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公开(公告)号:US07601872B2
公开(公告)日:2009-10-13
申请号:US11040662
申请日:2005-01-21
申请人: Yongliang Chu , Malek Masoud , Gulilat Gebeyehu
发明人: Yongliang Chu , Malek Masoud , Gulilat Gebeyehu
IPC分类号: C07C233/00 , C07C235/00 , C07C237/00 , C07C239/00 , C07C277/00 , C07C211/00 , A61K31/13 , A61K31/14 , A61K9/50 , A61K9/127 , C12N15/88
CPC分类号: A61K47/48046 , A61K9/16 , A61K31/14 , A61K38/28 , A61K38/40 , A61K47/543 , C07C211/21 , C07C211/63 , C07C211/64 , C07C229/26 , C07D209/48 , C07D241/12 , C12N15/88 , Y10S435/81
摘要: Disclosed are compounds capable of facilitating transport of biologically active agents or substances into cells having the general structure: wherein Q is selected from the group consisting of N, O and S; L is any bivalent organic radical capable of linking each Q, such as C, CH, (CH2)l, or {(CH2)i-Y—(CH2)j}k, wherein Y is selected from the group consisting of CH2, an ether, a polyether, an amide, a polyamide, an ester, a sulfide, a urea, a thiourea, a guanidyl, a carbamoyl, a carbonate, a phosphate, a sulfate, a sulfoxide, an imine, a carbonyl, and a secondary amino group and wherein Y is optionally substituted by —X1-L′-X2-Z or -Z; R1-R6, independently of one another, are selected from the group consisting of H, —(CH2)p-D-Z, an alkyl, an alkenyl, an aryl, and an alkyl or alkyl ether optionally substituted by one or more of an alcohol, an aminoalcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, an alkylthio, a urea, a thiourea, a guanidyl, or a carbamoyl group, and wherein at least one of R1, R3, R4 and R6 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group; and anyone of R1, R3, R4 and/or R6 may optionally be covalently linked with each other, with Y or with L when L is C or CH to form a cyclic moiety; Z is selected from the group consisting of amine, spermiyl, carboxyspermiyl, guanidyl, spermidinyl, putricinyl, diaminoalkyl, pyridyl, piperidinyl, pyrrolidinyl, polyamine, amino acid, peptide, and protein; X1 and X2, independently of one another, are selected from the group consisting of NH, O, S, alkylene, and arylene; L′ is selected from the group consisting of alkylene, alkenylene, alkynylene, arylene, alkylene ether, and polyether; D is Q or a bond; A1 and A2, independently of one another, are selected from the group consisting of CH2O, CH2S, CH2NH, C(O), C{NH), C(S) and (CH2)t; X is a physiologically acceptable anion; m, n, r, s, u, v, w and y are 0 or 1, with the proviso that when both m and n are 0 at least one of r, s, u and y is other than 0; i, j, k, l, p and are integers from 0 to about 100; q is an integer from 1 to about 1000; and a is the number of positive charge divided by the valence of the anion.
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公开(公告)号:US20090215067A1
公开(公告)日:2009-08-27
申请号:US12430747
申请日:2009-04-27
申请人: Gulilat Gebeyehu , Taysir M. Jaouni , Joel Jessee
发明人: Gulilat Gebeyehu , Taysir M. Jaouni , Joel Jessee
IPC分类号: C12Q1/68 , C07C229/02 , C07F9/02 , C12Q1/02
CPC分类号: C07C217/28 , C07C215/14
摘要: Cationic lipid compositions are provided that are useful for efficient delivery of macromolecules, such as nucleic acids, into a wide variety of eukaryotic cell types. Methods for using the compositions also are provided.
