Nucleic acid-containing lipid nanoparticle

A nucleic acid-containing lipid nanoparticle comprising

• an analog of a fatty acid ester of glycerol wherein the analog is not hydrolyzable by a lipase,
• a nucleic acid, and
• a cationic lipid,
• w
• wherein the cationic lipid is lipid A represented by at least one of the following formulas (I) to (IV), (V′) and (V″), and/or lipid B represented by at least one of the following formulas (CL-I) to (CL-XIX):
• formula (I)
• wherein
• R1 to R3 are the same or different and are each optionally substituted linear or branched C8-C24 alkyl, C8-C24 alkenyl or C8-C24 alkynyl;
• L1 to L3 are the same or different and are each absent, or —Z1—(CY1Y2)p1— or —Z2—(CY3Y4)p2—Z3—(CY5Y6)p3— wherein Yt to Y6 are the same or different and are each a hydrogen atom or optionally substituted C1-C4 alkyl;
• Zt to Z3 are the same or different and are each —O—, —NY7A—, —CO—O—, —O—CO—, —CO—NY7B—, —NY7C—CO— or —NY7D—CO—O— wherein Y7A to Y7D are the same or different and are each a hydrogen atom or optionally substituted C1-C4 alkyl;
• and p1 to p3 are the same or different and are each an integer from 1 to 5;
• X1 is optionally substituted C1-C4 alkyl;
• and
• A1 is a pharmaceutically acceptable anion,
• formula (II)
• wherein
• R4 to R6 are the same or different and are each optionally substituted linear or branched C8-C24 alkyl, C8-C24 alkenyl or C8-C24 alkynyl;
• L4 to L6 are the same or different and are each absent, or —Z4—(CY8Y9)p4— or —Z5—(CY10Y11)p5—Z6—(CY12Y13)p6— wherein Y8 to Y13 are the same or different and are each a hydrogen atom or optionally substituted C1-C4 alkyl;
• Z4 to Z6 are the same or different and are each —O—, —NY14A—, —CO—, —O—CO—, —CO—NY14B—, —NY14C—CO— or —NY14D—CO—O— wherein Y14A to Y14D are the same or different and are each a hydrogen atom or optionally substituted C1-C4 alkyl;
• p4 is an integer from 0 to 5;
• p5 is an integer from 1 to 5;
• and p6 is an integer from 0 to 5;
• L7 is absent, or —(CY15Y16)p7—, —(CY17Y18)p8—Z7—(CY19Y20)p9— or —(CY21Y22)p10—Z8—(CY23Y24)p11—Z9—(CY25Y26)p12— wherein Y15 to Y26 are the same or different and are each a hydrogen atom or optionally substituted C1-C4 alkyl;
• Z7 to Z9 are the same or different and are each —O—, —NY27A—, —CO—O—, —O—CO—, —CO—NY27B—, —NY27C—CO— or —NY27D—CO—O— wherein Y27A to Y27D are the same or different and are each a hydrogen atom or optionally substituted C1-C4 alkyl;
• p7 is an integer from 1 to 5;
• p8 is an integer from 0 to 5;
• p9 is an integer from 1 to 5;
• p10 is an integer from 0 to 5;
• p11 is an integer from 1 to 5;
• and p12 is an integer from 1 to 5;
• B1 is
• wherein X2 and X3 are the same or different and are each optionally substituted C1-C4 alkyl, or together form an optionally substituted C4-C6 hetero ring with the adjacent nitrogen atom;
• X4 is optionally substituted C1-C4 alkyl;
• X5 and X6 are the same or different and are each optionally substituted C1-C4 alkyl, or together form an optionally substituted C4-C6 hetero ring with the adjacent nitrogen atom;
• X7 is optionally substituted C1-C4 alkyl;
• Y28 to Y37 are the same or different and are each a hydrogen atom or optionally substituted C1-C4 alkyl;
• Z10 and Z11 are the same or different and are each —O—, —NY38A—, —CO—O—, —O—CO—, —CO—NY38B—, —NY38C—CO— or —NY38D—CO—O— wherein Y38A to Y38D are the same or different and are each a hydrogen atom or optionally substituted C1-C4 alkyl;
• p13 is an integer from 0 to 5;
• and p14 to p17 are the same or different and are each an integer from 1 to 5;
