Biocompatible polymer having shape recovery capability through light and thermal energy responsiveness, preparation method therefor, and uses thereof

Abstract

The present invention relates to: a polymer composition having shape recovery capability by light and thermal energy and comprising a copolymer containing lactone and glycidyl methacrylate and a photosensitizer; a polymer compound prepared therefrom; a preparation method therefor; and uses thereof. The compound according to the present invention has biocompatibility and can induce shape deformation and recovery within the body temperature range as well as by a light source, such as light, and thus can be used as a medical material, which is inserted into a site where thermal energy transfer is difficult, and is particularly useful when locally precise shape recovery characteristics are intended to be imparted.

Description

Biocompatible polymer having shape restoration ability through light and thermal energy response, method of manufacturing the same, and uses

[0001] The present invention relates to a polymer composition having shape restoration ability by light and thermal energy, comprising a copolymer containing lactone and glycidyl methacrylate and a photosensitizer, a polymer compound prepared therefrom, a method for preparing the same, and uses.

[0002] Recently, there has been an increasing demand for minimally invasive functionality in implantable medical devices to facilitate rapid patient recovery.

[0003] In metals, shape memory alloys, which are representative minimally invasive materials, are utilized, while in polymers, materials based on polyurethane and polycaprolactone are utilized. However, polymers such as polyurethane require thermal energy of about 60°C to return to their original form after minimally invasive use, and at this temperature, protein denaturation occurs, causing harmful side effects to the human body.

[0004] To solve these problems, the inventors developed a polycaprolactone-based material capable of recovering its shape by reacting at body temperature and applied it to a medical device (Republic of Korea Registered Patent No. 10-2355542, Republic of Korea Published Patent No. 10-2021-0158356, Republic of Korea Registered Patent No. 10-2516991, Republic of Korea Registered Patent No. 10-2610524).

[0005] However, in the case of internal organs, there are organs where it is difficult to directly transfer thermal energy, and for micro-organs, it is necessary to induce shape deformation through localized energy transfer.

[0006] Accordingly, in order to meet these requirements, the inventors made diligent efforts to develop a novel polymer material capable of shape deformation and restoration in response to light energy, which is biocompatible and provides minimally invasive functionality upon insertion into the body. As a result, they developed a biocompatible polymer capable of shape restoration in response to both heat and light.

[0007] The present invention aims to provide a composition for producing a shape-memory polymer that is biocompatible and has shape deformation and restoration characteristics in response to light and heat, a polymer compound and a shape-memory polymer produced using the same, a method for producing the same, and uses.

[0008] To achieve the above objective, the present invention provides a light and temperature-sensitive polymer composition comprising a copolymer comprising a lactone and glycidyl methacrylate and a photosensitizer.

[0009] In the present invention, the copolymer may be characterized as being one or more selected from the group consisting of the following chemical formulas (1) to (4):

[0010] [Chemical Formula (1)]

[0011]

[0012] In the above chemical formula (1),

[0013] R1, R2, and R3 are independently hydrogen (H) or an alkyl group having 1 to 6 carbon atoms, and

[0014] m and n are independent integers from 1 to 20, and

[0015] A, B1, and B2 are independently oxygen (O) or sulfur (S), and

[0016] x and y represent the mole percentage of the repeating unit, and

[0017] x+y is 100, and x is 80 to 99;

[0018] [Chemical Formula (2)]:

[0019]

[0020] In the above chemical formula (2),

[0021] x is an integer from 1 to 20, and

[0022] m and n represent the mole percentage of the repeating unit,

[0023] m+n is 100, and m is 80 to 99;

[0024] [Chemical formula (3)]:

[0025]

[0026] In the above chemical formula (3),

[0027] x and y are independent integers from 1 to 20, and

[0028] m and n represent the mole percentage of the repeating unit, and

[0029] m+n is 100, and m is 70 to 99;

[0030] [Chemical Formula (4)]:

[0031]

[0032] In the above chemical formula (4),

[0033] x and y are independent integers from 1 to 20, and

[0034] m and n represent the mole percentage of the repeating unit, and

[0035] m+n is 100, and m is 70 to 99.

[0036] In the present invention, the molar ratio of lactone to glycidyl methacrylate in the copolymer may be characterized as being 85:15 to 99:1.

[0037] In the present invention, the photosensitive agent may be characterized as being infrared responsive.

[0038] In the present invention, the photosensitizer may be characterized as being one or more selected from the group consisting of indocyanine green (ICG), azobenzene acrylamide (AzoAAM), poly(3-hexylthiophene), polydopamine nanoparticles, copper sulfide nanoparticles, and gold nanorods.

