Nucleic acid molecule delivery carriers based on polymers having ionizing moieties

Abstract

The present invention relates to a nucleic acid molecule (e.g., mRNA) delivery carrier based on a polymer having an ionized moiety. Specifically, the invention provides a novel polymer which can deliver all negatively charged genetic materials to a target site according to the length of monomers and polymers. The polymer according to the present invention can be effectively used in a gene therapeutic agent, a vaccine or the like containing a genetic material for therapeutic or prophylactic purposes, such as mRNA.

Description

Technical Field

[0001] The present invention relates to a nucleic acid molecule delivery carrier based on a polymer having an ionizable moiety, and more particularly, to a polymer based on poly(β - amino ester) or poly(β - amino acrylate). Further, the polymer of the present invention is synthesized into a triblock copolymer by binding PEG at both ends, thereby providing high mRNA delivery efficiency through pH sensitivity. Background Art

[0002] mRNA is a substance carrying genetic information and is used to produce proteins in the human body. Through mRNA delivery, it is possible to not only induce the production of proteins originally present in the human body but also induce the production of proteins not present in the body. After the outbreak of the COVID - 19 novel coronavirus, with the application of mRNA vaccines that activate the immune response through mRNA delivery, the development of mRNA delivery carriers is being actively carried out. Although several mRNA delivery carriers based on lipid nanoparticles have been developed, there are problems caused by rapid diffusion to other organs other than the target site (off - target effect) and high immunogenicity, which may cause various side effects such as myocarditis and pericarditis. Also, since the vaccine is administered at most 2 - 4 times, the possibility of these side effects increases. Therefore, there is a need to develop an mRNA delivery carrier with high mRNA expression efficiency, low off - target effect, relatively low immunogenicity, and few side effects.

[0003] In order to improve the disadvantages of the mRNA delivery carrier, during the research on mRNA delivery using polymers, the present researchers found a novel polymer with pH sensitivity and high in - vivo mRNA delivery efficiency, thus completing the present invention. Summary of the Invention

[0004] Technical Problem

[0005] An object of the present invention is to provide a nucleic acid molecule delivery carrier based on a polymer having pH sensitivity, so as to achieve high nucleic acid molecule delivery efficiency and low side effects.

[0006] One aspect of the object of the present invention aims to provide a polymer - based mRNA delivery carrier with a relatively long expression duration to overcome the disadvantage that the expression of mRNA is usually short.

[0007] An object of the present invention is to provide a novel polymer to provide a nucleic acid molecule delivery carrier based on a polymer having pH sensitivity.

[0008] Technical Solution

[0009] To achieve the above object, the present invention provides a polymer suitable for intracellular nucleic acid delivery, which comprises repeating units as shown in Chemical Formula 1 below.

[0010] Chemical Formula 1:

[0011]

[0012] In the formula, R1 is a bond or a C1-6 alkylene group,

[0013] R2 and R3 are each independently (i) hydrogen, (ii) a C1-6 alkyl group that can be substituted by an alkylamine or a hydroxyl group, (iii) a 5- or 6-membered carbocyclic or heterocyclic ring, or (iv) a C1-6 alkyl group substituted by a 5- or 6-membered carbocyclic or heterocyclic ring,

[0014] R2 and R3 can be connected together to form a C1-6 alkylene group,

[0015] The 5- or 6-membered carbocyclic or heterocyclic ring can be substituted by a C1-3 alkyl group or a C1-3 alkoxycarbonyl group,

[0016] X is a nitrogen atom or a bond. When X is a bond, R3 does not exist,

[0017] R4 is a straight-chain or branched C1-15 alkylene group, and 1 to 5 carbon atoms in the alkylene group can be substituted by oxygen or sulfur,

[0018] can represent a single bond or a double bond.

[0019] The repeating units can be n (an integer between 1 and 500). In this case, Chemical Formula 1 can be as follows.

[0020]

[0021] (The definitions are the same as those in Chemical Formula 1)

[0022] The present invention provides a polymer having repeating units as shown in Chemical Formula 2 below.

[0023] Chemical Formula 2:

[0024]

[0025] In the formula,

[0026] R5 is a C1-6 alkylene group,

[0027] R6 is a straight-chain or branched C1-15 alkylene group, and 1 to 5 carbon atoms in the alkylene group can be substituted by oxygen or sulfur,

[0028] It can represent a single bond or a double bond.

[0029] The repeating unit can be n (an integer between 1 and 500), and in this case, Chemical Formula 2 can be shown as follows.

[0030]

[0031] (The definition is the same as that in Chemical Formula 2)

[0032] In one embodiment, the polymer can be a polymer formed by the reaction between the repeating unit shown in Chemical Formula 1 and any one of the monomers shown in Chemical Formulas 3 to 13 below and any one of the monomers shown in Chemical Formulas 14 to 23 below.

[0033] and any one of the monomers shown in Chemical Formulas 14 to 23 below.

[0034]

[0035]

[0036] In one embodiment, the polymer can be a polymer formed by the reaction between the repeating unit shown in Chemical Formula 2 and the monomer shown in Chemical Formula 24 below and any one of the monomers shown in Chemical Formulas 14 to 23 below.

[0037]

[0038] The present invention provides a polymer comprising a repeating unit selected from the group consisting of the repeating units in the following table.

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[0213] (In the formula, n is an integer between 1 and 500)

[0214] In one embodiment, the polymer may further comprise a branched monomer represented by Chemical Formula 25 below.

[0215] Chemical Formula 25:

[0216]

[0217] When the polymer of the present invention contains the structure represented by Chemical Formula 25 as described above, the polymer may contain the structure represented by Chemical Formula 26 below.

[0218] Chemical Formula 26:

[0219]

[0220] R1 is a bond or a C1-6 alkylene group,

[0221] R2 and R3 are each independently (i) hydrogen, (ii) a C1-6 alkyl group that can be substituted by an alkylamine or a hydroxyl group, (iii) a 5- or 6-membered carbocyclic or heterocyclic ring, or (iv) a C1-6 alkyl group substituted by a 5- or 6-membered carbocyclic or heterocyclic ring,

[0222] R2 and R3 can be connected together to form a C1-6 alkylene group,

[0223] The 5- or 6-membered carbocyclic or heterocyclic ring can be substituted by a C1-3 alkyl group or a C1-3 alkoxycarbonyl group,

[0224] X is a nitrogen atom or a bond. When X is a bond, R3 does not exist,

[0225] R4 is a linear or branched C1-15 alkylene group, and 1 to 5 carbon atoms in the alkylene group can be substituted by oxygen or sulfur.

[0226] It can represent a single bond or a double bond.

[0227] The repeating unit can be n (an integer between 1 and 500). In this case, Chemical Formula 26 can be shown as follows.

[0228]

[0229] (The definition is the same as that in Chemical Formula 26)

[0230] When the polymer of the present invention contains the structure shown in Chemical Formula 25, the polymer can contain the structure shown in Chemical Formula 27 below.

[0231] Chemical Formula 27:

[0232]

[0233] In the formula,

[0234] R5 is a C1-6 alkylene group,

[0235] R6 is a linear or branched C1-15 alkylene group, and 1 to 5 carbon atoms in the alkylene group can be substituted by oxygen or sulfur.

[0236] It can represent a single bond or a double bond.

[0237] The repeating unit can be n (an integer between 1 and 500). In this case, Chemical Formula 27 can be shown as follows.

[0238]

[0239] (The definition is the same as that in Chemical Formula 27)

[0240] In one embodiment, one end or both ends of the polymer can be connected to a PEG-containing residue having the structure shown in Chemical Formula 28 below.

[0241] Chemical Formula 28:

[0242]

[0243] In the formula, represents a double bond or a triple bond,

[0244] n can be an integer in the range of 1 to 500.

[0245] The present invention provides a polymer nanoparticle formed by a complex of the polymer and a nucleic acid molecule. Preferably, the polymer nanoparticle of the present invention does not contain a lipid nanoparticle (LNP).

[0246] The nucleic acid molecule that can be included in the polymer nanoparticle of the present invention can be RNA. Preferably, the RNA is mRNA.

[0247] The nucleic acid molecule that can be included in the polymer nanoparticle of the present invention can be DNA.

[0248] The nucleic acid molecule in the polymer nanoparticle of the present invention can separate the nucleic acid molecule in a pH-dependent manner and deliver it into cells in the body.

[0249] When the nucleic acid molecule in the polymer nanoparticle of the present invention is delivered into the body, the expression of the nucleic acid molecule can be maintained for a longer time compared to when the same nucleic acid molecule is delivered into the body in the form of a non-polymeric lipid nanoparticle.

[0250] The present invention provides a method for delivering a nucleic acid molecule into a cell, the method using the polymer nanoparticle. Preferably, the nucleic acid molecule delivery method of the present invention does not use a lipid nanoparticle (LNP).

[0251] The polymer nanoparticle of the present invention can be delivered by methods such as parenteral, intramuscular, subcutaneous, or intravenous administration.

[0252] The present invention provides a pharmaceutical composition comprising the polymer nanoparticle. Preferably, the pharmaceutical composition of the present invention does not contain a lipid nanoparticle (LNP).

[0253] The pharmaceutical composition of the present invention comprising the polymer nanoparticle can be a gene therapy agent.

[0254] The pharmaceutical composition of the present invention comprising the polymer nanoparticle can be a vaccine.

[0255] Effects of the Invention

[0256] The nucleic acid molecule delivery carrier based on a pH-sensitive polymer of the present invention has high nucleic acid molecule delivery efficiency, and thus can be used as an excellent delivery carrier. In particular, the nucleic acid molecule delivery carrier of the present invention can be used as a therapeutic gene delivery carrier, an mRNA vaccine.

[0257] Moreover, the nucleic acid molecule can be delivered to a target site according to the length of the monomer and the polymer, and the nucleic acid molecule can be released by an additional stimulus-responsive linker in response to a specific stimulus.

[0258] Moreover, the nucleic acid molecule delivery vector of the present invention can be decomposed after releasing the nucleic acid molecule in the cell, so it has low side effects. BRIEF DESCRIPTION OF THE DRAWINGS

[0259] Figure 1 It is a schematic diagram for synthesizing the polymer delivery vector of the present invention and a schematic diagram of a polymer nanoparticle (PNP) comprising the polymer delivery vector and mRNA.

[0260] Figures 2a to 2e It is a chart showing the 1 1H-NMR results of polymers 1A to 1E.

[0261] Figures 3a to 3e It is a chart showing the 1 1H-NMR results of polymers 2A to 2E.

[0262] Figures 4a to 4e It is a chart showing the 1 1H-NMR results of polymers 3A to 3E.

[0263] Figures 5a to 5e It is a chart showing the 1 1H-NMR results of polymers 4A to 4E.

[0264] Figures 6a to 6e It is a chart showing the 1 1H-NMR results of polymers 5A to 5E.

[0265] Figures 7a to 7e It is a chart showing the 1 1H-NMR results of polymers 6A to 6E.

[0266] Figures 8a to 8e It is a chart showing the 1 1H-NMR results of polymers 7A to 7E.

[0267] Figures 9a to 9e It is a chart showing the 1 1H-NMR results of polymers 8A to 8E.

[0268] Figures 10a to 10e It is a chart showing the 1 1H-NMR results of polymers 9A to 9E.

[0269] Figures 11a to 11e It is a chart showing the 1 1H-NMR results of polymers 10A to 10E.

[0270] Figures 12a to 12e It is a chart showing the 1 1H-NMR results of polymers 11A to 11E.

[0271] Figure 13a and Figure 13b Graphs showing the 1 1H-NMR results of polymers PEG-1A and PEG-1B.

[0272] Figure 14a and Figure 14b Graphs showing the 1 1H-NMR results of polymers PEG-2A and PEG-2B.

[0273] Figure 15a and Figure 15b Graphs showing the 1 1H-NMR results of polymers PEG-3A and PEG-3B.

[0274] Figure 16a and Figure 16b Graphs showing the 1 1H-NMR results of polymers PEG-4A and PEG-4B.

[0275] Figures 17a to 17c Images showing the electrophoresis results of the polymer nanoparticles (PNPs) of the present invention.

[0276] Figure 18 Graphs showing the Zeta potential of the polymer nanoparticles (PNPs) of the present invention.

[0277] Figure 19 Images showing the in vivo delivery of mRNA by the polymer nanoparticles (PNPs) of the present invention.

[0278] Figure 20 Graphs showing the expression duration of the mRNA delivered by the polymer nanoparticles (PNPs) of the present invention. Detailed Description

[0279] The preparation examples and examples of the present invention will be described in detail so that those of ordinary skill in the art to which the present invention pertains can easily implement it. However, the present invention can be implemented in various forms and is not limited to the preparation examples and examples described herein.

[0280] Throughout this specification, unless otherwise specifically stated to the contrary, when a part "includes" a certain structural element, it means that other structural elements can also be included, rather than excluding other structural elements.

[0281] Throughout this specification, the meanings of "Polymer", "macromolecule", and "polymer" are the same and can be used interchangeably with each other.

[0282] In this specification, the term "repeating unit" used to describe a "polymer" refers to a structure that repeats the same structure two or more times over the entire length of the polymer, and the polymer does not necessarily consist only of the repeating unit. For example, in addition to a given repeating unit, the polymer may also contain a branched structure and / or a capping agent, etc.

[0283] As used in this specification, the term "substituted", such as "substituted alkyl", means that one or more hydrogen atoms of the alkyl are each independently replaced by a non-hydrogen substituent. The substituents may include any of the substituents described in this specification, such as halogen, hydroxy, alkyl, hydroxyalkyl, haloalkyl, cyanoalkyl, alkoxyalkyl, carbonyl (e.g., carboxy, alkoxycarbonyl, formyl or acyl), thiocarbonyl (e.g., thioester, thioacetate or thiocarboxylate), alkoxy, phosphoryl, phosphate, phosphonate, phosphonite, amino, amido, amidine, imine, cyano, nitro, azide, mercapto, alkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, heterocyclic group, aralkyl, aryl or heteroaryl, but are not limited thereto. Depending on the circumstances, the residue substituted on the hydrocarbon chain itself may also be substituted.

[0284] In the present invention, "alkyl" is a hydrocarbon having substituted or unsubstituted primary, secondary, tertiary, and / or quaternary carbon atoms, and includes saturated aliphatic groups which may be straight-chain, branched-chain, cyclic, or a combination thereof. For example, the alkyl may have 1 to 20 carbon atoms (i.e., C1-C20 alkyl), 1 to 10 carbon atoms (i.e., C1-C10 alkyl), or 1 to 6 carbon atoms (i.e., C1-C6 alkyl). Examples of suitable alkyls may include methyl (Me, -CH3), ethyl (Et, -CH2CH3), 1-propyl (n-Pr, n-propyl, -CH2CH2CH3), 2-propyl (i-Pr, i-propyl, -CH(CH3)2), 1-butyl (n-Bu, n-butyl, -CH2CH2CH2CH3), 2-methyl-1-propyl (i-Bu, i-butyl, -CH2CH(CH3)2), 2-butyl (s-Bu, s-butyl, -CH(CH3)CH2CH3), 2-methyl-2-propyl (t-Bu, t-butyl, -C(CH3)3), 1-pentyl (n-pentyl, -CH2CH2CH2CH2CH3), 2-pentyl (-CH(CH3)CH2CH2CH3), 3-pentyl (-CH(CH2CH3)2), 2-methyl-2-butyl (-C(CH3)2CH2CH3), 3-methyl-2-butyl (-CH(CH3)CH(CH3)2), 3-methyl-1-butyl (-CH2CH2CH(CH3)2), 2-methyl-1-butyl (-CH2CH(CH3)CH2CH3), 1-hexyl (-CH2CH2CH2CH2CH2CH3), 2-hexyl (-CH(CH3)CH2CH2CH2CH3), 3-hexyl (-CH(CH2CH3)(CH2CH2CH3)), 2-methyl-2-pentyl (-C(CH3)2CH2CH2CH3), 3-methyl-2-pentyl (-CH(CH3)CH(CH3)CH2CH3), 4-methyl-2-pentyl (-CH(CH3)CH2CH(CH3)2), 3-methyl-3-pentyl (-C(CH3)(CH2CH3)2), 2-methyl-3-pentyl (-CH(CH2CH3)CH(CH3)2), 2,3-dimethyl-2-butyl (-C(CH3)2CH(CH3)2), 3,3-dimethyl-2-butyl (-CH(CH3)C(CH3)3), and octyl (-(CH2)7CH3), but are not limited thereto.