• and
• A2 is a pharmaceutically acceptable anion,
• formula (III)
• wherein
• R7 to R9 are the same or different and are each optionally substituted linear or branched C8-C24 alkyl, C8-C24 alkenyl or C8-C24 alkynyl;
• L8 to L10 are the same or different and are each absent, or —Z1—(CY39Y40)p18— or —Z13—(CY41Y42)p19—Z14—(CY43Y44)p20— wherein Y39 to Y44 are the same or different and are each a hydrogen atom or optionally substituted C1-C4 alkyl;
• Z12 to Z14 are the same or different and are each —O—, —NY45A—, —CO—, —O—CO—, —CO—NY45B—, —NY45C—CO—, —NY45D—CO—O— or —CO— wherein Y45A to Y45D are the same or different and are each a hydrogen atom or optionally substituted C1-C4 alkyl;
• p18 is an integer from 0 to 5;
• p19 is an integer from 1 to 5;
• and p20 is an integer from 0 to 5;
• L11 is absent, or —(CY46Y47)p21—, —(CY48Y49)p22—Z15—(CY50Y51)p23— or —(CY2Y53)p24—Z16—(CY54Y55)p25—Z17—(CY56Y57)p26— wherein Y46 to Y57 are the same or different and are each a hydrogen atom or optionally substituted C1-C4 alkyl;
• Z15 to Z17 are the same or different and are each —O—, —NY58A—, —CO—O—, —O—CO—, —CO—NY58B—, —NY58C—CO—, —NY58D—CO—O— or —CO— wherein Y58A to Y58D are the same or different and are each a hydrogen atom or optionally substituted C1-C4 alkyl;
• p21 is an integer from 1 to 5;
• p22 is an integer from 0 to 5;
• p23 is an integer from 1 to 5;
• p24 is an integer from 0 to 5;
• p25 is an integer from 1 to 5;
• and p26 is an integer from 1 to 5;
• L12 is absent, or —(CY59Y60)p27—, —(CY61Y62)p28—Z18—(CY63Y64)p29— or —(CY65Y66)p3—Z19—(CY67Y68)p31—Z20—(CY69Y70)p32— wherein Y59 to Y70 are the same or different and are each a hydrogen atom or optionally substituted C1-C4 alkyl;
• Z18 to Z20 are the same or different and are each —O—, —NY71A—, —CO—O—, —O—CO—, —CO—NY71B—, —NY71C—CO—, —NY71D—CO—O— or —CO— wherein Y71A to Y71D are the same or different and are each a hydrogen atom or optionally substituted C1-C4 alkyl;
• p27 is an integer from 1 to 5;
• p28 is an integer from 0 to 5;
• p29 is an integer from 0 to 5;
• p30 is an integer from 0 to 5;
• p31 is an integer from 1 to 5;
• and p32 is an integer from 0 to 5;
• J1 and J2 are the same or different and are each CY72 or N wherein Y72 is a hydrogen atom, hydroxy, optionally substituted C1-C4 alkyl, optionally substituted C1-C4 alkoxy, or optionally substituted C1-C4 acyloxy;
• B2 is
• wherein X8 and X9 are the same or different and are each optionally substituted C1-C4 alkyl, or together form an optionally substituted C4-C6 hetero ring with the adjacent nitrogen atom;
• X10 is optionally substituted C1-C4 alkyl;
• X11 and X12 are the same or different and are each optionally substituted C1-C4 alkyl, or together form an optionally substituted C4-C6 hetero ring with the adjacent nitrogen atom;
• X13 is optionally substituted C1-C4 alkyl;
• Y73 to Y82 are the same or different and are each a hydrogen atom or optionally substituted C1-C4 alkyl;
• Z21 and Z22 are the same or different and are each —O—, —NY83A—, —CO—O—, —O—CO—, —CO—NY83B—, —NY83C—CO— or —NY83D—CO—O— wherein Y83A to Y83D are the same or different and are each a hydrogen atom or optionally substituted C1-C4 alkyl;
• p33 is an integer from 0 to 5;
• and p34 to p37 are the same or different and are each an integer from 1 to 5;
• and
• A3 is a pharmaceutically acceptable anion,
• formula (IV)
• wherein
• R10 to R12 are the same or different and are each optionally substituted linear or branched C8-C24 alkyl, C8-C24 alkenyl or C8-C24 alkynyl;
