Biocompatible polymer and preparation method thereof

Abstract

The present invention provides a biocompatible polymer that improves mechanical properties such as tensile strength and thermal and chemical stability while maintaining high biocompatibility, and a method for effectively manufacturing the same.

Description

Technology Field

[0001] The present invention relates to a biocompatible polymer and a method for manufacturing the same, wherein a functional group derived from a carbohydrate or a carbohydrate mimic is introduced at the chain end to exhibit high biocompatibility while having excellent mechanical properties such as tensile strength and thermal and chemical stability. Background Technology

[0003] Currently, the most widely used method for research on biocompatibility is the method using self-assembled monolayers (SAMs).

[0005] The most significant feature of these SAMs is the ability to obtain surfaces with desired properties by introducing self-assembling monomers onto a substrate surface; by introducing monomers with various functionalities, surfaces with biocompatibility can be realized. However, despite these characteristics, SAMs suffer from poor chemical stability and the potential for structural defects, and furthermore, they present a critical drawback: they lack the potential for in vivo applications.

[0007] Accordingly, Korean Patent Publication No. 2010-0078325 discloses a new self-assembling polymer in which a purine or a purine mimic is introduced as a brush. However, such brush polymers have low mechanical properties, such as tensile strength, making it difficult to apply them in various environments.

[0009] Accordingly, the present invention provides a biocompatible polymer and a method for manufacturing the same, which improves mechanical properties such as tensile strength and thermal and chemical stability while maintaining biocompatible characteristics. The problem to be solved

[0011] The present invention aims to provide a biocompatible polymer that improves mechanical properties, such as tensile strength, and thermal and chemical stability while maintaining biocompatibility.

[0013] The present invention also aims to provide a method for effectively manufacturing the biocompatible polymer described above.

[0015] The present invention also aims to provide a biocompatible member formed by processing the biocompatible polymer described above. means of solving the problem

[0017] The present invention provides a polymer having a terminal group represented by the following chemical formula 1.

[0018] [Chemical Formula 1]

[0019]

[0020] In the above chemical formula 1,

[0021] R1 and R2 are each independently hydrogen, or an alkyl having 1 to 20 carbon atoms;

[0022] n represents a repeating unit of carbon-carbon bonds containing R1, and is an integer from 1,000 to 10,000;

[0023] L is a linker connecting the polymer main chain and G, and

[0024] G is a functional group derived from carbohydrate or carbohydrate mimic.

[0026] In addition, the present invention provides a method for effectively manufacturing the polymer described above. The method for manufacturing the polymer comprises the step of performing an esterification reaction with a compound represented by the following chemical formula A and a compound represented by the following chemical formula B and comprising a carbohydrate or carbohydrate mimic-derived functional group.

[0027] [Chemical Formula A]

[0028]

[0029] In the above chemical formula A,

[0030] R1 and R2 are each independently hydrogen, or an alkyl having 1 to 20 carbon atoms;

[0031] n represents a repeating unit of carbon-carbon bonds containing R1, and is an integer from 1,000 to 10,000;

[0032] [Chemical Formula B]

[0033]

[0034] In the above chemical formula B,

[0035] L1 is a linker connecting the carboxyl group and G, and

[0036] G is a functional group derived from carbohydrate or carbohydrate mimic;

[0037] [Chemical Formula 1]

[0038]

[0039] In the above chemical formula 1,

[0040] R1 and R2 are each independently hydrogen, or an alkyl having 1 to 20 carbon atoms;

[0041] n represents a repeating unit of carbon-carbon bonds containing R1, and is an integer from 1,000 to 10,000;

[0042] L is a linker connecting the polyethylene main chain and G, and

[0043] G is a functional group derived from carbohydrate or carbohydrate mimic.

[0045] In addition, the present invention provides a biocompatible member formed by processing the above-described polymer.

[0047] A biocompatible polymer according to a specific embodiment of the invention, a method for manufacturing the same, and a biocompatible member formed by processing the same will be described in more detail below.

[0049] Throughout this specification, unless otherwise specifically stated, “include” or “contain” refers to the inclusion of any component (or constituent) without any particular limitation and should not be interpreted as excluding the addition of other components (or constituents).

[0051] Additionally, throughout this specification, “carbohydrate” and “carbohydrate mimic” may be defined as follows. Typically, a carbohydrate is a biomolecule composed of carbon (C), hydrogen (H), and oxygen (O) atoms, usually with a ratio of hydrogen atoms to oxygen atoms of 2:1, and generally C x (H2O) y It can be represented as (where x and y may differ). In particular, carbohydrate is a synonym for saccharide and includes sugars, starch, cellulose, etc., and can be classified, for example, into monosaccharides, disaccharides, oligosaccharides, and polysaccharides. In addition, carbohydrate mimics are compounds or functional groups having a structure similar to the aforementioned carbohydrate. Biocompatibility can be imparted by including such carbohydrates and carbohydrate mimics.

[0053] Furthermore, throughout this specification, "biocompatible" means a substance or entity that performs a desired function when introduced into an organism without inducing a significant inflammatory response, immunogenicity, or cytotoxicity in the native cells, tissues, or organs, or in the cells, tissues, or organs into which the substance or entity is introduced. For example, a biocompatible product is a product that performs a desired function when introduced into an organism without inducing a significant inflammatory response, immunogenicity, or cytotoxicity in the native cells, tissues, or organs.

[0055] In addition, in this specification, means a combination connected to another substituent or repeating unit.

[0057] The inventors have completed the present invention by discovering that when a functional group derived from a carbohydrate or a carbohydrate mimic is introduced to the end of the main chain forming the backbone of a polymer such as polyethylene, unlike conventional methods using self-assembled monolayers (SAM) or brush polymers that introduce functional groups to the side chain, i.e., the end of the brush, rather than the main chain of the polymer, it maintains high biocompatibility while exhibiting excellent mechanical properties such as tensile strength and thermal and chemical stability.

[0059] In particular, the polyethylene-based polymer of the present invention can not only effectively culture microorganisms through functional groups at the ends of the main chain, but can also be used as a medium to attach or detach specific substances such as proteins, DNA, and RNA, or to deliver such substances to living organisms, and can be used as an organic biopolymer exhibiting improved thermal and chemical stability and mechanical properties.

