Patent EP-3831413-A1 (EP)
Inventor: GOOD LIAM
IPC: C12N15/87
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<sub>1</sub> and G<sub>2</sub> independently represent a cationic group comprising biguanide or guanidine, wherein L<sub>1</sub> and L<sub>2</sub> are directly joined to a Nitrogen atom of the guanide;L<sub>1</sub> and L<sub>2</sub> are linking groups between the G<sub>1</sub> and G<sub>2</sub> cationic groups in the polymer and independently represent an aliphatic group containing C<sub>1</sub>-C<sub>140</sub> carbon atoms, for example an alkyl group such as methylene, ethylene, propylene, C<sub>4</sub>, C<sub>5</sub>, C<sub>6</sub>, C<sub>7</sub>, C<sub>8</sub>, C<sub>9</sub> or C<sub>10</sub>; C<sub>1</sub>-C<sub>10</sub>, -C<sub>20</sub>, - C<sub>30</sub>, -C<sub>40</sub>, -C<sub>50</sub> -C<sub>60</sub>, -C<sub>70</sub>, -C<sub>80</sub>, -C<sub>90</sub>, -C<sub>100</sub>, -C<sub>110</sub>, -C<sub>120</sub>, -C<sub>130</sub> or -C<sub>140</sub>, alkyl ; or a C<sub>1</sub>-C<sub>140</sub> (for example C<sub>1</sub>, C<sub>2</sub>, C<sub>3</sub>, C<sub>4</sub>, C<sub>5</sub>, C<sub>6</sub>, C<sub>7</sub>, C<sub>8</sub>, C<sub>9</sub> or C<sub>10</sub>; C<sub>1</sub>-C<sub>10</sub>, -C<sub>20</sub>, -C<sub>30</sub>, -C<sub>40</sub>, -C<sub>50</sub> -C<sub>60</sub>, -C<sub>70</sub>, -C<sub>80</sub>, - C<sub>90</sub>, -C<sub>100</sub>, -C<sub>110</sub>, -C<sub>120</sub>, -C<sub>130</sub> or -C<sub>140</sub>), 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<sub>3</sub> are optional end groups;X can be either present or absent;L<sub>3</sub>, L<sub>4</sub> and X are linking groups between the G<sub>4</sub> and G<sub>5</sub> cationic groups in the polymer and independently represent an aliphatic group containing C<sub>1</sub>-C<sub>140</sub> carbon atoms, for example an alkyl group such as methylene, ethylene, propylene, C<sub>4</sub>, C<sub>5</sub>, C<sub>6</sub>, C<sub>7</sub>, C<sub>8</sub>, C<sub>9</sub> or C<sub>10</sub>; C<sub>1</sub>-C<sub>10</sub>, -C<sub>20</sub>, -C<sub>30</sub>, - C<sub>40</sub>, -C<sub>50</sub> -C<sub>60</sub>, -C<sub>70</sub>, -C<sub>80</sub>, -C<sub>90</sub>, -C<sub>100</sub>, -C<sub>110</sub>, -C<sub>120</sub>, -C<sub>130</sub> or -C<sub>140</sub>, alkyl ; or L<sub>3</sub> and L<sub>4</sub> and X can independently be C<sub>1</sub>-C<sub>140</sub> (for example C<sub>1</sub>, C<sub>2</sub>, C<sub>3</sub>, C<sub>4</sub>, C<sub>5</sub>, C<sub>6</sub>, C<sub>7</sub>, C<sub>8</sub>, C<sub>9</sub> or C<sub>10</sub>; C<sub>1</sub>-C<sub>10</sub>, -C<sub>20</sub>, -C<sub>30</sub>, -C<sub>40</sub>, -C<sub>50</sub> -C<sub>60</sub>, -C<sub>70</sub>, -C<sub>80</sub>, -C<sub>90</sub>, -C<sub>100</sub>, -C<sub>110</sub>, -C<sub>120</sub>, -C<sub>130</sub> or -C<sub>140</sub>), 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<sub>4</sub>" and "G<sub>5</sub>" 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<sub>4</sub> and G<sub>5</sub> 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.