Compositions, kits, and surface treatment methods for polymer materials

Abstract

The present invention relates to a composition for surface treatment of polymeric materials, and more specifically, the composition contains a hyperbranched polyglycerol having a repeating unit derived from glycidol and containing an unsubstituted or substituted acrylate group at at least one end, thereby preventing protein adsorption on the surface of a polymeric material or an internal implant material containing a polymeric material that has been surface-treated with the composition, and has the effect of inhibiting fibrosis, thrombus formation, or the adsorption of inflammatory cells.

Description

[Technical Field]

[0001] The present invention relates to a composition, a kit, and a method for surface treatment of polymer materials. [Background technology]

[0002] In recent years, due to the aging population and advancements in medical devices, interest in and demand for artificial implants that assist in disease diagnosis and the function of internal tissues and organs have surged. The biomaterials that make up these implants come in various forms, including metals, ceramics, and polymers, and are widely applied in implantable devices such as catheters and stents that come into direct contact with blood, biosensors, and drug delivery systems. The biomaterials that make up artificial implants should be made of inert substances that do not affect internal bodily functions, and because they come into direct contact with internal tissues and blood for extended periods, they must be made of materials with excellent biocompatibility. For this reason, research into surface treatment technologies for biomaterials is continuously being conducted.

[0003] On the other hand, artificial biomaterials implanted from outside the body are recognized as foreign bodies by the body's immune system, triggering a foreign body reaction (Foreigin Body reaction). This begins with the adsorption of proteins from tissues and blood onto the surface of the material, followed by the denaturation of the adsorbed proteins, which then attract platelets, macrophages, and other cells to the surrounding area. Since most implants are too large to be swallowed by phagocytosis, the gathered macrophages fuse to form multinucleated giant cells (Foreigin Body giant cells), and signaling factors generated from these cells attract fibroblasts to the surrounding area, forming a fibrous capsule membrane made of collagen.

[0004] Biofouling refers to the adsorption of proteins onto the surface of biomaterials. This protein adsorption is a phenomenon that triggers a foreign body reaction, subsequently promoting fibrosis, thrombus formation, and the adsorption of inflammatory cells, thereby inducing inflammation. Therefore, surface treatment technologies that alter the surface properties of materials to suppress protein adsorption are attracting attention as a way to minimize the foreign body reaction that is a problem when implanting artificial biomaterials.

[0005] Anti-fouling coating refers to coating a surface with a biocompatible material to prevent the adhesion of biological substances such as proteins, cells, and microorganisms. In the case of conventional artificial implants, even medical-grade silicones and Gore-Tex, which are known to have high biocompatibility, often cause foreign body reactions, limiting their application due to side effects such as thrombus formation and inflammation and pain caused by hypertrophy of fibrous tissue. Many researchers have recognized the need for surface development of materials that prevent foreign body reactions, and surface treatment methods using polymers with anti-fouling properties are attracting attention. This improves the biocompatibility problem that induces foreign body reactions, making it possible to apply them to implantable medical devices and biosensors for disease diagnosis, with virtually unlimited potential applications. [Overview of the Initiative] [Problems that the invention aims to solve]

[0006] The present invention aims to provide a composition for surface treatment of polymer materials.

[0007] The present invention aims to provide a kit for surface treatment of polymer materials.

[0008] The present invention aims to provide an implantable material containing a surface-treated polymer material.

[0009] The present invention aims to provide a method for surface treatment of polymer materials. [Means for solving the problem]

[0010] 1. A surface treatment composition for polymer materials, comprising a hyperbranched polyglycerol having repeating units derived from glycidol and containing an unsubstituted or substituted acrylate group at at least one terminus.

[0011] 2. A surface treatment composition for polymer materials, wherein, in item 1 above, the number average molecular weight of the hyperbranched polyglycerol is 500 g / mol to 500,000 g / mol.

[0012] 3. In item 1 above, the hyperbranched polyglycerol is obtained by ring-opening addition polymerization of glycidol using tritylated triethylene glycol as an initiator, and is a surface treatment composition for polymer materials.

[0013] 4. In item 1 above, the substituted acrylate group is an acrylate in which the second carbon is substituted with a linear or branched alkyl group of C1 to C6, a surface treatment composition for polymer materials.

[0014] 5. In item 1 above, the hyperbranched polyglycerol is a hyperbranched polyglycerol in which at least a portion of the terminals are methacrylated, a surface treatment composition for polymer materials.

[0015] 6. In item 5 above, the methacrylated hyperbranched polyglycerol is produced by reacting the hyperbranched polyglycerol with glycidyl methacrylate, and is a surface treatment composition for polymer materials.

