Polymer compound having antithrombotic properties and shape memory properties

Abstract

The present invention relates to a polymer compound having antithrombotic properties and shape memory properties. The polymer compound according to the present invention is formed of a biocompatible material, has excellent shape restoring ability at a specific temperature to induce a customized shape when inserted into the body, and exhibits antithrombotic properties, and thus can be utilized as an excellent material for manufacturing a medical device in contact with a blood vessel.

Description

Polymer compounds with antithrombotic and shape memory properties

[0001] The present invention relates to a polymer compound having antithrombotic properties and shape memory properties, and more specifically, to a polymer compound having antithrombotic properties and shape memory properties that suppresses thrombus adhesion of a material to be inserted into the body and enables shape deformation and restoration at a specific temperature.

[0002]

[0003] A blood clot is the final product of blood clotting, a dark red mass formed by the aggregation of platelets and fibrin. Excessive thrombosis can block blood vessels, cutting off blood supply and causing life-threatening vascular diseases such as stroke and myocardial infarction.

[0004] For this reason, the risk of thrombosis must be considered when using medical devices that are inserted into blood vessels or come into contact with blood.

[0005] In order to impart antithrombotic properties that suppress the formation of blood clots, a method of coating the surface of a medical device with heparin or a heparin derivative is generally used. (U.S. Patent No. 7,468,210, U.S. Patent No. 5,837,313). However, when heparin or a heparin derivative is coated on the surface of a medical device, there is an advantage of lowering the rate of restenosis by preventing the coagulation of initial blood clots, but in the case of the method of introducing heparin or a heparin derivative to the surface of a conventional biomaterial by chemical reaction between substances, there is a problem that the introduction rate of heparin is low due to the high toxicity of residual chemical substances and uneven surface treatment, and the binding force between the medical device surface and heparin or a heparin derivative is weak, so that the heparin or heparin derivative is dissolved over time, and the antithrombotic properties are gradually reduced.

[0006] Accordingly, in order to solve such problems, the present invention has been completed by developing a novel polymer compound having antithrombotic properties and shape memory properties rather than coating heparin on the surface of a medical device as a result of extensive efforts.

[0007]

[0008] The present invention aims to provide a novel polymer composition having both antithrombotic properties and shape memory properties, a polymer compound comprising the polymer composition, a method for producing the same, and a use thereof.

[0009] To achieve the above purpose, the present invention provides a polymer composition comprising lactone, glycidyl methacrylate and maleic anhydride.

[0010] In the present invention, the lactone and glycidyl methacrylate form a copolymer, and the copolymer may be characterized by being at least one selected from the group consisting of the following chemical formulas (1) to (4):

[0011] Chemical formula (1)

[0012]

[0013] In the above chemical formula (1),

[0014] R1, R2 and R3 are each independently hydrogen (H) or an alkyl group having 1 to 6 carbon atoms,

[0015] m and n are integers from 1 to 20, independently of each other,

[0016] A, B1 and B2 are independently oxygen (O) or sulfur (S),

[0017] x and y represent the mole % of repeating units,

[0018] x+y is 100, and x is between 80 and 98;

[0019] Chemical formula (2)

[0020]

[0021] In the above chemical formula (2),

[0022] x is an integer from 1 to 20,

[0023] m and n represent the mole % of repeating units,

[0024] m+n is 100, and m is between 80 and 98;

[0025] Chemical formula (3)

[0026]

[0027] In the above chemical formula (3),

[0028] x and y are integers from 1 to 20, independently of each other,

[0029] m and n represent the mole % of repeating units,

[0030] m+n is 100, and m is between 70 and 99;

[0031] Chemical formula (4)

[0032]

[0033] In the above chemical formula (4),

[0034] x and y are integers from 1 to 20, independently of each other,

[0035] m and n represent the mole % of repeating units,

[0036] m+n is 100, and m is between 70 and 99.

[0037] In the present invention, it may be characterized in that the molar ratio of lactone and glycidyl methacrylate in the copolymer is 90:10 to 98:2.

[0038] In the present invention, it may be characterized in that the maleic anhydride is included in an amount of 2 to 18 wt% relative to the weight of the copolymer.

[0039] In the present invention, the polymer composition may be characterized by further including a crosslinking agent.

[0040] In the present invention, it may be characterized in that the crosslinking agent is included in an amount of 0.5 to 3.0 wt% relative to the total weight of the polymer composition.

