Novel compound having targeting site introduced through biodegradable linker and method for preparing same

Abstract

The present invention relates to a novel compound having a targeting site introduced through a biodegradable linker and a method for preparing same, and more specifically, to a compound useful for tissue- or organ-specific drug delivery by enabling various molecular designs according to target tissues or organs, and a method for preparing same.

Description

Novel compound having a targeting site introduced via a biodegradable linker and method for preparing the same

[0001] The present invention relates to a novel compound having a targeting site introduced through a biodegradable linker and a method for preparing the same. More specifically, it relates to a compound useful for tissue or organ-specific drug delivery, which allows for various molecular designs depending on the target tissue or organ, and a method for preparing the same.

[0002] In the treatment of anionic drugs, including nucleic acids, safe and efficient drug delivery technologies have been studied for a long time, and various carriers and delivery technologies have been developed. Carriers are broadly classified into viral carriers utilizing adenoviruses or retroviruses, and non-viral carriers utilizing cationic lipids and cationic polymers. Viral carriers are known to pose risks such as non-specific immune responses and face significant challenges in commercialization due to their complex production processes. Therefore, recent research trends are moving toward improving these shortcomings by utilizing non-viral carriers. Compared to viral carriers, non-viral carriers offer the advantages of fewer side effects in terms of in vivo safety and lower production costs in terms of economic feasibility.

[0003] Representative non-viral delivery vehicles used for the delivery of nucleic acid materials are lipoplexes and polyplexes. These cationic lipids or polycationic polymers have been the subject of extensive research because they stabilize anionic drugs and enhance intracellular delivery by forming complexes through electrostatic interactions (De Paula D, Bentley MV, Mahato RI, Hydrophobization and bioconjugation for enhanced siRNA delivery and targeting, RNA 13 (2007) 431-56; Gary DJ, Puri N, Won YY, Polymer-based siRNA delivery: Perspectives on the fundamental and phenomenological distinctions from polymer-based DNA delivery, J Control release 121 (2007) 64-73).

[0004] However, polycation polymers have problems with actual use due to cytotoxicity caused by multivalent cation charges, and nucleic acid-cationic lipid complexes are difficult to use in vivo due to low stability in the blood. In addition, ionic liposomes containing cationic lipids, neutral lipids, and fusogenic lipids have disadvantages such as complex synthesis methods for the cationic lipids used, cytotoxicity, and low efficiency of intracellular nucleic acid delivery.

[0005] The object of the present invention is to provide a compound useful for tissue or organ-specific drug delivery, which enables various molecular designs depending on the target tissue or organ, and a method for manufacturing the same.

[0006] A first aspect of the present invention provides a compound having a structure represented by the following chemical formula 1:

[0007] [Chemical Formula 1]

[0008]

[0009] In the above,

[0010] R1 is a tissue or organ targeting site (moiety for targeting tissue or organ) that is unprotected or protected by a protective device, and

[0011] R2 is a substituted or unsubstituted divalent saturated or unsaturated hydrocarbon group, and

[0012] R3 to R5 are each independently (i) a hydrogen atom (H), (ii) , (iii) , (iv) , (v) , (vi) , or (vii) However, at least one of R3 to R5 is any one of (ii) to (vii), and

[0013] R6 to R 17 Each is independently a substituted or unsubstituted divalent saturated or unsaturated hydrocarbon group, and

[0014] R 18 to R 23 Each is independently a substituted or unsubstituted monovalent saturated or unsaturated hydrocarbon group, and

[0015] L1 to L 14Each is independently selected from the group consisting of -C(O)O-, -OC(O)-, -OC(O)-L'-C(O)O-, -C(O)N(R')-, -N(R')C(O)-, -C(O)-, -C(S)-, -C(S)S-, -SC(S)-, -CH(OH)-, -P(O)(OR')O-, -S(O)2-, -SS-, arylene groups, and heteroarylene groups, wherein L' is a directly bonded, substituted or unsubstituted alkylene group or a substituted or unsubstituted alkenylene group, and R' is each independently selected from the group consisting of a hydrogen atom, a substituted or unsubstituted alkyl group and a substituted or unsubstituted alkenyl group, and

[0016] X is -OH or -SH, and

[0017] n is an integer greater than or equal to 1, and

[0018] m is 0 or 1, and when m is 1, N with R5 attached has a positive charge (+1).

[0019] In one embodiment, the targeting site of the tissue or organ (e.g., liver, lung, spleen, brain, heart, etc.) may be a site derived from amino acids, sugars, vitamins, peptides, proteins, hormones, antibodies, neurotransmitters, pharmaceutically active small molecules, endosome-degrading agents, cell membrane permeability agents, charge blockers, drugs, nucleic acids, or derivatives thereof.

[0020] In one embodiment, the tissue or organ targeting site may be protected by a protective device.

[0021] In one embodiment, the protecting group may be selected from the group consisting of a t-butyl carbamate group, a fluorenylmethyl carbamate group, a benzyl carbamate group, an acetamide group, a trifluoroacetamide group, a phthalimide group, a benzylamine group, a triphenylmethylamine group, a p-toluenesulfonamide group, a methyl ester group, an ethyl ester group, a t-butyl ester group, a benzyl ester group, and a St-butyl ester group.

[0022] More specifically, as mentioned above,

[0023] R1 is a site derived from unprotected or protected amino acids, sugars, vitamins, peptides, proteins, hormones, antibodies, neurotransmitters, pharmaceutically active small molecules, endosome-degrading agents, cell membrane permeability agents, charge blockers, drugs, nucleic acids, or derivatives thereof, and

[0024] R2 is substituted or unsubstituted divalent saturated or unsaturated C 2-20 It is a hydrocarbon group, and

[0025] R3 to R5 are each independently (i) a hydrogen atom (H), (ii) , (iii) , (iv) , (v) , (vi) , or (vii) However, at least two of R3 to R5 are any one of (ii) to (vii), and

[0026] R6 to R 17 Each is independently substituted or unsubstituted divalent saturated or unsaturated C 2-20 It is a hydrocarbon group, and

[0027] R 18 to R 23 Each is independently substituted or unsubstituted monovalent saturated or unsaturated C 2-20 It is a hydrocarbon group, and

[0028] L1 to L 14 -C(O)O-, -OC(O)-, -C(O)N(R')-, -N(R')C(O)-, -C(O)-, -C(S)-, -C(S)S-, -SC(S)-, -CH(OH)-, -P(O)(OR')O-, -S(O)2-, -SS-, C 6-20 C having an arylene group and one or more heteroatoms selected from N, O, and S 3-20Selected from the group consisting of heteroarylene groups, where L' is directly bonded, substituted, or unsubstituted C 1-13 alkylene group or substituted or unsubstituted C 2-13 It is an alkenylene group, and R' are each independently hydrogen atoms, substituted or unsubstituted C. 1-18 Alkyl groups and substituted or unsubstituted C 2-18 Selected from a group composed of alkenyl groups, and

[0029] X is -OH or -SH, and

[0030] n is an integer from 1 to 250 (or 1 to 200, or 1 to 150, or 1 to 100), and

[0031] m is 0 or 1, and when m is 1, N with R5 attached has a positive charge (+1).

[0032] More specifically, as mentioned above,

[0033] R1 is a site derived from unprotected or protected amino acids, sugars, vitamins, peptides, proteins, hormones, antibodies, neurotransmitters, pharmaceutically active small molecules, endosome-degrading agents, cell membrane permeability agents, charge blockers, drugs, nucleic acids, or derivatives thereof, and

[0034] R2 is substituted or unsubstituted divalent saturated or unsaturated C 2-10 It is a hydrocarbon group, and

[0035] R3 to R5 are each independently (i) a hydrogen atom (H), (ii) , (iii) , (iv) , (v) , (vi) , or (vii) However, at least two of R3 to R5 are any one of (ii) to (vii), and

[0036] R6 to R 17 Each is independently substituted or unsubstituted divalent saturated or unsaturated C2-10 It is a hydrocarbon group, and

[0037] R 18 to R 23 Each is independently substituted or unsubstituted monovalent saturated or unsaturated C 10-20 It is a hydrocarbon group, and

[0038] L1 to L 14 Each is independently selected from the group consisting of -C(O)O-, -OC(O)-, -C(O)N(R')-, and -N(R')C(O)-, where R' is each independently a hydrogen atom, and a substituted or unsubstituted C 1-4 Selected from the group consisting of alkyl groups, and

[0039] X is -OH or -SH, and

[0040] n is an integer from 1 to 50, and

[0041] m is 0 or 1, and when m is 1, N with R5 attached has a positive charge (+1).

[0042] More specifically, the compound of the present invention may have a structure selected from any one of the following compounds 1-A to 1-I:

[0043]

[0044]

[0045] A second aspect of the present invention provides a method for preparing a compound having a structure represented by Formula 1, comprising the step of reacting a compound of Formula a with a compound of Formula b:

[0046] [Chemical formula a]

[0047]

[0048] [Chemical formula b]

[0049]

[0050] [Chemical Formula 1]

[0051]

[0052] In the above,

[0053] R1 is an unprotected or protected tissue or organ targeting site, and

[0054] R2 is a substituted or unsubstituted divalent saturated or unsaturated hydrocarbon group, and

[0055] R3 to R5 are each independently (i) a hydrogen atom (H), (ii) , (iii) , (iv) , (v) , (vi) , or (vii) However, at least one of R3 to R5 is any one of (ii) to (vii), and

[0056] R6 to R 17 Each is independently a substituted or unsubstituted divalent saturated or unsaturated hydrocarbon group, and

[0057] R 18 to R 23 Each is independently a substituted or unsubstituted monovalent saturated or unsaturated hydrocarbon group, and

[0058] L1 is -C(O)N(R')-, and R' is each independently selected from the group consisting of a hydrogen atom, a substituted or unsubstituted alkyl group and a substituted or unsubstituted alkenyl group, and

[0059] L2 to L 14Each is independently selected from the group consisting of -C(O)O-, -OC(O)-, -OC(O)-L'-C(O)O-, -C(O)N(R')-, -N(R')C(O)-, -C(O)-, -C(S)-, -C(S)S-, -SC(S)-, -CH(OH)-, -P(O)(OR')O-, -S(O)2-, -SS-, arylene groups, and heteroarylene groups, wherein L' is a directly bonded, substituted or unsubstituted alkylene group or a substituted or unsubstituted alkenylene group, and R' is each independently selected from the group consisting of a hydrogen atom, a substituted or unsubstituted alkyl group and a substituted or unsubstituted alkenyl group, and

[0060] X is -OH or -SH, and

[0061] n is an integer greater than or equal to 1, and

[0062] m is 0 or 1, and when m is 1, N with R5 attached has a positive charge (+1).

[0063] A third aspect of the present invention provides a method for preparing a compound having a structure represented by Formula 1, comprising the step of reacting a compound of Formula c with a compound of Formula d:

[0064] [Chemical formula c]

[0065]

[0066] [Chemical formula d]

[0067]

[0068] [Chemical Formula 1]

[0069]

[0070] In the above,

[0071] R1 is an unprotected or protected tissue or organ targeting site, and

[0072] R2 is a substituted or unsubstituted divalent saturated or unsaturated hydrocarbon group, and

[0073] R3 to R5 are each independently (i) a hydrogen atom (H), (ii) , (iii) , (iv) , (v) , (vi) , or (vii) However, at least one of R3 to R5 is any one of (ii) to (vii), and

[0074] R6 to R 17 Each is independently a substituted or unsubstituted divalent saturated or unsaturated hydrocarbon group, and

[0075] R 18 to R 23 Each is independently a substituted or unsubstituted monovalent saturated or unsaturated hydrocarbon group, and

[0076] L2 is -N(R')C(O)-, and R' is each independently selected from the group consisting of a hydrogen atom, a substituted or unsubstituted alkyl group and a substituted or unsubstituted alkenyl group, and

[0077] L1 and L3 to L 14 Each is independently selected from the group consisting of -C(O)O-, -OC(O)-, -OC(O)-L'-C(O)O-, -C(O)N(R')-, -N(R')C(O)-, -C(O)-, -C(S)-, -C(S)S-, -SC(S)-, -CH(OH)-, -P(O)(OR')O-, -S(O)2-, -SS-, arylene groups, and heteroarylene groups, wherein L' is a directly bonded, substituted or unsubstituted alkylene group or a substituted or unsubstituted alkenylene group, and R' is each independently selected from the group consisting of a hydrogen atom, a substituted or unsubstituted alkyl group and a substituted or unsubstituted alkenyl group, and

[0078] X is -OH or -SH, and

[0079] n is an integer greater than or equal to 1, and

[0080] m is 0 or 1, and when m is 1, N with R5 attached has a positive charge (+1).

[0081] A fourth aspect of the present invention provides a drug delivery composition comprising a compound of the present invention.

[0082] The compound according to the present invention allows for various molecular designs depending on the target tissue or organ, making it useful for specifically delivering drugs to the target tissue or organ. In particular, due to the presence of tissue or organ targeting sites, the compound of the present invention can selectively deliver drugs to specific organs in vivo through specific transporters and receptors.

[0083] Figure 1 is a schematic diagram of the reaction for the synthesis process of the compounds of formulas 1-A and 1-B performed in Example 1.

[0084] Figure 2 is a schematic diagram of the reaction for the synthesis process of the compounds of formulas 1-C and 1-D performed in Example 2.

[0085] Figure 3 is a schematic diagram of the reaction for the synthesis process of the compounds of formulas 1-E and 1-F performed in Example 3.

[0086] Figure 4 is a schematic diagram of the reaction for the synthesis process of the compounds of formulas 1-G and 1-H performed in Example 4.

[0087] Figure 5 is a schematic diagram of the reaction for the synthesis process of a cationic lipid of Formula 2-E performed in an example of the preparation of a drug delivery composition.

[0088] The present invention will be described in more detail below.

[0089] A compound provided according to the first aspect of the present invention has a structure represented by the following chemical formula 1:

[0090] [Chemical Formula 1]

[0091]

[0092] In the above,

[0093] R1 is a tissue or organ targeting site (moiety for targeting tissue or organ) that is unprotected or protected by a protective device, and

[0094] R2 is a substituted or unsubstituted divalent saturated or unsaturated hydrocarbon group, and

[0095] R3 to R5 are each independently (i) a hydrogen atom (H), (ii) , (iii) , (iv) , (v) , (vi) , or (vii) However, at least one of R3 to R5 is any one of (ii) to (vii), and

[0096] R6 to R 17 Each is independently a substituted or unsubstituted divalent saturated or unsaturated hydrocarbon group, and

[0097] R 18 to R 23 Each is independently a substituted or unsubstituted monovalent saturated or unsaturated hydrocarbon group, and

[0098] L1 to L 14 Each is independently selected from the group consisting of -C(O)O-, -OC(O)-, -OC(O)-L'-C(O)O-, -C(O)N(R')-, -N(R')C(O)-, -C(O)-, -C(S)-, -C(S)S-, -SC(S)-, -CH(OH)-, -P(O)(OR')O-, -S(O)2-, -SS-, arylene groups, and heteroarylene groups, wherein L' is a directly bonded, substituted or unsubstituted alkylene group or a substituted or unsubstituted alkenylene group, and R' is each independently selected from the group consisting of a hydrogen atom, a substituted or unsubstituted alkyl group and a substituted or unsubstituted alkenyl group, and

[0099] X is -OH or -SH, and

[0100] n is an integer greater than or equal to 1, and

[0101] m is 0 or 1, and when m is 1, N with R5 attached has a positive charge (+1).

[0102] The scope of the compounds of the present invention includes not only those having the structure of Chemical Formula 1, but also their cationized forms.

[0103] In this specification, the expression “substituted or unsubstituted” means that, unless otherwise specified, the group is not substituted, or -OH, a halogen atom, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 alkyl halide group, C 1-6 Halogenated alkoxy group, C 3-20 Cycloalkyl group, C 3-20 heterocycloalkyl group, C 6-20 aryl group or C 3-20 This means that it is substituted with one or more substituents selected from heteroaryl groups. In addition, in one embodiment, the substituents may include amino acids, sugars, vitamins, peptides, proteins, hormones, antibodies, neurotransmitters, pharmaceutically active small molecules, endosome degrading agents, cell membrane permeability agents, charge blockers, drugs, nucleic acids, etc.

[0104] In this specification, the expression that any group (e.g., heteroaryl, heterocycloalkyl, etc.) is a “hetero” group means that, unless otherwise specified, the group has one or more (e.g., 1 to 3) hetero atoms selected from N, O and S.

[0105] In this specification, the “hydrocarbon group” may be branched or unbranched, annular or non-annular, or aromatic.

[0106] In one embodiment, the targeting site of the tissue or organ (e.g., liver, lung, spleen, brain, heart, etc.) may be a site derived from amino acids, sugars, vitamins, peptides, proteins, hormones, antibodies, neurotransmitters, pharmaceutically active small molecules, endosome-degrading agents, cell membrane permeability agents, charge blockers, drugs, nucleic acids, or derivatives thereof.

[0107] In one embodiment, the tissue or organ targeting site may be protected by a protective device.

[0108] In one embodiment, the protecting group may be selected from the group consisting of a t-butyl carbamate group, a fluorenylmethyl carbamate group, a benzyl carbamate group, an acetamide group, a trifluoroacetamide group, a phthalimide group, a benzylamine group, a triphenylmethylamine group, a p-toluenesulfonamide group, a methyl ester group, an ethyl ester group, a t-butyl ester group, a benzyl ester group, and a St-butyl ester group.

[0109] In the compound of the present invention, the L1 and L2 groups are introduced for the purpose of effectively releasing the drug by removing the polyethylene glycol (PEG)-derived site that performs a stealth function after the compound is introduced into the body and a certain period of time has passed.

[0110] Here, the term “stealth function” refers to a function that prevents substances such as proteins that degrade nanoparticles, etc., from recognizing the nanoparticles. If the compound of the present invention lacks a PEG-derived site that performs such a stealth function, the in vivo blood circulation time is reduced, and consequently, the nanoparticles degrade before the drug is delivered, making it impossible to effectively deliver the drug. However, after a sufficient amount of time has passed for the drug to be delivered, the PEG-derived site must be removed and the nanoparticles degrade to deliver the drug; at this time, L1 and L2 groups are introduced to effectively remove the PEG-derived site.