摘要翻译: 提供了阳离子脂质组合物,其可用于将大分子如核酸有效递送到各种真核细胞类型中。 还提供了使用组合物的方法。
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公开(公告)号:US20090143583A1
公开(公告)日:2009-06-04
申请号:US12353371
申请日:2009-01-14
申请人: Yongliang CHU , Malek MASOUD , Gulilat GEBEYEHU
发明人: Yongliang CHU , Malek MASOUD , Gulilat GEBEYEHU
IPC分类号: C07D403/12 , C07C233/49 , C07D413/12
CPC分类号: A61K47/48046 , A61K9/16 , A61K31/14 , A61K38/28 , A61K38/40 , A61K47/543 , C07C211/21 , C07C211/63 , C07C211/64 , C07C229/26 , C07D209/48 , C07D241/12 , C12N15/88 , Y10S435/81
摘要: Disclosed are compounds capable of facilitating transport of biologically active agents or substances into cells having the general structure: wherein Q is selected from the group consisting of N, O and S; L is any bivalent organic radical capable of linking each Q, such as C, CH, (CH2)l, or {(CH2)i-Y—(CH2)j}k, wherein Y is selected from the group consisting of CH2, an ether, a polyether, an amide, a polyamide, an ester, a sulfide, a urea, a thiourea, a guanidyl, a carbamoyl, a carbonate, a phosphate, a sulfate, a sulfoxide, an imine, a carbonyl, and a secondary amino group and wherein Y is optionally substituted by —X1-L′-X2-Z or -Z; R1-R6, independently of one another, are selected from the group consisting of H, —(CH2)p-D-Z, an alkyl, an alkenyl, an aryl, and an alkyl or alkyl ether optionally substituted by one or more of an alcohol, an aminoalcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, an alkylthio, a urea, a thiourea, a guanidyl, or a carbamoyl group, and wherein at least one of R1, R3, R4 and R6 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group; and anyone of R1, R3, R4 and/or R6 may optionally be covalently linked with each other, with Y or with L when L is C or CH to form a cyclic moiety; Z is selected from the group consisting of amine, spermiyl, carboxyspermiyl, guanidyl, spermidinyl, putricinyl, diaminoalkyl, pyridyl, piperidinyl, pyrrolidinyl, polyamine, amino acid, peptide, and protein; X1 and X2, independently of one another, are selected from the group consisting of NH, O, S, alkylene, and arylene; L′ is selected from the group consisting of alkylene, alkenylene, alkynylene, arylene, alkylene ether, and polyether; D is Q or a bond; A1 and A2, independently of one another, are selected from the group consisting of CH2O, CH2S, CH2NH, C(O), C{NH), C(S) and (CH2)t; X is a physiologically acceptable anion; m, n, r, s, u, v, w and y are 0 or 1, with the proviso that when both m and n are 0 at least one of r, s, u and y is other than 0; i, j, k, l, p and are integers from 0 to about 100; q is an integer from 1 to about 1000; and a is the number of positive charge divided by the valence of the anion.
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公开(公告)号:US07479573B2
公开(公告)日:2009-01-20
申请号:US11040687
申请日:2005-01-21
申请人: Yongliang Chu , Malek Masoud , Gulilat Gebeyehu
发明人: Yongliang Chu , Malek Masoud , Gulilat Gebeyehu
IPC分类号: C07C211/62 , C07C211/63 , C07C211/64 , A61K31/13 , A61K9/127 , A61K9/50 , C12N15/88
CPC分类号: A61K47/48046 , A61K9/16 , A61K31/14 , A61K38/28 , A61K38/40 , A61K47/543 , C07C211/21 , C07C211/63 , C07C211/64 , C07C229/26 , C07D209/48 , C07D241/12 , C12N15/88 , Y10S435/81
摘要: Disclosed are compounds capable of facilitating transport of biologically active agents or substances into cells having the general structure: wherein Q is selected from the group consisting of N, O and S; L is any bivalent organic radical capable of linking each Q, such as C, CH, (CH2)l, or {(CH2)i—Y—(CH2)j}k, wherein Y is selected from the group consisting of CH2, an ether, a polyether, an amide, a polyamide, an ester, a sulfide, a urea, a thiourea, a guanidyl, a carbamoyl, a carbonate, a phosphate, a sulfate, a sulfoxide, an imine, a carbonyl, and a secondary amino group and wherein Y is optionally substituted by —X1—L′—X2—Z or —Z; R1—R6, independently of one another, are selected from the group consisting of H, —(CH2)p-D-Z, an alkyl, an alkenyl, an aryl, and an alkyl or alkyl ether optionally