Biomaterials carrying cyclodextrins having improved absorption properties and used for the progressive and delayed release of therapeutic molecules

摘要

A method for preparing a biomaterial containing at least one bioactive molecule from a base biomaterial, comprising the following successive operations carried out on the base biomaterial:
a) application of a solid mixture of:
cyclodextrin(s) and/or cyclodextrin derivative(s) and/or cyclodextrin inclusion complex(es) and/or cyclodextrin derivative inclusion complex(es),at least one poly(carboxylic) acid,and optionally a catalyst;b) heating at a temperature between 100° C. and 200° C. for a period of 1 to 60 minutes;c) washing with water;d) drying,wherein at least one bioactive agent is incorporated in the biomaterial by impregnation of the biomaterial after the drying step in a concentrated solution of the bioactive agent.

主权项

1. A device for controlled release of at least one bioactive agent, wherein said device is an implant or a prosthesis and comprises at least one biomaterial comprising a base biomaterial modified by forming a cross-linked polymer bound to the base biomaterial by polymerizing onto the base material (1) a polycarboxylic acid of general formula wherein x≧3 and [Ac] is an organic moiety bearing x COOH groups with (2) at least one cyclodextrin monomer represented by general formula wherein [CD] is a cyclodextrin moiety bearing z OH groups, wherein the cyclodextrin monomer is at least one member selected from the group consisting of α-cyclodextrin; β-cyclodextrin; γ-cyclodextrin; amino, methyl, hydroxypropyl, sulfobutyl, carboxymethyl or carboxyl derivatives of α-cyclodextrin; amino, methyl, hydroxypropyl, sulfobutyl, carboxymethyl or carboxyl derivatives of β-cyclodextrin; amino, methyl, hydroxypropyl, sulfobutyl, carboxymethyl or carboxyl derivatives of γ-cyclodextrin; inclusion complexes of α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin or said derivatives with bioactive molecules, wherein the cross-linked polymer contains a repetition of the motif of general formula: wherein 2≦y≦(x−1), (x−y)≧1, and t≧2, y represents the number of carboxyl functions of the poly(carboxylic) acid esterified during polymerization, (x−y) represents the number of carboxyl functions of the poly(carboxylic) acid not esterified after polymerization, z represents the number of OH groups carried by the CD unit before esterification with the polycarboxylic acid, t represents the number of OH groups of the CD unit that underwent esterification with the polycarboxylic acid, (z−t) represents the remaining OH groups present on the polymerized CD unit, wherein the cross-linked polymer is bound to the base biomaterial by at least one of the following mechanisms:
chemical grafting by covalent bonds between the base biomaterial and the cross-linked polymer,physical grafting in the form of a coating resulting from cross-linking of the polymer formed by reaction between the polycarboxylic acid and the cyclodextrin monomer; wherein the base biomaterial has a porous structure or a non-porous structure, and wherein the device contains said at least one bioactive agent, wherein the bioactive agent forms a complex with the cyclodextrin units, and the bioactive agent is a therapeutic molecule.