[0041] In the present invention, the crosslinking agent may be characterized by being at least one selected from the group consisting of potassium persulfate, ammonium persulfate, benzoyl peroxide, diauryl peroxide, dicumyl peroxide, hydrogen peroxide, azobisisobutuyronitrile, Irgacure, Darocure, LAP (lithium phenyl-2,4,6-trimethylbenzoylphosphinate), TPO (diphenyl(2,4,6-trimethylbenzoyl)phosphine), and TPO-L (ethyl(2,4,6-trimethylbenzoyl)phenylphosphinate).

[0042] The present invention also provides a polymer composition, specifically a polymer compound in which lactone, glycidyl methacrylate, and maleic anhydride are crosslinked.

[0043] In the present invention, the polymer compound may be characterized by having antithrombotic properties and shape memory properties.

[0044] In the present invention, the polymer compound may be characterized by having a shape restoring ability of 70% or more at a temperature of 30 to 60°C.

[0045] The present invention also provides a method for producing a polymer compound, comprising the following steps:

[0046] (a) a step of preparing a copolymer comprising lactone and glycidyl methacrylate; and

[0047] (b) A step of inducing a chemical bond between the copolymer and maleic anhydride.

[0048] In the present invention, the copolymer may be characterized by being at least one selected from the group consisting of the chemical formulas (1) to (4).

[0049] In the present invention, the step (b) may be characterized by mixing maleic anhydride in an amount of 2 to 18 wt% relative to the weight of the copolymer.

[0050] In the present invention, the method for producing a polymer compound may further include, after step (b), a step (c) of crosslinking a polymer compound produced by chemically bonding the copolymer and maleic anhydride.

[0051] The present invention also provides a medical material comprising the polymer compound.

[0052] The present invention also provides a medical device manufactured from the medical material.

[0053] In the present invention, the medical device may be characterized as being a vascular or non-vascular stent.

[0054] In the present invention, the medical device may be characterized as being a device for vascular treatment or surgery.

[0055] In the present invention, the vascular treatment or surgical instrument may be characterized as being a lymphatic shunt or a vascular shunt.

[0056] In the present invention, the medical device may be characterized in that it is manufactured by extruding, injection molding, or three-dimensional printing the medical material.

[0057] The polymer compound according to the present invention is manufactured as a material compatible with the body, has excellent shape restoring ability at a specific temperature, can induce a customized shape when inserted into the body, and exhibits antithrombotic properties, so that it can be used as an excellent material for manufacturing medical devices that come into contact with blood vessels.

[0058]

[0059] Figure 1 confirms the crosslinking form of a polymer compound (Example 4) according to one embodiment of the present invention.

[0060] Figure 2 confirms the shape memory characteristics of a polymer compound (Example 1) according to one embodiment of the present invention.

[0061] Figure 3 confirms the antithrombotic properties of polymer compounds (Example 1, Example 4) according to some embodiments of the present invention.

[0062]

[0063] Hereinafter, the composition and effects of the present invention will be described in more detail through examples. These examples are intended solely to illustrate the present invention, and the scope of the present invention is not limited by these examples.

[0064] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. In general, the nomenclature used herein and the experimental methods described below are well known and commonly used in the art.

[0065] In the present invention, it should be understood that terms such as “include” or “have” are intended to specify the presence of a feature, number, step, operation, component, part or combination thereof described in the specification, but do not exclude in advance the possibility of the presence or addition of one or more other features, numbers, steps, operations, components, parts or combinations thereof.

[0066]

[0067] Polymer compositions and polymer compounds

[0068] In the present invention, a novel polymer compound having biocompatibility, antithrombotic properties, and shape memory properties was newly synthesized by mixing a lactone and glycidyl methacrylate copolymer with maleic anhydride.

[0069] In the present invention, “antithrombin property” means inhibiting the formation of blood clots when in contact with blood vessels or blood.

[0070] In the present invention, a "shape memory polymer (SMP)" means a polymer that has the property (i.e., shape memory property) of returning to its original shape when the object is made to have a certain shape under certain conditions and the shape is subsequently changed by an external impact, when the object is made to have the same initial conditions (temperature, light, pH, humidity, etc.).

[0071] Accordingly, the present invention relates, in one aspect, to a polymer composition comprising lactone, glycidyl methacrylate and maleic anhydride.

[0072] In the present invention, the polymer composition may be a composition for producing a polymer compound having antithrombotic properties and shape memory properties.

