US RE38,158 E1Granted

Adhesive sealant composition

AssigneeMinnesota Mining and Manufacturing Company

InventorsThomas H. Barrows, Terry W. Lewis, Myhanh T. Truong, Matthew T. Scholz

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Abstract

This invention is related to an adhesive composition which may be used to bond or seal tissue in vivo. The adhesive composition is readily formed from a two component mixture which includes a first part of a protein, preferably a serum albumin protein, in an aqueous buffer having a pH in the range of about 8.0-11.0 and a second part of a water-compatible or water-soluble bifunctional crosslinking agent. When the two parts of the mixture are combined, the mixture is initially a liquid which cures in vivo on the surface of tissue in less than about one minute to give a strong, flexible, pliant substantive composition which bonds to the tissue and is absorbed in about four to sixty days. The adhesive composition may be used either to bond tissue, to seal tissue or to prevent tissue adhesions caused by surgery.

Claims154

Dependent claims

An adhesive composition consisting essentially of

i) a first aqueous mixture of about 20-60 wt/vol % serum albumin in about 0.01-0.25 molar buffer at a pH in a range of about 8.0-11.0,
ii) a second aqueous mixture of about 50-800 mg/ml of a crosslinking agent having a molecular weight in a range of about 1,000-15,000, wherein the crosslinking agent is of the formula
G—LM—PEG—LM—G
wherein —PEG— is a diradical fragment represented by the formula
—O—(CH2—CH2—O—)a—
where a is an integer from 20-300;
wherein —LM— is a diradical fragment selected from the group consisting of a carbonate diradical of the formula, —C(O)—, a monoester diradical of the formula, —(CH2)bC(O)— where b is an integer from 1-5, a diester diradical of the formula, —C(O)—(CH2)c—C(O)— where c is an integer from 2-10 and where the aliphatic portion of the diradical may be saturated or unsaturated, a dicarbonate diradical of the formula —C(O)—O—(CH2)d—O—C(O)— where d is an integer from 2-10, and an oligomeric diradical represented by the formulas —R—C(O)—, —R—C(O)—(CH2)c—C(O)—, or —R—C(O)—O—(CH2)d—O—C(O)— where c is an integer from 2-10, d is an integer from 2-10, and R is a polymer or copolymer having 1-10 monomeric fragments selected from the group consisting of lactide, glycolide, trimethylene carbonate, caprolactone and p-dioxanone;
and
wherein —G is a leaving group selected from the group consisting of succinimidyl, maleimidyl, phthalimidyl, imidazolyl, nitrophenyl, or and tresyl, ;
and
wherein a combination of the first and second mixtures is initially liquid and then cures on the surface of tissue to give a flexible, substantive matrix which bonds to the tissue and has a burst strength greater than about 10 mmHg.

8 more elements

Dependencies are inferred from the claim text.