[0061] Specifically, the polymer of the present invention is characterized by having a terminal group represented by the above chemical formula 1.

[0063] Preferably, the polymer of the present invention may be represented by the following chemical formula 1-1 or chemical formula 1-2.

[0064] [Chemical Formula 1-1]

[0065]

[0066] [Chemical Formula 1-2]

[0067]

[0068] In the above chemical formulas 1-1 and 1-2, L, G, R1, R2, and n are as defined in chemical formula 1.

[0070] Meanwhile, in the above formulas 1 and 1-1 and 1-2, R1 and R2 may each be independently hydrogen, or an alkyl having 1 to 16 carbon atoms, an alkyl having 1 to 12 carbon atoms, an alkyl having 1 to 8 carbon atoms, or an alkyl having 1 to 3 carbon atoms. Preferably, R1 and R2 may each be independently hydrogen, or methyl, ethyl, or propyl. More preferably, R1 and R2 may both be hydrogen.

[0072] Additionally, n represents a repeating unit of carbon-carbon bonds containing R1, i.e., a repeating unit composed of two carbons, for example, a repeating unit of ethylene, and is an integer from 1,000 to 10,000. By introducing within the above range, mechanical properties such as tensile strength and properties such as thermal and chemical stability according to the main chain of a polymer such as polyethylene can be improved while maintaining the biocompatibility of the functional group derived from the carbohydrate or carbohydrate mimic. Preferably, n may be an integer from 2,000 to 9,500, an integer from 3,000 to 9,000, or an integer from 4,000 to 8,500. More preferably, n may be from 5,000 to 8,000.

[0074] In addition, L is a linker connecting the polymer main chain and G, and preferably, L may be represented by the following chemical formula 2.

[0075] [Chemical Formula 2]

[0076]

[0077] In the above chemical formula 2,

[0078] R3 is each independently hydrogen, or an alkyl having 1 to 20 carbon atoms;

[0079] m represents a repeating unit of carbon containing R3 and is an integer from 1 to 20.

[0081] In the above formula 2, R3 may each independently be hydrogen, or an alkyl having 1 to 16 carbon atoms, an alkyl having 1 to 12 carbon atoms, an alkyl having 1 to 8 carbon atoms, or an alkyl having 1 to 3 carbon atoms. Preferably, R3 may each independently be hydrogen, or methyl, ethyl, or propyl. More preferably, R3 may all be hydrogen.

[0083] Additionally, m represents a repeating carbon unit containing R3 and is an integer from 1 to 20. By introducing within the above range, mechanical properties such as tensile strength and properties such as thermal and chemical stability along the main chain of a polymer such as polyethylene can be improved while maintaining the biocompatibility of the carbohydrate or carbohydrate mimic-derived functional group. Preferably, m may be an integer from 1 to 16, an integer from 1 to 8, or an integer from 1 to 6. More preferably, m may be 1 to 4.

[0085] Meanwhile, in the above Chemical Formula 1 and Chemical Formulas 1-1 and 1-2, G is a functional group derived from a carbohydrate or a carbohydrate mimic. Preferably, G may be represented by the following Chemical Formula 3 or Chemical Formula 4.

[0086] [Chemical Formula 3]

[0087]

[0088] [Chemical Formula 4]

[0089]

[0090] In the above chemical formulas 3 and 4,

[0091] l represents the repeating unit of the carbohydrate monomer, where 0 < l ≤ 100;

[0092] E1, E2, E3, E4, E5, E6, E7, E8, E9, E 10 , E 11 , E 12 , E 13 and E14 J1 and J2 are selected from the group consisting of C, N, O, P, and S independently of each other;

[0093] G1, G2, G3, G4, G5, G6, G7, G8, G9, G 10 , G 11 , G 12 , G 13 , G 14 , G 15 , G 16 , G 17 , G 18 , G 19 , G 20 , G 21 , G 22 , G 23 , G 24 , G 25 , G 26 and G 27 E1, E2, E3, E4, E5, E6, E7, E8, E9, E 10 , E 11 , E 12 , E 13 and E 14 Selections within the category that do not violate the valence electron laws of the element type selected in, which may not be selected depending on the element type of E, and if selected, -H, -OH, -SH, -S - , -NH2, -NHR4, -N(R4)2, -N + (R4)3, -COOH, -COO - , -N + (R4)RCOO - , -PO3H, -PO3 - , -PO3 - RN + (R4)3, -SO3H, -SO3 - , -N + (R4)3R5SO3 - , -R4OH, -R4O - , -R4SH, -R4S - , -R4NH2, -R4NHR5, -R4N(R4)2, -R4N(R5)3 + , -R4COOH, -R4COO- , -R4N + (R5)3R6COO - , -R4PO3H, -R4PO3 - , -R4PO3 - R5N + (R6)3, and -R4N + (R5)3R6SO3 - Selected from a group consisting of;

[0094] Here, R4, R5, and R6 are hydrogen, or alkyls having 1 to 20 carbon atoms.

[0096] Specifically, the above G is a functional group derived from a monosaccharide form of carbohydrate or carbohydrate mimic of the above chemical formula 2, where E5 is an oxygen atom, and E1, E2, E3, E4, and E6 may be carbon atoms.

[0098] In addition, the above G is a functional group derived from a disaccharide form of carbohydrate or carbohydrate mimic in which l is 0 in the above chemical formula 3, where E5 and E17 are oxygen atoms, and the other E may be a carbon atom.

[0100] Preferably, the polymer of the present invention may be represented by the following formula 1-3 or formula 1-4.

[0101] [Chemical Formula 1-3]

[0102]

[0103] [Chemical Formula 1-4]

[0104]

[0105] In the above chemical formulas 1-3 and 1-4,

[0106] R1, R2, and R3 are each independently hydrogen, or an alkyl having 1 to 20 carbon atoms;

[0107] n represents a repeating unit of carbon-carbon bonds containing R1, each independently, and is an integer from 1,000 to 10,000;

[0108] m represents a repeating unit of carbon containing R3, each independently, and is an integer from 1 to 20.