[0073] In the present invention, the lactone and glycidyl methacrylate form a copolymer, and the copolymer may be characterized by being at least one selected from the group consisting of the following chemical formulas (1) to (4):

[0074] Chemical formula (1)

[0075]

[0076] In the above chemical formula (1),

[0077] R1, R2 and R3 are each independently hydrogen (H) or an alkyl group having 1 to 6 carbon atoms,

[0078] m and n are integers from 1 to 20, independently of each other,

[0079] A, B1 and B2 are independently oxygen (O) or sulfur (S),

[0080] x and y represent the mole % of repeating units,

[0081] x+y is 100, and x is between 80 and 98;

[0082] Chemical formula (2)

[0083]

[0084] In the above chemical formula (2),

[0085] x is an integer from 1 to 20,

[0086] m and n represent the mole % of repeating units,

[0087] m+n is 100, and m is between 80 and 98;

[0088] Chemical formula (3)

[0089]

[0090] In the above chemical formula (3),

[0091] x and y are integers from 1 to 20, independently of each other,

[0092] m and n represent the mole % of repeating units,

[0093] m+n is 100, and m is between 70 and 99;

[0094] Chemical formula (4)

[0095]

[0096] In the above chemical formula (4),

[0097] x and y are integers from 1 to 20, independently of each other,

[0098] m and n represent the mole % of repeating units,

[0099] m+n is 100, and m is between 70 and 99.

[0100] In the present invention, the chemical formula (1) can be represented by the following chemical formula (1'):

[0101] Chemical formula (1')

[0102]

[0103] In the above chemical formula (1')

[0104] m and n are integers from 1 to 20, independently of each other,

[0105] x and y represent the mole % of repeating units,

[0106] x+y is 100, and x is between 80 and 98.

[0107] In the present invention, the molar ratio of lactone and glycidyl methacrylate in the copolymer may be, but is not limited to, 90:10 to 98:2.

[0108] In one embodiment, in producing the copolymer, when epsilon caprolactone (ε-CL) is used, x may be 3, and when dipentaerythritol is used, y may be 1. In addition, the number of x may be controlled by using monomers such as α-acetolactone, β-propiolactone, γ-butyrolactone, and δ-valerolactone instead of epsilon caprolactone (ε-CL), and the number of y may be controlled by using an initiator for copolymer synthesis instead of dipentaerythritol, which can be easily controlled by a person skilled in the art.

[0109] In the present invention, the copolymers of the chemical formulas (1) to (4) are described in detail in Korean Patent No. 10-1906472, Korean Patent Publication No. 10-2021-0158356, Korean Patent No. 10-2598727, Korean Patent No. 10-2516991, and Korean Patent No. 10-2610524, which patent documents are incorporated herein by reference.

[0110] In the present invention, the maleic anhydride may be included in an amount of 2 to 18 wt% based on the weight of the copolymer, and for example, the maleic anhydride may be included in an amount of about 3 to about 15 wt% based on the weight of the copolymer, but is not limited thereto.

[0111]

[0112] In the present invention, if the amount of maleic anhydride is less than 2 wt% based on the weight of the copolymer, the antithrombotic properties may not be sufficiently exhibited, and if it exceeds 18 wt%, the shape memory properties may not be sufficiently exhibited.

[0113] In the present invention, the polymer composition may be characterized by further including a crosslinking agent.

[0114] In the present invention, it may be characterized in that the crosslinking agent is included in an amount of 0.5 to 3.0 wt% relative to the total weight of the polymer composition.

[0115] In the present invention, the crosslinking agent may be characterized by being at least one selected from the group consisting of potassium persulfate, ammonium persulfate, benzoyl peroxide, diauryl peroxide, dicumyl peroxide, hydrogen peroxide, azobisisobutuyronitrile, Irgacure, Darocure, lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), diphenyl(2,4,6-trimethylbenzoyl)phosphine (TPO), and ethyl(2,4,6-trimethylbenzoyl)phenylphosphinate (TPO-L), but is not limited thereto.

[0116] From another aspect, the present invention relates to the polymer composition, specifically to a polymer compound crosslinked with lactone, glycidyl methacrylate, and maleic anhydride.

[0117] In the present invention, the polymer compound may be a copolymer of lactone and glycidyl methacrylate to which maleic anhydride is chemically bonded.