[0039] In the present invention, the weight ratio of the photosensitizer and the copolymer in the polymer composition may be characterized as 0.06 : 99.94 to 24.90 : 75.10.

[0040] The present invention also provides a polymer compound in which the copolymer and the photosensitizer in the polymer composition are cross-linked.

[0041] The present invention also provides a shape memory polymer in which the polymer compound is cross-linked.

[0042] In the present invention, the shape memory polymer may be characterized by having a shape recovery ability of 85% or more at a temperature of 30 to 60°C.

[0043] In the present invention, the shape memory polymer may be characterized by having a shape recovery ability of 80% or more when irradiated with infrared rays.

[0044] In the present invention, the shape memory polymer may be characterized by having a shape recovery ability of 80% or more within 30 seconds upon infrared irradiation.

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

[0046] (a) A step of mixing a copolymer containing lactone and glycidyl methacrylate and a photosensitizer and reacting them by heat.

[0047] The present invention also provides a method for manufacturing a shape memory polymer comprising the following steps:

[0048] (a) a step of preparing a polymer compound by mixing a copolymer containing lactone and glycidyl methacrylate and a photosensitizer and reacting them by heat; and

[0049] (b) A step of preparing a shape memory polymer by additionally mixing a crosslinking agent into the polymer compound and performing a crosslinking reaction.

[0050] The present invention also provides a medical material comprising the polymer compound.

[0051] The present invention also provides a medical device made of the medical material.

[0052] In the present invention, the medical device may be characterized as being a surgical or procedural device for connecting or inserting into an internal tube.

[0053] In the present invention, the medical device may be characterized by connecting internal tubes having different diameters.

[0054] In the present invention, the internal tube may be characterized as being a blood vessel.

[0055] In the present invention, the lymph-venous anastomosis device may be characterized.

[0056] In the present invention, the medical device may be characterized as being a vascular stent or a non-vascular stent.

[0057] The compound according to the present invention is biocompatible and can induce shape deformation and restoration not only within the body temperature range but also by a light source such as light, so it can be used as a medical material inserted into areas where thermal energy transfer is difficult, and is particularly useful when it is desired to impart localized fine shape restoration characteristics.

[0058]

[0059] FIG. 1 shows the structure of a compound according to one embodiment (Example 3) of the present invention. 1 This is the result of H-NMR analysis.

[0060] Figure 2 is the result of confirming the shape restoration ability by heat of one embodiment (Example 3) according to the present invention.

[0061] Figure 3 is the result of confirming the shape restoration ability by light of one embodiment (Example 3) according to the present invention.

[0062] FIG. 4 is a schematic diagram showing an anastomosis of two internal tubes (e.g., lymphatic vessels and blood vessels) of different sizes (e.g., diameters) using a medical material according to the present invention.

[0063]

[0064] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by a skilled expert 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, terms such as “comprising” or “having” are intended to specify the existence of the features, numbers, steps, actions, components, parts, or combinations thereof described in the specification, and should be understood as not excluding in advance the existence or addition of one or more other features, numbers, steps, actions, components, parts, or combinations thereof.

[0066] In this invention, "shape memory polymer (SMP)" refers to a polymer material that has a fixed shape, is deformed and fixed under specific conditions such as heat or light to create a specific shape different from the original shape, and then returns to its original shape when specific conditions are applied again.

[0067] In the present invention, the terms “about” or “approximately” indicate an interval of accuracy understood by a person skilled in the art as still ensuring the technical effect of the feature. The terms typically indicate a deviation from the indicated value of ±20%, preferably ±15%, more preferably ±10%, and even more preferably ±5%.

[0068] Polymer compositions, polymer compounds, and shape memory polymers

[0069] In the present invention, it was confirmed that when a photosensitizer is mixed in a certain weight ratio with a copolymer containing lactone and glycidyl methacrylate, it exhibits shape memory properties not only with heat in the body temperature range but also with infrared irradiation, while having biocompatibility and minimal invasiveness.

[0070] Accordingly, in one aspect, the present invention relates to a light and heat-sensitive polymer composition comprising a copolymer comprising a lactone and glycidyl methacrylate and a photosensitizer.

[0071] In the present invention, the copolymer may be one or more compounds selected from the group consisting of the following chemical formulas (1) to (4).