[0110] Meanwhile, the weight-average molecular weight of the polymer according to the present invention is 20,000 g / mol to 400,000 g / mol. In order to improve excellent mechanical properties and thermal and chemical stability while maintaining biocompatibility, the weight-average molecular weight of the polymer may be 50,000 g / mol to 350,000 g / mol, or 100,000 g / mol to 300,000 g / mol, or 150,000 g / mol to 250,000 g / mol. If the weight-average molecular weight of the polymer is less than 20,000 g / mol, the mechanical properties may deteriorate. For example, the weight-average molecular weight of the polymer can be measured using a gel permeation chromatography (GPC) device and obtained by the polystyrene induction method. More specifically, the method for measuring the weight-average molecular weight will be explained in detail in the experimental examples described below.

[0112] The decomposition temperature (Td) of the polymer according to the present invention may be 300 ℃ or higher, or 300 ℃ to 500 ℃, or 350 ℃ or higher, or 350 ℃ to 495 ℃, or 400 ℃ or higher, or 400 ℃ to 490 ℃, or 420 ℃ or higher, or 420 ℃ to 490 ℃. Here, the Td of the polymer is preferably 300 ℃ or higher in terms of thermal stability. For example, the decomposition temperature (Td) of the polymer can be measured using a thermogravimetric analyzer (TGA). More specifically, the method for measuring the decomposition temperature (Td) will be explained in detail in the experimental examples described below.

[0114] In addition, regarding the excellent thermal stability of the polymer, the glass transition temperature (Tg) may be -50 ℃ to -130 ℃, or -60 ℃ to -120 ℃, or -70 ℃ to -110 ℃, and the melting point (Tm) may be 100 ℃ to 150 ℃, or 110 ℃ to 140 ℃, or 120 ℃ to 135 ℃. For example, the glass transition temperature (Tg) and melting point (Tm) of the polymer may be measured using a differential scanning calorimeter (DSC). More specifically, the method for measuring the glass transition temperature (Tg) and melting point (Tm) of the polymer will be explained in detail in the experimental examples described below.

[0116] In addition, the tensile strength of the polymer according to the present invention, measured by the method based on ASTM (American Society for Testing and Materials) D-412, may be 6 MPa or more, or 6 MPa to 30 MPa, or 6.5 MPa or more, or 6.5 MPa to 20 MPa, or 6.8 MPa or more, or 6.8 MPa to 18 MPa, or 7 MPa or more, or 7 MPa to 15 MPa. More specifically, the method for measuring the tensile strength will be explained in detail in the experimental examples described below.

[0118] In addition, the flexural modulus of the polymer according to the present invention, measured by the method based on ASTM D-790, is 6000 kgf / cm 2 or more than 6000 kgf / cm² 2 Up to 12,000 kgf / cm² 2 , or 6500 kgf / cm² 2 or more than 6500 kgf / cm² 2 Up to 11,000 kgf / cm² 2, or 6800 kgf / cm² 2 or higher or 6800 kgf / cm² 2 Up to 10,000 kgf / cm² 2 , or 7000 kgf / cm² 2 or more than 7000 kgf / cm² 2 Up to 9500 kgf / cm² 2 It may be. More specifically, the method for measuring the above flexural modulus will be explained in detail in the experimental examples described later.

[0120] In addition, the Izod impact strength of the polymer according to the present invention, measured by the method based on ASTM D-256, may be 5 kgf·cm / cm or more, or 5 kgf·cm / cm to 30 kgf·cm / cm, or 5.5 kgf·cm / cm or more, or 5.5 kgf·cm / cm to 25 kgf·cm / cm, or 5.8 kgf·cm / cm or more, or 5.8 kgf·cm / cm to 20 kgf·cm / cm, or 6 kgf·cm / cm or more, or 6 kgf·cm / cm to 15 kgf·cm / cm. More specifically, the method for measuring the Izod impact strength will be explained in detail in the experimental examples described below.

[0122] In addition, the spiral flow length of the polymer according to the present invention, measured by the method based on ASTM D-3123, may be 18 cm or more, or 18 cm to 50 cm, or 19 cm or more, or 18 cm to 45 cm, or 20 cm or more, or 20 cm to 40 cm, or 21 cm or more, or 21 cm to 35 cm. More specifically, the method for measuring the spiral flow length will be explained in detail in the experimental examples described below.

[0124] Meanwhile, the polymer of the present invention has excellent performance as a biocompatible material by introducing a terminal group containing a carbohydrate or carbohydrate mimic-derived functional group, as represented by Formula 1 above, to the end of the polymer main chain, such as polyethylene.

[0126] In the present invention, when the polymer is processed as a biocompatible material, it has the ability to enhance attachment, adsorption, or adhesion to cells, and has the ability to inhibit attachment, adsorption, or adhesion to pathogenic bacteria.

[0128] In the implementation of the present invention, the biocompatible polymer exhibits an enhancing ability for adsorption, attachment, or adhesion to HEp-2 cells, etc., and may exhibit an inhibitory ability for adsorption, attachment, or adhesion to pathogenic bacteria such as P. aeruginosa, S. aureus, S. epidermidis, E. faecalis, or E. coli.

[0130] Meanwhile, according to another embodiment of the invention, the present invention provides a method for effectively producing a polymer having a terminal group comprising a carbohydrate or a carbohydrate mimic-derived functional group at the end of a polymer main chain such as polyethylene, as represented by the above chemical formula 1.

[0132] The method for manufacturing the above polymer includes the step of performing an esterification reaction with a compound represented by the following chemical formula A and a compound represented by the following chemical formula B, which includes a carbohydrate or carbohydrate mimic-derived functional group.

[0133] [Chemical Formula A]

[0134]

[0135] In the above chemical formula A,

[0136] R1 and R2 are each independently hydrogen, or an alkyl having 1 to 20 carbon atoms;

[0137] n represents a repeating unit of carbon-carbon bonds containing R1, and is an integer from 1,000 to 10,000;

[0138] [Chemical Formula B]

[0139]

[0140] In the above chemical formula B,

[0141] L1 is a linker connecting the carboxyl group and G, and

[0142] G is a functional group derived from carbohydrate or carbohydrate mimic;

[0143] [Chemical Formula 1]

[0144]

[0145] In the above chemical formula 1,

[0146] R1 and R2 are each independently hydrogen, or an alkyl having 1 to 20 carbon atoms;

[0147] n represents a repeating unit of carbon-carbon bonds containing R1, and is an integer from 1,000 to 10,000;

[0148] L is a linker connecting the polyethylene main chain and G, and

[0149] G is a functional group derived from carbohydrate or carbohydrate mimic.

