Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Matrices
Reexamination Certificate
2001-09-19
2004-05-11
Webman, Edward J. (Department: 1617)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Matrices
C424S426000
Reexamination Certificate
active
06733787
ABSTRACT:
SUMMARY OF THE INVENTION
In a matrix for tissue repair comprising a biocompatible, bioerodable polymer, this invention provides the improvement wherein the polymer has a water solubility of about 0.01 to about 500 mg/mL at about 25° C. and an adhesive strength of about 600 to about 150,000 Pa so that the matrix is tissue adherent. One such matrix comprises a polymer that also has a glass transition temperature of less than 0° C. The improved matrices are useful for repairing tissues such as bone and cartilage, and for administering biologically active substances.
These improved matrices may further comprise a filler, a bioactive agent, or both.
In another aspect, this invention provides a pressure sensitive adhesive for tissue repair comprising (a) a biocompatible, bioerodable polymer which exhibits adhesive strength of about 600 to about 150,000 Pa, (b) a filler and (c) a bioactive agent. Further, this invention provides a pressure sensitive adhesive for tissue repair comprising a terpolymer of an &agr;-hydroxycarboxylic acid which exhibits adhesive strength of about 600 to about 150,000 Pa.
This invention also relates to methods for repairing bone or cartilage which comprise applying to the bone or cartilage an implant matrix of this invention.
In the methods of repairing bone or cartilage using a bioerodable implant matrix, this invention further provides the improvement comprising using a tissue-adherent implant matrix of this invention to repair the defect.
In another aspect this invention relates to implantable articles of manufacture for use in the release of a bioactive agent into a physiological environment, said articles comprising a biologically active agent disbursed in an implant matrix of this invention.
DETAILED DESCRIPTION OF THE INVENTION
The present invention is directed to improvements in matrices for tissue repair comprising biocompatible, bioerodable polymers. In one improvement, the matrix comprises a polymer which has a water solubility of about 0.01 to about 500 mg/mL at about 25° C. and an adhesive strength of about 600 to about 150,000 Pa so that the matrix is tissue adherent. One such matrix comprises a polymer that has a glass transition temperature of less than 0° C. The improved matrix can further comprise a filler or a bioactive agent, or both. An especially useful attribute of the improved matrices is that the matrix adheres to tissues such as bone or cartilage. In addition, the matrix has a texture like that of dough or putty; thus, it is particularly suitable for being molded to fit into a site needing repair.
In another aspect, this invention provides pressure sensitive adhesives for tissue repair comprising (a) a biocompatible, bioerodable polymer which exhibits adhesive strength of about 600 to about 150,000 Pa, (b) a filler and (c) a bioactive agent. Further, this invention provides pressure sensitive adhesives for tissue repair comprising a terpolymer of an &agr;-hydroxycarboxylic acid which exhibits adhesive strength of about 600 to about 150,000 Pa.
The implant matrices and adhesives of this invention can be applied to the bone-contacting surfaces of prosthetic appliances (as a cement), or they can be inserted into and around bone defects and cavities or cartilage surfaces (as a filler). The matrix or adhesive biodegrades gradually. As it biodegrades, it is replaced by developing bone or cartilage tissue in a manner which permits a natural healing of the tissue. Thus, it provides an effective means for treating or repairing bone or cartilage.
When the matrix or adhesive further comprises a bioactive agent, it serves as a depot device for release of the bioactive agent. Release of the agent occurs as the matrix or adhesive biodegrades after implantation.
Many attempts have been made to develop a repair matrix that could facilitate bone or cartilage repair and also deliver bioactive agents such as growth factors. Such a matrix could be used instead of bone grafts. Thus far, only matrices comprised of natural products such as collagen have shown promise. Collagen, however, is difficult to manufacture and control in order to meet regulatory standards. In addition, surgeons are not satisfied with collagen matrices because they are difficult to form and/or handle.
Other approaches to replace bone grafts have included conventional bioresorbable polymers, ceramics such as tricalcium phosphate (TCP), natural polymers, such as collagen, proteoglycans, starches, hyaluronic acid and modified bone matrix. To date these efforts have only produced delivery matrices which (a) impede healing, (b) provoke negative tissue reactions, (c) cannot be sterilized, (d) are difficult to use or (e) cannot be manufactured to the satisfaction of regulatory bodies.
For example, one approach was to use conventional bioresorbable polymers such as polylactide-co-glycolide (PLG) to administer growth factors. It was very difficult, however, to combine PLG with the growth factor without inactivating the growth factor. Other disadvantages encountered with PLG were that, when it was implanted, it inhibited the bone healing response and occasionally caused aseptic sinus tract and inflammation and destroyed surrounding bone.
Another attempt to develop an effective bone repair matrix involved implanting a bone growth factor absorbed on a ceramic such as TCP. The problem with this approach was that the TCP particles migrated out of the defect area too quickly to deliver the growth factor effectively.
A major problem encountered with previously tried delivery systems is that the bioerodable material could not be mixed with the growth factor prior to the time of surgery. Mixing the delivery matrix with the bioactive material immediately prior to, or during, the surgery process is very awkward and can lead to inconsistent results.
The bioerodable matrices and adhesives of this invention solve several of the problems encountered with previous delivery systems. They are especially useful in the delivery of bioactive proteins such as growth factors because the polymer component dissolves in solvents which are compatible with proteins. Thus, it is possible to formulate the bioactive component in the polymer adhesive matrix in advance, i.e., well before a surgical procedure, under acceptable regulatory conditions, including sterilization of the product without inactivating the bioactive components. Quality control during the preparation of delivery systems using the present adhesive products is, therefore, greatly improved.
Other advantages of the polymer implant matrices and adhesives of this invention are that they are biocompatible and bioerodable in vivo. The term “biocompatible” means that the polymer is non-toxic, non-mutagenic and, at most, elicits only a minimal to moderate inflammatory reaction. The term “bioerodable” means that the polymer either degrades or is resorbed after implantation into products that are used by, or are otherwise eliminated from, the body by existing biochemical pathways.
The present matrices comprise polymers that are bioerodable within a period of from about three hours to about two years. This period can be varied, depending upon the desired application. A preferred period is from about one day to about one month; another preferred period is from about two weeks to about three months. The period for bioerosion is the time after which the polymer will no longer be detectable at the site of implantation, using standard histological techniques.
Thus, an important advantage of the present polymer implant matrices is that a second surgical procedure to remove the matrix is not required because it degrades with time, and its degradation products are absorbed by the body.
One required feature of certain of the adhesive bioerodable polymers useful in the improved matrices of this invention is their water solubility. They are soluble in water at about 0.01 to about 500 mg/mL of water at about 25° C. (ambient temperature). Typically, the polymers are soluble in water at about 0.1 to about 500 mg/mL of water. Preferably they are soluble at about 5 to about 400
Deng Z. David
Glancy Todd P.
Peterson Dale R.
Barnes & Thornburg
DePuy Orthopaedics, Inc.
Webman Edward J.
LandOfFree
Bioerodable polymeric adhesives for tissue repair does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Bioerodable polymeric adhesives for tissue repair, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Bioerodable polymeric adhesives for tissue repair will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3265287