Composition for surface treatment of polymeric materials, kit and surface treatment method

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 for surface treatment of a polymeric material, a kit, and a method for surface treatment of a polymeric material. [Background technology]

[0002] In recent years, interest and demand for artificial implants that assist in the diagnosis of diseases and the functioning of internal tissues and organs has increased rapidly due to the progress of aging and the development of medical devices. Biomaterials that make up the implants come in the form of metals, ceramics, polymers, etc., and are used in a variety of applications in medical devices including catheters and stents that come into direct contact with blood, biosensors, drug delivery vehicles, and other implantable devices. Biomaterials that make up artificial implants should be made of inert substances that have no effect on activities in the body, and must be made of materials with excellent biocompatibility because they come into direct contact with internal tissues and blood for long periods of time. For this reason, research into surface treatment technologies for biomaterials is being continuously 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. Proteins in tissues and blood are first adsorbed to the surface of the material, which then denatures, causing platelets, macrophages, and other cells to gather around it. Most implants are too large to be engulfed by phagocytosis, so the macrophages that gather there fuse to form multinucleated giant cells (foreign body giant cells), which then emit signal factors that 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 causes a foreign body reaction, which then promotes fibrosis, thrombus formation, and the adsorption of inflammatory cells, inducing inflammation. Therefore, as a method to minimize the foreign body reaction that is a problem when implanting artificial biomaterials, surface treatment technologies that change the surface of materials to have properties that suppress protein adsorption have attracted attention.

[0005] Anti-fouling coating refers to coating a surface with a biocompatible material to prevent biological substances such as proteins, cells, and microorganisms from adhering to the surface. In the case of conventional artificial implants, even medical silicone and Gore-Tex (registered trademark), which are known to be highly biocompatible, often cause foreign body reactions, and their application was limited due to side effects such as inflammation and pain caused by thrombus formation and hypertrophy of fibrotic tissue. Many researchers feel the need to develop surfaces that prevent foreign body reactions, and surface treatment methods using polymers with anti-fouling properties are attracting attention. This will improve the biocompatibility problem that induces foreign body reactions, and make it possible to apply it to implantable medical devices and biosensors for disease diagnosis, with an unlimited range of applications. Summary of the Invention [Problem to be solved by the invention]

[0006] An object of the present invention is to provide a composition for surface treatment of polymeric materials.

[0007] An object of the present invention is to provide a kit for surface treatment of polymeric materials.

[0008] An object of the present invention is to provide an implant comprising a surface-treated polymeric material.

[0009] An object of the present invention is to provide a method for surface treatment of a polymeric material. [Means for solving the problem]

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

[0011] 2. The composition for surface treatment of polymeric materials according to item 1 above, wherein the hyperbranched polyglycerol has a number average molecular weight of 500 g / mol to 500,000 g / mol.

[0012] 3. A composition for surface treatment of polymeric materials according to the above item 1, wherein the hyperbranched polyglycerol is obtained by ring-opening addition polymerization of glycidol using tritylated triethylene glycol as an initiator.

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

[0014] 5. A composition for surface treatment of a polymer material according to item 1, wherein the hyperbranched polyglycerol is a hyperbranched polyglycerol at least a portion of whose ends are methacrylated.

[0015] 6. A composition for surface treatment of a polymer material according to item 5, wherein the methacrylated hyperbranched polyglycerol is produced by reacting the hyperbranched polyglycerol with glycidyl methacrylate.

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

[0017] 8. A kit for surface treatment of a polymeric material, comprising the composition according to any one of items 1 to 7 above and a crosslinker solution.

[0018] 9. The surface treatment kit for a polymer material according to item 8, wherein the crosslinking agent solution is produced by dissolving a crosslinking agent in a C1 to C6 alcohol, a C3 to C6 cycloalkanone, or a C3 to C6 oxacycloalkane.

[0019] 10. The surface treatment kit for a polymer material according to item 8, wherein the crosslinking agent is PETMP (pentaerythritol tetra(3-mercaptopropionate)).

[0020] 11. An implant comprising a polymeric material whose surface has been treated with the composition according to any one of items 1 to 7.