substituted by one or more of an alcohol, an aminoalcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, an alkylthio, a urea, a thiourea, a guanidyl, or a carbamoyl group, and wherein at least one of R1, R3, R4 and R6 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group; and anyone of R1, R3, R4 and/or R6 may optionally be covalently linked with each other, with Y or with L when L is C or CH to form a cyclic moiety; Z is selected from the group consisting of amine, spermiyl, carboxyspermiyl, guanidyl, spermidinyl, putricinyl, diaminoalkyl, pyridyl, piperidinyl, pyrrolidinyl, polyamine, amino acid, peptide, and protein; X1 and X2, independently of one another, are selected from the group consisting of NH, O, S, alkylene, and arylene; L′ is selected from the group consisting of alkylene, alkenylene, alkynylene, arylene, alkylene ether, and polyether; D is Q or a bond; A1 and A2, independently of one another, are selected from the group consisting of CH2O, CH2S, CH2NH, C(O), C{NH), C(S) and (CH2)t; X is a physiologically acceptable anion; m, n, r, s, u, v, w and y are 0 or 1, with the proviso that when both m and n are 0 at least one of r, s, u and y is other than 0; i, j, k, l, p and are integers from 0 to about 100; q is an integer from 1 to about 1000; and a is the number of positive charge divided by the valence of the anion.
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公开(公告)号:US20070202600A1
公开(公告)日:2007-08-30
申请号:US11617625
申请日:2006-12-28
申请人: Yongliang Chu , Malek Masoud , Gulilat Gebeyehu
发明人: Yongliang Chu , Malek Masoud , Gulilat Gebeyehu
IPC分类号: C12N15/88 , C07C229/20 , C07H21/02 , C07J9/00 , C12N15/87
CPC分类号: A61K47/48046 , A61K9/16 , A61K31/14 , A61K38/28 , A61K38/40 , A61K47/543 , C07C211/21 , C07C211/63 , C07C211/64 , C07C229/26 , C07D209/48 , C07D241/12 , C12N15/88 , Y10S435/81
摘要: Disclosed are compounds capable of facilitating transport of biologically active agents or substances into cells having the general structure: wherein Q is selected from the group consisting of N, O and S; L is any bivalent organic radical capable of linking each Q, such as C, CH, (CH2)I, or {(CH2)i—Y—(CH2)j}k, wherein Y is selected from the group consisting of CH2, an ether, a polyether, an amide, a polyamide, an ester, a sulfide, a urea, a thiourea, a guanidyl, a carbamoyl, a carbonate, a phosphate, a sulfate, a sulfoxide, an imine, a carbonyl, and a secondary amino group and wherein Y is optionally substituted by —X1—L′—X2—Z or —Z; R1-R6, independently of one another, are selected from the group consisting of H, —(CH2)p—D—Z, an alkyl, an alkenyl, an aryl, and an alkyl or alkyl ether optionally substituted by one or more of an alcohol, an aminoalcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, an alkylthio, a urea, a thiourea, a guanidyl, or a carbamoyl group, and wherein at least one of R1, R3, R4 and R6 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group; and anyone of R1, R3, R4 and/or R6 may optionally be covalently linked with each other, with Y or with L when L is C or CH to form a cyclic moiety; Z is selected from the group consisting of amine, spermiyl, carboxyspermiyl, guanidyl, spermidinyl, putricinyl, diaminoalkyl, pyridyl, piperidinyl, pyrrolidinyl, polyamine, amino acid, peptide, and protein; X1 and X2, independently of one another, are selected from the group consisting of NH, O, S, alkylene, and arylene; L′ is selected from the group consisting of alkylene, alkenylene, alkynylene, arylene, alkylene ether, and polyether; D is Q or a bond; A1 and A2, independently of one another, are selected from the group consisting of CH2O, CH2S, CH2NH, C(O), C{NH), C(S) and (CH2)t; X is a physiologically acceptable anion; m, n, r, s, u, v, w and y are 0 or 1, with the proviso that when both m and n are 0 at least one of r, s, u and y is other than 0; i, j, k, l, p and are integers from 0 to about 100; q is an integer from 1 to about 1000; and a is the number of positive charge divided by the valence of the anion.