[0016] 7. In item 1 above, the polymer material is thermoplastic polyurethane (TPU), polycarbonate (PC), polydimethylsiloxane (PDMS), polyvinyl chloride (PVC), polyethylene glycol (PEG), silicone, Teflon (PTFE, registered trademark), polystyrene, nylon, polyethylene terephthalate (PET), polyacrylate, polypropylene (PP), polyethylene (PE), polyether ether ketone (PEEK), polysulfone (PS), phenol resin (Phenol), epoxy resin, polyglycolide (PGA), polylactide (PLLA), polycaprolactone (PCL), PLGA (poly(lactic-co-glycolic A surface treatment composition for polymer materials, comprising at least one selected from the group consisting of (acid), PLCL (poly(e-caprolactone-co-lactide), polydioxanone (PDO), polytrimethylene carbonate (PTMC), polyanhydride, polyorthoester, polyphosphazene, hyaluronic acid, alginic acid, chitosan, collagen, gelatin, and polyamino acids.

[0017] 8. A kit for surface treatment of polymer materials, comprising the composition described in any of items 1 to 7 above and a crosslinking agent solution.

[0018] 9. In item 8 above, the crosslinking agent solution is prepared by dissolving the crosslinking agent in a C1-C6 alcohol, a C3-C6 cycloalkanone, or a C3-C6 oxacycloalkane, and is a kit for surface treatment of polymer materials.

[0019] 10. In item 8 above, the crosslinking agent is PETMP (pentaerythritol tetra(3-mercaptopropionate)), a kit for surface treatment of polymer materials.

[0020] 11. An implant for in vivo use, comprising a polymer material surface-treated with the composition according to any one of items 1 to 7 above.

[0021] 12. In item 11 above, the implant for in vivo use is a continuous glucose monitoring sensor.

[0022] 13. A method for surface treatment of a polymer material, comprising the step of treating at least a part of the surface of the polymer material with the composition according to any one of items 1 to 6 above and a crosslinking agent.

[0023] 14. In item 13 above, the step is performed by immersing the polymer material in the composition and then in the crosslinking agent, a method for surface treatment of a polymer material.

[0024] 15. In item 13 above, the crosslinking agent is PETMP (pentaerythritol tetra(3-mercaptopropionate)), a method for surface treatment of a polymer material.

[0025] 16. In item 13 above, the crosslinking agent is dissolved in an alcohol having 1 to 6 carbon atoms, a cycloalkanone having 3 to 6 carbon atoms, or an oxacycloalkane having 3 to 6 carbon atoms, a method for surface treatment of a polymer material.

[0026] 17. In item 13 above, the concentration of the crosslinking agent is 10 mM to 30 mM, a method for surface treatment of a polymer material.

[0027] 18. In item 13 above, the polymer material is thermoplastic polyurethane (TPU), polycarbonate (PC), polydimethylsiloxane (PDMS), polyvinyl chloride (PVC), polyethylene glycol (PEG), silicone, Teflon (PTFE, registered trademark), polystyrene, nylon, polyethylene terephthalate (PET), polyacrylate, polypropylene (PP), polyethylene (PE), polyether ether ketone (PEEK), polysulfone (PS), phenol resin, epoxy resin, polyglycolide (PGA), polylactide (PLLA), polycaprolactone (PCL), PLGA (poly(lactic-co-glycolic A surface treatment method for polymer materials, comprising at least one selected from the group consisting of (acid), PLCL (poly(e-caprolactone-co-lactide), polydioxanone (PDO), polytrimethylene carbonate (PTMC), polyanhydride, polyorthoester, polyphosphazene, hyaluronic acid, alginic acid, chitosan, collagen, gelatin, and polyamino acids. [Effects of the Invention]

[0028] An implantable material containing a polymer material surface-treated with the composition of the present invention inhibits the adsorption of endogenous proteins, surface fibrosis, and adsorption of inflammatory cells on the surface of the implantable material, ultimately preventing a decrease in performance even when implanted in the body.

[0029] Furthermore, an implantable material containing a polymer material surface-treated with the composition of the present invention can delay thrombus formation and inflammatory reactions that occur during implantation in the body. [Brief explanation of the drawing]