[0021] 12. The implant according to item 11, wherein the implant is a continuous blood glucose monitoring sensor.

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

[0023] 14. The surface treatment method for a polymer material according to item 13, wherein the step is carried out by immersing the polymer material in the composition and then immersing it in the crosslinking agent.

[0024] 15. The surface treatment method for a polymeric material according to item 13, wherein the crosslinking agent is PETMP (pentaerythritol tetra(3-mercaptopropionate)).

[0025] 16. The surface treatment method for a polymeric material according to item 13, wherein the crosslinking agent is dissolved in a C1 to C6 alcohol, a C3 to C6 cycloalkanone, or a C3 to C6 oxacycloalkane.

[0026] 17. The surface treatment method for a polymeric material according to item 13, wherein the concentration of the crosslinking agent is 10 mM to 30 mM.

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

[0028] An implant containing a polymeric material whose surface has been 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 implant, and ultimately prevents a decrease in performance when implanted in the body.

[0029] Furthermore, an implant material containing a polymeric material whose surface has been treated with the composition of the present invention can delay thrombus formation and inflammatory reactions that occur when the material is implanted in the body. [Brief description of the drawings]

[0030] [Figure 1] FIG. 1 shows a schematic diagram of the process of treating the surface of a polymeric material with hyperbranched polyglycerol having repeating units derived from glycidol and dopamine. [Diagram 2] FIG. 2 shows the process of synthesizing hyperbranched polyglycerol from triethylene glycol. [Diagram 3] FIG. 3 shows the results of 1H NMR analysis of H2 from FIG. [Figure 4] FIG. 4 shows the results of 1H NMR analysis of H3 from FIG. [Diagram 5] FIG. 5 shows the results of 1H NMR analysis of H4 from FIG. [Figure 6] FIG. 6 shows a process for synthesizing methacrylated hyperbranched polyglycerol from H4 in FIG. [Figure 7] FIG. 7 shows the results of 1H NMR analysis of methacrylated hyperbranched polyglycerol. [Figure 8] FIG. 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] FIG. 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] FIG. 10 shows the process and results of coating the surface of a polymer material using methacrylated hyperbranched polyglycerol and a PETMP reducing agent under methanol solvent conditions. [Figure 11] FIG. 11 shows the process and results of coating the surface of a polymer material using methacrylated hyperbranched polyglycerol and a PETMP reducing agent under ethanol and cyclopentanone solvent conditions. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

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

[0032] The present invention provides a composition for treating the surface of a polymeric material.

[0033] The composition for surface treatment of polymeric materials comprises a hyperbranched polyglycerol having repeating units derived from glycidol.

[0034] Hyperbranched polyglycerol is a polymer that contains a branched structure and many hydroxyl groups.

[0035] The number average molecular weight (Mn) of the hyperbranched polyglycerol may be, but is not limited to, 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, or 3,000 g / mol to 6,000 g / mol. The number average molecular weight may be, for example, a value calculated using the number of protons measured by NMR.

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

[0037] The hyperbranched polyglycerol may further include a polyethylene glycol group at one end. As an example, the hyperbranched polyglycerol may have a structure in which triethylene glycol is bound to one end.

[0038] The hyperbranched polyglycerol may be produced by a method known to those skilled in the art.

[0039] The hyperbranched polyglycerol may be obtained by ring-opening addition polymerization of glycidol using triethylene glycol having an acid-decomposable or photodecomposable protecting group attached thereto as an initiator. The protecting group means a group that is bonded so that a specific functional group does not participate in a reaction, and the acid-decomposable or photodecomposable protecting group means a protecting group that can be decomposed by acid or light to deprotect the bonded functional group.

[0040] The acid-labile or photolabile 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 having an acid-labile protecting group or a photolabile protecting group attached thereto may be tritylated triethylene glycol, specifically, S-tritylated triethylene glycol.

[0042] The hyperbranched polyglycerol may be a hyperbranched polyglycerol having repeating units derived from glycidol and containing an unsubstituted or substituted acrylate group at at least one terminus.

[0043] The unsubstituted acrylate group can be represented by Formula 1 below.