• L13 is absent, or —Z23—(CY83Y84)p38— or —Z24—(CY85Y86)p39—Z25—(CY87Y88)p40— wherein Y83 to Y88 are the same or different and are each a hydrogen atom or optionally substituted C1-C4 alkyl;
• Z23 to Z25 are the same or different and are each —O—, —NY89A—, —CO—O—, —O-CO—, —CO—NY89B—, —NY89C—CO— or —NY89D—CO—O— wherein Y89A to Y89D are the same or different and are each a hydrogen atom or optionally substituted C1-C4 alkyl;
• and p38 to p40 are the same or different and are each an integer from 1 to 5;
• L14 and L15 are the same or different and are each absent, or —Z26—(CY90Y91)p41— or —Z27—(CY92Y93)p42—Z28—(CY94Y95)p43— wherein Y90 to Y95 are the same or different and are each a hydrogen atom or optionally substituted C1-C4 alkyl;
• Z26 to Z28 are the same or different and are each —O—, —NY96A—, —CO—O—, —O—CO—, —CO—NY96B—, —NY96C—CO—, —NY96D—CO—O— or —CO— wherein Y96A to Y96D are the same or different and are each a hydrogen atom or optionally substituted C1-C4 alkyl;
• p41 is an integer from 0 to 5;
• p42 is an integer from 1 to 5;
• and p43 is an integer from 0 to 5;
• L16 is absent, or —(CY97Y98)p44—, —(CY99Y100)p45—Z29—(CY101Y102)p46— or —(CY103Y104)p47—Z30—(CY105Y106)p48—Z31—(CY107Y108)p49— wherein Y97 to Y108 are the same or different and are each a hydrogen atom or optionally substituted C1-C4 alkyl;
• Z29 to Z31 are the same or different and are each —O—, —NY109A, —CO—O—, —O-CO—, —CO—NY109B—, —NY109C—CO—, —NY109D—CO—O— or —CO— wherein Y109A to Y109D are the same or different and are each a hydrogen atom or optionally substituted C1-C4 alkyl;
• p44 is an integer from 1 to 5;
• p45 is an integer from 0 to 5;
• p46 is an integer from 1 to 5;
• p47 is an integer from 0 to 5;
• p48 is an integer from 1 to 5;
• and p49 is an integer from 1 to 5;
• J3 is CY110 or N wherein Y110 is a hydrogen atom, hydroxy, optionally substituted C1-C4 alkyl, optionally substituted C1-C4 alkoxy, or optionally substituted C1-C4 acyloxy;
• X14 and X15 are the same or different and are each optionally substituted C1-C4 alkyl, or together form an optionally substituted C4-C6 hetero ring with the adjacent nitrogen atom;
• and
• A4 is a pharmaceutically acceptable anion,
• formula (V′) or formula (V″)
• wherein
• R13 to R18 are the same or different and are each optionally substituted linear or branched C8-C24 alkyl, C8-C24 alkenyl or C8-C24 alkynyl;
• Y111 to Y114 are the same or different and are each a hydrogen atom, hydroxy or optionally substituted C1-C4 alkyl;
• L17 to L19 and L22 to L24 are the same or different and are each absent, or —Z32—(CY115Y116)p51— or —Z33—(CY17Y118)p52—Z34—(CY119Y120)p53— wherein Y115 to Y120 are the same or different and are each a hydrogen atom or optionally substituted C1-C4 alkyl;
• Z32 to Z34 are the same or different and are each —O—, —NY121A—, —CO—O—, —O—CO—, —CO—NY121B—, —NY121C—CO—, —NY121D—CO—O— or —CO— wherein Y121A to Y121D are the same or different and are each a hydrogen atom or optionally substituted C1-C4 alkyl;
• p51 is an integer from 0 to 5;
• p52 is an integer from 1 to 5;
• and p53 is an integer from 0 to 5;
• L20 and L25 are the same or different and are each absent, or —(CY122Y123)p54—, —(CY124Y125)p55—Z35—(CY126Y127)p56— or —(CY128Y129)p57—Z36—(CY130Y131)p58—Z37—(CY132Y133)p59— wherein Y122 to Y133 are the same or different and are each a hydrogen atom or optionally substituted C1-C4 alkyl;
• Z35 to Z37 are the same or different and are each —O—, —NY134A—, —CO—O—, —O—CO—, —CO—NY134B—, —NY134C—CO—, —NY134D—CO—O— or —CO— wherein Y134A to Y134D are the same or different and are each a hydrogen atom or optionally substituted C1-C4 alkyl;
