Supplemented and unsupplemented tissue sealants, methods of their production and use

Abstract

This invention provides supplemented tissue sealants, methods for their production and use thereof. Disclosed are tissue sealants supplemented with at least one cytotoxin or cell proliferation inhibiting composition. The composition may be further supplemented with, for example, one or more antibodies, analgesics, anticoagulants, anti-inflammatory compounds, antimicrobial compositions, cytokines, drugs, growth factors, interferons, hormones, lipids, deminearlized bone or bone morphogenetic proteins, cartilage inducing factors, oligonucleotides polymers, polysaccharides, polypeptides, protease inhibitors, vasoconstrictors or vasodilators, vitamins, minerals, stabilizers and the like.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application is a Continuation-in-Part Application of U.S. application Ser. No. 08 / 351,006, filed Dec. 7, 1994, abandonded, which is a Continuation-in-Part Application of U.S. application Ser. No. 08 / 328,552, filed Oct. 25, 1994, abandoned, which is a Continuation Application of U.S. application Ser. No. 08 / 031,164, filed Mar. 12, 1993, abandoned, which is a Continuation-in-Part Application of U.S. application Ser. Nos. 07 / 618,419 and 07 / 798,919, filed Nov. 27, 1990, and Nov. 27, 1991, respectively, both of which are abandoned, all of which are herein incorporated by reference.RIGHTS OF THE UNITED STATES GOVERNMENT IN THIS INVENTION[0002]Under a Cooperative Research and Development Agreement between The American National Red Cross and The U.S. Army Institute of Dental Research, the U.S. Government may have a non-exclusive, irrevocable, paid-up license in one or more embodiments of this invention.FIELD OF INVENTION[0003]This invention ...

AI Technical Summary

Benefits of technology

[0095]A sixth advantage is that the AB-supplemented FG of this invention, such as TET-FG, has unexpectedly increased the longevity and stability of the FG compared to that of the unsupplemented FG. This increased stability continues even after appreciable quantities of the AB are no longer remaining in the FG. For example, soaking a newly formed FG clot in a saturated solution of TET produced from free base TET, or in a solution of CIP HCl, produces a FG clot which is stable and preserved even after substantially all the TET or CIP has left the FG clot. While not wishing to be bound by any theory as to how this effect is produced, it is believed that the AB, such as TET or CIP, inhibits plasminogen which is in the TFC and breaks down the FG. Once the plasminogen is inhibited, its continued inhibition does not appear to depend on appreciable quantities of the TET or CIP remaining in the FG. As a result of this stabilizing effect, one can expect an increased storage shelf life of the TS, and possi

Problems solved by technology

However, it has not been established if any FGF growth factor is chemotactic for fibroblasts.

However, their use to promote wound healing has yielded inconsistent results (see, e.g., Carter et al., in Growth Factors and Other Aspects of Wound Healing: Biological and Clinical Implications, Alan R. Liss, Inc., New York, N.Y., pp.

The reasons for such inconsistent results are not known, but might be the result of difficulty in applying growth factors to a wound in a manner in which they can exhibit their normal array of biological activities.

However, this heat inactivation method may produce denatured proteins in the FG which may also be allergenic.

In addition, there is concern that this inactivation method will not inactivate prions which cause bovine spongiform encephalopathy, “mad cow disease,” which may be present in the TS due to the use of bovine proteins therein.

Although FG maintains hemostasis and reduces blood loss, it has not yet been shown to possess true wound healing properties.

Unfortunately, DBM materials have little clinical use unless combined with particulate marrow autografts.

There is a limit to the quantity of DBM that can be surgically placed into a recipient's bone to produce a therapeutic effect.

Soft-tissue collapse into the wound bed may likewise inhibit the proper migration of osteocompetent stem cells into the wound bed.

However, DBM in powder form is difficult to use.

Therefore, these results are inconsistent and confusing.

However, commercially available preparations of FG and other TSs are too dense to allow cell migration into and through them.

This limits their effectiveness in some in vivo uses.

However, the source of bone autografts is usually limited and the use of allogeneic bones involves a high risk of viral contamination.

However, one general problem with these techniques is that nonautologous cells

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