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公开(公告)号:US20070202598A1
公开(公告)日:2007-08-30
申请号:US11617614
申请日:2006-12-28
申请人: Yongliang Chu , Malek Masoud , Gulilat Gebeyehu
发明人: Yongliang Chu , Malek Masoud , Gulilat Gebeyehu
IPC分类号: C12N15/85 , C07C211/00 , C07C215/00 , C07C233/00 , C07H21/02 , C07H21/04
CPC分类号: A61K47/48046 , A61K9/16 , A61K31/14 , A61K38/28 , A61K38/40 , A61K47/543 , C07C211/21 , C07C211/63 , C07C211/64 , C07C229/26 , C07D209/48 , C07D241/12 , C12N15/88 , Y10S435/81
摘要: Disclosed are compounds capable of facilitating transport of biologically active agents or substances into cells having the general structure: wherein Q is selected from the group consisting of N, O and S; L is any bivalent organic radical capable of linking each Q, such as C, CH, (CH2)l, or {(CH2)i-Y—(CH2)j}k, wherein Y is selected from the group consisting of CH2, an ether, a polyether, an amide, a polyamide, an ester, a sulfide, a urea, a thiourea, a guanidyl, a carbamoyl, a carbonate, a phosphate, a sulfate, a sulfoxide, an imine, a carbonyl, and a secondary amino group and wherein Y is optionally substituted by -X1-L ′-X2-Z or -Z; R1-R6, independently of one another, are selected from the group consisting of H, —(CH2)p-D-Z, an alkyl, an alkenyl, an aryl, and an alkyl or alkyl ether optionally substituted by one or more of an alcohol, an aminoalcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, an alkylthio, a urea, a thiourea, a guanidyl, or a carbamoyl group, and wherein at least one of R1, R3, R4 and R6 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group; and anyone of R1, R3, R4 and/or R6 may optionally be covalently linked with each other, with Y or with L when L is C or CH to form a cyclic moiety; Z is selected from the group consisting of amine, spermiyl, carboxyspermiyl, guanidyl, spermidinyl, putricinyl, diaminoalkyl, pyridyl, piperidinyl, pyrrolidinyl, polyamine, amino acid, peptide, and protein; X1 and X2, independently of one another, are selected from the group consisting of NH, O, S, alkylene, and arylene; L′ is selected from the group consisting of alkylene, alkenylene, alkynylene, arylene, alkylene ether, and polyether; D is Q or a bond; Al and A2, independently of one another, are selected from the group consisting of CH2O, CH2S, CH2NH, C(O), C{NH), C(S) and (CH2)t; X is a physiologically acceptable anion; m, n, r, s, u, v, w and y are 0 or 1, with the proviso that when both m and n are 0 at least one of r, s, u and y is other than 0; i, j, k, l, p and are integers from 0 to about 100; q is an integer from 1 to about 1000; and a is the number of positive charge divided by the valence of the anion.
