Adhesive sealant composition

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.

Description

BACKGROUNDA variety of techniques have been used to bond or seal tissue. For example, different types of tissues have been mechanically bound or sealed with a number of procedures, materials and methods including sutures, staples, tapes and bandages. In some applications, these materials are made of absorbable materials which are intended to bond and / or seal tissue as it heals and then to be absorbed over a period of time.The common use of a medical adhesive or "tissue glue" has not found widespread application. To date, some adhesive materials are known which may be used to adhere or stick tissue such as skin. For example, cyanoacrylate adhesives such as HISTOACRYL adhesive available from B. Braun, Melsungen, Germany or VETBOND tissue adhesive available from 3M, St. Paul, Minn. may be used to bond tissue. In addition to cyanoacrylate adhesives, other types of materials have been reported to adhere to stick to skin. For example, U.S. Pat. No. 4,839,345 to Doi et al. reports a hydrat...

AI Technical Summary

Benefits of technology

Two component adhesives were prepared according to the process described in Example 6 except that the pH of the buffer in the protein solution was changed as listed in Table 2. The data indicate that a preferred pH range is about 8.44-10.0.

TABLE 2 Crosslinking agent Cure Protein PEG-SS2 Time Constistency HSA 130 mg/ml 10 min Initially softer Baxter 3400 mw adhesive, hardens Lot 2837A238AA with aging 40% 0.1 M pH 7.4 Carb/Bicarb HSA 130 mg/ml 20 sec Very elastic, good Sigma 3400 mw adhesive strength Lot 63H9041 not sticky 40% 0.1 M pH 8.44 Carb/Bicarb HSA 130 mg/ml 10 sec Hard gel, not sticky Sigma 3400 mw Lot 63H9041 40% 0.15 M pH 9.07 Carb/Bicarb HSA 130 mg/ml 5 sec Hard gel, not sticky Sigma 3400 mw Lot 63H9041 40% 0.2 M pH 9.52 Carb/Bicarb HSA 260 mg/ml 5 sec Hard gel, not sticky Sigma 3400 mw Lot 63H9041 40% 0.2 M pH 9.52 Carb/Bicarb HSA 130 mg/ml 7 sec Elastic to hard gel, Sigma 10,000 mw slightly sticky Lot 63H9041 40% 0.2 M pH 9.52 Carb/Bicarb HSA 260 mg/ml 7 sec Elastic to hard gel, Sigma 10,000 mw slightly sticky Lot 63H9041 40% 0.2 M pH 9.52 Carb/Bicarb HSA 130 mg/ml 25 s

Problems solved by technology

In sum, there are few available adhesive compositions that have sufficient strength, biocompatibility and bioabsorbability as well as other desired properties that would allow such compositions to be readily used in current medical procedures or practices.

The unavailability of a suitable tissue adhesive or sealant may be related to the stringent requirements that a suitable, useful tissue adhesive must meet.

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