[0151] The substituents L, G, R1, R2, and n in Chemical Formula 1 and Chemical Formulas A and B are as described above in the description related to the polymer, and a separate explanation is omitted.

[0153] Meanwhile, in the above chemical formula B, L1 is a linker connecting the carboxyl group and G, and preferably, L1 is represented by the following chemical formula C.

[0154] [Chemical Formula C]

[0155]

[0156] In the above chemical formula C,

[0157] R3 is each independently hydrogen, or an alkyl having 1 to 20 carbon atoms;

[0158] m represents a repeating unit of carbon containing R3 and is an integer from 1 to 20.

[0160] In the above chemical formula C, the substituents R3 and m are as described above in the description related to the polymer, and a separate explanation is omitted.

[0162] In the present invention, a method for preparing a polymer having a terminal group represented by Formula 1 is characterized by using a compound represented by Formula A and a compound represented by Formula B, which includes a functional group derived from a carbohydrate or a carbohydrate mimic, to perform an esterification reaction through a condensation reaction between the terminal OH group of Formula A and the carboxyl group of Formula B. Specific esterification reaction conditions will be described in detail in the examples described below.

[0164] For example, in the method for manufacturing the polymer, based on the number of moles of OH of the compound represented by the formula A, the compound represented by the formula B can be reacted in an amount of 1 mole to 1.5 moles, or 1.05 moles to 1.45 moles, or 1.1 moles to 1.4 moles.

[0166] In addition, the esterification reaction may be carried out in the presence of, for example, N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride, 4-(dimethylamino)pyridine, etc. As an example, the esterification reaction may be carried out under conditions of 60°C to 180°C or 80°C to 150°C at atmospheric pressure.

[0168] For example, the method for manufacturing the polymer may further include a step of polymerizing ethylene in the presence of diethyl zinc prior to the esterification reaction step to produce a compound represented by the chemical formula A. Specific conditions for the ethylene polymerization reaction will be described in detail in the synthesis examples described later.

[0170] In addition, the method for manufacturing the polymer may further include a step prior to the esterification reaction step of reacting a carbohydrate or a carbohydrate mimic compound with an alcohol compound containing a terminal carboxyl group to introduce a functional group containing a terminal carboxyl group to at least some of the hydroxyl groups contained in the carbohydrate or the carbohydrate mimic compound, thereby producing a compound represented by the chemical formula B. Specific reaction conditions for introducing the carboxyl group will be explained in detail in the content of the synthesis examples described later.

[0172] Meanwhile, according to another embodiment of the invention, the present invention introduces a functional group derived from a carbohydrate or a carbohydrate mimic to the end of a polymer main chain, thereby providing a biocompatible material with excellent mechanical properties such as tensile strength and thermal and chemical stability while maintaining biocompatibility.

[0174] Specifically, the present invention provides a biocompatible member formed by processing a polymer having a terminal group represented by the above chemical formula 1.

[0176] In the present invention, the polymer has the ability to attach, adsorb, or enhance adhesion to cells as a biocompatible material, and has the ability to inhibit attachment, adsorption, or adhesion to pathogenic bacteria. Accordingly, the biocompatible polymer according to the present invention can be used as a biocompatible material for manufacturing or coating various types of processed products that are inserted into or administered into the body, such as teeth, artificial joints, implants, etc. For example, the cells may be HEp-2 cells, and the pathogenic bacteria may be P. aeruginosa, S. aureus, S. epidermidis, E. faecalis, or E. coli.

[0178] In one aspect, the present invention provides a sensor or an adsorbent or separator utilizing the selective binding properties to proteins of a polymer having a polymer chain end comprising a carbohydrate or carbohydrate mimic-derived functional group represented by Formula 1, by introducing a carbohydrate or carbohydrate mimic-derived functional group to the end of the polymer main chain.

[0180] The polymer according to the present invention has good binding affinity with proteins and can selectively adsorb proteins, so it can be used as a material for separating or purifying proteins. For example, a coating film made of the polymer according to the present invention can selectively bind to and adsorb gamma-globulin.

[0182] The polymer according to the present invention can be used as a chemical sensor capable of detecting proteins. For example, the polymer according to the present invention can be coated on the surface of a prism, and proteins can be detected through plasmon resonance spectroscopy. In the implementation of the present invention, the detection of the protein or the detection of a specific protein can be achieved by using a surface plasmon resonance spectrometer to incident light on a prism coated with the polymer and measuring the change in reflectance resulting from the binding of the protein. Effects of the invention

[0184] According to the present invention, a biocompatible polymer is provided that improves mechanical properties such as tensile strength and thermal and chemical stability while maintaining high biocompatibility, and a method for effectively manufacturing the same is provided.

[0186] In addition, the present invention provides a biocompatible member formed by processing the biocompatible polymer described above. Brief explanation of the drawing

[0188] Figure 1 is a graph of bacterial adsorption over time (30 minutes, 2 hours) for polymers prepared according to Example 1 and Comparative Examples 1 to 3 of the present invention. Figure 2 is a graph of the adsorption experiment on Fibrinogen protein for polymers prepared according to Example 1 and Comparative Examples 1 to 3. Specific details for implementing the invention

[0189] Hereinafter, embodiments of the present invention will be described in more detail in the following examples. However, the following examples are merely illustrative of embodiments of the present invention, and the content of the present invention is not limited by the following examples.

[0191] <Examples and Comparative Examples>

[0192] Synthesis Example 1

[0193] [Reaction Equation 1]

[0194]

[0195] Polyethylene resin with hydroxyl groups introduced to the ends of the polymer chains was prepared through a reaction as shown in Reaction Scheme 1 above.