[0118] In another embodiment, the polymer compound may be a copolymer of the lactone and glycidyl methacrylate, in which maleic anhydride is chemically bonded and then thermally or photo-crosslinked.

[0119] In the present invention, the polymer compound may be characterized by having antithrombotic properties and shape memory properties.

[0120] For example, the polymer compound has an average shape recovery ability of about 70% or more, about 75% or more, or about 75% or more, at a temperature of 30 to 60°C after crosslinking, or any range of 30 to 60°C, for example, about 30°C, about 31°C, about 32°C, about 33°C, about 34°C, about 35°C, about 36°C, about 37°C, about 38°C, about 39°C, about 40°C, about 41°C, about 42°C, about 43°C, about 44°C, about 45°C, about 46°C, about 47°C, about 48°C, about 49°C, about 50°C, about 51°C, about 52°C, about 53°C, about 54°C, about 55°C, about 56°C, about 57°C, about 58°C, about 59°C, or about 60°C. It may be characterized by being 80% or more, for example, about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or about 100%, but is not limited thereto.

[0121] In the present invention, the polymer compound may have antithrombotic properties improved by at least about 10%, about 20%, about 30%, about 40%, or about 50% (e.g., reduced fiber-like shape development) compared to a copolymer crosslinked without maleic anhydride.

[0122]

[0123] Manufacturing method

[0124] In another aspect, the present invention relates to a method for producing a polymer compound, comprising the following steps:

[0125] (a) a step of preparing a copolymer comprising lactone and glycidyl methacrylate; and

[0126] (b) A step of inducing a chemical bond between the copolymer and maleic anhydride.

[0127] In the present invention, the copolymer may be characterized by being at least one selected from the group consisting of the chemical formulas (1) to (4).

[0128] Chemical formula (1)

[0129]

[0130] In the above chemical formula (1),

[0131] R1, R2 and R3 are each independently hydrogen (H) or an alkyl group having 1 to 6 carbon atoms,

[0132] m and n are integers from 1 to 20, independently of each other,

[0133] A, B1 and B2 are independently oxygen (O) or sulfur (S),

[0134] x and y represent the mole % of repeating units,

[0135] x+y is 100, and x is between 80 and 98;

[0136] Chemical formula (2)

[0137]

[0138] In the above chemical formula (2),

[0139] x is an integer from 1 to 20,

[0140] m and n represent the mole % of repeating units,

[0141] m+n is 100, and m is between 80 and 98;

[0142] Chemical formula (3)

[0143]

[0144] In the above chemical formula (3),

[0145] x and y are integers from 1 to 20, independently of each other,

[0146] m and n represent the mole % of repeating units,

[0147] m+n is 100, and m is between 70 and 99.;

[0148] Chemical formula (4)

[0149]

[0150] In the above chemical formula (4),

[0151] x and y are integers from 1 to 20, independently of each other,

[0152] m and n represent the mole % of repeating units,

[0153] m+n is 100, and m is between 70 and 99.

[0154] In the present invention, the step (b) may be characterized by mixing maleic anhydride in an amount of 2 to 18 wt%, for example, about 3 to 15 wt%, relative to the weight of the copolymer.

[0155] In the present invention, the maleic anhydride and the copolymer are first mixed using a mixing device such as a mixer or at a high temperature (about 100 to 140°C) in a solvent atmosphere, and then a crosslinking agent is added and then additionally mixed a second time to prepare a polymer composition, and then a polymer compound can be prepared through a crosslinking process.

[0156] In a preferred embodiment, the polymer compound according to the present invention can be prepared by the following reaction formula.

[0157] Reaction formula (1)

[0158]

[0159] In this case, the maleic anhydride shown in reaction formula (1) undergoes ring opening under hydration conditions, resulting in the formation of an -OH structure as shown in reaction formula (2).

[0160] Reaction formula (2)

[0161]

[0162] The above reaction can be easily understood by those skilled in the art by referring to the reference Chin-San Wu, "Physical properties and biodegradability of maleated-polycaprolactone / starch composite" Polymer Degradation and Stability (2003) 127-13.

[0163] In the present invention, the maleic anhydride and the copolymer can be prepared as a polymer compound by adding the maleic anhydride and the copolymer to an organic solvent such as xylene, stirring at a high temperature to dissolve them, then adding an initiator (e.g., BPO) and stirring to chemically bond (covalently bond) the maleic anhydride to the copolymer.