[0111] Meanwhile, in the compound of the present invention, L3 to L 14 The device was introduced for the purpose of reducing toxicity and side effects along with effective drug release.

[0112] More specifically, as mentioned above,

[0113] R1 may be a site derived from unprotected or protected amino acids, sugars, vitamins, peptides, proteins, hormones, antibodies, neurotransmitters, pharmaceutically active small molecules, endosome-degrading agents, cell membrane permeability agents, charge blockers, drugs, nucleic acids, or derivatives thereof, and

[0114] R2 is substituted or unsubstituted divalent saturated or unsaturated C 2-20 It can be a hydrocarbon group,

[0115] R3 to R5 are each independently (i) a hydrogen atom (H), (ii) , (iii) , (iv) , (v) , (vi) , or (vii) However, at least two of R3 to R5 may be any one of (ii) to (vii), and

[0116] R6 to R 17 Each is independently substituted or unsubstituted divalent saturated or unsaturated C 2-20 It can be a hydrocarbon group,

[0117] R 18 to R 23 Each is independently substituted or unsubstituted monovalent saturated or unsaturated C 2-20 It can be a hydrocarbon group,

[0118] L1 to L 14-C(O)O-, -OC(O)-, -C(O)N(R')-, -N(R')C(O)-, -C(O)-, -C(S)-, -C(S)S-, -SC(S)-, -CH(OH)-, -P(O)(OR')O-, -S(O)2-, -SS-, C 6-20 C having an arylene group and one or more heteroatoms selected from N, O, and S 3-20 It can be selected from the group consisting of heteroarylene groups, where L' is directly bonded, substituted, or unsubstituted C 1-13 alkylene group or substituted or unsubstituted C 2-13 It can be an alkenylene group, and R' are each independently hydrogen atoms, substituted or unsubstituted C 1-18 Alkyl groups and substituted or unsubstituted C 2-18 It can be selected from a group composed of alkenyl groups, and

[0119] n can be an integer from 1 to 250 (or 1 to 200, or 1 to 150, or 1 to 100).

[0120] More specifically, as mentioned above,

[0121] R1 may be a site derived from unprotected or protected amino acids, sugars, vitamins, peptides, proteins, hormones, antibodies, neurotransmitters, pharmaceutically active small molecules, endosome-degrading agents, cell membrane permeability agents, charge blockers, drugs, nucleic acids, or derivatives thereof, and

[0122] R2 is substituted or unsubstituted divalent saturated or unsaturated C 2-10 It can be a hydrocarbon group,

[0123] R3 to R5 are each independently (i) a hydrogen atom (H), (ii) , (iii) , (iv) , (v) , (vi) , or (vii) However, at least two of R3 to R5 may be any one of (ii) to (vii), and

[0124] R6 to R 17 Each is independently substituted or unsubstituted divalent saturated or unsaturated C 2-10 It can be a hydrocarbon group,

[0125] R 18 to R 23 Each is independently substituted or unsubstituted monovalent saturated or unsaturated C 10-20 It can be a hydrocarbon group,

[0126] L1 to L 14 Each can be independently selected from the group consisting of -C(O)O-, -OC(O)-, -C(O)N(R')-, and -N(R')C(O)-, where R' is independently a hydrogen atom, and a substituted or unsubstituted C 1-4 It can be selected from the group consisting of alkyl groups, and

[0127] n can be an integer from 1 to 50.

[0128] More specifically, the compound of the present invention may have a structure selected from any one of the following compounds 1-A to 1-I:

[0129]

[0130]

[0131] The compound according to the present invention allows for various molecular designs depending on the target tissue or organ, making it useful for specifically delivering drugs to the target tissue or organ. In particular, due to the presence of tissue or organ targeting sites, the compound of the present invention can selectively deliver drugs to specific organs in vivo through specific transporters and receptors.

[0132] In one embodiment, the “target tissue or organ targeting site” includes all molecules such as amino acids, sugars, vitamins, peptides, proteins, hormones, antibodies, neurotransmitters, pharmaceutically active small molecules, endosome-degrading agents, cell membrane permeability agents, charge blockers, drugs, nucleic acids, or derivatives thereof that can interact directly or indirectly with other compounds such as receptors. The sugar may include, but is not limited to, galactose, galactosamine, N-acetylgalactosamine, or combinations thereof. The hormone may include, but is not limited to, estrogen, testosterone, progesterone, glucocortisone, adrenaline, insulin, glucagon, cortisol, vitamin D, thyroid hormone, retinoic acid, growth hormone, or combinations thereof. The neurotransmitter may include growth factors such as VEGF, EGF, NGF, and PDGF; cholesterol; bile acids; It may include, but is not limited to, GABA, glutamate, acetylcholine, or combinations thereof.

[0133] In one embodiment, the “target tissue or organ targeting site” may be attached to the compound of the present invention using a linker molecule. The linker molecule may include, but is not limited to, amides, carbonyls, esters, peptides, disulfides, silanes, nucleosides, abasic nucleosides, polyethers, polyamines, polyamides, carbohydrates, lipids, polyhydrocarbons, phosphate esters, phosphoramidates, thiophosphates, alkyl phosphates, biodegradable linkers, photolabile linkers, etc.

[0134] A second aspect of the present invention provides a method for preparing a compound having a structure represented by Formula 1, comprising the step of reacting a compound of Formula a with a compound of Formula b:

[0135] [Chemical formula a]

[0136]

[0137] [Chemical formula b]

[0138]

[0139] [Chemical Formula 1]

[0140]

[0141] In the above,

[0142] L1 is -C(O)N(R')-, and R' is each independently selected from the group consisting of a hydrogen atom, a substituted or unsubstituted alkyl group and a substituted or unsubstituted alkenyl group, and

[0143] R1 to R 23 , L2 to L 14 , X, n and m are as defined in Chemical Formula 1 above.

[0144] In one embodiment of a method for preparing a compound according to the second aspect of the present invention, the reaction between the compound of formula a and the compound of formula b may be carried out in a solvent (e.g., tetrahydrofuran (THF), etc.) in the presence of a catalyst (e.g., N,N′dicyclohexylcarbodiimide (DCC), N-hydroxysuccinimide (NHS), etc.) at a temperature below room temperature (e.g., 0°C to 25°C), but is not limited thereto.

[0145] A third aspect of the present invention provides a method for preparing a compound having a structure represented by Formula 1, comprising the step of reacting a compound of Formula c with a compound of Formula d:

[0146] [Chemical formula c]

[0147]

[0148] [Chemical formula d]

[0149]

[0150] [Chemical Formula 1]

[0151]

[0152] In the above,

[0153] L2 is -N(R')C(O)-, and R' is each independently selected from the group consisting of a hydrogen atom, a substituted or unsubstituted alkyl group and a substituted or unsubstituted alkenyl group, and

[0154] R1 to R 23 , L1, L3 to L 14 , X, n and m are as defined in Chemical Formula 1 above.

[0155] In one embodiment of the method for preparing a compound according to the third aspect of the present invention, the reaction between the compound of formula c and the compound of formula d may be carried out in a solvent (e.g., dichloromethane (DCM), etc.) in the presence of a catalyst (e.g., N,N′ dicyclohexylcarbodiimide (DCC), 4-dimethylaminopyridine (DMAP), etc.) at a temperature below room temperature (e.g., 0°C to 25°C), but is not limited thereto.

[0156] The compound according to the present invention is useful for specifically delivering drugs to target tissues or organs (e.g., liver, lungs, spleen, brain, heart, etc.). In particular, due to the presence of tissue or organ targeting sites, the compound of the present invention can selectively deliver drugs to specific organs in vivo through specific transporters and receptors.

[0157] Accordingly, according to a third aspect of the present invention, a drug delivery composition comprising a compound of the present invention is provided. In one embodiment, the drug may be selected from nucleic acids, polypeptides, viruses, or combinations thereof.

[0158] The “nucleic acid” mentioned above may be, for example, DNA, RNA, siRNA, shRNA, miRNA, mRNA, aptamers, antisense oligonucleotides, or combinations thereof, but is not limited thereto.

[0159] The above “polypeptide” may refer to a protein having activity in the body, such as an antibody or a fragment thereof, a cytokine, a hormone or an analog thereof, or a protein that can be recognized as an antigen through a series of processes in the body, including a polypeptide sequence of an antigen, an analog thereof, or a precursor thereof.

[0160] In one embodiment, the drug delivery composition of the present invention includes a cationic lipid to form a complex with the drug, and the complex may be encapsulated inside a nanoparticle structure formed by an amphiphilic block copolymer.

[0161] In one embodiment, the amphiphilic block copolymer may be an AB-type block copolymer comprising a hydrophilic A block and a hydrophobic B block. The AB-type block copolymer forms core-shell type polymer nanoparticles in an aqueous solution, wherein the hydrophobic B block forms the core (inner wall) and the hydrophilic A block forms the shell (outer wall).

[0162] In one embodiment, the hydrophilic A block may be one or more selected from the group consisting of polyalkylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, polyacrylamide, and derivatives thereof.

[0163] More specifically, the hydrophilic A block may be one or more selected from the group consisting of monomethoxypolyethylene glycol (mPEG), monoacetoxypolyethylene glycol, polyethylene glycol, copolymers of polyethylene and propylene glycol, and polyvinylpyrrolidone.

[0164] Additionally, if necessary, a functional group, a ligand capable of reaching specific tissues or cells, or a functional group capable of promoting intracellular delivery can be chemically bonded to the terminal end of the hydrophilic A block to control the distribution of the nanoparticle delivery vehicle in the body or to increase the efficiency of the nanoparticle delivery vehicle being delivered into cells. In one embodiment, the functional group or ligand may be one or more selected from the group consisting of monosaccharides, polysaccharides, vitamins, peptides, proteins, and antibodies against cell surface receptors. More specifically, the functional group or ligand may be one or more selected from the group consisting of anisamide, vitamin B9 (folic acid), vitamin B12, vitamin A, galactose, lactose, mannose, hyaluronic acid, RGD peptide, NGR peptide, transferrin, and antibodies against transferrin receptors.

[0165] The above hydrophobic B block is a biocompatible biodegradable polymer, and in one embodiment, it may be one or more selected from the group consisting of polyester, polyanhydride, polyamino acid, polyorthoester, and polyphosphazine.

[0166] More specifically, the hydrophobic B block may be one or more selected from the group consisting of polylactide (PLA), polyglycolide, polycaprolactone, polydioxane-2-one, copolymers of polylactide and glycolide, copolymers of polylactide and polydioxane-2-one, copolymers of polylactide and polycaprolactone, and copolymers of polyglycolide and polycaprolactone.

[0167] In another embodiment, the hydrophobic B block is a biocompatible biodegradable polymer having repeating units of a structure represented by the following chemical formula e.

[0168] [Chemical formula e]

[0169]

[0170] In the above chemical formula e, R represents a branched alkylene group having 3 or more carbon atoms.

[0171] In one embodiment, the number of carbon atoms of R in the above formula e may be, for example, 3 or more, 4 or more, 5 or more, 6 or more, or 7 or more, and may also be 20 or less, 19 or less, 18 or less, 17 or less, 16 or less, 15 or less, 14 or less, or 13 or less, but is not limited thereto.

[0172] In one embodiment, in the above formula e, R may represent a branched alkylene group having 3 to 20 carbon atoms, more specifically a branched alkylene group having 3 to 17 carbon atoms, even more specifically a branched alkylene group having 3 to 15 carbon atoms, and even more specifically a branched alkylene group having 3 to 13 carbon atoms, but is not limited thereto.

[0173] In one embodiment, the hydrophobic B block may be a biocompatible biodegradable polymer having repeating units of a structure selected from the following, but is not limited thereto.

[0174]

[0175] In one embodiment, the repeating unit of the structure represented by the above formula e can be obtained by ring-opening polymerization of a lactone compound.

[0176] In addition, in one embodiment, the hydrophobic B block may be modified by chemically bonding tocopherol, cholesterol, or a fatty acid having 10 to 24 carbon atoms to the hydroxyl group at the end of the hydrophobic B block in order to increase the hydrophobicity of the hydrophobic B block and improve the stability of the nanoparticle.

[0177] In one embodiment, the drug delivery composition of the present invention may include a cationic compound.

[0178] The above cationic compound may be a cationic lipid, a cationic polymer, or a combination thereof, and more specifically, may be a cationic lipid. For example, the above cationic lipids are N,N-dioleyl-N,N-dimethylammonium chloride (DODAC), N,N-distearyl-N,N-dimethylammonium bromide (DDAB), N-(1-(2,3-dioleoyloxy)propyl-N,N,N-trimethylammonium chloride (DOTAP), N,N-dimethyl-(2,3-dioleoyloxy)propylamine (DODMA), N,N,N-trimethyl-(2,3-dioleoyloxy)propylamine (DOTMA), 1,2-diacyl-3-trimethylammonium-propane (TAP), 1,2-diacyl-3-dimethylammonium-propane (DAP), 3-beta-[N-(N',N',N'-trimethylaminoethane)carbamoyl]cholesterol (TC-cholesterol), It may be one or more combinations selected from the group consisting of 3-beta-[N-(N',N'-dimethylaminoethane)carbamoyl]cholesterol (DC-cholesterol), 3-beta-[N-(N'-monomethylaminoethane)carbamoyl]cholesterol (MC-cholesterol), 3-beta-[N-(aminoethane)carbamoyl]cholesterol (AC-cholesterol), cholesteryloxypropane-1-amine (COPA), N-(N'-aminoethane)carbamoylpropanoic tocopherol (AC-tocopherol), and N-(N'-methylaminoethane)carbamoylpropanoic tocopherol (MC-tocopherol), and more specifically, 3-beta-[N-(N',N',N'-trimethylaminoethane)carbamoyl]cholesterol (TC-cholesterol), It may be one or more selected from the group consisting of 3-beta[N-(N',N'-dimethylaminoethane)carbamoyl]cholesterol (DC-cholesterol), 3-beta[N-(N'-monomethylaminoethane)carbamoyl]cholesterol (MC-cholesterol), 3-beta[N-(aminoethane)carbamoyl]cholesterol (AC-cholesterol), N-(1-(2,3-dioleoyloxy)propyl-N,N,N-trimethylammonium chloride (DOTAP), N,N-dimethyl-(2,3-dioleoyloxy)propylamine (DODMA), and N,N,N-trimethyl-(2,3-dioleoyloxy)propylamine (DOTMA).

[0179] In one embodiment, the cationic lipid may be a lipid having the structure of the following chemical formula 2 or an ionized form thereof:

[0180] [Chemical Formula 2]

[0181]

[0182] In the above chemical formula 2,

[0183] M1 and M2 are each independently divalent linker groups, and

[0184] R1 and R2 are each independently substituted or unsubstituted carboncyclic or heterocyclic groups, and

[0185] R3 is a hydrogen atom, or optionally a substituted or unsubstituted organic group containing one or more heteroatoms, and

[0186] R4 to R 11 Each is independently a hydrogen atom, or a substituted or unsubstituted saturated or unsaturated hydrocarbon group, and

[0187] Me is a methyl group, and

[0188] a, b, c, and d are each independently integers from 1 to 20.

[0189] In the above Chemical Formula 2, the expression that any group is “substituted or unsubstituted” means that, unless otherwise specified, the group is not substituted, or a hydroxyl group or C 1-6 It means that it is substituted with an alkyl group.

[0190] According to one embodiment, in the above formula 2, M1 and M2 are each independently -C(O)O-, -OC(O)-, -OC(O)-M'-C(O)O-, -C(O)N(R')-, -N(R')C(O)-, -C(O)-, -C(S)-, -C(S)S-, -SC(S)-, -CH(OH)-, -P(O)(OR')O-, -S(O)2-, -SS-, arylene (more specifically C 6-20Aryllene, more specifically, C 6-10 Aryllene), and heteroarylene (more specifically, C having one or more (e.g., 1 to 3) heteroatoms selected from N, O, and S). 3-20 Heteroarylene, more specifically, C 3-10 It can be selected from the group consisting of heteroarylenes, where M' is direct bonding, C 1-13 Alkylene (more specifically, C 1-6 alkylene) or C 2-13 Alkenylene (more specifically, C 2-6 It can be alkenylene), and R' are each independently hydrogen atoms, C 1-18 Alkyl (more specifically, C 1-10 Alkyl, more specifically C 1-6 alkyl) and C 2-18 Alkenyl (more specifically, C 2-10 Alkenyl, more specifically C 2-6 It can be selected from a group consisting of alkenyls.

[0191] According to one embodiment, in the above formula 2, R1 and R2 are each independently substituted or unsubstituted C 3-20 cycloalkyl (more specifically, C 3-10 Cycloalkyl, more specifically C 3-6 cycloalkyl), substituted or unsubstituted C 3-20 Cycloalkenyl (more specifically, C 3-10 Cycloalkenyl, more specifically C 3-6 cycloalkenyl), substituted or unsubstituted C 6-20 Aryl (more specifically, C 6-10 aryls, more specifically C6-aryls), substituted or unsubstituted C 3-20 Heterocycloalkyl (more specifically, C 3-10 Heterocycloalkyl, more specifically C 3-6 heterocycloalkyl), substituted or unsubstituted C 3-20 Heterocycloalkenyl (more specifically, C3-10 Heterocycloalkenyl, more specifically C 3-6 heterocycloalkenyl), and substituted or unsubstituted C 3-20 Heteroaryl (more specifically, C 3-10 Heteroaryl, more specifically C 3-6 It can be selected from the group consisting of heteroaryls, wherein the heterocycloalkyl, heterocycloalkenyl, and heteroaryls each may independently have one or more (e.g., 1 to 3) hetero atoms selected from N, O, and S.