[0030] [Figure 1] Figure 1 schematically illustrates the process of treating the surface of a polymer material using hyperbranched polyglycerol and dopamine, which have repeating units derived from glycidol. [Figure 2] Figure 2 shows the process of synthesizing hyperbranched polyglycerol from triethylene glycol. [Figure 3] Figure 3 shows the results of the 1H NMR analysis of H2 in Figure 2. [Figure 4] Figure 4 shows the results of the 1H NMR analysis of H3 in Figure 2. [Figure 5] Figure 5 shows the results of the 1H NMR analysis of H4 in Figure 2. [Figure 6] Figure 6 shows the process of synthesizing methacrylated hyperbranched polyglycerol from H4 in Figure 2. [Figure 7] Figure 7 shows the results of 1H NMR analysis of methacrylated hyperbranched polyglycerol. [Figure 8] Figure 8 shows the process and results of coating the surface of a polymer material with hyperbranched polyglycerol and dopamine under basic buffer solvent conditions. [Figure 9] Figure 9 shows the process and results of coating the surface of a polymer material with hyperbranched polyglycerol and dopamine under methanol solvent conditions. [Figure 10] Figure 10 shows the process and results of coating the surface of a polymer material with methacrylated hyperbranched polyglycerol and a PETMP reducing agent under methanol solvent conditions. [Figure 11] Figure 11 shows the process and results of coating the surface of a polymer material with methacrylated hyperbranched polyglycerol and a PETMP reducing agent under conditions of ethanol and cyclopentanone solvent. [Modes for carrying out the invention]

[0031] The present invention will be described in detail below.

[0032] This invention provides a composition for surface treatment of polymer materials.

[0033] The surface treatment composition for polymer materials contains hyperbranched polyglycerol having repeating units derived from glycidol.

[0034] Hyperbranched polyglycerol is a polymer containing a branched structure and numerous hydroxyl groups.

[0035] The number-average molecular weight (Mn) of hyperbranched polyglycerols may be, but are not limited to, the following ranges: 500 g / mol to 500,000 g / mol, 650 g / mol to 400,000 g / mol, 800 g / mol to 300,000 g / mol, 950 g / mol to 200,000 g / mol, 1,100 g / mol to 100,000 g / mol, 1,400 g / mol to 50,000 g / mol, 2,000 g / mol to 25,000 g / mol, 2,500 g / mol to 12,000 g / mol, and 3,000 g / mol to 6,000 g / mol. The number-average molecular weight may also be calculated using the number of protons obtained by measuring NMR, for example.

[0036] The degree of branching (DB) of hyperbranched polyglycerols may be, but is not limited to, 0.4-1, 0.5-0.9, or 0.6-0.8.

[0037] Hyperbranched polyglycerol may further contain polyethylene glycol groups at one end. For example, hyperbranched polyglycerol may have a structure in which triethylene glycol is bonded to one end.

[0038] Hyperbranched polyglycerol may be manufactured by methods known to those skilled in the art.

[0039] Hyperbranched polyglycerol may be obtained by ring-opening addition polymerization of glycidol using triethylene glycol to which an acid-degradable protecting group or a photodegradable protecting group is attached as an initiator. A protecting group means a group to which a specific functional group is attached so as not to participate in the reaction, and an acid-degradable protecting group or a photodegradable protecting group means a protecting group to which the attached functional group can be deprotected by decomposition by acid or light.

[0040] The acid-degradable protecting group or photodegradable protecting group may be, but is not limited to, a tosyl group, an O-trityl group, an N-trityl group, or an S-trityl group.

[0041] The triethylene glycol to which an acid-degradable protecting group or a photodegradable protecting group is attached may be tritylated triethylene glycol, and more specifically, it may be S-tritylated triethylene glycol.

[0042] Hyperbranched polyglycerols may have repeating units derived from glycidol and contain at least one terminal unsubstituted or substituted acrylate group.

[0043] An unsubstituted acrylate group can be represented by the following chemical formula 1.

[0044] [ka]

[0045] The substituted acrylate group may have the second carbon of the chemical formula 1 substituted with a linear or branched alkyl group of C1 to C6. For example, the substituted acrylate group may be a methacrylate group.

[0046] According to one embodiment, the hyperbranched polyglycerol may be acrylicated hyperbranched polyglycerol. Specifically, the hyperbranched polyglycerol may have at least a portion of its terminal ends acrylicated.

[0047] According to one embodiment, the hyperbranched polyglycerol may be methacrylated hyperbranched polyglycerol. Specifically, the hyperbranched polyglycerol may have at least a portion of its terminal ends methacrylated. Methacrylated hyperbranched polyglycerol may be produced by known methods, for example, by reacting hyperbranched polyglycerol with glycidyl metacrylate.

[0048] Polymeric materials can be used as biomaterials. Biomaterials are a general term for materials that can be applied to living organisms as a means of diagnosing, treating, and preventing diseases, and refer to basic materials such as artificial organs, artificial tissues, and medical supplies that are used to replace damaged or dysfunctional human tissues and organs.

[0049] Polymer materials include thermoplastic polyurethane (TPU), polycarbonate (PC), polydimethylsiloxane (PDMS), polyvinyl chloride (PVC), polyethylene glycol (PEG), silicone, Teflon (PTFE, registered trademark), polystyrene, nylon, polyethylene terephthalate (PET), polyacrylate, polypropylene (PP), polyethylene (PE), polyether ether ketone (PEEK), polysulfone (PS), phenol resin, epoxy resin, polyglycolide (PGA), polylactide (PLLA), polycaprolactone (PCL), and PLGA (poly(lactic-co-glycolic The following may be selected, but are not limited to, at least one from the group consisting of poly(e-caprolactone-co-lactide), poly(e-caprolactone-co-lactide), polydioxanone (PDO), polytrimethylene carbonate (PTMC), polyanhydride, polyorthoester, polyphosphazene, hyaluronic acid, alginic acid, chitosan, collagen, gelatin, and polyamino acids.