[0197] First, a 100 mL glass reactor was prepared by repeatedly applying vacuum and nitrogen purging, and polymerization was carried out under an ethylene atmosphere. 30 mL of toluene, 2.5 mmol of MAO (methylaluminoxane) (Al / Zr = 2500), and 0.6 mmol of a diethyl zinc solution were added sequentially, and 1 μmol of a metallocene catalyst represented by Chemical Formula 5 below was added to initiate polymerization. Here, the metallocene catalyst represented by Chemical Formula 5 below was prepared by the method described in Korean Patent Registration Publication No. 1205747. Subsequently, polymerization was carried out by stirring at 70 °C for 20 minutes, after which the polymerization product was transferred to a beaker, an ethylene solution containing dissolved hydrochloric acid was added, and the mixture was stirred again for 10 minutes. After stirring was completed, the precipitated resin was filtered, washed several times with ethanol, and dried to produce a polyethylene resin with hydroxyl groups introduced at the ends (Mw: 195000 g / mol).

[0198] [Chemical Formula 5]

[0199]

[0201] Synthesis Example 2

[0202] [Reaction Equation 2]

[0203]

[0204] 3-hydroxypropanoic acid-beta-glucopyranoside was prepared through the reaction as shown in Reaction Scheme 2 above.

[0206] (Synthesis of beta-glucose pentaacetate)

[0207] First, beta-glucose pentaacetate was synthesized by combining acetic anhydride with beta-glucose in a pyridine solvent. Since the synthesis was performed using a method well known in the academic community, the detailed synthesis process is omitted.

[0209] (Synthesis of 3-hydroxypropanoic acid-beta-tetraacetylglucopyranoside)

[0210] 5 g (12.8 mmol) of beta-glucose pentaacetate, 1.53 g (17.1 mmol) of 3-hydroxypropanoic acid, and 2.32 g (17.1 mmol) of zinc(II) chloride were added to a 250 mL round-bottom flask, dissolved in 170 mL of toluene, and reacted at 65 °C for 2 hours while stirring. After the reaction time, the reaction mixture was cooled to room temperature, diluted with a sufficient amount of ethyl acetate, and the reaction was terminated using an aqueous solution of saturated sodium bicarbonate. The toluene / ethyl acetate mixture containing the product was separated using a separatory funnel, filtered using Celite, and the filtrate was washed with a sufficient amount of water using a separatory funnel. After the above process was completed, the filtrate was dehydrated using anhydrous magnesium sulfate to remove the solvent, and the product was purified using silica gel chromatography. (Petroleum ether : ethyl acetate = 3 : 2, Rf = 0.6)

[0212] (Synthesis of 3-hydroxypropanoic acid-beta-glucopyranoside)

[0213] In a 100 mL round-bottom flask, dissolve 2.21 g (3.83 mmol) of the above-synthesized 3-hydroxypropanoic acid-beta-tetraacetylglucopyranoside in a dichloromethane (DCM) / methylol (MeOH) mixed solvent (40 mL / 20 mL), then add 0.26 g of sodium methoxide (NaOCH3) and 0 o C to 5 o The reaction was carried out while maintaining the temperature at C for 2 hours with stirring. When the titration time was reached, the reaction was terminated using a small amount of acetic acid, and after removing the solvent, the product was purified using silica gel chromatography.

[0215] Comparative Synthesis Example 1

[0216] [Reaction Equation 3]

[0217]

[0218] Polyepichlorohydrin was prepared through the reaction as shown in Reaction Scheme 3 above.

[0220] First, 40 mL (512 mmol) of epichlorohydrin was placed in a 100 mL round-bottom flask and cooled to 5 °C under a nitrogen atmosphere. A solution of 2.56 mmol of initiator (TCHP, Triphenylcarbenium hexafluorophosphate) dissolved in dichloromethane was added to this mixture, and the mixture was stirred at room temperature for 4 days. The reaction product was dissolved in a small amount of dichloromethane, reprecipitated in methanol for purification, and dried under vacuum at 40 °C for 8 hours to prepare polyepichlorohydrin. Yield: 65%.

[0222] 1 H-NMR (300 MHz, CDCl3): δ(ppm) = 3.89-3.49 (br, 3H, OCH, OCH2,CH2Cl);

[0223] 13 C-NMR (75 MHz, CDCl3): δ(ppm) = 79.70, 70.32, 44.31;

[0224] FT-IR(in film): ν(cm -1 ) = 2960, 2915, 2873, 1427, 1348, 1299, 1263, 1132, 750, 707.

[0226] Comparative Synthesis Example 2

[0227] [Reaction Equation 4]

[0228]

[0229] 11-Mercaptoundecyl-beta-glucopyranoside was prepared through the reaction as shown in Reaction Scheme 4 above.

[0231] (Synthesis of beta-glucose pentaacetate)

[0232] Beta-glucose pentaacetate was synthesized by the reaction of acetic anhydride with beta-glucose in a pyridine solvent. Since the synthesis was performed using a method well known in the academic community, the detailed synthesis process is omitted.

[0234] (Synthesis of 11-bromoundecyl-beta-tetraacetyl glucopyranoside)

[0235] 5 g (12.8 mmol) of beta-glucose pentaacetate, 4.29 g (17.1 mmol) of 11-bromo-1-undecanol, and 2.32 g (17.1 mmol) of zinc(II) chloride were added to a 250 mL round-bottom flask, dissolved in 170 mL of toluene, and reacted at 65 °C for 2 hours while stirring. After the reaction time, the reaction mixture was cooled to room temperature, diluted with a sufficient amount of ethyl acetate, and the reaction was terminated using an aqueous solution of saturated sodium bicarbonate. The toluene / ethyl acetate mixture containing the product was separated using a separatory funnel, filtered using Celite, and the filtrate was thoroughly washed with a sufficient amount of water using a separatory funnel. After the above process was completed, the filtrate was dehydrated with anhydrous magnesium sulfate to remove the solvent, and the product was purified using silica gel chromatography. (Petroleum ether : ethyl acetate = 3 : 2, R f = 0.6)

[0237] (Synthesis of 11-Mercaptoundecyl-beta-tetraacetyl glucopyranoside)

[0238] 2.71 g (4.66 mmol) of the synthesized 11-bromoundecyl-beta-tetraacetylglucopyranoside and 1.6 g (14.0 mmol) of potassium thioacetate were added to a 100 mL round-bottom flask, dissolved in 35 mL of dimethylformamide, and reacted at room temperature for 2 hours while stirring. After the reaction is complete, the reaction mixture was diluted with a hexane / ethyl acetate mixed solvent (1:1), washed with water using a separatory funnel, dehydrated with anhydrous magnesium sulfate to remove the solvent, and then purified by silica gel chromatography. (Hexane : Ethyl acetate = 2 : 1, R f = 0.3)