[0164] In the present invention, the polymer compound may be a maleated copolymer. That is, the polymer compound may be a maleated copolymer or a maleate of the copolymer.

[0165] In the present invention, after step (b), a step (c) of crosslinking a polymer compound produced by chemically bonding the copolymer and maleic anhydride may be added to produce a crosslinked polymer compound.

[0166] In the present invention, the polymer compound can exhibit shape memory properties by applying a cross-linking process.

[0167] In the present invention, the initiator may be at least one selected from potassium persulfate, ammonium persulfate, benzoyl peroxide, diauryl peroxide, dicumyl peroxide, hydrogen peroxide, and azobisisobutyronitrile, but is not limited thereto.

[0168] In the present invention, the crosslinking may be characterized as photocrosslinking or thermal crosslinking, but is not limited thereto.

[0169] In the present invention, the crosslinking agent may be added in an amount of 0.1 to 5 wt%, for example, 0.5 to 3 wt%, preferably about 1 wt%, based on the total mixed weight of the copolymer and maleic anhydride.

[0170] In the present invention, the crosslinking agent is a thermal crosslinking agent, and after pouring the polymer compound into a mold, thermal crosslinking may be performed by applying a pressure of 1 to 20 MPa, for example, 5 to 10 MPa, preferably about 10 MPa, at 100 to 120°C, for example, 105 to 115°C, preferably about 110°C, for 5 minutes to 1 hour, for example, about 10 to about 40 minutes, preferably about 20 minutes.

[0171] In a preferred embodiment, the crosslinking agent is benzoyl peroxide, and the benzoyl peroxide can be added in an amount of about 1 wt% based on the total mixed weight of the copolymer and maleic anhydride.

[0172] In the present invention, the crosslinking agent is a photocrosslinking agent, and after pouring the polymer compound into a mold, UV (about 365 nm) is irradiated at 100 to 500 mW / cm 2 century, preferably 200 to 300 mW / cm 2 century, for example, about 265 mW / cm 2 The photocrosslinking may be carried out by irradiating for 100 to 1000 seconds, preferably 200 to 500 seconds, for example, for about 240 seconds to about 300 seconds.

[0173] In a preferred embodiment, the crosslinking agent may be Iragcure 2959, and the Iragcure 2959 may be added in an amount of about 1 wt% based on the total mixed weight of the copolymer and maleic anhydride.

[0174]

[0175] use

[0176] The polymer compound described above possesses biocompatibility, antithrombotic properties, and shape memory properties, making it suitable as a medical material. In particular, the polymer compound according to the present invention can be applied to various vascular procedures or surgeries, including microvessels such as lymphatic vessels and vascular grafts.

[0177] Therefore, the present invention relates to a medical material comprising the polymer compound from another aspect.

[0178] In another aspect, the present invention relates to a medical device manufactured from the above medical material.

[0179] In one aspect, the medical device may be inserted or implanted into the body.

[0180] In the present invention, the medical device may be a vascular or non-vascular stent, but is not limited thereto.

[0181] In the present invention, the medical device may be a vascular treatment or surgical device, but is not limited thereto.

[0182] In one aspect, the medical device may be a medical device inserted or implanted into the body during vascular treatment or surgery.

[0183] In the present invention, the vascular surgical or treatment device may be a lymphatic shunt or a vascular shunt, but is not limited thereto.

[0184] In the present invention, the medical device can be manufactured by extruding, injection molding, or 3D printing the medical material, but the manufacturing method is not limited thereto.

[0185] In another aspect, the present invention relates to a treatment or surgical method comprising a step of inserting or implanting the polymer compound, the medical material or the medical device into an individual in need thereof.

[0186] In another aspect, the present invention relates to the use of the polymer compound, the medical material or the medical device for treatment or surgery.

[0187] In another aspect, the present invention relates to the use of the polymer compound for the manufacture of the medical material or the medical device.

[0188] In the above method or use, the polymer compound, the medical material or the medical device may be characterized by having biocompatibility, antithrombotic properties and shape memory properties, and may be characterized by being used for vascular, lymphatic or non-vascular anastomosis.

[0189] The subject is a mammal including a human, and may be selected from the group consisting of, for example, a human, a rat, a mouse, a guinea pig, a hamster, a rabbit, a monkey, a dog, a cat, a cow, a horse, a pig, a sheep and a goat, and is preferably a human, but is not limited thereto, and may be used interchangeably with terms such as “subject” and “patient”.