• p54 is an integer from 1 to 5;
• p55 is an integer from 0 to 5;
• p56 is an integer from 1 to 5;
• p57 is an integer from 0 to 5;
• p58 is an integer from 1 to 5;
• and p59 is an integer from 1 to 5;
• L21 and L26 are the same or different and are each absent, or —(CY135Y136)p60—, —(CY137Y138)p61—Z38—(CY139Y140)p62— or —(CY141Y142)p63—Z39—(CY143Y144)p64—Z40—(CY145Y146)p65— wherein Y135 to Y146 are the same or different and are each a hydrogen atom or optionally substituted C1-C4 alkyl;
• Z38 to Z40 are the same or different and are each —O—, —NY147A—CO—O—, —O—CO—, —CO—NY147B—, —NR147C—CO—, —NY147D—CO—O— or —CO— wherein Y147A to Y147D are the same or different and are each a hydrogen atom or optionally substituted C1-C4 alkyl;
• p60 is an integer from 1 to 5;
• p61 is an integer from 0 to 5;
• p62 is an integer from 0 to 5;
• p63 is an integer from 0 to 5;
• p64 is an integer from 1 to 5;
• and p65 is an integer from 0 to 5;
• B3 and B4 are the same or different and are each
• wherein X16 and X17 are the same or different and are each optionally substituted C1-C4 alkyl, or together form an optionally substituted C4-C6 hetero ring with the adjacent nitrogen atom;
• X18 is optionally substituted C1-C4 alkyl;
• X19 and X20 are the same or different and are each optionally substituted C1-C4 alkyl, or together form an optionally substituted C4-C6 hetero ring with the adjacent nitrogen atom;
• X21 is optionally substituted C1-C4 alkyl;
• Y148 to Y157 are the same or different and are each a hydrogen atom or optionally substituted C1-C4 alkyl;
• Z41 and Z42 are the same or different and are each —O—, —NY158A—, —CO—, —O—CO—, —CO—NY158B—, —NY158C—CO— or —NY158D—CO—O— wherein Y158A to Y158D are the same or different and are each a hydrogen atom or optionally substituted C1-C4 alkyl;
• p66 is an integer from 0 to 5;
• and p67 to p70 are the same or different and are each an integer from 1 to 5;
• and
• A5 and A6 are the same or different and are each a pharmaceutically acceptable anion,
• formula (CL-I)
• wherein
• R101 and R102 are the same or different and are each linear or branched C10-C24 alkyl, C10-C24 alkenyl or C10-C24 alkynyl;
• L101 and L102 are each a hydrogen atom, or together form a single bond or C2-C8 alkylene;
• L103 is a single bond, —CO— or —CO—O—;
• when L103 is a single bond,
• X101 is a hydrogen atom, C1-C6 alkyl, C3-C6 alkenyl, pyrrolidin-3-yl, piperidin-3-yl, piperidin-4-yl, or C1-C6 alkyl or C3-C6 alkenyl substituted with one to three same or different substituents selected from amino, monoalkylamino, dialkylamino, trialkylammonio, hydroxy, alkoxy, carbamoyl, monoalkylcarbamoyl, dialkylcarbamoyl, pyrrolidinyl, piperidyl and morpholinyl;
• and
• when L103 is —CO— or —CO—O—,
• X101 is pyrrolidin-2-yl, pyrrolidin-3-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, morpholin-2-yl, morpholin-3-yl, or C1-C6 alkyl or C3-C6 alkenyl substituted with one to three same or different substituents selected from amino, monoalkylamino, dialkylamino, trialkylammonio, hydroxy, alkoxy, carbamoyl, monoalkylcarbamoyl, dialkylcarbamoyl, pyrrolidinyl, piperidyl and morpholinyl, and at least one of the substituents is amino, monoalkylamino, dialkylamino, trialkylammonio, pyrrolidinyl, piperidyl or morpholinyl,
• formula (CL-II)
• wherein
• R103 and R104 are the same or different and are each linear or branched C12-C24 alkyl, C12-C24 alkenyl or C12-C24 alkynyl;
