Organic acids as catalysts for the erosion of polymers

Claim 2

A controlled release device for the delivery of drugs or other biological beneficial substances which comprises: (a) an acid labile polymer, and (b) an erosion catalyzing amount up to a maximum of about 25 percent, by weight, based on (a), of at least one organic carboxylic acid and mixtures thereof selected from the group consisting of 2-fluorostearic acid, 2-fluoropalmitic acid, 2-fluoromyristic acid, 2-nitro-stearic acid, 2,2-difluorostearic acid, 2,3-difluorostearic acid, o-fluorobenzoic acid, p-fluorobenzoic acid, o-nitrobenzoic acid, p-nitrobenzoic acid, p-trifluoromethyl benzoic acid, o-trifluoromethyl benzoic acid, 4-trifluoromethyl-1-naphthoic acid, N-dodecyl phthalamic acid, N-methyl-N-dodecyl phthalamic acid, N-methyl-N-octadecyl phthalamic acid, N-octadecyl phthalamic acid, N-butyl-phthalamic acid, and N-methyl-N-octadecyl-5-nitro-phthalamic acid incorporated within the matrix of said acid labile polymer.

Claim 3

The controlled drug release device of claim 1, further comprising an effective amount up to 70 percent, by weight, based on (a) and (b), of a drug or other biologically beneficial substance incorporated within or surrounded by the matrix of said acid labile polymer.

Claim 4

The controlled drug release device of claim 2, wherein the drug or biological beneficial substance is a protein drug, a desensitizing agent, a vaccine, an anti-infective, an antiallergenic, a steroidal anti-inflammatory, a decongestant, a miotic, an anticholinergic, a sympathomimetic, a sedative; a hypnotic, a psychic energizer, a tranquilizer, an androgenic steroid, an estrogen, a progestational agent, a humoral agent, an antipyretic analgesic, an antispasmotic, an antimalarial, an antihistamine, a cardioactive agent, a non-steroidal anti-inflammatory, an antiparkinsonian agent, an antihypertensive agent, a β-adrenergic blocking agent, a nutritional agent, a herbicide, a pesticide, a biocide, a fertilizer or an antifouling compound.

Claim 5

The controlled drug release device of claim 1, wherein said acid labile polymer is a polymer of di(or a higher functionality) ketene acetal and polyols of the formula: ##STR10## wherein n is an integer substantially greater than 10; and wherein R 1 and R 2 are hydrogen or the same or different essentially hydrocarbon groups and may be separate groups or may form parts of a cyclic group; R is a quadrivalent organic grouping; R 3 and R 4 are hydrogen or the same or different essentially hydrocarbon groups and may be separate groups or may form parts of a cyclic group; R 5 is an essentially hydrocarbon group which is the residue of a polyol R 5 (OH) a wherein a is an integer equal to two or more, such polyol being a single molecular species or a mixture of molecular species; and wherein such linear chain may be crosslinked with other similar chains, and wherein R may be a single quadrivalent radical attached to all the interim acetal forming oxygen atoms, may be a spiro structure, may be an open chain aliphatic group, or may contain a carbocyclic group and wherein additionally, R 5 may contain some mer units that are alkylene or contain a carbocyclic group and including polymers having the repeat units ##STR11## wherein n is an integer substantially greater than 10; wherein R 1 , R 2 , R 3 and R 4 are the same or different essentially hydrocarbon groups, R 1 and R 2 being separate groups or parts of a cyclic group and R 3 and R 4 being separate groups or parts of a cyclic group; R 5 is an essentially hydrocarbon group which is the residue of a polyol R 5 (OH) a wherein a is an integer equal to two or more, such polyol being a single molecular species or a mixture of molecular species; R 6 is a valence bond or an essentially hydrocarbon group; R 7 and R 8 are hydrogen or essentially hydrocarbon groups which may be separate groups or may form parts of a cyclic group; and wherein such linear chains may be crosslinked to similar chains and wherein the group ##STR12## may be selected from the classic alkylene end groups containing a carbocyclic ring.

Claim 6

The controlled drug release device of claim 1, wherein said acid labile polymer is a polyorthocarbonate of the formula ##STR13## wherein R 1 is a multivalent hydrocarbon radical, R 2 and R 3 are hydrocarbon radicals with at least one of R 2 and R 3 bonded to the dioxycarbon through an oxygen linkage and n is a repeating mer unit.

Claim 7

The controlled drug release device of claim 1, wherein said organic acid is selected from the group consisting of 2-fluorostearic acid, p-trifluoromethyl benzoic acid, N-dodecyl phthalamic acid, N-octadecyl phthalamic acid, N-methyl-N-octadecyl phthalamic acid, N-butyl phthalamic acid, and the corresponding terephthalamic acid derivatives, phthalic acid, and N-methyl-N-octadecyl-5-nitro-phthalamic acid.

Claim 8

The controlled drug release device of claim 1, wherein said acid labile polymer is a polymer of DETOSU 1,6-hexanediol/trans cyclohexanedimethanol wherein DETOSU is 3,9-bis(ethylidene)-2,4,8,10-tetraoxospiro[5,5]-undecane.