[0285] In addition, the term "alkyl" used throughout the specification, examples, and claims is intended to include both unsubstituted and substituted alkyls, where the latter refers to an alkyl residue having a substituent that replaces the hydrogen on more than one carbon atom of the hydrocarbon backbone, including haloalkyls such as trifluoromethyl.

[0286] The term "alkylene" as used in this specification may be branched, straight-chain, cyclic, or a combination thereof, and refers to a divalent saturated hydrocarbon group induced by removing two hydrogen atoms from the same carbon atom or two different carbon atoms of the parent alkane. For example, the alkylene may have 1 to 20 carbon atoms, 1 to 10 carbon atoms, or 1 to 6 carbon atoms. Examples of suitable alkylene include methylene (-CH2-) and 1,2-ethylene (-CH2-CH2-), etc., but are not limited thereto.

[0287] The term "heterocycle" as used in this specification refers to a substituted or unsubstituted, monovalent or divalent, saturated or partially saturated non-aromatic ring structure, preferably a 3- to 10-membered ring, more preferably a 3- to 7-membered ring, and the ring structure contains more than 1 heteroatom, preferably 1 to 4 heteroatoms, more preferably 1 to 2 heteroatoms. The terms "heterocyclic group", "heterocycle", "heterocyclic", and "heterocycloalkyl" also include polycyclic systems having more than 2 rings, where two adjacent rings share more than 2 carbons, and more than one of the rings in the ring is a heterocycle. For example, another ring may be cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, and / or heterocyclic group. The bicyclic polycyclic heterocyclic system may be a fused ring system, a bridged ring system, or a spiro ring system. The substituted heterocycle includes a heterocycle substituted with any substituent disclosed in this specification, for example, including a carbonyl group. For example, the heterocyclic group includes piperidine, piperazine, pyrrolidine, morpholine, lactone, lactam, etc. Additional exemplary heterocycles may include dihydropyridyl, dihydroindolyl, tetrahydropyridyl (piperidyl), tetrahydrothienyl, sulfoxytetrahydrothienyl, indolyl, piperidyl, 4-piperidyl, pyrrolidinyl, 2-pyrrolidoneyl, pyrroline, tetrahydrofuryl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, octahydroisoquinolinyl, 6H-1,2,5-thiadiazinyl, 2H,6H-1,5,2-dithiazinyl, pyranyl, chromanyl, xanthenyl, phenothiazinyl, 2H-pyrrolyl, 3H-indolyl, 4H-quinolizinyl, phthalazinyl, naphthyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl, pteridinyl, 4aH-carbazolyl, carbazolyl, β-carbolinyl, phenanthridinyl, acridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, furazanyl, phenoxazinyl, isochromanyl, chromanyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, piperazinyl, quinuclidinyl, morpholinyl, and oxazolidinyl (each of which may be substituted or unsubstituted), but are not limited thereto.

[0288] The term "carbocyclic ring" as used in this specification can be a monocyclic, bicyclic or polycyclic ring, and refers to a non-aromatic saturated or unsaturated, monovalent or divalent ring in which each atom of the ring is carbon. A cycloalkyl group can have 3 to 7 carbon atoms as a monocyclic ring, 7 to 12 carbon atoms as a bicyclic ring, and about 20 or fewer carbon atoms as a polycyclic ring. A monocyclic cycloalkyl group has 3 to 7 ring atoms, more typically 5 or 6 ring atoms. A bicyclic cycloalkyl group can have 7 to 12 ring atoms and can be a fused ring system, a spiro ring system or a bridged ring system. In an exemplary cycloalkyl group, the atoms can be arranged in a bicyclic [4,5], [5,5], [5,6] or [6,6] system. In a particular embodiment, the cycloalkyl group contains 3 to 20 atoms or 3 to 10 atoms, or more preferably, contains 3 to 7 atoms. Examples of cycloalkyl groups can include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, etc. Unless otherwise specified, the cycloalkyl group can be substituted with one or more substituents described in this specification.

[0289] The term "alkoxycarbonyl" as used in this specification refers to the group -C(=O)OR. The R is an alkyl group as defined in this specification and can be substituted or unsubstituted.

[0290] In this specification, according to the convention used in the art, the used in a chemical structural formula represents a single bond or a double bond.

[0291] In this specification, according to the convention used in the art, the used in a chemical structural formula represents a bond connecting to another monomer.

[0292] The term "amine" as used in this specification refers to -NH2 in which the hydrogen atom is substituted or unsubstituted by substituents such as an alkyl group, an aryl group, etc. In this case, the alkyl group, aryl group, etc. substituting the hydrogen atom are as defined in this specification and can be substituted or unsubstituted.

[0293] The term "amine monomer" as used in this specification is a monomer containing an amine functional group, and preferably, can be selected from the group consisting of amine monomers shown in Table 1 below.

[0294] Table 1

[0295]

[0296] The term "acrylate monomer" as used in this specification is a monomer in the form of an ester derivative of acrylic acid, and can be selected from the group consisting of acrylate monomers shown in Table 2 below.

[0297] Table 2

[0298]

[0299] The term "alkynoate monomer" used in this specification is a monomer in the form of an ester derivative of an alkynoic acid, and may be selected from the group consisting of alkynoate monomers shown in Table 3 below.

[0300] Table 3

[0301]

[0302] The polymer of the present invention simultaneously contains an amine monomer and an acrylate or alkynoate monomer, and is characterized in that the two monomers are alternately connected (refer to the schematic diagram of Figure 1 ).

[0303] The polymer of the present invention is characterized by having an ionizable moiety, wherein the "ionizable moiety" refers to the moiety in the polymer that ionizes according to the pH. For example, it may be a tertiary amine present in the chemical structure of the polymer, and those skilled in the art know that those moieties can be ionized according to the pH.

[0304] Hereinafter, the present invention will be described in more detail by way of examples. However, the following examples are for illustrative purposes only and are not intended to limit the scope of the present invention.

[0305] Preparation Example 1

[0306] Preparation of Polymer 1A

[0307]

[0308] Charge acrylate monomer A (1000 mg) into a two-neck round-bottom flask, and then charge amine monomer 1 into the flask such that the molar ratio of amine monomer 1 to acrylate monomer A is 1.04. Charge dichloromethane (CH 2 Cl 2 , DCM) into the flask such that the final concentration is 1000 mg / ml. Then, reflux the reaction at a temperature of 50 °C for 48 hours to obtain Polymer 1A of the present invention having an ionizable moiety.

[0309] Preparation Example 2

[0310] Preparation of Polymer 1B

[0311]

[0312] Charge acrylate monomer B (1000 mg) into a two-neck round-bottom flask, and then charge amine monomer 1 into the flask such that the molar ratio of amine monomer 1 to acrylate monomer B is 1.04. Charge DCM into the flask such that the final concentration is 1000 mg / ml. Then, reflux the reaction at a temperature of 50 °C for 48 hours to obtain Polymer 1B of the present invention having an ionizable moiety.

[0313] Preparation Example 3

[0314] Preparation of Polymer 1C

[0315]

[0316] Charge acrylate monomer C (1000 mg) into a two-necked round-bottom flask, and then charge amine monomer 1 into the flask such that its molar ratio to the acrylate monomer is 1.04. Charge DCM into the flask such that the final concentration is 1000 mg / ml. Then, reflux the reaction at a temperature of 50 °C for 48 hours to obtain Polymer 1C with an ionizable moiety of the present invention.

[0317] Preparation Example 4

[0318] Preparation of Polymer 1D

[0319]

[0320] Charge acrylate monomer D (1000 mg) into a two-necked round-bottom flask, and then charge amine monomer 1 into the flask such that its molar ratio to the acrylate monomer is 1.04. Charge DCM into the flask such that the final concentration is 1000 mg / ml. Then, reflux the reaction at a temperature of 50 °C for 48 hours to obtain Polymer 1D with an ionizable moiety of the present invention.

[0321] Preparation Example 5

[0322] Preparation of Polymer 1E

[0323]

[0324] Charge acrylate monomer E (1000 mg) into a two-necked round-bottom flask, and then charge amine monomer 1 into the flask such that its molar ratio to the acrylate monomer is 1.04. Charge DCM into the flask such that the final concentration is 2500 mg / ml. Then, reflux the reaction at a temperature of 50 °C for 48 hours to obtain Polymer 1E with an ionizable moiety of the present invention.

[0325] Preparation Example 6

[0326] Preparation of Polymer 2A

[0327]

[0328] Charge acrylate monomer A (1000 mg) into a 20-ml vial, and then charge amine monomer 2 into the vial such that its molar ratio to the acrylate monomer is 1.04. Charge dimethyl sulfoxide (DMSO) into the vial such that the final concentration is 1000 mg / ml. Then, react at a temperature of 90 °C for 24 hours to obtain Polymer 2A with an ionizable moiety of the present invention.

[0329] Preparation Example 7

[0330] Preparation of Polymer 2B

[0331]

[0332] Charge acrylate monomer B (1000 mg) into a 20 ml vial, and then charge amine monomer 2 into the vial such that the molar ratio thereof to the acrylate monomer is 1.04. Charge DMSO into the vial such that the final concentration is 1000 mg / ml. Then, react at a temperature of 90 °C for 24 hours to obtain Polymer 2B having an ionizable moiety of the present invention.

[0333] Preparation Example 8

[0334] Preparation of Polymer 2C

[0335]

[0336] Charge acrylate monomer C (1000 mg) into a 20 ml vial, and then charge amine monomer 2 into the vial such that the molar ratio thereof to the acrylate monomer is 1.04. Charge DMSO into the vial such that the final concentration is 1000 mg / ml. Then, react at a temperature of 90 °C for 24 hours to obtain Polymer 2C having an ionizable moiety of the present invention.

[0337] Preparation Example 9

[0338] Preparation of Polymer 2D

[0339]

[0340] Charge acrylate monomer D (1000 mg) into a 20 ml vial, and then charge amine monomer 2 into the vial such that the molar ratio thereof to the acrylate monomer is 1.04. Charge DMSO into the vial such that the final concentration is 1000 mg / ml. Then, react at a temperature of 90 °C for 24 hours to obtain Polymer 2D having an ionizable moiety of the present invention.

[0341] Preparation Example 10

[0342] Preparation of Polymer 2E

[0343]

[0344] The acrylate monomer E (1000 mg) was placed into a 20 ml vial, and then the amine monomer 2 was placed into the vial such that its molar ratio to the acrylate monomer was 1.04. DMSO was placed into the vial such that the final concentration was 2500 mg / ml. Then, the reaction was carried out at a temperature of 90 °C for 24 hours to obtain the polymer 2E with an ionizable moiety of the present invention.

[0345] Preparation Example 11

[0346] Preparation of Polymer 3A

[0347]

[0348] The acrylate monomer A (1000 mg) was placed into a 20 ml vial, and then the amine monomer 3 was placed into the vial such that its molar ratio to the acrylate monomer was 1.04. DMSO was placed into the vial such that the final concentration was 1000 mg / ml. Then, the reaction was carried out at a temperature of 90 °C for 24 hours to obtain the polymer 3A with an ionizable moiety of the present invention.

[0349] Preparation Example 12

[0350] Preparation of Polymer 3B

[0351]

[0352] The acrylate monomer B (1000 mg) was placed into a 20 ml vial, and then the amine monomer 3 was placed into the vial such that its molar ratio to the acrylate monomer was 1.04. DMSO was placed into the vial such that the final concentration was 1000 mg / ml. Then, the reaction was carried out at a temperature of 90 °C for 24 hours to obtain the polymer 3B with an ionizable moiety of the present invention.

[0353] Preparation Example 13

[0354] Preparation of Polymer 3C

[0355]

[0356] The acrylate monomer C (1000 mg) was placed into a 20 ml vial, and then the amine monomer 3 was placed into the vial such that its molar ratio to the acrylate monomer was 1.04. DMSO was placed into the vial such that the final concentration was 1000 mg / ml. Then, the reaction was carried out at a temperature of 90 °C for 24 hours to obtain the polymer 3C with an ionizable moiety of the present invention.

[0357] Preparation Example 14

[0358] Preparation of Polymer 3D

[0359]

[0360] Charge acrylate monomer D (1000 mg) into a 20-ml vial, and then charge amine monomer 3 into the vial such that the molar ratio thereof to the acrylate monomer is 1.04. Charge DMSO into the vial such that the final concentration is 1000 mg / ml. Then, react at a temperature of 90 °C for 24 hours to obtain polymer 3D with an ionizable moiety of the present invention.

[0361] Preparation Example 15

[0362] Preparation of Polymer 3E

[0363]

[0364] Charge acrylate monomer E (1000 mg) into a 20-ml vial, and then charge amine monomer 3 into the vial such that the molar ratio thereof to the acrylate monomer is 1.04. Charge DMSO into the vial such that the final concentration is 2500 mg / ml. Then, react at a temperature of 90 °C for 24 hours to obtain polymer 3E with an ionizable moiety of the present invention.

[0365] Preparation Example 16

[0366] Preparation of Polymer 4A

[0367]

[0368] Charge acrylate monomer A (1000 mg) into a 20-ml vial, and then charge amine monomer 4 into the vial such that the molar ratio thereof to the acrylate monomer is 1.04. Charge DMSO into the vial such that the final concentration is 1000 mg / ml. Then, react at a temperature of 90 °C for 24 hours to obtain polymer 4A with an ionizable moiety of the present invention.

[0369] Preparation Example 17

[0370] Preparation of Polymer 4B

[0371]

[0372] Charge acrylate monomer B (1000 mg) into a 20-ml vial, and then charge amine monomer 4 into the vial such that the molar ratio thereof to the acrylate monomer is 1.04. Charge DMSO into the vial such that the final concentration is 1000 mg / ml. Then, react at a temperature of 90 °C for 24 hours to obtain polymer 4B with an ionizable moiety of the present invention.

[0373] Preparation Example 18

[0374] Preparation of Polymer 4C

[0375]

[0376] Charge acrylate monomer C (1000 mg) into a 20-ml vial, and then charge amine monomer 4 into the vial such that the molar ratio thereof to the acrylate monomer is 1.04. Charge DMSO into the vial such that the final concentration is 1000 mg / ml. Then, react at a temperature of 90 °C for 24 hours to obtain polymer 4C with an ionizable moiety of the present invention.

[0377] Preparation Example 19

[0378] Preparation of Polymer 4D

[0379]

[0380] Charge acrylate monomer D (1000 mg) into a 20-ml vial, and then charge amine monomer 4 into the vial such that the molar ratio thereof to the acrylate monomer is 1.04. Charge DMSO into the vial such that the final concentration is 1000 mg / ml. Then, react at a temperature of 90 °C for 24 hours to obtain polymer 4D with an ionizable moiety of the present invention.