[0240] (Synthesis of 11-Mercaptoundecyl-beta-glucopyranoside)

[0241] In a 100 mL round-bottom flask, 2.21 g (3.83 mmol) of the 11-mercaptoundecyl-beta-tetraacetylglucopyranoside synthesized above was dissolved in a dichloromethane (DCM) / methanol (MeOH) mixed solvent (40 mL / 20 mL), and then sodium methoxide (NaOCH₄) 3, Add 0.26 g and react for 2 hours while stirring at a temperature of 0–5 ℃. When the titration time is reached, terminate the reaction using a small amount of acetic acid, remove the solvent, and purify the product using silica gel chromatography. (Dichloromethane : Methanol = 9 : 1)

[0243] Example 1

[0244] [Reaction Equation 5]

[0245]

[0246] A polymer (PE-Glucose) in which glucose-derived functional groups were introduced to the ends of the polyethylene main chain was prepared through a reaction as shown in Reaction Scheme 5 above.

[0248] First, 800 mg (2.73 OH mmol) of the compound obtained in Synthesis Example 1, 755 mg (3.94 mmol) of N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride, 240 mg (1.97 mmol) of 4-(dimethylamino)pyridine, and 680 mg (3.28 mmol) of the compound obtained in Synthesis Example 2 were dissolved in 20 mL of 1,2,4-trichlorobenzene and stirred while heating at 120 °C for 24 hours. After the reaction was completed, the mixture was cooled to room temperature and precipitated in 200 mL of methanol. The precipitation solvent was removed, and the remaining solid material was dried under vacuum at 40 °C for 8 hours to obtain a polymer (PE-Glucose) in which glucose-derived functional groups were introduced to the ends of the polyethylene main chain.

[0250] Comparative Example 1

[0251] Polyethylene obtained in Synthesis Example 1 above, in which an OH group is introduced at the end of the polymer main chain, was prepared as Comparative Example 1.

[0253] Comparative Example 2

[0254] A solution of 894 mg (9.66 mmol) of the polyepichlorohydrin compound obtained in Comparative Synthesis Example 1 dissolved in 6 mL of dimethylformaldehyde was added to a solution of 585 mg (2.42 mmol) of sodium 11-beta-glucopyranosylundecyl thioleate and 1630 mg (7.25 mmol) of sodium dodecyl thioleate obtained in Comparative Synthesis Example 2 dissolved in 30 mL of dimethylformaldehyde. This mixture was stirred at room temperature for one day, then extracted with chloroform, washed with water to remove the solvent, and precipitated in hexane. Subsequently, the polymer was purified using a dialysis membrane and dried under vacuum at 40 °C for 8 hours to obtain the target compound (PECH_Glu25).

[0256] 1 H-NMR (300 MHz, DMSO-d6): δ(ppm) = 5.10-3.20 (glucose), 3.70-3.59 (br, OCH, OCH2), 2.75-2.52 (m, CH2SCH2), 1.57-1.13 (m, CH2), 0.88 (t, CH3).

[0258] Comparative Example 3

[0259] A solution of 894 mg (9.66 mmol) of the polyepichlorohydrin compound obtained in Comparative Synthesis Example 1, dissolved in 6 mL of dimethylacetamide, was added to a solution of 1876 mg (4.83 mmol) of sodium 11-glucopyranosyl-beta-undecyl thioleate and 1083 mg (4.83 mmol) of dodecyl thioleate obtained in Comparative Synthesis Example 2, dissolved in 30 mL of dimethylformaldehyde. This mixture was stirred at room temperature for one day, then extracted with chloroform, washed with water to remove the solvent, and precipitated in hexane. Subsequently, the polymer was purified using a dialysis membrane and dried under vacuum at 40 °C for 8 hours to obtain the target compound (PECH_Glu50).

[0261] 1 H-NMR (300 MHz, DMSO-d6): δ(ppm)= 5.10-3.20 (glucose), 3.70-3.59 (br, OCH, OCH2), 2.75-2.52 (m, CH2SCH2), 1.57-1.13 (m, CH2), 0.88 (t, CH3).

[0263] <Test Example 1>

[0264] The properties of the polymers prepared in the above examples and comparative examples were evaluated as follows.

[0266] 1) Weight-average molecular weight (Mw):

[0267] A Waters PL-GPC220 instrument was used for gel permeation chromatography (GPC), and a Polymer Laboratories PLgel MIX-B 300 mm long column was used. The measurement temperature was 160 °C, 1,2,4-trichlorobenzene was used as the solvent, and the flow rate was set to 1 mL / min. Polyethylene samples according to the examples and comparative examples were each pretreated by dissolving them in trichlorobenzene containing 0.0125% BHT at 160 °C for 10 hours using the GPC analyzer (PL-GP220), prepared to a concentration of 10 mg / 10 mL, and supplied in a volume of 200 μL. The values ​​of Mw and Mn were derived using a calibration curve formed using a polystyrene standard specimen. Nine types of polystyrene standard specimens with weight-average molecular weights of 2000 g / mol, 10000 g / mol, 30000 g / mol, 70000 g / mol, 200000 g / mol, 700000 g / mol, 2000000 g / mol, 4000000 g / mol, and 10000000 g / mol were used.

[0269] 2) Degradation temperature (Td, ℃):

[0270] The thermogravimetric analysis (TGA) device used was a thermogravimetric analyzer (TGA, TA550) from TA Instruments (New Castle, Delaware, USA), and the degradation temperature was measured while increasing the temperature from 25 ℃ to 600 ℃ at a rate of 30 ℃ / min.

[0272] 3) Glass transition temperature (Tg, °C) and melting temperature (Tm, °C):

[0273] Using a Differential Scanning Calorimeter (DSC, TA2000) from TA Instruments (New Castle, Delaware, USA), the temperature was increased from -100 ℃ to 200 ℃ at a rate of 10 ℃ / min and maintained at this temperature for 1 minute, then lowered from 200 ℃ to -100 ℃ at a rate of 10 ℃ / min and maintained for 1 minute. The glass transition temperature and melting temperature were measured while increasing the temperature again from -100 ℃ to 200 ℃ at a rate of 10 ℃ / min (2nd cycle).

