US 6,197,325 B1Granted

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

AssigneeAmerican National Red Cross

InventorsMartin James MacPhee, William Nash Drohan, Carlos I. Lasa, Jr., Gene Liau, Christian Haudenschild

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Abstract

This invention provides methods for the localized delivery of supplemented tissue sealants, wherein the supplemented tissue sealants comprise at least one composition which is selected from one or more antibodies, analgesics, anticoagulants, anti-inflammatory compounds, antimicrobial compositions, antiproliferatives, cytokines, cytotoxins, drugs, growth factors, interferons, hormones, lipids, demineralized bone or bone morphogenetic proteins, cartilage inducing factors, oligonucleotides polymers, polysaccharides, polypeptides, protease inhibitors, vasoconstrictors or vasodilators, vitamins, minerals, stabilizers and the like. Further provided are methods of using the site-specific supplemented tissue sealants, including preparation of a biomaterial.

Claims48

Dependent claims

A method of localized sustained delivery of a supplement to promote generation or regeneration of bone and/or cartilage, said method comprising:

(a) preparing a biocompatible, supplemented tissue sealant composition comprising:
(i) at least one supplement selected from the group consisting of a cytotoxin or cell proliferation inhibiting compound, an osteogenic compound, an osteoconductive compound, a cartilage inducing compound, an oligonucleotide or polynucleotide, a compound that inhibits the differentiation of cells involved in the formation or metabolism of bone, a compound that induces the differentiation of cells involved in the formation or metabolism of bone, and a compound that prevents resorption of bone, in an amount which promotes generation or regeneration of bone and/or cartilage;
and
(ii) fibrinogen, or a derivative or metabolite thereof selected from the group consisting of fibrin I and fibrin II, in an amount which forms a fibrin matrix in the presence of thrombin and Ca++ and water;
and
(b) applying said composition of step (a) to a site in need of newly formed bone and/or cartilage under conditions which induce formation of a fibrin matrix at a concentration which provides sustained delivery of an amount of said supplement effective to promote the generation or regeneration of bone and/or cartilage,
wherein said amount of said supplement is greater than the amount which is soluble in said fibrin matrix;
and
wherein said fibrin matrix provides a scaffold that determines the shape and location of said newly formed bone and/or cartilage;
and
further wherein said sustained delivery is for a period greater than the period obtained according to simple diffusion kinetics.

8 more elements

A method of localized sustained delivery of a supplement to promote generation or regeneration of bone and/or cartilage, said method comprising:

(a) preparing a biocompatible, supplemented tissue sealant composition comprising:
(i) at least one supplement selected from the group consisting of an osteogenic protein, an osteoconductive protein, a cartilage inducing protein, a polypeptide, a hormone, a cytokine, a cytotoxin or cell proliferation inhibiting protein, a protein that inhibits the differentiation of cells involved in the formation or metabolism of bone, a protein that induces the differentiation of cells involved in the formation or metabolism of bone, and a protein that prevents resorption of bone, in an amount which promotes generation or regeneration of bone and/or cartilage;
and
(ii) fibrinogen, or a derivative or metabolite thereof selected from the group consisting of fibrin I and fibrin II, in an amount which forms a fibrin matrix in the presence of thrombin and Ca++ and water;
and
(b) applying said composition of step (a) to a site in need of newly formed bone and/or cartilage under conditions which induce formation of a fibrin matrix at a concentration which provides sustained delivery of an amount of said supplement effective to promote the generation or regeneration of bone and/or cartilage;
wherein said fibrin matrix provides a scaffold that determines the shape and location of said newly formed bone and/or cartilage;
and
further wherein said sustained delivery is for a period greater than the period obtained according to simple diffusion kinetics.

6 more elements

Dependencies are inferred from the claim text.

Facts

Application: 08/474,084Filed 7 Jun 1995 · continuation in part
Priority: 27 Nov 1990
Granted: 6 Mar 2001
Term ends: Not estimatedThe source records don’t support an estimate.

Classification52 codes

A61K 31/00
Medicinal preparations containing organic active ingredients
A61K 31/513
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
A61B 17/00491
Surgical instruments, devices or methods: surgical glue applicators
A61K 31/65
Medicinal preparations containing organic active ingredients: tetracyclines

Family

Application07/618,419Parent of this continuation-in-part · filed 27 Nov 1990
Application07/798,919Parent of this continuation-in-part · filed 27 Nov 1991
Application08/031,164Parent of this continuation · filed 12 Mar 1993
Application08/328,552Parent of this continuation-in-part · filed 25 Oct 1994
Application08/351,006Parent of this continuation-in-part · filed 7 Dec 1994
Application08/328,552Parent of this continuation
Application08/031,164Parent of this continuation-in-part
US 6,197,325 B1This patent

From the US filing history. Foreign family members aren’t listed.