Inorganic phosphates reversibly grafted with bioactive compounds and a method of their preparation

Abstract

Biologically active solid systems are disclosed, containing immobilized organic compounds, such as medicines, in the form of materials appropriate as bone fillers, implant coatings or other alike systems, of the common formula B—P-A, where B is an inorganic support consisting of calcium phosphate, calcium hydroxyphosphate (hydroxyapatite), their mixture, or some other biocompatible mixture containing these or other insoluble inorganic phosphates, —P— is a phosphoryl group —P—O—, and A is the residue of the immobilized, organic, biologically active compound, such as a medicine, containing unprotonated amine and/or hydroxide group(s), and a method of their preparation consisting of the treatment of inorganic phosphate with a grafting reagent and consequent reaction with organic compound. As a grafting reagent, phosphorus pentachloride is applied and all operations are completed in an aprotic solvent. The advantage of the above product is the extension of the time duration of release of the immobilized organic compound such as a medicine from the surface, the release of the organic compound in its initial, unaltered, fully biologically active form, in the absence of any toxic or alien side products of hydrolytic decomposition of the immobilized system.

Description

Claims

1. Biocompatible and bioactive solid materials of the common formula B—P-A, where B is an inorganic support consisting of calcium phosphate, calcium hydroxyphosphate (hydroxyapatite), their mixture or some other biocompatible mixture containing these or other insoluble inorganic phosphates, —P— is the phosphoryl group —P—O—, and A is the residue of a bioactive organic compound such as a medicine, containing unprotonated amine and/or hydroxide group(s).

2. Immobilized systems, such as medicines, from claim 1 containing 0.5 to 2 mass percent of phosphoryl groups —P—.

3. Method of preparation of immobilized organic systems such as medicines of the common formula B—P-A, from claim 1, including the treatment of calcium phosphate or hydroxyphosphate, or their mixture, or another mixture containing those or other insoluble inorganic phosphate, with a grafting reagent with consequent reaction with biologically active organic compounds containing unprotonated amine and/or hydroxide groups in which the grafting reagent is phosphorus pentachloride, PCl5, and all operations are performed in an aprotic solvent.

4. Method from claim 3 in which phosphorus pentachloride is used in the amount of up to 7 mass percent out of the amount of calcium phosphate, or another insoluble inorganic phosphate or hydroxyphosphate or their mixture.