[0044] [ka]

[0045] The substituted acrylate group may be one in which the carbon number 2 in the above Chemical Formula 1 is substituted with a C1 to C6 linear or branched alkyl group. For example, the substituted acrylate group may be a methacrylate group.

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

[0047] According to one embodiment, the hyperbranched polyglycerol may be a methacrylated hyperbranched polyglycerol. Specifically, the hyperbranched polyglycerol may have at least a portion of its terminals methacrylated. The methacrylated hyperbranched polyglycerol may be produced by a known method, for example, by reacting the hyperbranched polyglycerol with glycidyl methacrylate.

[0048] Polymeric materials can be used as biomaterials. Biomaterials are a general term for materials that can be applied to the living body for the diagnosis, treatment, and prevention of diseases, and are the basic materials for artificial organs, artificial tissues, and medical supplies used to replace damaged or non-functional human tissues and organs.

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

[0050] The term "surface treatment" means modifying the surface of a treatment target to change the surface properties, and the treatment includes coating the surface, and can be performed to minimize physical, chemical or biological phenomena and reactions that may occur on the surface of the treatment target. Specifically, when the treatment target is a polymeric material, the surface treatment can be performed to minimize the adsorption of inflammatory cells or inflammatory reactions.

[0051] The composition can be used, for example, after the prior application of a dopamine solution on the surface of a polymeric material, where a coating film can be formed on the surface of the polymeric material by a thiol-ene click chemical reaction between the dopamine coated on the surface of the polymeric material and the hyperbranched polyglycerol.

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

[0053] The hyperbranched polyglycerol contained in the composition of the present invention has a high density due to its branched structure, and can prevent adhesion of proteins to the surface of polymeric materials due to steric hindrance, thereby suppressing fibrosis. Furthermore, the hyperbranched polyglycerol contains many hydroxyl groups, and therefore has high hydrophilicity and excellent biocompatibility. Due to these properties, polymeric materials surface-treated with the composition of the present invention can be used as components of implants.

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

[0055] The present invention also provides a kit for surface treatment of a polymeric material.

[0056] A kit for surface treatment of a polymeric material can include a composition for surface treatment of a polymeric material, which contains the hyperbranched polyglycerol.

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

[0058] The hyperbranched polyglycerol may be a hyperbranched polyglycerol having a repeating unit derived from glycidol and containing an unsubstituted or substituted acrylate group at at least one end. In this case, the kit may further include a crosslinking agent solution. The crosslinking agent solution may be prepared by dissolving a 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), specifically, the crosslinking agent may be prepared by dissolving a crosslinking agent in cyclopentanone or tetrahydrofuran, more specifically, the crosslinking agent may be prepared by dissolving a crosslinking agent in cyclopentanone, but is not limited thereto. The crosslinking agent is not particularly limited as long as it can crosslink the polymer material and the hyperbranched polyglycerol, and may be, for example, PETMP (pentaerythritol tetra(3-mercaptopropionate), but is not limited thereto. PETMP has four thiol groups, and under conditions of light irradiation or heating at an appropriate temperature, crosslinks are formed between the methacrylic groups of the methacrylated hyperbranched polyglycerol and the surface of the polymer material, allowing the composition of the present invention to be applied more stably to the surface of the polymer material.

[0059] The present invention also provides an implant.

[0060] The implant comprises a polymeric material that has been surface-treated with the composition for surface treatment of polymeric materials.

[0061] An implant is a material that can be implanted or transplanted into the body, and includes materials that can exist in the body permanently or semi-permanently as well as materials that can exist temporarily.

[0062] The surface-treated polymer material contained in the implant may be disposed on the outermost part of the implant, in which case the surface-treated polymer material disposed on the outermost part reduces proteins adsorbed onto the implant, thereby inhibiting fibrosis, thrombus formation, or adsorption of inflammatory cells in the body.

[0063] The implantable material may be 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, supports for tissue regeneration, drug delivery vehicles, and gene delivery vehicles, and may specifically be a biosensor, and more specifically may be a continuous blood glucose monitoring sensor, but is not limited to these.

[0064] The present invention also provides a method for treating the surface of a polymeric material.