[0050] The term "surface treatment" refers to modifying the surface of an object to be treated, thereby altering its properties. Treatment includes coating the surface and can be carried out to minimize any physical, chemical, or biological phenomena and reactions that may occur on the surface of the object being treated. Specifically, if the object being treated is a polymer material, surface treatment can be carried out to minimize the adsorption of inflammatory cells or inflammatory reactions.

[0051] The composition can be used, for example, after first applying a dopamine solution to the surface of a polymer material. In this case, a coating film can be formed on the surface of the polymer material by a thiol-enclic chemical reaction between the dopamine coated on the surface of the polymer material and hyperbranched polyglycerol.

[0052] The composition can be used, for example, together with a crosslinking agent. In this case, a crosslink is formed between the surface of the polymer material and the hyperbranched polyglycerol, allowing for more stable surface treatment of the polymer material.

[0053] The hyperbranched polyglycerol contained in the composition of the present invention is dense due to its branched structure, which prevents proteins from adhering to the surface of polymer materials due to steric hindrance, thereby exhibiting an effect of suppressing fibrillation. Furthermore, because hyperbranched polyglycerol contains numerous hydroxyl groups, it has high hydrophilicity and excellent biocompatibility. Due to these properties, polymer materials surface-treated with the composition of the present invention can be used as components of implantable materials.

[0054] When the surface of a polymer material is treated with the composition of the present invention and dopamine or a crosslinking agent, the inflammatory response in the body can be delayed even when the surface-treated polymer material is implanted in the body.

[0055] Furthermore, the present invention provides a kit for surface treatment of polymer materials.

[0056] The surface treatment kit for polymer materials may include a surface treatment composition for polymer materials containing the hyperbranched polyglycerol.

[0057] The kit may further include a dopamine solution. The dopamine solution can be prepared, for example, by dissolving dopamine in a buffer solution or methanol under basic conditions; specifically, by dissolving dopamine in methanol, but is not limited to this. If the kit further includes a dopamine solution, it may also further include an oxidizing agent. The oxidizing agent may be, for example, NaIO4, but is not limited to this.

[0058] The hyperbranched polyglycerol may have repeating units derived from glycidol and contain an unsubstituted or substituted acrylate group at at least one terminus. In this case, the kit may further include a crosslinking agent solution. The crosslinking agent solution can be prepared by dissolving the crosslinking agent in, for example, a C1-C6 alcohol (e.g., methanol, ethanol), a C3-C6 cycloalkanone (e.g., cyclopentanone), or a C3-C6 oxacycloalkane (e.g., tetrahydrofuran), and more specifically, by dissolving the crosslinking agent in cyclopentanone or tetrahydrofuran, and more specifically, by dissolving the crosslinking agent in cyclopentanone, but is not limited to these. The crosslinking agent is not particularly limited as long as it can crosslink the polymer material with the hyperbranched polyglycerol, and may, for example, be PETMP (pentaerythritol tetra(3-mercaptopropionate)), but is not limited to this. PETMP has four thiol groups, and under light irradiation or heating conditions at an appropriate temperature, it can form crosslinks between the methacrylate groups of methacrylated hyperbranched polyglycerol and the surface of the polymer material, thereby allowing the composition of the present invention to be applied to the surface of the polymer material in a more stable manner.

[0059] Furthermore, the present invention provides an implantable material for internal transplantation.

[0060] The implantable material includes a polymer material that has been surface-treated with the aforementioned surface treatment composition for polymer materials.

[0061] Implantable materials are materials that can be implanted or transplanted into the body, and include not only materials that can exist permanently or semi-permanently in the body, but also materials that can exist temporarily.

[0062] The surface-treated polymer material contained in the implant may be placed on the outermost layer of the implant. In this case, the surface-treated polymer material placed on the outermost layer reduces the amount of protein adsorbed onto the implant, thereby inhibiting fibrosis, thrombus formation, or adsorption of inflammatory cells in the body.

[0063] Examples of implantable materials include at least one selected from the group consisting of biosensors, artificial blood vessels, catheters, drains, shunts, cannulas, tubes, guidewires, bone chips, conduits, pins, rods, screws, plates, sutures, patches, balloons, stents, membranes, dental implants, dental materials, tissue regeneration supports, drug delivery systems, and gene delivery systems. Specifically, these may be biosensors, and more specifically, continuous glucose monitoring sensors, but are not limited to these.