[0072] Chemical formula (1)

[0073]

[0074] In the above chemical formula (1),

[0075] R1, R2, and R3 are independently hydrogen (H) or an alkyl group having 1 to 6 carbon atoms, and

[0076] m and n are independent integers from 1 to 20, and

[0077] A, B1, and B2 are independently oxygen (O) or sulfur (S), and

[0078] x and y represent the mole percentage of the repeating unit, and

[0079] x+y is 100, and x is 70 to 99.

[0080] The above chemical formula (1) can be represented by the following chemical formula (1'):

[0081] Chemical formula (1')

[0082]

[0083] In the above chemical formula (1')

[0084] m and n are independent integers from 1 to 20, and

[0085] x and y represent the mole percentage of the repeating unit, and

[0086] x+y is 100, and x is 80 to 99.

[0087] In the above chemical formula (1) or (1'), x and y represent the mole% of the repeating unit, x+y is 100, and x can be 80 to 99, 80 to 95, 88 to 99, or 88 to 94.

[0088] In the present invention, the 2-arm copolymer of formula (1) is described in detail in Korean Patent No. 10-2355542, and the entire text of Korean Patent No. 10-2355542 is incorporated into the present invention by reference.

[0089]

[0090] Chemical formula (2)

[0091]

[0092] In the above chemical formula (2),

[0093] x is an integer from 1 to 20, and

[0094] m and n represent the mole percentage of the repeating unit,

[0095] m+n is 100, and m is 70 to 99.

[0096] In the above chemical formula (2), m can be 80 to 96.

[0097] In the present invention, the 4-arm copolymer of formula (2) is described in detail in Korean Patent Publication No. 10-2021-0158356, and the entire text of Korean Patent Publication No. 10-2021-0158356 is incorporated by reference into the present invention.

[0098] Chemical formula (3)

[0099]

[0100] In the above chemical formula (3),

[0101] x and y are independent integers from 1 to 20, and

[0102] m and n represent the mole percentage of the repeating unit, and

[0103] m+n is 100, and m is 70 to 99.

[0104] In the present invention, the 6-arm copolymer of formula (3) is described in detail in Korean Patent No. 10-2516991, and the entire text of Korean Patent No. 10-2516991 is incorporated by reference into the present invention.

[0105] Chemical formula (4)

[0106]

[0107] In the above chemical formula (4),

[0108] x and y are independent integers from 1 to 20, and

[0109] m and n represent the mole percentage of the repeating unit, and

[0110] m+n is 100, and m is 70 to 99.

[0111] In the present invention, the 8-arm copolymer of formula (4) is described in detail in Korean Patent No. 10-2610524, and the entire text of Korean Patent No. 10-2610524 is incorporated by reference into the present invention.

[0112]

[0113] In any one copolymer of the present invention, the lactone may use ε-caprolactone as a monomer, and as another embodiment, monomers such as α-acetolactone, β-propiolactone, γ-butyrolactone, and δ-valerolactone may be used.

[0114] In one embodiment, the molar ratio of lactone to glycidyl methacrylate in the copolymer may be characterized as being in any range from 85:15 to 99:1 or within that range.

[0115] In another embodiment, the polycaprolactone-polyglycidyl methacrylate copolymer may be characterized in that the molar ratio of polycaprolactone to polyglycidyl methacrylate in the copolymer is 90:10 to 98:2.

[0116] In the present invention, the photosensitizer may be characterized as being infrared responsive and may be characterized as being responsive to light of about 790 to 820 nm, for example, about 800 to 810 nm, for example, about 808 nm.

[0117] In the present invention, the photosensitizer is indocyanine green (ICG), azobenzene acrylamide (AzoAAM) (C. Zhao, J. Lu and XX Zhu, ACS Appl. Polym. Mater., 2020, 2, 256-262), poly(3-hexylthiophene) (H. Inoue, T. Hirai, H. Hanochi, K. Oyama, H. Mayama, Y. Nakamura and S. Fujii, Macromolecules, 2019, 52, 708-717), polydopamine nanoparticles (X. Di, Y. Kang, F. Li, R. Yao, Q. Chen, C. Hang, Y. Xu, Y. Wang, P. Sun and G. Wu, Colloids Surf., It may be characterized by being one or more selected from the group consisting of B, 2019, 177, 149-159), copper sulfide nanoparticles (K. Poudel, RK Thapa, M. Gautam, W. Ou, ZC Soe, B. Gupta, HB Ruttala, HN Thuy, PC Dai, JH Jeong, SK Ku, HG Choi, CS Yong and JO Kim, Nanomed. Nanotechnol. Biol. Med., 2019, 21, 102042) and gold nanorods (JH Choi, H. Seo, JH Park, JH Son, DI Kim, J. Kim, GD Moon and DC Hyun, Colloids Surf., B, 2019, 173, 258-265), but is not limited thereto.