[0192] According to one embodiment, in the above formula 2, R3 is a hydrogen atom, substituted or unsubstituted C 1-6 Alkyl, substituted or unsubstituted C 3-6 Carbon cyclic group, -(CH2) n Q, - (CH2) n It can be selected from the group consisting of CHQR, -CHQR, and -CQ(R)2, where each R is independently a hydrogen atom, C 1-3 Alkyl and C 2-3 It can be selected from the group consisting of alkenyls; Q is a carbon cyclic group, a heterocyclic group, -OR, -O(CH2) n N(R)2, -C(O)OR, -OC(O)R, -CX3, -CX2H, -CXH2, -CN, -N(R)2, -C(O)N(R)2, -N(R)C(O)R, -N(R)S(O)2R, -N(R)C(O)N(R)2, -N(R)C(S)N(R)2, -N(R)R 12 , N(R)S(O)2R 12 , -O(CH2) n OR, -N(R)C(=NR 13 )N(R)2, -N(R)C(=CHR 13 )N(R)2, -OC(O)N(R)2, -N(R)C(O)OR, -N(OR)C(O)R, -N(OR)S(O)2R, -N(OR)C(O)OR, -N(OR)C(O)N(R)2, -N(OR)C(S)N(R)2, -N(OR)C(=NR13 )N(R)2, -N(OR)C(=CHR 13 )N(R)2, -C(=NR 13 )N(R)2, - C(=NR 13 It can be selected from the group consisting of )R, -C(O)N(R)OR, and -C(R)N(R)2C(O)OR, where each n is independently an integer from 1 to 5, and R 12 is C 3-6 Selected from the group consisting of carbon-cyclic groups and heterocyclic groups, and R 13 H, CN, NO2, C 1-6 Alkyl, -OR, -S(O)2R, -S(O)2N(R)2, C 2-6 Alkenyl, C 3-6 Selected from the group consisting of carbon cyclic groups and heterocyclic groups, where each R is independently a hydrogen atom, C 1-3 Alkyl and C 2-3 Selected from the group consisting of alkenyls, each X is independently selected from the group consisting of F, CI, Br, and I, provided that R3 is -(CH2) n Q, -(CH2) n In the case of CHQR, -CHQR or -CQ(R)2, (i) if n is 1, 2, 3, 4 or 5, Q is not -N(R)2, or (ii) if n is 1 or 2, Q is not a 5-, 6- or 7-membered heterocycloalkyl.

[0193] According to one embodiment, in the above chemical formula 2, R4 to R 11 Each independently consists of hydrogen atoms, C 1-3 Alkyl and C 2-3 It can be selected from a group composed of alkenils.

[0194] According to one embodiment, in the above formula 2, a, b, c, and d may each be an integer from 1 to 15 independently.

[0195] More specifically, in the above chemical formula 2, M1 and M2 can each independently be -C(O)O- or -OC(O)-.

[0196] More specifically, in the above chemical formula 2, R1 and R2 are each independently substituted or unsubstituted C 3-6 It can be a cycloalkyl.

[0197] More specifically, in the above chemical formula 2, R3 is a hydrogen atom or a substituted or unsubstituted C 1-3 It may be an alkyl, and more specifically, an unsubstituted C 1-3 C substituted with an alkyl or hydroxyl group 1-3 It can be an alkyl.

[0198] More specifically, in the above chemical formula 2, R4 to R 11 It can be a hydrogen atom.

[0199] More specifically, in the above chemical formula 2, a, b, c, and d may each independently be integers from 3 to 11, and even more specifically, integers from 5 to 9.

[0200] More specifically, the lipid of Formula 2 may have a structure selected from any one of the following compounds 2-A to 2-O:

[0201]

[0202]

[0203] In another embodiment, the cationic lipid may be a lipid having any one of the structures shown in Formula 3 below or an ionized form thereof:

[0204] [Chemical Formula 3]

[0205]

[0206]

[0207]

[0208] In each of the structures shown in Chemical Formula 3 above, at least two (more specifically, two to seven) of the R groups are Rx, and the remaining R groups are Ry,

[0209] Rx is independent of each , , and Selected from, where a, b, and c are each independently integers from 2 to 20, R1 is a substituted or unsubstituted saturated or unsaturated divalent hydrocarbon group, and R2 is a substituted or unsubstituted unsaturated monovalent hydrocarbon group, represents a substituted or unsubstituted methylene group, and

[0210] Each Ry is independently an H, or a substituted or unsubstituted alkyl group, and the two non-H Rys can be connected to each other with the nitrogen atoms to which they are attached to form a ring structure, and

[0211] L is each independently a substituted or unsubstituted alkylene group and may optionally have an ether bond (-O-), a thioether bond (-S-), or a disulfide bond (-SS-) within its structure.

[0212] In the above Chemical Formula 3, the expression “substituted or unsubstituted” means that, unless otherwise specified, the group is not substituted, or -OH, a halogen atom, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 alkyl halide group, C 1-6 Halogenated alkoxy group, C 3-20 Cycloalkyl group, C 3-20 heterocycloalkyl group, C 6-20 aryl group or C 3-20 It means that it is substituted with one or more substituents selected from heteroaryl groups.

[0213] According to one embodiment, in the above chemical formula 3, the Rx are each independently , , and Selected from, where a, b, and c can each independently be integers from 2 to 20 or from 2 to 15, and R1 is a substituted or unsubstituted saturated or unsaturated 2-valent C 1-12 It may be a hydrocarbon group, and R2 is a substituted or unsubstituted unsaturated monovalent C 2-24 It can be a hydrocarbon group, represents a substituted or unsubstituted methylene group.

[0214] According to one embodiment, in the above formula 3, a, b, and c may each independently be integers from 2 to 15, and more specifically, may each independently be integers from 3 to 12. More specifically, a may be an integer from 5 to 7, and b and c may each independently be integers from 3 to 11, but are not limited thereto.

[0215] According to one embodiment, in the above chemical formula 3, Ry is each independently H or C 1-20 It may be an alkyl group, wherein each of the alkyl groups is independently unsubstituted or -OH, C 1-20 Alkyl, C 1-20 Alkoxy, -NH2, -NH(C 1-20 alkyl), -N(C 1-20 Alkyl)2, optionally substituted C 3-20 Carbon cyclic group (e.g., C 3-20 Cycloalkyl group or C 6-20 aryl group) and arbitrarily substituted C 3-20 Heterocyclic groups (e.g., C 3-20 heterocycloalkyl group or C 3-20It may be substituted by one or more selected from heteroaryl groups, wherein the heterocyclic group may have one or more (e.g., 1 to 3) heteroatoms selected from N, O, and S, and the two non-H Ry groups may be connected to each other with the nitrogen atoms to which they are attached to form a ring structure having one or more heteroatoms selected from N and O. Furthermore, the alkyl group or alkoxy group here is, more specifically, C 1-10 alkyl groups or alkoxy groups, more specifically C 1-6 It may be an alkyl group or an alkoxy group, but is not limited thereto.

[0216] According to one embodiment, in the above formula 3, L is each independently C 1-20 alkylene group (more specifically, C 1-10 An alkylene group, more specifically, C 1-6 It may be an alkylene group), each independently unsubstituted, or -OH, C 1-20 Alkyl, C 1-20 Alkoxy, -NH2, -NH(C 1-20 alkyl), -N(C 1-20 Alkyl)2, optionally substituted C 3-20 Carbon cyclic group (e.g., C 3-20 Cycloalkyl group or C 6-20 aryl group) and arbitrarily substituted C 3-20 Heterocyclic groups (e.g., C 3-20 heterocycloalkyl group or C 3-20 It may be substituted by one or more selected from heteroaryl groups, wherein the heterocyclic group may have one or more (e.g., 1 to 3) heteroatoms selected from N, O, and S. Furthermore, the alkyl group or alkoxy group is, more specifically, C 1-10 alkyl groups or alkoxy groups, more specifically C 1-6 It may be an alkyl group or an alkoxy group, but is not limited thereto.

[0217] More specifically, in the above chemical formula 3, Ry is each independently H or C 1-10 It may be an alkyl group, wherein each of the alkyl groups is independently unsubstituted or -OH, C 1-10 Alkyl, C 1-10 Alkoxy, -NH2, -NH(C 1-10 alkyl), -N(C 1-10 Alkyl)2, optionally substituted C 3-10 carbon cyclic groups and arbitrarily substituted C 3-10 It can be substituted by one or more selected from heterocyclic groups, wherein the heterocyclic group may have one or more (e.g., 1 to 3) heteroatoms selected from N, O and S, and the two non-H Rys are connected to each other with the nitrogen atoms to which they are attached, thereby forming a ring structure having one or more heteroatoms selected from N and O.

[0218] More specifically, in the above chemical formula 3, L is independently C 1-10 It may be an alkylene group, each independently unsubstituted, or -OH, C 1-10 Alkyl, C 1-10 Alkoxy, -NH2, -NH(C 1-10 alkyl), -N(C 1-10 Alkyl)2, optionally substituted C 3-10 carbon cyclic groups and arbitrarily substituted C 3-10 It may be substituted by one or more selected from heterocyclic groups, wherein the heterocyclic group may have one or more (e.g., 1 to 3) heteroatoms selected from N, O and S.

[0219] More specifically, in the above chemical formula 3, the Rx are each independently , and Selected from, where a, b, and c can each independently be integers from 3 to 12, and R1 is substituted or unsubstituted C1-12 Alkylene group, substituted or unsubstituted C 2-12 alkenylene group or substituted or unsubstituted C 2-12 It may be an alkynylene group, and R2 is a substituted or unsubstituted C 2-24 alkenyl group or substituted or unsubstituted C 2-24 It can be an alkynyl group, represents a substituted or unsubstituted methylene group.

[0220] More specifically, in the above chemical formula 3, Ry is each independently H or C 1-6 The alkyl group may be an alkyl group, wherein each alkyl group may be independently unsubstituted or substituted by one or more selected from -OH and -NH2, and the two non-H Ry groups may be connected to each other with the nitrogen atoms to which they are attached to form a ring structure having one or more heteroatoms selected from N and O.

[0221] More specifically, in the above chemical formula 3, L is each independently unsubstituted C 1-6 It can be an alkylene group.

[0222] Specifically, the lipid of the above chemical formula 3 may have any one of the following structures:

[0223]

[0224] In each of the above structures, R1 to R7 are each independently , , and Selected from, where a, b, and c are each independently integers from 2 to 20, R1 is a substituted or unsubstituted saturated or unsaturated divalent hydrocarbon group, and R2 is a substituted or unsubstituted unsaturated monovalent hydrocarbon group, represents a substituted or unsubstituted methylene group.

[0225] More specifically, the lipid of Formula 3 may have a structure selected from any one of the following compounds 3-A to 3-V:

[0226]

[0227]

[0228]

[0229] In another embodiment, the cationic lipid may be a lipid having the structure of the following chemical formula 4 or an ionized form thereof:

[0230] [Chemical Formula 4]

[0231]

[0232] In the above chemical formula 4,

[0233] M1 and M2 are each independently divalent linker groups, and

[0234] R1 and R2 are each independently substituted or unsubstituted carboncyclic or heterocyclic groups, and

[0235] R3 is a hydrogen atom, or optionally a substituted or unsubstituted organic group containing one or more heteroatoms, and

[0236] R4 to R7 are each independently hydrogen atoms, or substituted or unsubstituted saturated or unsaturated hydrocarbon groups, and

[0237] a and b are each independently integers from 1 to 20.

[0238] In the following Chemical Formula 4, the expression “substituted or unsubstituted” means that, unless otherwise specified, the group is not substituted, or -OH, a halogen atom, C 1-8 alkyl group (more specifically, C 3-7 alkyl group) or C 1-8 alkyl halide (more specifically, C 3-7This means that it is substituted with one or more substituents selected from alkyl halide groups.

[0239] According to one embodiment, in the above formula 4, M1 and M2 are each independently -C(O)O-, -OC(O)-, -OC(O)-M'-C(O)O-, -C(O)N(R')-, -N(R')C(O)-, -C(O)-, -C(S)-, -C(S)S-, -SC(S)-, -CH(OH)-, -P(O)(OR')O-, -S(O)2-, -SS-, arylene (more specifically C 6-20 Aryllene, more specifically, C 6-10 Aryllene), and heteroarylene (more specifically, C having one or more (e.g., 1 to 3) heteroatoms selected from N, O, and S). 3-20 Heteroarylene, more specifically, C 3-10 It can be selected from the group consisting of heteroarylenes, where M' is direct bonding, C 1-13 Alkylene (more specifically, C 1-6 alkylene) or C 2-13 Alkenylene (more specifically, C 2-6 It can be alkenylene), and R' are each independently hydrogen atoms, C 1-18 Alkyl (more specifically, C 1-10 Alkyl, more specifically C 1-6 alkyl) and C 2-18 Alkenyl (more specifically, C 2-10 Alkenyl, more specifically C 2-6 It can be selected from a group consisting of alkenyls.

[0240] According to one embodiment, in the above formula 4, R1 and R2 are each independently substituted or unsubstituted C 3-20 cycloalkyl (more specifically, C 3-15 Cycloalkyl, more specifically C 6-15 cycloalkyl), substituted or unsubstituted C 3-20 Cycloalkenyl (more specifically, C 3-15Cycloalkenyl, more specifically C 6-15 cycloalkenyl), substituted or unsubstituted C 6-20 Aryl (more specifically, C 6-14 aryl), substituted or unsubstituted C 3-20 Heterocycloalkyl (more specifically, C 3-15 heterocycloalkyl), substituted or unsubstituted C 3-20 Heterocycloalkenyl (more specifically, C 3-15 heterocycloalkenyl), and substituted or unsubstituted C 3-20 Heteroaryl (more specifically, C 3-15 It can be selected from the group consisting of heteroaryls, wherein the heterocycloalkyl, heterocycloalkenyl, and heteroaryls each may independently have one or more (e.g., 1 to 3) hetero atoms selected from N, O, and S.

[0241] According to one embodiment, in the above chemical formula 4, R3 is a hydrogen atom, substituted or unsubstituted C 1-6 Alkyl, substituted or unsubstituted C 3-6 Carbon cyclic group, -(CH2) n Q, - (CH2) n It can be selected from the group consisting of CHQR, -CHQR, and -CQ(R)2, where each R is independently a hydrogen atom, C 1-3 Alkyl and C 2-3 It can be selected from the group consisting of alkenyls; Q is a carbon cyclic group, a heterocyclic group, -OR, -O(CH2) n N(R)2, -C(O)OR, -OC(O)R, -CX3, -CX2H, -CXH2, -CN, -N(R)2, -C(O)N(R)2, -N(R)C(O)R, -N(R)S(O)2R, -N(R)C(O)N(R)2, -N(R)C(S)N(R)2, -N(R)R 12 , N(R)S(O)2R 12 , -O(CH2) n OR, -N(R)C(=NR 13)N(R)2, -N(R)C(=CHR 13 )N(R)2, -OC(O)N(R)2, -N(R)C(O)OR, -N(OR)C(O)R, -N(OR)S(O)2R, -N(OR)C(O)OR, -N(OR)C(O)N(R)2, -N(OR)C(S)N(R)2, -N(OR)C(=NR 13 )N(R)2, -N(OR)C(=CHR 13 )N(R)2, -C(=NR 13 )N(R)2, - C(=NR 13 It can be selected from the group consisting of )R, -C(O)N(R)OR, and -C(R)N(R)2C(O)OR, where each n is independently an integer from 1 to 5, and R 12 is C 3-6 Selected from the group consisting of carbon-cyclic groups and heterocyclic groups, and R 13 H, CN, NO2, C 1-6 Alkyl, -OR, -S(O)2R, -S(O)2N(R)2, C 2-6 Alkenyl, C 3-6 Selected from the group consisting of carbon cyclic groups and heterocyclic groups, where each R is independently a hydrogen atom, C 1-3 Alkyl and C 2-3 Selected from the group consisting of alkenyls, each X is independently selected from the group consisting of F, CI, Br, and I, provided that R3 is -(CH2) n Q, -(CH2) n In the case of CHQR, -CHQR or -CQ(R)2, (i) if n is 1, 2, 3, 4 or 5, Q is not -N(R)2, or (ii) if n is 1 or 2, Q is not a 5-, 6- or 7-membered heterocycloalkyl.

[0242] According to one embodiment, in the above chemical formula 4, R4 to R7 are each independently hydrogen atoms, C 1-3 Alkyl and C 2-3 It can be selected from a group composed of alkenils.

[0243] According to one embodiment, in the above formula 4, a and b may each independently be integers from 1 to 15, and more specifically, integers from 3 to 13.

[0244] More specifically, in the above chemical formula 4, M1 and M2 can each be independently selected from the group consisting of -C(O)O-, -OC(O)-, -C(O)N(R')- and -N(R')C(O)-, where R' is as previously defined.

[0245] More specifically, in the above chemical formula 4, R1 and R2 are each independently substituted or unsubstituted C 3-15 It can be a cycloalkyl.

[0246] More specifically, in the above chemical formula 4, R3 is a hydrogen atom, or a substituted or unsubstituted C 1-3 It can be an alkyl.

[0247] More specifically, in the above chemical formula 4, R4 to R7 may be hydrogen atoms.

[0248] More specifically, in the above chemical formula 4, a and b can each independently be integers from 5 to 11, and more specifically, integers from 5 to 9.

[0249] According to one embodiment, in the above chemical formula 4, R1 and R2 are different from each other, wherein R1 is a substituted or unsubstituted C 6-15 It may be a cycloalkyl, and R2 is a substituted or unsubstituted C 3-6 It can be a cycloalkyl.