[0064] Furthermore, the present invention provides a method for surface treatment of polymer materials.

[0065] As an example, a surface treatment method for a polymer material may include the step of treating a polymer material coated with dopamine with a surface treatment composition for polymer materials containing the hyperbranched polyglycerol.

[0066] The polymer materials, surface treatments, and compositions may be within the aforementioned range, but are not limited thereto.

[0067] Polymer materials coated with dopamine can be manufactured by methods known to those skilled in the art, for example, by dip-coating the polymer material in a dopamine solution, but are not limited thereto.

[0068] Alternatively, a surface treatment method for a polymer material may include the step of treating at least a portion of the surface of the polymer material with a surface treatment composition for polymer materials and a crosslinking agent, which comprises hyperbranched polyglycerol having an unsubstituted or substituted acrylate group at at least one terminal.

[0069] The substituted acrylate group may have the second carbon of the acrylate substituted, specifically, the second carbon of the acrylate may be substituted with a C1-C6 linear or branched alkyl group. According to one embodiment, the substituted acrylate group may be a methacrylate.

[0070] According to one embodiment, a surface treatment method for a polymer material may include the step of treating at least a portion of the surface of the polymer material with a surface treatment composition for polymer materials containing methacrylated hyperbranched polyglycerol and a crosslinking agent.

[0071] The step of treating a surface treatment composition and crosslinking agent for a polymer material comprising hyperbranched polyglycerol having at least one terminal unsubstituted or substituted acrylate group can be carried out by methods known to those skilled in the art, for example, by immersing the polymer material in the composition and then in the crosslinking agent, but is not limited thereto.

[0072] The crosslinking agent is not particularly limited as long as it can crosslink the polymer material with hyperbranched polyglycerol, and may, for example, be PETMP (pentaerythritol tetra(3-mercaptopropionate)), but is not limited thereto. The crosslinking agent can be dissolved in, for example, C1-C6 alcohols (e.g., methanol, ethanol), C3-C6 cycloalkanones (e.g., cyclopentanone), or C3-C6 oxacycloalkanes (e.g., tetrahydrofuran), and more specifically, it can be dissolved in cyclopentanone or tetrahydrofuran, and more specifically, it can be dissolved in cyclopentanone, but is not limited thereto. The concentration of the crosslinking agent may be, for example, 10mM to 30mM, 12mM to 29mM, 15mM to 28mM, 16mM to 26mM, 18mM to 25mM, 18.5mM to 24.5mM, 19mM to 24mM, or 19.5mM to 23.5mM, but is not limited to these ranges.

[0073] The polymer material targeted by the surface treatment method for polymer materials may be contained within an implant, and specifically, may be placed on the outermost surface of the implant. The implant may be within the aforementioned range, but is not limited to these.

[0074] Using a polymer material surface-treated by the method of the present invention, or an implantable material containing such polymer material, has the effect of preventing the adsorption of proteins to the surface, thereby inhibiting fibrosis, thrombus formation, or adsorption of inflammatory cells in the body.

[0075] The present invention will be specifically described below with reference to examples. [Examples]

[0076] The inventors have confirmed that hyperbranched polyglycerol (HPG), a polyol containing numerous hydroxyl groups (-OH) and exhibiting a branched structure, and dopamine (Figure 1) can be used as antifouling coating materials. Because HPG is high-density, it prevents protein adsorption due to steric hindrance, and its high hydrophilicity suggests biocompatibility.

[0077] Analytical equipment and conditions 1 The 1H NMR spectrum was measured using a nuclear magnetic resonance spectrometer (Agilent 400 MHz FT-NMR). Molecular weight and polydispersity index (PDI) values ​​were measured using gel permeation chromatography (GPC, Agilent 1260 infinity) in an aqueous buffer containing 0.05 M sodium nitrate (NaNO3). A Shodex SB-803HQ column was used at 35°C with a flow rate of 1.0 ml / min.

[0078] The hydrophilicity of the substrate was evaluated using a water contact angle meter (Phoenix 300).

[0079] The surface morphology and roughness of the substrate were measured using an atomic force microscope (Multimode V_AFM, Veeco). Samples were measured under Tapping Mode in Air conditions. The chemical composition of the substrate surface was analyzed using an X-ray photoelectron spectrometer (XPS, K-alpha, ThermoFisher). As part of the preparation of samples for thickness analysis, the substrate was cross-sectioned using a microtome (Ultramicrotome, CR-X, RMC). To measure the surface morphology and thickness, the substrate was coated with metal, and then images of the top and cross-section were taken at 14kV using a cold scanning electron microscope (Cold FE-SEM, S-4800, Hitachi High-Technologies).

