Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Implant or insert
Reexamination Certificate
2000-06-16
2001-08-21
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Implant or insert
C424S422000, C424S423000, C424S444000, C514S774000, C530S354000
Reexamination Certificate
active
06277394
ABSTRACT:
TECHNICAL FIELD
This invention is in the general field of biomaterials. More specifically, the invention is directed to biomedical implants, their composition and methods of preparation and use.
BACKGROUND OF THE INVENTION
Biomaterials have been used for implantation into the human body to act as supports for wound and solid tissue healing. Matrices useful for this purpose should have the ability to adhere and conform to the wound site and surrounding tissue. Ideally, they also should facilitate accumulation of fibroblasts, endothelial cells and wound healing regulatory cells to promote connective tissue deposition and angiogenesis.
U.S. Pat. No. 4,849,285 to Dillon is directed to a composite, self-supporting agglomerated microstructure useful as a surgical implant. The macrostructure is a matrix of polytetrafluoroethylene resin and cured silicone that has uniformly distributed within it a particulate material. These particulates have a maximum size of about 2000 microns and may be hydroxyapatite or tricalcium phosphate. This particular macrostructure, therefore, is a composite of ceramic particulate material and organic biomaterials that is uniformly permeated by a network of open pores. The pores are formed by incorporating sodium chloride into the composite and thereafter leaching it out in the manufacturing process.
U.S. Pat. No. 4,843,112 to Gerhart et al. is to a bone cement composed of a particulate biocompatible calcium phosphate ceramic and a resorbable calcium salt disperses in a crosslinked biodegradable polyester matrix. Pores are created in the matrix by body fluids creating small voids or cavities in the polymer matrix.
U.S. Pat. No. 5,141,522 to Landi et al. describes a composite of two or more biocompatible polymers useful for mammalian tissue repair. One of the polymers is polytetrafluoroethylene (PTFE), which is the reinforcing binder. A bioabsorbable component that may be a lactone, carbonate or a lactide, is contained within the structure of the PTFE and serves to enhance ingrowth of tissue.
Additional disclosures of PTFE compositions useful as implants include, but are not limited to U.S. Pat. Nos. 5,141,522; 5,098,779; and 4,863,974. The PTFE component of these compositions serves as a nonabsorbable microfibrillar structural support. A bioabsorbable component is contained or coated on the structural support. The PTFE is polymerized prior to implantation of the compositions.
U.S. Pat. No. 4,373,217 to Draenert is directed to a polymeric implant material that has an acrylate, polymethacrylate or copolymer base with dispersed resorbable tricalcium phosphate of 50 to 300 microns with an available pore volume of less than 0.1 mL/g. This particular material is said to allow for a firm bond between implant and body tissue. Resorption of tricalcium phosphate particles at the surface of the implant are resorbed into the body is said to promote bone growth in the marginal porosity produced. In order to ensure absorption of liquid monomer into the porous calcium phosphate, a filler that is also resorbable in the body is included to fill the pore volumes of the calcium phosphate.
U.S. Pat. No. 4,898,734 to Mathiowitz et al. also involves a precast solid polymeric implant material. A continuous polymeric matrix made of, for example, polyurethane or polystyrene, is embedded with microcapsules or microspheres that may contain material for subsequent release. The spheres may be removed from the matrix by bioerosion. For creation of a vascular graft, erodible microspheres are entrapped within a tube-shaped slower-degrading polymer matrix. Rapid erosion of the spheres results in pores for cell seeding and vascularization with the matrix providing support until there is sufficient cell growth to create structural integrity.
U.S. Pat. No. 4,950,483 to Ksander et al. describes a collagen implant useful for wound healing. The implant is made of collagen and has a bulk density of 0.01 to 0.03 g/cm
3
and is said to have a pore size sufficient to permit cell ingrowth. Bioactive agents such as FGF and TGF-&bgr; may be incorporated into the implant.
U.S. Pat. No. 5,077,049 to Dunn et al. is directed to a method for restoring periodontal tissue. A biodegradable liquid polymeric systems designed to generate a porous structure when cured into a barrier membrane, is administered to the soft-tissue defect. The pores will form as a result of water-soluble material included in the liquid material. The liquid material injected into the defect provides a scaffold that is filled with new bone cells that gradually replace the water-soluble polymer.
U.S. Pat. No. 4,902,295 to Walthall et al. involves a transplantable artificial tissue. The tissue is made by mixing a polymerizing matrix with reversible gel precursors in an aqueous solution with viable cells. The gel, which may be alginate, a gum or agarose, is then dissolved to provide a porous matrix for implantation.
None of the above-described references describes a biomedical implant material with a differentially degradable matrix and porosifying agent where polymerization occurs in situ or where the matrix is precast and is made of a biopolymeric material.
DISCLOSURE OF THE INVENTION
Accordingly, one aspect of the present invention is an in situ polymerizing biomedical implant useful for implantation into a patient comprising a slowly biodegradable matrix material and a biodegradable porosifying agent.
Another aspect of the invention is a precast biomedical implant useful for implantation into a patient comprising a slowly biodegradable polymeric matrix or a nonbiodegradable ceramic matrix and a biodegradable porosifying agent.
A further aspect of the invention is a method for repair of mammalian tissue using the above-described implants.
MODES OF CARRYING OUT THE INVENTION
Definitions
As used herein, certain terms will be used which have defined meanings.
By “biodegradable” or “bioerodible” as it relates to the porosifying agent is intended a material that will dissolve in situ as a result of exposure to an aqueous environment in less than a week, preferably about 1 and 72 hours, more preferably between about 2 and 12 hours. Dissolution may occur as a result of a number of different mechanisms such as simple diffusion, hydrolysis, enzymatic cleavage, ion exchange, autocatalysis, osmosis, degradation, free-radical cleavage, radiation effect, thermal melting, and chemical dissolution. Hydrolysis is the preferred mechanism for biodegradation. As such, the biodegradation of the porosifying material is distinguishable from prior art “leaching” of water-soluble drugs and salts, such as particulate calcium salts, e.g., tricalcium phosphate. Typically, these water-soluble drugs or salts merely create small voids or cavities on the surface of the matrix in contrast to the porous network provided by the biodegradable porosifying agents described herein.
By “slowly biodegradable” or “slowly bioerodible” as it relates to the matrix material is intended a material that will not dissolve in situ (or in an aqueous environment) within a week, or may dissolve in a period of from about one week to 24 months, preferably a period of between about 1 to 12 months. It also is intended to exclude material such as a polyether that is only degradable outside the range of normal body temperature and in organic solvents. Examples of this type of excluded polyether include low molecular weight aliphatic polyethers which are soluble in aqueous solutions of methanol, ethanol or acetone.
The term “porosifying agent” intends particulate materials that include but are not limited to materials in the form of solid or hollow spheres, extruded rods, or other convenient shapes. Typically, the particulate has a mean diameter of between about 10 and 500 &mgr;m, more typically between about 20 and 200 &mgr;m. The particles are generally spherical in shape but other shapes such as rhombic, irregular, stellate and other crystalline type shapes may be used. The agents are present in a concentration of at least about 12% per volume of the matrix material, preferably the concentra
Channavajjala Lakshmi
Cohesion Technologies, Inc.
McCutchen Doyle Brown & Enersen LLP
Page Thurman K.
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