[0250] More specifically, the lipid of the above formula 4 may have a structure selected from any one of the following compounds 4-A to 4-R:

[0251]

[0252] In another embodiment, the cationic lipid may be a lipid having the structure of the following chemical formula 5:

[0253] [Chemical Formula 5]

[0254]

[0255] In the above chemical formula 5,

[0256] R1 is a substituted or unsubstituted alkylene group, alkenylene group, or alkynylene group, and

[0257] R2, R3, and R4 are each independently substituted or unsubstituted alkylene groups, alkenylene groups, or alkynylene groups, and

[0258] R5, R6, and R7 are each independently substituted or unsubstituted saturated or unsaturated monovalent hydrocarbon groups, and

[0259] R8 and R9 are each independently a substituted or unsubstituted alkyl group, alkenyl group, alkynyl group, or carboncyclic group, or each independently -R 10 -(L4) n -R 11 And,

[0260] R 10 Each is independently a substituted or unsubstituted alkylene group, and

[0261] R 11 Each is independently a substituted or unsubstituted saturated or unsaturated monovalent hydrocarbon group, and

[0262] L1, L2, L3 and L4 are each independently selected from the group consisting of -C(O)O-, -OC(O)-, -OC(O)-L'-C(O)O-, -C(O)N(R')-, -N(R')C(O)-, -C(O)-, -C(S)-, -C(S)S-, -SC(S)-, -CH(OH)-, -P(O)(OR')O-, -S(O)2-, -SS-, alkenylene, alkynylene, arylene, and heteroarylene, wherein L' is a direct bond, alkylene, alkenylene, or alkynylene, and R' is each independently selected from the group consisting of a hydrogen atom, alkyl, alkenyl, and alkynylene, and

[0263] n is 0 or 1, and

[0264] X - is a pharmaceutically acceptable monovalent anion.

[0265] In the above Chemical Formula 5, the expression “substituted or unsubstituted” means that, unless otherwise specified, the group is not substituted, or -OH, a halogen atom, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 alkyl halide group, C 1-6 Halogenated alkoxy group, C 3-20 Cycloalkyl group, C 3-20 heterocycloalkyl group, C 6-20 aryl group or C 3-20 It means that it is substituted with one or more substituents selected from heteroaryl groups.

[0266] In the above chemical formula 5, the expression that any group (e.g., heteroaryl, heterocycloalkyl, etc.) is a “hetero” group means that, unless otherwise specified, the group has one or more (e.g., 1 to 3) hetero atoms selected from N, O and S.

[0267] In the above chemical formula 5, the “monovalent hydrocarbon group” may be branched or unbranched, cyclic or non-cyclic, or aromatic.

[0268] According to one embodiment, in the above chemical formula 5,

[0269] The above R1 is a substituted or unsubstituted C 1-6 Alkylene group, C 2-6 alkenylene group or C 2-6 It can be an alkynylene group,

[0270] The above R2 and R3 and R4 are each independently substituted or unsubstituted C 3-12 Alkylene group, C 3-12 alkenylene group or C 3-12 It can be an alkynylene group,

[0271] The above R5, R6, and R7 are each independently substituted or unsubstituted saturated or unsaturated monovalent C 3-20 It can be a hydrocarbon group,

[0272] The above R8 and R9 are each independently substituted or unsubstituted C 1-6 Alkyl group, C 2-6 alkenyl group, C 2-6 alkynyl group or C 3-6 It is a carbon cyclic group, or each independently -R 10 -(L4) n -R 11 It could be,

[0273] The above R 10 Each is independently substituted or unsubstituted C 3-12 It can be an alkylene group, and

[0274] The above R 11 Each is independently substituted or unsubstituted saturated or unsaturated monovalent C 3-20 It can be a hydrocarbon group,

[0275] The above L1, L2, L3, and L4 are each independently -C(O)O-, -OC(O)-, -OC(O)-L'-C(O)O-, -C(O)N(R')-, -N(R')C(O)-, -C(O)-, -C(S)-, -C(S)S-, -SC(S)-, -CH(OH)-, -P(O)(OR')O-, -S(O)2-, -SS-, C 2-6 Alkenylene, C 2-6 alkynylene, C 6-20 Arylene, and C 3-20 It can be selected from the group consisting of heteroarylenes, where L' is a direct bond, C 1-13 Alkylene, C 2-13 Alkenylene or C 2-13 It can be alkynylene, where R' are independently hydrogen atoms, C 1-18 Alkyl, C 2-18 Alkenyl and C 2-18 It can be selected from a group composed of alkinyls, and

[0276] n is 0 or 1, and

[0277] X - It may be a monovalent anion of a pharmaceutically acceptable inorganic or organic acid.

[0278] More specifically, in the above chemical formula 5,

[0279] The above R1 is a substituted or unsubstituted C 3-4 Alkylene group, C 3-4 alkenylene group or C 3-4 It can be an alkynylene group,

[0280] The above R2 and R3 and R4 are each independently substituted or unsubstituted C 6-8 Alkylene group, C 6-8 alkenylene group or C 6-8 It can be an alkynylene group,

[0281] The above R5, R6, and R7 are each independently substituted or unsubstituted saturated or unsaturated monovalent C 5-15 It can be a hydrocarbon group,

[0282] The above R8 and R9 are each independently substituted or unsubstituted C 1-2 Alkyl group, C 2-3 alkenylene group or C 2-3 It is an alkynylene group, or each independently -R 10 -(L4) n -R 11 It could be,

[0283] R 10 Each is independently substituted or unsubstituted C 6-8 It can be an alkylene group, and

[0284] R 11 Each is independently substituted or unsubstituted saturated or unsaturated monovalent C 5-15 It can be a hydrocarbon group,

[0285] The above L1, L2, L3, and L4 are each independently -C(O)O-, -OC(O)-, -C(O)N(R')-, -N(R')C(O)-, -P(O)(OR')O-, -SS-, C 2-5 Alkenylene and C 2-5It can be selected from the group consisting of alkynylenes, where R' is independently a hydrogen atom, C 1-6 Alkyl, C 2-6 Alkenyl and C 2-6 It can be selected from a group composed of alkinyls, and

[0286] n is 0 or 1, and

[0287] X - is halide (F - , Cl - , Br - , I - ), nitrate anion (NO3 - ), benzoate anion (C6H5COO - ), methanesulfonate anion, acetate anion (CH3COO - )(=AcO - ), or trihaloacetate anion (CF3COO - It can be.

[0288] More specifically, in the above chemical formula 5,

[0289] The above R1 is a substituted or unsubstituted C 3-4 It can be an alkylene group, and

[0290] The above R2 and R3 and R4 are each independently substituted or unsubstituted C 6-8 It can be an alkylene group, and

[0291] The above R5, R6, and R7 are each independently substituted or unsubstituted saturated or unsaturated monovalent C 5-15 It can be a hydrocarbon group,

[0292] The above R8 and R9 are each independently substituted or unsubstituted C 1-2 It is an alkyl group, or each independently -R 10 -(L4) n -R 11 It could be,

[0293] R 10 Each is independently substituted or unsubstituted C 6-8 It can be an alkylene group, and

[0294] R 11 Each is independently substituted or unsubstituted saturated or unsaturated monovalent C 5-15 It can be a hydrocarbon group,

[0295] The above L1, L2, L3, and L4 are each independently -C(O)O-, -OC(O)-, -C(O)N(R')-, -N(R')C(O)-, -P(O)(OR')O-, -SS-, and C 2-5 It can be selected from the group consisting of alkenylenes, where R' is independently a hydrogen atom and C 1-6 It can be selected from the group consisting of alkyl groups, and

[0296] n is 0 or 1, and

[0297] X - is Cl - , Br - , or acetate anion (CH3COO - )(=AcO - It can be.

[0298] More specifically, the cationic lipid may have a structure selected from any one of the following compounds 5-A to 5-Q:

[0299]

[0300]

[0301]

[0302] In another embodiment, the cationic lipid may be a lipid having the structure of the following chemical formula 6 or an ionized form thereof:

[0303] [Chemical Formula 6]

[0304]

[0305] In the above chemical formula 6,

[0306] R1 is a substituted or unsubstituted alkyl group, alkenyl group, or alkynyl group, and

[0307] R2 is a substituted or unsubstituted alkylene group, alkenylene group, or alkynylene group, and

[0308] R3 is an unsubstituted alkylene group, and

[0309] R is a hydrogen atom (H) or And, where R4 is a substituted or unsubstituted alkyl group, alkenyl group, or alkynyl group, R5 is a substituted or unsubstituted alkylene group, alkenylene group, or alkynylene group, and * indicates the point of attachment to the nitrogen atom.

[0310] In the above Chemical Formula 6, the expression “substituted or unsubstituted” means that, unless otherwise specified, the group is not substituted, or -OH, a halogen atom, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 alkyl halide group, C 1-6 Halogenated alkoxy group, C 3-20 Cycloalkyl group, C 3-20 heterocycloalkyl group, C 6-20 aryl group or C 3-20 It means that it is substituted with one or more substituents selected from heteroaryl groups.

[0311] In the above chemical formula 6, “alkyl,” “alkenyl,” “alkynyl,” “alkylene,” “alkenylene,” and “alkynylene” may each independently be branched or unbranched, or cyclic or non-cyclic.

[0312] According to one embodiment, in the above chemical formula 6,

[0313] R1 and R4 are each independently substituted or unsubstituted C 1-30 Alkyl groups, substituted or unsubstituted C 2-30 alkenyl group, or substituted or unsubstituted C 2-30 It can be an alkynyl group,

[0314] R2 and R5 are each independently substituted or unsubstituted C 1-15 Alkylene group, substituted or unsubstituted C 2-15alkenylene group, or substituted or unsubstituted C 2-15 It can be an alkynylene group,

[0315] R3 is unsubstituted C 2-9 It can be an alkylene group.

[0316] More specifically, in the above chemical formula 6,

[0317] R1 and R4 are each independently substituted or unsubstituted C 1-20 Alkyl groups, substituted or unsubstituted C 2-20 alkenyl group, or substituted or unsubstituted C 2-20 It can be an alkynyl group,

[0318] R2 and R5 are each independently substituted or unsubstituted C 1-12 Alkylene group, substituted or unsubstituted C 2-12 alkenylene group, or substituted or unsubstituted C 2-12 It can be an alkynylene group,

[0319] R3 is unsubstituted C 2-7 It can be an alkylene group.

[0320] More specifically, in the above chemical formula 6,

[0321] R1 and R4 are each independently substituted or unsubstituted C 5-20 Alkyl groups, substituted or unsubstituted C 5-20 alkenyl group, or substituted or unsubstituted C 5-20 It can be an alkynyl group,

[0322] R2 and R5 are each independently substituted or unsubstituted C 3-12 Alkylene group, substituted or unsubstituted C 3-12 alkenylene group, or substituted or unsubstituted C 3-12 It can be an alkynylene group,

[0323] R3 is unsubstituted C 2-5 It can be an alkylene group.

[0324] More specifically, the lipid of the above formula 6 may have a structure selected from any one of the following compounds 6-A to 6-L:

[0325]

[0326]

[0327] In another embodiment, the cationic lipid may be a lipid having the structure of the following chemical formula 7:

[0328] [Chemical Formula 7]

[0329]

[0330] In the above chemical formula 7,

[0331] R1, R2, and R3 are each independently substituted or unsubstituted alkyl groups, and

[0332] R4 is a substituted or unsubstituted divalent hydrocarbon group, and

[0333] R5, R6, R7, and R8 are each independently substituted or unsubstituted saturated or unsaturated divalent hydrocarbon groups, and

[0334] R9 and R 10 Each is independently a substituted or unsubstituted saturated or unsaturated monovalent hydrocarbon group, and

[0335] L1, L2, L3 and L4 are each independently selected from the group consisting of -C(O)O-, -OC(O)-, -OC(O)-L'-C(O)O-, -C(O)N(R')-, -N(R')C(O)-, -C(O)-, -C(S)-, -C(S)S-, -SC(S)-, -CH(OH)-, -P(O)(OR')O- and -S(O)2-, where L' is a direct bond, alkylene, alkenylene, or alkynylene, and R' is each independently selected from the group consisting of a hydrogen atom, alkyl, alkenyl, and alkynyl, and

[0336] X - is a monovalent anion.

[0337] In the above Chemical Formula 7, the expression “substituted or unsubstituted” means that, unless otherwise specified, the group is not substituted, or -OH, a halogen atom, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 alkyl halide group, C 1-6 Halogenated alkoxy group, C 3-20 Cycloalkyl group, C 3-20 heterocycloalkyl group, C 6-20 aryl group or C 3-20 It means that it is substituted with one or more substituents selected from heteroaryl groups.

[0338] In the above chemical formula 7, the expression that any group (e.g., heteroaryl, heterocycloalkyl, etc.) is a “hetero” group means that, unless otherwise specified, the group has one or more (e.g., 1 to 3) hetero atoms selected from N, O and S.

[0339] In the above chemical formula 7, the “monovalent hydrocarbon group” and the “divalent hydrocarbon group” may be branched or unbranched, cyclic or non-cyclic.

[0340] In the above chemical formula 7, “alkyl,” “alkenyl,” “alkynyl,” “alkylene,” “alkenylene,” and “alkynylene” may each independently be branched or unbranched, or cyclic or non-cyclic.

[0341] According to one embodiment, in the above chemical formula 7,

[0342] R1, R2, and R3 are each independently substituted or unsubstituted C 1-6 It can be an alkyl group, and

[0343] R4 is a substituted or unsubstituted divalent C 2-6 It can be a hydrocarbon group,

[0344] R5, R6, R7, and R8 are each independently substituted or unsubstituted saturated or unsaturated divalent C 2-20 It can be a hydrocarbon group,

[0345] R9 and R10 Each is independently substituted or unsubstituted saturated or unsaturated monovalent C 2-20 It can be a hydrocarbon group,

[0346] L1, L2, L3, and L4 are each independently selected from the group consisting of -C(O)O-, -OC(O)-, -OC(O)-L'-C(O)O-, -C(O)N(R')-, -N(R')C(O)-, -C(O)-, -C(S)-, -C(S)S-, -SC(S)-, -CH(OH)-, -P(O)(OR')O-, and -S(O)2-, where L' is a direct bond, C 1-13 Alkylene, C 2-13 Alkenylene or C 2-13 It is alkynylene, and R' are independently hydrogen atoms, C 1-18 Alkyl, C 2-18 Alkenyl and C 2-18 Selected from a group composed of alkinyls,

[0347] X - It can be a monovalent anion of an inorganic or organic acid.

[0348] More specifically, in the above chemical formula 7,

[0349] R1, R2, and R3 are each independently substituted or unsubstituted C 1-3 It can be an alkyl group, and

[0350] R4 is substituted or unsubstituted C 2-4 It can be an alkylene group, and

[0351] R5, R6, R7, and R8 are each independently substituted or unsubstituted C 2-13 alkylene group or C 2-13 It can be an alkenylene group,

[0352] R9 and R 10 Each is independently substituted or unsubstituted C 6-20 Alkyl group, C 6-20 alkenyl group or C 6-20 It can be an alkynyl group,

[0353] L1, L2, L3, and L4 can each be independently selected from the group consisting of -C(O)O-, -OC(O)-, -C(O)N(R')-, -N(R')C(O)-, and -P(O)(OR')O-, where R' is independently a hydrogen atom and C 1-6 It can be selected from the group consisting of alkyl groups, and

[0354] X - is F - , Cl - , Br - , I - , nitrate anion, benzoate anion, methanesulfonate anion, acetate anion (CH3COO - )(=AcO - ), or trihaloacetate anion (CF3COO - It can be.

[0355] More specifically, the lipid of the above formula 7 may have a structure selected from any one of the following compounds 7-A and 7-B:

[0356]

[0357] In another embodiment, the cationic lipid may be a lipid having the structure of the following chemical formula 8:

[0358] [Chemical Formula 8]

[0359]

[0360] In the above chemical formula 8,

[0361] R p and R q Each is independently a hydrogen atom (H) or a substituted or unsubstituted monovalent saturated or unsaturated hydrocarbon group, and optionally R p and R q They can bond and form rings together with the oxygen atoms to which they are attached, and

[0362] R1 and R2 are each independently substituted or unsubstituted alkylene groups, and

[0363] n is an integer greater than or equal to 0 or 1, and

[0364] Each m is independently 0 or 1, and when m is 1, the N with R attached pointed to by m carries a univalent positive charge (+1), and

[0365] R3 to R7 are each independently (i) a hydrogen atom (H), (ii) , (iii) or However, at least (n+2) of R3 to R7 present in the molecule are any one of (ii) to (iv), and

[0366] R8, R 10 , R 11 and R 13 Each is independently a substituted or unsubstituted divalent saturated or unsaturated hydrocarbon group, and

[0367] R9, R 12 and R 14 Each is independently a substituted or unsubstituted monovalent saturated or unsaturated hydrocarbon group, and

[0368] L1 and L2 are each independently selected from the group consisting of -C(O)O-, -OC(O)-, -OC(O)-L'-C(O)O-, -C(O)N(R')-, -N(R')C(O)-, -C(O)-, -C(S)-, -C(S)S-, -SC(S)-, -CH(OH)-, -P(O)(OR')O-, -S(O)2-, -SS-, arylene groups, and heteroarylene groups, wherein L' is a directly bonded, substituted or unsubstituted alkylene group or substituted or unsubstituted alkenylene group, and R' is each independently selected from the group consisting of a hydrogen atom, a substituted or unsubstituted alkyl group and a substituted or unsubstituted alkenyl group, and

[0369] X is -OH or -SH.

[0370] According to one embodiment, in the above chemical formula 8, the R p , R q , R1~R 14One or more of the may be further substituted with one or more moieties specifically suitable for a target tissue or organ (e.g., liver, lung, spleen, brain, heart, etc.), preferably one or more moieties selected from one or more amino acids, sugars, vitamins, peptides, proteins, hormones, or antibodies, or derivatives thereof.

[0371] The range of cationic lipids available for use in the present invention includes not only those having the structure of Formula 8 but also their cationic forms.

[0372] In the above Chemical Formula 8, the expression “substituted or unsubstituted” means that, unless otherwise specified, the group is not substituted, or -OH, a halogen atom, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 alkyl halide group, C 1-6 Halogenated alkoxy group, C 3-20 Cycloalkyl group, C 3-20 heterocycloalkyl group, C 6-20 aryl group or C 3-20 This means that it is substituted with one or more substituents selected from heteroaryl groups. In addition, in one embodiment, the substituent may include amino acids, sugars, vitamins, peptides, proteins, hormones, or antibodies.

[0373] In the above chemical formula 8, the expression that any group (e.g., heteroaryl, heterocycloalkyl, etc.) is a “hetero” group means that, unless otherwise specified, the group has one or more (e.g., 1 to 3) hetero atoms selected from N, O and S.