[0190]

[0191] Hereinafter, the present invention will be described in more detail through examples. These examples are intended solely to illustrate the present invention, and it will be apparent to those skilled in the art that the scope of the present invention is not limited by these examples.

[0192]

[0193] [Example]

[0194] Polymer comprising maleic anhydride and 6-arm PCL-PGMA copolymer

[0195]

[0196]

[0197]

[0198] In a three-necked flask, maleic anhydride (TCI chemical) and a copolymer of caprolactone and glycidyl methacrylate (6arm PCL-PGMA, INNOSELF 1-6, 94% PCL-06% PGMA, TMDLAB co., Ltd.) with a six-arm structure were added to xylene (Xylene, Daejung chemicals & metals CO., LTD.) (solvent) and stirred at 120℃ for 2 hours to dissolve. Afterwards, benzoyl peroxide (Benzoyl peroxide, Sigma-aldrich) was additionally added and stirred for 2 hours. Afterwards, the final reactant was precipitated in methanol (Methanol, Daejung chemicals & metals CO., LTD.) at 4℃, filtered, and vacuum dried.

[0199] After mixing 1 wt% of Irgacure 2959 (Sigma-aldrich), a crosslinking agent, into a polymer composition containing maleic anhydride prepared for film production, the crosslinking agent was heated to 265 mW / cm 2 The sample was obtained by irradiating it with UV (365 nm) for 4 minutes.

[0200]

[0201] [Comparative Example 1]

[0202] 6arm PCL-PGMA

[0203] A copolymer of caprolactone and glycidyl methacrylate with a six-arm structure (6-arm PCL-PGMA, INNOSELF 1-6, 94% PCL-06% PGMA, TMDLAB co., Ltd.) was used as a comparative example. For film production, 1 wt% of Irgacure 2959 (Sigma-Aldrich), a crosslinking agent, was mixed into the polymer, and the film yield was 265 mW / cm 2 The sample was obtained by irradiating it with UV (365 nm) for 4 minutes.

[0204]

[0205] [Comparative Example 2]

[0206] 6arm PCL-PGMA containing 20% ​​maleic anhydride

[0207]

[0208]

[0209]

[0210] A copolymer of caprolactone and glycidyl methacrylate containing 20% ​​maleic anhydride was prepared in the same manner as in the examples. 1 wt% of Irgacure 2959 (Sigma-Aldrich), a crosslinking agent, was mixed into the polymer containing maleic anhydride prepared for film production, and then the crosslinking agent was 265 mW / cm 2 The sample was obtained by irradiating it with UV (365 nm) for 4 minutes.

[0211]

[0212] [Experimental Example 1] Crosslinking Characteristics

[0213]

[0214] The crosslinking characteristics of the polymer compound of the present invention were examined. To this end, the final reactant was prepared with the composition of Example 4 having the highest content of maleic anhydride, filtered, and vacuum-dried (see Examples). Then, Irgacure2959 (photoinitiator, Sigma Aldrich), a backlight initiator, was dissolved in N-methyl-2-pyrrolidone (NMP, Sigma Aldrich) at a concentration of 1 g / 1 ml and added in an amount of 1% relative to the weight of the final reactant (polymer compound). The dissolved polymer compound solution was applied to a slide glass and then subjected to a 265 mW / cm 2 A sample was obtained by irradiating the film with UV (365 nm) for 300 seconds. Afterwards, the manufactured film was placed in chloroform to check the degree of dissolution to confirm the crosslinking state.

[0215] As a result, it was confirmed that a network was formed by a cross-linking reaction, as shown in Fig. 1, and that it existed in a solid form without being dissolved in chloroform solvent.

[0216]

[0217] [Experimental Example 2] Confirmation of the degree of maleic anhydride inclusion

[0218]

[0219] The content of maleic anhydride in copolymers of caprolactone and glycidyl methacrylate containing maleic anhydride was calculated using the samples of Examples 1 to 4 and Comparative Example 2. 1 g of the polymer sample was placed in 100 ml of xylene, heated, and then the heated solution was titrated with a 0.1 N ethanolic potassium hydroxide solution. The acid number of the solution was calculated using Equation (1), and the degree of maleic anhydride introduced was calculated using Equation (2).