[0080] Step 1. Synthesis and analysis of biocompatible polymers 1-1. Hyperbranched polyglycerol (HPG) Tosylation was performed using triethylene glycol (H2), followed by trityl modification bonding (H3). Using the trityl-modified triethylene glycol as an initiator, a glycid monomer (glycidol) was subjected to ring-opening polymerization (H4) on the hydroxyl group (Figure 2).

[0081] The synthesis methods for H2, H3, and H4 shown in Figure 2 are as follows.

[0082] To synthesize H2, 1.1 g, 1.0 eq of 4-toluenesulfonyl chloride and 10 ml of dichloromethane were added to a round-bottom flask with a single neck. After cooling to 0°C, 1.0 g, 1.2 eq of triethylene glycol and 0.79 g, 1.3 eq of triethylamine were added, and the mixture was stirred for 2 hours. Subsequently, an unreactive gas was formed using argon at room temperature, and the mixture was stirred for 24 hours. After the reaction was complete, the resulting solid was removed by filtration under reduced pressure. The filtrate was concentrated in a vacuum evaporator and separated using silica gel chromatography under conditions of 20% hexane and 80% ethyl acetate. 1 H NMR (400MHz, CDCl3): δ7.81-7.79(d,2H),7.35-7.33(d,2H),4.18-4.15(t,J=4.8Hz,2H),3.73-3.59(m,11H),2.45(s,3H), Figure 3).

[0083] To synthesize H3, a solution of sodium hydroxide (74 mg, 1.25 eq) dissolved in 1.0 ml of distilled water was added to a solution of triphenylmethanethiol (0.51 g, 1.25 eq) dissolved in ethanol / toluene (1:1, 5.0 ml) and stirred. Then, H2 (1.0 g, 1.2 eq) was dissolved in ethanol / toluene (1:1, 5.0 ml) and added to the previously stirred solution. After reacting at room temperature for 18 hours, the mixture was poured into a prepared saturated sodium bicarbonate solution. The organic solution layer was washed by extraction three times with sodium bicarbonate and three times with brine. The mixture was then dried over magnesium sulfate, concentrated under high vacuum using a vacuum evaporator, and separated by silica gel chromatography, increasing the proportion of ethyl acetate from 50% hexane, 50% ethyl acetate to 25% hexane, 75% ethyl acetate. 1 H NMR (400MHz, DMSO): δ:7.43-7.25(m,12H),7.42-7.40(m,3H),3.72-3.68(m,2H),3.60-3.55(m,4H),3.47-3.43(m,2H),2.46-2.42(t,2H), Figure 4).

[0084] To synthesize H4, H3 (0.1 g, 1.0 eq) and sodium hydride (68 mg, 0.1 eq) were dried under high vacuum for 10 minutes. The gas in the flask was then replaced with nitrogen, and glycid monomer (1.903 ml, 0.1 eq) was added using a syringe pump at 95°C for 20 hours. After the injection was complete, an additional 4 hours of reaction were carried out to allow all remaining glycid monomers to react, and the mixture was cooled to room temperature. After dissolving in a minimum amount of methanol, the mixture was precipitated with diethyl ether, and the solid was separated using a centrifuge. After repeating the precipitation three times, the mixture was dried under high vacuum. 1 H NMR (400MHz, DMSO): δ:7.43-7.25(m,12H),7.42-7.40(m,3H),4.79-4.42(m,114H),3.75-3.27(m,614H), Figure 5).

[0085] H4 1By \(^1H\) NMR analysis, the alkyl chains of the hydroxy group (4.79 ppm - 4.42 ppm) and the polyether group (3.75 ppm - 3.27 ppm) were confirmed. NMR was measured, and the molecular weight of the polymer was examined using the calculation based on the number of protons. The degree of polymerization (DP) was calculated as "the value obtained by subtracting 1 from [the integral value of the \(^1H\) proton NMR signal corresponding to the hydroxy group / the integral value of the \(^1H\) proton NMR signal corresponding to the trityl initiator]" (Figure 5). 1 The integral value of the \(^1H\) proton NMR signal corresponding to the trityl initiator 1 was calculated as "the value obtained by subtracting 1 from [the integral value of the \(^1H\) proton NMR signal corresponding to the hydroxy group / the integral value of the \(^1H\) proton NMR signal corresponding to the trityl initiator]" (Figure 5).

