Methods for sealing an orifice in tissue using an aldol-crosslinked polymeric hydrogel adhesive
First Claim
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1. A method for sealing an orifice in tissue in the body of a living animal comprising:
- applying to the orifice (a) a first aqueous solution comprising from about 5% to about 40% by weight of a polysaccharide that has been oxidized to provide an oxidized polysaccharide that contains aldehyde groups, said polysaccharide having a molecular weight of about 1,000 to about 1,000,000 Daltons, and said oxidized polysaccharide having an equivalent weight per aldehyde group of about 90 to about 1500 Daltons, such that the oxidized polysaccharide has on average more than two aldehyde groups per chain, followed by (b) a second aqueous solution comprising from about 5% to about 40% by weight of a poly(hydroxylic) compound that has been derivatized to provide a derivatized poly(hydroxylic) compound that contains acetoacetate groups, said poly(hydroxylic) compound having a molecular weight of less than or equal to about 100,000 Daltons, and said derivatized poly(hydroxylic) compound having an equivalent weight per acetoacetate group of about 100 to about 2000 Daltons, such that the derivatized poly(hydroxylic) compound has on average more than two acetoacetate groups per molecule, or applying the second aqueous solution followed by the first aqueous solution and mixing the first and second aqueous solutions on the orifice, or premixing the first and second aqueous solutions and applying the resulting mixture to the orifice before the resulting mixture completely cures, thereby forming on said orifice a resorbable adhesive hydrogel, and allowing the hydrogel to remain on said orifice until said hydrogel is resorbed;
provided that;
(i) at least one of the first aqueous solution or the second aqueous solution further comprises a base catalyst;
or (ii) a base catalyst is applied to the orifice as a neat liquid or as part of a third aqueous solution, and said neat liquid or third aqueous solution is mixed with both the first aqueous and second aqueous solutions on the orifice or said neat liquid or third aqueous solution is premixed with both the first and second aqueous solutions, and the resulting mixture is subsequently applied to the orifice before the resulting mixture completely cures;
or (iii) a combination of (i) and (ii).
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Abstract
Methods for sealing an orifice in tissue in the body of a living animal using an adhesive formed by reacting an oxidized polysaccharide with a poly(hydroxylic) compound derivatized with acetoacetate groups in the presence of a base catalyst are disclosed. Methods for using the adhesive for medical and veterinary applications such as topical wound closure; and surgical procedures, such as intestinal anastomosis, vascular anastomosis, tissue repair, and ophthalmic procedures; and drug delivery are described.
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Citations
29 Claims
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1. A method for sealing an orifice in tissue in the body of a living animal comprising:
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applying to the orifice (a) a first aqueous solution comprising from about 5% to about 40% by weight of a polysaccharide that has been oxidized to provide an oxidized polysaccharide that contains aldehyde groups, said polysaccharide having a molecular weight of about 1,000 to about 1,000,000 Daltons, and said oxidized polysaccharide having an equivalent weight per aldehyde group of about 90 to about 1500 Daltons, such that the oxidized polysaccharide has on average more than two aldehyde groups per chain, followed by (b) a second aqueous solution comprising from about 5% to about 40% by weight of a poly(hydroxylic) compound that has been derivatized to provide a derivatized poly(hydroxylic) compound that contains acetoacetate groups, said poly(hydroxylic) compound having a molecular weight of less than or equal to about 100,000 Daltons, and said derivatized poly(hydroxylic) compound having an equivalent weight per acetoacetate group of about 100 to about 2000 Daltons, such that the derivatized poly(hydroxylic) compound has on average more than two acetoacetate groups per molecule, or applying the second aqueous solution followed by the first aqueous solution and mixing the first and second aqueous solutions on the orifice, or premixing the first and second aqueous solutions and applying the resulting mixture to the orifice before the resulting mixture completely cures, thereby forming on said orifice a resorbable adhesive hydrogel, and allowing the hydrogel to remain on said orifice until said hydrogel is resorbed;
provided that;
(i) at least one of the first aqueous solution or the second aqueous solution further comprises a base catalyst;
or(ii) a base catalyst is applied to the orifice as a neat liquid or as part of a third aqueous solution, and said neat liquid or third aqueous solution is mixed with both the first aqueous and second aqueous solutions on the orifice or said neat liquid or third aqueous solution is premixed with both the first and second aqueous solutions, and the resulting mixture is subsequently applied to the orifice before the resulting mixture completely cures;
or(iii) a combination of (i) and (ii). - View Dependent Claims (3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 25, 26, 27, 28, 29)
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2. A method for bonding at least two anatomical sites together comprising:
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applying to at least one of the at least two anatomical sites (a) a first aqueous solution comprising from about 5% to about 40% by weight of a polysaccharide that has been oxidized to provide an oxidized polysaccharide that contains aldehyde groups, said polysaccharide having a molecular weight of about 1,000 to about 1,000,000 Daltons, and said oxidized polysaccharide having an equivalent weight per aldehyde group of about 90 to about 1500 Daltons, such that the oxidized polysaccharide has on average more than two aldehyde groups per chain, followed by (b) a second aqueous solution comprising from about 5% to about 40% by weight of a poly(hydroxylic) compound that has been derivatized to provide a derivatized poly(hydroxylic) compound that contains acetoacetate groups, said poly(hydroxylic) compound having a molecular weight of less than or equal to about 100,000 Daltons, and said derivatized poly(hydroxylic) compound having an equivalent weight per acetoacetate group of about 100 to about 2000 Daltons, such that the derivatized poly(hydroxylic) compound has on average more than two acetoacetate groups per molecule, or applying the second aqueous solution followed by the first aqueous solution and mixing the first and second aqueous solutions on the at least one site, or premixing the first and second aqueous solutions and applying the resulting mixture to the at least one site before the resulting mixture completely cures, and contacting the at least two anatomical sites together;
provided that;
(i) at least one of the first aqueous solution or the second aqueous solution further comprises a base catalyst;
or(ii) a base catalyst is applied to the at least one site as a neat liquid or as part of a third aqueous solution, and said neat liquid or third aqueous solution is mixed with both the first aqueous and second aqueous solutions on said at least one site or said neat liquid or third aqueous solution is premixed with both the first and second aqueous solutions, and the resulting mixture is subsequently applied to the at least one site before the resulting mixture completely cures;
or(iii) a combination of (i) and (ii). - View Dependent Claims (22, 23)
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Specification