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

[0066] The polymeric materials, surface treatments and compositions may be within the ranges set forth above, but are not limited to these.

[0067] The dopamine-coated polymeric material can be prepared by a method known to those skilled in the art, for example, but not limited to, dip-coating the polymeric material in a dopamine solution.

[0068] Alternatively, a method for treating the surface of a polymeric material can include treating at least a portion of a surface of the polymeric material with a composition for treating the surface of a polymeric material, the composition including a hyperbranched polyglycerol having an unsubstituted or substituted acrylate group at at least one terminus, and a crosslinking agent.

[0069] The substituted acrylate group may be substituted at the 2nd carbon of the acrylate, specifically, the 2nd carbon of the acrylate may be substituted with a C1 to C6 linear or branched alkyl. According to one embodiment, the substituted acrylate group may be a methacrylate.

[0070] According to one embodiment, a method for treating a surface of a polymeric material can include treating at least a portion of a surface of the polymeric material with a composition for treating a surface of a polymeric material comprising a methacrylated hyperbranched polyglycerol and a crosslinking agent.

[0071] The step of treating a polymeric material containing a hyperbranched polyglycerol having an unsubstituted or substituted acrylate group at at least one end with a surface treatment composition and a crosslinking agent can be carried out by a method known to those skilled in the art, for example, by immersing the polymeric material in the composition and then immersing it 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 and the hyperbranched polyglycerol, and may be, for example, PETMP (pentaerythritol tetra(3-mercaptopropionate), but is not limited thereto. The crosslinking agent can be dissolved in, for example, C1-C6 alcohol (e.g., methanol, ethanol), C3-C6 cycloalkanone (e.g., cyclopentanone), or C3-C6 oxacycloalkane (e.g., tetrahydrofuran), 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 crosslinker may be, for example, but is not limited to, 10 mM to 30 mM, 12 mM to 29 mM, 15 mM to 28 mM, 16 mM to 26 mM, 18 mM to 25 mM, 18.5 mM to 24.5 mM, 19 mM to 24 mM, or 19.5 mM to 23.5 mM.

[0073] The polymeric material to be treated by the surface treatment method for the polymeric material may be included in an implant, specifically, may be disposed on the outermost part of the implant. The implant may be within the above-mentioned range, but is not limited thereto.

[0074] The use of a polymeric material that has been surface-treated by the method of the present invention, or an implant material containing such a polymeric material, has the effect of preventing the adsorption of proteins to the surface, thereby inhibiting fibrosis, thrombus formation, or the 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 an antifouling coating material. HPG has a high density, which prevents protein adsorption through steric hindrance, and is highly hydrophilic, which is expected to make it biocompatible.

[0077] Analytical equipment and conditions 1 H NMR spectra were 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 aqueous buffer containing 0.05 M sodium nitrate (NaNO3). A Shodex SB-803HQ column was used at 35 °C, and the flow rate was set at 1.0 ml / min.

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

[0079] The surface morphology and roughness of the substrates were measured using an atomic force microscope (Multimode V_AFM, Veeco). The samples were measured using Tapping Mode in Air. The chemical composition of the substrate surface was analyzed using an X-ray photoelectron spectroscopy device (XPS, K-alpha, ThermoFisher). In the process of preparing the samples for thickness analysis, the cross-section of the substrate was cut using a microtome (Ultramicrotome, CR-X, RMC). To measure the surface morphology and thickness, images of the top and cross-section of the substrate were taken at 14 kV using a low-temperature scanning electron microscope (Cold FE-SEM, S-4800, Hitachi High-Technologies) after metal coating treatment.