[0086] Therefore, the molecular weight of the polymer was calculated by the formula [the molecular weight before polymerization + the degree of polymerization × the molecular weight of the repeating unit of the monomer]. (M n =M I +DP·M glycidol =M I +[I OH / I Trityl -1]·M glycidol ; M n : The molecular weight of the polymer, M I : The molecular weight of the polymer initiator, I OH : The value obtained by integrating the signal of \(^1H\) NMR corresponding to the hydroxy group, 1 : The value obtained by integrating the signal of \(^1H\) NMR corresponding to the trityl initiator, I Trityl : The value obtained by integrating the signal of \(^1H\) NMR corresponding to the trityl initiator, 1 : The value obtained by integrating the signal of \(^1H\) NMR corresponding to the trityl initiator, M glycidol : The molecular weight of the repeating unit of the monomer)

[0087] The integral value of the NMR signal corresponding to the hydroxy group (4.79 ppm - 4.42 ppm) was 124.40, and it has 15 protons per unit of the trityl initiator. Therefore, using the said calculation formula, the molecular weight of "350.48 + [((124.40 / 15) - 1) × 74.079] = 890.76" was confirmed.

[0088] 1-2. Methacrylated hyperbranched polyglycerol The H4 polymer obtained by the method described above was reacted with glycidyl methacrylic acid to modify and bond the H4 polymer to the glycidyl methacrylic acid. Subsequently, a crosslinking reaction was carried out with a reducing agent containing thiol groups, and the polymer was coated onto a substrate (Figure 6).

[0089] After modified bonding, NMR analysis revealed that the double bond signal of the alkyl group of methacrylic acid was observed around 5.5 ppm–6.0 ppm, and a signal decay was observed around 4.0 ppm–5.0 ppm for the hydroxyl group due to the modified bonding (Figure 7).

[0090] Step 2. Evaluation of polymer immobilization ability on polyurethane substrate - evaluation of stability To coat HPG onto a TPU (Thermo Plastic Polyurethane) substrate, the following three methods were used.

[0091] 2-1. Oxidative polymerization coating In the field of dopamine coating, we adopted a continuous coating strategy in which polydopamine formation is induced by oxidative polymerization using 1.0 M basic buffer (pH 8.5), and then HPG is coated onto it by a thiol enclick chemical reaction.

[0092] Dopamine and HPG were dissolved in 1M Tris-HCl pH 8.5 buffer, and then sequentially coated and dried for 24 hours. A buffer solution containing 2 mg / ml of dopamine was prepared, the substrate was immersed in it for 24 hours, and then thoroughly washed with the buffer. After drying, the substrate was coated by immersion in a buffer solution containing 2 mg / ml of HS-HPG for another 24 hours, and then thoroughly washed with the buffer (Figure 8a).

[0093] When the contact angles were measured, contact angles of 16°, 24°, 37°, and 55° were obtained (Figure 8b).

[0094] 2-2. Dip coating / injection coating in a methanol solvent environment The coating was performed using a method different from the dopamine and HPG polymer coating method described in "2-1" above. Specifically, after changing the solvent from the 1.0 M Tris-HCl pH 8.5 buffer solution used in "2-1" to methanol, the dopamine coating and HPG polymer coating were performed using different methods: dip coating and spray coating, respectively (Figure 9a).

[0095] For the dopamine coating, the dip coating method was used, which involved immersing the TPU substrate in a 40 mM dopamine solution with an oxidizing agent for 5 minutes, followed by drying. Specifically, a dopamine solution was prepared by dissolving dopamine in methanol, and the TPU substrate was immersed in this solution before coating with an oxidizing agent (NaIO4). Subsequently, for the HPG coating, the spray coating method was used, which involved spraying the HPG solution onto the substrate using a sprayer, followed by drying.

[0096] As a result, the contact angle after dopamine dip coating was 61°-76°, and the contact angle after HPG spray coating was approximately 39° (Figure 9b).

[0097] 2-3. Methacrylic HPG coating To achieve more stable fixation on the substrate, a crosslinking agent was used to induce HPG coating through crosslinking on the substrate.

[0098] As a reducing agent, a PETMP (pentaerythritol tetra(3-mercaptopropionate)) crosslinking agent having four thiol groups was used.

[0099] A high-concentration methacrylate polymer coating of 100 mg / ml was applied using methanol as a solvent for 5 seconds, and then crosslinking was formed using a reducing agent. The concentration of the PETMP reducing agent was varied to find the conditions under which the lowest contact angle was formed. As a result, a contact angle of approximately 20° was achieved before washing under a 25 mM PETMP condition. The contact angle after washing was measured to be approximately 47° (Figure 10b).

[0100] Next, we attempted to find the optimal conditions by varying the number of immersions and the duration of immersion in a reducing agent solution of PETMP 25 mM dissolved in ethanol or cyclopentanone. The coating solvent was set to ethanol, which dissolves the polymer, and cyclopentanone, which does not dissolve the polymer, considering whether the pre-coated polymer would be washed away during crosslinking. When the number of immersions was 1 (1 second), it was observed that the contact angle of cyclopentanone (30°) was lower than that of ethanol (45°). Additional experiments were conducted using cyclopentanone as the solvent under various conditions. When the number of immersions was changed to 5 and the immersion time to 10 minutes, the contact angles were confirmed to be 63° and 66°, respectively (Figure 11b).

