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US 6,306,243 B1Granted
pH-modified biocompatible monomer and polymer compositions
AssigneeClosure Medical Corporation
InventorsJeffrey G. Clark, Jeffrey C. Leung
Life of this patent
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Abstract
The pH-modified monomer and polymer compositions are useful as biomedical and surgical adhesives, sealants, implants and bioactive agent release carriers or matrices. They comprise a monomer or polymer; and an effective amount of an acidic or basic pH modifier effective to modify the pH of an immediate in vivo environment of the composition to a pH range at which the polymer biodegrades at a different rate than at physiologic pH. The invention also relates to in vivo applications in which surfaces are joined or treated with such pH-modified biocompatible compositions.
Claims30
A method comprising:
- (a) applying to an in vivo surface a biocompatible composition comprising:
- (1) at least one monomer which forms a polymer in situ at a physiologic pH;
- and
- (2) an effective amount of at least one biocompatible pH modifier to modify the pH of an immediate in vivo environment of said polymer to a pH range at which said polymer biodegrades at a different rate than it does at physiologic pH, without said pH modifier significantly affecting the monomer's polymerization in situ, said at least one biocompatible pH modifier being thoroughly mixed with said at least one monomer;
- and
- (b) allowing the monomer composition to polymerize in situ,
- wherein said pH modifier is in at least one form selected from the group consisting of:
- (a) insoluble in the monomer,
- (b) in a microcapsule,
- (c) chemically protected and insoluble in the monomer,
- (d) chemically protected and basic,
- (e) acidic and chemically protected form of at least one member selected from the group consisting of amino acids;
- di-acids and salts thereof;
- polyacids and salts thereof;
- esters that are easily hydrolyzable in vivo;
- lactones that are easily hydrolyzable in vivo;
- organic carbonates;
- enolic compounds;
- acidic phenols;
- polyphenolic compounds;
- aromatic alcohols;
- boron-containing compounds;
- sulfonic acids and salts thereof;
- sulfinic acids and salts thereof;
- phosphorus-containing compounds;
- acid halides;
- chloroformates;
- acid gases;
- acid anhydrides;
- inorganic acids and salts thereof;
- and polymers having functional groups of at least one member selected from the group consisting of amino acids, di-acids and salts thereof, polyacids and salts thereof, lactones that are easily hydrolyzable in vivo, organic carbonates, enolic compounds, acidic phenols, polyphenolic compounds, aromatic alcohols, boron-containing compounds, sulfonic acids and salts thereof, sulfinic acids and salts thereof, phosphorus-containing compounds, acid halides, chloroformates, acid gases, acid anhydrides, and inorganic acids and salts thereof, and
- (f) acidic and chemically protected form of at least one member selected from the group consisting of D-galacturonic acid;
- succinic acid and succinic anhydride;
- glycolic acid;
- poly(acrylic acid);
- acetic acid;
- diglycolic ahyhdride;
- citraconic anhydride;
- maleic anhydride;
- diethyl oxalate;
- Meldrum's acid;
- diethyl carbonate;
- dipropyl carbonate;
- diethyl pyrocarbonate;
- diallyl pyrocarbonate;
- di-tert-butyl dicarbonate;
- ascorbic acid;
- catechin;
- D-glucosamine hydrochloride;
- 4-hydroxy-ephedrin hydrochloride;
- boric acid;
- nitric acid;
- hydrochloric acid;
- sulfuric acid;
- ethanesulfonic acid;
- p-toluenesulfonic acid;
- 2-aminoethylphosphoric acid;
- methylphosphonic acid;
- dimethylphosphinic acid;
- methyl chloroformate;
- sulfur dioxide;
- carbon dioxide;
- and combinations of the above materials.
60 more elements
A method of regulating a rate of in vivo biodegradation of a polymer formed in vivo from at least one monomer that forms a polymer at a physiologic pH, comprising:
- combining said at least one monomer with an effective amount of at least one biocompatible pH modifier to modify a pH of an immediate in situ environment of the polymer to a pH range at which the polymer's biodegradation proceeds at a different rate than it does at physiologic pH;
- allowing the polymer to form in vivo;
- and
- maintaining the thus-formed polymer in vivo for a time sufficient to effect biodegradation of the polymer,
- wherein said pH modifier is in at least one form selected from the group consisting of:
- (a) insoluble in the monomer,
- (b) in a microcapsule,
- (c) chemically protected and insoluble in the monomer,
- (d) chemically protected and basic,
- (e) acidic and chemically protected form of at least one member selected from the group consisting of amino acids;
- di-acids and salts thereof;
- polyacids and salts thereof;
- esters that are easily hydrolyzable in vivo;
- lactones that are easily hydrolyzable in vivo;
- organic carbonates;
- enolic compounds;
- acidic phenols;
- polyphenolic compounds;
- aromatic alcohols;
- boron-containing compounds;
- sulfonic acids and salts thereof;
- sulfinic acids and salts thereof;
- phosphorus-containing compounds;
- acid halides;
- chloroformates;
- acid gases;
- acid anhydrides;
- inorganic acids and salts thereof;
- and polymers having functional groups of at least one member selected from the group consisting of amino acids, di-acids and salts thereof, polyacids and salts thereof, lactones that are easily hydrolyzable in vivo, organic carbonates, enolic compounds, acidic phenols, polyphenolic compounds, aromatic alcohols, boron-containing compounds, sulfonic acids and salts thereof, sulfinic acids and salts thereof, phosphorus-containing compounds, acid halides, chloroformates, acid gases, acid anhydrides, and inorganic acids and salts thereof, and
- (f) acidic and chemically protected form of at least one member selected from the group consisting of D-galacturonic acid;
- succinic acid and succinic anhydride;
- glycolic acid;
- poly(acrylic acid);
- acetic acid;
- diglycolic ahyhdride;
- citraconic anhydride;
- maleic anhydride;
- diethyl oxalate;
- Meldrum's acid;
- diethyl carbonate;
- dipropyl carbonate;
- diethyl pyrocarbonate;
- diallyl pyrocarbonate;
- di-tert-butyl dicarbonate;
- ascorbic acid;
- catechin;
- D-glucosamine hydrochloride;
- 4-hydroxy-ephedrin hydrochloride;
- boric acid;
- nitric acid;
- hydrochloric acid;
- sulfuric acid;
- ethanesulfonic acid;
- p-toluenesulfonic acid;
- 2-aminoethylphosphoric acid;
- methylphosphonic acid;
- dimethylphosphinic acid;
- methyl chloroformate;
- sulfur dioxide;
- carbon dioxide;
- and combinations of the above materials.
58 more elements
Dependencies are inferred from the claim text.