[0381] Preparation Example 20

[0382] Preparation of Polymer 4A

[0383]

[0384] Charge acrylate monomer E (1000 mg) into a 20-ml vial, and then charge amine monomer 4 into the vial such that the molar ratio thereof to the acrylate monomer is 1.04. Charge DMSO into the vial such that the final concentration is 2500 mg / ml. Then, react at a temperature of 90 °C for 24 hours to obtain polymer 4E with an ionizable moiety of the present invention.

[0385] Preparation Example 21

[0386] Preparation of Polymer 5A

[0387]

[0388] Charge acrylate monomer A (1000 mg) into a two-necked round-bottom flask, and then charge amine monomer 5 into the flask such that the molar ratio thereof to the acrylate monomer is 1.04. Charge DCM into the flask such that the final concentration is 1000 mg / ml. Then, reflux and react at a temperature of 50 °C for 48 hours to obtain polymer 5A with an ionizable moiety of the present invention.

[0389] Preparation Example 22

[0390] Preparation of Polymer 5B

[0391]

[0392] Charge acrylate monomer B (1000 mg) into a two-necked round-bottom flask, and then charge amine monomer 5 into the flask such that the molar ratio thereof to the acrylate monomer is 1.04. Charge DCM into the flask such that the final concentration is 1000 mg / ml. Then, reflux the reaction at a temperature of 50 °C for 48 hours to obtain Polymer 5B having an ionizable moiety of the present invention.

[0393] Preparation Example 23

[0394] Preparation of Polymer 5C

[0395]

[0396] Charge acrylate monomer C (1000 mg) into a two-necked round-bottom flask, and then charge amine monomer 5 into the flask such that the molar ratio thereof to the acrylate monomer is 1.04. Charge DCM into the flask such that the final concentration is 1000 mg / ml. Then, reflux the reaction at a temperature of 50 °C for 48 hours to obtain Polymer 5C having an ionizable moiety of the present invention.

[0397] Preparation Example 24

[0398] Preparation of Polymer 5D

[0399]

[0400] Charge acrylate monomer D (1000 mg) into a two-necked round-bottom flask, and then charge amine monomer 5 into the flask such that the molar ratio thereof to the acrylate monomer is 1.04. Charge DCM into the flask such that the final concentration is 1000 mg / ml. Then, reflux the reaction at a temperature of 50 °C for 48 hours to obtain Polymer 5D having an ionizable moiety of the present invention.

[0401] Preparation Example 25

[0402] Preparation of Polymer 5E

[0403]

[0404] Charge acrylate monomer E (1000 mg) into a two-necked round-bottom flask, and then charge amine monomer 5 into the flask such that the molar ratio thereof to the acrylate monomer is 1.04. Charge DCM into the flask such that the final concentration is 1000 mg / ml. Then, reflux the reaction at a temperature of 50 °C for 48 hours to obtain Polymer 5E having an ionizable moiety of the present invention.

[0405] Preparation Example 26

[0406] Preparation of Polymer 6A

[0407]

[0408] Charge acrylate monomer A (1000 mg) into a 20 ml vial, and then charge amine monomer 6 into the vial such that the molar ratio thereof to the acrylate monomer is 1.04. Charge DMSO into the vial such that the final concentration is 1000 mg / ml. Then, react at a temperature of 90 °C for 24 hours to obtain Polymer 6A having an ionizable moiety of the present invention.

[0409] Preparation Example 27

[0410] Preparation of Polymer 6B

[0411]

[0412] Charge acrylate monomer B (1000 mg) into a 20 ml vial, and then charge amine monomer 6 into the vial such that the molar ratio thereof to the acrylate monomer is 1.04. Charge DMSO into the vial such that the final concentration is 1000 mg / ml. Then, react at a temperature of 90 °C for 24 hours to obtain Polymer 6B having an ionizable moiety of the present invention.

[0413] Preparation Example 28

[0414] Preparation of Polymer 6C

[0415]

[0416] Charge acrylate monomer C (1000 mg) into a 20 ml vial, and then charge amine monomer 6 into the vial such that the molar ratio thereof to the acrylate monomer is 1.04. Charge DMSO into the vial such that the final concentration is 1000 mg / ml. Then, react at a temperature of 90 °C for 24 hours to obtain Polymer 6C having an ionizable moiety of the present invention.

[0417] Preparation Example 29

[0418] Preparation of Polymer 6D

[0419]

[0420] Charge acrylate monomer D (1000 mg) into a 20-ml vial, and then charge amine monomer 6 into the vial such that its molar ratio to the acrylate monomer is 1.04. Charge DMSO into the vial such that the final concentration is 1000 mg / ml. Then, react at a temperature of 90 °C for 24 hours to obtain polymer 6D with an ionizable moiety of the present invention.

[0421] Preparation Example 30

[0422] Preparation of Polymer 6E

[0423]

[0424] Charge acrylate monomer E (1000 mg) into a 20-ml vial, and then charge amine monomer 6 into the vial such that its molar ratio to the acrylate monomer is 1.04. Charge DMSO into the vial such that the final concentration is 2500 mg / ml. Then, react at a temperature of 90 °C for 24 hours to obtain polymer 6E with an ionizable moiety of the present invention.

[0425] Preparation Example 31

[0426] Preparation of Polymer 7A

[0427]

[0428] Charge acrylate monomer A (1000 mg) into a 20-ml vial, and then charge amine monomer 7 into the vial such that its molar ratio to the acrylate monomer is 1.04. Charge DMSO into the vial such that the final concentration is 1000 mg / ml. Then, react at a temperature of 90 °C for 24 hours to obtain polymer 7A with an ionizable moiety of the present invention.

[0429] Preparation Example 32

[0430] Preparation of Polymer 7B

[0431]

[0432] Charge acrylate monomer B (1000 mg) into a 20-ml vial, and then charge amine monomer 7 into the vial such that its molar ratio to the acrylate monomer is 1.04. Charge DMSO into the vial such that the final concentration is 1000 mg / ml. Then, react at a temperature of 90 °C for 24 hours to obtain polymer 7B with an ionizable moiety of the present invention.

[0433] Preparation Example 33

[0434] Preparation of Polymer 7C

[0435]

[0436] 1000 mg of acrylate monomer C was placed into a 20 ml vial, and then amine monomer 7 was placed into the vial such that its molar ratio to the acrylate monomer was 1.04. DMSO was placed into the vial such that the final concentration was 1000 mg / ml. Then, the reaction was carried out at a temperature of 90 °C for 24 hours to obtain polymer 7C with an ionizable moiety of the present invention.

[0437] Production Example 34

[0438] Preparation of Polymer 7D

[0439]

[0440] 1000 mg of acrylate monomer D was placed into a 20 ml vial, and then amine monomer 7 was placed into the vial such that its molar ratio to the acrylate monomer was 1.04. DMSO was placed into the vial such that the final concentration was 1000 mg / ml. Then, the reaction was carried out at a temperature of 90 °C for 24 hours to obtain polymer 7D with an ionizable moiety of the present invention.

[0441] Production Example 35

[0442] Preparation of Polymer 7E

[0443]

[0444] 1000 mg of acrylate monomer E was placed into a 20 ml vial, and then amine monomer 7 was placed into the vial such that its molar ratio to the acrylate monomer was 1.04. DMSO was placed into the vial such that the final concentration was 2500 mg / ml. Then, the reaction was carried out at a temperature of 90 °C for 24 hours to obtain polymer 7E with an ionizable moiety of the present invention.

[0445] Production Example 36

[0446] Preparation of Polymer 8A

[0447]

[0448] 1000 mg of acrylate monomer A was placed into a 20 ml vial, and then amine monomer 8 was placed into the vial such that its molar ratio to the acrylate monomer was 1.04. DMSO was placed into the vial such that the final concentration was 1000 mg / ml. Then, the reaction was carried out at a temperature of 90 °C for 24 hours to obtain polymer 8A with an ionizable moiety of the present invention.

[0449] Production Example 37

[0450] Preparation of Polymer 8B

[0451]

[0452] Charge acrylate monomer B (1000 mg) into a 20-ml vial, and then charge amine monomer 8 into the vial such that its molar ratio to the acrylate monomer is 1.04. Charge DMSO into the vial such that the final concentration is 1000 mg / ml. Then, react at a temperature of 90 °C for 24 hours to obtain polymer 8B with an ionizable moiety of the present invention.

[0453] Preparation Example 38

[0454] Preparation of Polymer 8C

[0455]

[0456] Charge acrylate monomer C (1000 mg) into a 20-ml vial, and then charge amine monomer 8 into the vial such that its molar ratio to the acrylate monomer is 1.04. Charge DMSO into the vial such that the final concentration is 1000 mg / ml. Then, react at a temperature of 90 °C for 24 hours to obtain polymer 8C with an ionizable moiety of the present invention.

[0457] Preparation Example 39

[0458] Preparation of Polymer 8D

[0459]

[0460] Charge acrylate monomer D (1000 mg) into a 20-ml vial, and then charge amine monomer 8 into the vial such that its molar ratio to the acrylate monomer is 1.04. Charge DMSO into the vial such that the final concentration is 1000 mg / ml. Then, react at a temperature of 90 °C for 24 hours to obtain polymer 8D with an ionizable moiety of the present invention.

[0461] Preparation Example 40

[0462] Preparation of Polymer 8E

[0463]

[0464] Charge acrylate monomer E (1000 mg) into a 20-ml vial, and then charge amine monomer 8 into the vial such that its molar ratio to the acrylate monomer is 1.04. Charge DMSO into the vial such that the final concentration is 2500 mg / ml. Then, react at a temperature of 90 °C for 24 hours to obtain polymer 8E with an ionizable moiety of the present invention.

[0465] Preparation Example 41

[0466] Preparation of Polymer 9A

[0467]

[0468] Charge acrylate monomer A (1000 mg) into a 20-ml vial, and then charge amine monomer 9 into the vial such that the molar ratio thereof to the acrylate monomer is 1.04. Charge DMSO into the vial such that the final concentration is 1000 mg / ml. Then, react at a temperature of 90 °C for 24 hours to obtain Polymer 9A with an ionizable moiety of the present invention.

[0469] Preparation Example 42

[0470] Preparation of Polymer 9B

[0471]

[0472] Charge acrylate monomer B (1000 mg) into a 20-ml vial, and then charge amine monomer 9 into the vial such that the molar ratio thereof to the acrylate monomer is 1.04. Charge DMSO into the vial such that the final concentration is 1000 mg / ml. Then, react at a temperature of 90 °C for 24 hours to obtain Polymer 9B with an ionizable moiety of the present invention.

[0473] Preparation Example 43

[0474] Preparation of Polymer 9C

[0475]

[0476] Charge acrylate monomer C (1000 mg) into a 20-ml vial, and then charge amine monomer 9 into the vial such that the molar ratio thereof to the acrylate monomer is 1.04. Charge DMSO into the vial such that the final concentration is 1000 mg / ml. Then, react at a temperature of 90 °C for 24 hours to obtain Polymer 9C with an ionizable moiety of the present invention.

[0477] Preparation Example 44

[0478] Preparation of Polymer 9D

[0479]

[0480] Charge acrylate monomer D (1000 mg) into a 20-ml vial, and then charge amine monomer 9 into the vial such that the molar ratio thereof to the acrylate monomer is 1.04. Charge DMSO into the vial such that the final concentration is 1000 mg / ml. Then, react at a temperature of 90 °C for 24 hours to obtain Polymer 9D with an ionizable moiety of the present invention.

[0481] Preparation Example 45

[0482] Preparation of Polymer 9E

[0483]

[0484] The acrylate monomer E (1000 mg) was placed into a 20 ml vial, and then the amine monomer 9 was placed into the vial such that the molar ratio thereof to the acrylate monomer was 1.04. DMSO was placed into the vial such that the final concentration was 2500 mg / ml. Then, the reaction was carried out at a temperature of 90 °C for 24 hours to obtain the polymer 9E having an ionizable moiety of the present invention.

[0485] Preparation Example 46

[0486] Preparation of Polymer 10A

[0487]

[0488] The acrylate monomer A (1000 mg) was placed into a 20 ml vial, and then the amine monomer 10 was placed into the vial such that the molar ratio thereof to the acrylate monomer was 1.04. DMSO was placed into the vial such that the final concentration was 1000 mg / ml. Then, the reaction was carried out at a temperature of 90 °C for 24 hours to obtain the polymer 10A having an ionizable moiety of the present invention.

[0489] Preparation Example 47

[0490] Preparation of Polymer 10B

[0491]

[0492] The acrylate monomer B (1000 mg) was placed into a 20 ml vial, and then the amine monomer 10 was placed into the vial such that the molar ratio thereof to the acrylate monomer was 1.04. DMSO was placed into the vial such that the final concentration was 1000 mg / ml. Then, the reaction was carried out at a temperature of 90 °C for 24 hours to obtain the polymer 10B having an ionizable moiety of the present invention.

[0493] Preparation Example 48

[0494] Preparation of Polymer 10C

[0495]

[0496] Charge acrylate monomer C (1000 mg) into a 20-ml vial, and then charge amine monomer 10 into the vial such that its molar ratio to the acrylate monomer is 1.04. Charge DMSO into the vial such that the final concentration is 1000 mg / ml. Then, react at a temperature of 90 °C for 24 hours to obtain polymer 10C with an ionizable moiety of the present invention.

[0497] Preparation Example 49

[0498] Preparation of Polymer 10D

[0499]

[0500] Charge acrylate monomer D (1000 mg) into a 20-ml vial, and then charge amine monomer 10 into the vial such that its molar ratio to the acrylate monomer is 1.04. Charge DMSO into the vial such that the final concentration is 1000 mg / ml. Then, react at a temperature of 90 °C for 24 hours to obtain polymer 10D with an ionizable moiety of the present invention.

[0501] Preparation Example 50

[0502] Preparation of Polymer 10E

[0503]

[0504] Charge acrylate monomer E (1000 mg) into a 20-ml vial, and then charge amine monomer 10 into the vial such that its molar ratio to the acrylate monomer is 1.04. Charge DMSO into the vial such that the final concentration is 2500 mg / ml. Then, react at a temperature of 90 °C for 24 hours to obtain polymer 10E with an ionizable moiety of the present invention.

[0505] Preparation Example 51

[0506] Preparation of Polymer 11A

[0507]

[0508] Charge acrylate monomer A (1000 mg) into a 20-ml vial, and then charge amine monomer 11 into the vial such that its molar ratio to the acrylate monomer is 1.04. Charge DMSO into the vial such that the final concentration is 1000 mg / ml. Then, react at a temperature of 90 °C for 24 hours to obtain polymer 11A with an ionizable moiety of the present invention.

[0509] Preparation Example 52

[0510] Preparation of Polymer 11B

[0511]

[0512] Charge acrylate monomer B (1000 mg) into a 20-ml vial, and then charge amine monomer 11 into the vial such that the molar ratio of it to the acrylate monomer is 1.04. Charge DMSO into the vial such that the final concentration is 1000 mg / ml. Then, react at a temperature of 90 °C for 24 hours to obtain polymer 11B with an ionizable moiety of the present invention.

[0513] Preparation Example 53

[0514] Preparation of Polymer 11C

[0515]

[0516] Charge acrylate monomer C (1000 mg) into a 20-ml vial, and then charge amine monomer 11 into the vial such that the molar ratio of it to the acrylate monomer is 1.04. Charge DMSO into the vial such that the final concentration is 1000 mg / ml. Then, react at a temperature of 90 °C for 24 hours to obtain polymer 11C with an ionizable moiety of the present invention.

[0517] Preparation Example 54

[0518] Preparation of Polymer 11D

[0519]

[0520] Charge acrylate monomer D (1000 mg) into a 20-ml vial, and then charge amine monomer 11 into the vial such that the molar ratio of it to the acrylate monomer is 1.04. Charge DMSO into the vial such that the final concentration is 1000 mg / ml. Then, react at a temperature of 90 °C for 24 hours to obtain polymer 11D with an ionizable moiety of the present invention.