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公开(公告)号:US07145039B2
公开(公告)日:2006-12-05
申请号:US11040562
申请日:2005-01-21
申请人: Yongliang Chu , Malek Masoud , Gulilat Gebeyehu
发明人: Yongliang Chu , Malek Masoud , Gulilat Gebeyehu
IPC分类号: C07C215/18 , C12N15/88
CPC分类号: A61K47/48046 , A61K9/16 , A61K31/14 , A61K38/28 , A61K38/40 , A61K47/543 , C07C211/21 , C07C211/63 , C07C211/64 , C07C229/26 , C07D209/48 , C07D241/12 , C12N15/88 , Y10S435/81
摘要: Disclosed are compounds capable of facilitating transport of biologically active agents or substances into cells having the general structure: wherein Q is selected from the group consisting of N, O and S; L is any bivalent organic radical capable of linking each Q, such as C, CH, (CH2)l, or {(CH2)i-Y—(CH2)j}k, wherein Y is selected from the group consisting of CH2, an ether, a polyether, an amide, a polyamide, an ester, a sulfide, a urea, a thiourea, a guanidyl, a carbamoyl, a carbonate, a phosphate, a sulfate, a sulfoxide, an imine, a carbonyl, and a secondary amino group and wherein Y is optionally substituted by —X1—L′—X2—Z or —Z; R1–R6, independently of one another, are selected from the group consisting of H, —(CH2)p-D—Z, an alkyl, an alkenyl, an aryl, and an alkyl or alkyl ether optionally substituted by one or more of an alcohol, an aminoalcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, an alkylthio, a urea, a thiourea, a guanidyl, or a carbamoyl group, and wherein at least one of R1, R3, R4 and R6 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group; and anyone of R1, R3, R4 and/or R6 may optionally be covalently linked with each other, with Y or with L when L is C or CH to form a cyclic moiety; Z is selected from the group consisting of amine, spermiyl, carboxyspermiyl, guanidyl, spermidinyl, putricinyl, diaminoalkyl, pyridyl, piperidinyl, pyrrolidinyl, polyamine, amino acid, peptide, and protein; X1 and X2, independently of one another, are selected from the group consisting of NH, O, S, alkylene, and arylene; L′ is selected from the group consisting of alkylene, alkenylene, alkynylene, arylene, alkylene ether, and polyether; D is Q or a bond; A1 and A2, independently of one another, are selected from the group consisting of CH2O, CH2S, CH2NH, C(O), C{NH), C(S) and (CH2)t; X is a physiologically acceptable anion; m, n, r, s, u, v, w and y are 0 or 1, with the proviso that when both m and n are 0 at least one of r, s, u and y is other than 0; i, j, k, l, p and are integers from 0 to about 100; q is an integer from 1 to about 1000; and a is the number of positive charge divided by the valence of the anion.
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公开(公告)号:US20060147514A1
公开(公告)日:2006-07-06
申请号:US11369715
申请日:2006-03-06
申请人: Gulilat Gebeyehu , Donna Fox , Martha Ogilvie
发明人: Gulilat Gebeyehu , Donna Fox , Martha Ogilvie
CPC分类号: C12N15/88
摘要: The present invention relates to a method for introducing one or more antisense oligonucleotides into one or more eucaryotic cells using one or more lipid formulations comprising one or more cationic lipids of Formula I and optionally at least one neutral lipid. In particular, the present invention relates to a method for introducing one or more antisense oligonucleotides into one or more eucaryotic cells using a lipid formulation comprising dimethyldioctadecylammonium bromide (DDAB) and at least one neutral lipid, especially dioleylphosphatidylethanolamine (DOPE). The invention also relates to kits for carrying out the invention, compositions for carrying out the invention, and compositions formed while carrying out the invention. Further, the present invention relates to a method for inhibiting or preventing cell growth or proliferation, and a method for inhibiting or preventing expression of one or more proteins.
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公开(公告)号:US06989434B1
公开(公告)日:2006-01-24
申请号:US09326106
申请日:1999-06-04
申请人: Gulilat Gebeyehu , Joel A. Jessee
发明人: Gulilat Gebeyehu , Joel A. Jessee
CPC分类号: A61K48/00 , A61K47/543 , C07H1/00
摘要: The present invention provides certain cationic lipids containing stigmasterol, ergosterol and cholic acid groups. Compounds of the invention are useful, either alone or in combination with other lipid aggregate-forming components (e.g., DOPE, DOSPA, DOTMA or cholesterol) for formulation into liposomes or other lipid aggregates. Such aggregates are cationic, and able to form stable complexes with anionic macromolecules, such as nucleic acids. The cationic lipids of the invention are useful in methods of transfecting cells, particularly to introduce nucleic acids into cells. The invention also related to kits for the preparation of lipid aggregates and to lipid aggregates and compositions for transfection of cells.