[0374] In the above chemical formula 8, the “hydrocarbon group” may be branched or unbranched, cyclic or non-cyclic, or aromatic.

[0375] More specifically, in the above chemical formula 8,

[0376] R p and R qis independently a hydrogen atom (H), or a substituted or unsubstituted C 1-6 It can be an alkyl group, and optionally R p and R q They can bond and form rings together with the oxygen atoms to which they are attached, and

[0377] R1 and R2 are each independently substituted or unsubstituted C 1-4 It can be an alkylene group, and

[0378] n can be 0 or 1, and

[0379] R8, R 10 , R 11 and R 13 Each is independently substituted or unsubstituted divalent saturated or unsaturated C 2-20 It can be a hydrocarbon group,

[0380] R9, R 12 and R 14 are independently substituted or unsubstituted monovalent saturated or unsaturated C 2-20 It can be a hydrocarbon group,

[0381] L1 and L2 are each independently -C(O)O-, -OC(O)-, -C(O)N(R')-, -N(R')C(O)-, -C(O)-, -C(S)-, -C(S)S-, -SC(S)-, -CH(OH)-, -P(O)(OR')O-, -S(O)2-, -SS-, C 6-20 C having an arylene group and one or more heteroatoms selected from N, O, and S 3-20 It can be selected from the group consisting of heteroarylene groups, where L' is directly bonded, substituted, or unsubstituted C 1-13 alkylene group or substituted or unsubstituted C 2-13 It can be an alkenylene group, and R' are each independently hydrogen atoms, substituted or unsubstituted C 1-18 Alkyl groups and substituted or unsubstituted C 2-18 It can be selected from the group composed of alkenyl groups.

[0382] More specifically, in the above chemical formula 8,

[0383] R p and R q is independently a hydrogen atom (H), or a substituted or unsubstituted C 2-4 It can be an alkyl group, and optionally R p and R q They can bond and form rings together with the oxygen atoms to which they are attached, and

[0384] R1 and R2 are each independently substituted or unsubstituted C 2-4 It can be an alkylene group, and

[0385] n can be 0, and

[0386] m can be 0, and

[0387] R3, R4 and R6 each independently (ii) , (iii) or It could be,

[0388] R8, R 10 , R 11 and R 13 Each is independently substituted or unsubstituted divalent saturated or unsaturated C 2-10 It can be a hydrocarbon group,

[0389] R9, R 12 and R 14 are independently substituted or unsubstituted monovalent saturated or unsaturated C 10-20 It can be a hydrocarbon group,

[0390] L1 and L2 can each be independently selected from the group consisting of -C(O)O-, -OC(O)-, -C(O)N(R')-, and -N(R')C(O)-, where R' is each independently a hydrogen atom, and a substituted or unsubstituted C 1-4 It can be selected from the group consisting of alkyl groups, and

[0391] X can be -OH.

[0392] More specifically, the lipid of the above formula 8 may have a structure selected from any one of the following compounds 8-A to 8-E:

[0393]

[0394] In another embodiment, the cationic lipid may be a lipid having a structure represented by the following chemical formula 9:

[0395] [Chemical Formula 9]

[0396]

[0397] In the above chemical formula 9,

[0398] R1 and R2 are each independently a hydrogen atom (H) or a substituted or unsubstituted monovalent saturated or unsaturated hydrocarbon group, and

[0399] R3 and R4 are each independently substituted or unsubstituted alkylene groups, and

[0400] R5 to R7, R 15 and R 16 Each independently (i) a hydrogen atom (H), (ii) , (iii) or However, provided that R5 to R7 and R present in the molecule 15 and R 16 At least two of them are any one of (ii) to (iv), and

[0401] a and b are each independently 0 or 1, and if a is 1, then R 15 N with attached has a positive charge (+1), and if b is 1, R 16 This attached N carries a positive charge (+1), and

[0402] R8, R 10 , R 11 and R 13 Each is independently a substituted or unsubstituted divalent saturated or unsaturated hydrocarbon group, and

[0403] R9, R 12 and R14 Each is independently a substituted or unsubstituted monovalent saturated or unsaturated hydrocarbon group, and

[0404] L1 and L2 are each independently selected from the group consisting of -C(O)O-, -OC(O)-, -OC(O)-L'-C(O)O-, -C(O)N(R')-, -N(R')C(O)-, -C(O)-, -C(S)-, -C(S)S-, -SC(S)-, -CH(OH)-, -P(O)(OR')O-, -S(O)2-, -SS-, arylene groups, and heteroarylene groups, wherein L' is a directly bonded, substituted or unsubstituted alkylene group or substituted or unsubstituted alkenylene group, and R' is each independently selected from the group consisting of a hydrogen atom, a substituted or unsubstituted alkyl group and a substituted or unsubstituted alkenyl group, and

[0405] X is -OH or -SH.

[0406] According to one embodiment, in the above formula 9, one or more of R3 to R7 may be further substituted with one or more moieties specifically suitable for a target tissue or organ (e.g., liver, lung, spleen, brain, heart, etc.), preferably selected from one or more amino acids, sugars, vitamins, peptides, proteins, hormones, antibodies, neurotransmitters, small molecules having pharmaceutical activity, endosome-degrading agents, cell membrane permeability agents, charge blockers, drugs, nucleic acids, or derivatives thereof.

[0407] The range of cationic lipids available for use in the present invention includes not only those having the structure of Formula 9 but also their cationic forms.

[0408] In the above Chemical Formula 9, the expression “substituted or unsubstituted” means that, unless otherwise specified, the group is not substituted, or -OH, a halogen atom, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 alkyl halide group, C 1-6Halogenated alkoxy group, C 3-20 Cycloalkyl group, C 3-20 heterocycloalkyl group, C 6-20 aryl group or C 3-20 This means that it is substituted with one or more substituents selected from heteroaryl groups. In addition, in one embodiment, the substituent may include amino acids, sugars, vitamins, peptides, proteins, hormones, or antibodies.

[0409] In the above chemical formula 9, the expression that any group (e.g., heteroaryl, heterocycloalkyl, etc.) is a “hetero” group means that, unless otherwise specified, the group has one or more (e.g., 1 to 3) hetero atoms selected from N, O and S.

[0410] In the above chemical formula 9, the “hydrocarbon group” may be branched or unbranched, cyclic or non-cyclic, or aromatic.

[0411] More specifically, in the above chemical formula 9,

[0412] R1 and R2 are each independently hydrogen atoms (H) or substituted or unsubstituted C. 1-6 It can be an alkyl group, and

[0413] R3 and R4 are each independently substituted or unsubstituted C 1-6 It can be an alkylene group, and

[0414] R8, R 10 , R 11 and R 13 Each is independently substituted or unsubstituted divalent saturated or unsaturated C 2-20 It can be a hydrocarbon group,

[0415] R9, R 12 and R 14 are independently substituted or unsubstituted monovalent saturated or unsaturated C 2-20 It can be a hydrocarbon group,

[0416] L1 and L2 are each independently -C(O)O-, -OC(O)-, -C(O)N(R')-, -N(R')C(O)-, -C(O)-, -C(S)-, -C(S)S-, -SC(S)-, -CH(OH)-, -P(O)(OR')O-, -S(O)2-, -SS-, C 6-20 C having an arylene group and one or more heteroatoms selected from N, O, and S 3-20 It can be selected from the group consisting of heteroarylene groups, where L' is directly bonded, substituted, or unsubstituted C 1-13 alkylene group or substituted or unsubstituted C 2-13 It can be an alkenylene group, and R' are each independently hydrogen atoms, substituted or unsubstituted C 1-18 Alkyl groups and substituted or unsubstituted C 2-18 It can be selected from the group composed of alkenyl groups.

[0417] More specifically, in the above chemical formula 9,

[0418] R1 and R2 are each independently substituted or unsubstituted C 1-3 It can be an alkyl group, and

[0419] R3 and R4 are each independently substituted or unsubstituted C 2-4 It can be an alkylene group, and

[0420] R5 to R7 are each independently (ii) , (iii) or It could be,

[0421] a and b are 0, and

[0422] R8, R 10 , R 11 and R 13 Each is independently substituted or unsubstituted divalent saturated or unsaturated C 2-10 It can be a hydrocarbon group,

[0423] R9, R 12 and R 14are independently substituted or unsubstituted monovalent saturated or unsaturated C 8-20 It can be a hydrocarbon group,

[0424] L1 and L2 are each independently selected from the group consisting of -C(O)O-, -OC(O)-, -C(O)N(R')-, and -N(R')C(O)-, where R' is each independently a hydrogen atom, and a substituted or unsubstituted C 1-4 It can be selected from the group consisting of alkyl groups.

[0425] More specifically, the lipid of the above formula 9 may have a structure selected from any one of the following compounds 9-A to 9-D:

[0426]

[0427] In another embodiment, the cationic lipid may be a lipid having a structure represented by the following chemical formula 10:

[0428] [Chemical Formula 10]

[0429]

[0430] In the above chemical formula 1,

[0431] Each R is independently a substituted or unsubstituted alkylene group, and

[0432] Each A independently (i) a hydrogen atom (H), (ii) , (iii) or (iv) However, at least one A is any one of (ii) to (iv), and

[0433] R 11 , R 13 , R 14 and R 16 Each is independently a substituted or unsubstituted divalent saturated or unsaturated hydrocarbon group, and

[0434] R 12 , R 15 and R 17Each is independently a substituted or unsubstituted monovalent saturated or unsaturated hydrocarbon group, and

[0435] L1 and L2 are each independently selected from the group consisting of -C(O)O-, -OC(O)-, -OC(O)-L'-C(O)O-, -C(O)N(R')-, -N(R')C(O)-, -C(O)-, -C(S)-, -C(S)S-, -SC(S)-, -CH(OH)-, -P(O)(OR')O-, -S(O)2-, -SS-, arylene groups, and heteroarylene groups, wherein L' is a directly bonded, substituted or unsubstituted alkylene group or substituted or unsubstituted alkenylene group, and R' is each independently selected from the group consisting of a hydrogen atom, a substituted or unsubstituted alkyl group and a substituted or unsubstituted alkenyl group, and

[0436] X is -OH or -SH, and

[0437] n is an integer greater than or equal to 1.

[0438] According to one embodiment, in the above formula 10, A may be further substituted with one or more moieties specifically suitable for a target tissue or organ (e.g., liver, lung, spleen, brain, heart, etc.), preferably selected from amino acids, sugars, vitamins, peptides, proteins, hormones, antibodies, neurotransmitters, small molecules having pharmaceutical activity, endosome-degrading agents, cell membrane permeability agents, charge blockers, drugs, nucleic acids, or derivatives thereof.

[0439] The range of cationic lipids available for use in the present invention includes not only those having the structure of Formula 10 but also their cationic forms.

[0440] In the above Chemical Formula 10, the expression “substituted or unsubstituted” means that, unless otherwise specified, the group is not substituted, or -OH, a halogen atom, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 alkyl halide group, C1-6 Halogenated alkoxy group, C 3-20 Cycloalkyl group, C 3-20 heterocycloalkyl group, C 6-20 aryl group or C 3-20 This means that it is substituted with one or more substituents selected from heteroaryl groups. In addition, in one embodiment, the substituent may include amino acids, sugars, vitamins, peptides, proteins, hormones, antibodies, neurotransmitters, pharmaceutically active small molecules, endosome-degrading agents, cell membrane permeability agents, charge blockers, drugs, nucleic acids, or derivatives thereof.

[0441] In the above chemical formula 10, the expression that any group (e.g., heteroaryl, heterocycloalkyl, etc.) is a “hetero” group means that, unless otherwise specified, the group has one or more (e.g., 1 to 3) hetero atoms selected from N, O and S.

[0442] In the above chemical formula 10, the “hydrocarbon group” may be branched or unbranched, cyclic or non-cyclic, or aromatic.

[0443] More specifically, in the above chemical formula 10,

[0444] Each R is independently substituted or unsubstituted C 1-4 alkylene group (more specifically, C 2-4 An alkylene group, more specifically, C 2-3 It can be an alkylene group,

[0445] Each A independently (i) a hydrogen atom (H), (ii) , (iii) or (iv) However, at least two A's may be any one of (ii) to (iv), and

[0446] R 11 , R 13 , R 14 and R 16 Each is independently substituted or unsubstituted divalent saturated or unsaturated C2-20 Hydrocarbon group (more specifically, C 2-10 Hydrocarbon group, more specifically C 2-7 It can be a hydrocarbon group,

[0447] R 12 , R 15 and R 17 Each is independently substituted or unsubstituted monovalent saturated or unsaturated C 2-20 Hydrocarbon group (more specifically, C 10-20 Hydrocarbon group, more specifically C 12-17 It can be a hydrocarbon group,

[0448] L1 and L2 are each independently -C(O)O-, -OC(O)-, -C(O)N(R')-, and -N(R')C(O)-, -C(O)-, -C(S)-, -C(S)S-, -SC(S)-, -CH(OH)-, -P(O)(OR')O-, -S(O)2-, -SS-, C 6-20 C having an arylene group and one or more (e.g., 1 to 3) heteroatoms selected from N, O, and S 3-20 It can be selected from the group consisting of heteroarylene groups, where L' is directly bonded, substituted, or unsubstituted C 1-13 alkylene group or substituted or unsubstituted C 2-13 It can be an alkenylene group, and R' are each independently hydrogen atoms, substituted or unsubstituted C 1-18 Alkyl groups and substituted or unsubstituted C 2-18 It can be selected from a group composed of alkenyl groups, and

[0449] n can be an integer from 1 to 5, more specifically from 1 to 4, and even more specifically from 1 to 3.

[0450] In one embodiment, the lipid of Formula 10 may have a structure represented by any one of the following formulas:

[0451]

[0452] In the above,

[0453] R1 to R5 are each independently substituted or unsubstituted alkylene groups, and

[0454] R6 to R 10 Each independently (i) a hydrogen atom (H), (ii) , (iii) or (iv) However, at least one of R6 to R8 is any one of (ii) to (iv), and

[0455] R 11 , R 13 , R 14 and R 16 Each is independently a substituted or unsubstituted divalent saturated or unsaturated hydrocarbon group, and

[0456] R 12 , R 15 and R 17 Each is independently a substituted or unsubstituted monovalent saturated or unsaturated hydrocarbon group, and

[0457] L1 and L2 are each independently selected from the group consisting of -C(O)O-, -OC(O)-, -OC(O)-L'-C(O)O-, -C(O)N(R')-, -N(R')C(O)-, -C(O)-, -C(S)-, -C(S)S-, -SC(S)-, -CH(OH)-, -P(O)(OR')O-, -S(O)2-, -SS-, arylene groups, and heteroarylene groups, wherein L' is a directly bonded, substituted or unsubstituted alkylene group or substituted or unsubstituted alkenylene group, and R' is each independently selected from the group consisting of a hydrogen atom, a substituted or unsubstituted alkyl group and a substituted or unsubstituted alkenyl group, and

[0458] X is -OH or -SH.

[0459] More specifically, in the above chemical formula 10, R 11 ~R 17One or more of the may be further substituted with one or more moieties selected from one or more amino acids, sugars, vitamins, peptides, proteins, hormones, antibodies, neurotransmitters, pharmaceutically active small molecules, endosome-degrading agents, cell membrane permeability agents, charge blockers, drugs, nucleic acids, or derivatives thereof, which are specifically suitable for a target tissue or organ (e.g., liver, lung, spleen, brain, heart, etc.).

[0460] More specifically, in the above chemical formula 10,

[0461] R1 to R5 are each independently substituted or unsubstituted C 1-4 It can be an alkylene group, and

[0462] R 11 , R 13 , R 14 and R 16 Each is independently substituted or unsubstituted divalent saturated or unsaturated C 2-20 It can be a hydrocarbon group,

[0463] R 12 , R 15 and R 17 Each is independently substituted or unsubstituted monovalent saturated or unsaturated C 2-20 It can be a hydrocarbon group,

[0464] L1 and L2 are each independently -C(O)O-, -OC(O)-, -C(O)N(R')-, and -N(R')C(O)-, -C(O)-, -C(S)-, -C(S)S-, -SC(S)-, -CH(OH)-, -P(O)(OR')O-, -S(O)2-, -SS-, C 6-20 C having an arylene group and one or more (e.g., 1 to 3) heteroatoms selected from N, O, and S 3-20 It can be selected from the group consisting of heteroarylene groups, where L' is directly bonded, substituted, or unsubstituted C 1-13 alkylene group or substituted or unsubstituted C 2-13It can be an alkenylene group, and R' are each independently hydrogen atoms, substituted or unsubstituted C 1-18 Alkyl groups and substituted or unsubstituted C 2-18 It can be selected from the group composed of alkenyl groups.

[0465] More specifically, in the above chemical formula 10,

[0466] R1 to R5 are each independently substituted or unsubstituted C 2-4 alkylene group (more specifically, C 2-3 It can be an alkylene group,

[0467] R6 to R 10 Each independently (i) a hydrogen atom (H), (ii) , (iii) or (iv) However, at least two of R6 to R8 may be any one of (ii) to (iv), and

[0468] R 11 , R 13 , R 14 and R 16 Each is independently substituted or unsubstituted divalent saturated or unsaturated C 2-10 Hydrocarbon group (more specifically, C 2-7 It can be a hydrocarbon group,

[0469] R 12 , R 15 and R 17 Each is independently substituted or unsubstituted monovalent saturated or unsaturated C 10-20 Hydrocarbon group (more specifically, C 12-17 It can be a hydrocarbon group,

[0470] L1 and L2 can each be independently selected from the group consisting of -C(O)O-, -OC(O)-, -C(O)N(R')-, and -N(R')C(O)-, where R' is each independently a hydrogen atom, and a substituted or unsubstituted C 1-4 It can be selected from the group consisting of alkyl groups, and

[0471] X can be -OH.

[0472] More specifically, the lipid of the above formula 10 may have any one structure selected from the following compounds 10-A to 10-O:

[0473]

[0474]

[0475]

[0476]

[0477] In one embodiment, the drug delivery composition of the present invention may further include a fused lipid to increase the efficiency of delivery of an active ingredient into the body.