[0220] As a result, as shown in Table 3, the content of maleic anhydride in the polymer tended to increase as the reaction amount of maleic anhydride increased. However, as a result of comparing Example 4 and Comparative Example 2, it was confirmed that when reacting using 15 wt% or more of maleic anhydride compared to the caprolactone and glycidyl methacrylate copolymer, the content of maleic anhydride in the final polymer composition did not increase significantly.

[0221] In addition, as shown in Experimental Example 3, a decrease in shape memory characteristics was observed in Comparative Example 2, confirming that a reaction using more than 20 wt% of maleic anhydride compared to the caprolactone and glycidyl methacrylate copolymer is not suitable.

[0222]

[0223] Equation (1)

[0224]

[0225] Equation (2)

[0226]

[0227]

[0228]

[0229]

[0230] [Experimental Example 3] Shape Restoration

[0231]

[0232] In order to compare the shape recovery ability of Examples 1 to 4 and Comparative Example 2, each sample was stretched to 100%, the stretched sample was exposed to a temperature of 40 to 45°C, and the shape recovery ability (%) was confirmed according to Equation (3).

[0233]

[0234] Equation (3)

[0235]

[0236]

[0237] As a result, as shown in Fig. 2 and Table 4, in the case of the example, a shape recovery ability of 80% or more was shown at all tensile ratios tested, whereas in the case of comparative example 2, the shape was deformed and fixed, but the recovery ability was low at 70% or less.

[0238]

[0239]

[0240]

[0241] [Experimental Example 4] In vitro antithrombotic properties

[0242]

[0243] In order to confirm the antithrombotic properties of Examples 1 and 4 and Comparative Example 1, 10 mL of blood collected from the ear vein of SPF New Zealand White Rabbit (3-3.5 kg / Male, Dooyeol Bio) was centrifuged for 10 minutes. When the blood cells sedimented, the supernatant was separated and centrifuged again for 20 minutes to obtain a platelet pellet. The obtained platelet pellet was dispersed in PBS (Phosphate buffer solution, Lonza Bioscience) solution, applied onto the samples of Examples and Comparative Examples, and incubated in a 37°C incubator for 1 hour. Afterwards, the surface of the sample was washed with PBS solution and fixed by immersion in a fixative (Karnovsky's fixative, 2% glutaraldehyde, 2% paraformaldehyde in 0.1 M phosphate buffer, pH 7.4). In order to confirm the platelet activation shape on the surface of the examples and comparative examples where the blood clot was applied, the surface was observed using a scanning electron microscope (SEM, Zeiss LSM 700).

[0244] As a result, as shown in Fig. 3, in the case of Comparative Example 1, it was confirmed that a fiber-like shape was developed from a roundly formed platelet on the surface, and that this part was evenly formed on the surface of the Comparative Example, indicating that the platelet was activated. However, in the case of Examples 1 and 4, in which maleic anhydride was introduced, it was confirmed that the fiber-like shape was less formed from the platelet and that surface activation was less.

[0245] Through this, it was confirmed that the copolymer of caprolactone and glycidyl methacrylate containing maleic anhydride has antithrombotic properties compared to a polymer not containing maleic anhydride, and can exhibit shape memory properties through a crosslinking process.

[0246]

[0247] While specific aspects of the present invention have been described in detail above, it will be apparent to those skilled in the art that these specific descriptions merely represent preferred embodiments and are not intended to limit the scope of the present invention. Therefore, the substantial scope of the present invention is defined by the appended claims and their equivalents.

[0248]

[0249] [Assignment Information 1]

[0250] [Project ID] 1465040845

[0251] [Project Number] RS-2023-002655566

[0252] [Ministry Name] Ministry of Health and Welfare

[0253] [Name of Project Management (Specialist) Agency] Korea Health Industry Development Institute

[0254] [Research Project Name] Innovative Medical Device Company Technology Commercialization Support Project (R&D)

[0255] [Research Project Name] Global Joint Research and Medical Device Development on the Biofilm Reduction Effect of Polycaprolactone-Based Materials

[0256] [Name of the project performing organization] TMD Lab Co., Ltd.

[0257] Research Period: July 1, 2023 - December 31, 2025

[0258]

[0259] [Assignment Information 2]

[0260] [Project ID] 1711200487

[0261] [Project Number] RS-2023-00302125

[0262] [Ministry Name] Ministry of Science and ICT

[0263] [Name of Project Management (Specialist) Institution] National Research Foundation of Korea

[0264] [Research Project Name] Future Convergence Technology Development Project

[0265] [Research Project Title] Development of Source Technology for Energy-Responsive Self-Structured Medical Materials Applicable to Biosystems

[0266] [Name of the project performing organization] TMD Lab Co., Ltd.