• p101 and p102 are the same or different and are each an integer from 0 to 3;
• L106 and L107 are each a hydrogen atom, or together form a single bond or C2-C8 alkylene;
• L104 and L105 are the same or different and are each —O—, —CO—O— or —O—CO—;
• L108 is a single bond, —CO— or —CO—O—;
• when L108 is a single bond,
• X102 is a hydrogen atom, C1-C6 alkyl, C3-C6 alkenyl, pyrrolidin-2-yl, pyrrolidin-3-yl, piperidin-3-yl, piperidin-4-yl, or C1-C6 alkyl or C3-C6 alkenyl substituted with one to three same or different substituents selected from amino, monoalkylamino, dialkylamino, trialkylammonio, hydroxy, alkoxy, carbamoyl, monoalkylcarbamoyl, dialkylcarbamoyl, pyrrolidinyl, piperidyl and morpholinyl;
• and
• when L108 is —CO— or —CO—O—,
• X102 is pyrrolidin-2-yl, pyrrolidin-3-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, morpholin-2-yl, morpholin-3-yl, or C1-C6 alkyl or C3-C6 alkenyl substituted with one to three same or different substituents selected from amino, monoalkylamino, dialkylamino, trialkylammonio, hydroxy, alkoxy, carbamoyl, monoalkylcarbamoyl, dialkylcarbamoyl, pyrrolidinyl, piperidyl and morpholinyl, and at least one of the substituents is amino, monoalkylamino, dialkylamino, trialkylammonio, pyrrolidinyl, piperidyl or morpholinyl,
• formula (CL-III)
• wherein
• R105 is linear or branched C8-C24 alkyl, C8-C24 alkenyl or C8-C24 alkynyl;
• R106 is linear or branched C8-C24 alkyl, C8-C24 alkenyl, C8-C24 alkynyl, C8-C24 alkyloxyethyl, C8-C24 alkyloxypropyl, C8-C24 alkenyloxyethyl, C8-C24 alkenyloxypropyl, C8-C24 alkynyloxyethyl or C8-C24 alkynyloxypropyl;
• X103 and X104 are the same or different and are each C1-C3 alkyl, or together form C2-C8 alkylene, or X103 forms C2-C8 alkylene together with L111;
• L111 is a hydrogen atom, C1-C6 alkyl, C3-C6 alkenyl, amino, monoalkylamino, hydroxy, alkoxy, carbamoyl, monoalkylcarbamoyl, dialkylcarbamoyl, or C1-C6 alkyl or C3-C6 alkenyl substituted with one to three same or different substituents selected from amino, monoalkylamino, hydroxy, alkoxy, carbamoyl, monoalkylcarbamoyl and dialkylcarbamoyl, or forms C2-C8 alkylene together with X103;
• L109 is C1-C6 alkylene;
• L110 is a single bond, or C1-C6 alkylene, provided that the sum of the numbers of carbon atoms of L109 and L110 is 7 or less;
• when L111 is a hydrogen atom, L110 is a single bond;
• and when L111 forms C2-C6 alkylene together with X103, L110 is a single bond, or methylene or ethylene,
• formula (CL-IV)
• wherein
• R107 is linear or branched C8-C24 alkyl, C8-C24 alkenyl or C8-C24 alkynyl;
• R108 is linear or branched C8-C24 alkyl, C8-C24 alkenyl, C8-C24 alkynyl, C8-C24 alkyloxyethyl, C8-C24 alkyloxypropyl, C8-C24 alkenyloxyethyl, C8-C24 alkenyloxypropyl, C8-C24 alkynyloxyethyl, C8-C24 alkynyloxypropyl, C8-C24 alkyloxyethoxyethyl, C8-C24 alkenyloxyethoxyethyl or C8-C24 alkynyloxyethoxyethyl;
• and
• X105 is a hydrogen atom or optionally substituted C1-C4 alkyl,
• formula (CL-V)
• wherein
• R109 is linear or branched C8-C24 alkyl, C8-C24 alkenyl or C8-C24 alkynyl;
• R110 is linear or branched C8-C24 alkyl, C8-C24 alkenyl, C8-C24 alkynyl, C8-C24 alkyloxyethyl, C8-C24 alkyloxypropyl, C8-C24 alkenyloxyethyl, C8-C24 alkenyloxypropyl, C8-C24 alkynyloxyethyl or C8-C24 alkynyloxypropyl;
• L112 is C1-C3 alkylene;
• and
• X105′ is a hydrogen atom or C1-C3 alkyl,
• formula (CL-VI)
• wherein
• R111 and R112 are the same or different and are each optionally substituted linear or branched C8-C24 alkyl, C8-C24 alkenyl or C8-C24 alkynyl;
