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US 6,143,352 AGranted
pH-modified biocompatible monomer and polymer compositions
AssigneeClosure Medical Corporation
InventorsJeffrey G. Clark, Jeffrey C. Leung
Life of this patent
Estimating the term…
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.
Claims50
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;
- (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 wherein said pH modifier is insoluble in the monomer, or in a microcapsule or chemically protected form;
- and
- (3) at least one thickening agent different from said pH modifier;
- and
- (b) allowing the monomer composition to polymerize in situ.
4 more elements
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 two different biocompatible pH modifiers having different release rates 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 modifiers significantly affecting the monomer's polymerization in situ, said at least two biocompatible pH modifiers being thoroughly mixed with said at least one monomer and said pH modifiers being insoluble in the monomer, or in a microcapsule or chemically protected form;
- and
- (b) allowing the monomer composition to polymerize in situ.
3 more elements
A biocompatible monomer composition, comprising:
- (a) at least one monomer comprised of a 1,1-disubstituted ethylene monomer, which forms a polymer in vivo at a physiologic pH;
- and
- (b) an effective amount of a biocompatible pH modifier to regulate, after in vivo polymerization of the monomer in situ, the pH of an immediate in vivo environment of the polymer to a pH range at which the polymer biodegrades in vivo at a different rate than it does at physiologic pH, without significantly affecting in situ polymerization of the monomer,
- 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.
57 more elements
A biocompatible composition, comprising:
- (a) a polymer whose in vivo biodegradation produces formaldehyde;
- and
- (b) an effective amount of at least one biocompatible pH modifier to modify the pH of an immediate environment of the biocompatible composition in situ to a pH range at which the polymer's in situ biodegradation proceeds at a rate different than at physiologic pH,
- wherein said pH modifier is in at least one form selected from the group consisting of:
- (a) insoluble in monomer from which said polymer is formed,
- (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.
57 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 (1) 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 and (2) at least one thickening agent different from said pH modifier;
- 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 insoluble in the monomer, or in a microcapsule or chemically protected form.
2 more elements
A biocompatible monomer composition, comprising:
- (a) at least one monomer comprised of a 1,1-disubstituted ethylene, which forms a polymer in vivo at a physiologic pH;
- (b) an effective amount of a biocompatible pH modifier to regulate, after in vivo polymerization of the monomer in situ, the pH of an immediate in vivo environment of the polymer to a pH range at which the polymer biodegrades in vivo at a different rate than it does at physiologic pH, without significantly affecting in situ polymerization of the monomer;
- and
- (c) at least one thickening agent different from said pH modifier,
- wherein said pH modifier is insoluble in the monomer, or in a microcapsule or chemically protected form.
2 more elements
A biocompatible composition, comprising:
- (a) a polymer whose in vivo biodegradation produces formaldehyde;
- (b) an effective amount of at least one biocompatible pH modifier to modify the pH of an immediate environment of the biocompatible composition in situ to a pH range at which the polymer's in situ biodegradation proceeds at a rate different than at physiologic pH;
- and
- (c) at least one thickening agent different from said pH modifier,
- wherein said pH modifier is insoluble in the monomer, or in a microcapsule or chemically protected form.
2 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 two different biocompatible pH modifiers having different release rates 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 modifiers are insoluble in the monomer, or in a microcapsule or chemically protected form.
2 more elements
A biocompatible monomer composition, comprising:
- (a) at least one monomer comprised of a 1,1-disubstituted ethylene monomer, which forms a polymer in vivo at a physiologic pH;
- and
- (b) an effective amount of at least two biocompatible pH modifiers having different release rates to regulate, after in vivo polymerization of the monomer in situ, the pH of an immediate in vivo environment of the polymer to a pH range at which the polymer biodegrades in vivo at a different rate than it does at physiologic pH, without significantly affecting in situ polymerization of the monomer,
- wherein said pH modifiers are insoluble in the monomer, or in a microcapsule or chemically protected form.
1 more element
A biocompatible composition, comprising:
- (a) a polymer whose in vivo biodegradation produces formaldehyde;
- and
- (b) an effective amount of at least two biocompatible pH modifiers having different release rates to modify the pH of an immediate environment of the biocompatible composition in situ to a pH range at which the polymer's in situ biodegradation proceeds at a rate different than at physiologic pH,
- wherein said pH modifiers are insoluble in the monomer, or in a microcapsule or chemically protected form.
1 more element
Dependencies are inferred from the claim text.