Polymer-based nucleic acid molecule transporters having ionizable moieties

Abstract

The present invention relates to polymer-based nucleic acid molecule (e.g., mRNA) transporters having ionizable moieties. More specifically, the present invention provides novel polymers that can transport any negatively charged dielectric substance to a desired site, depending on the length of the monomer and polymer. The polymers of the present invention can be effectively used in gene therapy agents or vaccines containing genetic material, such as mRNA, for therapeutic or prophylactic purposes.

Description

[Technical Field]

[0001] The present invention relates to polymer-based nucleic acid molecule transporters having ionizable moieties, and more specifically to the use of polymers based on poly-β-amino esters or poly-β-amino acrylates. Furthermore, the polymers of the present invention can provide high mRNA transport efficiency due to pH sensitivity by synthesizing triple copolymers with PEG attached to both ends. [Background technology]

[0002] mRNA is a substance that contains genetic information for protein production in the human body. mRNA delivery can induce the production of proteins naturally present in the human body, as well as proteins not present in the body. Since the COVID-19 pandemic, the use of mRNA vaccines that activate immune responses through mRNA delivery has led to active development of mRNA delivery systems. While several lipid nanoparticle-based mRNA delivery systems have been developed, they have problems due to rapid diffusion to organs other than the target site (off-target effects) and high immunogenicity, which can lead to various side effects such as myocarditis and pericarditis. Furthermore, vaccines require up to two to four doses, increasing the likelihood of exposure to these side effects. Therefore, there is a need for the development of mRNA delivery systems with high mRNA expression efficiency, low off-target effects, relatively low immunogenicity, and minimal side effects.

[0003] While studying mRNA transport using polymers to improve the drawbacks of the above-mentioned mRNA transporters, the present inventors discovered a novel polymer that is pH-sensitive and has high mRNA transport efficiency in vivo, leading to the completion of the present invention. Summary of the Invention [Problem to be solved by the invention]

[0004] The present invention aims to provide a polymer-based nucleic acid molecule transporter that is pH-sensitive for high nucleic acid molecule transport efficiency and low side effects.

[0005] One aspect of the present invention aims to provide a polymer-based mRNA transporter with a relatively long duration of expression in order to overcome the drawback that mRNA expression is generally short.

[0006] The present invention aims to provide novel polymers for providing polymer-based nucleic acid molecule transporters that are pH sensitive. [Means for solving the problem]

[0007] To achieve the above object, the present invention provides a polymer suitable for intracellular nucleic acid transport, which comprises a repeating unit of the following general formula (1):

[0008] [ka] ···(1)

[0009] In the formula, R1 is a bond or C1-6 alkylene; R2 and R3 are each independently (i) hydrogen, (ii) C1-6 alkyl optionally substituted with alkylamine or hydroxy, (iii) a 5- or 6-membered carbocyclic or heterocyclic ring, or (iv) C1-6 alkyl substituted with a 5- or 6-membered carbocyclic or heterocyclic ring; R2 and R3 may be bonded to each other to form a C1-6 alkylene group, the 5- or 6-membered carbocyclic or heterocyclic ring may be substituted with C1-3 alkyl or C1-3 alkoxyacyl; X is a nitrogen atom or a bond, and when X is a bond, R3 is absent; R4 is a straight or branched C1-15 alkylene, in which 1 to 5 carbon atoms may be replaced by oxygen or sulfur; JPEG2026503871000003.jpg25 may represent a single or double bond.

[0010] The number of the repeating units may be n (an integer of 1 to 500), and in that case, general formula (1) is represented as follows: JPEG2026503871000004.jpg2580 (The definitions of the groups are as defined for general formula (1) above.)

[0011] The present invention provides a polymer having a repeating unit of the following general formula (2):

[0012] [ka] ···(2)

[0013] During the ceremony, R5 is C1-6 alkylene; R6 is a straight or branched C1-15 alkylene, in which 1 to 5 carbon atoms may be replaced by oxygen or sulfur; JPEG2026503871000006.jpg25 may represent a single or double bond.

[0014] The number of the repeating units may be n (an integer of 1 to 500), and in that case, general formula (2) is represented as follows: JPEG2026503871000007.jpg2480 (The definitions of the groups are as defined for general formula (2) above.)

[0015] In one embodiment, the polymer may be a polymer in which the repeating unit of general formula (1) is formed by a reaction between any one of the monomers of the following general formulae (3) to (13) and any one of the monomers of the following general formulae (14) to (23). JPEG2026503871000008.jpg9482 JPEG2026503871000009.jpg8680

[0016] In one embodiment, the polymer may be a polymer in which the repeating unit of the general formula (2) is formed by a reaction between a monomer of the following general formula (24) and any one of the monomers of the following general formulae (14) to (23). JPEG2026503871000010.jpg10982

[0017] The present invention provides a polymer comprising a repeating unit selected from the group consisting of the repeating units in the table below. JPEG2026503871000011.jpg10878 JPEG2026503871000012.jpg9480 JPEG2026503871000013.jpg10080 JPEG2026503871000014.jpg11280 JPEG2026503871000015.jpg10380 JPEG2026503871000016.jpg10780 JPEG2026503871000017.jpg10380 JPEG2026503871000018.jpg9180 JPEG2026503871000019.jpg9080 JPEG2026503871000020.jpg11380 JPEG2026503871000021.jpg9580 JPEG2026503871000022.jpg11080 JPEG2026503871000023.jpg10780 JPEG2026503871000024.jpg10180 JPEG2026503871000025.jpg11477 JPEG2026503871000026.jpg10880 JPEG2026503871000027.jpg11479 JPEG2026503871000028.jpg10380 JPEG2026503871000029.jpg11478 JPEG2026503871000030.jpg10880 JPEG2026503871000031.jpg10980 JPEG2026503871000032.jpg9680 JPEG2026503871000033.jpg10480 JPEG2026503871000034.jpg5180 JPEG2026503871000035.jpg11478 JPEG2026503871000036.jpg11477 JPEG2026503871000037.jpg10880 JPEG2026503871000038.jpg10680 JPEG2026503871000039.jpg11477 JPEG2026503871000040.jpg11477 JPEG2026503871000041.jpg11478 JPEG2026503871000042.jpg11479 JPEG2026503871000043.jpg11180 JPEG2026503871000044.jpg11478 JPEG2026503871000045.jpg10680 JPEG2026503871000046.jpg10680 JPEG2026503871000047.jpg9580 JPEG2026503871000048.jpg9280 JPEG2026503871000049.jpg11476 JPEG2026503871000050.jpg10380 JPEG2026503871000051.jpg10580 JPEG2026503871000052.jpg9580 JPEG2026503871000053.jpg9280 JPEG2026503871000054.jpg11477 JPEG2026503871000055.jpg11478 JPEG2026503871000056.jpg11476 JPEG2026503871000057.jpg11476 JPEG2026503871000058.jpg11477 JPEG2026503871000059.jpg11477 JPEG2026503871000060.jpg11477 JPEG2026503871000061.jpg11477 JPEG2026503871000062.jpg11480 JPEG2026503871000063.jpg11080 JPEG2026503871000064.jpg11480 JPEG2026503871000065.jpg10480 JPEG2026503871000066.jpg10580 JPEG2026503871000067.jpg9780 JPEG2026503871000068.jpg9380 JPEG2026503871000069.jpg11478 JPEG2026503871000070.jpg10380 JPEG2026503871000071.jpg10280 JPEG2026503871000072.jpg9680 JPEG2026503871000073.jpg9280 JPEG2026503871000074.jpg11476 JPEG2026503871000075.jpg10680 JPEG2026503871000076.jpg10580 JPEG2026503871000077.jpg9680 JPEG2026503871000078.jpg9380 JPEG2026503871000079.jpg11476 JPEG2026503871000080.jpg10380 JPEG2026503871000081.jpg10380 JPEG2026503871000082.jpg9680 JPEG2026503871000083.jpg9280 JPEG2026503871000084.jpg11477 JPEG2026503871000085.jpg10480 JPEG2026503871000086.jpg10480 JPEG2026503871000087.jpg9780 JPEG2026503871000088.jpg9480 JPEG2026503871000089.jpg11477 JPEG2026503871000090.jpg11477 JPEG2026503871000091.jpg11477 JPEG2026503871000092.jpg10980 JPEG2026503871000093.jpg10480 JPEG2026503871000094.jpg11479 JPEG2026503871000095.jpg11476 JPEG2026503871000096.jpg11479 JPEG2026503871000097.jpg11480 JPEG2026503871000098.jpg11180 JPEG2026503871000099.jpg11478 JPEG2026503871000100.jpg10380 JPEG2026503871000101.jpg10680 JPEG2026503871000102.jpg9580 JPEG2026503871000103.jpg9380 JPEG2026503871000104.jpg11478 JPEG2026503871000105.jpg10280 JPEG2026503871000106.jpg10480 JPEG2026503871000107.jpg9580 JPEG2026503871000108.jpg9280 JPEG2026503871000109.jpg11478 JPEG2026503871000110.jpg11476 JPEG2026503871000111.jpg11479 JPEG2026503871000112.jpg11477 JPEG2026503871000113.jpg11476 JPEG2026503871000114.jpg11477 JPEG2026503871000115.jpg11477 JPEG2026503871000116.jpg11477 JPEG2026503871000117.jpg11480 JPEG2026503871000118.jpg11080 JPEG2026503871000119.jpg11477 JPEG2026503871000120.jpg10580 JPEG2026503871000121.jpg10480 JPEG2026503871000122.jpg9680 JPEG2026503871000123.jpg9280 JPEG2026503871000124.jpg11477 JPEG2026503871000125.jpg10380 JPEG2026503871000126.jpg10280 JPEG2026503871000127.jpg9480 JPEG2026503871000128.jpg9180 JPEG2026503871000129.jpg11477 JPEG2026503871000130.jpg11473 JPEG2026503871000131.jpg11478 JPEG2026503871000132.jpg11280 JPEG2026503871000133.jpg11080 JPEG2026503871000134.jpg11477 JPEG2026503871000135.jpg10380 JPEG2026503871000136.jpg10380 JPEG2026503871000137.jpg10980 JPEG2026503871000138.jpg10780 JPEG2026503871000139.jpg11477 JPEG2026503871000140.jpg11477 JPEG2026503871000141.jpg10680 JPEG2026503871000142.jpg11280 JPEG2026503871000143.jpg11380 JPEG2026503871000144.jpg11480 JPEG2026503871000145.jpg11480 JPEG2026503871000146.jpg11480 JPEG2026503871000147.jpg11477 JPEG2026503871000148.jpg11479 JPEG2026503871000149.jpg11480 JPEG2026503871000150.jpg11480 JPEG2026503871000151.jpg11080 JPEG2026503871000152.jpg10980 JPEG2026503871000153.jpg11479 JPEG2026503871000154.jpg11480 JPEG2026503871000155.jpg11480 JPEG2026503871000156.jpg11380 JPEG2026503871000157.jpg11480 JPEG2026503871000158.jpg11478 JPEG2026503871000159.jpg11280 JPEG2026503871000160.jpg11180 JPEG2026503871000161.jpg11180 JPEG2026503871000162.jpg11380 JPEG2026503871000163.jpg11080 JPEG2026503871000164.jpg11480 JPEG2026503871000165.jpg11480 JPEG2026503871000166.jpg11480 JPEG2026503871000167.jpg11280 JPEG2026503871000168.jpg11180 JPEG2026503871000169.jpg11479 JPEG2026503871000170.jpg11280 JPEG2026503871000171.jpg11479 JPEG2026503871000172.jpg11280 JPEG2026503871000173.jpg11180 JPEG2026503871000174.jpg11280 JPEG2026503871000175.jpg11480 JPEG2026503871000176.jpg11480 JPEG2026503871000177.jpg11380 JPEG2026503871000178.jpg11380 JPEG2026503871000179.jpg11479 JPEG2026503871000180.jpg11479 JPEG2026503871000181.jpg11180 JPEG2026503871000182.jpg11180 JPEG2026503871000183.jpg11480 JPEG2026503871000184.jpg11480 (wherein n is an integer of 1 to 500)

[0018] In one embodiment, the polymer may further comprise a branched monomer of the following general formula (25):

[0019] [ka] ···(twenty five)

[0020] When the polymer according to the present invention contains the structure of the general formula (25), the polymer may contain the structure of the following general formula (26).

[0021] [ka] ···(26)

[0022] R1 is a bond or C1-6 alkylene; R2 and R3 are each independently (i) hydrogen, (ii) C1-6 alkyl optionally substituted with alkylamine or hydroxy, (iii) a 5- or 6-membered carbocyclic or heterocyclic ring, or (iv) C1-6 alkyl substituted with a 5- or 6-membered carbocyclic or heterocyclic ring; R2 and R3 may be bonded to each other to form a C1-6 alkylene group, the 5- or 6-membered carbocyclic or heterocyclic ring may be substituted with C1-3 alkyl or C1-3 alkoxyacyl; X is a nitrogen atom or a bond, and when X is a bond, R3 is absent; R4 is a straight or branched C1-15 alkylene, in which 1 to 5 carbon atoms may be replaced by oxygen or sulfur; JPEG2026503871000187.jpg25 may represent a single or double bond.

[0023] The number of the repeating units may be n (an integer of 1 to 500), and in that case, general formula (26) is represented as follows: JPEG2026503871000188.jpg2980 (The definition of the groups is as defined for the general formula (26) above.)

[0024] When the polymer according to the present invention contains the structure of the general formula (25), the polymer may contain the structure of the following general formula (27).

[0025] [ka] ···(27)

[0026] During the ceremony, R5 is C1-6 alkylene; R6 is a straight or branched C1-15 alkylene, in which 1 to 5 carbon atoms may be replaced by oxygen or sulfur; JPEG2026503871000190.jpg25 may represent a single or double bond.

[0027] The number of the repeating units may be n (an integer of 1 to 500), and in that case, general formula (27) is represented as follows: JPEG2026503871000191.jpg2880 (The definition of the groups is as defined for the general formula (27) above.)

[0028] In one embodiment, the polymer may be linked at one or both ends to a PEG-containing residue having the structure of general formula (28):

[0029] [ka] ···(28)

[0030] During the ceremony, JPEG2026503871000193.jpg25 represents a double or triple bond, n may be an integer ranging from 1 to 500. The present invention provides polymeric nanoparticles in which the polymer and a nucleic acid molecule are complexed. The polymeric nanoparticles according to the present invention preferably do not include lipid nanoparticles (LNPs).

[0031] The nucleic acid molecule that can be contained in the polymer nanoparticles according to the present invention may be RNA, preferably mRNA.

[0032] The nucleic acid molecules that may be contained in the polymer nanoparticles according to the present invention may be DNA.

[0033] The polymeric nanoparticles of the present invention may allow nucleic acid molecules to be separated in a pH-dependent manner and delivered to cells in the body.

[0034] The polymeric nanoparticles of the present invention, when delivered to the body, may maintain expression of a nucleic acid molecule for a longer period of time than when the same nucleic acid molecule is delivered to the body in the form of a non-polymeric lipid nanoparticle.

[0035] The present invention provides a method for delivering nucleic acid molecules into cells using the polymer nanoparticles. The method for delivering nucleic acid molecules according to the present invention preferably does not use lipid nanoparticles (LNPs).

[0036] The polymeric nanoparticles of the present invention may be delivered by parenteral, intramuscular, subcutaneous or intravenous administration.

