Collagen Corporation

Matrix Pharmaceuticals, Inc.

Other

Oncogen

Matrix Pharmaceutical, Inc.

Matrix Pharmaceutical, Inc./project Hear

Edward E Luck

Dennis M Brown

John R Daniels

Daniel R Twardzik

Anthony F Purchio

David H Sierra

Antiproliferative compositions are provided which are capable of sustained release of an antiproliferative agent, particularly a TGF-.beta., at a site proximal to a target cell. The compositions are effective in inhibiting proliferation of the target cell, particularly when used in combination with a vasoconstrictive agent.

TGF-.beta. protein compositions for inhibition of cell proliferation

The present invention provides a surgical adhesive comprising, in an aqueous composition, fibrinogen, FXIII, collagen, thrombin, Ca.sup.2+ and optionally, an antifibrinolytic agent. The present adhesive may be formed from the patient's plasma without the use of any added reagents for concentration or isolation of the fibrinogen. Conveniently, the adhesive is formulated as a two-part composition which is mixed together just prior to use.

Surgical adhesive material

A pharmaceutical composition and method of treating cellular disorders involving abnormal solid cellular growths which comprises administering a pharmaceutical composition containing cytotoxic agents in combination with a vasoconstrictive drug. Enhanced effectiveness of the composition is observed, with reduced cytotoxic effects on cells distant from the site of introduction. Agents may be included to enhance therapeutic gain and reduce adverse affects to normal tissue.

Treatments employing vasoconstrictive substances in combination with

Treatment of cellular disorders involving abnormal solid cellular growths involves introduction of cytotoxic reagents dispersed in a physiologically acceptable proteinaceous matrix into the solid cellular growth or area of an existing or removed solid cellular growth. Enhanced effectiveness of the drug is observed, with reduced cytotoxic effects on cells distant from the site of introduction. Other drugs may be included to enhance therapeutic gain and reduce adverse affects to normal tissue.

Treatments employing drug-containing matrices for introduction into

Collagen, available from domestic animals, is freed of noncollagen proteins, glycosaminoglycans and lipids by enzymatic treatment with a proteolytic enzyme to yield a product which is soluble in dilute acidic aqueous solutions (collagen in solution--CIS). The naturally occurring collagen is modified by removal of certain terminal peptide chains, which are described as telopeptides. The modified collagen, so derived, is described as atelopeptide collagen. Native collagen is immunogenic, while atelopeptide collagen is nonimmunogenic or possessed of a negligibly low level of immunogenicity. The collagen in solution is then treated according to a specific regimen under conditions whereby the collagen slowly separates from solution while exposed to mild shear forces. This procedure results in the formation of a fibrous precipitate composed of regularly ordered fibers of collagen possessed of a rope-like structure. These resulting aggregates are referred to as native fibrous micropolymers (NFM). Once the regimen or procedure is completed, and the fiber mass has been formed, the fibrous micropolymers may be freed of salt, taken up in a different solution or modified. For example, cross-links may then be introduced to stabilize the fibers. The products find wide use as packing, membranes, fibers, bags, supports, integuments, and are especially suitable for biologic implantation or application.

Non-antigenic collagen and articles of manufacture

Method for decontaminating proteinaceous host materials from microorganisms, while retaining chemical, physical and physiological properties of said host proteinaceous materials, said method comprising substantially dehydrating said host proteinaceous material, preferably by lyophilization, and subjecting said host material to a lethal dosage of microwave energy while said host material is maintained in substantially ambient conditions.

Microwave sterilization of dry protein

Collagen, available from domestic animals, is freed of noncollagen proteins, glycosaminoglycans and lipids by enzymatic treatment with a proteolytic enzyme to yield a product which is soluble in dilute acidic aqueous solutions (collagen in solution--CIS). The naturally occurring collagen is modified by removal of certain terminal peptide chains, which are described as telopeptides. The modified collagen, so derived, is described as atelopeptide collagen. Native collagen is immunogenic, while atelopeptide collagen is nonimmunogenic or possessed of a negligibly low level of immunogenicity. The collagen in solution is then treated according to a specific regimen under conditions whereby the collagen slowly separates from solution while exposed to mild shear forces. This procedure results in the formation of a fibrous precipitate composed of regularly ordered fibers of collagen possessed of a ropelike structure. These resulting aggregates are referred to as native fibrous micropolymers (NFM). Once the regimen or procedure is completed, and the fiber mass has been formed, the fibrous micropolymers may be freed of salt, taken up in a different solution or modified. For example, cross-links may then be introduced to stabilize the fibers. The products find wide use as packing, membranes, fibers, bags, supports, integuments, and are especially suitable for biologic implantation or application.

The naturally occurring collagen is modified by removal of certain terminal peptide chains, which are described as telopeptides. The modified collagen, so derived, is described as atelopeptide collagen. Native collagen is immunogenic, while atelopeptide collagen is nonimmunogenic or possessed of a negligibly low level of immunogenicity. The collagen in solution is then treated according to a specific regimen under conditions whereby the collagen slowly separates from solution while exposed to mild shear forces. This procedure results in the formation of a fibrous precipitate composed of regularly ordered fibers of collagen possessed of a ropelike structure. These resulting aggregates are referred to as native fibrous micropolymers (NFM). Once the regimen or procedure is completed, and the fiber mass has been formed, the fibrous micropolymers may be freed of salt, taken up in a different solution or modified. For example, cross-links may then be introduced to stabilize the fibers. The products find wide use as packing, membranes, fibers, bags, supports, integuments, and are especially suitable for biologic implantation or application.

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Menlo Park, CA, United States of America

Edward E Luck