• X106 and X107 are the same or different and are each C1-C3 alkyl, or together form C2-C8 alkylene;
• p103, p104 and p105 are the same or different and are each 0 or 1, provided that p103, p104 and p105 are not 0 at the same time;
• and
• L113 and L114 are the same or different and are each O, S or NH,
• formula (CL-VII)
• wherein
• R113 and R114 are the same or different and are each optionally substituted linear or branched C8-C24 alkyl, C8-C24 alkenyl or C8-C24 alkynyl;
• R105 is a hydrogen atom, hydroxy, optionally substituted C1-C4 alkyl, C1-C4 alkoxy or C1-C4 acyloxy;
• X109 and X10 are the same or different and are each C1-C3 alkyl, or together form C2-C8 alkylene;
• L105 is —CO—O—, —O—CO—, —NHCO— or —CONH—;
• p106 is an integer from 0 to 3;
• and
• p107 is an integer from 1 to 4,
• formula (CL-VIII)
• wherein
• R116 and R17 are the same or different and are each optionally substituted linear or branched C8-C24 alkyl, C8-C24 alkenyl, C8-C24 alkynyl, C7-C20 alkyloxy C1-C3 alkyl, C7-C20 alkenyloxy C1-C3 alkyl or C7-C20 alkynyloxy C1-C3 alkyl;
• B100 is a hydrogen atom, C1-C3 alkyl, hydroxy C2-C4 alkyl, C1-C3 dialkylamino C2-C4 alkyl, formula (A):
• wherein X111 and X112 are the same or different and are each a hydrogen atom or C1-C3 alkyl, or X111 and X112 optionally form a C2-C6 nitrogen-containing hetero ring together with the nitrogen atom to which they are bonded;
• and p110 is an integer from 2 to 6,
• or formula (B):
• wherein X113 and X114 are the same or different and are each a hydrogen atom or C1 to C3 alkyl, or X113 and X114 optionally form a C2-C6 nitrogen-containing hetero ring together with the nitrogen atom to which they are bonded;
• and p111 is an integer from 1 to 6;
• P108 is an integer from 0 to 4;
• P109 is an integer from 1 to 4, provided that when P108 is 0, P109 is not 1;
• L116 is the same or different on each carbon to which it is bonded and is a hydrogen atom or C1-C3 alkyl;
• and
• L17 is the same or different on each carbon to which it is bonded and is a hydrogen atom or C1-C3 alkyl,
• formula (CL-IX)
• wherein
• X115 and X116 are the same or different and are each a hydrogen atom or C1-C3 alkyl;
• L118 and L119 are the same or different and are each optionally substituted linear or branched C8-C24 alkylene or C8-C24 alkenylene;
• M101 and M102 are the same or different and are each selected from the group consisting of —C═C—, —OC(O)—, —C(O)O—, —SC(O)—, —C(O)S—, —OC(S)—, —C(S)O—, —SS—, —C(R″)═N—, —N═C(R″)—, —C(R″)═N—O—, —O—N═C(R″)—, —N(R″)C(O)—, —C(O)N(R″)—, —N(R″)C(S)—, —C(S)N(R″)—, —N(R″)C(O)N(R′″)—, —N(R″)C(O)O—, —OC(O)N(R″)— and —OC(O)O—;
• R″ and R′″ are the same or different and are each a hydrogen atom or C1-C3 alkyl;
• and
• R118 and R119 are the same or different and are each optionally substituted linear or branched C1-C16 alkyl or C2-C16 alkenyl,
• formula (CL-X)
• wherein
• X117 and X118 are the same or different and are each a hydrogen atom, optionally substituted C1-C6 alkyl, heterocyclyl or polyamine, or X117 and X118 optionally form, together with the nitrogen to which they are bonded, a 4- to 7-membered monocyclic hetero ring optionally containing one or two additional heteroatoms selected from N, O and S in addition to the nitrogen;
• and
• R120 and R121 are the same or different and are each optionally substituted linear or branched C4-C24 alkyl or C4-C24 alkenyl,
• formula (CL-XI)
• wherein
• X119 and X120 are the same or different and are each a hydrogen atom, optionally substituted linear or branched C1-C20 alkyl, C1-C20 alkenyl, C1-C20 alkynyl or C6-C20 acyl;
