IONTOPHORETIC DELIVERY OF BISPHOSPHONATES TO THE ALVEOLAR BONE

摘要

The present invention relates to methods of inhibiting alveolar bone resorption or the undesirable movement of teeth of a human or other animal comprising: a) administering a reservoir to the gingival tissue of the oral cavity such that the reservoir is in contact with the exposed tissue nearest to the alveolar bone to be treated wherein the reservoir is a composition having a pH which maintains an active compound in a negatively charged state and comprises a safe and effective amount of the active compound having structure (I) wherein: n is an integer from 0 to 7 (preferably from 0 to 3, more preferably 1); R1 is hydrogen, chloro, amino, or hydroxy (preferably hydrogen or hydroxy); X is -NH-, quaternary amine, oxygen, sulfur, or a single bond (preferably -NH- or single bond); R2 is a 5- to 7-membered carbocycle (preferably 6- to 7-membered, more preferably benzene or cycloheptyl), a 5- to 7-membered heterocycle having from 1 to 3 heteroatoms (preferably a 6-membered heterocycle having 1 or 2 nitrogen atoms, wherein a ring nitrogen may be quaternarized), -NH¿2?, amino substituted with one alkyl or two alkyl (preferably C1-C5) groups to give a secondary or tertiary amine, respectively, quaternary amino, or hydrogen; wherein if R?2¿ is a substituted 5- to 7-membered carbocycle or heterocycle, the substituent is one or more substituents selected from the group consisting of substituted and unsubstituted, saturated or unsaturated alkyl having from 1 to about 6 carbon atoms, substituted and unsubstituted aryl, substituted and unsubstituted benzyl, hydroxy, halogen, carbonyl, alkoxy, nitro, amido, amino, substituted amino, carboxylate, and combinations thereof; each R3 is, independently, hydrogen, or substituted or unsubstituted alkyl (saturated or unsaturated) having from 1 to about 4 carbon atoms; or their pharmaceutically-acceptable salts and esters; and b) passing a safe and effective amount of electrical current through two electrodes, one electrode being a negative electrode in contact with the reservoir, the second electrode being a positive electrode in contact with the human or other animal being treated.