[0037] The present invention provides a pharmaceutical composition comprising the polymer nanoparticles. The pharmaceutical composition according to the present invention preferably does not comprise lipid nanoparticles (LNPs).

[0038] The pharmaceutical composition containing the polymer nanoparticles of the present invention may be a gene therapy agent.

[0039] The pharmaceutical composition comprising the polymeric nanoparticles of the present invention may be a vaccine. [Effects of the Invention]

[0040] The pH-sensitive polymer-based nucleic acid molecule transporter of the present invention has high transport efficiency of nucleic acid molecules and can be used as an excellent transporter. In particular, the nucleic acid molecule transporter of the present invention can be used for therapeutic gene delivery and mRNA vaccines.

[0041] Furthermore, depending on the length of the monomer and polymer, the nucleic acid molecule can be transported to a desired site, and the nucleic acid molecule can be released in response to a specific stimulus via an additional stimulus-sensitive linker.

[0042] Furthermore, the nucleic acid molecule transporter of the present invention can be degraded after releasing the nucleic acid molecule inside the cell, and therefore has fewer side effects. [Brief explanation of the drawings]

[0043] [Figure 1] FIG. 1 is a schematic diagram of the synthesis of a polymer transporter according to the present invention, and a schematic diagram of a polymeric nanoparticle (PNP) comprising the polymer transporter and mRNA. [Figure 2A] 1 is a graph showing the results of 1H-NMR of polymers 1A to 1E. [Figure 2B] 1 is a graph showing the results of 1H-NMR of polymers 1A to 1E. [Figure 2C] 1 is a graph showing the results of 1H-NMR of polymers 1A to 1E. [Figure 2D] 1 is a graph showing the results of 1H-NMR of polymers 1A to 1E. [Figure 2E] 1 is a graph showing the results of 1H-NMR of polymers 1A to 1E. [Figure 3A] 1 is a graph showing the results of 1H-NMR of polymers 2A to 2E. [Figure 3B] 1 is a graph showing the results of 1H-NMR of polymers 2A to 2E. [Figure 3C] 1 is a graph showing the results of 1H-NMR of polymers 2A to 2E. [Figure 3D] 1 is a graph showing the results of 1H-NMR of polymers 2A to 2E. [Figure 3E] 1 is a graph showing the results of 1H-NMR of polymers 2A to 2E. [Figure 4A] 1 is a graph showing the results of 1H-NMR of polymers 3A to 3E. [Figure 4B] 1 is a graph showing the results of 1H-NMR of polymers 3A to 3E. [Figure 4C]1 is a graph showing the results of 1H-NMR of polymers 3A to 3E. [Figure 4D] 1 is a graph showing the results of 1H-NMR of polymers 3A to 3E. [Figure 4E] 1 is a graph showing the results of 1H-NMR of polymers 3A to 3E. [Figure 5A] 1 is a graph showing the results of 1H-NMR of polymers 4A to 4E. [Figure 5B] 1 is a graph showing the results of 1H-NMR of polymers 4A to 4E. [Figure 5C] 1 is a graph showing the results of 1H-NMR of polymers 4A to 4E. [Figure 5D] 1 is a graph showing the results of 1H-NMR of polymers 4A to 4E. [Figure 5E] 1 is a graph showing the results of 1H-NMR of polymers 4A to 4E. [Figure 6A] 1 is a graph showing the results of 1H-NMR of polymers 5A to 5E. [Figure 6B] 1 is a graph showing the results of 1H-NMR of polymers 5A to 5E. [Figure 6C] 1 is a graph showing the results of 1H-NMR of polymers 5A to 5E. [Figure 6D] 1 is a graph showing the results of 1H-NMR of polymers 5A to 5E. [Figure 6E] 1 is a graph showing the results of 1H-NMR of polymers 5A to 5E. [Figure 7A] 1 is a graph showing the results of 1H-NMR of polymers 6A to 6E. [Figure 7B] 1 is a graph showing the results of 1H-NMR of polymers 6A to 6E. [Figure 7C] 1 is a graph showing the results of 1H-NMR of polymers 6A to 6E. [Figure 7D] 1 is a graph showing the results of 1H-NMR of polymers 6A to 6E. [Figure 7E] 1 is a graph showing the results of 1H-NMR of polymers 6A to 6E. [Figure 8A] 1 is a graph showing the results of 1H-NMR of polymers 7A to 7E. [Figure 8B] 1 is a graph showing the results of 1H-NMR of polymers 7A to 7E. [Figure 8C] 1 is a graph showing the results of 1H-NMR of polymers 7A to 7E. [Figure 8D] 1 is a graph showing the results of 1H-NMR of polymers 7A to 7E. [Figure 8E] 1 is a graph showing the results of 1H-NMR of polymers 7A to 7E. [Figure 9A] 1 is a graph showing the results of 1H-NMR of polymers 8A to 8E. [Figure 9B] 1 is a graph showing the results of 1H-NMR of polymers 8A to 8E. [Figure 9C] 1 is a graph showing the results of 1H-NMR of polymers 8A to 8E. [Figure 9D] 1 is a graph showing the results of 1H-NMR of polymers 8A to 8E. [Figure 9E] 1 is a graph showing the results of 1H-NMR of polymers 8A to 8E. [Figure 10A] 1 is a graph showing the results of 1H-NMR of polymers 9A to 9E. [Figure 10B] 1 is a graph showing the results of 1H-NMR of polymers 9A to 9E. [Figure 10C] 1 is a graph showing the results of 1H-NMR of polymers 9A to 9E. [Figure 10D] 1 is a graph showing the results of 1H-NMR of polymers 9A to 9E. [Figure 10E] 1 is a graph showing the results of 1H-NMR of polymers 9A to 9E. [Figure 11A] 1 is a graph showing the results of 1H-NMR of polymers 10A to 10E. [Figure 11B] 1 is a graph showing the results of 1H-NMR of polymers 10A to 10E. [Figure 11C] 1 is a graph showing the results of 1H-NMR of polymers 10A to 10E. [Figure 11D] 1 is a graph showing the results of 1H-NMR of polymers 10A to 10E. [Figure 11E] 1 is a graph showing the results of 1H-NMR of polymers 10A to 10E. [Figure 12A] 1 is a graph showing the 1H-NMR results of polymers 11A to 11E. [Figure 12B] 1 is a graph showing the 1H-NMR results of polymers 11A to 11E. [Figure 12C] 1 is a graph showing the 1H-NMR results of polymers 11A to 11E. [Figure 12D] 1 is a graph showing the 1H-NMR results of polymers 11A to 11E. [Figure 12E] 1 is a graph showing the 1H-NMR results of polymers 11A to 11E. [Figure 13A] 1 is a graph showing the 1H-NMR results of polymers PEG-1A and PEG-1B. [Figure 13B] 1 is a graph showing the 1H-NMR results of polymers PEG-1A and PEG-1B. [Figure 14A] 1 is a graph showing the 1H-NMR results of polymers PEG-2A and PEG-2B. [Figure 14B] 1 is a graph showing the 1H-NMR results of polymers PEG-2A and PEG-2B. [Figure 15A] 1 is a graph showing the 1H-NMR results of polymers PEG-3A and PEG-3B. [Figure 15B] 1 is a graph showing the 1H-NMR results of polymers PEG-3A and PEG-3B. [Figure 16A] 1 is a graph showing the H-NMR results of polymers PEG-4A and PEG-4B. [Figure 16B] 1 is a graph showing the H-NMR results of polymers PEG-4A and PEG-4B. [Figure 17A] 1 is a photograph showing the results of electrophoresis of polymer nanoparticles (PNP) according to the present invention. [Figure 17B] 1 is a photograph showing the results of electrophoresis of polymer nanoparticles (PNP) according to the present invention. [Figure 17C]1 is a photograph showing the results of electrophoresis of polymer nanoparticles (PNP) according to the present invention. [Figure 18] 1 is a graph showing the zeta potential of polymer nanoparticles (PNPs) according to the present invention. [Figure 19] 1 is a photograph showing in vivo mRNA delivery by polymeric nanoparticles (PNPs) of the present invention. [Figure 20] 1 is a graph showing the duration of expression of mRNA transported in polymeric nanoparticles (PNPs) according to the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0044] The present invention will be described in detail below with reference to the following examples so that those skilled in the art can easily carry out the present invention. However, since the present invention can be embodied in various forms, it is not limited to the following examples.

[0045] Throughout this specification, when a part is said to "comprise" a certain element, this does not mean that it excludes other elements, but that it may further include other elements, unless otherwise specified.

[0046] Throughout this specification, the terms "polymer," "macromolecule," and "polymeric" are used interchangeably and with the same meaning.

[0047] As used herein, the term "repeating unit" when describing a "polymer" refers to a structure in which the same structure is repeated two or more times throughout the length of the polymer, and does not necessarily mean that the polymer is composed solely of that repeating unit. For example, a polymer may further include branched structures and / or end-capping agents in addition to a given repeating unit.

[0048] As used herein, the term "substituted," e.g., "substituted alkyl," means that at least one hydrogen atom of an alkyl is independently replaced with a non-hydrogen substituent. The substituents include any of the substituents described herein, such as, but not limited to, halogen, hydroxyl, alkyl, hydroxyalkyl, haloalkyl, cyanoalkyl, alkoxyalkyl, carbonyl (e.g., carboxyl, alkoxycarbonyl, formyl, or acyl), thiocarbonyl (e.g., thioester, thioacetate, or thioformate), alkoxyl, phosphoryl, phosphate, phosphonate, phosphinate, amino, amido, amidine, imine, cyano, nitro, azido, sulfhydryl, alkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, heterocyclyl, aralkyl, aryl, or heteroaryl. Residues substituted on the hydrocarbon chain may, in some cases, be substituted themselves.

[0049] In the present invention, an "alkyl group" is a substituted or unsubstituted hydrocarbon having primary, secondary, tertiary, and / or quaternary carbon atoms, including saturated aliphatic groups that may be linear, branched, cyclic, or a combination thereof. For example, an alkyl group may have 1 to 20 carbon atoms (i.e., C1 to C20 alkyl), 1 to 10 carbon atoms (i.e., C1 to C10 alkyl), or 1 to 6 carbon atoms (i.e., C1 to C6 alkyl).Examples of suitable alkyl groups include methyl (Me, -CH), ethyl (Et, -CHCH), 1-propyl (n-Pr, n-propyl, -CHCHCH), 2-propyl (i-Pr, i-propyl, -CH(CH)), 1-butyl (n-Bu, n-butyl, -CHCHCHCHCH), 2-methyl-1-propyl (i-Bu, i-butyl, -CHCH(CH)), 2-butyl (s-Bu, s-butyl, -CH(CH)). 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 (-CH2CH2CH2CH2CH2CH2CH3), 2-hexyl (-CH(CH3)CH2CH2CH2CH2CH3), 3-hexyl (-CH(CH2CH3)(CH2CH2CH3)), 2-methyl-2-pentyl (-C(CH3)2CH2CH2CH3), 3-methyl-2-pentyl (-CH(CH3)CH(CH3)CH2CH3), 4-methyl Examples include, but are not limited to, 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).

[0050] Furthermore, the term "alkyl," as used throughout the specification, examples, and claims, is intended to include both unsubstituted and substituted alkyl groups, the latter of which refers to alkyl residues having substituents replacing a hydrogen on at least one carbon of the hydrocarbon backbone, including haloalkyl groups such as trifluoromethyl.

[0051] The term "alkylene," as used herein, refers to a saturated hydrocarbon group having two valencies, which may be branched, straight-chain, cyclic, or a combination thereof, and which is derived by removing two hydrogen atoms from the same carbon atom or two different carbon atoms of a parent alkane. For example, an alkylene group may have 1 to 20 carbon atoms, 1 to 10 carbon atoms, or 1 to 6 carbon atoms. Examples of suitable alkylene groups include, but are not limited to, methylene (-CH-) and 1,2-ethylene (-CH-CH-).

[0052] As used herein, the term "heterocycle" refers to a substituted or unsubstituted, monovalent or divalent, saturated or partially saturated, non-aromatic ring system, preferably a 3- to 10-membered ring, more preferably a 3- to 7-membered ring, whose ring system contains at least one heteroatom, preferably 1 to 4 heteroatoms, more preferably 1 to 2 heteroatoms. The terms "heterocyclyl," "heterocycle," "heterocyclic," and "heterocycloalkyl" also include polycyclic ring systems having at least two cyclic rings in which at least two carbons are common to two or more adjacent rings, where at least one of the rings is heterocyclic; for example, the other cyclic rings may be cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, and / or heterocyclyl. Bicyclic and polycyclic heterocyclic ring systems may be fused, bridged, or spiro ring systems. Substituted heterocycles include heterocyclic rings containing, for example, carbonyl groups, substituted with any of the substituents disclosed herein. Heterocyclyl groups include, for example, piperidine, piperazine, pyrrolidine, morpholine, lactones, lactams, and the like.Further exemplary heterocycles include dihydropyridyl, dihydroindolyl, tetrahydropyridyl (piperidyl), tetrahydrothiophenyl, sulfur-oxidized tetrahydrothiophenyl, indolenyl, piperidinyl, 4-piperidinyl, pyrrolidinyl, 2-pyrrolidonyl, pyrrolinyl, tetrahydrofuranyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, octahydroisoquinolinyl, 6H-1,2,5-thiadiazinyl, 2H,6H-1,5,2-dithiazinyl, pyranyl, chromenyl, xanthenyl, phenoxathinyl, 2H-pyrrolyl, 3H-indophenyl, 4H-pyrrolyl ... Examples of alkyl groups include, but are not limited to, aryl, 4H-quinolidinyl, 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).

[0053] As used herein, the term "carbocycle" refers to a non-aromatic saturated or unsaturated, monovalent or divalent ring, which may be monocyclic, bicyclic, or polycyclic, in which each atom of the ring is carbon. Cycloalkyl groups may have 3 to 7 carbon atoms as monocycles, 7 to 12 carbon atoms as bicycles, and up to about 20 carbon atoms as polycycles. Monocyclic cycloalkyls have 3 to 7 ring atoms, more typically 5 or 6 ring atoms. Bicyclic cycloalkyls may have 7 to 12 ring atoms and may be fused, spirocyclic, or bridged ring systems. In exemplary cycloalkyl groups, the atoms may be arranged in a bicyclo[4,5], [5,5], [5,6], or [6,6] system. In certain embodiments, cycloalkyls contain 3 to 20 atoms, or 3 to 10 atoms, and more preferably 3 to 7 atoms. Examples of cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, etc. Unless otherwise specified, cycloalkyl may be optionally substituted with at least one substituent described herein.

[0054] The term "alkoxyacyl," as used herein, refers to the group -C(=O)OR, where R is alkyl, as defined herein, and may be substituted or unsubstituted.

[0055] In this specification, the term " JPEG2026503871000194.jpg25" represents a single or double bond, according to convention used in the art.

[0056] In this specification, the term " JPEG2026503871000195.jpg29" represents a bond connected to other entities, according to conventions used in the art.

[0057] The term "amine" as used herein refers to -NH in which the hydrogen atom is substituted or unsubstituted with a substituent such as alkyl, aryl, etc., wherein the substituent such as alkyl or aryl replacing the hydrogen atom is as defined herein and may be substituted or unsubstituted.

[0058] As used herein, the term "amine monomer" refers to a monomer that contains an amine functional group and may preferably be selected from the group consisting of the amine monomers set forth in Table 1 below.