[0275] 4) Tensile strength (MPa):

[0276] Tensile strength (MPa) was measured under conditions of 500 mm / min using the method according to ASTM D-412.

[0278] 5) Flexural modulus (kgf / cm²) 2 ):

[0279] Flexural modulus (kgf / cm2) was measured according to the ASTM D-790 method.

[0281] 6) Izod impact strength (Izod impact strength test, kg.cm / cm):

[0282] The Izod impact strength (Izod impact strength test, kg.cm / cm) was measured according to the ASTM D-256 method.

[0284] 7) Spiral flow length (cm):

[0285] The spiral flow length was measured according to the ASTM D-3123 method.

[0287] The polymer properties of the examples and comparative examples measured by the above-described method are summarized in Table 1 below.

[0288] Example 1 Comparative Example 1 Comparative Example 2 Comparative Example 3 polymer polyethylene polyethylene Polyepichlorohydrin Polyepichlorohydrin Crystallinity Semi-crystalline Semi-crystalline Amorphous Amorphous Type Solid phase (powder) Solid phase (powder) solid phase liquid Polymerization method metallocene polymerization metallocene polymerization Cationic polymerization Cationic polymerization Carbohydrate-derived functional group binding site The end of the chain No functional group Each brush tip Each brush tip Td (°C) 450 450 210 230 Tg (°C) -100 -100 70 28 Tm (℃) 130 130 Unmeasurable Unmeasurable Molecular weight (Mw, x1000 g / mol) 200 200 33 42 Degree of polymerization (n of Formula 1) 7000 7000 100 100 Tensile strength (MPa) 7 7 3 Unmeasurable Flexural modulus(kgf / cm 2 ) 7000 7000 2300 Unmeasurable Izod impact strength (kgf-cm / cm)*2 6 6 2 Unmeasurable Spiral flow (cm) * 5 21 21 15 Unmeasurable

[0289] Referring to Table 1 above, it was confirmed that the polyethylene of Example 1 according to the present invention has a carbohydrate functional group at the end of the polymer chain, and thus possesses excellent biocompatibility as described in Test Example 2 below, while also having excellent mechanical properties, processability (flowability), and thermal properties compared to the polymers of Comparative Examples 2 and 3.

[0291] <Test Example 2>

[0292] Biocompatibility tests were performed using the polymers prepared in the above examples and comparative examples in the following manner.

[0294] 1) Experiment on bacterial adsorption over time (30 minutes, 2 hours)

[0295] The polymers prepared in Example 1 or Comparative Examples 1 to 3 were each dissolved in TCB (trichlorobenzene) and DMF (dimethylformamide) solvents, respectively. The solutions filtered through a 0.2 micrometer syringe filter were then dip-coated onto a polyethylene terephthalate substrate and dried in a vacuum oven at 60°C for one day. Adsorption and sterilization experiments were conducted on the prepared films using four types of pathogenic bacteria. The experimental method involved 10 for each polymer 7 Placed into a medium containing four pathogenic bacteria quantified to a concentration of CFU / mL, adsorbed for 30 minutes and 2 hours, then removed and desorbed using an ultrasonic device, and then inoculated the desorbed bacteria onto a semi-solid medium 37 o The amount adsorbed was calculated after growing it in an incubator for one day.

[0297] The experiment was repeated three times, and the averaged values ​​are shown in Table 1 below. The adsorption graph of bacteria over time (30 min, 2 hours) for the polymers of the examples and comparative examples is shown in Figure 1.

[0299] 2) Adsorption experiment for fibrinogen protein

[0300] The polymers prepared in Example 1 or Comparative Examples 1 to 3 were dissolved in TCB and DMF solvents, respectively, and the solutions filtered through a 0.2 micrometer syringe filter were spin-coated onto a gold-coated prism and dried in a vacuum oven at 60°C for one day. Adsorption experiments were performed on the polymer-coated prisms for three different proteins using a surface plasmon resonance spectrometer. The concentration of each protein was adjusted to 1 mg / mL, and the change in reflectance due to adsorption is shown in Figure 2.

[0302] The results of reflectance measurements according to Fibrinogen protein adsorption for the polymers of the examples and comparative examples measured in this way are shown in Table 2 below.

[0303] division hour Example 1 Comparative Example 1 Comparative Example 2 Comparative Example 3 P. aeruginosa adsorption capacity (mm 2 ) 0.5h 1933 1273 1415 1910 2h 5386 11561 5759 5551 E. faecalis adsorption capacity (mm 2 ) 0.5h 3.8 153 2.6 2.1 2h 5.9 175 5.4 7.6 S. aureus adsorption capacity (mm 2 ) 0.5h 471 2694 642 371 2h 1509 2494 1660 632 E. coli adsorption capacity (mm 2 ) 0.5h 13.2 10.4 5.2 9.2 2h 152 69 122 107 Fibrinogen protein adsorption Reflectio(%, 600s) 0 1.21 0.06 0

[0304] Referring to Table 2 above, it was confirmed that the polyethylene of Example 1 according to the present invention, having a carbohydrate functional group at the end of the polymer chain, maintains excellent mechanical properties, processability (flowability), and thermal properties as described in Test Example 1 above, while having selective adsorption capacity in which the adsorption of pathogenic bacteria P. aeruginosa, E. faecalis, and S. aureus is inhibited and the adsorption of E. coli is increased, and the adsorption of Fibrinogen protein is inhibited compared to the polymer of Comparison 1, and has biocompatible properties.

[0306] Accordingly, it can be seen that the polyethylene of Example 1 according to the present invention has a carbohydrate functional group at the end of the polymer chain, thereby maintaining high biocompatibility compared to the polymer of Comparative Example 1, while improving mechanical properties such as tensile strength, processability (flowability), and thermal and chemical stability compared to the polymers of Comparative Examples 2 and 3.