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

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

[0082] To synthesize H2, 4-toluenesulfonyl chloride (1.1 g, 1.0 eq) and 10 ml of dichloromethane were added to a single-necked round-bottom flask, cooled to 0°C, triethylene glycol (1.0 g, 1.2 eq) and triethylamine (0.79 g, 1.3 eq) were added, and the mixture was stirred for 2 hours. After that, a non-reactive gas was generated at room temperature using argon, and the mixture was stirred for 24 hours. After the reaction was completed, the solid formed was removed by filtration under reduced pressure. The filtrate was concentrated using a reduced pressure concentration evaporator, and separated using silica gel chromatography under the 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, it was poured into the prepared saturated sodium bicarbonate solution. The organic solution layer was extracted and washed three times with sodium bicarbonate and three times with salt water. It was then dried over magnesium sulfate and concentrated under high vacuum using a reduced pressure concentration evaporator, and separated using silica gel chromatography while increasing the ratio 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, and then the gas in the flask was replaced with nitrogen, and glycidyl monomer (1.903 ml, 0.1 eq) was added using a syringe pump at 95°C for 20 hours. After the injection was completed, the reaction was continued for another 4 hours to ensure that all the remaining glycidyl monomer had reacted, and then cooled to room temperature. The mixture was then dissolved in a minimum amount of methanol, precipitated with diethyl ether, and the solid was separated using a centrifuge. The precipitation was repeated three times, and 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 1H NMR analysis confirmed the presence of alkyl chains with hydroxyl groups (4.79 ppm-4.42 ppm) and polyether groups (3.75 ppm-3.27 ppm). The molecular weight of the polymer was determined by measuring the NMR and calculating the number of protons. The degree of polymerization (DP) was calculated by dividing the number of protons by the number of protons corresponding to the hydroxyl groups. 1 H proton NMR signal integrals corresponding to trityl initiator 1 The H proton NMR signal integral was subtracted by 1 (Figure 5).

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

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

[0088] 1-2.Methacrylated hyperbranched polyglycerol The H4 polymer obtained by the above method was reacted with glycidyl methacrylate to modify and bond the H4 polymer to the glycidyl methacrylate. After that, a crosslinking reaction was carried out with a reducing agent having a thiol group, and the polymer was coated on a substrate (Figure 6).

[0089] After the modified conjugation, NMR analysis showed that the double bond signal of the alkyl group of methacrylic acid was observed at around 5.5 ppm-6.0 ppm, and the signal attenuation of the hydroxyl group due to the modified conjugation was observed at around 4.0 ppm-5.0 ppm (Figure 7).

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

[0091] 2-1.Oxidation polymerization coating In the field of dopamine coating, we adopted a sequential coating strategy in which polydopamine was induced to form by oxidative polymerization using 1.0 M basic buffer (pH 8.5), and then HPG was coated on it by thiol-ene click chemistry.

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

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

[0094] 2-2. Dip coating / spray coating in a methanol solvent environment The dopamine and HPG polymer coating methods were performed using methods different from those 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, i.e., immersion coating and spray coating, respectively (Figure 9a).

[0095] The dip coating used for dopamine coating was performed by immersing the substrate in a 40 mM dopamine solution containing an oxidizing agent for 5 minutes, followed by drying. Specifically, dopamine was dissolved in methanol to prepare a dopamine solution, and the TPU substrate was immersed in the solution, followed by adding an oxidizing agent (NaIO4) to perform coating. The spray coating used for HPG coating was performed by spraying the HPG solution onto the substrate with a sprayer, followed by drying.

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

[0097] 2-3.Methacrylated HPG coating To immobilize it more stably on the substrate, a cross-linking agent was used to induce the HPG coating on the substrate by cross-linking.

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

[0099] A high concentration methacrylated polymer coating of 100 mg / ml was applied in methanol as a solvent for 5 seconds, after which a reducing agent was used to form cross-links. 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 about 20° was achieved before washing under the condition of 25 mM PETMP. The contact angle after washing was measured to be about 47° (Figure 10b).

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

[0101] The methods and results of "2-1. Oxidative polymerization coating," "2-2. Coating in a methanol solvent environment," and "2-3. Methacrylated HPG coating" are summarized in Table 1 below.

[0102] [Table 1]

Claims

1. A composition for surface treatment of polymeric materials, comprising a hyperbranched polyglycerol having repeating units derived from glycidol and containing an unsubstituted or substituted acrylate group at at least one end.

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

3. 2. The composition for surface treatment of polymeric materials according to claim 1, wherein the hyperbranched polyglycerol is obtained by ring-opening addition polymerization of glycidol using tritylated triethylene glycol as an initiator.