[0059] [Table 1]

[0060] The term "acrylate monomer" as used herein refers to a monomer in the form of an ester derivative of acrylic acid, and may be selected from the group consisting of the acrylate monomers set forth in Table 2 below.

[0061] [Table 2]

[0062] As used herein, the term "alkynoate monomer" refers to a monomer in the form of an ester derivative of an alkynoic acid, and may be selected from the group consisting of the alkynoate monomers set forth in Table 3 below.

[0063] [Table 3]

[0064] The polymers according to the present invention are characterized by comprising an amine monomer and an acrylate or alkynoate monomer, the two monomers being linked together in alternating fashion (see schematic diagram in FIG. 1).

[0065] The polymers of the present invention are characterized by having an ionizable moiety, where "ionizable moiety" refers to a part of the polymer that is ionizable depending on pH. For example, it may be a tertiary amine present in the polymer chemical structure, and those skilled in the art will be familiar with which moieties are ionizable depending on pH.

[0066] The present invention will be described in more detail below with reference to examples. However, the following examples are for illustrative purposes only and are not intended to limit the scope of the present invention.

[0067] [Manufacturing Example 1] Preparation of Polymer 1A JPEG2026503871000199.jpg1882 Acrylate Monomer A (1000 mg) was placed in a two-neck round-bottom flask, followed by amine Monomer 1 at a molar ratio of 1.04 to the acrylate monomer. Dichloromethane (CHCl; DCM) was added to the flask to a final concentration of 1000 mg / mL. The mixture was then refluxed at 50°C for 48 hours to yield Polymer 1A having an ionizable moiety according to the present invention.

[0068] [Manufacturing Example 2] Preparation of Polymer 1B JPEG2026503871000200.jpg1582 Acrylate Monomer B (1000 mg) was placed in a two-neck round-bottom flask, followed by the addition of Amine Monomer 1 at a molar ratio of 1.04 to the acrylate monomer. DCM was added to the flask to a final concentration of 1000 mg / mL. The mixture was then refluxed at 50°C for 48 hours to yield Polymer 1B having an ionizable moiety according to the present invention.

[0069] [Manufacturing Example 3] Preparation of Polymer 1C JPEG2026503871000201.jpg1782 Acrylate Monomer C (1000 mg) was placed in a two-neck round-bottom flask, and then amine Monomer 1 was added to the flask at a molar ratio of 1.04 to the acrylate monomer. DCM was added to the flask to a final concentration of 1000 mg / mL. The mixture was then refluxed at 50°C for 48 hours to yield Polymer 1C having an ionizable moiety according to the present invention.

[0070] [Manufacturing Example 4] Fabrication of polymer 1D JPEG2026503871000202.jpg1682 Acrylate Monomer D (1000 mg) was placed in a two-neck round-bottom flask, followed by the addition of Amine Monomer 1 at a molar ratio of 1.04 to the acrylate monomer. DCM was added to the flask to a final concentration of 1000 mg / mL. The mixture was then refluxed at 50°C for 48 hours to yield Polymer 1D having an ionizable moiety according to the present invention.

[0071] [Manufacturing Example 5] Preparation of Polymer 1E JPEG2026503871000203.jpg1282 Acrylate Monomer E (1000 mg) was placed in a two-neck round-bottom flask, followed by the addition of Amine Monomer 1 at a molar ratio of 1.04 to the acrylate monomer. DCM was added to the flask to a final concentration of 2500 mg / mL. The mixture was then refluxed at 50°C for 48 hours to yield Polymer 1E having an ionizable moiety according to the present invention.

[0072] [Manufacturing Example 6] Preparation of Polymer 2A JPEG2026503871000204.jpg1582 Acrylate Monomer A (1000 mg) was placed in a 20 mL vial, and then amine Monomer 2 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. Dimethyl sulfoxide (DMSO) was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain Polymer 2A having an ionizable moiety according to the present invention.

[0073] [Manufacturing Example 7] Preparation of Polymer 2B JPEG2026503871000205.jpg1582 Acrylate Monomer B (1000 mg) was placed in a 20 mL vial, and then amine Monomer 2 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain Polymer 2B having an ionizable moiety according to the present invention.

[0074] [Manufacturing Example 8] Production of Polymer 2C JPEG2026503871000206.jpg1682 Acrylate Monomer C (1000 mg) was placed in a 20 mL vial, and then amine Monomer 2 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain Polymer 2C having an ionizable moiety according to the present invention.

[0075] [Manufacturing Example 9] Polymer 2D fabrication JPEG2026503871000207.jpg1282 Acrylate Monomer D (1000 mg) was placed in a 20 mL vial, and then amine Monomer 2 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain Polymer 2D having an ionizable moiety according to the present invention.

[0076] [Manufacturing Example 10] Production of Polymer 2E JPEG2026503871000208.jpg1482 Acrylate Monomer E (1000 mg) was placed in a 20 mL vial, and then amine Monomer 2 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 2500 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain Polymer 2E having an ionizable moiety according to the present invention.

[0077] [Manufacturing Example 11] Preparation of Polymer 3A JPEG2026503871000209.jpg1882 Acrylate Monomer A (1000 mg) was placed in a 20 mL vial, and then amine Monomer 3 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain Polymer 3A having an ionizable moiety according to the present invention.

[0078] [Manufacturing Example 12] Preparation of Polymer 3B JPEG2026503871000210.jpg1982 Acrylate Monomer B (1000 mg) was placed in a 20 mL vial, and then amine Monomer 3 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain Polymer 3B having an ionizable moiety according to the present invention.

[0079] [Manufacturing Example 13] Polymer 3C production JPEG2026503871000211.jpg1882 Acrylate monomer C (1000 mg) was placed in a 20 mL vial, and then amine monomer 3 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain polymer 3C having an ionizable moiety according to the present invention.

[0080] [Manufacturing Example 14] Polymer 3D Fabrication JPEG2026503871000212.jpg1782 Acrylate Monomer D (1000 mg) was placed in a 20 mL vial, and then amine Monomer 3 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain Polymer 3D having an ionizable moiety according to the present invention.

[0081] [Manufacturing Example 15] Production of Polymer 3E JPEG2026503871000213.jpg1482 Acrylate Monomer E (1000 mg) was placed in a 20 mL vial, and then amine Monomer 3 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 2500 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain Polymer 3E having an ionizable moiety according to the present invention.

[0082] [Manufacturing Example 16] Preparation of Polymer 4A JPEG2026503871000214.jpg1882 Acrylate Monomer A (1000 mg) was placed in a 20 mL vial, and then amine Monomer 4 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain Polymer 4A having an ionizable moiety according to the present invention.

[0083] [Manufacturing Example 17] Preparation of Polymer 4B JPEG2026503871000215.jpg1782 Acrylate Monomer B (1000 mg) was placed in a 20 mL vial, and then amine Monomer 4 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain Polymer 4B having an ionizable moiety according to the present invention.

[0084] [Manufacturing Example 18] Production of Polymer 4C JPEG2026503871000216.jpg1982 Acrylate monomer C (1000 mg) was placed in a 20 mL vial, and then amine monomer 4 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain polymer 4C having an ionizable moiety according to the present invention.

[0085] [Manufacturing Example 19] Polymer 4D Fabrication JPEG2026503871000217.jpg1882 Acrylate monomer D (1000 mg) was placed in a 20 mL vial, and then amine monomer 4 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain polymer 4D having an ionizable moiety according to the present invention.

[0086] [Manufacturing Example 20] Preparation of Polymer 4A JPEG2026503871000218.jpg1482 Acrylate Monomer E (1000 mg) was placed in a 20 mL vial, and then amine Monomer 4 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 2500 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain Polymer 4E having an ionizable moiety according to the present invention.

[0087] [Manufacturing Example 21] Preparation of Polymer 5A JPEG2026503871000219.jpg1282 Acrylate Monomer A (1000 mg) was placed in a two-neck round-bottom flask, and then amine Monomer 5 was added to the flask at a molar ratio of 1.04 to the acrylate monomer. DCM was added to the flask to a final concentration of 1000 mg / mL. The mixture was then refluxed at 50°C for 48 hours to yield Polymer 5A having an ionizable moiety according to the present invention.

[0088] [Manufacturing Example 22] Preparation of Polymer 5B JPEG2026503871000220.jpg1282 Acrylate Monomer B (1000 mg) was placed in a two-neck round-bottom flask, followed by the addition of Amine Monomer 5 at a molar ratio of 1.04 to the acrylate monomer. DCM was added to the flask to a final concentration of 1000 mg / mL. The mixture was then refluxed at 50°C for 48 hours to yield Polymer 5B having an ionizable moiety according to the present invention.

[0089] [Manufacturing Example 23] Preparation of Polymer 5C JPEG2026503871000221.jpg1582 Acrylate Monomer C (1000 mg) was placed in a two-neck round-bottom flask, and then amine Monomer 5 was added to the flask at a molar ratio of 1.04 to the acrylate monomer. DCM was added to the flask to a final concentration of 1000 mg / mL. The mixture was then refluxed at 50°C for 48 hours to yield Polymer 5C having an ionizable moiety according to the present invention.

[0090] [Manufacturing Example 24] Fabrication of Polymer 5D JPEG2026503871000222.jpg1182 Acrylate Monomer D (1000 mg) was placed in a two-neck round-bottom flask, followed by the addition of Amine Monomer 5 at a molar ratio of 1.04 to the acrylate monomer. DCM was added to the flask to a final concentration of 1000 mg / mL. The mixture was then refluxed at 50°C for 48 hours to yield Polymer 5D having an ionizable moiety according to the present invention.

[0091] [Manufacturing Example 25] Production of Polymer 5E JPEG2026503871000223.jpg982 Acrylate Monomer E (1000 mg) was placed in a two-neck round-bottom flask, and then amine Monomer 5 was added to the flask at a molar ratio of 1.04 to the acrylate monomer. DCM was added to the flask to a final concentration of 1000 mg / mL. The mixture was then refluxed at 50°C for 48 hours to yield Polymer 5E having an ionizable moiety according to the present invention.

[0092] [Manufacturing Example 26] Preparation of Polymer 6A JPEG2026503871000224.jpg1882 Acrylate Monomer A (1000 mg) was placed in a 20 mL vial, and then amine Monomer 6 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain Polymer 6A having an ionizable moiety according to the present invention.

[0093] [Manufacturing Example 27] Preparation of Polymer 6B JPEG2026503871000225.jpg1782 Acrylate Monomer B (1000 mg) was placed in a 20 mL vial, and then amine Monomer 6 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain Polymer 6B having an ionizable moiety according to the present invention.

[0094] [Manufacturing Example 28] Preparation of Polymer 6C JPEG2026503871000226.jpg1782 Acrylate Monomer C (1000 mg) was placed in a 20 mL vial, and then amine Monomer 6 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain Polymer 6C having an ionizable moiety according to the present invention.

[0095] [Manufacturing Example 29] Preparation of Polymer 6D JPEG2026503871000227.jpg1782 Acrylate Monomer D (1000 mg) was placed in a 20 mL vial, and then amine Monomer 6 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain Polymer 6D having an ionizable moiety according to the present invention.

[0096] [Manufacturing Example 30] Preparation of Polymer 6E JPEG2026503871000228.jpg1582 Acrylate Monomer E (1000 mg) was placed in a 20 mL vial, and then amine Monomer 6 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 2500 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain Polymer 6E having an ionizable moiety according to the present invention.

[0097] [Manufacturing Example 31] Preparation of Polymer 7A JPEG2026503871000229.jpg2382 Acrylate Monomer A (1000 mg) was placed in a 20 mL vial, and then amine Monomer 7 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain Polymer 7A having an ionizable moiety according to the present invention.

[0098] [Manufacturing Example 32] Preparation of Polymer 7B JPEG2026503871000230.jpg1982 Acrylate Monomer B (1000 mg) was placed in a 20 mL vial, and then amine Monomer 7 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain Polymer 7B having an ionizable moiety according to the present invention.

[0099] [Manufacturing Example 33] Preparation of Polymer 7C JPEG2026503871000231.jpg2282 Acrylate monomer C (1000 mg) was placed in a 20 mL vial, and then amine monomer 7 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain polymer 7C having an ionizable moiety according to the present invention.

[0100] [Manufacturing Example 34] Preparation of Polymer 7D JPEG2026503871000232.jpg2182 Acrylate Monomer D (1000 mg) was placed in a 20 mL vial, and then amine Monomer 7 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain Polymer 7D having an ionizable moiety according to the present invention.

[0101] [Manufacturing Example 35] Preparation of Polymer 7E JPEG2026503871000233.jpg1382 Acrylate Monomer E (1000 mg) was placed in a 20 mL vial, and then amine Monomer 7 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 2500 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain Polymer 7E having an ionizable moiety according to the present invention.

[0102] [Manufacturing Example 36] Preparation of Polymer 8A JPEG2026503871000234.jpg2082 Acrylate Monomer A (1000 mg) was placed in a 20 mL vial, and then amine Monomer 8 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain Polymer 8A having an ionizable moiety according to the present invention.

[0103] [Manufacturing Example 37] Preparation of Polymer 8B JPEG2026503871000235.jpg2382 Acrylate Monomer B (1000 mg) was placed in a 20 mL vial, and then amine Monomer 8 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90°C for 24 hours to yield Polymer 8B having an ionizable moiety according to the present invention.

[0104] [Manufacturing Example 38] Preparation of Polymer 8C JPEG2026503871000236.jpg2182 Acrylate monomer C (1000 mg) was placed in a 20 mL vial, and then amine monomer 8 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain polymer 8C having an ionizable moiety according to the present invention.

[0105] [Manufacturing Example 39] Preparation of Polymer 8D JPEG2026503871000237.jpg2182 Acrylate monomer D (1000 mg) was placed in a 20 mL vial, and then amine monomer 8 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain polymer 8D having an ionizable moiety according to the present invention.

[0106] [Manufacturing Example 40] Preparation of Polymer 8E JPEG2026503871000238.jpg1982 Acrylate Monomer E (1000 mg) was placed in a 20 mL vial, and then amine Monomer 8 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 2500 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain Polymer 8E having an ionizable moiety according to the present invention.

[0107] [Manufacturing Example 41] Preparation of Polymer 9A JPEG2026503871000239.jpg2182 Acrylate Monomer A (1000 mg) was placed in a 20 mL vial, and then amine Monomer 9 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain Polymer 9A having an ionizable moiety according to the present invention.

[0108] [Manufacturing Example 42] Preparation of Polymer 9B JPEG2026503871000240.jpg2182 Acrylate Monomer B (1000 mg) was placed in a 20 mL vial, and then amine Monomer 9 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90°C for 24 hours to yield Polymer 9B having an ionizable moiety according to the present invention.

[0109] [Manufacturing Example 43] Preparation of Polymer 9C JPEG2026503871000241.jpg2282 Acrylate monomer C (1000 mg) was placed in a 20 mL vial, and then amine monomer 9 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain polymer 9C having an ionizable moiety according to the present invention.

[0110] [Manufacturing Example 44] Preparation of Polymer 9D JPEG2026503871000242.jpg2082 Acrylate monomer D (1000 mg) was placed in a 20 mL vial, and then amine monomer 9 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain polymer 9D having an ionizable moiety according to the present invention.