Claim 9

A process for catalyzing the erosion of an acid liable polymer, comprising incorporating within the matrix of an acid labile polymer an erosion catalyzing amount up to a maximum of about 25 percent by weight, based on the weight of said acid labile polymer, of at least one organic carboxylic acid and mixtures thereof selected from the group consisting of 2-fluorostearic acid, 2-fluoropalmitic acid, 2-fluoromyristic acid, 2-nitro-stearic acid, 2,2-difluorostearic acid, 2,3-difluorostearic acid, o-fluoro-benzoic acid, p-fluorobenzoic acid, o-nitrobenzoic acid, p-nitrobenzoic acid, p-trifluoromethyl benzoic acid, o-trifluoromethyl benzoic acid, 4-triflu-oromethyl-1-naphthoic acid, N-dodecyl phthalamic acid, N-octadecyl phthalamic acid N-methy-N-dodecyl phthalamic acid, N-methyl-N-octadecyl phthalamic acid, N-butyl phthalamic acid, and N-methyl-N-octadecyl-5-nitro-phthalic acid.

Claim 10

A process for catalyzing the erosion of an acid liable polymer, comprising incorporating within the matrix of an acid labile polymer an erosion catalyzing amount up to a maximum of about 25 percent by weight, based on the weight of said acid labile polymer, of at least one organic carboxylic acid and mixtures thereof selected from the group consisting of 2-fluorostearic acid, 2-fluoropalmitic acid, 2-fluoromyristic acid, 2-nitro-stearic acid, 2,2-difluorostearic acid, 2,3-difluorostearic acid, o-fluoro-benzoic acid, p-fluorobenzoic acid, o-nitrobenzoic acid, p-nitrobenzoic acid, p-trifluoromethyl benzoic acid, o-trifluoromethyl benzoic acid, 4-triflu-oromethyl-1-naphthoic acid, N-dodecyl phthalamic acid, N-octadecyl phthalamic acid N-methy-N-dodecyl phthalamic acid, N-methyl-N-octadecyl phthalamic acid, N-butyl phthalamic acid, and N-methyl-N-octadecyl-5-nitro-phthalic acid.

Claim 11

The process for catalyzing the erosion of an acid labile polymer of claim 8, wherein said acid labile polymer is a polymer of di(or a higher functionality) ketene acetals and polyols of the formula: ##STR14## wherein n is an integer substantially greater than 10; and wherein R 1 and R 2 are hydrogen or the same or different essentially hydrocarbon groups and may be separate groups or may form parts of a cyclic group; R is a quadrivalent organic grouping; R 3 and R 4 are hydrogen or the same or different essentially hydrocarbon groups and may be separate groups or may form parts of a cyclic group; R 5 is an essentially hydrocarbon group which is the residue of a polyol R 5 (OH) a wherein a is an integer equal to two or more, such polyol being a single molecular species or a mixture of molecular species; and wherein such linear chain may be crosslinked with other similar chains, and wherein R may be a single quadrivalent radical attached to all the interim acetal forming oxygen atoms, may be a spiro structure, may be an open chain aliphatic group, or may contain a carbocyclic group and wherein additionally, R 5 may contain some mer units that are alkylene or contain a carbocyclic group and including polymers having the repeat units ##STR15## wherein n is an integer substantially greater than 10; wherein R 1 , R 2 , R 3 and R 4 are the same or different essentially hydrocarbon groups, R 1 and R 2 being separate groups or parts of a cyclic group and R 3 and R 4 being separate groups or parts of a cyclic group; R 5 is an essentially hydrocarbon group which is the residue of a polyol R 5 (OH) a wherein a is an integer equal to two or more, such polyol being a single molecular species or a mixture of molecular species; R 6 is a valence bond or an essentially hydrocarbon group; R 7 and R 8 are hydrogen or essentially hydrocabon groups which may be separate groups or may form parts of a cyclic group; and wherein such linear chains may be crosslinked to similar chains and wherein the group ##STR16## may be selected from the classic alkylene end groups containing a carbocyclic ring.

Claim 12

The process for catalyzing the erosion of an acid labile polymer of claim 8, wherein said acid labile polymer is a polyorthocarbonate of the formula: ##STR17## wherein R 1 is a multivalent hydrocarbon radical, R 2 and R 3 are hydrocarbon radicals with at least one of R 2 and R 3 bonded to the dioxycarbon through an oxygen linkage and n is a repeating mer unit.

Claim 13

The process for catalyzing the erosion of an acid labile polymer of claim 8, wherein said organic acid is selected from the group consisting of 2-fluorostearic acid, p-trifluoromethyl benzoic acid, N-dodecyl phthalamic acid, N-octadecyl phthalamic acid, N-methyl-N-octadecyl phthalamic acid, N-butyl phthalamic acid, and the corresponding terephthalamic acid derivatives, phthalic acid, dodecylbenzenesulfonic acid, and N-methyl-N-octadecyl-5-nitro-phthalamic acid.