[0267] Research Period: September 1, 2023 - December 31, 2027

Claims

1. A polymer composition comprising lactone, glycidyl methacrylate and maleic anhydride, The above lactone and glycidyl methacrylate form a copolymer, The polymer composition is characterized in that the copolymer is at least one selected from the group consisting of the following chemical formulas (1) to (4): Chemical formula (1) In the above chemical formula (1), R1, R2 and R3 are each independently hydrogen (H) or an alkyl group having 1 to 6 carbon atoms, m and n are integers from 1 to 20, independently of each other, A, B1 and B2 are independently oxygen (O) or sulfur (S), x and y represent the mole % of repeating units, x+y is 100, and x is between 80 and 98; Chemical formula (2) In the above chemical formula (2), x is an integer from 1 to 20, m and n represent the mole % of repeating units, m+n is 100, and m is between 80 and 98; Chemical formula (3) In the above chemical formula (3), x and y are integers from 1 to 20, independently of each other, m and n represent the mole % of repeating units, m+n is 100, and m is between 70 and 99; Chemical formula (4) In the above chemical formula (4), x and y are integers from 1 to 20, independently of each other, m and n represent the mole % of repeating units, m+n is 100, and m is between 70 and 99.

2. A polymer composition according to claim 1, characterized in that the molar ratio of lactone and glycidyl methacrylate in the copolymer is 90:10 to 98:

2.

3. A polymer composition according to claim 1, characterized in that the maleic anhydride is contained in an amount of 2 to 18 wt% relative to the weight of the copolymer.

4. A polymer composition further comprising a crosslinking agent according to claim 1.

5. A polymer composition according to claim 4, characterized in that the crosslinking agent is included in an amount of 0.5 to 3.0 wt% relative to the total weight of the polymer composition.

6. In the fifth paragraph, the crosslinking agent is at least one selected from the group consisting of potassium persulfate, ammonium persulfate, benzoyl peroxide, diauryl peroxide, dicumyl peroxide, hydrogen peroxide, azobisisobutuyronitrile, Irgacure, Darocure, lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), diphenyl(2,4,6-trimethylbenzoyl)phosphine (TPO), and ethyl(2,4,6-trimethylbenzoyl)phenylphosphinate (TPO-L).

7. A polymer compound in which the polymer composition of any one of claims 1 to 6 is crosslinked.

8. A polymer compound according to claim 7, characterized in that the polymer compound has antithrombotic properties and shape memory properties.

9. In the 8th paragraph, the polymer compound has a shape restoring ability of 70% or more at a temperature of 30 to 60°C. 10.(a) a step of preparing a copolymer comprising lactone and glycidyl methacrylate; and (b) a method for producing a polymer compound according to claim 7, comprising a step of inducing a chemical bond between the copolymer and maleic anhydride; A method for producing a polymer compound, characterized in that the copolymer is at least one selected from the group consisting of the following chemical formulas (1) to (4): Chemical formula (1) In the above chemical formula (1), R1, R2 and R3 are each independently hydrogen (H) or an alkyl group having 1 to 6 carbon atoms, m and n are integers from 1 to 20, independently of each other, A, B1 and B2 are independently oxygen (O) or sulfur (S), x and y represent the mole % of repeating units, x+y is 100, and x is between 80 and 98; Chemical formula (2) In the above chemical formula (2), x is an integer from 1 to 20, m and n represent the mole % of repeating units, m+n is 100, and m is between 80 and 98; Chemical formula (3) In the above chemical formula (3), x and y are integers from 1 to 20, independently of each other, m and n represent the mole % of repeating units, m+n is 100, and m is between 70 and 99; Chemical formula (4) In the above chemical formula (4), x and y are integers from 1 to 20, independently of each other, m and n represent the mole % of repeating units, m+n is 100, and m is between 70 and 99.

11. A method for producing a polymer compound, characterized in that in the step (b), maleic anhydride is mixed in an amount of 2 to 18 wt% relative to the weight of the copolymer.

12. In paragraph 10, after step (b), (c) A method for producing a polymer compound, further comprising a step of crosslinking a polymer compound produced by chemically bonding the copolymer and maleic anhydride.

13. A medical material containing the polymer compound of Article 7.

14. Medical devices manufactured from medical materials of Article 13.

Images