[0118] In one embodiment, the photosensitizer may be indocyanine green, which can be represented by the following chemical formula.

[0119]

[0120] According to an experimental example of the present invention, it was confirmed that when the weight ratio of the photosensitizer and the copolymer in the polymer composition is 0.05:99.95, the shape memory polymer produced based on the polymer composition does not effectively exhibit shape memory properties due to infrared radiation, and when the ratio is 25:75, the shape memory polymer produced based on the polymer composition does not effectively exhibit shape memory properties due to heat and infrared radiation.

[0121] Accordingly, it is preferable that the photosensitizer in the polymer composition be included in an amount exceeding 0.05 parts by weight relative to 99.95 parts by weight of the copolymer, and in an amount less than 25 parts by weight relative to 80 parts by weight of the copolymer.

[0122] In one embodiment, the weight ratio of the photosensitizer to the copolymer in the polymer composition may be characterized as about 0.06 : about 99.94 to about 20.00 : about 80.00, about 0.06 : about 99.94 to about 22.00 : about 78.00, about 0.06 : about 99.94 to about 23.00 : about 77.00, about 0.06 : about 99.94 to about 24.00 : about 76.00, or about 0.06 : about 99.94 to about 24.90 : about 75.10.

[0123] In another embodiment, the weight ratio of the photosensitizer to the copolymer in the polymer composition may be characterized as about 0.08 : about 99.92 to about 20.00 : about 80.00, about 0.08 : about 99.92 to about 22.00 : about 78.00, about 0.08 : about 99.92 to about 23.00 : about 77.00, about 0.08 : about 99.92 to about 24.00 : about 76.00, or about 0.08 : about 99.92 to about 24.90 : about 75.10.

[0124] In another embodiment, the weight ratio of the photosensitizer to the copolymer in the polymer composition may be characterized as about 0.10 : about 99.90 to about 20.00 : about 80.00, about 0.10 : about 99.90 to about 22.00 : about 78.00, about 0.10 : about 99.90 to about 23.00 : about 77.00, about 0.10 : about 99.90 to about 24.00 : about 76.00, or about 0.10 : about 99.90 to about 24.90 : about 75.10.

[0125] In the present invention, the weight ratio of the photosensitizer and the copolymer in the polymer composition may be characterized as being in any range of about 0.1 : about 99.9 to about 20.0 : about 80.0, or about 0.1 : about 99.9 to about 20.0 : about 80.0.

[0126] For example, the weight ratio of the photosensitizer to the copolymer in the polymer composition may be about 0.1 : about 99.9, about 0.5 : about 99.5, about 1.0 : about 99.0, about 1.5 : about 98.5, or about 20.0 : about 80:0.

[0127] In the present invention, the polymer composition may further include an initiator, which may be benzoyl peroxide in one embodiment but is not limited thereto, and may use potassium persulfate, ammonium persulfate, diauryl peroxide, dicumyl peroxide, hydrogen peroxide, or azobisisobutyronitrile.

[0128] In the present invention, the initiator may be included in an amount of about 0.1 to 5 weight%, for example, about 0.5 to 2 weight%, relative to the total weight of the mixture of the copolymer and the photosensitizer.

[0129] In one embodiment, the copolymer and the photosensitizer can be combined by thermally reacting with the initiator.

[0130] Accordingly, in another aspect, the present invention relates to a polymer compound in which the copolymer and the photosensitizer in the polymer composition are cross-linked.

[0131] In the present invention, the polymer compound may be cross-linked to have shape memory properties. In one embodiment, the polymer compound may be the compound of FIG. 1.

[0132] In one embodiment, the polymer compound can be bonded (photocrosslinked) by the photocrosslinking agent.

[0133] Accordingly, in another aspect, the present invention relates to a shape memory polymer in which the polymer compound is cross-linked.

[0134] In the present invention, the crosslinking agent may be one or more selected from the group consisting of potassium persulfate, ammonium persulfate, benzoyl peroxide, diuryl peroxide, dicumyl peroxide, hydrogen peroxide, azobisisobutyronitrile, 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), but is not limited thereto.

[0135] In the present invention, the crosslinking may be thermal crosslinking or photocrosslinking.

[0136] In one embodiment, the crosslinking agent is a photocrosslinking agent, and the photocrosslinking agent may be included in an amount of about 0.5 to 3 weight percent relative to the total weight of the mixture of the copolymer and the photosensitizer.