[0111] [Manufacturing Example 45] Preparation of Polymer 9E JPEG2026503871000243.jpg1882 Acrylate monomer E (1000 mg) was placed in a 20 mL vial, and then amine monomer 9 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 2500 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain polymer 9E having an ionizable moiety according to the present invention.

[0112] [Manufacturing Example 46] Preparation of Polymer 10A JPEG2026503871000244.jpg2182 Acrylate monomer A (1000 mg) was placed in a 20 mL vial, and then amine monomer 10 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain polymer 10A having an ionizable moiety according to the present invention.

[0113] [Manufacturing Example 47] Preparation of Polymer 10B JPEG2026503871000245.jpg2082 Acrylate monomer B (1000 mg) was placed in a 20 mL vial, and then amine monomer 10 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90° C. for 24 hours to obtain polymer 10B having an ionizable moiety according to the present invention.

[0114] [Manufacturing Example 48] Preparation of Polymer 10C JPEG2026503871000246.jpg1982 Acrylate monomer C (1000 mg) was placed in a 20 mL vial, and then amine monomer 10 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain polymer 10C having an ionizable moiety according to the present invention.

[0115] [Manufacturing Example 49] Preparation of Polymer 10D JPEG2026503871000247.jpg2382 Acrylate monomer D (1000 mg) was placed in a 20 mL vial, and then amine monomer 10 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain polymer 10D having an ionizable moiety according to the present invention.

[0116] [Manufacturing Example 50] Production of Polymer 10E JPEG2026503871000248.jpg2082 Acrylate monomer E (1000 mg) was placed in a 20 mL vial, and then amine monomer 10 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 2500 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain polymer 10E having an ionizable moiety according to the present invention.

[0117] [Manufacturing Example 51] Preparation of Polymer 11A JPEG2026503871000249.jpg1982 Acrylate monomer A (1000 mg) was placed in a 20 mL vial, and then amine monomer 11 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain polymer 11A having an ionizable moiety according to the present invention.

[0118] [Manufacturing Example 52] Preparation of Polymer 11B JPEG2026503871000250.jpg1982 Acrylate monomer B (1000 mg) was placed in a 20 mL vial, and then amine monomer 11 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain polymer 11B having an ionizable moiety according to the present invention.

[0119] [Manufacturing Example 53] Preparation of Polymer 11C JPEG2026503871000251.jpg1882 Acrylate monomer C (1000 mg) was placed in a 20 mL vial, and then amine monomer 11 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain polymer 11C having an ionizable moiety according to the present invention.

[0120] [Manufacturing Example 54] Preparation of Polymer 11D JPEG2026503871000252.jpg2082 Acrylate monomer D (1000 mg) was placed in a 20 mL vial, and then amine monomer 11 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 1000 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain polymer 11D having an ionizable moiety according to the present invention.

[0121] [Manufacturing Example 55] Preparation of Polymer 11E JPEG2026503871000253.jpg1882 Acrylate monomer E (1000 mg) was placed in a 20 mL vial, and then amine monomer 11 was added to the vial at a molar ratio of 1.04 to the acrylate monomer. DMSO was added to the vial to a final concentration of 2500 mg / mL. The mixture was then reacted at 90°C for 24 hours to obtain polymer 11E having an ionizable moiety according to the present invention.

[0122] [Manufacturing Example 56] Production of Polymer 1F JPEG2026503871000254.jpg2282 Alkynoate monomer F (500 mg) was placed in a round-bottom flask, and then amine monomer 1 was added to the flask so that the molar ratio of the acrylate monomer to the monomer was 1.04. Then, 4 mL of dichloromethane was added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 1F having an ionizable moiety of the present invention.

[0123] [Manufacturing Example 57] Preparation of Polymer 1G JPEG2026503871000255.jpg1682 Alkynoate monomer G (500 mg) was placed in a round-bottom flask, and then amine monomer 1 was added to the flask so that the molar ratio of the alkynoate monomer to the amine monomer was 1.04. Then, 4 mL of dichloromethane was added to the flask. The mixture was allowed to react at room temperature for 6 hours to obtain polymer 1G having an ionizable moiety of the present invention.

[0124] [Manufacturing Example 58] Production of Polymer 1H JPEG2026503871000256.jpg1782 Alkynoate monomer H (500 mg) was placed in a round-bottom flask, and then amine monomer 1 was added to the flask so that the molar ratio to the alkynoate monomer was 1.04. Then, 4 mL of dichloromethane was added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 1H having an ionizable moiety of the present invention.

[0125] [Manufacturing Example 59] Preparation of polymer 1I JPEG2026503871000257.jpg1782 Alkynoate monomer I (500 mg) was placed in a round-bottom flask, and then amine monomer 1 was added to the flask so that the molar ratio of alkynoate monomer to the amine monomer was 1.04. Then, 4 mL of dichloromethane was added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 1I having an ionizable moiety of the present invention.

[0126] [Manufacturing Example 60] Preparation of Polymer 1J JPEG2026503871000258.jpg1382 Alkynoate monomer J (500 mg) was placed in a round-bottom flask, and then amine monomer 1 was added to the flask so that the molar ratio of alkynoate monomer to the amine monomer was 1.04. Then, 4 mL of dichloromethane was added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 1J having an ionizable moiety of the present invention.

[0127] [Manufacturing Example 61] Production of Polymer 2F JPEG2026503871000259.jpg1882 Alkynoate monomer F (500 mg) was placed in a round-bottom flask, and then amine monomer 2 was added to the flask so that the molar ratio of the alkynoate monomer to the amine monomer was 1.04. Then, 4 mL of dichloromethane was added to the flask. The mixture was then allowed to react at room temperature for 6 hours to obtain polymer 2F having an ionizable moiety of the present invention.

[0128] [Manufacturing Example 62] Preparation of Polymer 2G JPEG2026503871000260.jpg1882 Alkynoate monomer G (500 mg) was placed in a round-bottom flask, and then amine monomer 2 was added to the flask so that the molar ratio to the alkynoate monomer was 1.04. Then, 4 mL of dichloromethane was added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 2G having an ionizable moiety of the present invention.

[0129] [Manufacturing Example 63] Production of Polymer 2H JPEG2026503871000261.jpg2082 Alkynoate monomer H (500 mg) was placed in a round-bottom flask, and then amine monomer 2 was added to the flask in a molar ratio of 1.04 to the alkynoate monomer. 4 mL of dichloromethane was then added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 2H having an ionizable moiety of the present invention.

[0130] [Manufacturing Example 64] Preparation of polymer 2I JPEG2026503871000262.jpg1682 Alkynoate monomer I (500 mg) was placed in a round-bottom flask, and then amine monomer 2 was added to the flask in a molar ratio of 1.04 to the alkynoate monomer. Then, 4 mL of dichloromethane was added to the flask. The mixture was then allowed to react at room temperature for 6 hours to obtain polymer 2I having an ionizable moiety of the present invention.

[0131] [Manufacturing Example 65] Production of Polymer 2J JPEG2026503871000263.jpg1182 Alkynoate monomer J (500 mg) was placed in a round-bottom flask, and then amine monomer 2 was added to the flask in a molar ratio of 1.04 to the alkynoate monomer. 4 mL of dichloromethane was then added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 2J having an ionizable moiety of the present invention.

[0132] [Manufacturing Example 66] Production of Polymer 3F JPEG2026503871000264.jpg1782 Alkynoate monomer F (500 mg) was placed in a round-bottom flask, and then amine monomer 3 was added to the flask so that the molar ratio of the alkynoate monomer to the amine monomer was 1.04. Then, 4 mL of dichloromethane was added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 3F having an ionizable moiety of the present invention.

[0133] [Manufacturing Example 67] Production of Polymer 3G JPEG2026503871000265.jpg2082 Alkynoate monomer G (500 mg) was placed in a round-bottom flask, and then amine monomer 3 was added to the flask so that the molar ratio to the alkynoate monomer was 1.04. Then, 4 mL of dichloromethane was added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 3G having an ionizable moiety of the present invention.

[0134] [Manufacturing Example 68] Polymer 3H production JPEG2026503871000266.jpg1982 Alkynoate monomer H (500 mg) was placed in a round-bottom flask, and then amine monomer 3 was added to the flask so that the molar ratio to the alkynoate monomer was 1.04. Then, 4 mL of dichloromethane was added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 3H having an ionizable moiety of the present invention.

[0135] [Manufacturing Example 69] Preparation of polymer 3I JPEG2026503871000267.jpg1782 Alkynoate monomer I (500 mg) was placed in a round-bottom flask, and then amine monomer 3 was added to the flask in a molar ratio of 1.04 to the alkynoate monomer. 4 mL of dichloromethane was then added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 3I having an ionizable moiety of the present invention.

[0136] [Manufacturing Example 70] Production of Polymer 3J JPEG2026503871000268.jpg1682 Alkynoate monomer J (500 mg) was placed in a round-bottom flask, and then amine monomer 3 was added to the flask so that the molar ratio to the alkynoate monomer was 1.04. Then, 4 mL of dichloromethane was added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 3J having an ionizable moiety of the present invention.

[0137] [Manufacturing Example 71] Preparation of Polymer 4F JPEG2026503871000269.jpg1882 Alkynoate monomer F (500 mg) was placed in a round-bottom flask, and then amine monomer 4 was added to the flask so that the molar ratio of the alkynoate monomer to the amine monomer was 1.04. Then, 4 mL of dichloromethane was added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 4F having an ionizable moiety of the present invention.

[0138] [Manufacturing Example 72] Polymer 4G production JPEG2026503871000270.jpg1982 Alkynoate monomer G (500 mg) was placed in a round-bottom flask, and then amine monomer 4 was added to the flask so that the molar ratio of the alkynoate monomer to the amine monomer was 1.04. Then, 4 mL of dichloromethane was added to the flask. The mixture was allowed to react at room temperature for 6 hours to obtain polymer 4G having an ionizable moiety of the present invention.

[0139] [Manufacturing Example 73] Polymer 4H production JPEG2026503871000271.jpg1982 Alkynoate monomer H (500 mg) was placed in a round-bottom flask, and then amine monomer 4 was added to the flask so that the molar ratio of the alkynoate monomer to the amine monomer was 1.04. Then, 4 mL of dichloromethane was added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 4H having an ionizable moiety of the present invention.

[0140] [Manufacturing Example 74] Preparation of Polymer 4I JPEG2026503871000272.jpg1882 Alkynoate monomer I (500 mg) was placed in a round-bottom flask, and then amine monomer 4 was added to the flask in a molar ratio of 1.04 to the alkynoate monomer. 4 mL of dichloromethane was then added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 4I having an ionizable moiety according to the present invention.

[0141] [Manufacturing Example 75] Polymer 4J production JPEG2026503871000273.jpg1682 Alkynoate monomer J (500 mg) was placed in a round-bottom flask, and then amine monomer 4 was added to the flask in a molar ratio of 1.04 to the alkynoate monomer. 4 mL of dichloromethane was then added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 4J having an ionizable moiety of the present invention.

[0142] [Manufacturing Example 76] Production of Polymer 5F JPEG2026503871000274.jpg1482 Alkynoate monomer F (500 mg) was placed in a round-bottom flask, and then amine monomer 5 was added to the flask so that the molar ratio of the alkynoate monomer to the amine monomer was 1.04. Then, 4 mL of dichloromethane was added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 5F having an ionizable moiety of the present invention.

[0143] [Manufacturing Example 77] Polymer 5G production JPEG2026503871000275.jpg1382 Alkynoate monomer G (500 mg) was placed in a round-bottom flask, and then amine monomer 5 was added to the flask so that the molar ratio to the alkynoate monomer was 1.04. Then, 4 mL of dichloromethane was added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 5G having an ionizable moiety of the present invention.

[0144] [Manufacturing Example 78] Production of Polymer 5H JPEG2026503871000276.jpg1382 Alkynoate monomer H (500 mg) was placed in a round-bottom flask, and then amine monomer 5 was added to the flask in a molar ratio of 1.04 to the alkynoate monomer. 4 mL of dichloromethane was then added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 5H having an ionizable moiety of the present invention.

[0145] [Manufacturing Example 79] Preparation of polymer 5I JPEG2026503871000277.jpg1382 Alkynoate monomer I (500 mg) was placed in a round-bottom flask, and then amine monomer 5 was added to the flask in a molar ratio of 1.04 to the alkynoate monomer. 4 mL of dichloromethane was then added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 5I having an ionizable moiety of the present invention.

[0146] [Manufacturing Example 80] Production of Polymer 5J JPEG2026503871000278.jpg1382 Alkynoate monomer J (500 mg) was placed in a round-bottom flask, and then amine monomer 5 was added to the flask in a molar ratio of 1.04 to the alkynoate monomer. 4 mL of dichloromethane was then added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 5J having an ionizable moiety of the present invention.

[0147] [Manufacturing Example 81] Preparation of Polymer 6F JPEG2026503871000279.jpg1582 Alkynoate monomer F (500 mg) was placed in a round-bottom flask, and then amine monomer 6 was added to the flask so that the molar ratio to the alkynoate monomer was 1.04. Then, 4 mL of dichloromethane was added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 6F having an ionizable moiety of the present invention.

[0148] [Manufacturing Example 82] Production of Polymer 6G JPEG2026503871000280.jpg1582 Alkynoate monomer G (500 mg) was placed in a round-bottom flask, and then amine monomer 6 was added to the flask so that the molar ratio to the alkynoate monomer was 1.04. Then, 4 mL of dichloromethane was added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 6G having an ionizable moiety of the present invention.

[0149] [Manufacturing Example 83] Production of Polymer 6H JPEG2026503871000281.jpg1982 Alkynoate monomer H (500 mg) was placed in a round-bottom flask, and then amine monomer 6 was added to the flask so that the molar ratio to the alkynoate monomer was 1.04. Then, 4 mL of dichloromethane was added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 6H having an ionizable moiety of the present invention.

[0150] [Manufacturing Example 84] Preparation of polymer 6I JPEG2026503871000282.jpg1782 Alkynoate monomer I (500 mg) was placed in a round-bottom flask, and then amine monomer 6 was added to the flask in a molar ratio of 1.04 to the alkynoate monomer. Then, 4 mL of dichloromethane was added to the flask. The mixture was then allowed to react at room temperature for 6 hours to obtain polymer 6I having an ionizable moiety according to the present invention.

[0151] [Manufacturing Example 85] Production of Polymer 6J JPEG2026503871000283.jpg1582 Alkynoate monomer J (500 mg) was placed in a round-bottom flask, and then amine monomer 6 was added to the flask in a molar ratio of 1.04 to the alkynoate monomer. Then, 4 mL of dichloromethane was added to the flask. The mixture was allowed to react at room temperature for 6 hours to obtain polymer 6J having an ionizable moiety of the present invention.

[0152] [Manufacturing Example 86] Preparation of Polymer 7F JPEG2026503871000284.jpg2082 Alkynoate monomer F (500 mg) was placed in a round-bottom flask, and then amine monomer 7 was added to the flask so that the molar ratio to the alkynoate monomer was 1.04. Then, 4 mL of dichloromethane was added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 7F having an ionizable moiety of the present invention.

[0153] [Manufacturing Example 87] Production of Polymer 7G JPEG2026503871000285.jpg1882 Alkynoate monomer G (500 mg) was placed in a round-bottom flask, and then amine monomer 7 was added to the flask so that the molar ratio to the alkynoate monomer was 1.04. Then, 4 mL of dichloromethane was added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 7G having an ionizable moiety of the present invention.