[0521] Preparation Example 55

[0522] Preparation of Polymer 11E

[0523]

[0524] Charge acrylate monomer E (1000 mg) into a 20-ml vial, and then charge amine monomer 11 into the vial such that the molar ratio of it to the acrylate monomer is 1.04. Charge DMSO into the vial such that the final concentration is 2500 mg / ml. Then, react at a temperature of 90 °C for 24 hours to obtain polymer 11E with an ionizable moiety of the present invention.

[0525] Preparation Example 56

[0526] Preparation of Polymer 1F

[0527]

[0528] Charge the alkynoate monomer F (500 mg) into a round-bottom flask, then charge amine monomer 1 into the flask such that its molar ratio to the acrylate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react for 6 hours at room temperature to obtain the polymer 1F with an ionizable moiety of the present invention.

[0529] Preparation Example 57

[0530] Preparation of Polymer 1G

[0531]

[0532] Charge the alkynoate monomer G (500 mg) into a round-bottom flask, then charge amine monomer 1 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react for 6 hours at room temperature to obtain the polymer 1G with an ionizable moiety of the present invention.

[0533] Preparation Example 58

[0534] Preparation of Polymer 1H

[0535]

[0536] Charge the alkynoate monomer H (500 mg) into a round-bottom flask, then charge amine monomer 1 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react for 6 hours at room temperature to obtain the polymer 1H with an ionizable moiety of the present invention.

[0537] Preparation Example 59

[0538] Preparation of Polymer 1I

[0539]

[0540] Charge the alkynoate monomer I (500 mg) into a round-bottom flask, then charge amine monomer 1 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react for 6 hours at room temperature to obtain the polymer 1I with an ionizable moiety of the present invention.

[0541] Preparation Example 60

[0542] Preparation of Polymer 1J

[0543]

[0544] The alkynoate monomer J (500 mg) was charged into a round-bottom flask, and then the amine monomer 1 was charged into the flask such that its molar ratio to the alkynoate monomer was 1.04, and 4 mL of dichloromethane was charged into the flask. Then, the reaction was carried out at room temperature for 6 hours to obtain the polymer 1J with an ionizable moiety of the present invention.

[0545] Preparation Example 61

[0546] Preparation of Polymer 2F

[0547]

[0548] The alkynoate monomer F (500 mg) was charged into a round-bottom flask, and then the amine monomer 2 was charged into the flask such that its molar ratio to the alkynoate monomer was 1.04, and 4 mL of dichloromethane was charged into the flask. Then, the reaction was carried out at room temperature for 6 hours to obtain the polymer 2F with an ionizable moiety of the present invention.

[0549] Preparation Example 62

[0550] Preparation of Polymer 2G

[0551]

[0552] The alkynoate monomer G (500 mg) was charged into a round-bottom flask, and then the amine monomer 2 was charged into the flask such that its molar ratio to the alkynoate monomer was 1.04, and 4 mL of dichloromethane was charged into the flask. Then, the reaction was carried out at room temperature for 6 hours to obtain the polymer 2G with an ionizable moiety of the present invention.

[0553] Preparation Example 63

[0554] Preparation of Polymer 2H

[0555]

[0556] The alkynoate monomer H (500 mg) was charged into a round-bottom flask, and then the amine monomer 2 was charged into the flask such that its molar ratio to the alkynoate monomer was 1.04, and 4 mL of dichloromethane was charged into the flask. Then, the reaction was carried out at room temperature for 6 hours to obtain the polymer 2H with an ionizable moiety of the present invention.

[0557] Preparation Example 64

[0558] Preparation of Polymer 2I

[0559]

[0560] Charge the alkynoate monomer I (500 mg) into a round-bottom flask, and then charge the amine monomer 2 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 2I with an ionizable moiety of the present invention.

[0561] Preparation Example 65

[0562] Preparation of Polymer 2J

[0563]

[0564] Charge the alkynoate monomer J (500 mg) into a round-bottom flask, and then charge the amine monomer 2 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 2J with an ionizable moiety of the present invention.

[0565] Preparation Example 66

[0566] Preparation of Polymer 3F

[0567]

[0568] Charge the alkynoate monomer F (500 mg) into a round-bottom flask, and then charge the amine monomer 3 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 3F with an ionizable moiety of the present invention.

[0569] Preparation Example 67

[0570] Preparation of Polymer 3G

[0571]

[0572] Charge the alkynoate monomer G (500 mg) into a round-bottom flask, and then charge the amine monomer 3 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 3G with an ionizable moiety of the present invention.

[0573] Preparation Example 68

[0574] Preparation of Polymer 3H

[0575]

[0576] The alkynoate monomer H (500 mg) was charged into a round-bottom flask, and then the amine monomer 3 was charged into the flask such that its molar ratio to the alkynoate monomer was 1.04, and 4 mL of dichloromethane was charged into the flask. Then, the reaction was carried out at room temperature for 6 hours to obtain the polymer 3H having an ionizable moiety of the present invention.

[0577] Preparation Example 69

[0578] Preparation of Polymer 3I

[0579]

[0580] The alkynoate monomer I (500 mg) was charged into a round-bottom flask, and then the amine monomer 3 was charged into the flask such that its molar ratio to the alkynoate monomer was 1.04, and 4 mL of dichloromethane was charged into the flask. Then, the reaction was carried out at room temperature for 6 hours to obtain the polymer 3I having an ionizable moiety of the present invention.

[0581] Preparation Example 70

[0582] Preparation of Polymer 3J

[0583]

[0584] The alkynoate monomer J (500 mg) was charged into a round-bottom flask, and then the amine monomer 3 was charged into the flask such that its molar ratio to the alkynoate monomer was 1.04, and 4 mL of dichloromethane was charged into the flask. Then, the reaction was carried out at room temperature for 6 hours to obtain the polymer 3J having an ionizable moiety of the present invention.

[0585] Preparation Example 71

[0586] Preparation of Polymer 4F

[0587]

[0588] The alkynoate monomer F (500 mg) was charged into a round-bottom flask, and then the amine monomer 4 was charged into the flask such that its molar ratio to the alkynoate monomer was 1.04, and 4 mL of dichloromethane was charged into the flask. Then, the reaction was carried out at room temperature for 6 hours to obtain the polymer 4F having an ionizable moiety of the present invention.

[0589] Preparation Example 72

[0590] Preparation of Polymer 4G

[0591]

[0592] Charge the alkynoate monomer G (500 mg) into a round-bottom flask, and then charge the amine monomer 4 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 4G with an ionizable moiety of the present invention.

[0593] Preparation Example 73

[0594] Preparation of Polymer 4H

[0595]

[0596] Charge the alkynoate monomer H (500 mg) into a round-bottom flask, and then charge the amine monomer 4 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 4H with an ionizable moiety of the present invention.

[0597] Preparation Example 74

[0598] Preparation of Polymer 4I

[0599]

[0600] Charge the alkynoate monomer I (500 mg) into a round-bottom flask, and then charge the amine monomer 4 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 4I with an ionizable moiety of the present invention.

[0601] Preparation Example 75

[0602] Preparation of Polymer 4J

[0603]

[0604] Charge the alkynoate monomer J (500 mg) into a round-bottom flask, and then charge the amine monomer 4 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 4J with an ionizable moiety of the present invention.

[0605] Preparation Example 76

[0606] Preparation of Polymer 5F

[0607]

[0608] Charge the alkynoate monomer F (500 mg) into a round-bottom flask, and then charge the amine monomer 5 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 5F with an ionizable moiety of the present invention.

[0609] Preparation Example 77

[0610] Preparation of Polymer 5G

[0611]

[0612] Charge the alkynoate monomer G (500 mg) into a round-bottom flask, and then charge the amine monomer 5 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 5G with an ionizable moiety of the present invention.

[0613] Preparation Example 78

[0614] Preparation of Polymer 5H

[0615]

[0616] Charge the alkynoate monomer H (500 mg) into a round-bottom flask, and then charge the amine monomer 5 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 5H with an ionizable moiety of the present invention.

[0617] Preparation Example 79

[0618] Preparation of Polymer 5I

[0619]

[0620] Charge the alkynoate monomer I (500 mg) into a round-bottom flask, and then charge the amine monomer 5 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 5I with an ionizable moiety of the present invention.

[0621] Preparation Example 80

[0622] Preparation of Polymer 5J

[0623]

[0624] Charge the alkynoate monomer J (500 mg) into a round-bottom flask, and then charge the amine monomer 5 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 5J with an ionizable moiety of the present invention.

[0625] Preparation Example 81

[0626] Preparation of Polymer 6F

[0627]

[0628] Charge the alkynoate monomer F (500 mg) into a round-bottom flask, and then charge the amine monomer 6 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 6F with an ionizable moiety of the present invention.

[0629] Preparation Example 82

[0630] Preparation of Polymer 6G

[0631]

[0632] Charge the alkynoate monomer G (500 mg) into a round-bottom flask, and then charge the amine monomer 6 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 6G with an ionizable moiety of the present invention.

[0633] Preparation Example 83

[0634] Preparation of Polymer 6H

[0635]

[0636] Charge the alkynoate monomer H (500 mg) into a round-bottom flask, and then charge the amine monomer 6 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 6H with an ionizable moiety of the present invention.

[0637] Preparation Example 84

[0638] Preparation of Polymer 6I

[0639]

[0640] Charge the alkynoate monomer I (500 mg) into a round-bottom flask, then charge the amine monomer 6 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 6I with an ionizable moiety of the present invention.

[0641] Preparation Example 85

[0642] Preparation of Polymer 6J

[0643]

[0644] Charge the alkynoate monomer J (500 mg) into a round-bottom flask, then charge the amine monomer 6 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 6J with an ionizable moiety of the present invention.

[0645] Preparation Example 86

[0646] Preparation of Polymer 7F

[0647]

[0648] Charge the alkynoate monomer F (500 mg) into a round-bottom flask, then charge the amine monomer 7 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 7F with an ionizable moiety of the present invention.

[0649] Preparation Example 87

[0650] Preparation of Polymer 7G

[0651]

[0652] Charge the alkynoate monomer G (500 mg) into a round-bottom flask, then charge the amine monomer 7 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 7G with an ionizable moiety of the present invention.

[0653] Preparation Example 88

[0654] Preparation of Polymer 7H

[0655]

[0656] The alkynoate monomer H (500 mg) was charged into a round-bottom flask, and then the amine monomer 7 was charged into the flask such that its molar ratio to the alkynoate monomer was 1.04, and 4 mL of dichloromethane was charged into the flask. Then, the reaction was carried out at room temperature for 6 hours to obtain the polymer 7H with an ionizable moiety of the present invention.

[0657] Preparation Example 89

[0658] Preparation of Polymer 7I

[0659]

[0660] The alkynoate monomer I (500 mg) was charged into a round-bottom flask, and then the amine monomer 7 was charged into the flask such that its molar ratio to the alkynoate monomer was 1.04, and 4 mL of dichloromethane was charged into the flask. Then, the reaction was carried out at room temperature for 6 hours to obtain the polymer 7I with an ionizable moiety of the present invention.

[0661] Preparation Example 90

[0662] Preparation of Polymer 7J

[0663]

[0664] The alkynoate monomer J (500 mg) was charged into a round-bottom flask, and then the amine monomer 7 was charged into the flask such that its molar ratio to the alkynoate monomer was 1.04, and 4 mL of dichloromethane was charged into the flask. Then, the reaction was carried out at room temperature for 6 hours to obtain the polymer 7J with an ionizable moiety of the present invention.

[0665] Preparation Example 91

[0666] Preparation of Polymer 8F

[0667]

[0668] The alkynoate monomer F (500 mg) was charged into a round-bottom flask, and then the amine monomer 8 was charged into the flask such that its molar ratio to the alkynoate monomer was 1.04, and 4 mL of dichloromethane was charged into the flask. Then, the reaction was carried out at room temperature for 6 hours to obtain the polymer 8F with an ionizable moiety of the present invention.

[0669] Preparation Example 92

[0670] Preparation of Polymer 8G

[0671]

[0672] Charge the alkynoate monomer G (500 mg) into a round-bottom flask, and then charge the amine monomer 8 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 8G with an ionizable moiety of the present invention.

[0673] Preparation Example 93

[0674] Preparation of Polymer 8H

[0675]

[0676] Charge the alkynoate monomer H (500 mg) into a round-bottom flask, and then charge the amine monomer 8 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 8H with an ionizable moiety of the present invention.

[0677] Preparation Example 94

[0678] Preparation of Polymer 8I

[0679]

[0680] Charge the alkynoate monomer I (500 mg) into a round-bottom flask, and then charge the amine monomer 8 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 8I with an ionizable moiety of the present invention.

[0681] Preparation Example 95

[0682] Preparation of Polymer 8J

[0683]

[0684] Charge the alkynoate monomer J (500 mg) into a round-bottom flask, and then charge the amine monomer 8 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 8J with an ionizable moiety of the present invention.

[0685] Preparation Example 96

[0686] Preparation of Polymer 9F

[0687]

[0688] Charge the alkynoate monomer F (500 mg) into a round-bottom flask, then charge the amine monomer 9 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 9F with an ionizable moiety of the present invention.

[0689] Preparation Example 97

[0690] Preparation of Polymer 9G

[0691]

[0692] Charge the alkynoate monomer G (500 mg) into a round-bottom flask, then charge the amine monomer 9 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 9G with an ionizable moiety of the present invention.

[0693] Preparation Example 98

[0694] Preparation of Polymer 9H

[0695]

[0696] Charge the alkynoate monomer H (500 mg) into a round-bottom flask, then charge the amine monomer 9 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 9H with an ionizable moiety of the present invention.

[0697] Preparation Example 99

[0698] Preparation of Polymer 9I

[0699]

[0700] Charge the alkynoate monomer I (500 mg) into a round-bottom flask, then charge the amine monomer 9 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 9I with an ionizable moiety of the present invention.

[0701] Preparation Example 100

[0702] Preparation of Polymer 9J

[0703]

[0704] Charge the alkynoate monomer J (500 mg) into a round-bottom flask, and then charge the amine monomer 9 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 9J with an ionizable moiety of the present invention.

[0705] Preparation Example 101

[0706] Preparation of Polymer 10F

[0707]

[0708] Charge the alkynoate monomer F (500 mg) into a round-bottom flask, and then charge the amine monomer 10 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 10F with an ionizable moiety of the present invention.

[0709] Preparation Example 102

[0710] Preparation of Polymer 10G

[0711]

[0712] Charge the alkynoate monomer G (500 mg) into a round-bottom flask, and then charge the amine monomer 10 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 10G with an ionizable moiety of the present invention.

[0713] Preparation Example 103

[0714] Preparation of Polymer 10H

[0715]

[0716] Charge the alkynoate monomer H (500 mg) into a round-bottom flask, and then charge the amine monomer 10 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 10H with an ionizable moiety of the present invention.

[0717] Preparation Example 104

[0718] Preparation of Polymer 10I

[0719]

[0720] Charge the alkynoate monomer I (500 mg) into a round-bottom flask, then charge the amine monomer 10 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 10I with an ionizable moiety of the present invention.

[0721] Preparation Example 105

[0722] Preparation of Polymer 10J

[0723]

[0724] Charge the alkynoate monomer J (500 mg) into a round-bottom flask, then charge the amine monomer 10 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 10J with an ionizable moiety of the present invention.

[0725] Preparation Example 106

[0726] Preparation of Polymer 11F

[0727]

[0728] Charge the alkynoate monomer F (500 mg) into a round-bottom flask, then charge the amine monomer 11 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 11F with an ionizable moiety of the present invention.