[0137] In a preferred embodiment, the photocrosslinking agent may be Iragcure 2959, and the Iragcure 2959 may be added in an amount of about 1% by weight relative to the total weight of the mixture of the copolymer and the photosensitizer.

[0138] In the present invention, the shape memory polymer may be characterized by having a shape recovery ability of 85% or more at a temperature of 30 to 60°C.

[0139] In the present invention, the shape memory polymer, after crosslinking, at a temperature of 35°C to 60°C, or any range of 35°C to 60°C, for example, at a temperature of about 35°C to 43°C, or any temperature of 35°C to 58°C, for example, 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, or about 58°C, has an average shape recovery ability of 85% or more, for example, about 86% or more, about 87% or more, about It may be characterized as being 88% or more, approximately 89% or more, approximately 90% or more, approximately 91% or more, approximately 92% or more, approximately 93% or more, approximately 94% or more, approximately 95% or more, approximately 96% or more, approximately 97% or more, approximately 98% or more, approximately 99% or more, or approximately 100%, but is not limited thereto.

[0140] Meanwhile, the shape memory polymer may be characterized by having a shape recovery ability of 80% or more when irradiated with infrared rays.

[0141] In one embodiment, the shape memory polymer may be characterized by having a shape recovery ability of 80% or more within 30 seconds upon infrared irradiation.

[0142] For example, the shape memory polymer may be characterized by having an average shape recovery ability of 80% or more, e.g., 81% or more, 82% or more, 83% or more, 84% or more, 85% or more, 86% or more, 87% or more, 88% or more, 89% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 100% or more, within about 30 seconds, e.g., within about 25 seconds, but is not limited thereto.

[0143] The shape memory polymer of the present invention has the advantage of being imparted with more than 80% shape memory properties by heat and light, and thus has the advantage as a various medical material for application to the human body where highly precise shape memory properties are required.

[0144] In the present invention, 'polymer compound' refers to a state in which a copolymer and a photosensitizer are combined by a thermal reaction, and 'shape memory polymer' refers to a state in which this polymer compound is further cross-linked by a cross-linking agent.

[0145]

[0146] Manufacturing method

[0147] The present invention also provides a method for preparing a polymer compound comprising the step of (a) mixing a copolymer comprising a lactone and glycidyl methacrylate and a photosensitizer and reacting them by heat.

[0148] The present invention also provides a method for manufacturing a shape memory polymer comprising: (b) a step of additionally mixing a crosslinking agent into the polymer compound prepared in step (a) and crosslinking it to produce a shape memory polymer.

[0149] In the present invention, step (a) may be characterized by mixing an initiator together and reacting it by heat, and the reaction may be carried out by stirring at a temperature of 110 to 130°C for about 1 to 8 hours.

[0150] In one embodiment, the above step (a) may be a step of mixing a copolymer comprising lactone and glycidyl methacrylate and a photosensitizer, additionally mixing benzoyl peroxide as an initiator, and then stirring to heat react at a temperature of about 120°C for about 2 hours.

[0151] In the present invention, the final reaction product of the heat reaction in step (a) can be precipitated in methanol at about 4°C, filtered, and then vacuum dried to produce a polymer compound.

[0152] In the present invention, step (b) applies UV at 100 to 500 mW / cm² 2 It can be cross-linked by irradiating with intensity for 1 to 20 minutes.

[0153] In one embodiment, step (b) involves mixing Irgacure with the polymer compound prepared in step (a) and approximately 265 mW / cm² 2 It may be a step of photocrosslinking by irradiating with intensity for about 4 minutes.

[0154]

[0155] use

[0156] In another aspect, the present invention relates to a medical material comprising the polymer compound or the shape memory polymer.

[0157] In another aspect, the present invention relates to a medical device manufactured from the medical material.

[0158] In the present invention, the medical material or medical device may be for implantation in the body, but is not limited thereto.

[0159] In the present invention, the medical material or medical device may be a surgical or procedural device for connecting or inserting into an internal tube, but is not limited thereto. In one embodiment, the internal tube may be a blood vessel.

[0160] In the present invention, the medical material or medical device may be a surgical or procedural device for connecting internal tubes having different diameters, but is not limited thereto.

[0161] In the present invention, the medical material or medical device may be an anastomosis device capable of anastomosis of internal tubes, for example, a lymphatic-venous anastomosis device.

[0162] In another aspect, the present invention provides the medical material or the medical device for use in surgery or procedures.