[0154] [Manufacturing Example 88] Production of Polymer 7H JPEG2026503871000286.jpg1882 Alkynoate monomer H (500 mg) was placed in a round-bottom flask, and then amine monomer 7 was added to the flask so that the molar ratio to the alkynoate monomer was 1.04. Then, 4 mL of dichloromethane was added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 7H having an ionizable moiety of the present invention.

[0155] [Manufacturing Example 89] Preparation of polymer 7I JPEG2026503871000287.jpg2082 Alkynoate monomer I (500 mg) was placed in a round-bottom flask, and then amine monomer 7 was added to the flask so that the molar ratio to the alkynoate monomer was 1.04. Then, 4 mL of dichloromethane was added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 7I having an ionizable moiety of the present invention.

[0156] [Example 90] Production of Polymer 7J JPEG2026503871000288.jpg1482 Alkynoate monomer J (500 mg) was placed in a round-bottom flask, and then amine monomer 7 was added to the flask in a molar ratio of 1.04 to the alkynoate monomer. 4 mL of dichloromethane was then added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 7J having an ionizable moiety of the present invention.

[0157] [Manufacturing Example 91] Preparation of Polymer 8F JPEG2026503871000289.jpg1982 Alkynoate monomer F (500 mg) was placed in a round-bottom flask, and then amine monomer 8 was added to the flask so that the molar ratio to the alkynoate monomer was 1.04. Then, 4 mL of dichloromethane was added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 8F having an ionizable moiety of the present invention.

[0158] [Manufacturing Example 92] Preparation of Polymer 8G JPEG2026503871000290.jpg1882 Alkynoate monomer G (500 mg) was placed in a round-bottom flask, and then amine monomer 8 was added to the flask so that the molar ratio to the alkynoate monomer was 1.04. Then, 4 mL of dichloromethane was added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 8G having an ionizable moiety of the present invention.

[0159] [Manufacturing Example 93] Production of Polymer 8H JPEG2026503871000291.jpg2082 Alkynoate monomer H (500 mg) was placed in a round-bottom flask, and then amine monomer 8 was added to the flask in a molar ratio of 1.04 to the alkynoate monomer. 4 mL of dichloromethane was then added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 8H having an ionizable moiety of the present invention.

[0160] [Manufacturing Example 94] Preparation of polymer 8I JPEG2026503871000292.jpg1982 Alkynoate monomer I (500 mg) was placed in a round-bottom flask, and then amine monomer 8 was added to the flask in a molar ratio of 1.04 to the alkynoate monomer. 4 mL of dichloromethane was then added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 8I having an ionizable moiety of the present invention.

[0161] [Manufacturing Example 95] Production of Polymer 8J JPEG2026503871000293.jpg1882 Alkynoate monomer J (500 mg) was placed in a round-bottom flask, and then amine monomer 8 was added to the flask in a molar ratio of 1.04 to the alkynoate monomer. 4 mL of dichloromethane was then added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 8J having an ionizable moiety of the present invention.

[0162] [Manufacturing Example 96] Preparation of Polymer 9F JPEG2026503871000294.jpg1882 Alkynoate monomer F (500 mg) was placed in a round-bottom flask, and then amine monomer 9 was added to the flask so that the molar ratio to the alkynoate monomer was 1.04. Then, 4 mL of dichloromethane was added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 9F having an ionizable moiety of the present invention.

[0163] [Manufacturing Example 97] Preparation of Polymer 9G JPEG2026503871000295.jpg1882 Alkynoate monomer G (500 mg) was placed in a round-bottom flask, and then amine monomer 9 was added to the flask in a molar ratio of 1.04 to the alkynoate monomer. 4 mL of dichloromethane was then added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 9G having an ionizable moiety of the present invention.

[0164] [Manufacturing Example 98] Polymer 9H manufacturing JPEG2026503871000296.jpg1882 Alkynoate monomer H (500 mg) was placed in a round-bottom flask, and then amine monomer 9 was added to the flask in a molar ratio of 1.04 to the alkynoate monomer. Then, 4 mL of dichloromethane was added to the flask. The mixture was then allowed to react at room temperature for 6 hours to obtain polymer 9H having an ionizable moiety according to the present invention.

[0165] [Example 99] Preparation of Polymer 9I JPEG2026503871000297.jpg2082 Alkynoate monomer I (500 mg) was placed in a round-bottom flask, and then amine monomer 9 was added to the flask in a molar ratio of 1.04 to the alkynoate monomer. Then, 4 mL of dichloromethane was added to the flask. The mixture was then allowed to react at room temperature for 6 hours to obtain polymer 9I having an ionizable moiety according to the present invention.

[0166] [Manufacturing Example 100] Production of Polymer 9J JPEG2026503871000298.jpg1982 Alkynoate monomer J (500 mg) was placed in a round-bottom flask, and then amine monomer 9 was added to the flask in a molar ratio of 1.04 to the alkynoate monomer. 4 mL of dichloromethane was then added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 9J having an ionizable moiety according to the present invention.

[0167] [Manufacturing Example 101] Production of Polymer 10F JPEG2026503871000299.jpg2082 Alkynoate monomer F (500 mg) was placed in a round-bottom flask, and then amine monomer 10 was added to the flask so that the molar ratio of the alkynoate monomer to the monomer was 1.04. Then, 4 mL of dichloromethane was added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 10F having an ionizable moiety according to the present invention.

[0168] [Manufacturing Example 102] Production of Polymer 10G JPEG2026503871000300.jpg2282 Alkynoate monomer G (500 mg) was placed in a round-bottom flask, and then amine monomer 10 was added to the flask in a molar ratio of 1.04 to the alkynoate monomer. 4 mL of dichloromethane was then added to the flask. The mixture was then allowed to react at room temperature for 6 hours to obtain polymer 10G having an ionizable moiety of the present invention.

[0169] [Manufacturing Example 103] Production of Polymer 10H JPEG2026503871000301.jpg2582 Alkynoate monomer H (500 mg) was placed in a round-bottom flask, and then amine monomer 10 was added to the flask in a molar ratio of 1.04 to the alkynoate monomer. Then, 4 mL of dichloromethane was added to the flask. The mixture was then allowed to react at room temperature for 6 hours to obtain polymer 10H having an ionizable moiety according to the present invention.

[0170] [Manufacturing Example 104] Preparation of Polymer 10I JPEG2026503871000302.jpg2282 Alkynoate monomer I (500 mg) was placed in a round-bottom flask, and then amine monomer 10 was added to the flask in a molar ratio of 1.04 to the alkynoate monomer. 4 mL of dichloromethane was then added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 10I having an ionizable moiety according to the present invention.

[0171] [Manufacturing Example 105] Production of Polymer 10J JPEG2026503871000303.jpg2082 Alkynoate monomer J (500 mg) was placed in a round-bottom flask, and then amine monomer 10 was added to the flask so that the molar ratio to the alkynoate monomer was 1.04. Then, 4 mL of dichloromethane was added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 10J having an ionizable moiety according to the present invention.

[0172] [Manufacturing Example 106] Production of Polymer 11F JPEG2026503871000304.jpg1782 Alkynoate monomer F (500 mg) was placed in a round-bottom flask, and then amine monomer 11 was added to the flask so that the molar ratio to the alkynoate monomer was 1.04. Then, 4 mL of dichloromethane was added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 11F having an ionizable moiety of the present invention.

[0173] [Manufacturing Example 107] Preparation of Polymer 11G JPEG2026503871000305.jpg2082 Alkynoate monomer G (500 mg) was placed in a round-bottom flask, and then amine monomer 11 was added to the flask in a molar ratio of 1.04 to the alkynoate monomer. 4 mL of dichloromethane was then added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 11G having an ionizable moiety of the present invention.

[0174] [Manufacturing Example 108] Production of Polymer 11H JPEG2026503871000306.jpg1982 Alkynoate monomer H (500 mg) was placed in a round-bottom flask, and then amine monomer 11 was added to the flask in a molar ratio of 1.04 to the alkynoate monomer. 4 mL of dichloromethane was then added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 11H having an ionizable moiety according to the present invention.

[0175] [Manufacturing Example 109] Preparation of Polymer 11I JPEG2026503871000307.jpg2082 Alkynoate monomer I (500 mg) was placed in a round-bottom flask, and then amine monomer 11 was added to the flask in a molar ratio of 1.04 to the alkynoate monomer. Then, 4 mL of dichloromethane was added to the flask. The mixture was then allowed to react at room temperature for 6 hours to obtain polymer 11I having an ionizable moiety according to the present invention.

[0176] [Manufacturing Example 110] Production of Polymer 11J JPEG2026503871000308.jpg1782 Alkynoate monomer J (500 mg) was placed in a round-bottom flask, and then amine monomer 11 was added to the flask in a molar ratio of 1.04 to the alkynoate monomer. 4 mL of dichloromethane was then added to the flask, and the mixture was allowed to react at room temperature for 6 hours to obtain polymer 11J having an ionizable moiety according to the present invention.

[0177] [Manufacturing Example 111] Preparation of polymer PEG-1A JPEG2026503871000309.jpg3182 Polymer 1A prepared in the same manner as in Preparation Example 1 and 648.8 mg of PEG-acrylate were dissolved in CHCl to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was allowed to react under reflux at 50°C for 24 hours, after which PEG-1A was obtained.

[0178] [Manufacturing Example 112] Preparation of polymer PEG-1B JPEG2026503871000310.jpg3282 Polymer 1B prepared in the same manner as in Preparation Example 2 and 752.3 mg of PEG-acrylate were dissolved in CHCl to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was allowed to react under reflux at 50°C for 24 hours, yielding PEG-1B.

[0179] [Manufacturing Example 113] Preparation of polymer PEG-1C JPEG2026503871000311.jpg3482 Polymer 1C prepared in the same manner as in Preparation Example 3 and 858.7 mg of PEG-acrylate were dissolved in CHCl to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was allowed to react under reflux at 50°C for 24 hours, yielding PEG-1C.

[0180] [Manufacturing Example 114] Preparation of polymer PEG-1D JPEG2026503871000312.jpg3482 Polymer 1D prepared in the same manner as in Preparation Example 4 and 858.7 mg of PEG-acrylate were dissolved in CHCl to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was allowed to react under reflux at 50°C for 24 hours, after which PEG-1D was obtained.

[0181] [Manufacturing Example 115] Preparation of polymer PEG-1E JPEG2026503871000313.jpg2382 Polymer 1E prepared in the same manner as in Preparation Example 5 and 563.0 mg of PEG-acrylate were dissolved in CHCl to a concentration of 2500 mg / mL, and the solution was added to a flask. The mixture was allowed to react under reflux at 50°C for 24 hours, after which PEG-1E was obtained.

[0182] [Manufacturing Example 116] Preparation of polymer PEG-2A JPEG2026503871000314.jpg2382 Polymer 2A prepared in the same manner as in Preparation Example 6 and 648.8 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90° C. for 24 hours, after which PEG-2A was obtained.

[0183] [Manufacturing Example 117] Preparation of polymer PEG-2B JPEG2026503871000315.jpg2482 Polymer 2B prepared in the same manner as in Preparation Example 7 and 752.3 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90° C. for 24 hours, after which PEG-2B was obtained.

[0184] [Manufacturing Example 118] Preparation of polymer PEG-2C JPEG2026503871000316.jpg2382 Polymer 2C prepared in the same manner as in Preparation Example 8 and 858.7 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90° C. for 24 hours, after which PEG-2C was obtained.

[0185] [Manufacturing Example 119] Preparation of polymer PEG-2D JPEG2026503871000317.jpg2882 Polymer 2D prepared in the same manner as in Preparation Example 9 and 858.7 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90° C. for 24 hours, after which PEG-2D was obtained.

[0186] [Manufacturing Example 120] Preparation of polymer PEG-2E JPEG2026503871000318.jpg1982 Polymer 2E prepared in the same manner as in Preparation Example 10 and 563.0 mg of PEG-acrylate were dissolved in DMSO to a concentration of 2500 mg / mL, and the solution was added to a flask. The mixture was reacted at 90° C. for 24 hours, after which PEG-2E was obtained.

[0187] [Manufacturing Example 121] Preparation of polymer PEG-3A JPEG2026503871000319.jpg3582 Polymer 3A prepared in the same manner as in Preparation Example 11 and 648.8 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90° C. for 24 hours, after which PEG-3A was obtained.

[0188] [Manufacturing Example 122] Preparation of polymer PEG-3B JPEG2026503871000320.jpg3782 Polymer 3B prepared in the same manner as in Preparation Example 12 and 752.3 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90° C. for 24 hours, after which PEG-3B was obtained.

[0189] [Manufacturing Example 123] Preparation of polymer PEG-3C JPEG2026503871000321.jpg3582 Polymer 3C prepared in the same manner as in Preparation Example 13 and 858.7 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90° C. for 24 hours, after which PEG-3C was obtained.

[0190] [Manufacturing Example 124] Preparation of polymer PEG-3D JPEG2026503871000322.jpg3382 Polymer 3D prepared in the same manner as in Preparation Example 14 and 858.7 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90°C for 24 hours, after which PEG-3D was obtained.

[0191] [Manufacturing Example 125] Preparation of polymer PEG-3E JPEG2026503871000323.jpg3482 Polymer 3E prepared in the same manner as in Preparation Example 15 and 563.0 mg of PEG-acrylate were dissolved in DMSO to a concentration of 2500 mg / mL, and the solution was added to a flask. The mixture was reacted at 90° C. for 24 hours, after which PEG-3E was obtained.

[0192] [Manufacturing Example 126] Preparation of polymer PEG-4A JPEG2026503871000324.jpg3482 Polymer 4A prepared in the same manner as in Preparation Example 16 and 648.8 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90° C. for 24 hours, after which PEG-4A was obtained.

[0193] [Manufacturing Example 127] Preparation of polymer PEG-4B JPEG2026503871000325.jpg3282 Polymer 4B prepared in the same manner as in Preparation Example 17 and 752.3 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90° C. for 24 hours, after which PEG-4B was obtained.

[0194] [Manufacturing Example 128] Preparation of polymer PEG-4C JPEG2026503871000326.jpg3682 Polymer 4C prepared in the same manner as in Preparation Example 18 and 858.7 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90°C for 24 hours, after which PEG-4C was obtained.

[0195] [Manufacturing Example 129] Preparation of polymer PEG-4D JPEG2026503871000327.jpg4382 Polymer 4D prepared in the same manner as in Preparation Example 19 and 858.7 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90°C for 24 hours, after which PEG-4D was obtained.

[0196] [Manufacturing Example 130] Preparation of polymer PEG-4E JPEG2026503871000328.jpg3082 Polymer 4E prepared in the same manner as in Preparation Example 20 and 563.0 mg of PEG-acrylate were dissolved in DMSO to a concentration of 2500 mg / mL, and the solution was added to a flask. The mixture was reacted at 90° C. for 24 hours, after which PEG-4E was obtained.

[0197] [Manufacturing Example 131] Preparation of polymer PEG-5A JPEG2026503871000329.jpg2282 Polymer 5A prepared in the same manner as in Preparation Example 21 and 648.8 mg of PEG-acrylate were dissolved in CHCl to a concentration of 1000 mg / mL and added to a flask. The mixture was allowed to react under reflux at 50°C for 24 hours, after which PEG-5A was obtained.