[0101] Table 1 below summarizes the methods and results for "2-1. Oxidative polymerization coating," "2-2. Coating in a methanol solvent environment," and "2-3. Methacrylic HPG coating."

[0102] [Table 1]

Claims

1. The invention comprises a terminally modified hyperbranched polyglycerol having repeating units derived from glycidol, wherein at least one terminal of the hyperbranched polyglycerol contains an unsubstituted or substituted acrylate group, The hyperbranched polyglycerol is a surface treatment composition for polymer materials, comprising structural units derived from tritylated triethylene glycol as an initiator and structural units derived from a ring-opening addition polymer of glycidol.

2. The surface treatment composition for polymer materials according to claim 1, wherein the number-average molecular weight of the terminally modified hyperbranched polyglycerol is 500 g / mol to 500,000 g / mol.

3. The surface treatment composition for polymer materials according to claim 1, wherein the substituted acrylate group is an acrylate in which the second carbon is substituted with a linear or branched alkyl group of C1 to C6.

4. The surface treatment composition for polymer materials according to claim 1, wherein the end-modified hyperbranched polyglycerol is a hyperbranched polyglycerol in which at least a portion of the ends are methacrylated.

5. The methacrylated hyperbranched polyglycerol comprises structural units derived from a ring-opening addition polymer of glycidol and structural units derived from glycidyl methacrylate, according to claim 4, for surface treatment of polymer materials.

6. The polymer material is thermoplastic polyurethane (TPU), polycarbonate (PC), polydimethylsiloxane (PDMS), polyvinyl chloride (PVC), polyethylene glycol ( (glycol, PEG), silicone, Teflon (PTFE, Teflon, registered trademark), polystyrene, nylon, polyethylene terephthalate (PET), polyacrylate, polypropylene (PP), polyethylene (PE), polyetheretherketone (PEEK), polysulfone (PS), phenol resin, epoxy, polyglycolide (PGA), polylactide (PLLA), polycaprolactone (PCL), PLGA (poly(lactic-co-glycolic A surface treatment composition for polymer materials according to claim 1, comprising at least one selected from the group consisting of acid, PLCL (poly(e-caprolactone-co-lactide), polydioxanone (PDO), polytrimethylene carbonate (PTMC), polyanhydride, polyorthoester, polyphosphazene, hyaluronic acid, alginic acid, chitosan, collagen, gelatin, and polyamino acids.

7. A kit for surface treatment of polymer materials, comprising the composition and crosslinking agent solution according to any one of claims 1 to 6.

8. The surface treatment kit for polymer materials according to claim 7, wherein the crosslinking agent is PETMP (pentaerythritol tetra(3-mercaptopropionate)).

9. An implantable material comprising a polymer material surface-treated with the composition described in any one of claims 1 to 6.

10. The implantable material according to claim 9, wherein the implantable material is a continuous blood glucose monitoring sensor.

11. A method for surface treatment of a polymer material, comprising the step of treating at least a portion of the surface of the polymer material with the composition and crosslinking agent described in any one of claims 1 to 5.

12. The surface treatment method for a polymer material according to claim 11, wherein the step is performed by immersing the polymer material in the composition and then immersing it in the crosslinking agent.

13. The surface treatment method for a polymer material according to claim 11, wherein the crosslinking agent is PETMP (pentaerythritol tetra(3-mercaptopropionate)).

14. The surface treatment method for a polymer material according to claim 11, wherein the crosslinking agent is dissolved in a C1-C6 alcohol, a C3-C6 cycloalkanone, or a C3-C6 oxacycloalkane.

15. The surface treatment method for a polymer material according to claim 11, wherein the concentration of the crosslinking agent is 10 mM to 30 mM.

16. The polymer material is thermoplastic polyurethane (TPU), polycarbonate (PC), polydimethylsiloxane (PDMS), polyvinyl chloride (PVC), polyethylene glycol ( (glycol, PEG), silicone, Teflon (PTFE, Teflon, registered trademark), polystyrene, nylon, polyethylene terephthalate (PET), polyacrylate, polypropylene (PP), polyethylene (PE), polyetheretherketone (PEEK), polysulfone (PS), phenol resin, epoxy, polyglycolide (PGA), polylactide (PLLA), polycaprolactone (PCL), PLGA (poly(lactic-co-glycolic A method for surface treatment of a polymer material according to claim 11, wherein the material is at least one selected from the group consisting of acid, PLCL (poly(e-caprolactone-co-lactide), polydioxanone (PDO), polytrimethylene carbonate (PTMC), polyanhydride, polyorthoester, polyphosphazene, hyaluronic acid, alginic acid, chitosan, collagen, gelatin, and polyamino acids.

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