Patent EP-2766047-A1 (EP)
Inventor: GOOD LIAM
IPC: A61K47/48
Filed: 2012-10-11
Abstract: A method for promoting entry of an agent (introduced agent) into a cell, the method comprising the step of complexing the introduced agent in the presence of an entry- promoting agent and then exposing to cells, wherein the entry-promoting agent comprises a linear and/or branched or cyclic polymonoguanide/polyguanidine, polybiguanide, analogue or derivative thereof according to the following Formula 1a &b. The method also provides a means for formation of nanoparticles formed between the entry promoting agent and the introduced agent. wherein: "n", refers to number of repeating units in the polymer, and n can vary from 2 to 1000, for example from 2 or 5 to 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800 or 900; G 1  and G 2  independently represent a cationic group comprising biguanide or guanidine, wherein L 1 , and L 2  are directly joined to a Nitrogen atom of the guanide; L 1  and L 2  are linking groups between the G 1  and G 2  cationic groups in the polymer and independently represent an aliphatic group containing C 1 -C 40  carbon atoms, for example an alkyl group such as methylene, ethylene, propylene, C 4 , C 5 , C 6 , C 7 , C 8 , C 9  or C 10 ; C 1 -C 10 , -C 20 , - C 30 , -C 40 , -C 50  -C 60  -C 70 , -C 80 , -C 9 0, -C- 100 , -C 110 , -C 120 , -C 130  or -C 140 , alkyl; or a C 1 -C 140  (for example C 1  , C 2 ,C 3 , C 4 , C 5 , C 6 , C 7 , C 8 , C 9  or C 10 ; C 1 -C 10 , -C 20 , -C 30 , -C 40 , -C 50  -C 60 , -C 70 , -C 80 , - C 90 , -C 100 , -C 11 0, -C 120 , -C 130 o or -C 140 ), cycloaliphatic, heterocyclic, aromatic, aryl, alkylaryl, arylalkyl, or oxyalkylene radical; or a polyalkylene radical optionally interrupted by one or more, preferably one, oxygen, nitrogen or sulphur atoms, functional groups or saturated or unsaturated cyclic moiety; N and G 3  are optional end groups; X can be either present or absent; L 3 , L 4  and X are linking groups between the G4 and G5 cationic groups in the polymer and independently represent an aliphatic group containing C 1 -C 140  carbon atoms, for example an alkyl group such as methylene, ethylene, propylene, C 4 , C 5 , C 6 , C 7 , C 8 , C 9  or C 10 ; C 1 -C 10 , -C 20 , -C 30 , - C 40 , -C 50  -C 60 , -C 70 , -C 80 , -C 90 , -C 100 , -C 110 , -C 120 , -C 130  or -C 140 , alkyl; or L 3  and L 4  and X can independently be C 1 -C 140  (for example C 1 ,C 2 , C 3 , C 4 , C 5 , C 6 , C 7 , C 8 , C 9  or C 10 ; C 1 -C 10 , -C 20 , -C 30 , -C 40 , -C 50  -C 60 , -C 70 , -C 80 , -C 90 , -C 100 , -C 110 , -C 120 , -C 130  or -C 140 ), cycloaliphatic, heterocyclic, aromatic, aryl, alkylaryl, arylalkyl, oxyalkylene radicals; or a polyalkylene radical optionally interrupted by one or more, preferably one, oxygen, nitrogen or sulphur atoms, functional groups as well as saturated or unsaturated cyclic moiety; "G 4 " and "G 5 " are cationic moieties and can be same or different, and at least one of them is a biguanidine moiety or carbamoylguanidine, and the other moiety may be biguanidine or carbamoylguanidine or amine; and cationic moieties G 4  and G 5  do not contain single guanidine groups. The entry-promoting agent may comprise homogeneous or heterogeneous mixture of one or more of agents arising from formulae 1 a and b, for example polyhexamethylene biguanide (PHMB), polyhexamethylene monoguanide (PHMG), polyethylene biguanide (PEB), polytetramethylene biguanide (PTMB), polyethylene hexamethylene biguanide (PEHMB), polymethylene biguanides (PMB), poly(allylbiguanidnio-co-allylamine), poly(N- vinylbiguanide), polyallybiguanide.