[0163] In another aspect, the present invention provides a use of the polymer compound or the shape memory polymer for manufacturing medical materials or medical devices.

[0164] In another aspect, the present invention provides a procedure or surgical method comprising the step of inserting or implanting the medical material or medical device into an individual requiring it. The procedure or surgical method may further comprise the step of irradiating infrared rays after the insertion or implantation step.

[0165] The medical material or medical device according to the present invention is particularly suitable for surgical procedures involving the anastomosis of internal tubes of different sizes, such as organs or blood vessels. This is because, when the medical material or medical device according to the present invention is inserted into internal tubes of different sizes and shape restoration is induced simultaneously, the connection effect may be reduced due to the step difference between the large and small parts; however, the present invention improves the connection effect by inserting the medical material or medical device according to the present invention into internal tubes of different sizes and then sequentially inducing shape restoration.

[0166] In one embodiment, the medical material or medical device according to the present invention is positioned between a first blood vessel and a second blood vessel to primarily exhibit shape memory properties due to body temperature, and the anastomosis efficiency can be improved by locally irradiating infrared light with a pinpoint, such as a laser pointer, to a site requiring more precise anastomosis.

[0167] In another embodiment, when intending to anastomose blood vessels of different sizes, the present invention may fix a part of the medical material or medical device according to the present invention by irradiating it with light (i.e., restoring its shape) on a first blood vessel, and then fix another part by sequentially positioning it on a second blood vessel and irradiating it with light (i.e., restoring its shape).

[0168] Although the above embodiment was described using blood vessels as an example, it is applicable to various internal vessels.

[0169] In particular, the medical material or medical device according to the present invention has the advantage of being applicable to areas requiring localized, precise shape restoration. That is, the medical material or medical device according to the present invention is useful in that it can induce shape restoration by locally irradiating infrared rays to surgical sites such as internal micro-organs, lymphatic vessels, blood vessels, and organs, where it is difficult to induce precise shape restoration by applying heat.

[0170] In addition, the present invention has the advantage that, when additional restoration ability needs to be provided depending on the prognosis after surgery, for example, shape restoration can be induced primarily by heat (body temperature) during the surgery stage, and additional shape restoration can be induced by irradiating light depending on the prognosis after surgery.

[0171] The medical material or medical device according to the present invention may be a vascular procedure or surgical device, and may be a vascular stent, a zebra, a stent for internal insertion into a blood vessel, or a support for supporting the outer wall of a blood vessel, but is not limited thereto.

[0172] The medical material or medical device according to the present invention may be a non-vascular stent, but is not limited thereto.

[0173] In the present invention, the medical material or medical device may be implanted in one or more areas selected from the group consisting of the eye, nose, paranasal sinus, jaw, face, cheekbone, forehead, skin tissue depression, intraosseous hip joint, and shoulder joint, but is not limited thereto.

[0174] The present invention can be utilized as a medical material or medical device for humans or animals.

[0175] The present invention can be used not only as a medical material alone but also by mixing with other medical materials to complement each other's characteristics.

[0176]

[0177] Examples

[0178] The present invention will be described in more detail below through examples. These examples are solely for illustrating the present invention, and it will be obvious to those skilled in the art that the scope of the present invention is not to be interpreted as being limited by these examples.

[0179]

[0180] Example. A polymer obtained by mixing a six-armed polycaprolactone-polyglycidyl methacrylate copolymer with indocyanine green using a thermal initiator.

[0181]

[0182] Example Composition (Weight Ratio) Indocyanine Green 6 arm PCL-PGMA (INNOSELF) BPO Example 1 ICG-INNOSELF (0.1 / 99.9) 0.199.91 Example 2 ICG-INNOSELF (0.5 / 99.5) 0.599.51 Example 3 ICG-INNOSELF (1.0 / 99.0) 1.099.01 Example 4 ICG-INNOSELF (1.5 / 98.5) 1.598.51 Example 5 ICG-INNOSELF (20 / 80) 20.080.01

[0183]

[0184] Indocyanine green (TCI chemical) and a 6-arm caprolactone and glycidyl methacrylate copolymer (6arm 94PCL-06PGMA, INNOSELF 1-6, TMDLAB co., Ltd.) were placed in a three-necked flask in xylene (Daejung chemicals & metals CO., LTD.) at a volume approximately 50 times the weight of the raw material (indocyanine / 6arm PCL-PGMA) and dissolved by stirring at 120°C for 1 hour. Subsequently, benzoyl peroxide (Sigma-Aldrich) was added and stirred at 120°C for 2 hours. The final reaction product was then precipitated in methanol (Daejung chemicals & metals CO., LTD.) at 4°C at a volume approximately 300 times the weight of the raw material, filtered, and vacuum dried.