[0198] [Manufacturing Example 132] Preparation of polymer PEG-5B JPEG2026503871000330.jpg2582 Polymer 5B prepared in the same manner as in Preparation Example 22 and 752.3 mg of PEG-acrylate were dissolved in CHCl to a concentration of 1000 mg / mL and added to a flask. The mixture was allowed to react under reflux at 50°C for 24 hours, after which PEG-5B was obtained.

[0199] [Manufacturing Example 133] Preparation of polymer PEG-5C JPEG2026503871000331.jpg2482 Polymer 5C prepared in the same manner as in Preparation Example 23 and 858.7 mg of PEG-acrylate were dissolved in CHCl to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was allowed to react under reflux at 50°C for 24 hours, after which PEG-5C was obtained.

[0200] [Manufacturing Example 134] Preparation of polymer PEG-5D JPEG2026503871000332.jpg2482 Polymer 5D prepared in the same manner as in Preparation Example 24 and 858.7 mg of PEG-acrylate were dissolved in CHCl to a concentration of 1000 mg / mL, and the solution was added to a flask. The reaction was carried out under reflux at 50°C for 24 hours, after which PEG-5D was obtained.

[0201] [Manufacturing Example 135] Preparation of polymer PEG-5E JPEG2026503871000333.jpg2182 Polymer 5E prepared in the same manner as in Preparation Example 25 and 563.0 mg of PEG-acrylate were dissolved in CHCl to a concentration of 2500 mg / mL, and the solution was added to a flask. The mixture was allowed to react under reflux at 50°C for 24 hours, after which PEG-5E was obtained.

[0202] [Manufacturing Example 136] Preparation of polymer PEG-6A JPEG2026503871000334.jpg3582 Polymer 6A prepared in the same manner as in Preparation Example 26 and 648.8 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90°C for 24 hours, after which PEG-6A was obtained.

[0203] [Manufacturing Example 137] Preparation of polymer PEG-6B JPEG2026503871000335.jpg3482 Polymer 6B prepared in the same manner as in Preparation Example 27 and 752.3 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90° C. for 24 hours, after which PEG-6B was obtained.

[0204] [Manufacturing Example 138] Preparation of polymer PEG-6C JPEG2026503871000336.jpg3382 Polymer 6C prepared in the same manner as in Preparation Example 28 and 858.7 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90°C for 24 hours, after which PEG-6C was obtained.

[0205] [Manufacturing Example 139] Preparation of polymer PEG-6D JPEG2026503871000337.jpg3482 Polymer 6D prepared in the same manner as in Preparation Example 29 and 858.7 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90°C for 24 hours, after which PEG-6D was obtained.

[0206] [Manufacturing Example 140] Preparation of polymer PEG-6E JPEG2026503871000338.jpg2882 Polymer 6E prepared in the same manner as in Preparation Example 30 and 563.0 mg of PEG-acrylate were dissolved in DMSO to a concentration of 2500 mg / mL, and the solution was added to a flask. The mixture was reacted at 90°C for 24 hours, after which PEG-6E was obtained.

[0207] [Manufacturing Example 141] Preparation of polymer PEG-7A JPEG2026503871000339.jpg3482 Polymer 7A prepared in the same manner as in Preparation Example 31 and 648.8 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90° C. for 24 hours, after which PEG-7A was obtained.

[0208] [Manufacturing Example 142] Preparation of polymer PEG-7B JPEG2026503871000340.jpg3482 Polymer 7B prepared in the same manner as in Preparation Example 32 and 752.3 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90° C. for 24 hours, after which PEG-7B was obtained.

[0209] [Manufacturing Example 143] Preparation of polymer PEG-7C JPEG2026503871000341.jpg3682 Polymer 7C prepared in the same manner as in Preparation Example 33 and 858.7 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90°C for 24 hours, after which PEG-7C was obtained.

[0210] [Manufacturing Example 144] Preparation of polymer PEG-7D JPEG2026503871000342.jpg3182 Polymer 7D prepared in the same manner as in Preparation Example 34 and 858.7 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90°C for 24 hours, after which PEG-7D was obtained.

[0211] [Manufacturing Example 145] Preparation of polymer PEG-7E JPEG2026503871000343.jpg3182 Polymer 7E prepared in the same manner as in Preparation Example 35 and 563.0 mg of PEG-acrylate were dissolved in DMSO to a concentration of 2500 mg / mL, and the solution was added to a flask. The mixture was reacted at 90°C for 24 hours, after which PEG-7E was obtained.

[0212] [Manufacturing Example 146] Preparation of polymer PEG-8A JPEG2026503871000344.jpg3682 Polymer 8A prepared in the same manner as in Preparation Example 36 and 648.8 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90°C for 24 hours, after which PEG-8A was obtained.

[0213] [Manufacturing Example 147] Preparation of polymer PEG-8B JPEG2026503871000345.jpg3982 Polymer 8B prepared in the same manner as in Preparation Example 37 and 752.3 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90° C. for 24 hours, after which PEG-8B was obtained.

[0214] [Manufacturing Example 148] Preparation of polymer PEG-8C JPEG2026503871000346.jpg4582 Polymer 8C prepared in the same manner as in Preparation Example 38 and 858.7 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90°C for 24 hours, after which PEG-8C was obtained.

[0215] [Manufacturing Example 149] Preparation of polymer PEG-8D JPEG2026503871000347.jpg4782 Polymer 8D prepared in the same manner as in Preparation Example 39 and 858.7 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90°C for 24 hours, after which PEG-8D was obtained.

[0216] [Manufacturing Example 150] Preparation of polymer PEG-8E Polymer 8E prepared in the same manner as in Preparation Example 40 and 563.0 mg of PEG-acrylate were dissolved in DMSO to a concentration of 2500 mg / mL, and the solution was added to a flask. The mixture was reacted at 90°C for 24 hours, after which PEG-8E was obtained.

[0217] [Manufacturing Example 151] Preparation of polymer PEG-9A JPEG2026503871000348.jpg4582 Polymer 9A prepared in the same manner as in Preparation Example 41 and 648.8 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90° C. for 24 hours, after which PEG-9A was obtained.

[0218] [Manufacturing Example 152] Preparation of polymer PEG-9B JPEG2026503871000349.jpg4782 Polymer 9B prepared in the same manner as in Preparation Example 42 and 752.3 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90° C. for 24 hours, after which PEG-9B was obtained.

[0219] [Manufacturing Example 153] Preparation of polymer PEG-9C JPEG2026503871000350.jpg4782 Polymer 9C prepared in the same manner as in Preparation Example 43 and 858.7 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90°C for 24 hours, after which PEG-9C was obtained.

[0220] [Manufacturing Example 154] Preparation of polymer PEG-9D JPEG2026503871000351.jpg4982 Polymer 9D prepared in the same manner as in Preparation Example 44 and 858.7 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90°C for 24 hours to obtain PEG-9D.

[0221] [Manufacturing Example 155] Preparation of polymer PEG-9E JPEG2026503871000352.jpg3382 Polymer 9E prepared in the same manner as in Preparation Example 45 and 563.0 mg of PEG-acrylate were dissolved in DMSO to a concentration of 2500 mg / mL, and the solution was added to a flask. The mixture was reacted at 90°C for 24 hours, after which PEG-9E was obtained.

[0222] [Example 156] Preparation of polymer PEG-10A JPEG2026503871000353.jpg4682 Polymer 10A prepared in the same manner as in Preparation Example 46 and 648.8 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90°C for 24 hours, after which PEG-10A was obtained.

[0223] [Example 157] Preparation of polymer PEG-10B JPEG2026503871000354.jpg4682 Polymer 10B prepared in the same manner as in Preparation Example 47 and 752.3 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90°C for 24 hours, after which PEG-10B was obtained.

[0224] [Example 158] Preparation of polymer PEG-10C JPEG2026503871000355.jpg4682 Polymer 10C prepared in the same manner as in Preparation Example 48 and 858.7 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90°C for 24 hours, after which PEG-10C was obtained.

[0225] [Manufacturing Example 159] Preparation of polymer PEG-10D JPEG2026503871000356.jpg4682 Polymer 10D prepared in the same manner as in Preparation Example 49 and 858.7 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90°C for 24 hours, after which PEG-10D was obtained.

[0226] [Manufacturing Example 160] Preparation of polymer PEG-10E JPEG2026503871000357.jpg3882 Polymer 10E prepared in the same manner as in Preparation Example 50 and 563.0 mg of PEG-acrylate were dissolved in DMSO to a concentration of 2500 mg / mL, and the solution was added to a flask. The mixture was reacted at 90°C for 24 hours, after which PEG-10E was obtained.

[0227] [Manufacturing Example 161] Preparation of polymer PEG-11A JPEG2026503871000358.jpg4582 Polymer 11A prepared in the same manner as in Preparation Example 51 and 648.8 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90° C. for 24 hours, after which PEG-11A was obtained.

[0228] [Manufacturing Example 162] Preparation of polymer PEG-11B JPEG2026503871000359.jpg4782 Polymer 11B prepared in the same manner as in Preparation Example 52 and 752.3 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90° C. for 24 hours, after which PEG-11B was obtained.

[0229] [Manufacturing Example 163] Preparation of polymer PEG-11C JPEG2026503871000360.jpg4682 Polymer 11C prepared in the same manner as in Preparation Example 53 and 858.7 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90° C. for 24 hours, after which PEG-11C was obtained.

[0230] [Example 164] Preparation of polymer PEG-11D JPEG2026503871000361.jpg4282 Polymer 11D prepared in the same manner as in Preparation Example 54 and 858.7 mg of PEG-acrylate were dissolved in DMSO to a concentration of 1000 mg / mL, and the solution was added to a flask. The mixture was reacted at 90°C for 24 hours, after which PEG-11D was obtained.

[0231] [Manufacturing Example 165] Preparation of polymer PEG-11E JPEG2026503871000362.jpg3682 Polymer 11E prepared in the same manner as in Preparation Example 55 and 563.0 mg of PEG-acrylate were dissolved in DMSO to a concentration of 2500 mg / mL, and the solution was added to a flask. The mixture was reacted at 90°C for 24 hours, after which PEG-11E was obtained.

[0232] [Manufacturing Example 166] Preparation of polymer PEG-1F JPEG2026503871000363.jpg4082 Polymer 1F prepared in the same manner as in Preparation Example 56 and 329.5 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-1F was obtained.

[0233] [Manufacturing Example 167] Preparation of polymer PEG-1G JPEG2026503871000364.jpg3882 Polymer 1G prepared in the same manner as in Preparation Example 57 and 383.0 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-1G was obtained.

[0234] [Example 168] Preparation of polymer PEG-1H JPEG2026503871000365.jpg4282 Polymer 1H prepared in the same manner as in Preparation Example 58 and 438.3 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-1H was obtained.

[0235] [Manufacturing Example 169] Preparation of polymer PEG-1I JPEG2026503871000366.jpg3882 Polymer 1I prepared in the same manner as in Preparation Example 59 and 438.3 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-1I was obtained.

[0236] [Manufacturing Example 170] Preparation of polymer PEG-1J JPEG2026503871000367.jpg3182 Polymer 1J prepared in the same manner as in Preparation Example 60 and 285.3 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-1J was obtained.

[0237] [Example 171] Preparation of polymer PEG-2F JPEG2026503871000368.jpg2882 Polymer 2F prepared in the same manner as in Preparation Example 61 and 329.5 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-2F was obtained.

[0238] [Manufacturing Example 172] Preparation of polymer PEG-2G JPEG2026503871000369.jpg2982 Polymer 2G prepared in the same manner as in Preparation Example 62 and 383.0 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-2G was obtained.

[0239] [Manufacturing Example 173] Preparation of polymer PEG-2H JPEG2026503871000370.jpg3082 Polymer 2H prepared in the same manner as in Preparation Example 63 and 438.3 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-2H was obtained.

[0240] [Manufacturing Example 174] Preparation of polymer PEG-2I JPEG2026503871000371.jpg2982 Polymer 2I prepared in the same manner as in Preparation Example 64 and 438.3 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-2I was obtained.

[0241] [Manufacturing Example 175] Preparation of polymer PEG-2J JPEG2026503871000372.jpg2482 Polymer 2J prepared in the same manner as in Preparation Example 65 and 285.3 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-2J was obtained.

[0242] [Manufacturing Example 176] Preparation of polymer PEG-3F JPEG2026503871000373.jpg4382 Polymer 3F prepared in the same manner as in Preparation Example 66 and 329.5 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-3F was obtained.

[0243] [Example 177] Preparation of polymer PEG-3G JPEG2026503871000374.jpg4582 Polymer 3G prepared in the same manner as in Preparation Example 67 and 383.0 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-3G was obtained.

[0244] [Manufacturing Example 178] Preparation of polymer PEG-3H JPEG2026503871000375.jpg4282 Polymer 3H prepared in the same manner as in Preparation Example 68 and 438.3 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-3H was obtained.

[0245] [Manufacture Example 179] Preparation of polymer PEG-3I JPEG2026503871000376.jpg5082 Polymer 3I prepared in the same manner as in Preparation Example 69 and 438.3 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-3I was obtained.

[0246] [Manufacturing Example 180] Preparation of polymer PEG-3J JPEG2026503871000377.jpg3582 Polymer 3J prepared in the same manner as in Preparation Example 70 and 285.3 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-3J was obtained.

[0247] [Manufacturing Example 181] Preparation of polymer PEG-4F JPEG2026503871000378.jpg4082 Polymer 4F prepared in the same manner as in Preparation Example 71 and 329.5 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-4F was obtained.

[0248] [Manufacturing Example 182] Preparation of polymer PEG-4G JPEG2026503871000379.jpg3982 Polymer 4G prepared in the same manner as in Preparation Example 72 and 383.0 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-4G was obtained.

[0249] [Manufacturing Example 183] Preparation of polymer PEG-4H JPEG2026503871000380.jpg3882 Polymer 4H prepared in the same manner as in Preparation Example 73 and 438.3 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-4H was obtained.

[0250] [Manufacturing Example 184] Preparation of polymer PEG-4I JPEG2026503871000381.jpg4482 Polymer 4I prepared in the same manner as in Preparation Example 74 and 438.3 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-4I was obtained.

[0251] [Manufacturing Example 185] Preparation of polymer PEG-4J JPEG2026503871000382.jpg3982 Polymer 4J prepared in the same manner as in Preparation Example 75 and 285.3 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-4J was obtained.

[0252] [Manufacturing Example 186] Preparation of polymer PEG-5F JPEG2026503871000383.jpg3182 Polymer 5F prepared in the same manner as in Preparation Example 76 and 329.5 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-5F was obtained.

[0253] [Manufacturing Example 187] Preparation of polymer PEG-5G JPEG2026503871000384.jpg3082 Polymer 5G prepared in the same manner as in Preparation Example 77 and 383.0 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-5G was obtained.

[0254] [Manufacturing Example 188] Preparation of polymer PEG-5H JPEG2026503871000385.jpg2682 Polymer 5H prepared in the same manner as in Preparation Example 78 and 438.3 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-5H was obtained.

[0255] [Manufacturing Example 189] Preparation of polymer PEG-5I JPEG2026503871000386.jpg2982 Polymer 5I prepared in the same manner as in Preparation Example 79 and 438.3 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-5I was obtained.