[0478] In one embodiment, the fusion lipid may be one or more combinations selected from the group consisting of phospholipids, PEGylated lipids, cholesterol, and tocopherol.

[0479] Specifically, the phospholipid may be one or more selected from the group consisting of phosphatidylethanolamin (PE), phosphatidylcholine (PC), and phosphatidic acid. The phosphatidylethanolamin (PE), phosphatidylcholine (PC), and phosphatidic acid may be in a form combined with one or two C10-24 fatty acids. The cholesterol and tocopherol include analogs, derivatives, and metabolites of cholesterol and tocopherol, respectively.

[0480] Specifically, the PEG lipid refers to a polyethylene glycol (PEG)-modified lipid, which is a type of PEG derivative with a lipid moiety attached, such as DMG or DSPE, and has been widely used to improve the circulation time of active ingredients encapsulated in lipid nanoparticles and to reduce non-specific absorption. The PEG lipid may be one or more combinations selected from the group consisting of PEG-modified phosphatidylethanolamine, PEG-modified phosphatidic acid, PEG-modified ceramide, PEG-modified dialkylamine, PEG-modified diacylglycerol, and PEG-modified dialkylglycerol. For example, the PEG lipids include 1,2-dimyristoyl-sn-glycerol methoxypolyethylene glycol (PEG-DMG), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)](PEG-DSPE), PEG-disteryl glycerol (PEG-DSG), PEG-dipalmitoleyl, PEG-dioleyl, PEG-distearyl, PEG-diacylglycamide (PEG-DAG), PEG-dipalmitoyl phosphatidylethanolamine (PEG-DPPE), or PEG-1,2-dimyristyloxylpropyl-3-amine (PEG-c-DMA).

[0481] Specifically, the fused lipid is dilauroyl phosphatidylethanolamine, dimyristoyl phosphatidylethanolamine, dipalmitoyl phosphatidylethanolamine, distearoyl phosphatidylethanolamine, dioleoyl phosphatidylethanolamine, dilinoleoyl phosphatidylethanolamine, 1-palmitoyl-2-oleoyl phosphatidylethanolamine, 1,2-diphytanoyl-3-sn-phosphatidylethanolamine, dilauroyl phosphatidylcholine, dimyristoyl phosphatidylcholine, dipalmitoyl phosphatidylcholine, distearoyl phosphatidylcholine, dioleoyl phosphatidylcholine, dilinoleoyl phosphatidylcholine, 1-palmitoyl-2-oleoyl phosphatidylcholine, 1,2-diphytanoyl-3-sn-phosphatidylcholine, dilauroyl phosphatidic acid,It may be one or more combinations selected from the group consisting of dimyristoyl phosphatidic acid, dipalmitoyl phosphatidic acid, distearoyl phosphatidic acid, dioleoyl phosphatidic acid, dilinoleoyl phosphatidic acid, 1-palmitoyl-2-oleoyl phosphatidic acid, 1,2-diphytanoyl-3-sn-phosphatidic acid, cholesterol, and tocopherol.

[0482] More specifically, the fused lipid is dioleoyl phosphatidylethanolamine (DOPE), 1,2-dipalmitoleoyl-sn-glycero-3-phosphocholine (DPPC), distearoyl phosphatidylcholine (DSPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1-octadecanoyl-sn-glycero-3-phosphocholine (18:0 Lyso PC), 1-9z-octadecanoyl-sn-glycero-3-phosphocholine (1-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine, 18:1 Lyso PC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1-oleoyl-2-hydroxy-sn-glycero-3-phosphoethanolamine (18:1 Lyso PE), 1-sterol-2-oleoyl-sn-glycero-3-phosphoethanolamine (1-stearoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine, 18:0-18:1 PE), 1-sterol-2-linoleoyl-sn-glycero-3-phosphoethanolamine (1-stearoyl-2-linoleoyl-sn-glycero-3-phosphoethanolamine, 18:0-18:2 PE), 1,2-dilinoleoyl-sn-glycero-3-phosphoethanolamine (1,2-dilinoleoyl-sn-glycero-3-phosphoethanolamine, 18:2 PE), 1-stearoyl-2-hydroxy-sn-glycero-3-phospho-(1'-rac-glycerol), 18:0 Lyso PG), 1-oleoyl-2-hydroxy-sn-glycero-phospho-(1'-rac-glycerol), 18:1 Lyso PG), 1,2-dipalmitoleoyl-sn-glycero-3-phosphoethanolamine (DPPE), It may be one or more combinations selected from the group consisting of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), 1,2-dioleoyl-3-dimethylammonium-propane (DODAP), 1,2-dioleoyl-sn-glycero-3-phosphate (18PA), cholesterol, and tocopherol.

[0483] In one embodiment of the present invention, the fusion lipid may be distearoyl phosphatidylcholine, cholesterol, or a combination thereof.

[0484] In one embodiment, the fused lipid content may be 1 wt% or more, 2 wt% or more, 3 wt% or more, 4 wt% or more, or 5 wt% or more based on the dry weight of the total composition, and may also be 40 wt% or less, 35 wt% or less, 30 wt% or less, 25 wt% or less, or 20 wt% or less.

[0485] In one embodiment, the relative amount of the fused lipid to the cationic compound may be 0.05 parts by weight or more, 0.06 parts by weight or more, 0.07 parts by weight or more, 0.08 parts by weight or more, 0.09 parts by weight or more, or 0.1 parts by weight or more, based on 1 part by weight of the cationic compound, and may also be 6 parts by weight or less, 5.5 parts by weight or less, 5 parts by weight or less, 4.5 parts by weight or less, 4 parts by weight or less, or 3.8 parts by weight or less, but is not limited thereto.

[0486] In one embodiment, when a phospholipid is used as the fused lipid, the relative amount used may be 0.03 parts by weight or more, 0.04 parts by weight or more, 0.05 parts by weight or more, or 0.06 parts by weight or more based on 1 part by weight of the cationic compound, and may also be 4 parts by weight or less, 3.9 parts by weight or less, 3.7 parts by weight or less, 3.5 parts by weight or less, 3.3 parts by weight or less, 3.1 parts by weight or less, 3 parts by weight or less, 2.9 parts by weight or less, or 2.7 parts by weight or less, but is not limited thereto.

[0487] In one embodiment, when cholesterol is used as the fused lipid, the relative amount used may be 0.02 parts by weight or more, 0.03 parts by weight or more, or 0.04 parts by weight or more based on 1 part by weight of the cationic compound, and may also be 2 parts by weight or less, 1.9 parts by weight or less, 1.7 parts by weight or less, 1.5 parts by weight or less, 1.3 parts by weight or less, or 1.1 parts by weight or less, but is not limited thereto.

[0488] In addition, in one embodiment, the drug delivery composition of the present invention may further include one or more additive components (hereinafter, “optional additive components”) that are typically included in drug delivery compositions.

[0489] In one embodiment, the optional additive component may be one or more selected from, for example, pH modifiers (e.g., acidifying agents, alkalizing agents, buffering agents), tonicity modifiers, bulking agents (e.g., sugars, polyols, amino acids, polymers, proteins, etc.), wetting agents, solubilizing agents, surfactants, antioxidants, antimicrobial agents, chelating agents, complexing agents, etc., but is not limited thereto.

[0490] In one embodiment, the pH adjuster may be one or more selected from acetate, citrate, tartrate, histidine, glutamate, phosphate, Tris, glycine, bicarbonate, succinate, sulfate, nitrate, etc., but is not limited thereto.

[0491] In one embodiment, the intestinal regulator may be one or more selected from mannitol, sorbitol, lactose, dextrose, trehalose, sodium chloride, potassium chloride, glycerol, glycerin, propylene glycol, etc., but is not limited thereto.

[0492] In one embodiment, the bulking agent may be one or more selected from sugars and polyols including sucrose, trehalose, glucose, lactose sorbitol, mannitol, glycerol, etc.; amino acids including arginine, aspartic acid, glutamic acid, lysine, proline, glycine, histidine, methionine, alanine, etc.; polymers and proteins including gelatin, polyvinylpyrrolidone (PVP), polylactate-co-glycolate (PLGA), polyethylene glycol (PEG), dextran, cyclodextran, or derivatives thereof, starch derivatives, hydroxylamine sulfate (HAS), bovine serum albumin (BSA), etc., or combinations thereof, but is not limited thereto.

[0493] In one embodiment, the wetting agent and / or solubilizing agent is lecithin, PEG 300, PEG 600, PEG 1000, polyoxyethylene lauryl ether (e.g., Brij 30, Brij 35, Brij 56, Brij 76, Brij 97), polypropylene glycol (PPG) 2000, glucoside alkyl ethers, polyoxyethylene glycol octylphenol ethers, polyoxyethylene glycol alkylphenol ethers, glycerol alkyl esters, polysorbates 20, polysorbates 40, polysorbates 60, polysorbates 80, sorbitan monolaurate (Span It may be one or more selected from, but not limited to, sorbitan monooleate (Span 80), sorbitan trioleate (Span 85), cocamide monoethanolamine (cocamide MEA), cocamide diethanolamine (cocamide DEA), dodecyldimethylamine oxide, poloxamer, polyvinylpyrrolidone K25, polyvinyl alcohol, oligolactic acid, sodium dioctyl sulfosuccinate, diethylene glycol monolaurate, triethanolamine oleate, sodium oleate, potassium oleate, ethyl oleate, oleic acid, ethyl laurate, sodium lauryl sulfate, etc.

[0494] In one embodiment, the antioxidant may be one or more selected from tocopherol (vitamin E), tocopherol alpha, alpha tocopherol hydrogen succinate, ascorbic acid, accorbyl palmitate, butylated hydroxy anisole (BHA), butylated hydroxy toluene (BHT), monothioglycerol, potassium metabisulfite, propionic acid, propyl gallate, sodium ascorbate, sodium bisulfite, sodium metabisulfite, sodium sulfite, histamine, methionine, glutathione, poly(ethylamine), etc., but is not limited thereto.

[0495] In one embodiment, the antimicrobial agent may be one or more selected from benzalkonium chloride, benzethonium chloride, benzyl alcohol, bronopol, cetrimid, cetylpyridinium chloride, chlorhexidine, chlorobutanol, chlorocresol, chloroxylenol, cresol, metacresol, ethyl alcohol, glycerin, hexatidine, imidurea, phenol, phenoxyethanol, phenylethyl alcohol, phenylmercury nitrate, propylene glycol, thimerosal, etc., but is not limited thereto.

[0496] In one embodiment, the chelating agent may be one or more selected from ethylenediaminetetraacetic acid (EDTA), disodium edetate, dipotassium edetate, edetic acid, fumaric acid, malic acid, phosphoric acid, sodium edetate, tartaric acid, diethylenetriaminepentaacetic acid (DPTA), citric acid, hexaphosphate, thiolglycolic acid, zinc, etc., but is not limited thereto.

[0497] When any of the above additive components are used in the drug delivery composition of the present invention, the content of each additive may be, for example, 0.01 wt% or more, 0.05 wt% or more, or 0.1 wt% or more based on the dry weight of the total composition, and may also be 10 wt% or less, 5 wt% or less, or 1 wt% or less, but is not limited thereto.

[0498] The present invention will be explained in more detail below based on the following examples, but these are for the purpose of explaining the invention and do not limit the scope of the invention in any way.

[0499] [Example]

[0500] Example 1

[0501] Compounds of the following chemical formulas 1-A and 1-B (compound 1-A and compound 1-B, respectively) were prepared according to the synthesis outline shown in Fig. 1.

[0502] [Chemical Formula 1-A]

[0503]

[0504] [Chemical Formula 1-B]

[0505]

[0506] (1) Synthesis of compound A / B-1

[0507]

[0508] 6-bromohexanoic acid (5.00 g, 25.6 mmol, 1.00 eq) and dichloromethane (DCM) (50.0 mL) were mixed at 25°C. N,N′dicyclohexylcarbodiimide (DCC) (5.81 g, 28.2 mmol, 1.10 eq) and 4-dimethylaminopyridine (DMAP) (0.16 g, 1.28 mmol, 0.05 eq) were added to this mixture at 0°C. The mixture was stirred at 0°C for 30 minutes. Subsequently, 1-undecanol (4.64 g, 26.9 mmol, 1.05 eq) was added to the mixture. The mixture was stirred at 25°C for 20 hours under a nitrogen (N2) atmosphere. The residue was diluted with a 1% HCl aqueous solution (100 mL) and extracted three times with DCM (100 mL). The bound organic layer was dried with Na2SO4, filtered, and concentrated under reduced pressure to obtain the residue. The residue was purified by silica gel column chromatography (ethyl acetate / hexane (EA / Hex) = 1 / 20 to 1 / 10) to obtain compound A / B-1 (7.88 g, 22.6 mmol, yield 88.3%).

[0509] 1 HNMR (400 MHz, CHLOROFORM-d)δ0.88 (t, 3 H) 1.26-1.35 (m, 16 H) 1.45 - 1.51 (m, 2 H) 1.59-1.75 (m, 4 H) 1.85-1.93 (m, 2 H) 2.30-2.33 (t, 2 H) 3.39 - 3.42 (t, 2 H) 4.05-4.08 (t, 2 H)

[0510] (2) Synthesis of Compound A / B-2

[0511]

[0512] Compound A / B-1 (7.11 g, 20.4 mmol, 1.00 eq) and dimethylformamide (DMF) (100 mL) were mixed at 25°C. Acrylic acid (2.64 g, 36.6 mmol, 1.80 eq) and K2CO3 (11.25 g, 81.4 mmol, 4.00 eq) were added to this mixture at 25°C. The mixture was stirred at 25°C for 72 hours under a nitrogen (N2) atmosphere. After the reaction was complete, the residue was diluted with a 1% HCl aqueous solution (100 mL) and extracted three times with DCM (100 mL). The bound organic layer was dried with Na2SO4, filtered, and concentrated under reduced pressure to obtain the residue. The residue was purified by silica gel column chromatography (EA / Hex=1 / 10) to obtain compound A / B-2 (5.90 g, 17.3 mmol, yield 85.0%).

[0513] 1 HNMR (400 MHz, CHLOROFORM-d)δ0.88 (t, 3 H) 1.26 - 1.35 (m, 16 H) 1.39 - 1.45 (m, 2 H) 1.59-1.72 (m, 6 H) 2.32 (t, 2 H) 4.06 (t, 2 H) 4.16 (t, 2 H) 5.81 (dd, 1H) 6.12 (dd, 1H) 6.40 (dd, 1H)

[0514] (3) Synthesis of Compound A / B-3

[0515]

[0516] Compound A / B-2 (4.17 g, 12.3 mmol, 2.50 eq) and isopropyl alcohol (50 mL) were mixed at 25°C. 6-aminohexanoic acid (0.64 g, 4.90 mmol, 1.00 eq) was added to this mixture at 25°C. The mixture was stirred at 100°C for 20 hours. The reaction mixture was concentrated to obtain the residue. The residue was purified by silica gel column chromatography (DCM / methanol (MeOH)=12 / 1) to obtain compound A / B-3 (2.87 g, 3.53 mmol, yield 72.1%).

[0517] 1 HNMR (400 MHz, CHLOROFORM-d)δ0.88 (t, 6 H) 1.26 - 1.49 (m, 40 H) 1.59 - 1.69 (m, 14 H) 2.28 - 2.35 (m, 6 H) 2.39 - 2.45 (m, 6 H) 2.77 (t, 4 H) 4.06 (t, 8 H)

[0518] (4) Synthesis of Compound A / B-4

[0519]

[0520] Compound A / B-3 (0.17 g, 0.21 mmol, 1.20 eq) and DCM (5 mL) were mixed at 25°C. DCC (0.07 g, 0.29 mmol, 1.70 eq) and DMAP (0.01 g, 0.09 mmol, 0.5 eq) were added to this mixture at 0°C. The mixture was stirred at 0°C for 30 minutes. Subsequently, Boc-NH-PEG(2K)-NH2 (0.36 g, 0.17 mmol, 1.00 eq) was added to the mixture. The mixture was stirred at 25°C for 20 hours under a nitrogen (N2) atmosphere. The reaction mixture was concentrated to obtain the residue. The residue was purified by silica gel column chromatography (DCM / MeOH=12 / 1) to obtain compound A / B-4 (0.31 g, 0.11 mmol, yield 64.7%).

[0521] 1 HNMR (400 MHz, CHLOROFORM-d)δ0.88 (t, 6 H) 1.26 - 1.44 (m, 49 H) 1.60 - 1.67 (m, 14 H) 2.10 - 2.20 (m, 2 H) 2.31 (t, 4 H) 2.40 - 2.43 (m, 6 H) 2.75 (t, 4 H) 3.45 - 3.66 (m, 180 H) 4.06 (t, 8 H)

[0522] (5) Synthesis of Compound A / B-5

[0523]

[0524] Compound A / B-4 (0.35 g, 0.12 mmol, 1.00 eq) and DCM (2 mL) were mixed at 25°C. Trifluoroacetic acid (TFA) (2 mL) was added to this mixture at 25°C. The mixture was stirred at 25°C for 1 hour under a nitrogen (N2) atmosphere. The reaction mixture was concentrated to obtain the residue. The residue was purified by silica gel column chromatography (DCM / MeOH=8 / 1) to obtain compound A / B-5 (0.31 g, 0.11 mmol, yield 92.8%).

[0525] 1 HNMR (400 MHz, CHLOROFORM-d)δ0.88 (t, 6 H) 1.26 - 1.40 (m, 40 H) 1.60 - 1.68 (m, 14 H) 2.10 - 2.20 (m, 2 H) 2.31 (t, 4 H) 2.86 (t, 4 H) 3.00 - 3.10 (m, 2 H) 3.18 - 3.84 (m, 184 H) 4.05 (t, 4 H) 4.09 (t, 4 H)

[0526] (6) Synthesis of Compound 1-A

[0527]

[0528] Boc-Phe-OH (0.014 g, 0.05 mmol, 1.00 eq) and tetrahydrofuran (THF) (5 mL) were mixed at 25°C. DCC (0.014 g, 0.07 mmol, 1.25 eq) and N-hydroxysuccinimide (NHS) (0.009 g, 0.08 mmol, 1.5 eq) were added to this mixture at 25°C. The mixture was stirred at 25°C for 20 hours. Subsequently, compound A / B-5 (0.147 g, 0.05 mmol, 1.00 eq) and THF (10 mL) were added to the mixture. The mixture was stirred at 25°C for 3 hours under a nitrogen (N2) atmosphere. The reaction mixture was concentrated to obtain the residue. The residue was purified by silica gel column chromatography (DCM / MeOH=10 / 1) to obtain compound A (0.12 g, 0.04 mmol, yield 75.2%).