Claims

Claim 1 Polymer having a terminal group represented by the following chemical formula 1: [Chemical Formula 1] In the above Chemical Formula 1, R1 and R2 are each independently hydrogen or an alkyl group having 1 to 20 carbon atoms; n represents a repeating unit of carbon-carbon bonds including R1, and is an integer from 1,000 to 10,000; L is a linker connecting the polymer main chain and G, represented by the following Chemical Formula 2, where G is a functional group derived from a carbohydrate or a carbohydrate mimic, [Chemical Formula 2] In the above chemical formula 2, R3 is independently hydrogen or an alkyl having 1 to 20 carbon atoms; m represents a repeating carbon unit containing R3 and is an integer from 1 to 20. Claim 2 In claim 1, a polymer represented by the following chemical formula 1-1 or chemical formula 1-2: [Chemical formula 1-1] [Chemical Formula 1-2] In the above chemical formulas 1-1 and 1-2, L, G, R1, R2, and n are as defined in claim 1. Claim 3 A polymer in which, in paragraph 1 or 2, R1 and R2 are both hydrogen. Claim 4 delete Claim 5 In paragraph 1, R3 is a polymer in which all of it is hydrogen. Claim 6 The polymer according to claim 1 or 2, wherein G is represented by the following chemical formula 3 or chemical formula 4: [Chemical Formula 3] [Chemical Formula 4] In the above chemical formulas 3 and 4, l represents a repeating unit of the carbohydrate monomer, where 0 < l ≤ 100; E1, E2, E3, E4, E5, E6, E7, E8, E9, E 10 , E 11 , E 12 , E 13 and E 14 J1 and J2 are selected from the group consisting of C, N, O, P, and S independently of each other; G1, G2, G3, G4, G5, G6, G7, G8, G9, G 10 , G 11 , G 12 , G 13 , G 14 , G 15 , G 16 , G 17 , G 18 , G 19 , G 20 , G 21 , G 22 , G 23 , G 24 , G 25 , G 26 and G 27 E1, E2, E3, E4, E5, E6, E7, E8, E9, E 10 , E 11 , E 12 , E 13 and E 14 Selections within the category that do not violate the valence electron laws of the element type selected in, which may not be selected depending on the element type of E, and if selected, -H, -OH, -SH, -S - , -NH2, -NHR4, -N(R4)2, -N + (R4)3, -COOH, -COO - , -N + (R4)RCOO - , -PO3H, -PO3 - , -PO3 - RN + (R4)3, -SO3H, -SO3 - , -N + (R4)3R5SO3 - , -R4OH, -R4O - , -R4SH, -R4S - , -R4NH2, -R4NHR5, -R4N(R4)2, -R4N(R5)3 + , -R4COOH, -R4COO - , -R4N + (R5)3R6COO - , -R4PO3H, -R4PO3 - , -R4PO3 - R5N + (R6)3, and -R4N + (R5)3R6SO3 - Selected from the group consisting of; where R4, R5, and R6 are hydrogen, or alkyl having 1 to 20 carbon atoms. Claim 7 In claim 6, G is a functional group derived from a monosaccharide form of the above chemical formula 3, or a carbohydrate mimic, wherein E5 is an oxygen atom and E1, E2, E3, E4, and E6 are carbon atoms, a polymer. Claim 8 In claim 6, G is a functional group derived from a disaccharide form of carbohydrate or carbohydrate mimic in the above chemical formula 4 in which l is 0, wherein E5 and E17 are oxygen atoms and the other E is a carbon atom, a polymer. Claim 9 In claim 1, the polymer represented by the following chemical formula 1-3 or chemical formula 1-4: [Chemical formula 1-3] [Chemical Formula 1-4] In the above chemical formulas 1-3 and 1-4, R1, R2, and R3 are each independently hydrogen or an alkyl having 1 to 20 carbon atoms; n is each independently a repeating unit of carbon-carbon bonds containing R1, and is an integer from 1000 to 10000; and m is each independently a repeating unit of carbon containing R3, and is an integer from 1 to 20. Claim 10 A polymer according to claim 1, wherein the weight-average molecular weight of the polymer is 20,000 g / mol to 400,000 g / mol. Claim 11 A polymer according to claim 1, wherein the decomposition temperature (Td) of the polymer is 300 ℃ or higher. Claim 12 A polymer according to claim 1, wherein the glass transition temperature (Tg) of the polymer is -50 ℃ to -130 ℃ and the melting point (Tm) is 100 ℃ to 150 ℃. Claim 13 A polymer having an enhancing ability for attachment, adsorption, or adhesion to a cell, in claim 1. Claim 14 In paragraph 13, the above cells are polymers, which are HEp-2 cells. Claim 15 A polymer having the ability to inhibit attachment, adsorption, or adhesion to pathogenic bacteria in claim 1. Claim 16 In paragraph 15, the above pathogenic bacteria is a polymer, P. aeruginosa, S. aureus, S. epidermidis, E. faecalis, or E. coli. Claim 17 A method for preparing a polymer having a terminal group represented by the following chemical formula 1, comprising the step of performing an esterification reaction between a compound represented by the following chemical formula A and a compound represented by the following chemical formula B and comprising a functional group derived from a carbohydrate or a carbohydrate mimic: [Chemical Formula A] In the above formula A, R1 and R2 are each independently hydrogen or an alkyl having 1 to 20 carbon atoms; n represents a repeating unit of carbon-carbon bonds including R1, and is an integer from 1000 to 10000; [Formula B] In the above chemical formula B, L1 is a linker connecting the carboxyl group and G, and G is a functional group derived from a carbohydrate or a carbohydrate mimic; [Chemical Formula 1] In the above chemical formula 1, R1 and R2 are each independently hydrogen or an alkyl group having 1 to 20 carbon atoms; n represents a repeating unit of carbon-carbon bonds including R1, and is an integer from 1000 to 10000; L is a linker connecting the polyethylene main chain and G, and G is a functional group derived from carbohydrate or carbohydrate mimic. Claim 18 In claim 17, a method for manufacturing a polymer in which L1 is represented by the following chemical formula C: [Chemical Formula C] In the above chemical formula C, R3 is independently hydrogen or an alkyl having 1 to 20 carbon atoms; m represents a repeating carbon unit containing R3 and is an integer from 1 to 20. Claim 19 A biocompatible member formed by processing the polymer of claim 1.

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