[0729] Preparation Example 107

[0730] Preparation of Polymer 11G

[0731]

[0732] Charge the alkynoate monomer G (500 mg) into a round-bottom flask, then charge the amine monomer 11 into the flask such that its molar ratio to the alkynoate monomer is 1.04, and charge 4 mL of dichloromethane into the flask. Then, react at room temperature for 6 hours to obtain the polymer 11G with an ionizable moiety of the present invention.

[0733] Preparation Example 108

[0734] Preparation of Polymer 11H

[0735]

[0736] The alkynoate monomer H (500 mg) was charged into a round-bottom flask, and then the amine monomer 11 was charged into the flask such that its molar ratio to the alkynoate monomer was 1.04, and 4 mL of dichloromethane was charged into the flask. Then, the reaction was carried out at room temperature for 6 hours to obtain the polymer 11H having an ionizable moiety of the present invention.

[0737] Preparation Example 109

[0738] Preparation of Polymer 11I

[0739]

[0740] The alkynoate monomer I (500 mg) was charged into a round-bottom flask, and then the amine monomer 11 was charged into the flask such that its molar ratio to the alkynoate monomer was 1.04, and 4 mL of dichloromethane was charged into the flask. Then, the reaction was carried out at room temperature for 6 hours to obtain the polymer 11I having an ionizable moiety of the present invention.

[0741] Preparation Example 110

[0742] Preparation of Polymer 11J

[0743]

[0744] The alkynoate monomer J (500 mg) was charged into a round-bottom flask, and then the amine monomer 11 was charged into the flask such that its molar ratio to the alkynoate monomer was 1.04, and 4 mL of dichloromethane was charged into the flask. Then, the reaction was carried out at room temperature for 6 hours to obtain the polymer 11J having an ionizable moiety of the present invention.

[0745] Preparation Example 111

[0746] Preparation of Polymer PEG-1A

[0747]

[0748] The polymer 1A prepared according to Preparation Example 1 and 648.8 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in CH 2 Cl 2 to a concentration of 1000 mg / ml and added to the flask. The reaction was refluxed at 50 °C for 24 hours, and then PEG-1A was obtained.

[0749] Preparation Example 112

[0750] Preparation of Polymer PEG-1B

[0751]

[0752] The polymer 1B prepared according to Preparation Example 2 and 752.3 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in CH 2 Cl 2 to a concentration of 1000 mg / ml and added to a flask. The reaction was refluxed at 50 °C for 24 hours, and then PEG-1B was obtained.

[0753] Preparation Example 113

[0754] Preparation of polymer PEG-1C

[0755]

[0756] The polymer 1C prepared according to Preparation Example 3 and 858.7 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in CH 2 Cl 2 to a concentration of 1000 mg / ml and added to a flask. The reaction was refluxed at 50 °C for 24 hours, and then PEG-1C was obtained.

[0757] Preparation Example 114

[0758] Preparation of polymer PEG-1D

[0759]

[0760] The polymer 1D prepared according to Preparation Example 4 and 858.7 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in CH 2 Cl 2 to a concentration of 1000 mg / ml and added to a flask. The reaction was refluxed at 50 °C for 24 hours, and then PEG-1D was obtained.

[0761] Preparation Example 115

[0762] Preparation of polymer PEG-1E

[0763]

[0764] The polymer 1E prepared according to Preparation Example 5 and 563.0 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in CH 2 Cl 2 to a concentration of 2500 mg / ml and added to a flask. The reaction was refluxed at 50 °C for 24 hours, and then PEG-1E was obtained.

[0765] Preparation Example 116

[0766] Preparation of Polymer PEG-2A

[0767]

[0768] The polymer 2A prepared according to Preparation Example 6 and 648.8 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 1000 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-2A was obtained.

[0769] Preparation Example 117

[0770] Preparation of Polymer PEG-2B

[0771]

[0772] The polymer 2B prepared according to Preparation Example 7 and 752.3 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 1000 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-2B was obtained.

[0773] Preparation Example 118

[0774] Preparation of Polymer PEG-2C

[0775]

[0776] The polymer 2C prepared according to Preparation Example 8 and 858.7 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 1000 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-2C was obtained.

[0777] Preparation Example 119

[0778] Preparation of Polymer PEG-2D

[0779]

[0780] The polymer 2D prepared according to Preparation Example 9 and 858.7 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 1000 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-2D was obtained.

[0781] Preparation Example 120

[0782] Preparation of Polymer PEG-2E

[0783]

[0784] The polymer 2E prepared according to Preparation Example 10 and 563.0 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 2500 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-2E was obtained.

[0785] Preparation Example 121

[0786] Preparation of Polymer PEG-3A

[0787]

[0788] The polymer 3A prepared according to Preparation Example 11 and 648.8 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 1000 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-3A was obtained.

[0789] Preparation Example 122

[0790] Preparation of Polymer PEG-3B

[0791]

[0792] The polymer 3B prepared according to Preparation Example 12 and 752.3 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 1000 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-3B was obtained.

[0793] Preparation Example 123

[0794] Preparation of Polymer PEG-3C

[0795]

[0796] The polymer 3C prepared according to Preparation Example 13 and 858.7 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 1000 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-3C was obtained.

[0797] Preparation Example 124

[0798] Preparation of Polymer PEG-3D

[0799]

[0800] The polymer 3D prepared according to Preparation Example 14 and 858.7 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 1000 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-3D was obtained.

[0801] Preparation Example 125

[0802] Preparation of Polymer PEG-3E

[0803]

[0804] The polymer 3E prepared according to Preparation Example 15 and 563.0 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 2500 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-3E was obtained.

[0805] Preparation Example 126

[0806] Preparation of Polymer PEG-4A

[0807]

[0808] The polymer 4A prepared according to Preparation Example 16 and 648.8 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 1000 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-4A was obtained.

[0809] Preparation Example 127

[0810] Preparation of Polymer PEG-4B

[0811]

[0812] The polymer 4B prepared according to Preparation Example 17 and 752.3 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 1000 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-4B was obtained.

[0813] Preparation Example 128

[0814] Preparation of Polymer PEG-4C

[0815]

[0816] The polymer 4C prepared according to Preparation Example 18 and 858.7 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 1000 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-4C was obtained.

[0817] Preparation Example 129

[0818] Preparation of Polymer PEG-4D

[0819]

[0820] The polymer 4D prepared according to Preparation Example 19 and 858.7 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 1000 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-4D was obtained.

[0821] Preparation Example 130

[0822] Preparation of Polymer PEG-4E

[0823]

[0824] The polymer 4E prepared according to Preparation Example 20 and 563.0 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 2500 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-4E was obtained.

[0825] Preparation Example 131

[0826] Preparation of Polymer PEG-5A

[0827]

[0828] The polymer 5A prepared according to Preparation Example 21 and 648.8 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in CH 2 Cl 2 to a concentration of 1000 mg / ml and added to a flask. The reaction was refluxed at a temperature of 50 °C for 24 hours, and then PEG-5A was obtained.

[0829] Preparation Example 132

[0830] Preparation of Polymer PEG-5B

[0831]

[0832] The polymer 5B prepared according to Preparation Example 22 and 752.3 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in CH 2 Cl 2 to a concentration of 1000 mg / ml and added to a flask. The reaction was refluxed at 50 °C for 24 hours, and then PEG-5B was obtained.

[0833] Preparation Example 133

[0834] Preparation of polymer PEG-5C

[0835]

[0836] The polymer 5C prepared according to Preparation Example 23 and 858.7 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in CH 2 Cl 2 to a concentration of 1000 mg / ml and added to a flask. The reaction was refluxed at 50 °C for 24 hours, and then PEG-5C was obtained.

[0837] Preparation Example 134

[0838] Preparation of polymer PEG-5D

[0839]

[0840] The polymer 5D prepared according to Preparation Example 24 and 858.7 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in CH 2 Cl 2 to a concentration of 1000 mg / ml and added to a flask. The reaction was refluxed at 50 °C for 24 hours, and then PEG-5D was obtained.

[0841] Preparation Example 135

[0842] Preparation of polymer PEG-5E

[0843]

[0844] The polymer 5E prepared according to Preparation Example 25 and 563.0 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in CH 2 Cl 2 to a concentration of 2500 mg / ml and added to a flask. The reaction was refluxed at 50 °C for 24 hours, and then PEG-5E was obtained.

[0845] Preparation Example 136

[0846] Preparation of Polymer PEG-6A

[0847]

[0848] Dissolve the polymer 6A prepared according to Preparation Example 26 and 648.8 mg of polyethylene glycol acrylate (PEG-acrylate) in DMSO to a concentration of 1000 mg / ml, and add it to a flask. React at a temperature of 90 °C for 24 hours, and then obtain PEG-6A.

[0849] Preparation Example 137

[0850] Preparation of Polymer PEG-6B

[0851]

[0852] Dissolve the polymer 6B prepared according to Preparation Example 27 and 752.3 mg of polyethylene glycol acrylate (PEG-acrylate) in DMSO to a concentration of 1000 mg / ml, and add it to a flask. React at a temperature of 90 °C for 24 hours, and then obtain PEG-6B.

[0853] Preparation Example 138

[0854] Preparation of Polymer PEG-6C

[0855]

[0856] Dissolve the polymer 6C prepared according to Preparation Example 28 and 858.7 mg of polyethylene glycol acrylate (PEG-acrylate) in DMSO to a concentration of 1000 mg / ml, and add it to a flask. React at a temperature of 90 °C for 24 hours, and then obtain PEG-6C.

[0857] Preparation Example 139

[0858] Preparation of Polymer PEG-6D

[0859]

[0860] Dissolve the polymer 6D prepared according to Preparation Example 29 and 858.7 mg of polyethylene glycol acrylate (PEG-acrylate) in DMSO to a concentration of 1000 mg / ml, and add it to a flask. React at a temperature of 90 °C for 24 hours, and then obtain PEG-6D.

[0861] Preparation Example 140

[0862] Preparation of Polymer PEG-6E

[0863]

[0864] The polymer 6E prepared according to Preparation Example 30 and 563.0 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 2500 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-6E was obtained.

[0865] Preparation Example 141

[0866] Preparation of Polymer PEG-7A

[0867]

[0868] The polymer 7A prepared according to Preparation Example 31 and 648.8 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 1000 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-7A was obtained.

[0869] Preparation Example 142

[0870] Preparation of Polymer PEG-7B

[0871]

[0872] The polymer 7B prepared according to Preparation Example 32 and 752.3 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 1000 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-7B was obtained.

[0873] Preparation Example 143

[0874] Preparation of Polymer PEG-7C

[0875]

[0876] The polymer 7C prepared according to Preparation Example 33 and 858.7 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 1000 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-7C was obtained.

[0877] Preparation Example 144

[0878] Preparation of Polymer PEG-7D

[0879]

[0880] The polymer 7D prepared according to Preparation Example 34 and 858.7 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 1000 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-7D was obtained.

[0881] Preparation Example 145

[0882] Preparation of Polymer PEG-7E

[0883]

[0884] The polymer 7E prepared according to Preparation Example 35 and 563.0 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 2500 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-7E was obtained.

[0885] Preparation Example 146

[0886] Preparation of Polymer PEG-8A

[0887]

[0888] The polymer 8A prepared according to Preparation Example 36 and 648.8 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 1000 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-8A was obtained.

[0889] Preparation Example 147

[0890] Preparation of Polymer PEG-8B

[0891]

[0892] The polymer 8B prepared according to Preparation Example 37 and 752.3 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 1000 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-8B was obtained.

[0893] Preparation Example 148

[0894] Preparation of Polymer PEG-8C

[0895]

[0896] The polymer 8C prepared according to Preparation Example 38 and 858.7 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 1000 mg / ml and added to a flask. The reaction was carried out at 90 °C for 24 hours, and then PEG-8C was obtained.

[0897] Preparation Example 149

[0898] Preparation of Polymer PEG-8D

[0899]

[0900] The polymer 8D prepared according to Preparation Example 39 and 858.7 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 1000 mg / ml and added to a flask. The reaction was carried out at 90 °C for 24 hours, and then PEG-8D was obtained.

[0901] Preparation Example 150

[0902] Preparation of Polymer PEG-8E

[0903] The polymer 8E prepared according to Preparation Example 40 and 563.0 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 2500 mg / ml and added to a flask. The reaction was carried out at 90 °C for 24 hours, and then PEG-8E was obtained.

[0904] Preparation Example 151

[0905] Preparation of Polymer PEG-9A

[0906]

[0907] The polymer 9A prepared according to Preparation Example 41 and 648.8 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 1000 mg / ml and added to a flask. The reaction was carried out at 90 °C for 24 hours, and then PEG-9A was obtained.

[0908] Preparation Example 152

[0909] Preparation of Polymer PEG-9B

[0910]

[0911] The polymer 9B prepared according to Preparation Example 42 and 752.3 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 1000 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-9B was obtained.

[0912] Preparation Example 153

[0913] Preparation of Polymer PEG-9C

[0914]

[0915] The polymer 9C prepared according to Preparation Example 43 and 858.7 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 1000 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-9C was obtained.

[0916] Preparation Example 154

[0917] Preparation of Polymer PEG-9D

[0918]

[0919] The polymer 9D prepared according to Preparation Example 44 and 858.7 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 1000 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-9D was obtained.

[0920] Preparation Example 155

[0921] Preparation of Polymer PEG-9E

[0922]

[0923] The polymer 9E prepared according to Preparation Example 45 and 563.0 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 2500 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-9E was obtained.

[0924] Preparation Example 156

[0925] Preparation of Polymer PEG-10A

[0926]

[0927] The polymer 10A prepared according to Preparation Example 46 and 648.8 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 1000 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-10A was obtained.

[0928] Preparation Example 157

[0929] Preparation of polymer PEG-10B

[0930]

[0931] The polymer 10B prepared according to Preparation Example 47 and 752.3 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 1000 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-10B was obtained.

[0932] Preparation Example 158

[0933] Preparation of polymer PEG-10C

[0934]

[0935] The polymer 10C prepared according to Preparation Example 48 and 858.7 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 1000 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-10C was obtained.

[0936] Preparation Example 159

[0937] Preparation of polymer PEG-10D

[0938]

[0939] The polymer 10D prepared according to Preparation Example 49 and 858.7 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 1000 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-10D was obtained.

[0940] Preparation Example 160

[0941] Preparation of polymer PEG-10E

[0942]

[0943] The polymer 10E prepared according to Preparation Example 50 and 563.0 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 2500 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-10E was obtained.

[0944] Preparation Example 161

[0945] Preparation of polymer PEG-11A

[0946]

[0947] The polymer 11A prepared according to Preparation Example 51 and 648.8 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 1000 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-11A was obtained.

[0948] Preparation Example 162

[0949] Preparation of polymer PEG-11B

[0950]

[0951] The polymer 11B prepared according to Preparation Example 52 and 752.3 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 1000 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-11B was obtained.

[0952] Preparation Example 163

[0953] Preparation of polymer PEG-11C

[0954]

[0955] The polymer 11C prepared according to Preparation Example 53 and 858.7 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 1000 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-11C was obtained.

[0956] Preparation Example 164

[0957] Preparation of polymer PEG-11D

[0958]

[0959] The polymer 11D prepared according to Preparation Example 54 and 858.7 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 1000 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-11D was obtained.

[0960] Preparation Example 165

[0961] Preparation of polymer PEG-11E

[0962]

[0963] The polymer 11E prepared according to Preparation Example 55 and 563.0 mg of polyethylene glycol acrylate (PEG-acrylate) were dissolved in DMSO to a concentration of 2500 mg / ml and added to a flask. The reaction was carried out at a temperature of 90 °C for 24 hours, and then PEG-11E was obtained.