[0529] 1 HNMR (400 MHz, CHLOROFORM-d)δ0.88 (t, 6 H) 1.26 - 1.42 (m, 49 H) 1.60 - 1.69 (m, 14 H) 2.17 (t, 2 H) 2.31 (t, 4 H) 2.42 (br s, 4 H) 2.76 (br s, 4 H) 3.00 - 3.10 (m, 2 H) 3.39 - 3.84 (m, 182 H) 4.05 (t, 8 H) 4.15 (br s, 1 H) 7.12 - 7.29 (m, 5 H)

[0530] (7) Synthesis of Compound 1-B

[0531]

[0532] Compound 1-A (0.13 g, 0.04 mmol, 1.00 eq) and DCM (2 mL) were mixed at 25°C. TFA (2 mL) was added to this mixture at 25°C. The mixture was stirred at 25°C for 1 hour under a nitrogen (N2) atmosphere. The reaction mixture was concentrated to obtain the residue. The residue was purified by silica gel column chromatography (DCM / MeOH=8 / 1) to obtain Compound 1-B (0.12 g, 0.11 mmol, yield 92.1%).

[0533] 1 HNMR (400 MHz, DMSO-d6)δ0.88 (t, 6 H) 1.24 - 1.32 (m, 40 H) 1.53 - 1.60 (m, 14 H) 2.05 (t, 2 H) 2.29 (t, 4 H) 2.80 (br s, 4 H) 2.80 - 3.84 (m, 184 H) 3.98 - 4.06 (m, 9 H) 7.24 - 7.33 (m, 5 H) 7.8 - 7.9 (m, 1 H) 8.10 - 8.15 (m, 2 H), 8.40 - 8.55 (m, 1 H)

[0534] Example 2

[0535] Compounds of the following chemical formulas 1-C and 1-D (compound 1-C and compound 1-D, respectively) were prepared according to the synthesis outline shown in Fig. 2.

[0536] [Chemical Formula 1-C]

[0537]

[0538] [Chemical Formula 1-D]

[0539]

[0540] (1) Synthesis of compound 1-C

[0541]

[0542] Boc-Try-OH (0.015 g, 0.05 mmol, 1.00 eq) and THF (5 mL) were mixed at 25°C. DCC (0.014 g, 0.07 mmol, 1.25 eq) and NHS (0.009 g, 0.08 mmol, 1.5 eq) were added to this mixture at 25°C. The mixture was stirred at 25°C for 20 hours. Subsequently, compound A / B-5 (0.149 g, 0.05 mmol, 1.00 eq) and THF (10 mL) were added to the mixture. The mixture was stirred at 25°C for 3 hours under a nitrogen (N2) atmosphere. The reaction mixture was concentrated to obtain the residue. The residue was purified by silica gel column chromatography (DCM / MeOH=10 / 1) to obtain compound C (0.13 g, 0.04 mmol, yield 80.1%).

[0543] 1 HNMR (400 MHz, DMSO-d6)δ0.88 (t, 6 H) 1.16 - 1.31 (m, 49 H) 1.50 - 1.55 (m, 14 H) 2.00 - 2.10 (m, 2 H) 2.26 - 2.37 (m, 8 H) 2.50 - 2.65 (m, 4 H) 2.85 - 2.95 (m, 2 H) 3.05 - 3.80 (m, 182 H) 3.96 - 3.99 (m, 9 H) 6.63 (d, 2 H) 6.71 (br s, 1 H) 7.00 (d, 2 H) 7.72 - 7.95 (m, 2 H) 9.12 (s, 1 H)

[0544] (2) Synthesis of Compound 1-D

[0545]

[0546] Compound 1-C (0.13 g, 0.04 mmol, 1.00 eq) and DCM (2 mL) were mixed at 25°C. TFA (2 mL) was added to this mixture at 25°C. The mixture was stirred at 25°C for 1 hour under a nitrogen (N2) atmosphere. The reaction mixture was concentrated to obtain the residue. The residue was purified by silica gel column chromatography (DCM / MeOH=8 / 1) to obtain Compound 1-D (0.12 g, 0.11 mmol, yield 92.1%).

[0547] 1 HNMR (400 MHz, CHLOROFORM-d)δ0.88 (t, 6 H) 1.24 - 1.32 (m, 40 H) 1.53 - 1.60 (m, 14 H) 2.05 - 2.10 (m, 2 H) 2.29 (t, 4 H) 2.85 - 2.87 (m, 4 H) 3.00 - 3.15 (m, 6 H) 2.80 - 3.84 (m, 182 H) 4.04 - 4.11 (m, 9 H) 6.84 (d, 2 H) 7.10 (d, 2 H)

[0548] Example 3

[0549] Compounds of the following chemical formulas 1-E and 1-F (compound 1-E and compound 1-F, respectively) were prepared according to the synthesis outline shown in Fig. 3.

[0550] [Chemical Formula 1-E]

[0551]

[0552] [Chemical Formula 1-F]

[0553]

[0554] (1) Synthesis of compound E / F-1

[0555]

[0556] Fmoc-Phe-OH (0.05 g, 0.20 mmol, 1.5 eq) and DCM (5 mL) were mixed at 25°C. DCC (0.05 g, 0.23 mmol, 1.70 eq) and DMAP (0.08 g, 0.07 mmol, 0.5 eq) were added to this mixture at 0°C. The mixture was stirred at 0°C for 30 minutes. Subsequently, Fmoc-NH-PEG(2K)-OH (0.30 g, 0.14 mmol, 1.00 eq) and DCM (5 mL) were added to the mixture. The mixture was stirred at 25°C for 20 hours under a nitrogen (N2) atmosphere. The reaction mixture was concentrated to obtain the residue. The residue was purified by silica gel column chromatography (DCM / MeOH = 20 / 1 to 15 / 1) to obtain compound E / F-1 (0.22 g, 0.09 mmol, yield 65.1%).

[0557] 1 HNMR (400 MHz, CHLOROFORM-d)δ1.42 (s, 9 H) 3.01 - 3.20 (m, 2 H) 3.62 - 3.68 (m, 178 H) 4.20 - 4.38 (m, 3 H) 4.40 - 4.45 (m, 2 H) 4.58 - 4.65 (m, 1 H) 4.95 - 5.05 (m, 1 H) 5.40 - 5.45 (m, 1 H) 7.15 - 7.33 (m, 7 H) 7.38 - 7.43 (m, 2 H) 7.60 (d, 2 H) 7.76 (d, 2 H)

[0558] (2) Synthesis of Compound E / F-2

[0559]

[0560] Compound E / F-1 (0.22 g, 0.09 mmol, 1.00 eq) and DMF (5 mL, in 5% piperazine & 2% 1,8-diazabicyclo[5.4.0]undes-7-ene (DBU)) were mixed at 25°C. The mixture was stirred at 25°C for 30 minutes under a nitrogen (N2) atmosphere. The reaction mixture was concentrated to obtain the residue. The residue was purified by silica gel column chromatography (DCM / MeOH=12 / 1) to obtain compound E / F-2 (0.20 g, 0.09 mmol, yield 99.0%).

[0561] 1 HNMR (400 MHz, CHLOROFORM-d)δ1.42 (s, 9 H) 2.60 - 4.05 (m, 180 H) 4.20 - 4.40 (m, 2 H) 4.60 - 4.80 (m, 1 H) 5.00 - 5.10 (m, 1 H) 7.16 - 7.30 (m, 5H)

[0562] (3) Synthesis of Compound 1-E

[0563]

[0564] Compound A / B-3 (0.08 g, 0.10 mmol, 1.20 eq) and DCM (5 mL) were mixed at 25°C. DCC (0.03 g, 0.16 mmol, 1.70 eq) and DMAP (0.06 g, 0.05 mmol, 0.5 eq) were added to this mixture at 0°C. The mixture was stirred at 0°C for 30 minutes. Subsequently, Compound E / F-2 (0.18 g, 0.08 mmol, 1.00 eq) and DCM (5 mL) were added to the mixture. The mixture was stirred at 25°C for 20 hours under a nitrogen (N2) atmosphere. The reaction mixture was concentrated to obtain the residue. The residue was purified by silica gel column chromatography (DCM / MeOH=10 / 1) to obtain Compound E (0.15 g, 0.05 mmol, yield 61.8%).

[0565] 1HNMR (400 MHz, CHLOROFORM-d)δ0.88 (t, 6 H) 1.28 - 1.42 (m, 49 H) 1.60 - 1.66 (m, 14 H) 2.10 - 2.20 (m, 2 H) 2.31 (t, 4 H) 2.40 - 2.43 (m, 6 H) 2.74 - 2.75 (m, 4 H) 3.00 - 3.20 (m, 2 H) 3.45 - 3.66 (m, 178 H) 4.05 (t, 8 H) 4.20 - 4.30 (m, 2 H) 4.60 - 4.65 (m, 1 H) 4.95 - 5.10 (m, 1 H) 6.10 - 6.30 (m, 1 H) 7.16 - 7.28 (m, 5 H)

[0566] (4) Synthesis of Compound 1-F

[0567]

[0568] Compound 1-E (0.14 g, 0.05 mmol, 1.00 eq) and DCM (2 mL) were mixed at 25°C. TFA (2 mL) was added to this mixture at 25°C. The mixture was stirred at 25°C for 1 hour under a nitrogen (N2) atmosphere. The reaction mixture was concentrated to obtain the residue. The residue was purified by silica gel column chromatography (DCM / MeOH=8 / 1) to obtain compound F (0.12 g, 0.11 mmol, yield 92.1%).

[0569] 1 HNMR (400 MHz, CHLOROFORM-d)δ0.89 (t, 6 H) 1.26 - 1.40 (m, 40 H) 1.62 - 1.71 (m, 14 H) 2.17 (t, 2 H) 2.31 (t, 4 H) 2.41 - 2.43 (m, 6 H) 2.76 (br s, 4 H) 2.80 - 3.10 (m, 2 H) 3.44 - 3.84 (m, 179 H) 4.05 (t, 8 H) 4.26 - 4.27 (m, 2 H) 4.90 (br s, 1 H) 6.30 (br s, 2 H) 7.22 - 7.33 (m, 5H)

[0570] Example 4

[0571] Compounds of the following chemical formulas 1-G and 1-H (compound 1-G and compound 1-H, respectively) were prepared according to the synthesis outline shown in Fig. 4.

[0572] [Chemical Formula 1-G]

[0573]

[0574] [Chemical Formula 1-H]

[0575]

[0576] (1) Synthesis of compound G / H-1

[0577]

[0578] 6-bromohexanoic acid (8.00 g, 41.0 mmol, 1.00 eq) and DCM (50.0 mL) were mixed at 25°C. DCC (9.31 g, 45.1 mmol, 1.10 eq) and DMAP (0.25 g, 2.05 mmol, 0.05 eq) were added to this mixture at 0°C. The mixture was stirred at 0°C for 30 minutes. Subsequently, 2-hexyldecan-1-ol (10.4 g, 43.1 mmol, 1.05 eq) was added to the mixture. The mixture was stirred at 25°C for 20 hours under a nitrogen (N2) atmosphere. The residue was diluted with a 1% HCl aqueous solution (150 mL) and extracted three times with DCM (150 mL). The bound organic layer was dried with Na2SO4, filtered, and concentrated under reduced pressure to obtain the residue. The residue was purified by silica gel column chromatography (EA / Hex=1 / 30) to obtain compound G / H-1 (16.1 g, 38.4 mmol, yield 93.6%).

[0579] 1HNMR (400 MHz, CHLOROFORM-d)δ0.88 (t, 6 H) 1.20 - 1.30 (m, 24 H) 1.45 - 1.53 (m, 2 H) 1.62-1.69 (m, 3 H) 1.85-1.91 (m, 2 H) 2.33 (t, 2 H) 3.40 (t, 2H) 3.97 (d, 2H)

[0580] (2) Synthesis of Compound G / H-2

[0581]

[0582] Compound G / H-1 (16.1 g, 38.4 mmol, 1.00 eq) and DMF (100 mL) were mixed at 25°C. Acrylic acid (4.98 g, 69.1 mmol, 1.80 eq) and K2CO3 (21.2 g, 153.6 mmol, 4.00 eq) were added to this mixture at 25°C. The mixture was stirred at 25°C for 72 hours under a nitrogen (N2) atmosphere. After the reaction was complete, the residue was diluted with a 1% HCl aqueous solution (150 mL) and extracted three times with DCM (150 mL). The bound organic layer was dried with Na2SO4, filtered, and concentrated under reduced pressure to obtain the residue. The residue was purified by silica gel column chromatography (EA / Hex=1 / 20) to obtain compound G / H-2 (13.2 g, 32.3 mmol, yield 84.1%).

[0583] 1 HNMR (400 MHz, CHLOROFORM-d)δ0.90 (t, 6 H) 1.20 - 1.31 (m, 24 H) 1.39 - 1.46 (m, 2 H) 1.62-1.73 (m, 5 H) 2.32 (t, 2 H) 3.97 (d, 2 H) 4.16 (t, 2 H) 5.81 (dd, 1H) 6.11 (dd, 1H) 6.40 (dd, 1H)

[0584] (3) Synthesis of Compound G / H-3

[0585]

[0586] Compound G / H-2 (10.3 g, 25.2 mmol, 2.20 eq) and butanol (50 mL) were mixed at 25°C. 6-aminohexanoic acid (1.50 g, 11.4 mmol, 1.00 eq) was added to this mixture at 25°C. The mixture was stirred at 100°C for 20 hours. The reaction mixture was concentrated to obtain the residue. The residue was purified by silica gel column chromatography (DCM / MeOH=20 / 1) to obtain compound G / H-3 (7.62 g, 8.00 mmol, yield 70.1%).

[0587] 1 HNMR (400 MHz, CHLOROFORM-d)δ0.88 (t, 12 H) 1.26 - 1.48 (m, 56 H) 1.61 - 1.70 (m, 12 H) 2.20 - 2.30 (m, 6 H) 2.40 - 2.50 (m, 6 H) 2.70 - 2.80 (m, 4 H) 3.97 (d, 4 H) 4.05 (t, 4 H)

[0588] (4) Synthesis of Compound G / H-4

[0589]

[0590] Compound G / H-3 (0.783 g, 0.82 mmol, 1.15 eq) and DCM (5 mL) were mixed at 25°C. DCC (0.29 g, 1.40 mmol, 1.70 eq) and DMAP (0.05 g, 0.4 mmol, 0.5 eq) were added to this mixture at 0°C. The mixture was stirred at 0°C for 30 minutes. Subsequently, Boc-NH-PEG(2K)-NH2 (1.50 g, 0.71 mmol, 1.00 eq) was added to the mixture. The mixture was stirred at 25°C for 20 hours under a nitrogen (N2) atmosphere. The reaction mixture was concentrated to obtain the residue. The residue was purified by silica gel column chromatography (DCM / MeOH=15 / 1) to obtain compound G / H-4 (1.61 g, 0.53 mmol, yield 74.3%).

[0591] 1 HNMR (400 MHz, CHLOROFORM-d)δ0.88 (t, 12 H) 1.26 - 1.44 (m, 65 H) 1.62 - 1.67 (m, 12 H) 2.10 - 2.20 (m, 2 H) 2.32 (t, 4 H) 2.40 - 2.43 (m, 6 H) 2.75 (t, 4 H) 3.45 - 3.80 (m, 180 H) 3.97 (d, 4 H) 4.05 (t, 4 H) 5.00 (br s, 1 H) 6.10 (br s, 1 H)

[0592] (5) Synthesis of Compound G / H-5

[0593]

[0594] Compound G / H-4 (0.8 g, 0.26 mmol, 1.00 eq) and DCM (4 mL) were mixed at 25°C. TFA (4 mL) was added to this mixture at 25°C. The mixture was stirred at 25°C for 1 hour under a nitrogen (N2) atmosphere. The reaction mixture was concentrated to obtain the residue. The residue was purified by silica gel column chromatography (DCM / MeOH=8 / 1) to obtain compound G / H-5 (0.76 g, 0.26 mmol, yield 98.1%).

[0595] 1 HNMR (400 MHz, CHLOROFORM-d)δ.88 (t, 12 H) 1.26 - 1.43 (m, 56 H) 1.64 - 1.69 (m, 12 H) 2.10 - 2.20 (m, 2 H) 2.32 (t, 4 H) 2.87 - 3.82 (m, 188 H) 3.97 (d, 4 H) 4.11 (t, 4 H) 7.86 (br s, 2 H)

[0596] (6) Synthesis of Compound 1-G

[0597]

[0598] Boc-Phe-OH (0.060 g, 0.23 mmol, 1.00 eq) and THF (5 mL) were mixed at 25°C. DCC (0.058 g, 0.28 mmol, 1.25 eq) and NHS (0.039, 0.34 mmol, 1.5 eq) were added to this mixture at 25°C. The mixture was stirred at 25°C for 20 hours. Subsequently, compound G / H-5 (0.632 g, 0.23 mmol, 1.00 eq) and THF (10 mL) were added to the mixture. The mixture was stirred at 25°C for 3 hours under a nitrogen (N2) atmosphere. The reaction mixture was concentrated to obtain the residue. The residue was purified by silica gel column chromatography (DCM / MeOH=10 / 1) to obtain compound 1-G (0.343 g, 0.11 mmol, yield 47.6%).