• R122 and R123 are the same or different and are each optionally substituted linear or branched C1-C30 alkyl, C2-C30 alkenyl or C2-C30 alkynyl;
• and
• p112, p113 and p114 are the same or different and are each 0, or an arbitrary positive integer,
• formula (CL-XII)
• wherein
• X121 and X122 are the same or different and are each a hydrogen atom, C1-C6 alkyl, cycloalkyl or cycloalkenyl, or X121 and X122 optionally form a C2-C6 nitrogen-containing hetero ring together with the nitrogen atom to which they are bonded;
• L120 and L121 are the same or different and are each —O—, —OC(O)— or —(O)CO—;
• and
• R124 and R125 are the same or different and are each optionally substituted linear or branched C8-C24 alkyl or C8-C24 alkenyl,
• formula (CL-XIII)
• wherein
• R126 and R127 are the same or different and are each optionally substituted linear or branched C8-C24 alkyl, C8-C24 alkenyl, C8-C24 alkynyl, C8-C24 heteroalkyl, C8-C24 heteroalkenyl or C8-C24 heteroalkynyl;
• X123 is a hydrogen atom or optionally substituted C1-C6 alkyl;
• X124 is C1-C6 alkyl, substituted C1-C6 alkyl which is substituted with —NR4aR4b, or optionally substituted C3-C7 heterocyclyl;
• R4a and R4b are the same or different and are each a hydrogen atom, C(═NH)NH2 or optionally substituted C1-C6 alkyl, or R4a and R4b optionally form optionally substituted C3-C7 heterocyclyl;
• X123 and X124 optionally form optionally substituted C3-C7 heterocyclyl together with the nitrogen atom to which they are bonded,
• provided that X123 and X124 do not form imidazolyl, benzimidazolyl, or succinimidyl, and only one primary amine is allowed to be present on any one of X123 and X124, or any primary amine is not present on any one of X123 and X124, and neither X123 nor X124 is substituted amide;
• when each of R126 and R127 is C11 alkyl or C15 alkyl, X123 is not a hydrogen atom;
• when each of R126 and R127 is C16 alkyl or C17 alkyl, R126 and R127 are not substituted with OH;
• when each of R126 and R127 is C17 alkyl, X123 and X124 are not substituted with OH;
• and
• when each of R126 and R127 is C18 alkyl, X124 is not substituted with optionally substituted imidazolyl,
• formula (CL-XIV)
• wherein
• X125 and X126 are the same or different and are each a hydrogen atom, optionally substituted C1-C6 alkyl, heterocyclyl or polyamine, or X125 and X126 optionally form, together with the nitrogen to which they are bonded, a 4- to 7-membered monocyclic hetero ring optionally containing one or two additional heteroatoms selected from N, O and S in addition to the nitrogen;
• R130 is a hydrogen atom or C1-C6 alkyl;
• and
• R128 and R129 are the same or different and are each optionally substituted linear or branched C4-C24 alkyl or C4-C24 alkenyl,
• formula (CL-XV)
• wherein
• X127 and X128 are each independently C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl, or
• X127 and X128 form, together with the nitrogen atom to which they are bonded, a hetero ring having one or two nitrogen atoms;
• L122 is —C(O)O—, —OC(O)—, —C(O)N(X130)—, —N(X130)C(O)—, —OC(O)O—, —OC(O)N(X130)—, —N(X130)C(O)N(X130)—, or —N(X130)C(O)O—;
• each X130 present is independently a hydrogen atom or C1-C3 alkyl;
• a is 1, 2, 3, 4, 5, or 6;
• b is 0, 1, 2, or 3;
• X129 is absent, or hydrogen or C1-C3 alkyl;
• R131 and R132 are each independently alkyl having 12 to 24 carbon atoms, alkenyl having 12 to 24 carbon atoms, or alkoxy having 12 to 24 carbon atoms, which has one or more biodegradable groups;