[0964] Preparation Example 166

[0965] Preparation of polymer PEG-1F

[0966]

[0967] The polymer 1F prepared according to Preparation Example 56 and 329.5 mg of polyethylene glycol alkynoate (PEG-alkynoate) were dissolved in 4 mL of CH 2 Cl 2 and added to a flask. The reaction was carried out at room temperature for 24 hours, and then PEG-1F was obtained.

[0968] Preparation Example 167

[0969] Preparation of polymer PEG-1G

[0970]

[0971] The polymer 1G prepared according to Preparation Example 57 and 383.0 mg of polyethylene glycol alkynoate (PEG-alkynoate) were dissolved in 4 mL of CH 2 Cl 2 and added to a flask. The reaction was carried out at room temperature for 24 hours, and then PEG-1G was obtained.

[0972] Preparation Example 168

[0973] Preparation of polymer PEG-1H

[0974]

[0975] The polymer 1H prepared according to Preparation Example 58 and 438.3 mg of polyethylene glycol alkynoate were dissolved in 4 mL of CH 2 Cl 2 and added to a flask. The reaction was carried out at room temperature for 24 hours, and then PEG-1H was obtained.

[0976] Preparation Example 169

[0977] Preparation of Polymer PEG-1I

[0978]

[0979] The polymer 1I prepared according to Preparation Example 59 and 438.3 mg of polyethylene glycol alkynoate were dissolved in 4 mL of CH 2 Cl 2 and added to a flask. The reaction was carried out at room temperature for 24 hours, and then PEG-1I was obtained.

[0980] Preparation Example 170

[0981] Preparation of Polymer PEG-1J

[0982]

[0983] The polymer 1J prepared according to Preparation Example 60 and 285.3 mg of polyethylene glycol alkynoate were dissolved in 4 mL of CH 2 Cl 2 and added to a flask. The reaction was carried out at room temperature for 24 hours, and then PEG-1J was obtained.

[0984] Preparation Example 171

[0985] Preparation of Polymer PEG-2F

[0986]

[0987] The polymer 2F prepared according to Preparation Example 61 and 329.5 mg of polyethylene glycol alkynoate were dissolved in 4 mL of CH 2 Cl 2 and added to a flask. The reaction was carried out at room temperature for 24 hours, and then PEG-2F was obtained.

[0988] Preparation Example 172

[0989] Preparation of Polymer PEG-2G

[0990]

[0991] The polymer 2G prepared according to Preparation Example 62 and 383.0 mg of polyethylene glycol alkynoate (PEG-alkynoate) were dissolved in 4 mL of CH 2 Cl 2 and added to a flask. The reaction was carried out at room temperature for 24 hours, and then PEG-2G was obtained.

[0992] Preparation Example 173

[0993] Preparation of polymer PEG-2H

[0994]

[0995] The polymer 2H prepared according to Preparation Example 63 and 438.3 mg of polyethylene glycol alkynoate (PEG-alkynoate) were dissolved in 4 mL of CH 2 Cl 2 and added to a flask. The reaction was carried out at room temperature for 24 hours, and then PEG-2H was obtained.

[0996] Preparation Example 174

[0997] Preparation of polymer PEG-2I

[0998]

[0999] The polymer 2I prepared according to Preparation Example 64 and 438.3 mg of polyethylene glycol alkynoate (PEG-alkynoate) were dissolved in 4 mL of CH 2 Cl 2 and added to a flask. The reaction was carried out at room temperature for 24 hours, and then PEG-2I was obtained.

[1000] Preparation Example 175

[1001] Preparation of polymer PEG-2J

[1002]

[1003] The polymer 2J prepared according to Preparation Example 65 and 285.3 mg of polyethylene glycol alkynoate (PEG-alkynoate) were dissolved in 4 mL of CH 2 Cl 2 and added to a flask. The reaction was carried out at room temperature for 24 hours, and then PEG-2J was obtained.

[1004] Preparation Example 176

[1005] Preparation of polymer PEG-3F

[1006]

[1007] The polymer 3F prepared according to Preparation Example 66 and 329.5 mg of polyethylene glycol alkynoate (PEG-alkynoate) were dissolved in 4 mL of CH 2 Cl 2 and added to a flask. The reaction was carried out at room temperature for 24 hours, and then PEG-3F was obtained.

[1008] Preparation Example 177

[1009] Preparation of polymer PEG-3G

[1010]

[1011] The polymer 3G prepared according to Preparation Example 67 and 383.0 mg of polyethylene glycol alkynoate (PEG-alkynoate) were dissolved in 4 mL of CH 2 Cl 2 and added to a flask. The reaction was carried out at room temperature for 24 hours, and then PEG-3G was obtained.

[1012] Preparation Example 178

[1013] Preparation of polymer PEG-3H

[1014]

[1015] The polymer 3H prepared according to Preparation Example 68 and 438.3 mg of polyethylene glycol alkynoate (PEG-alkynoate) were dissolved in 4 mL of CH 2 Cl 2 and added to a flask. The reaction was carried out at room temperature for 24 hours, and then PEG-3H was obtained.

[1016] Preparation Example 179

[1017] Preparation of polymer PEG-3I

[1018]

[1019] The polymer 3I prepared according to Preparation Example 69 and 438.3 mg of polyethylene glycol alkynoate (PEG-alkynoate) were dissolved in 4 mL of CH 2 Cl 2 and added to a flask. The reaction was carried out at room temperature for 24 hours, and then PEG-3I was obtained.

[1020] Preparation Example 180

[1021] Preparation of polymer PEG-3J

[1022]

[1023] The polymer 3J prepared according to Preparation Example 70 and 285.3 mg of polyethylene glycol alkynoate (PEG-alkynoate) were dissolved in 4 mL of CH 2 Cl 2 and added to a flask. The reaction was carried out at room temperature for 24 hours, and then PEG-3J was obtained.

[1024] Preparation Example 181

[1025] Preparation of polymer PEG-4F

[1026]

[1027] The polymer 4F prepared according to Preparation Example 71 and 329.5 mg of polyethylene glycol alkynoate (PEG-alkynoate) were dissolved in 4 mL of CH 2 Cl 2 and added to a flask. The reaction was carried out at room temperature for 24 hours, and then PEG-4F was obtained.

[1028] Preparation Example 182

[1029] Preparation of polymer PEG-4G

[1030]

[1031] The polymer 4G prepared according to Preparation Example 72 and 383.0 mg of polyethylene glycol alkynoate (PEG-alkynoate) were dissolved in 4 mL of CH 2 Cl 2 and added to a flask. The reaction was carried out at room temperature for 24 hours, and then PEG-4G was obtained.

[1032] Preparation Example 183

[1033] Preparation of polymer PEG-4H

[1034]

[1035] The polymer 4H prepared according to Preparation Example 73 and 438.3 mg of polyethylene glycol alkynoate (PEG-alkynoate) were dissolved in 4 mL of CH 2 Cl 2 and added to a flask. The reaction was carried out at room temperature for 24 hours, and then PEG-4H was obtained.

[1036] Preparation Example 184

[1037] Preparation of polymer PEG-4I

[1038]

[1039] The polymer 4I prepared according to Preparation Example 74 and 438.3 mg of polyethylene glycol alkynoate (PEG-alkynoate) were dissolved in 4 mL of CH 2 Cl 2 and added to a flask. The reaction was carried out at room temperature for 24 hours, and then PEG-4I was obtained.

[1040] Preparation Example 185

[1041] Preparation of polymer PEG-4J

[1042]

[1043] The polymer 4J prepared according to Preparation Example 75 and 285.3 mg of polyethylene glycol alkynoate (PEG-alkynoate) were dissolved in 4 mL of CH 2 Cl 2 and added to a flask. The reaction was carried out at room temperature for 24 hours, and then PEG-4J was obtained.

[1044] Preparation Example 186

[1045] Preparation of polymer PEG-5F

[1046]

[1047] The polymer 5F prepared according to Preparation Example 76 and 329.5 mg of polyethylene glycol alkynoate (PEG-alkynoate) were dissolved in 4 mL of CH 2 Cl 2 and added to a flask. The reaction was carried out at room temperature for 24 hours, and then PEG-5F was obtained.

[1048] Preparation Example 187

[1049] Preparation of polymer PEG-5G

[1050]

[1051] The polymer 5G prepared according to Preparation Example 77 and 383.0 mg of polyethylene glycol alkynoate (PEG-alkynoate) were dissolved in 4 mL of CH 2 Cl 2 and added to a flask. The reaction was carried out at room temperature for 24 hours, and then PEG-5G was obtained.

[1052] Preparation Example 188

[1053] Preparation of polymer PEG-5H

[1054]

[1055] The polymer 5H prepared according to Preparation Example 78 and 438.3 mg of polyethylene glycol alkynoate were dissolved in 4 mL of CH 2 Cl 2 and added to a flask. The reaction was carried out at room temperature for 24 hours, and then PEG-5H was obtained.

[1056] Preparation Example 189

[1057] Preparation of polymer PEG-5I

[1058]

[1059] The polymer 5I prepared according to Preparation Example 79 and 438.3 mg of polyethylene glycol alkynoate were dissolved in 4 mL of CH 2 Cl 2 and added to a flask. The reaction was carried out at room temperature for 24 hours, and then PEG-5I was obtained.

[1060] Preparation Example 190

[1061] Preparation of polymer PEG-5J

[1062]

[1063] The polymer 5J prepared according to Preparation Example 80 and 285.3 mg of polyethylene glycol alkynoate were dissolved in 4 mL of CH 2 Cl 2 and added to a flask. The reaction was carried out at room temperature for 24 hours, and then PEG-5J was obtained.

[1064] Preparation Example 191

[1065] Preparation of polymer PEG-6F

[1066]

[1067] The polymer 6F prepared according to Preparation Example 81 and 329.5 mg of polyethylene glycol alkynoate were dissolved in 4 mL of CH 2 Cl 2 and added to a flask. The reaction was carried out at room temperature for 24 hours, and then PEG-6F was obtained.

[1068] Preparation Example 192

[1069] Preparation of Polymer PEG-6G

[1070]

[1071] Dissolve the polymer 6G prepared according to Preparation Example 82 and 383.0 mg of polyethylene glycol alkynoate (PEG-alkynoate) in 4 mL of CH 2 Cl 2 and add it to a flask. React at room temperature for 24 hours, and then obtain PEG-6G.

[1072] Preparation Example 193

[1073] Preparation of Polymer PEG-6H

[1074]

[1075] Dissolve the polymer 6H prepared according to Preparation Example 83 and 438.3 mg of polyethylene glycol alkynoate (PEG-alkynoate) in 4 mL of CH 2 Cl 2 and add it to a flask. React at room temperature for 24 hours, and then obtain PEG-6H.

[1076] Preparation Example 194

[1077] Preparation of Polymer PEG-6I

[1078]

[1079] Dissolve the polymer 6I prepared according to Preparation Example 84 and 438.3 mg of polyethylene glycol alkynoate (PEG-alkynoate) in 4 mL of CH 2 Cl 2 and add it to a flask. React at room temperature for 24 hours, and then obtain PEG-6I.

[1080] Preparation Example 195

[1081] Preparation of Polymer PEG-6J

[1082]

[1083] Dissolve the polymer 6J prepared according to Preparation Example 85 and 285.3 mg of polyethylene glycol alkynoate (PEG-alkynoate) in 4 mL of CH 2 Cl 2 and add it to a flask. React at room temperature for 24 hours, and then obtain PEG-6J.

[1084] Preparation Example 196

[1085] Preparation of Polymer PEG-7F

[1086]

[1087] Dissolve the polymer 7F prepared according to Preparation Example 86 and 329.5 mg of polyethylene glycol alkynoate (PEG-alkynoate) in 4 mL of CH 2 Cl 2 and add it to a flask. React at room temperature for 24 hours to obtain PEG-7F.

[1088] Preparation Example 197

[1089] Preparation of Polymer PEG-7G

[1090]

[1091] Dissolve the polymer 7G prepared according to Preparation Example 87 and 383.0 mg of polyethylene glycol alkynoate (PEG-alkynoate) in 4 mL of CH 2 Cl 2 and add it to a flask. React at room temperature for 24 hours to obtain PEG-7G.

[1092] Preparation Example 198

[1093] Preparation of Polymer PEG-7H

[1094]

[1095] Dissolve the polymer 7H prepared according to Preparation Example 88 and 438.3 mg of polyethylene glycol alkynoate (PEG-alkynoate) in 4 mL of CH 2 Cl 2 and add it to a flask. React at room temperature for 24 hours to obtain PEG-7H.

[1096] Preparation Example 199

[1097] Preparation of Polymer PEG-7I

[1098]

[1099] Dissolve the polymer 7I prepared according to Preparation Example 89 and 438.3 mg of polyethylene glycol alkynoate (PEG-alkynoate) in 4 mL of CH 2 Cl 2 and add it to a flask. React at room temperature for 24 hours to obtain PEG-7I.

[1100] Preparation Example 200

[1101] Preparation of Polymer PEG-7J

[1102]

[1103] Dissolve the polymer 7J prepared according to Preparation Example 90 and 285.3 mg of polyethylene glycol alkynoate (PEG-alkynoate) in 4 mL of CH 2 Cl 2 and add it to a flask. React at room temperature for 24 hours, and then obtain PEG-7J.

[1104] Preparation Example 201

[1105] Preparation of Polymer PEG-8F

[1106]

[1107] Dissolve the polymer 8F prepared according to Preparation Example 91 and 329.5 mg of polyethylene glycol alkynoate (PEG-alkynoate) in 4 mL of CH 2 Cl 2 and add it to a flask. React at room temperature for 24 hours, and then obtain PEG-8F.

[1108] Preparation Example 202

[1109] Preparation of Polymer PEG-8G

[1110]

[1111] Dissolve the polymer 8G prepared according to Preparation Example 92 and 383.0 mg of polyethylene glycol alkynoate (PEG-alkynoate) in 4 mL of CH 2 Cl 2 and add it to a flask. React at room temperature for 24 hours, and then obtain PEG-8G.

[1112] Preparation Example 203

[1113] Preparation of Polymer PEG-8H

[1114]

[1115] Dissolve the polymer 8H prepared according to Preparation Example 93 and 438.3 mg of polyethylene glycol alkynoate (PEG-alkynoate) in 4 mL of CH 2 Cl 2 and add it to a flask. React at room temperature for 24 hours, and then obtain PEG-8H.

[1116] Preparation Example 204

[1117] Preparation of Polymer PEG-8I

[1118]

[1119] Dissolve 438.3 mg of the polymer 8I prepared according to the above Preparation Example 94 and poly(ethylene glycol) alkynoate in 4 mL of CH 2 Cl 2 , and add it to a flask. React at room temperature for 24 hours to obtain PEG-8I.

[1120] Preparation Example 205

[1121] Preparation of Polymer PEG-8J

[1122]

[1123] Dissolve 285.3 mg of the polymer 8J prepared according to the above Preparation Example 95 and poly(ethylene glycol) alkynoate in 4 mL of CH 2 Cl 2 , and add it to a flask. React at room temperature for 24 hours to obtain PEG-8J.

[1124] Preparation Example 206

[1125] Preparation of Polymer PEG-9F

[1126]

[1127] Dissolve 329.5 mg of the polymer 9F prepared according to the above Preparation Example 96 and poly(ethylene glycol) alkynoate in 4 mL of CH 2 Cl 2 , and add it to a flask. React at room temperature for 24 hours to obtain PEG-9F.