[0256] [Manufacturing Example 190] Preparation of polymer PEG-5J JPEG2026503871000387.jpg2482 Polymer 5J prepared in the same manner as in Preparation Example 80 and 285.3 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-5J was obtained.

[0257] [Manufacturing Example 191] Preparation of polymer PEG-6F JPEG2026503871000388.jpg3482 Polymer 6F prepared in the same manner as in Preparation Example 81 and 329.5 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-6F was obtained.

[0258] [Manufacturing Example 192] Preparation of polymer PEG-6G JPEG2026503871000389.jpg3782 Polymer 6G prepared in the same manner as in Preparation Example 82 and 383.0 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-6G was obtained.

[0259] [Manufacturing Example 193] Preparation of polymer PEG-6H JPEG2026503871000390.jpg3682 Polymer 6H prepared in the same manner as in Preparation Example 83 and 438.3 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-6H was obtained.

[0260] [Manufacturing Example 194] Preparation of polymer PEG-6I JPEG2026503871000391.jpg3382 Polymer 6I prepared in the same manner as in Preparation Example 84 and 438.3 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-6I was obtained.

[0261] [Manufacturing Example 195] Preparation of polymer PEG-6J JPEG2026503871000392.jpg3082 Polymer 6J prepared in the same manner as in Preparation Example 85 and 285.3 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-6J was obtained.

[0262] [Manufacturing Example 196] Preparation of polymer PEG-7F JPEG2026503871000393.jpg3482 Polymer 7F prepared in the same manner as in Preparation Example 86 and 329.5 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-7F was obtained.

[0263] [Manufacturing Example 197] Preparation of polymer PEG-7G JPEG2026503871000394.jpg3882 Polymer 7G prepared in the same manner as in Preparation Example 87 and 383.0 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-7G was obtained.

[0264] [Manufacturing Example 198] Preparation of polymer PEG-7H JPEG2026503871000395.jpg3682 Polymer 7H prepared in the same manner as in Preparation Example 88 and 438.3 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-7H was obtained.

[0265] [Manufacturing Example 199] Preparation of polymer PEG-7I JPEG2026503871000396.jpg3682 Polymer 7I prepared in the same manner as in Preparation Example 89 and 438.3 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-7I was obtained.

[0266] [Manufacturing Example 200] Preparation of polymer PEG-7J JPEG2026503871000397.jpg3382 Polymer 7J prepared in the same manner as in Preparation Example 90 and 285.3 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-7J was obtained.

[0267] [Manufacturing Example 201] Preparation of polymer PEG-8F JPEG2026503871000398.jpg4382 Polymer 8F prepared in the same manner as in Preparation Example 91 and 329.5 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-8F was obtained.

[0268] [Manufacturing Example 202] Preparation of polymer PEG-8G JPEG2026503871000399.jpg4182 Polymer 8G prepared in the same manner as in Preparation Example 92 and 383.0 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-8G was obtained.

[0269] [Manufacturing Example 203] Preparation of polymer PEG-8H JPEG2026503871000400.jpg4882 Polymer 8H prepared in the same manner as in Preparation Example 93 and 438.3 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-8H was obtained.

[0270] [Manufacturing Example 204] Preparation of polymer PEG-8I JPEG2026503871000401.jpg5182 Polymer 8I prepared in the same manner as in Preparation Example 94 and 438.3 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-8I was obtained.

[0271] [Manufacturing Example 205] Preparation of polymer PEG-8J JPEG2026503871000402.jpg3882 Polymer 8J prepared in the same manner as in Preparation Example 95 and 285.3 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-8J was obtained.

[0272] [Manufacturing Example 206] Preparation of polymer PEG-9F JPEG2026503871000403.jpg4582 Polymer 9F prepared in the same manner as in Preparation Example 96 and 329.5 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-9F was obtained.

[0273] [Manufacturing Example 207] Preparation of polymer PEG-9G JPEG2026503871000404.jpg4882 Polymer 9G prepared in the same manner as in Preparation Example 97 and 383.0 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-9G was obtained.

[0274] [Manufacturing Example 208] Preparation of polymer PEG-9H JPEG2026503871000405.jpg5182 Polymer 9H prepared in the same manner as in Preparation Example 98 and 438.3 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-9H was obtained.

[0275] [Manufacturing Example 209] Preparation of polymer PEG-9I JPEG2026503871000406.jpg5182 Polymer 9I prepared in the same manner as in Preparation Example 99 and 438.3 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-9I was obtained.

[0276] [Manufacturing Example 210] Preparation of polymer PEG-9J JPEG2026503871000407.jpg3582 Polymer 9J prepared in the same manner as in Preparation Example 100 and 285.3 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-9J was obtained.

[0277] [Manufacturing Example 211] Preparation of polymer PEG-10F JPEG2026503871000408.jpg4582 Polymer 10F prepared in the same manner as in Preparation Example 101 and 329.5 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-10F was obtained.

[0278] [Manufacturing Example 212] Preparation of polymer PEG-10G JPEG2026503871000409.jpg4682 Polymer 10G prepared in the same manner as in Preparation Example 102 and 383.0 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-10G was obtained.

[0279] [Manufacturing Example 213] Preparation of polymer PEG-10H JPEG2026503871000410.jpg4782 Polymer 10H prepared in the same manner as in Preparation Example 103 and 438.3 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-10H was obtained.

[0280] [Manufacturing Example 214] Preparation of polymer PEG-10I JPEG2026503871000411.jpg4982 Polymer 10I prepared in the same manner as in Preparation Example 104 and 438.3 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-10I was obtained.

[0281] [Manufacturing Example 215] Preparation of polymer PEG-10J JPEG2026503871000412.jpg3582 Polymer 10J prepared in the same manner as in Preparation Example 105 and 285.3 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-10J was obtained.

[0282] [Manufacturing Example 216] Preparation of polymer PEG-11F JPEG2026503871000413.jpg4682 Polymer 11F prepared in the same manner as in Preparation Example 106 and 329.5 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-11F was obtained.

[0283] [Manufacturing Example 217] Preparation of polymer PEG-11G JPEG2026503871000414.jpg4582 Polymer 11G prepared in the same manner as in Preparation Example 107 and 383.0 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-11G was obtained.

[0284] [Manufacturing Example 218] Preparation of polymer PEG-11H JPEG2026503871000415.jpg4782 Polymer 11H prepared in the same manner as in Preparation Example 108 and 438.3 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-11H was obtained.

[0285] [Manufacturing Example 219] Preparation of polymer PEG-11I JPEG2026503871000416.jpg4082 Polymer 11I prepared in the same manner as in Preparation Example 109 and 438.3 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-11I was obtained.

[0286] [Manufacturing Example 220] Preparation of polymer PEG-11J JPEG2026503871000417.jpg3582 Polymer 11J prepared in the same manner as in Preparation Example 110 and 285.3 mg of PEG-alkynoate were dissolved in 4 mL of CHCl and added to a flask. The mixture was allowed to react at room temperature for 24 hours, after which PEG-11J was obtained.

[0287] [Manufacturing Example 221] Preparation of polymer b3A JPEG2026503871000418.jpg3380 Amine monomer 3, acrylate monomer A, and branched chain unit were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. Then, dimethylformamide (N,N-dimethylformamide; DMF) was added to the flask to a concentration of 150 mg / mL, and the mixture was reacted at 90°C for 48 hours. After cooling to room temperature, a terminal capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was reacted at room temperature for 24 hours, after which b3A was obtained. The reaction formula used in this specification is JPEG2026503871000419.jpg39 indicates that a multi-step reaction occurs, and omits intermediates, a notation familiar to those skilled in the art.

[0288] [Manufacturing Example 222] Production of polymer b3B JPEG2026503871000420.jpg3280 Amine monomer 3, acrylate monomer B, and branched chain unit were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was reacted at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was reacted at room temperature for 24 hours, yielding b3B.

[0289] [Manufacturing Example 223] Production of polymer b3C JPEG2026503871000421.jpg3380 Amine monomer 3, acrylate monomer C, and branched chain units were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was reacted at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was reacted at room temperature for 24 hours, yielding b3C.

[0290] [Manufacturing Example 224] Fabrication of polymer b3D JPEG2026503871000422.jpg3180 Amine monomer 3, acrylate monomer D, and branched chain units were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was reacted at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was reacted at room temperature for 24 hours, yielding b3D.

[0291] [Manufacturing Example 225] Production of polymer b3E JPEG2026503871000423.jpg3180 Amine monomer 3, acrylate monomer E, and branched chain unit were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was reacted at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was reacted at room temperature for 24 hours, yielding b3E.

[0292] [Manufacturing Example 226] Preparation of polymer b4A JPEG2026503871000424.jpg3380 Amine monomer 4, acrylate monomer A, and branched chain units were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was reacted at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was reacted at room temperature for 24 hours, yielding b4A.

[0293] [Example 227] Production of polymer b4B JPEG2026503871000425.jpg3280 Amine monomer 4, acrylate monomer B, and branched chain unit were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was reacted at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was reacted at room temperature for 24 hours, yielding b4B.

[0294] [Example 228] Polymer b4C production JPEG2026503871000426.jpg3480 Amine monomer 4, acrylate monomer C, and branched chain units were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was reacted at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was reacted at room temperature for 24 hours, yielding b4C.

[0295] [Manufacture Example 229] Production of polymer b4D JPEG2026503871000427.jpg3280 Amine monomer 4, acrylate monomer D, and branched chain units were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was reacted at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was reacted at room temperature for 24 hours, yielding b4D.

[0296] [Manufacturing Example 230] Production of polymer b4E JPEG2026503871000428.jpg3280 Amine monomer 4, acrylate monomer E, and branched chain unit were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was reacted at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was reacted at room temperature for 24 hours, yielding b4E.

[0297] [Manufacturing Example 231] Preparation of polymer b7A JPEG2026503871000429.jpg3580 Amine monomer 7, acrylate monomer A, and branched chain unit were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was reacted at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was reacted at room temperature for 24 hours, yielding b7A.

[0298] [Manufacturing Example 232] Production of polymer b7B JPEG2026503871000430.jpg3580 Amine monomer 7, acrylate monomer B, and branched chain units were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was reacted at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was reacted at room temperature for 24 hours, yielding b7B.

[0299] [Manufacturing Example 233] Preparation of polymer b7C JPEG2026503871000431.jpg3580 Amine monomer 7, acrylate monomer C, and branched chain units were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was reacted at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was reacted at room temperature for 24 hours, yielding b7C.

[0300] [Manufacturing Example 234] Preparation of polymer b7D JPEG2026503871000432.jpg3380 Amine monomer 7, acrylate monomer D, and branched chain units were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was reacted at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was reacted at room temperature for 24 hours, yielding b7D.

[0301] [Manufacturing Example 235] Production of polymer b7E JPEG2026503871000433.jpg3480 Amine monomer 7, acrylate monomer E, and branched chain unit were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was allowed to react at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was allowed to react at room temperature for 24 hours, yielding b7E.

[0302] [Manufacturing Example 236] Preparation of polymer b8A JPEG2026503871000434.jpg3480 Amine monomer 8, acrylate monomer A, and branched chain unit were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was reacted at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was reacted at room temperature for 24 hours, yielding b8A.

[0303] [Manufacturing Example 237] Production of polymer b8B JPEG2026503871000435.jpg3280 Amine monomer 8, acrylate monomer B, and branched chain unit were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was reacted at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was reacted at room temperature for 24 hours, yielding b8B.

[0304] [Manufacturing Example 238] Preparation of polymer b8C JPEG2026503871000436.jpg3480 Amine monomer 8, acrylate monomer C, and branched chain units were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was reacted at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was reacted at room temperature for 24 hours, yielding b8C.

[0305] [Manufacture Example 239] Preparation of polymer b8D JPEG2026503871000437.jpg3380 Amine monomer 8, acrylate monomer D, and branched chain unit were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was reacted at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was reacted at room temperature for 24 hours, yielding b8D.

[0306] [Example 240] Production of polymer b8E JPEG2026503871000438.jpg3580 Amine monomer 8, acrylate monomer E, and branched chain unit were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was reacted at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was reacted at room temperature for 24 hours, yielding b8E.

[0307] [Manufacturing Example 241] Preparation of polymer b9A JPEG2026503871000439.jpg3580 Amine monomer 9, acrylate monomer A, and branched chain units were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was reacted at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was reacted at room temperature for 24 hours, yielding b9A.

[0308] [Manufacturing Example 242] Preparation of polymer b9B JPEG2026503871000440.jpg3580 Amine monomer 9, acrylate monomer B, and branched chain units were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was allowed to react at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was allowed to react at room temperature for 24 hours, yielding b9B.

[0309] [Manufacturing Example 243] Preparation of polymer b9C JPEG2026503871000441.jpg3580 Amine monomer 9, acrylate monomer C, and branched chain units were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was allowed to react at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was allowed to react at room temperature for 24 hours, yielding b9C.

[0310] [Manufacturing Example 244] Preparation of polymer b9D JPEG2026503871000442.jpg3780 Amine monomer 9, acrylate monomer D, and branched chain units were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was allowed to react at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was allowed to react at room temperature for 24 hours, yielding b9D.

[0311] [Manufacturing Example 245] Production of polymer b9E JPEG2026503871000443.jpg3780 Amine monomer 9, acrylate monomer E, and branched chain unit were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was allowed to react at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was allowed to react at room temperature for 24 hours, yielding b9E.

[0312] [Manufacturing Example 246] Preparation of polymer b10A JPEG2026503871000444.jpg3380 Amine monomer 10, acrylate monomer A, and branched chain units were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was reacted at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was reacted at room temperature for 24 hours, yielding b10A.

[0313] [Example 247] Preparation of polymer b10B JPEG2026503871000445.jpg3480 Amine monomer 10, acrylate monomer B, and branched chain unit were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. Then, DMF was added to the flask to a concentration of 150 mg / mL, and the mixture was reacted at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was reacted at room temperature for 24 hours, after which b10B was obtained.

[0314] [Example 248] Preparation of polymer b10C JPEG2026503871000446.jpg3580 Amine monomer 10, acrylate monomer C, and branched chain units were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was reacted at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was reacted at room temperature for 24 hours to obtain b10C.

[0315] [Example 249] Preparation of polymer b10D JPEG2026503871000447.jpg3580 Amine monomer 10, acrylate monomer D, and branched chain units were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was reacted at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was reacted at room temperature for 24 hours to obtain b10D.

[0316] [Example 250] Production of polymer b10E JPEG2026503871000448.jpg3480 Amine monomer 10, acrylate monomer E, and branched chain unit were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was reacted at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was reacted at room temperature for 24 hours, yielding b10E.

[0317] [Manufacturing Example 251] Preparation of polymer b11A JPEG2026503871000449.jpg3580 Amine monomer 11, acrylate monomer A, and branched chain unit were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was reacted at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was reacted at room temperature for 24 hours, yielding b11A.

[0318] [Manufacturing Example 252] Preparation of polymer b11B JPEG2026503871000450.jpg3380 Amine monomer 11, acrylate monomer B, and branched chain units were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was reacted at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was reacted at room temperature for 24 hours, yielding b11B.

[0319] [Manufacturing Example 253] Preparation of polymer b11C JPEG2026503871000451.jpg3280 Amine monomer 11, acrylate monomer C, and branched chain units were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was reacted at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was reacted at room temperature for 24 hours to obtain b11C.