摘要翻译: 本发明提供了含有豆甾醇,麦角固醇和胆酸基团的某些阳离子脂质。 本发明的化合物单独使用或与其它脂质聚集体形成组分(例如,DOPE,DOSPA,DOTMA或胆固醇)组合用于制剂成脂质体或其它脂质聚集体。 这种聚集体是阳离子的,能够与阴离子大分子如核酸形成稳定的络合物。 本发明的阳离子脂质可用于转染细胞的方法,特别是将核酸引入细胞中。 本发明还涉及用于制备脂质聚集体和用于转染细胞的脂质聚集体和组合物的试剂盒。
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公开(公告)号:US20050164971A1
公开(公告)日:2005-07-28
申请号:US11040449
申请日:2005-01-21
申请人: Yongliang Chu , Malek Masoud , Gulilat Gebeyehu
发明人: Yongliang Chu , Malek Masoud , Gulilat Gebeyehu
IPC分类号: C12N15/09 , A61K9/127 , A61K31/14 , A61K47/16 , A61K47/18 , A61K47/22 , C07C211/21 , C07C211/63 , C07C211/64 , C07C215/18 , C07C217/08 , C07C229/26 , C07C237/10 , C07C279/08 , C07D211/26 , C07D213/38 , C07D241/12 , C07D273/08 , C07D291/02 , C12N5/10 , A61K48/00 , C07D41/02 , C12N15/85
CPC分类号: A61K9/16 , A61K31/14 , A61K38/28 , A61K38/40 , A61K47/543 , C07C211/21 , C07C211/63 , C07C211/64 , C07C229/26 , C07D209/48 , C07D241/12 , C12N15/88 , Y10S435/81
摘要: Disclosed are compounds capable of facilitating transport of biologically active agents or substances into cells having the general structure: wherein Q is selected from the group consisting of N, O and S; L is any bivalent organic radical capable of linking each Q, such as C, CH, (CH2)l, or {(CH2)i-Y—(CH2)j}k, wherein Y is selected from the group consisting of CH2, an ether, a polyether, an amide, a polyamide, an ester, a sulfide, a urea, a thiourea, a guanidyl, a carbamoyl, a carbonate, a phosphate, a sulfate, a sulfoxide, an imine, a carbonyl, and a secondary amino group and wherein Y is optionally substituted by —X1-L′-X2-Z or -Z; R1-R6, independently of one another, are selected from the group consisting of H, —(CH2)p-D-Z, an alkyl, an alkenyl, an aryl, and an alkyl or alkyl ether optionally substituted by one or more of an alcohol, an aminoalcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, an alkylthio, a urea, a thiourea, a guanidyl, or a carbamoyl group, and wherein at least one of R1, R3, R4 and R6 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group; and anyone of R1, R3, R4 and/or R6 may optionally be covalently linked with each other, with Y or with L when L is C or CH to form a cyclic moiety; Z is selected from the group consisting of amine, spermiyl, carboxyspermiyl, guanidyl, spermidinyl, putricinyl, diaminoalkyl, pyridyl, piperidinyl, pyrrolidinyl, polyamine, amino acid, peptide, and protein; X1 and X2, independently of one another, are selected from the group consisting of NH, O, S, alkylene, and arylene; L′ is selected from the group consisting of alkylene, alkenylene, alkynylene, arylene, alkylene ether, and polyether; D is Q or a bond; A1 and A2, independently of one another, are selected from the group consisting of CH2O, CH2S, CH2NH, C(O), C{NH), C(S) and (CH2)t; X is a physiologically acceptable anion; m, n, r, s, u, v, w and y are 0 or 1, with the proviso that when both m and n are 0 at least one of r, s, u and y is other than 0; i, j, k, l, p and are integers from 0 to about 100; q is an integer from 1 to about 1000; and a is the number of positive charge divided by the valence of the anion.
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