Quarternization of the additive amino alkylmethacrylate copolymer E for improving permeability and solubility of pharmaceuticals
View Patent ↗The present invention relates to a strategy for improving the permeability and solubility of pharmaceuticals, based on adding a chemically modified amino alkyl methacrylate copolymer E, wherein the chemical modification is the quaternization of a fraction of the existing amino alkyl groups.
1. An aminoalkyl methacrylate copolymer E, comprising at least one quaternized aminoalkyl group and at least one non-quaternized aminoalkyl group, wherein the aminoalkyl methacrylate copolymer E has formula (I)
wherein m is the total number of butyl methacrylate groups,
n is the total number of aminoalkyl groups,
o is the total number of methyl methacrylate groups,
q is the total number of quaternized aminoalkyl groups, and
m, n, o and q are each at least 1; and
wherein the proportion of the quaternized aminoalkyl groups relative to the total number of the aminoalkyl groups is more than 10% and less than 100%.
2. A method of producing the aminoalkyl methacrylate copolymer E according to claim 1 , comprising
reacting a methyl iodide with at least one aminoalkyl group of an aminoalkyl methacrylate copolymer precursor.
3. The method according to claim 2 , wherein the reacting is carried out in the presence of methanol as a solvent.
4. A method for improving the permeability and solubility of a pharmaceutical composition, comprising
administering an aminoalkyl methacrylate copolymer E according to claim 1 with the pharmaceutical composition.
5. A pharmaceutical formulation comprising at least one pharmaceutical compound and the aminoalkyl methacrylate copolymer E according to claim 1 .
6. The aminoalkyl methacrylate copolymer E according to claim 1 , wherein the proportion of the quaternized aminoalkyl groups relative to the total number of the aminoalkyl groups is more than 20% and less than 100%.
7. A pharmaceutical formulation comprising at least one pharmaceutical compound and an aminoalkyl methacrylate copolymer E according to claim 6 .
8. The aminoalkyl methacrylate copolymer E according to claim 1 , wherein the proportion of the quaternized aminoalkyl groups relative to the total number of the aminoalkyl groups is from 22 to 65%.
9. The aminoalkyl methacrylate copolymer E according to claim 1 , wherein the aminoalkyl methacrylate copolymer with the quaternized aminoalkyl groups has a greater permeability-promoting action in comparison to an aminoalkyl methacrylate copolymer precursor.