[1128] Preparation Example 207

[1129] Preparation of Polymer PEG-9G

[1130]

[1131] Dissolve 383.0 mg of the polymer 9G prepared according to the above Preparation Example 97 and poly(ethylene glycol) alkynoate in 4 mL of CH 2 Cl 2 , and add it to a flask. React at room temperature for 24 hours to obtain PEG-9G.

[1132] Preparation Example 208

[1133] Preparation of Polymer PEG-9H

[1134]

[1135] Dissolve the polymer 9H prepared according to the said Preparation Example 98 and 438.3 mg of polyethylene glycol alkynoate (PEG-alkynoate) in 4 mL of CH 2 Cl 2 and add it to a flask. React at room temperature for 24 hours, then obtain PEG-9H.

[1136] Preparation Example 209

[1137] Preparation of Polymer PEG-9I

[1138]

[1139] Dissolve the polymer 9I prepared according to the said Preparation Example 99 and 438.3 mg of polyethylene glycol alkynoate (PEG-alkynoate) in 4 mL of CH 2 Cl 2 and add it to a flask. React at room temperature for 24 hours, then obtain PEG-9I.

[1140] Preparation Example 210

[1141] Preparation of Polymer PEG-9J

[1142]

[1143] Dissolve the polymer 9J prepared according to the said Preparation Example 100 and 285.3 mg of polyethylene glycol alkynoate (PEG-alkynoate) in 4 mL of CH 2 Cl 2 and add it to a flask. React at room temperature for 24 hours, then obtain PEG-9J.

[1144] Preparation Example 211

[1145] Preparation of Polymer PEG-10F

[1146]

[1147] Dissolve the polymer 10F prepared according to the said Preparation Example 101 and 329.5 mg of polyethylene glycol alkynoate (PEG-alkynoate) in 4 mL of CH 2 Cl 2 and add it to a flask. React at room temperature for 24 hours, then obtain PEG-10F.

[1148] Preparation Example 212

[1149] Preparation of Polymer PEG-10G

[1150]

[1151] Dissolve the polymer 10G prepared according to the described Preparation Example 102 and 383.0 mg of polyethylene glycol alkynoate (PEG-alkynoate) in 4 mL of CH 2 Cl 2 and add it to a flask. React at room temperature for 24 hours, then obtain PEG-10G.

[1152] Preparation Example 213

[1153] Preparation of Polymer PEG-10H

[1154]

[1155] Dissolve the polymer 10H prepared according to the described Preparation Example 103 and 438.3 mg of polyethylene glycol alkynoate (PEG-alkynoate) in 4 mL of CH 2 Cl 2 and add it to a flask. React at room temperature for 24 hours, then obtain PEG-10H.

[1156] Preparation Example 214

[1157] Preparation of Polymer PEG-10I

[1158]

[1159] Dissolve the polymer 10I prepared according to the described Preparation Example 104 and 438.3 mg of polyethylene glycol alkynoate (PEG-alkynoate) in 4 mL of CH 2 Cl 2 and add it to a flask. React at room temperature for 24 hours, then obtain PEG-10I.

[1160] Preparation Example 215

[1161] Preparation of Polymer PEG-10J

[1162]

[1163] Dissolve the polymer 10J prepared according to the described Preparation Example 105 and 285.3 mg of polyethylene glycol alkynoate (PEG-alkynoate) in 4 mL of CH 2 Cl 2It was added to a flask in [the substance]. The reaction was carried out at room temperature for 24 hours, and then PEG-10J was obtained.

[1164] Preparation Example 216

[1165] Preparation of Polymer PEG-11F

[1166]

[1167] The polymer 11F prepared according to the said Preparation Example 106 and 329.5 mg of polyethylene glycol alkynoate (PEG-alkynoate) were dissolved in 4 mL of CH 2 Cl 2 It was added to a flask in [the substance]. The reaction was carried out at room temperature for 24 hours, and then PEG-11F was obtained.

[1168] Preparation Example 217

[1169] Preparation of Polymer PEG-11G

[1170]

[1171] The polymer 11G prepared according to the said Preparation Example 107 and 383.0 mg of polyethylene glycol alkynoate (PEG-alkynoate) were dissolved in 4 mL of CH 2 Cl 2 It was added to a flask in [the substance]. The reaction was carried out at room temperature for 24 hours, and then PEG-11G was obtained.

[1172] Preparation Example 218

[1173] Preparation of Polymer PEG-11H

[1174]

[1175] The polymer 11H prepared according to the said Preparation Example 108 and 438.3 mg of polyethylene glycol alkynoate (PEG-alkynoate) were dissolved in 4 mL of CH 2 Cl 2 It was added to a flask in [the substance]. The reaction was carried out at room temperature for 24 hours, and then PEG-11H was obtained.

[1176] Preparation Example 219

[1177] Preparation of Polymer PEG-11I

[1178]

[1179] The polymer 11I prepared according to the said Preparation Example 109 and 438.3 mg of polyethylene glycol alkynoate (PEG-alkynoate) were dissolved in 4 mL of CH2 Cl 2 in, and added to the flask. React at room temperature for 24 hours, then PEG-11I was obtained.

[1180] Preparation Example 220

[1181] Preparation of Polymer PEG-11J

[1182]

[1183] The polymer 11J prepared according to the Preparation Example 110 and 285.3 mg of polyethylene glycol alkynoate (PEG-alkynoate) were dissolved in 4 mL of CH 2 Cl 2 in, and added to the flask. React at room temperature for 24 hours, then PEG-11J was obtained.

[1184] Preparation Example 221

[1185] Preparation of Polymer b3A

[1186]

[1187] The amine monomer 3, acrylate monomer A and branched monomer were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. Then, N,N-dimethylformamide (DMF) was put into the flask so that the concentration was 150 mg / ml, and the reaction was carried out at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added in a molar ratio of 2, and the reaction was carried out at room temperature for 24 hours, then b3A was obtained. In the reaction formula in this specification, the indicating that multiple-step reactions occur and intermediates are omitted, is a symbol well-known to those of ordinary skill in the art.

[1188] Preparation Example 222

[1189] Preparation of Polymer b3B

[1190]

[1191] The amine monomer 3, acrylate monomer B and branched monomer were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask so that the concentration was 150 mg / ml, and the reaction was carried out at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added in a molar ratio of 2, and the reaction was carried out at room temperature for 24 hours, then b3B was obtained.

[1192] Preparation Example 223

[1193] Preparation of Polymer b3C

[1194]

[1195] The amine monomer 3, acrylate monomer C and branched monomer were added to a round-bottom flask at a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added at a molar ratio of 2, and reacted at room temperature for 24 hours, and then b3C was obtained.

[1196] Preparation Example 224

[1197] Preparation of Polymer b3D

[1198]

[1199] The amine monomer 3, acrylate monomer D and branched monomer were added to a round-bottom flask at a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added at a molar ratio of 2, and reacted at room temperature for 24 hours, and then b3D was obtained.

[1200] Preparation Example 225

[1201] Preparation of Polymer b3E

[1202]

[1203] The amine monomer 3, acrylate monomer E and branched monomer were added to a round-bottom flask at a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added at a molar ratio of 2, and reacted at room temperature for 24 hours, and then b3E was obtained.

[1204] Preparation Example 226

[1205] Preparation of Polymer b4A

[1206]

[1207] The amine monomer 4, acrylate monomer A and branched monomer were added to a round-bottom flask at a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added at a molar ratio of 2, and reacted at room temperature for 24 hours to obtain b4A.

[1208] Preparation Example 227

[1209] Preparation of Polymer b4B

[1210]

[1211] The amine monomer 4, acrylate monomer B and branched monomer were added to a round-bottom flask at a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added at a molar ratio of 2, and reacted at room temperature for 24 hours to obtain b4B.

[1212] Preparation Example 228

[1213] Preparation of Polymer b4C

[1214]

[1215] The amine monomer 4, acrylate monomer C and branched monomer were added to a round-bottom flask at a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added at a molar ratio of 2, and reacted at room temperature for 24 hours to obtain b4C.

[1216] Preparation Example 229

[1217] Preparation of Polymer b4D

[1218]

[1219] The amine monomer 4, acrylate monomer D and branched monomer were added to a round-bottom flask at a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added at a molar ratio of 2, and reacted at room temperature for 24 hours to obtain b4D.

[1220] Preparation Example 230

[1221] Preparation of Polymer b4E

[1222]

[1223] The amine monomer 4, acrylate monomer E and branched monomer were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added in a 2-molar ratio, and reacted at room temperature for 24 hours to obtain b4E.

[1224] Preparation Example 231

[1225] Preparation of Polymer b7A

[1226]

[1227] The amine monomer 7, acrylate monomer A and branched monomer were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added in a 2-molar ratio, and reacted at room temperature for 24 hours to obtain b7A.

[1228] Preparation Example 232

[1229] Preparation of Polymer b7B

[1230]

[1231] The amine monomer 7, acrylate monomer B and branched monomer were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added in a 2-molar ratio, and reacted at room temperature for 24 hours to obtain b7B.

[1232] Preparation Example 233

[1233] Preparation of Polymer b7C

[1234]

[1235] The amine monomer 7, acrylate monomer C and branched monomer were added to a round-bottom flask at a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added at a 2 molar ratio, and reacted at room temperature for 24 hours to obtain b7C.

[1236] Preparation Example 234

[1237] Preparation of Polymer b7D

[1238]

[1239] The amine monomer 7, acrylate monomer D and branched monomer were added to a round-bottom flask at a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added at a 2 molar ratio, and reacted at room temperature for 24 hours to obtain b7D.

[1240] Preparation Example 235

[1241] Preparation of Polymer b7E

[1242]

[1243] The amine monomer 7, acrylate monomer E and branched monomer were added to a round-bottom flask at a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added at a 2 molar ratio, and reacted at room temperature for 24 hours to obtain b7E.

[1244] Preparation Example 236

[1245] Preparation of Polymer b8A

[1246]

[1247] The amine monomer 8, acrylate monomer A and branched monomer were added to a round-bottom flask at a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added at a 2 molar ratio, and reacted at room temperature for 24 hours to obtain b8A.

[1248] Preparation Example 237

[1249] Preparation of Polymer b8B

[1250]

[1251] The amine monomer 8, acrylate monomer B, and branched monomer were added to a round-bottom flask at a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added at a molar ratio of 2, and reacted at room temperature for 24 hours to obtain b8B.

[1252] Preparation Example 238

[1253] Preparation of Polymer b8C

[1254]

[1255] The amine monomer 8, acrylate monomer C, and branched monomer were added to a round-bottom flask at a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added at a molar ratio of 2, and reacted at room temperature for 24 hours to obtain b8C.

[1256] Preparation Example 239

[1257] Preparation of Polymer b8D

[1258]

[1259] The amine monomer 8, acrylate monomer D, and branched monomer were added to a round-bottom flask at a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added at a molar ratio of 2, and reacted at room temperature for 24 hours to obtain b8D.

[1260] Preparation Example 240

[1261] Preparation of Polymer b8E

[1262]

[1263] The amine monomer 8, acrylate monomer E and branched monomer were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added in a molar ratio of 2, and reacted at room temperature for 24 hours to obtain b8E.

[1264] Preparation Example 241

[1265] Preparation of Polymer b9A

[1266]

[1267] The amine monomer 9, acrylate monomer A and branched monomer were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added in a molar ratio of 2, and reacted at room temperature for 24 hours to obtain b9A.

[1268] Preparation Example 242

[1269] Preparation of Polymer b9B

[1270]

[1271] The amine monomer 9, acrylate monomer B and branched monomer were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added in a molar ratio of 2, and reacted at room temperature for 24 hours to obtain b9B.

[1272] Preparation Example 243

[1273] Preparation of Polymer b9C

[1274]

[1275] The amine monomer 9, acrylate monomer C and branched monomer were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added in a molar ratio of 2, and reacted at room temperature for 24 hours to obtain b9C.

[1276] Preparation Example 244

[1277] Preparation of Polymer b9D

[1278]

[1279] The amine monomer 9, acrylate monomer D and branched monomer were added to a round-bottom flask at a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added at a molar ratio of 2, and reacted at room temperature for 24 hours to obtain b9D.

[1280] Preparation Example 245

[1281] Preparation of Polymer b9E

[1282]

[1283] The amine monomer 9, acrylate monomer E and branched monomer were added to a round-bottom flask at a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added at a molar ratio of 2, and reacted at room temperature for 24 hours to obtain b9E.

[1284] Preparation Example 246

[1285] Preparation of Polymer b10A

[1286]

[1287] The amine monomer 10, acrylate monomer A and branched monomer were added to a round-bottom flask at a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added at a molar ratio of 2, and reacted at room temperature for 24 hours to obtain b10A.

[1288] Preparation Example 247

[1289] Preparation of Polymer b10B

[1290]

[1291] The amine monomer 10, acrylate monomer B, and branched monomer were added to a round-bottom flask at a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added at a 2-molar ratio, and reacted at room temperature for 24 hours to obtain b10B.

[1292] Preparation Example 248

[1293] Preparation of Polymer b10C

[1294]

[1295] The amine monomer 10, acrylate monomer C, and branched monomer were added to a round-bottom flask at a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added at a 2-molar ratio, and reacted at room temperature for 24 hours to obtain b10C.

[1296] Preparation Example 249

[1297] Preparation of Polymer b10D

[1298]

[1299] The amine monomer 10, acrylate monomer D, and branched monomer were added to a round-bottom flask at a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added at a 2-molar ratio, and reacted at room temperature for 24 hours to obtain b10D.

[1300] Preparation Example 250

[1301] Preparation of Polymer b10E

[1302]

[1303] The amine monomer 10, acrylate monomer E, and branched monomer were added to a round-bottom flask at a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added at a 2-molar ratio, and reacted at room temperature for 24 hours to obtain b10E.

[1304] Preparation Example 251

[1305] Preparation of Polymer b11A

[1306]

[1307] The amine monomer 11, acrylate monomer A and branched monomer were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added in a molar ratio of 2, and reacted at room temperature for 24 hours to obtain b11A.

[1308] Preparation Example 252

[1309] Preparation of Polymer b11B

[1310]

[1311] The amine monomer 11, acrylate monomer B and branched monomer were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added in a molar ratio of 2, and reacted at room temperature for 24 hours to obtain b11B.

[1312] Preparation Example 253

[1313] Preparation of Polymer b11C

[1314]

[1315] The amine monomer 11, acrylate monomer C and branched monomer were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added in a molar ratio of 2, and reacted at room temperature for 24 hours to obtain b11C.

[1316] Preparation Example 254

[1317] Preparation of Polymer b11D

[1318]

[1319] The amine monomer 11, acrylate monomer D and branched monomer were added to a round-bottom flask at a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added at a molar ratio of 2, and reacted at room temperature for 24 hours to obtain b11D.

[1320] Preparation Example 255

[1321] Preparation of Polymer b11E

[1322]

[1323] The amine monomer 11, acrylate monomer E and branched monomer were added to a round-bottom flask at a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added at a molar ratio of 2, and reacted at room temperature for 24 hours to obtain b11E.

[1324] Preparation Example 256

[1325] Preparation of Polymer b12A

[1326]

[1327] The amine monomer 12, acrylate monomer A and branched monomer were added to a round-bottom flask at a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added at a molar ratio of 2, and reacted at room temperature for 24 hours to obtain b12A.

[1328] Preparation Example 257

[1329] Preparation of Polymer b12B

[1330]

[1331] The amine monomer 12, acrylate monomer B and branched monomer were added to a round-bottom flask at a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added at a molar ratio of 2, and reacted at room temperature for 24 hours to obtain b12B.

[1332] Production Example 258

[1333] Preparation of Polymer b12C

[1334]

[1335] The amine monomer 12, acrylate monomer C and branched monomer were added to a round-bottom flask at a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added at a molar ratio of 2, and reacted at room temperature for 24 hours to obtain b12C.