[0320] [Example 254] Preparation of polymer b11D JPEG2026503871000452.jpg3380 Amine monomer 11, acrylate monomer D, and branched chain units were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was reacted at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was reacted at room temperature for 24 hours to obtain b11D.

[0321] [Manufacturing Example 255] Preparation of polymer b11E JPEG2026503871000453.jpg3380 Amine monomer 11, acrylate monomer E, and branched chain unit were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was reacted at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was reacted at room temperature for 24 hours, yielding b11E.

[0322] [Example 256] Preparation of polymer b12A JPEG2026503871000454.jpg3380 Amine monomer 12, acrylate monomer A, and branched chain unit were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was reacted at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was reacted at room temperature for 24 hours to obtain b12A.

[0323] [Example 257] Preparation of polymer b12B JPEG2026503871000455.jpg3280 Amine monomer 12, acrylate monomer B, and branched chain unit were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was reacted at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was reacted at room temperature for 24 hours, yielding b12B.

[0324] [Example 258] Preparation of polymer b12C JPEG2026503871000456.jpg3580 Amine monomer 12, acrylate monomer C, and branched chain units were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was reacted at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was reacted at room temperature for 24 hours to obtain b12C.

[0325] [Example 259] Preparation of polymer b12D JPEG2026503871000457.jpg3380 Amine monomer 12, acrylate monomer D, and branched chain unit were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was reacted at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was reacted at room temperature for 24 hours to obtain b12D.

[0326] [Manufacturing Example 260] Production of polymer b12E JPEG2026503871000458.jpg3480 Amine monomer 12, acrylate monomer E, and branched chain unit were added to a round-bottom flask in a molar ratio of 0.4:1:0.2. DMF was then added to the flask to a concentration of 150 mg / mL, and the mixture was reacted at 90°C for 48 hours. After cooling to room temperature, an end-capping agent was dissolved in DMF at a concentration of 150 mg / mL and added in a 2 molar ratio. The mixture was reacted at room temperature for 24 hours to obtain b12E. [Example]

[0327] Fabrication of polymer nanoparticles (PNPs) mRNA was added to the polymer produced by any one of the methods in Production Examples 1 to 260, and polymer nanoparticles (PNPs), which are nucleic acid transporters of the present invention, were produced by the following method.

[0328] The polymers prepared by any one of Preparation Examples 1 to 260 were diluted in 25 mM sodium acetate buffer at pH 5.0 in the appropriate ratio for each polymer. Then, 6 μL of the polymer solution was mixed with 6 μL of mRNA solution at a concentration of 1 mg / mL, and the mixture was allowed to stabilize at 4°C for 30 minutes. The mixture was then diluted with 38 μL of PBS to a total volume of 50 μL and used in the following test examples.

[0329] [Test Example 1] Analysis of the synthesized polymer The polymers obtained by the methods of Production Examples 1 to 260 were analyzed by the following methods.

[0330] 1.1 1 H-NMR The synthesized polymer was dissolved in deuterated chloroform (CDCl3) as a solvent. 1 The polymers were analyzed by H-NMR, and the results are shown in Figures 2 to 16. As shown in Figures 2 to 16, it was found that all polymers were successfully produced.

[0331] 1.2 Hydrophobic gel permeation chromatography The solvent was removed from the synthesized polymer, and then the polymer was dissolved in tetrahydrofuran (THF) at a concentration of 1-3 mg / mL and analyzed using hydrophobic gel permeation chromatography (Hydrophobic GPC).

[0332] [Test Example 2] Analysis of transporters in polymer nanoparticles (PNPs) Polymer nanoparticles (PNPs) produced in the same manner as in Example 1 were analyzed by the following method.

[0333] 2.1 Agarose gel electrophoresis For pH-sensitive polymers, the N / P ratio (the ratio of amines (N) in the polymer to the ratio of phosphates (P) in the mRNA) of the mRNA and polymer were adjusted and subjected to agarose gel electrophoresis. 5 μL of the polymer solution was dissolved in 25 mM NaOAc buffer at pH 5.0, and 5 μL of mRNA at a concentration of 200 ng / 5 μL was mixed and gently vortexed. The mixture was then 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 shown in Figures 17A-17C, complexes formed with different polymer N / P (polymer / mRNA) ratios. No mRNA bands formed in the gel, indicating that the complex was over the injection port. For example, the 6B polymer completely complexed from an N / P ratio of 4.

[0334] 2.2 Zeta potential and dynamic light scattering measurements For pH-sensitive polymers, the N / P ratio was adjusted for each polymer, and 6 μL of the solution was dissolved in 25 mM NaOAc buffer at pH 5.0. 6 μL of luciferase mRNA (FLuc) of SEQ ID NO: 1 at a concentration of 1 mg / mL was mixed and gently vortexed. The mixture was then stabilized at 4°C for 30 minutes, and 38 μL of PBS was added to bring the final volume to 50 μL.

[0335] The zeta potential and size of the polymer-mRNA complex were measured by diluting the complex solution 10-fold with distilled water and measuring it using a zeta potential meter and dynamic light scattering (DLS) instrument. As shown in Figure 18, the zeta potential was confirmed to change depending on the pH. This confirmed that positively charged mRNA complexes are formed at low pH and become neutral at in vivo pH, confirming low toxicity and high mRNA delivery efficiency.

[0336] [Test Example 3] Confirmation of mRNA expression in vivo of polymer nanoparticles (PNPs) The polymer nanoparticles prepared according to Example 1 were injected intramuscularly into animals, and mRNA expression was confirmed.

[0337] 3.1 Confirmation of in vivo mRNA expression Representative polymers were synthesized according to the method described in Preparation Example 1, and polymer nanoparticles were prepared according to Preparation Example 261 and screened for mRNA expression levels. The polymer-mRNA complexes used for intracorporeal injection to confirm mRNA expression were formed as follows: The weight ratio of each pH-sensitive, micellar polymer was adjusted, and 6 μL of a solution dissolved in 25 mM NaOAc buffer at pH 5.0 was mixed with 6 μL of FLuc (SEQ ID NO: 1) at a concentration of 1 mg / mL and vortexed gently. The mixture was then stabilized at 4°C for 30 minutes, and 38 μL of PBS was added to bring the final volume to 50 μL. Lipid nanoparticles (LNPs) used as a comparison group were prepared using the following method: The ionized lipid (SM-102):DSPC:cholesterol:PEG-lipid molar ratio was 50:10:38.5:1.5 and dissolved in ethanol. Next, mRNA diluted in 25 mM sodium acetate buffer, pH 5.0, was mixed with the ethanol-dissolved mixture at a volume ratio of 3:1 and an N / P ratio of 5.67. PBS was then added and centrifuged at 1000 xg for 5 minutes in a 100 kDa Amicon tube, followed by at least three rounds of centrifugation. Finally, the mixture was diluted with PBS to a concentration of 6 μg / 50 μL.

[0338] [Table 4]

[0339] To confirm in vivo mRNA expression using the composition, luciferase mRNA (FLuc) of SEQ ID NO: 1 was injected into the non-abdominal muscle (Gastrocnemius) of a mouse hind leg at a concentration of 6 μg / 50 μL. 24 hours later, mRNA expression was confirmed. Luciferin was intraperitoneally injected into each individual mouse at a concentration of 15 mg / mL in 200 μL. 10 minutes after luciferin injection, mRNA expression was confirmed with a 15-second exposure time.

[0340] As a result, as shown in Table 5 below, when mRNA was transported using the polymers of the present invention, mRNA expression was confirmed to be equal to or greater than that of free mRNA (as used herein, "free mRNA" means mRNA without a transporter), and 22 of the polymers were confirmed to have higher mRNA expression than lipid nanoparticle (LNP) transporters. Furthermore, experiments using representative branched polymers also showed higher mRNA expression rates than free mRNA. Therefore, it can be seen that the transporters of the present invention can be used as mRNA transporters.

[0341] [Table 5] JPEG2026503871000461.jpg7482

[0342] [Test Example 4] Confirmation of mRNA expression in vivo of polymer nanoparticles (PNPs) containing PEG The mRNA expression efficiency was confirmed using polymer nanoparticles (PNPs) containing PEG at both ends.

[0343] The polymer nanoparticles prepared according to Example 1 were intramuscularly injected into animals, and the expression rate of mRNA was confirmed.

[0344] Eight polymers (PEG-1A, PEG-1B, PEG-2A, PEG-2B, PEG-3A, PEG-3B, PEG-4A, and PEG-4B) prepared according to the manufacturing examples were screened for mRNA expression efficiency in vivo. To confirm mRNA expression, polymer-mRNA complexes were formed for intracorporeal injection as follows: 6 μL of a solution prepared by adjusting the weight ratio of each polymer and dissolving it in 25 mM NaOAc buffer at pH 5.0 was mixed with 6 μL of luciferase mRNA (FLuc) of SEQ ID NO: 1 at a concentration of 1 mg / mL and vortexed gently. The mixture was then stabilized at 4°C for 30 minutes, and 38 μL of PBS was added to bring the final volume to 50 μL.

[0345] To confirm in vivo mRNA expression, the composition was injected into the non-abdominal muscle (Gastrocnemius) of the hind limb of mice. Then, 24 hours after intramuscular injection, mRNA expression was confirmed. Luciferin was intraperitoneally injected into each individual at a concentration of 15 mg / mL in 200 μL. Ten minutes after luciferin injection, mRNA expression was confirmed with a 15-second exposure time.

[0346] As a result, as shown in Figure 19, when PEG was incorporated into both termini of the polymers produced in Production Examples 111 to 220 and mRNA expression of representative polymers was examined, it was confirmed that the expression rate was equal to or higher than that of free mRNA. Furthermore, while 1B produced in Production Example 2 had poor solubility, PEG-1B, which had PEG attached to both termini, showed improved solubility and significantly increased mRNA expression. Therefore, it can be seen that the transporters of the present invention can be useful as mRNA transporters.

[0347] [Test Example 5] Confirmation of in vivo expression retention time of PEG-containing polymer nanoparticles (PNPs) To confirm the mRNA expression retention time, a polymer-mRNA complex was prepared using a representative polymer from the Preparation Example in the same manner as in Test Example 3, and then injected into the hind leg of a mouse, followed by measurement for 20 days. The results are shown in Figure 20.

[0348] As shown in Figure 20, in the case of the lipid nanoparticle-mRNA complex (LNP-mRNA), expression peaked at 4 hours and then declined to below baseline levels by approximately 48 hours. In contrast, all polymer nanoparticle-mRNA complexes used in the study maintained mRNA expression for a longer period than the lipid nanoparticle-mRNA complex. In particular, the 6B and 8C polymer complexes maintained mRNA expression for more than 10 days, which means that gene therapy can be performed with significantly less frequent administration than conventional methods.

Claims

1. A polymer suitable for intracellular nucleic acid delivery, comprising a repeating unit of general formula 1: 【Chemistry 1】 ・・・（１） During the ceremony, R １ is a bond or C1-6 alkylene; R ２ and R ３ are each independently (i) hydrogen, (ii) C1-6 alkyl optionally substituted with alkylamine or hydroxy, (iii) a 5- or 6-membered carbocyclic or heterocyclic ring, or (iv) C1-6 alkyl substituted with a 5- or 6-membered carbocyclic or heterocyclic ring; The R ２ and R ３ may be bonded to each other to form a C1-6 alkylene; the 5- or 6-membered carbocyclic or heterocyclic ring is optionally substituted with C1-3 alkyl or C1-3 alkoxyacyl; X is a nitrogen atom or a bond, and when X is a bond, ３ does not exist, R ４ is a straight or branched C1-15 alkylene, in which 1 to 5 carbon atoms may be replaced by oxygen or sulfur; 【change】 represents a single or double bond.

2. A polymer suitable for intracellular nucleic acid delivery, comprising a repeating unit of general formula 2: 【Chemistry 2】 ・・・（２） During the ceremony, R ５ is C1-6 alkylene, R ６ is a straight or branched C1-15 alkylene, in which 1 to 5 carbon atoms may be replaced by oxygen or sulfur; 【change】 represents a single or double bond.

3. The polymer according to claim 1, wherein the repeating unit of general formula (1) is formed by a reaction between any one of monomers of the following general formulae 3 to 13 and any one of monomers of the following general formulae 14 to 23:

4. The polymer according to claim 2, wherein the repeating unit of general formula (2) is formed by a reaction between a monomer of the following general formula (24) and any one of monomers of the following general formulas (14) to (23):

5. A polymer comprising repeating units selected from the group consisting of repeating units having the chemical structures set forth in the table below.

6. The polymer according to any one of claims 1 to 5, comprising a branched-chain monomer of the following general formula (25): 【Transformation 3】 ・・・（２５）

7. The polymer according to any one of claims 1, 3 and 6, comprising a structure of the following general formula (26): 【Chemistry 4】 ・・・（２６） R １ is a bond or C1-6 alkylene; R ２ and R ３ are each independently (i) hydrogen, (ii) C1-6 alkyl optionally substituted with alkylamine or hydroxy, (iii) a 5- or 6-membered carbocyclic or heterocyclic ring, or (iv) C1-6 alkyl substituted with a 5- or 6-membered carbocyclic or heterocyclic ring; The R ２ and R ３ may be bonded to each other to form a C1-6 alkylene; the 5- or 6-membered carbocyclic or heterocyclic ring is optionally substituted with C1-3 alkyl or C1-3 alkoxyacyl; X is a nitrogen atom or a bond, and when X is a bond, ３ does not exist, R ４ is a straight or branched C1-15 alkylene, in which 1 to 5 carbon atoms may be replaced by oxygen or sulfur; 【change】 represents a single or double bond.

8. The polymer according to any one of claims 2, 4 and 6, comprising a structure of the following general formula (27): 【Transformation 5】 ・・・（２７） During the ceremony, R ５ is C1-6 alkylene, R ６ is a straight or branched C1-15 alkylene, in which 1 to 5 carbon atoms may be replaced by oxygen or sulfur; 【change】 represents a single or double bond.

9. The polymer according to any one of claims 1 to 8, wherein one or both ends of the polymer are linked to a PEG-containing residue comprising the structure of the following general formula (28): 【Transformation 6】 ・・・（２８） During the ceremony, 【change】 represents a double or triple bond, n is an integer ranging from 1 to 500.

10. A polymer nanoparticle comprising a complex of the polymer according to any one of claims 1 to 9 and a nucleic acid molecule.

11. The polymeric nanoparticle of claim 10 , wherein the nucleic acid molecule is RNA.

12. The polymeric nanoparticle of claim 10 , wherein the nucleic acid molecule is DNA.

13. The polymeric nanoparticles according to any one of claims 10 to 12, wherein nucleic acid molecules are separated in a pH-dependent manner and transported into cells in the body.

14. 12. The polymeric nanoparticle of claim 11, wherein when delivered into the body, expression of the nucleic acid molecule is maintained for a longer period of time than when the same nucleic acid molecule is delivered into the body in the form of a non-polymeric lipid nanoparticle.

15. A method for transporting nucleic acid molecules into cells using the polymeric nanoparticles of any one of claims 10 to 14.

16. 16. The method of claim 15, wherein the polymeric nanoparticles are delivered by parenteral, intramuscular, subcutaneous or intravenous administration.

17. A pharmaceutical composition comprising the polymeric nanoparticles according to any one of claims 10 to 14.

18. The pharmaceutical composition of claim 17, which is a gene therapy agent.

19. 18. The pharmaceutical composition of claim 17, which is a vaccine.

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