[0599] 1 HNMR (400 MHz, CHLOROFORM-d)δ0.88 (t, 12 H) 1.24 - 1.32 (m, 65 H) 1.40 - 1.57 (m, 12 H) 2.00 - 2.10 (m, 2 H) 2.27 - 2.40 (m, 8 H) 2.63 (br s, 4 H) 2.65 - 3.00 (m, 2 H) 3.17 - 3.70 (m, 180 H) 3.90 (d, 4 H) 3.97 (br s, 4 H) 4.20 (br s, 1 H) 6.80 (m, 1 H), 7.05 - 7.20 (m, 5 H) 7.70 - 7.80 (m, 1H) 7.90 - 8.00 (m, 1 H)

[0600] (7) Synthesis of Compound 1-H

[0601]

[0602] Compound G (0.34 g, 0.11 mmol, 1.00 eq) and DCM (2 mL) were mixed at 25°C. TFA (2 mL) was added to this mixture at 25°C. The mixture was stirred at 25°C for 1 hour under a nitrogen (N2) atmosphere. The reaction mixture was concentrated to obtain the residue. The residue was purified by silica gel column chromatography (DCM / MeOH=8 / 1) to obtain compound 1-H (0.30 g, 0.10 mmol, yield 91.2%).

[0603] 1 HNMR (400 MHz, DMSO-d6)δ0.88 (t, 12 H) 1.24 - 1.32 (m, 56 H) 1.53 - 1.60 (m, 14 H) 2.05 - 2.10 (m, 2 H) 2.29 (t, 4 H) 2.80 (br s, 4 H) 3.00 - 3.80 (m, 182 H) 3.90 - 4.04 (m, 9 H) 7.23 - 7.34 (m, 5 H) 7.8 - 7.9 (m, 1 H) 8.10 - 8.25 (m, 2 H), 8.40 - 8.55 (m, 1 H)

[0604] [Example of preparation of a drug delivery composition]

[0605] 1. Synthesis of cationic lipids of chemical formula 2-E

[0606] A compound of the following chemical formula 2-E was prepared according to the synthesis outline shown in Fig. 5.

[0607] [Chemical Formula 2-E]

[0608]

[0609] (1) Synthesis of 1-cyclopropylnonan-1-ol

[0610] Cyclopropanecarbaldehyde (46.0 g, 656 mmol, 1.00 eq) was added to a 1000 mL 3-neck RBF, and after adding THF, octyl magnesium bromide (2.00 M, 492 mL, 1.50 eq) was added under a nitrogen atmosphere. After stirring the mixture at -65°C for 3 hours, 700 mL of a saturated aqueous solution of NH4Cl was poured in at 15°C to separate the organic layer from the aqueous layer. The aqueous layer was further extracted with EtOAc (200 mL x 3). The organic layer was collected, concentrated under vacuum, and purified using a silica column with a petroleum ether:EtOAc ratio of 100:1 to obtain 1-cyclopropylnonan-1-ol (59.5 g, 49.2%), a colorless oil.

[0611] 1 H NMR (400 MHz, CHLOROFORM-d):δ2.63 (td, 1H), 1.47 - 1.31 (m, 5H), 1.29 - 1.09 (m, 6H), 0.73 - 0.61 (m, 6H), 0.37 - 0.19 (m, 3H), 0.10 - 0.06 (m, 3H)

[0612] (2) Synthesis of 1-cyclopropylnonyl 8-bromooctanoate

[0613] DCM (600 mL), 1-cyclopropylnonan-1-ol (59.5 g, 325 mmol, 1.00 eq), 8-bromooctanic acid (94.4 g, 423 mmol, 1.30 eq), EDCI (93.6 g, 488 mmol, 1.50 eq), DMAP (39.8 g, 326 mmol, 1.00 eq), and TEA (32.9 g, 326 mmol, 45.3 mL, 1.00 eq) were added to a 1000 mL 3-neck RBF and stirred under a nitrogen environment at 25°C for 16 hours. The reaction mixture was concentrated under vacuum to obtain the residue. The obtained residue was purified using a silica column with a petroleum ether:EtOAc ratio of 100:1 to 1:1. Through this process, 1-cyclopropylnonyl 8-bromooctanoate (21.0 g, 53.9 mmol, 16.6% yield) was obtained as a light yellow oil.

[0614] 1 H NMR (400 MHz, CHLOROFORM-d):δ0.05 - 0.16 (m, 2 H) 0.16 - 0.34 (m, 2 H) 0.57 - 0.67 (m, 2 H) 0.67 -0.80 (m, 1 H) 1.02 (br s, 9 H) 1.05 (br s, 2 H) 1.07 - 1.15 (m, 6 H) 1.16 - 1.29 (m, 2 H) 1.34 - 1.44 (m, 4 H) 1.48 - 1.66(m, 2 H) 2.05 (t, 2 H) 3.06 - 3.33 (m, 2 H) 3.97 - 4.07 (m, 1) H)

[0615] (3) Synthesis of the compound of chemical formula 2-E

[0616] 1-cyclopropylnonyl 8-bromooctanoate (4.78 g, 12.3 mmol, 2.50 eq), 2-aminoethanol (2-aminoethanol, MEA) (0.30 g, 4.91 mmol, 1.00 eq), and Na2CO3 (521 mg, 4.91 mmol, 1.00 eq) were added to 5 mL of EtOH in a 100 mL 3-neck RBF and purged with nitrogen three times. The mixture was stirred at 95°C for 16 hours. The mixture in the reactor was concentrated under vacuum to obtain the residue. Subsequently, the residue was purified using a silica column with a DCM:MeOH ratio of 100:1 to 10:1 to obtain a yellow oil of the compound of formula 2-E (1.00 g, 1.47 mmol, 30.0% yield).

[0617] 1 H NMR (400 MHz, CHLOROFORM-d):δ= 4.27 (td, 2H), 3.53 (t, 2H), 2.57 (t, 2H), 2.47 - 2.40 (m, 4H), 2.30 (t, 4H), 1.70 - 1.57 (m, 10H), 1.48 - 1.39 (m, 4H), 1.36 - 1.26 (m, 33H), 0.95 (dt, 2H), 0.89 (t, 6H), 0.60 - 0.42 (m, 4H), 0.41 - 0.22 (m, 4H)

[0618] 2. Preparation of raw materials

[0619] As shown in the table below, the substances required for formulation preparation were dissolved in each dilution solvent to the required concentrations. When dissolving, the substances were brought to room temperature before adding the solvent and dissolving them.

[0620]

[0621] 3. Mixing of raw materials

[0622] The required amounts of raw materials were taken and mixed according to the ratio of cationic lipid of chemical formula 2-E : DOPE : cholesterol : DMG-PEG : respective compounds 1-A, 1-B, 1-D, or 1-F = 49.75 : 9.95 : 38.31 : 1.49 : 0.5, with the NP ratio (amine group of lipid: phosphate group of mRNA) set to 6. Ethanol was added to the ethanol layer so that the sum of all raw materials was within 12.5 mM, and the aqueous phase and ethanol phase were mixed while maintaining a volume ratio of 3:1. Buffer exchange was performed as follows to lower the total ethanol content after mixing: the mixture was concentrated by centrifuging at 4,000 rpm using an Amicon-Ultra tube filter (Merk Millipore, UFC505096 or UFC805024, pore size: 50K or 100K, volume 0.5 mL or 4 mL or 15 mL), and then the process of diluting with PBS and centrifuging to concentrate was repeated to perform buffer exchange.

[0623] The specific process sequence is as follows.

[0624] 1) Two autoclaved tubes were prepared (tubes (A), (B)).

[0625] 2) In Tube (A), the cationic lipid of formula 2-E and DOPE, cholesterol, DMG-PEG, and respective compounds 1-A, 1-B, 1-D, or 1-F were added in sequence according to the experimental conditions and mixed by vortexing after addition.

[0626] 3) Ethanol was added as needed in the ethanol phase so that the total of all raw materials was within 6.25-12.5 mM.

[0627] 4) mRNA and 20 mM sodium acetate buffer (pH 4.6) were mixed in Tube (B). The ratio was calculated so that the volume of the aqueous phase was three times the volume of the ethanol phase.

[0628] 5) Mixing of tube (A) and tube (B) was performed using a Microfluidics (Ignite, Precision Nanosystem) instrument. The Microfluidics operating conditions were a Flow Rate Ratio (FRR) of C:R=3:1 and a Total Flow Rate (TRR) of 12 mL / min.

[0629] 6) The resulting mixture from step 5) was centrifuged at 4,000 rpm using an Amicon-Ultra tube filter (50K) to concentrate it, then diluted with PBS and centrifuged to concentrate it again to remove excess ethanol, and then concentrated to a final x mg / mL (theoretical concentration).

[0630] 7) Once concentrated to the desired concentration, it was sterilized using a 0.22 µm pore size filter.

[0631] 3. Evaluation of Physical Properties of the Formulation

[0632] 1) For the prepared formulations, particle characteristics (i.e., zeta-average particle size, polydispersity index (PDI), and zeta-potential) were determined using a particle size analyzer (Dynamic Light Scattering, DLS), and the results are shown in Table 1 below.

[0633] 2) For the prepared formulations, mRNA encapsulation efficiency was confirmed through a Ribo-green assay, and the results are shown in Table 1 below.

[0634] [Table 1]

[0635]

Claims

1. Compound having a structure represented by the following chemical formula 1: [Chemical Formula 1] As mentioned above, R1 is a tissue or organ targeting site (moiety for targeting tissue or organ) that is unprotected or protected by a protective device, and R2 is a substituted or unsubstituted divalent saturated or unsaturated hydrocarbon group, and R3 to R5 are each independently (i) a hydrogen atom (H), (ii) , (iii) , (iv) , (v) , (we) , or (vii) However, at least one of R3 to R5 is any one of (ii) to (vii), and R6 to R 17 Each is independently a substituted or unsubstituted divalent saturated or unsaturated hydrocarbon group, and R 18 to R 23 Each is independently a substituted or unsubstituted monovalent saturated or unsaturated hydrocarbon group, and L1 to L 14 Each is independently selected from the group consisting of -C(O)O-, -OC(O)-, -OC(O)-L'-C(O)O-, -C(O)N(R')-, -N(R')C(O)-, -C(O)-, -C(S)-, -C(S)S-, -SC(S)-, -CH(OH)-, -P(O)(OR')O-, -S(O)2-, -SS-, arylene groups, and heteroarylene groups, wherein L' is a directly bonded, substituted or unsubstituted alkylene group or substituted or unsubstituted alkenylene group, and R' is each independently selected from the group consisting of a hydrogen atom, a substituted or unsubstituted alkyl group and a substituted or unsubstituted alkenyl group, and X is -OH or -SH, and n is an integer greater than or equal to 1, and m is 0 or 1, and when m is 1, N with R5 attached has a positive charge (+1).

2. In claim 1, the tissue or organ targeting site is a compound, wherein the site is derived from an amino acid, sugar, vitamin, peptide, protein, hormone, antibody, neurotransmitter, pharmaceutically active small molecule, endosome-degrading agent, cell membrane permeability agent, charge blocker, drug, nucleic acid, or a derivative thereof.

3. A compound according to claim 1, wherein the protecting group is selected from the group consisting of a t-butyl carbamate group, a fluorenylmethyl carbamate group, a benzyl carbamate group, an acetamide group, a trifluoroacetamide group, a phthalimide group, a benzylamine group, a triphenylmethylamine group, a p-toluenesulfonamide group, a methyl ester group, an ethyl ester group, a t-butyl ester group, a benzyl ester group, and a St-butyl ester group.

4. In Paragraph 1, R1 is a site derived from unprotected or protected amino acids, sugars, vitamins, peptides, proteins, hormones, antibodies, neurotransmitters, pharmaceutically active small molecules, endosome-degrading agents, cell membrane permeability agents, charge blockers, drugs, nucleic acids, or derivatives thereof, and R2 is substituted or unsubstituted divalent saturated or unsaturated C 2-20 It is a hydrocarbon group, and R3 to R5 are each independently (i) a hydrogen atom (H), (ii) , (iii) , (iv) , (v) , (we) , or (vii) However, at least two of R3 to R5 are any one of (ii) to (vii), and R6 to R 17 Each is independently substituted or unsubstituted divalent saturated or unsaturated C 2-20 It is a hydrocarbon group, and R 18 to R 23 Each is independently substituted or unsubstituted monovalent saturated or unsaturated C 2-20 It is a hydrocarbon group, and L1 to L 14 -C(O)O-, -OC(O)-, -C(O)N(R')-, -N(R')C(O)-, -C(O)-, -C(S)-, -C(S)S-, -SC(S)-, -CH(OH)-, -P(O)(OR')O-, -S(O)2-, -SS-, C 6-20 C having an arylene group and one or more heteroatoms selected from N, O, and S 3-20 Selected from the group consisting of heteroarylene groups, where L' is directly bonded, substituted, or unsubstituted C 1-13 alkylene group or substituted or unsubstituted C 2-13 It is an alkenylene group, and R' are each independently hydrogen atoms, substituted or unsubstituted C. 1-18 Alkyl groups and substituted or unsubstituted C 2-18 Selected from a group composed of alkenyl groups, and X is -OH or -SH, and n is an integer from 1 to 250, and A compound in which m is 0 or 1, and when m is 1, N with R5 attached carries a positive charge (+1).

5. In Paragraph 1, R1 is a site derived from unprotected or protected amino acids, sugars, vitamins, peptides, proteins, hormones, antibodies, neurotransmitters, pharmaceutically active small molecules, endosome-degrading agents, cell membrane permeability agents, charge blockers, drugs, nucleic acids, or derivatives thereof, and R2 is substituted or unsubstituted divalent saturated or unsaturated C 2-10 It is a hydrocarbon group, and R3 to R5 each independently (i) hydrogen atoms (H), , (iii) , (iv) , (v) , (we) , or (vii) However, at least two of R3 to R5 are any one of (ii) to (vii), and R6 to R 17 Each is independently substituted or unsubstituted divalent saturated or unsaturated C 2-10 It is a hydrocarbon group, and R 18 to R 23 Each is independently substituted or unsubstituted monovalent saturated or unsaturated C 10-20 It is a hydrocarbon group, and L1 to L 14 Each is independently selected from the group consisting of -C(O)O-, -OC(O)-, -C(O)N(R')-, and -N(R')C(O)-, where R' is each independently a hydrogen atom, and a substituted or unsubstituted C 1-4 Selected from the group consisting of alkyl groups, and X is -OH or -SH, and n is an integer from 1 to 50, and A compound in which m is 0 or 1, and when m is 1, N with R5 attached carries a positive charge (+1).

6. In claim 1, a compound having a structure selected from any one of the following compounds 1-A to 1-I:

7. A method for preparing a compound having a structure represented by Chemical Formula 1, comprising the step of reacting a compound of Chemical Formula a with a compound of Chemical Formula b: [Chemical formula a] [Chemical formula b] [Chemical Formula 1] As mentioned above, R1 is an unprotected or protected tissue or organ targeting site, and R2 is a substituted or unsubstituted divalent saturated or unsaturated hydrocarbon group, and R3 to R5 are each independently (i) a hydrogen atom (H), (ii) , (iii) , (iv) , (v) , (we) , or (vii) However, at least one of R3 to R5 is any one of (ii) to (vii), and R6 to R 17 Each is independently a substituted or unsubstituted divalent saturated or unsaturated hydrocarbon group, and R 18 to R 23 Each is independently a substituted or unsubstituted monovalent saturated or unsaturated hydrocarbon group, and L1 is -C(O)N(R')-, and R' is each independently selected from the group consisting of a hydrogen atom, a substituted or unsubstituted alkyl group and a substituted or unsubstituted alkenyl group, and L2 to L 14 Each is independently selected from the group consisting of -C(O)O-, -OC(O)-, -OC(O)-L'-C(O)O-, -C(O)N(R')-, -N(R')C(O)-, -C(O)-, -C(S)-, -C(S)S-, -SC(S)-, -CH(OH)-, -P(O)(OR')O-, -S(O)2-, -SS-, arylene groups, and heteroarylene groups, wherein L' is a directly bonded, substituted or unsubstituted alkylene group or substituted or unsubstituted alkenylene group, and R' is each independently selected from the group consisting of a hydrogen atom, a substituted or unsubstituted alkyl group and a substituted or unsubstituted alkenyl group, and X is -OH or -SH, and n is an integer greater than or equal to 1, and m is 0 or 1, and when m is 1, N with R5 attached has a positive charge (+1).

8. A method for preparing a compound having a structure represented by Chemical Formula 1, comprising the step of reacting a compound of Chemical Formula c with a compound of Chemical Formula d: [Chemical formula c] [Chemical formula d] [Chemical Formula 1] As mentioned above, R1 is an unprotected or protected tissue or organ targeting site, and R2 is a substituted or unsubstituted divalent saturated or unsaturated hydrocarbon group, and R3 to R5 are each independently (i) a hydrogen atom (H), (ii) , (iii) , (iv) , (v) , (we) , or (vii) However, at least one of R3 to R5 is any one of (ii) to (vii), and R6 to R 17 Each is independently a substituted or unsubstituted divalent saturated or unsaturated hydrocarbon group, and R 18 to R 23 Each is independently a substituted or unsubstituted monovalent saturated or unsaturated hydrocarbon group, and L2 is -N(R')C(O)-, and R' is each independently selected from the group consisting of a hydrogen atom, a substituted or unsubstituted alkyl group and a substituted or unsubstituted alkenyl group, and L1 and L3 to L 14 Each is independently selected from the group consisting of -C(O)O-, -OC(O)-, -OC(O)-L'-C(O)O-, -C(O)N(R')-, -N(R')C(O)-, -C(O)-, -C(S)-, -C(S)S-, -SC(S)-, -CH(OH)-, -P(O)(OR')O-, -S(O)2-, -SS-, arylene groups, and heteroarylene groups, wherein L' is a directly bonded, substituted or unsubstituted alkylene group or substituted or unsubstituted alkenylene group, and R' is each independently selected from the group consisting of a hydrogen atom, a substituted or unsubstituted alkyl group and a substituted or unsubstituted alkenyl group, and X is -OH or -SH, and n is an integer greater than or equal to 1, and m is 0 or 1, and when m is 1, N with R5 attached has a positive charge (+1).

9. A drug delivery composition comprising a compound of any one of claims 1 to 6.

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