -30 ° C) and fixed in shape, and time The strain recovery rate (%) was calculated from the angle recovered along the way, and the results are shown in FIG. 5 below.

Referring to FIG. 5, Comparative Example 3 (SC_PEG10k) and Example (SC_PRX_PEG0.5k), which had a significantly high crosslinking density, showed high recovery rates in both air and water environments.

In addition, in the case of the embodiment (SC_PRX_PEG0.5k) showing the highest recovery rate in the air, it is estimated that it showed a fast recovery rate against temperature change due to the slidable bridge points formed on α-CD.

DSC analysis

Analysis was performed by differential scanning calorimetry on the shape memory polymers of Examples and Comparative Examples 1 and 3, and the results are shown in FIG. 6 .

Referring to FIG. 6, the slope and ΔCp value of the example (SC_PRX_PEG0.5k) show the highest values among the shape memory polymer samples. The example with a large △Cp value (SC_PRX_PEG0.5k), which means heat capacity, means that it contains more energy than other samples, and because of this, the difference in shape memory speed shown in Figure 5 above is It can be seen that the molecular mobility of rotaxane is shown.

drug dissolution test

For Example, Comparative Example 1 and Comparative Example 3, a dissolution test was performed by putting 1 mg of Naproxen drug into 600 mg of shape memory polymer, and the results are shown in FIG. 7 .

Referring to FIG. 7, as a result of analyzing the drug dissolution characteristics of Comparative Example 3 (SC_PEG10k), Example (SC_PRX_PEG0.5k), and Comparative Example 1 (SC), which showed the best physical properties, polycaprolactone was decomposed, and the drug was released after 40 days. It was confirmed that the gradual elution occurred over

Referring to b of FIG. 7 , it can be seen that drug elution characteristics appear due to the biodegradation characteristics of caprolactone through the fact that almost no drug elution is observed when the polymer is made only from vegetable oil.

Mechanical properties after dissolution test

Mechanical property tests were performed on the examples, Comparative Examples 1 and 3 that had undergone the drug dissolution test, and the results are shown in FIG. 8 .

Looking at Figures 8a, b, it can be confirmed that the change in tensile strength and elongation of the sample as a result of the degradation of biodegradable polycaprolactone when analyzing the drug dissolution characteristics. It can be confirmed that the example (SC_PRX_PEG0.5k), which basically had a high tensile strength, maintained as high as the tensile strength of the initial SC (Comparative Example 1) that was not decomposed even after 40 days of dissolution of the drug. In addition, it can be seen that the overall tensile elongation before and after decomposition was not significantly affected.

Looking at Figures 8c, d, as confirmed in Figure 7 above, it is a result showing that there is no difference in mechanical properties when there is no biodegradable caprolactone.

Claims (15)

Copolymers in which vegetable oils and bio-derived polymers are polymerized; and
A supramolecular crosslinking agent comprising a linear polymer, a cyclic polysaccharide, and a spacer substituted for the cyclic polysaccharide;
The spacer may be polyethylene glycol having a methacrylic or acrylic derivative; And at least one of a polycaprolactone polymerizer having a methacrylic or acrylic derivative,
The molecular weight of the spacer is 100 g / mol to 10,000 g / mol,
The spacer is substituted for the cyclic polysaccharide of the supramolecular crosslinking agent to connect the supramolecular crosslinking agent and the copolymer,
The supramolecular crosslinking agent is in the form of clathrates of 10 to 80 cyclic polysaccharides in the main chain of a linear polymer,
The crosslinking density is 5X10 ^-3 to 20X10 ^-3 mol/cm ³ , and the tensile strength is 1.5 MPa or more shape memory polymer. According to claim 1,
The supramolecular crosslinker has a main chain of 10,000 g/mol to 1,000,000 g/mol of a linear polymer inserted into an annular portion of a cyclic polysaccharide,
The cyclic polysaccharide is a shape memory polymer provided to be reversibly movable in the linear polymer backbone. delete According to claim 1,
The shape memory polymer is a shape memory polymer that has a recovery time of less than 70 seconds from being folded in half at a temperature of -30℃ to 0℃. According to claim 1,
The bio-derived polymer is 1 selected from the group consisting of polycaprolactone (PCL), polylactic acid (PLA), poly(D,L-lactic acid-co-glycolic acid) (PLGA) and polyhydroxyalkanoate (PHA). Shape-memory polymers that are more than species. According to claim 1,
The cyclic polysaccharide is a shape memory polymer containing at least one of α-cyclodextrin, β-cyclodextrin and γ-cyclodextrin. According to claim 1,
The content of the supramolecular crosslinking agent is a shape memory polymer, characterized in that 0.5wt% to 5wt% based on the total weight of the shape memory polymer. According to claim 1,
The shape memory polymer is a shape memory polymer for drug elution. According to claim 8,
A shape memory polymer that continuously dissolves the drug during the first dissolution time. According to claim 9,
The first dissolution time is 30 days or more shape memory polymer. According to claim 8,
The shape memory polymer has a tensile strength of 0.4 MPa or more after 40 days of dissolution of the drug. In the method for producing the shape memory polymer of any one of claims 1, 2, 4 to 1,
preparing a supramolecular crosslinking agent by mixing a linear polymer, a cyclic polysaccharide, and a spacer; and
Preparing a shape memory polymer by mixing the prepared supramolecular crosslinking agent and the copolymer; Including,
The copolymer is a polymerized vegetable oil and bio-derived polymer,
The supramolecular crosslinking agent is in the form of inclusion of 10 to 80 cyclic polysaccharides in the main chain of a linear polymer,
The crosslinking density is 5X10 ^-3 to 20X10 ^-3 mol/cm ³ , and the tensile strength is a method for producing a shape memory polymer having a shape memory polymer of 1.5 MPa or more. According to claim 12,
The step of preparing a crosslinking agent is to prepare a crosslinking agent in a form in which 10 to 80 cyclic polysaccharides are bonded to linear polyethylene glycol. According to claim 12,
The step of preparing a shape memory polymer is a method for producing a shape memory polymer that is performed by mixing 0.5wt% to 5wt% of a crosslinking agent based on the total weight of the shape memory polymer. According to claim 12,
The step of preparing a shape memory polymer is a method for producing a shape memory polymer in which a spacer connects a cyclic polysaccharide and a copolymer of a supramolecular crosslinking agent.

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