Drug – bio-affecting and body treating compositions – Extract – body fluid – or cellular material of undetermined... – Digestive system
Reexamination Certificate
1999-06-10
2002-04-23
Witz, Jean C. (Department: 1651)
Drug, bio-affecting and body treating compositions
Extract, body fluid, or cellular material of undetermined...
Digestive system
C514S002600, C514S021800
Reexamination Certificate
active
06375989
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to a bioactive extract or concentrate prepared from basement membranes of natural tissues and the use of those extracts to promote cell growth and proliferation. More particularly, this invention is directed to submucosal tissue extracts and their preparation and use in promoting cell growth in vitro and in vivo.
BACKGROUND AND SUMMARY OF THE INVENTION
It has been reported that various basement membranes and other extracellular matrices can be utilized as tissue graft constructs or as cell culture substrates. Several matrix products derived from complex substrates are commercially available for use in supporting cell growth in vitro. For example, Becton Dickinson currently offers two such products: Human Extracellular Matrix and MATRIGEL® Basement Membrane Matrix. Human Extracellular Matrix is a chromatographically partially purified matrix extract derived from human placenta and comprises laminin, collagen IV, and heparin sulfate proteoglycan. (Kleinman, HK et al., U.S. Pat. No. 4,829,000 (1989)) MATRIGEL® is a soluble basement membrane extract of the Engelbreth-Holm-Swarm (EHS) tumor, gelled to form a reconstituted basement membrane. Both of these matrix products require costly biochemical isolation, purification, and synthesis techniques and thus production costs are high.
Submucosal tissue harvested from warm blooded vertebrates is a collagenous matrix that has shown great promise as a unique graft material for inducing the repair of damaged or diseased tissues in vivo, and for inducing the proliferation and differentiation of cell populations in vitro. Submucosal tissue consists primarily of extracellular matrix material prepared by mechanically removing selected portions of the mucosa and the external muscle layers and then by lysing resident cells with hypotonic washes. Preliminary biochemical analyses show that the composition of small intestinal submucosa is similar to that of other basement membrane/extracellular matrix structures, and consists of a complex array of collagens, proteoglycans, glycosaminoglycans, and glycoproteins. The major components commonly identified in extracellular matrix tissues similar to submucosal tissue include the cell adhesion proteins, fibronectin, vitronectin, thrombospondin, and laminin; the structural components, collagens and elastin; and the proteoglycans, serglycin, versican, decorin, and perlecan.
Numerous studies have shown that submucosal tissue is capable of inducing host tissue proliferation, remodeling and regeneration of tissue structures following implantation in a number of in vivo microenvironments including lower urinary tract, body wall, tendon, ligament, bone, cardiovascular tissues and the central nervous system. Upon implantation, cellular infiltration and a rapid neovascularization are observed and the submucosa extracellular matrix material is remodeled into host replacement tissue with site-specific structural and functional properties.
Submucosal tissue can be obtained from various sources, including intestinal tissue harvested from animals raised for meat production, including, for example, pigs, cattle and sheep or other warm-blooded vertebrates. As a tissue graft, submucosal tissue undergoes remodeling and induces the growth of endogenous tissues upon implantation into a host. It has been used successfully in vascular grafts, urinary bladder and hernia repair, replacement and repair of tendons and ligaments, and dermal grafts. The preparation and use of submucosa as a tissue graft composition is described in U.S. Pat. Nos. 4,902,508; 5,281,422; 5,275,826; 5,554,389 and other related U.S. patents.
Direct interactions between extracellular matrix components and cells are known to mediate processes which are fundamental to migration, proliferation and differentiation during development. However, the role of the extracellular matrix in wound healing and tissue regeneration has been less well studied. It has been found in accordance with the present invention that submucosal tissue can be extracted to provide compositions comprising isolated bioactive components of the submucosal tissue in their active form. Such an enriched extract can be utilized as an additive for tissue culture media to promote in vitro cell growth and proliferation, and also can be used as an active ingredient for wound healing compositions such as topically applied creams and bandages.