[1336] Production Example 259

[1337] Preparation of Polymer b12D

[1338]

[1339] The amine monomer 12, acrylate monomer D and branched monomer were added to a round-bottom flask at a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added at a molar ratio of 2, and reacted at room temperature for 24 hours to obtain b12D.

[1340] Production Example 260

[1341] Preparation of Polymer b12E

[1342]

[1343] The amine monomer 12, acrylate monomer E and branched monomer were added to a round-bottom flask at a molar ratio of 0.4:1:0.2. Then, DMF was charged into the flask to a concentration of 150 mg / ml and reacted at a temperature of 90 °C for 48 hours. Then, after cooling to room temperature, the capping agent was dissolved in DMF at a concentration of 150 mg / ml and added at a molar ratio of 2, and reacted at room temperature for 24 hours to obtain b12E.

[1344] Example 1

[1345] Preparation of Polymer Nanoparticles (PNP)

[1346] mRNA was added to the polymers prepared by any one of the methods described in Preparation Examples 1 to 260, and polymer nanoparticles (PNPs) were prepared by the following method as the nucleic acid delivery carrier of the present invention.

[1347] The polymers prepared by any one of the methods described in Preparation Examples 1 to 260 were diluted in a 25 mM sodium acetate buffer at pH 5.0 at different ratios for each polymer. Then, 6 μl of the polymer solution and 6 μl of the mRNA solution with a concentration of 1 mg / ml were mixed, and then stabilized at a temperature of 4 °C for 30 minutes. Then, it was diluted with 38 μl of PBS so that the total volume was 50 μl and used in the following Test Examples.

[1348] Test Example 1

[1349] Analysis of the synthesized polymers

[1350] The polymers obtained by the methods described in Preparation Examples 1 to 260 were analyzed by the following method.

[1351] 1.1. 1 1H-NMR

[1352] The synthesized polymers were subjected to 1 1H-NMR analysis using deuterated chloroform (CDCl3) solvent, and the results are shown in Figures 2 to 16. As shown in Figures 2 to 16, it was confirmed that all the polymers were prepared normally.

[1353] 1.2. Hydrophobic gel permeation chromatography

[1354] The solvent was removed from the synthesized polymers, and then they were dissolved in tetrahydrofuran (THF) solvent at a concentration of 1 to 3 mg / ml and analyzed by hydrophobic gel permeable chromatography (Hydrophobic GPC).

[1355] Test Example 2

[1356] Analysis of the polymer nanoparticle (PNP) delivery carrier

[1357] The polymer nanoparticles (PNPs) prepared according to Example 1 were analyzed by the following method.

[1358] 2.1. Agarose gel electrophoresis

[1359] The agarose gel electrophoresis of pH-sensitive polymers was carried out by adjusting the N / P ratio of mRNA to the polymer (the ratio of amine (N) contained in the polymer to phosphate (P) contained in mRNA). The pH of 25 mM NaOAc buffer was adjusted to 5.0, 5 μl of the solution dissolving the polymer according to the N / P ratio and 5 μl of mRNA with a concentration of 200 ng / 5 μl were mixed and gently vortexed. Then, it was stabilized at 4 °C for 30 minutes, loaded onto a 1 w / v% agarose gel containing GelRed, and electrophoresed at 100 V for 10 minutes. As a result of the experiment, as Figures 17a to 17c shown, it was confirmed that when complexes were formed at the N / P (Polymer / mRNA) ratio of each polymer, the mRNA band hung at the injection port and did not form in the gel. As an example, the 6B polymer started to form complete complexes from an N / P ratio of 4.

[1360] 2.2. Measurement of Zeta potential and dynamic light scattering

[1361] For pH-sensitive polymers, 6 μl of the solution adjusting the N / P ratio of each polymer and dissolved in 25 mM NaOAc buffer at pH 5.0 and 6 μl of luciferase mRNA (FLuc) with a concentration of 1 mg / ml of SEQ ID NO:1 were mixed and gently vortexed. Then, it was stabilized at 4 °C for 30 minutes, and 38 μl of PBS was added to make the final volume 50 μl.

[1362] For the measurement of the Zeta potential and size of the polymer-mRNA complex, the complex solution as described above was diluted 10-fold in distilled water, and measured using a Zeta potential analyzer and a dynamic light scattering (DLS) instrument. As Figure 18 shown, it was confirmed that the Zeta potential changed according to pH. Thus, it was confirmed that mRNA complexes were formed due to positive charges at low pH, and since it became neutral at the pH in vivo, it could have low toxicity and high mRNA delivery efficiency.

[1363] Test Example 3

[1364] Confirmation of mRNA expression of polymer nanoparticles (PNP) in vivo

[1365] The expression of mRNA was confirmed by intramuscular injection of the polymer nanoparticles prepared according to Example 1 into animals.

[1366] 3.1. Confirmation of mRNA expression in vivo

[1367] Representative polymers were synthesized according to the methods described in the Preparation Examples, and polymer nanoparticles were prepared according to Preparation Example 261 for mRNA expression level screening. The method for forming the polymer-mRNA complex for in vivo injection to confirm the mRNA expression is as follows. 6 μl of a solution prepared by adjusting the weight ratio of each polymer having pH sensitivity and a micelle structure and dissolved in a pH 5.0, 25 mM NaOAc buffer and 6 μl of FLuc of SEQ ID NO:1 at a concentration of 1 mg / ml were mixed and gently vortexed. Then, it was stabilized at a temperature of 4°C for 30 minutes and 38 μl of PBS was added to make the final volume 50 μl. Lipid nanoparticles (LNPs) used as a control group were prepared by the following preparation method. Ionizable lipid (SM-102):DSPC:cholesterol:PEG-lipid were dissolved in ethanol at a molar ratio of 50:10:38.5:1.5. Then, the mRNA diluted in a 25 mM, pH 5.0 sodium acetate buffer and the mixture dissolved in ethanol were mixed so that the volume ratio was 3:1 and the N / P ratio was 5.67. Then, PBS was added and centrifuged at 1000 g for 5 minutes 3 times or more using a 100 kDa Amicon. Finally, it was diluted with PBS so that the concentration of mRNA was 6 μg / 50 μl.

[1368] Table 4

[1369]

[1370] To confirm in vivo mRNA expression using the composition, luciferase mRNA (FLuc) of SEQ ID NO:1 was injected into the gastrocnemius muscle of the hind leg of a mouse at a concentration of 6 μg / 50 μl. Then, mRNA expression was confirmed 24 hours later. 200 μl of luciferin at a concentration of 15 mg / ml was injected into the abdominal cavity of each individual. 10 minutes after injecting luciferin, the exposure time was set to 15 seconds and mRNA expression was confirmed.

[1371] As a result, as shown in Table 5 below, it was confirmed that when the polymer of the present invention was used to deliver mRNA, mRNA expression equal to or higher than that of free mRNA (in the present specification, free mRNA refers to mRNA without a delivery carrier) was exhibited, and among them, 22 polymers exhibited higher mRNA expression than the lipid nanoparticle (LNP) delivery carrier. Also, in the experiment using a representative branched polymer, higher mRNA expression than free mRNA was exhibited. Therefore, it can be seen that the delivery carrier of the present invention can be used as an mRNA delivery carrier.

[1372] Table 5

[1373]

[1374]

[1375] Test Example 4

[1376] Confirmation of mRNA expression of polymer nanoparticles (PNPs) containing PEG in vivo

[1377] Confirmation of the mRNA expression efficiency using polymer nanoparticles (PNPs) having PEG at both ends.

[1378] The expression rate of mRNA was confirmed by intramuscular injection of the polymer nanoparticles prepared according to Example 1 into an animal.

[1379] The mRNA expression efficiency in vivo of 8 polymers (PEG-1A, PEG-1B, PEG-2A, PEG-2B, PEG-3A, PEG-3B, PEG-4A, PEG-4B) prepared according to the preparation examples was screened. The method for forming a polymer-mRNA complex for in vivo injection to confirm the mRNA expression was as follows. 6 μl of a solution in which the weight ratio of each polymer was adjusted and dissolved in a pH 5.0, 25 mM NaOAc buffer solution and 6 μl of luciferase mRNA (FLuc) of SEQ ID NO:1 at a concentration of 1 mg / ml were mixed and gently vortexed. Then, it was stabilized at a temperature of 4°C for 30 minutes and 38 μl of PBS was added so that the final volume was 50 μl.

[1380] To confirm in vivo mRNA expression, the composition was injected into the gastrocnemius muscle of the hind leg of a mouse. Then, mRNA expression was confirmed 24 hours after injection. 200 μl of luciferin at a concentration of 15 mg / ml was injected into the abdominal cavity of each individual. 10 minutes after injecting luciferin, the exposure time was set to 15 seconds and mRNA expression was confirmed.

[1381] As a result, as Figure 19 shown, PEG was included at both ends of the polymers prepared according to Preparation Examples 111 to 220, and as a result of confirming the mRNA expression of the representative polymers at this time, it was confirmed that the expression rate equal to or higher than that of free mRNA was exhibited. Also, it was confirmed that the solubility of 1B prepared according to Preparation Example 2 was poor, but the solubility of PEG-1B in which PEG was bound to both ends was improved, and the mRNA expression was significantly increased. Therefore, it can be seen that the delivery carrier of the present invention can be effectively used as an mRNA delivery carrier.

[1382] Test Example 5

[1383] Confirmation of the expression maintenance time of polymer nanoparticles (PNP) containing PEG in vivo

[1384] To confirm the expression maintenance time of mRNA, after preparing a polymer-mRNA complex using the representative polymer of the preparation example as in Test Example 3, it was injected into the hind leg of a mouse and measured for up to 20 days, and the results are shown in Figure 20 as follows.

[1385] As Figure 20 shown, it was confirmed that the expression of the lipid nanoparticle-mRNA complex (LNP-mRNA) reached a peak at 4 hours and then decreased below the baseline value at about 48 hours, while the expression time of all the polymer nanoparticle-mRNA complexes used in the test was maintained longer than that of the lipid nanoparticle-mRNA complex. In particular, it was confirmed that the mRNA expression of the 6B and 8C polymer complexes was maintained for more than 10 days, indicating that the dosing frequency can be significantly reduced compared to the existing methods in the development of gene therapeutics.

Claims

1. A polymer suitable for intracellular nucleic acid delivery, characterized in that, it comprises repeating units represented by Chemical Formula 1 below: Chemical Formula 1: In the said formula, R1 is a bond or a C1-6 alkylene group, R2 and R3 are each independently (i) hydrogen, (ii) a C1-6 alkyl group that can be substituted by alkylamine or hydroxyl group, (iii) a 5- or 6-membered carbocyclic or heterocyclic ring, or (iv) a C1-6 alkyl group substituted by a 5- or 6-membered carbocyclic or heterocyclic ring, the said R2 and R3 can be connected together to form a C1-6 alkylene group, the said 5- or 6-membered carbocyclic or heterocyclic ring can be substituted by a C1-3 alkyl group or a C1-3 alkoxycarbonyl group, X is a nitrogen atom or a bond, when X is a bond, the said R3 does not exist, R4 is a straight-chain or branched C1-15 alkylene group, and 1 to 5 carbon atoms in the said alkylene group can be substituted by oxygen or sulfur, represents a single bond or a double bond.

2. A polymer suitable for intracellular nucleic acid delivery, characterized in that, it comprises repeating units represented by Chemical Formula 2 below: Chemical Formula 2: In the said formula, R5 is a C1-6 alkylene group, R6 is a straight-chain or branched C1-15 alkylene group, and 1 to 5 carbon atoms in the said alkylene group can be substituted by oxygen or sulfur, represents a single bond or a double bond.

3. The polymer suitable for intracellular nucleic acid delivery according to claim 1, characterized in that, the repeating units represented by Chemical Formula 1 are formed by the reaction between any one of the monomers represented by Chemical Formula 3 to Chemical Formula 13 below and any one of the monomers represented by Chemical Formula 14 to Chemical Formula 23 below:

4. The polymer suitable for intracellular nucleic acid delivery according to claim 2, characterized in that, the repeating units represented by Chemical Formula 2 are formed by the reaction between the monomer represented by Chemical Formula 24 below and any one of the monomers represented by Chemical Formula 14 to Chemical Formula 23 below:

5. A polymer, characterized in that, it comprises repeating units selected from the group consisting of repeating units having the chemical structures shown in the following table:

6. The polymer according to any one of claims 1 to 5, characterized in that, it comprises a branched monomer represented by Chemical Formula 25 below: Chemical Formula 25:

7. The polymer according to any one of claims 1, 3 and 6, characterized in that, it comprises the structure shown in Chemical Formula 26 below: Chemical Formula 26: R1 is a bond or a C1-6 alkylene group, R2 and R3 are each independently (i) hydrogen, (ii) a C1-6 alkyl group that can be substituted by alkylamine or hydroxyl group, (iii) a 5- or 6-membered carbocyclic or heterocyclic ring, or (iv) a C1-6 alkyl group substituted by a 5- or 6-membered carbocyclic or heterocyclic ring, the said R2 and R3 can be connected together to form a C1-6 alkylene group, the said 5- or 6-membered carbocyclic or heterocyclic ring can be substituted by a C1-3 alkyl group or a C1-3 alkoxycarbonyl group, X is a nitrogen atom or a bond, when X is a bond, the said R3 does not exist, R4 is a straight-chain or branched C1-15 alkylene group, and 1 to 5 carbon atoms in the said alkylene group can be substituted by oxygen or sulfur, represents a single bond or a double bond.

8. The polymer according to any one of claims 2, 4 and 6, characterized in that, it comprises the structure shown in Chemical Formula 27 below: Chemical Formula 27: In the said formula, R5 is a C1-6 alkylene group, R6 is a linear or branched C1-15 alkylene group, and 1 to 5 carbon atoms in the alkylene group can be substituted by oxygen or sulfur. represents a single bond or a double bond.

9. The polymer according to any one of claims 1 to 8, characterized in that, one end or both ends of the polymer are connected to a PEG-containing residue having a structure represented by the following Chemical Formula 28: Chemical Formula 28: In the formula, represents a double bond or a triple bond, n is an integer in the range of 1 to 500.

10. A polymer nanoparticle, characterized in that, a complex is formed by the polymer according to any one of claims 1 to 9 and a nucleic acid molecule.

11. The polymer nanoparticle according to claim 10, characterized in that, the nucleic acid molecule is RNA.

12. The polymer nanoparticle according to claim 10, characterized in that, the nucleic acid molecule is DNA.

13. The polymer nanoparticle according to any one of claims 10 to 12, characterized in that, the separated nucleic acid separates the nucleic acid molecule in a pH-dependent manner and delivers it into cells in the body.

14. The polymer nanoparticle according to claim 11, characterized in that, when the nucleic acid molecule in the polymer nanoparticle is delivered into the body, compared with when the same nucleic acid molecule is delivered into the body in the form of a non-polymeric lipid nanoparticle, the expression of the nucleic acid molecule is maintained for a longer time.

15. A method for delivering a nucleic acid molecule into a cell, characterized in that, using the polymer nanoparticle according to any one of claims 10 to 14.

16. The method for delivering a nucleic acid molecule into a cell according to claim 15, characterized in that, the polymer nanoparticle is delivered by a method of parenteral, intramuscular, subcutaneous or intravenous administration.

17. A pharmaceutical composition, characterized in that, comprising the polymer nanoparticle according to any one of claims 10 to 14.

18. The pharmaceutical composition according to claim 17, characterized in that, the pharmaceutical composition is a gene therapy agent.

19. The pharmaceutical composition according to claim 17, characterized in that, the pharmaceutical composition is a vaccine.

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