Patent ID: 6110453
Filing Date: 2000-08-29
Classification: A61K,C08F,Y10S

Abstract:
A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a polymer capable of releasing nitric oxide, said polymer comprising a polymeric backbone, wherein said polymeric backbone is of a polymer selected from the group consisting of a polyolefin, a polyether, a polyester, a polyamide, a polyurethane, a polypeptide, and a starburst dendrimer, and at least one nitric oxide-releasing [N.sub.2 O.sub.2 ] functional group selected from the group consisting of X--[--N(O)NO] and [N(O)NO--]--X, wherein X is an organic moiety covalently bonded to said [N.sub.2 O.sub.2 ], and the [N.sub.2 O.sub.2 ] group is covalently bonded in said polymer through said organic moiety X, and wherein X.brket open-st.N(O)NO] or N[(O)NO.brket close-st.X is selected from a moiety of the formula: ##STR8## R.sub.6 and R.sub.7 are the same or different and may be hydrogen, C.sub.3-8 cycloalkyl, C.sub.1-12 straight or branched chain alkyl, benzyl, benzoyl, phthaloyl, acetyl, trifluoroacetyl, p-toluyl, t-butoxycarbonyl, or 2,2,2-trichloro-t-butoxycarbonyl, f is an integer from 0 to 12, with the proviso that when B is the substituted piperazine moiety; ##STR9## then f is an integer from 2 to 12; ##STR10## wherein R.sub.8 is hydrogen, C.sub.3-8 cycloalkyl, C.sub.1-12 straight or branched chain alkyl, benzyl, benzoyl, phthaloyl, acetyl, trifluoroacetyl, p-toluyl, t-butoxycarbonyl, or 2,2,2-tri-chloro-t-butoxycarbonyl, R.sub.9 is hydrogen or a C.sub.1 -C.sub.12 straight or branched chain alkyl, and g is 2 to 6; ##STR11## wherein R.sub.1 and R.sub.2 are independently selected from the group consisting of a straight chain or branched chain C.sub.1 -C.sub.12 alkyl group and a benzyl group, with the proviso that no branch occur on the alpha carbon atom, or else R.sub.1 and R.sub.2 together with the nitrogen atom they are bonded to form a heterocyclic group, M.sup.+.times. is a pharmaceutically acceptable cation, and x is the valence of the cation;K[(M).sub.x.sup.x' (L).sub.y (R.sup.1 R.sup.2 N--N.sub.2 O.sub.2)--](d)wherein M is a pharmaceutically acceptable metal, or where x is at least two, a mixture of two different pharmaceutically acceptable metals, L is a ligand different from (R.sup.1 R.sup.2 N--N.sub.2 O.sub.2) and is bound to at least one metal, R.sup.1 and R.sup.2 are each organic moieties and may be the same or different (with the proviso that where M is copper, x is one, L is methanol, and y is one, that at least one of R.sup.1 or R.sup.2 is not ethyl), x is an integer of from 1 to 10, x' is the formal oxidation state of the metal M, and is an integer of from 1 to 6, y is an integer of from 1 to 18, and where y is at least 2, the ligands L may be the same or different, z is an integer of from 1 to 20, and K is a pharmaceutically acceptable counterion to render the compound neutral to the extent necessary;[R--N(H)N(NO)O--].sub.y X (e)wherein R is C.sub.2-8 lower alkyl, phenyl, benzyl, or C.sub.3-8 cycoloalkyl, any of which R groups may be substituted by one to three substituents, which are the same or different, selected from the group consisting of halo, hydroxy, C.sub.1-8 alkoxy, --NH.sub.2, --C(O)N.sub.2, --CH(O), --C(O)OH, and --NO.sub.2, X is a pharmaceutically acceptable cation, a pharmaceutically acceptable metal center, or a pharmaceutically acceptable organic group selected from the group consisting of C.sub.1-8 lower alkyl, --C(O)CH.sub.3, and --C(O)NH.sub.2, and y is one to three, consistent with the valence of X; ##STR12## wherein R.sub.1 and R.sub.2 are independently chosen from C.sub.1-12 straight chain alkyl, C.sub.1-12 alkoxy or acyloxy substituted straight chain alkyl, C.sub.2-12 hydroxy or halo substituted straight chain alkyl, C.sub.3-12 branched chain alkyl, C.sub.3-12 hydroxy, halo, alkoxy, or acyloxy substituted branched chain alkyl, C.sub.3-12 straight chain olefinic and C.sub.3-12 branched chain olefinic which are unsubstituted or substituted with hydroxy, alkoxy, acyloxy, halo or benzyl, or R.sub.1 and R.sub.2 together with the nitrogen atom to which they are bonded form a heterocyclic group, and R.sub.3 is a group selected from C.sub.1-12 straight chain and C.sub.3-12 branched chain alkyl which are unsubstituted or substituted by hydroxy, halo, acyloxy or alkoxy, C.sub.2-12 straight chain or C.sub.3-12 branched chain olefinic which are unsubstituted or substituted by halo, alkoxy, acyloxy or hydroxy, C.sub.1-12 unsubstituted or substituted acyl, sulfonyl and carboxamido; or R.sub.3 is a group of the formula --(CH.sub.2).sub.n --ON.dbd.N(O)NR.sub.1 R.sub.2, wherein n is an integer of 2-8, and R.sub.1 and R.sub.2 are as defined above; with the proviso that R.sub.1, R.sub.2 and R.sub.3 do not contain a halo or a hydroxy substituent .alpha. to a heteroatom.