REFERENCES:
patent: 4743552 (1988-05-01), Friedman et al.
patent: 4801299 (1989-01-01), Brendel et al.
patent: 4829000 (1989-05-01), Kleinman et al.
patent: 4902508 (1990-02-01), Badylak et al.
patent: 5217954 (1993-06-01), Foster et al.
patent: 5275826 (1994-01-01), Badylak et al.
patent: 5281422 (1994-01-01), Badylak et al.
patent: 5478739 (1995-12-01), Slivka et al.
patent: 5518915 (1996-05-01), Naughton et al.
patent: 5554389 (1996-09-01), Badylak et al.
patent: 5714458 (1998-02-01), Adami et al.
patent: WO 96/24661 (1996-08-01), None
patent: WO 98/25549 (1998-06-01), None
Hodde et al., Glycosaminoglycan Content of Small Intestinal Submucosa: A Bioscaffold for Tissue Replacement,Tissue Engineering, vol. 2, No. 3, 1996, pp. 209-217.
Cartlidge, S.A., and Elder, J.B., Transforming growth factor &agr; and epidermal growth factor levels in normal human gastrointestinal mucosa.British J. of Cancer, vol. 60, No. 5, Nov. 1989, pp 657-660.
Vukicevic et al., Identification of Multiple Active Growth Factors in Basement Membrane Matrigel Suggets Caution in Interpretation of Cellular Activity Related to Extracellular Matrix Components.Experimental Cell Research, vol. 202, No. 1, Sep. 1992, pp 1-8.
Nice et al., The Major Colonic Cell Mitogen Extractable from Colonic Mucosa Is an N Terminally Extended Form of Basic Fibroblast Growth Factor.J. of Biol. Chem., vol. 266, No. 22, Aug. 5, 1991, pp. 14425-14430.
Breen et al.,Methods in Carbohydrate Chemistry. vol. 7, New York: Academic Press 1976, pp. 101-115.
Blumenkrantz, and Asboe-Hanson, Analytical Biochemistry, vol. 54, 1973, p. 484.
Linhardt,Current Protocols in Molecular Biology, New York: Wiley & Sons, 1994, unit 17 13 B.
Zohse et al., J. of Biol. Chem., vol. 267, pp 243-247, 1992.
Badylak S.T., Boder G.B., Morff R., Lantz G., Directed Connective Tissue Remodeling Upon a Biologic Collagen Substrate.J. Cell Biochem.Supplement 16F, p. 124, 1992.
Kuo C.Y., Burghen G.A., and Herrod H.G., Biohybrid Islet-Gland Equivalent for Transplantation.Journal of Cellular BiochemistrySupplement 18C, PZ110, Feb. 13-26, 1994.
Kleinman H.K., McGarvey M.L., Hassell J.R., Star V.L., Cannon F.B., Laurie G.W., and Martin G.R. Basement Membrane Complexes with Biological Activity,Biochemistry25:312-318, 1986.
Freshney R.I.Cultures of Animal Cells: A Manual of Basic Technique. Chapters 12 and 13, pp. 155-185, Alan R. Liss, Inc.,New York, 1994.
El-Housseiny. E; et al., Orthotopic Implantation of Primary N-[4-(5-Nitro-2-furyl)-2-thiazoiyl]formamide-induced Bladder Cancer in Bladder Submucosa: An Animal Model for Bladder Cancer Study ,Cancer Research, vol. 43:617-620, Feb. 1983.
Kashtan, H. et al., Intra-rectal injection of tumor cells: a novel animal model of rectal cancer,Surgical Oncology, 1:251-256, 1992.
Sigma 1994 Catalogue and Price List, Plant Cell Culture Equipment, p. 160.
Demain,Manual Of Industrial Microbiology and Biotechnology, pp. 249-262, American Society for Microbiology; Washington, D.C., 1986.
Badylak Stephen F.
Brightman Andrew O.
Hodde Jason P.
McPherson Timothy B.
Voytik-Harbin Sherry L.
Barnes & Thornburg
Purdue Research Foundation
Witz Jean C.
LandOfFree
Submucosa extracts does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Submucosa extracts, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Submucosa extracts will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2821426