[0185] After mixing 1 wt% of the crosslinking agent Irgacure 2959 (Sigma-Aldrich) into a polymer composition containing indocyanine green prepared for the manufacture of a light-sensitive shape memory film, 265 mW / cm² 2A sample was obtained by irradiating with UV light of intensity (365 nm) for 4 minutes.

[0186]

[0187] Comparative Example. A polymer obtained by mixing a six-arm polycaprolactone-polyglycidyl methacrylate copolymer with indocyanine green using a thermal initiator.

[0188]

[0189] Comparative Example Composition (Weight Ratio) Indocyanine Green 6 arm PCL-PGMA (INNOSELF) BPO Comparative Example 1 ICG-INNOSELF (0.05 / 99.95) 0.05 99.95 1 Comparative Example 2 ICG-INNOSELF (25 / 75) 25.0 75.01

[0190]

[0191] A copolymer of caprolactone and glycidyl methacrylate containing indocyanine green was prepared according to the composition in Table 2 in the same manner as in the examples. For film preparation, 1 wt% of the crosslinking agent Irgacure 2959 (Sigma-Aldrich) was mixed into the prepared polymer containing indocyanine green, and then 265 mW / cm² 2 A sample was obtained by irradiating with UV light of intensity (365 nm) for 4 minutes.

[0192]

[0193] Experimental Example 1. Thermal Properties

[0194] To verify the thermal characteristics of the examples and comparative examples, the melting temperature before crosslinking was measured in the temperature range from -70°C to 150°C using Differential Scanning Calorimetry (DSC).

[0195] As a result, as shown in Table 3, both the examples and comparative examples showed a melting temperature in the body temperature range of 35°C to 40°C, and through this, it was confirmed that shape recovery can be induced in response to body temperature when manufacturing medical devices for internal implantation.

[0196]

[0197] Distinction Tm (°C△H m (J / g) Example 1 39.42 44.78 Example 2 39.88 44.82 Example 3 40.42 45.21 Example 4 40.85 45.55 Example 5 40.94 46.27 Comparative Example 1 39.11 44.74 Comparative Example 2 41.25 46.68

[0198]

[0199] Experimental Example 2. Shape memory characteristics

[0200] 2-1. Shape Restoration Ability by Heat

[0201] To compare the shape memory characteristics of the examples and comparative examples, a film-shaped sample was stretched to a certain length at 40-60°C and then fixed at 4°C to measure the stretched length.

[0202] First, to verify the shape recovery characteristics due to heat, the sample was placed at a temperature of 35-50°C to expose the recovered length, and then the shape recovery ability (%) was verified according to Equation (1).

[0203] ----- Equation (1)

[0204]

[0205] As a result, as shown in Table 4, Example and Comparative Example 1 exhibited a shape recovery ability (or shape recovery power) of 85% or more by thermal energy, confirming that shape recovery by thermal energy is possible even in materials containing indocyanine green, whereas Comparative Example 2 showed a somewhat lower shape recovery ability of 72%.

[0206]

[0207] Classification Initial Length (mm) Deformation Length (mm) Recovery Length (mm) Shape Restoration Ability (%) Example 1 10 20 10.892 Example 2 10 20 11.189 Example 3 10 20 11.1588.5 Example 4 10 20 11.3486.6 Example 5 10 20 11.4285.8 Comparative Example 1 10 20 10.6593.5 Comparative Example 2 10 20 12.872.0

[0208]

[0209] 2-2. Shape Restoration Ability by Light

[0210] To compare the shape memory characteristics of the examples and comparative examples, a film-shaped sample was stretched to a certain length at 40-60°C and then fixed at 4°C to measure the stretched length.

[0211] In addition, to verify the shape recovery characteristics by light energy, the sample was exposed to an infrared lamp (GM Meditech, GM-543, 20W), the time required for shape recovery was measured, and the shape recovery ability (%) was verified according to Equation (1).

[0212] ----- Equation (1)

[0213]

[0214] As a result, as shown in Table 5, it was confirmed that more than 80% of the restoration was achieved within 20 seconds in all of the examples, but no restoration ability was observed in Comparative Example 1, and a low restoration rate of 52% was observed in Comparative Example 2.