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

5. The composition for surface treatment of a polymer material according to claim 1 , wherein the hyperbranched polyglycerol is a hyperbranched polyglycerol at least a portion of whose ends is methacrylated.

6. The composition for surface treatment of polymeric materials according to claim 5, wherein the methacrylated hyperbranched polyglycerol is produced by reacting the hyperbranched polyglycerol with glycidyl methacrylate.

7. The polymeric material may be thermoplastic polyurethane (TPU), polycarbonate (PC), polydimethylsiloxane (PDMS), polyvinyl chloride (PVC), polyethylene glycol (PEG), or the like. glycol, PEG), silicone, Teflon (PTFE, Teflon, registered trademark), polystyrene, nylon, polyethylene terephthalate (PET), polyacrylate, polypropylene (PP), polyethylene (PE), polyether ether ketone (PEEK), polysulfone (PS), phenolic resin, epoxy, polyglycolide (PGA), polylactide (PLLA), polycaprolactone (PCL), and poly(lactic-co-glycolic 2. The composition for surface treatment of a polymer material according to claim 1, which is at least one selected from the group consisting of poly(e-caprolactone-co-lactide), polydioxanone (PDO), polytrimethylene carbonate (PTMC), polyanhydride, polyorthoester, polyphosphazene, hyaluronic acid, alginic acid, chitosan, collagen, gelatin, and polyamino acid.

8. A kit for surface treatment of a polymeric material, comprising the composition according to any one of claims 1 to 7 and a crosslinking agent solution.

9. The kit for surface treatment of polymeric materials according to claim 8, wherein the crosslinking agent solution is prepared by dissolving a crosslinking agent in a C1 to C6 alcohol, a C3 to C6 cycloalkanone, or a C3 to C6 oxacycloalkane.

10. 9. The kit for surface treatment of a polymer material according to claim 8, wherein the crosslinking agent is PETMP (pentaerythritol tetra(3-mercaptopropionate), pentaerythritol tetrakis(3-mercaptopropionate)).

11. An implant comprising a polymeric material whose surface has been treated with the composition according to any one of claims 1 to 7.

12. 12. The implant of claim 11, wherein the implant is a continuous blood glucose monitoring sensor.

13. A method for treating the surface of a polymeric material, comprising the step of treating at least a part of the surface of the polymeric material with the composition according to any one of claims 1 to 6 and a crosslinking agent.

14. The method for treating a surface of a polymeric material according to claim 13, wherein the step is performed by immersing the polymeric material in the composition and then immersing the polymeric material in the crosslinking agent.

15. 14. The method for treating a polymeric material surface according to claim 13, wherein the crosslinking agent is PETMP (pentaerythritol tetra(3-mercaptopropionate), pentaerythritol tetrakis(3-mercaptopropionate)).

16. 14. The method for treating a surface of a polymeric material according to claim 13, wherein the crosslinking agent is dissolved in a C1 to C6 alcohol, a C3 to C6 cycloalkanone, or a C3 to C6 oxacycloalkane.

17. The method for treating a surface of a polymeric material according to claim 13, wherein the concentration of the crosslinking agent is 10 mM to 30 mM.

18. The polymeric material may be thermoplastic polyurethane (TPU), polycarbonate (PC), polydimethylsiloxane (PDMS), polyvinyl chloride (PVC), polyethylene glycol (PEG), or the like. glycol, PEG), silicone, Teflon (PTFE, Teflon, registered trademark), polystyrene, nylon, polyethylene terephthalate (PET), polyacrylate, polypropylene (PP), polyethylene (PE), polyether ether ketone (PEEK), polysulfone (PS), phenolic resin, epoxy, polyglycolide (PGA), polylactide (PLLA), polycaprolactone (PCL), and poly(lactic-co-glycolic The surface treatment method of claim 13, wherein the polymeric material is at least one selected from the group consisting of poly(e-caprolactone-co-lactide), polydioxanone (PDO), polytrimethylene carbonate (PTMC), polyanhydride, polyorthoester, polyphosphazene, hyaluronic acid, alginic acid, chitosan, collagen, gelatin, and polyamino acid.

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