• each biodegradable group independently interrupts the alkyl group, the alkenyl group, or the alkoxy group having 12 to 24 carbon atoms, or substitutes a terminal of the alkyl group, the alkenyl group, or the alkoxy group having 12 to 24 carbon atoms (wherein the interrupting biodegradable group is —C(O)O—, —OC(O)—, —C(O)N(X130)—, or —N(X130)C(O)—, and the group having the terminal biodegradable group is —C(O)O-C1-C4 alkyl, —OC(O)—C1-C4 alkyl, —C(O)N(X130)—C1-C4 alkyl, or —N(X130)C(O)—C1-C4 alkyl);
• and
• R131 and R132 each have at least four carbon atoms between the biodegradable group and the asterisked (*) tertiary carbon atom,
• formula (CL-XVI)
• wherein
• R133 and R134 are the same or different and are each linear or branched C1-C9 alkyl, C2—C11 alkenyl or C2-C11 alkynyl;
• L123 and L124 are the same or different and are each linear C5-C18 alkylene or linear C5—C18 alkenylene, or forms a hetero ring with N;
• L125 is a single bond, or —CO—O—, thereby forming -L124-CO—OR134;
• L127 is S or O;
• L126 is a single bond or linear or branched C1-C6 alkylene, or forms a hetero ring with N;
• L128 is linear or branched C1-C6 alkylene;
• and
• X131 and X132 are the same or different and are each hydrogen or linear or branched C1—C6 alkyl,
• formula (CL-XVII)
• wherein
• L131 is C2-C4 alkylene or —CH2—S—CH2CH2—;
• L129 and L130 are the same or different and are each C1-C6 alkyl;
• R135 and R136 are the same or different and are each C10-C30 alkyl or C10-C30 alkenyl;
• and
• X133 and X134 are the same or different and are each hydrogen, C1-C6 alkyl or —CH2CH2OH,
• formula (CL-XVIII)
• wherein
• R137 and R38 are the same or different and are each linear or branched C8-C24 alkyl, C8—C24 alkenyl, C8-C24 alkynyl, C8-C24 alkylthioethyl, C8-24 alkenylthioethyl, or C8-C24 alkynylthioethyl;
• X135 is a hydrogen atom, C1-C3 alkyl, hydroxy C2-C4 alkyl, formula (C):
• wherein X136 and X137 are the same or different and are each a hydrogen atom or C1-C3 alkyl, or X136 and X137 optionally form a C2-C6 nitrogen-containing hetero ring together with the nitrogen atom to which they are bonded;
• L132 is S or O;
• and p115 is an integer from 2 to 4,
• formula (D):
• wherein X138 and X139 are the same or different and are each a hydrogen atom or C1 to C3 alkyl, or X138 and X139 optionally form a C3-C6 nitrogen-containing hetero ring together with the nitrogen atom to which they are bonded;
• and p116 is an integer from 1 to 4, or formula (E):
• wherein X140 and X141 are the same or different and are each a hydrogen atom or C1 to C3 alkyl, or X140 and X141 optionally form a C3-C6 nitrogen-containing hetero ring together with the nitrogen atom to which they are bonded;
• and p117 is an integer from 1 to 4, and
• formula (CL-XIX)
• wherein
• R139 and R140 are the same or different and are each linear or branched C8-C24 alkyl, C8—C24 alkenyl or C8-C24 alkynyl;
• L133 is S or O;
• and
• X142 is a hydrogen atom, C1-C3 alkyl, hydroxy C2-C4 alkyl, formula (F):
• wherein X143 and X144 are the same or different and are each a hydrogen atom or C1-C3 alkyl, or X143 and X144 optionally form a C2-C6 nitrogen-containing hetero ring together with the nitrogen atom to which they are bonded;
• L134 is S or O;
• and p118 is an integer from 2 to 4, or formula (G):
• wherein X145 and X146 are the same or different and are each a hydrogen atom or C1 to C3 alkyl, or X145 and X146 optionally form a C3-C6 nitrogen-containing hetero ring together with the nitrogen atom to which they are bonded;
• and p119 is an integer from 1 to 4.