[0215]

[0216] Classification Initial Length (mm) Deformation Length (mm) Recovery Length (mm) Shape Restoration Ability (%) Shape Recovery Speed ​​(sec) Example 1 10 20 11.88 224 Example 2 10 20 11.58 518 Example 3 10 20 11.28 817 Example 4 10 20 11.15 88 517 Example 5 10 20 11.32 86 815 Comparative Example 1 10 20 17.030 - Comparative Example 2 10 20 14.85 2.022

[0217]

[0218] Foregoing, specific parts of the present invention have been described in detail. It will be apparent to those skilled in the art that such specific descriptions are merely preferred embodiments and do not limit the scope of the invention. Accordingly, the actual scope of the invention is defined by the appended claims and their equivalents.

[0219]

[0220] This research was conducted as part of the Future Convergence Technology Development Program (STEAM Research) titled “Development of Source Technology for Energy-Responsive Self-Structural-Change Medical Materials Applicable to Biological Systems” (Project No. RS-2023-00302125, Project ID: 1711200487), supported by the Ministry of Science and ICT. (Lead Organization: TMDLAB Co., Ltd., Managing Organization: National Research Foundation of Korea)

Claims

1. A light and temperature-sensitive polymer composition comprising a copolymer containing a lactone and glycidyl methacrylate and a photosensitizer.

2. A polymer composition according to claim 1, characterized in that the copolymer is one or more 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 independently hydrogen (H) or an alkyl group having 1 to 6 carbon atoms, and m and n are independent integers from 1 to 20, and A, B1, and B2 are independently oxygen (O) or sulfur (S), and x and y represent the mole percentage of the repeating unit, and x+y is 100, and x is 80 to 99; [Chemical Formula (2)] In the above chemical formula (2), x is an integer from 1 to 20, and m and n represent the mole percentage of the repeating unit, m+n is 100, and m is 80 to 99; [Chemical Formula (3)] In the above chemical formula (3), x and y are independent integers from 1 to 20, and m and n represent the mole percentage of the repeating unit, and m+n is 100, and m is 70 to 99; [Chemical Formula (4)] In the above chemical formula (4), x and y are independent integers from 1 to 20, and m and n represent the mole percentage of the repeating unit, and m+n is 100, and m is 70 to 99.

3. A polymer composition according to claim 2, characterized in that the molar ratio of lactone to glycidyl methacrylate in the copolymer is 85:15 to 99:

1.

4. In claim 1, the photosensitizer is a polymer composition that is infrared responsive.

5. A polymer composition according to claim 4, wherein the photosensitizer is one or more selected from the group consisting of indocyanine green (ICG), azobenzene acrylamide (AzoAAM), poly(3-hexylthiophene), polydopamine nanoparticles, copper sulfide nanoparticles, and gold nanorods.

6. A polymer composition according to claim 1, wherein the weight ratio of the photosensitizer to the copolymer in the polymer composition is 0.06 : 99.94 to 24.90 : 75.

10.

7. A polymer compound in which a copolymer and a photosensitizer in a polymer composition of any one of claims 1 to 6 are cross-linked.

8. A shape memory polymer in which the polymer compound of claim 7 is cross-linked.

9. In claim 8, the shape memory polymer is a shape memory polymer having a shape recovery ability of 85% or more at a temperature of 30 to 60°C.

10. In claim 8, the shape memory polymer is a shape memory polymer having a shape recovery ability of 80% or more upon infrared irradiation.

11. In paragraph 10, the shape memory polymer is a shape memory polymer having a shape recovery ability of 80% or more within 30 seconds upon infrared irradiation.

12. A method for preparing the polymer compound of claim 7 comprising the following steps: (a) A step of mixing a copolymer containing lactone and glycidyl methacrylate and a photosensitizer and reacting them by heat.

13. Method for manufacturing a shape memory polymer of claim 8 comprising the following steps: (a) a step of preparing a polymer compound by mixing a copolymer containing lactone and glycidyl methacrylate and a photosensitizer and reacting them by heat; and (b) A step of preparing a shape memory polymer by additionally mixing a crosslinking agent into the polymer compound and performing a crosslinking reaction.

14. A medical material comprising the polymer compound of claim 7.

15. A medical device manufactured from the medical material of Paragraph 14.

16. In paragraph 15, the medical device is a medical device that is a surgical or procedural device for connecting or inserting into an internal tube.

17. In paragraph 16, the medical device is characterized by connecting internal tubes having different diameters.

18. A medical device according to claim 17, characterized in that the internal tube is a blood vessel.

19. A medical device characterized by being the lymph-venous anastomosis device according to claim 18.

20. A medical device according to claim 16, characterized in that the medical device is a vascular stent or a non-vascular stent.

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