Compositions: ceramic – Ceramic compositions
Reexamination Certificate
1998-03-19
2001-11-27
Koslow, C. Melissa (Department: 1755)
Compositions: ceramic
Ceramic compositions
C501S123000, C106S035000, C623S023610, C623S023560, C423S306000, C423S307000, C423S308000, C423S311000, C423S312000, C423S314000, C423S315000, C423S316000
Reexamination Certificate
active
06323146
ABSTRACT:
FIELD OF THE INVENTION
This invention is directed to a synthetic biomaterial compound based on stabilized calcium phosphates and more particularly to the molecular, structural and physical characterization of this compound. This compound which in the alternative may be referred to as Skelite,™ has applications in the treatment of various bone related clinical conditions such as for the repair and restoration of natural bone compromised by disease, trauma or genetic influences.
BACKGROUND OF THE INVENTION
Bone is a complex mineralizing system composed of an inorganic or mineral phase, an organic matrix phase, and water. The inorganic mineral phase is composed mainly of crystalline calcium phosphate salts while the organic matrix phase consists mostly of collagen and other noncollagenous proteins. Calcification of bone depends on the close association between the organic and inorganic phases to produce a mineralized tissue.
The process of bone growth is regulated to meet both structural and functional requirements. The cells involved in the processes of bone formation, maintenance, and resorption are osteoblasts, osteocytes, and osteoclasts. Osteoblasts synthesize the organic matrix, osteoid, of bone which after calcium phosphate crystal growth and collagen assembly becomes mineralized. Osteocytes regulate the flux of calcium and phosphate between the bone mineral and the extracellular fluid. Osteoclasts function to resorb bone and are essential in the process of bone remodeling. Disturbing the natural balance of bone formation and resorption leads to various bone disorders. Increased osteoclast activity has been demonstrated to lead to bone disease characterized by a decrease in bone density such as that seen in osteoporosis, osteitis fibrosa and in Paget's disease. All of these diseases are a result of increased bone resorption.
In order to understand the mechanisms involved which regulate bone cell function, it is important to be able to assess the normal function of bone cells and also the degree of perturbation of this activity in various bone diseases. This will lead to the identification of drugs targeted to restore abnormal bone cell activity back to within normal levels. Together with the identification of the etiology of abnormal and normal bone cell activity and the assessment of this activity, is the desire and need to develop compositions and methods for the treatment of abnormal bone cell activity, as a result of disease, surgical removal or physiological trauma all of which lead to bone tissue loss. Therapeutics which provide for the replacement and repair of bone tissue, such as with the use of bone implants, are highly desired.
Several groups have attempted to provide compositions suitable for the therapeutic replacement of bone tissue. U.S. Pat. No. 4,871,578 discloses a process for the formation of a non-porous smooth coating of hydroxyapatite suitable for implant use. U.S. Pat. No. 4,983,182 discloses a ceramic implant which comprises a sintered body of zirconia and a coating of &agr;-TCP and zirconia, or hydroxyapatite and zirconia. U.S. Pat. No. 4,988,362 discloses a composition for the fusion of a bioceramic to another bioceramic. U.S. Pat. No. 4,990,163 discloses a coating used for the production of bioceramics which consist of &agr;-TCP and &bgr;-TCP. Although these different compositions may be used as biocompatible coatings for implants and the like, none of these compositions have been demonstrated to participate in the natural bone remodeling process. Furthermore, none of the prior compositions developed, can be manipulated to reliably produce a range of films, thicker coatings and bulk ceramic pieces which share a common composition and morphology which leads to similar bloactive performance in vivo and in vitro.
It has therefore long been the goal of biomaterials researeh in the field of orthopedics to develop synthetic structures exhibiting comprehensive bioactivity. Bioactive synthetic substrates and scaffolds capable of incorporation into the natural process of bone remodeling are of interest in applications which include not only in vitro bone cell assays (Davies, J., G. Shapiro and B. Lowenberg.
Cells and Materials
3(3) 1993; pp. 245-56), but also in vivo resorbable bone cements (Gerhart, T., R. Miller, J. Kleshinski and W. Hayes.
J Biomed Mater Res
22 1988; pp. 1071-82 and Kurashina, K., H. Kurita, M. Hirano, J. deBlieck, C. Klein and K. deGroot.
Journal of Materials Science: Materials in Medicine
6 1995; pp. 340-7), implantable coatings which enhance the bonding of natural bone to the implant (Tofe, A., G. Brewster and M. Bowerman.
Characterization and Performance of Calcium Phosphate Coatings for Implants
edited by E. Horowitz and J. Parr. Philadelphia: ASTM, pp. 9-15 (1994), various forms of implantable prostheses and bone repair agents (Tolman, D. and W. Laney.
Mayo Clin Proc
68 1993; pp. 323-31 and Levitt, S., P. Crayton, E. Monroe and R. Condrate.
J Biomed Mater Res
3 1969; pp. 683-5), and ex vivo tissue engineering (Kadiyala,S., N. Jaiswal, S. Bruder.
Tissue Engin
3(2) 1997; pp. 173-84). The prime objective for such materials in vivo is to combine the stimulation of osteogenic activity in associated bone tissues for optimum healing, with the capability to be progressively resorbed by osteoclasts during normal continuous remodeling (Conklin, J., C. Cotell, T. Barnett and D. Hansen.
Mat Res Soc Symp Proc
414 1996; pp. 65-70). In vitro, related functions are to provide standardized laboratory test substrates on which osteoclast resorptive function or osteoblast production of mineralized bone matrix can be assessed and quantified (Davies, J., G. Shapiro and B. Lowenberg.
Cells and Materials
3(3) 1993; pp. 245-56). Such substrates must be stable and insoluble in the biological environment until acted upon by osteoclasts, the specific bone mineral resorbing cells.
While calcium hydroxyapatite (Ca
5
(OH)(PO
4
)
3
or HA) is the primary inorganic component of natural bone (Yamashita, K., T. Arashi, K. Kitagaki, S. Yamada and T. Umegaki.
J Am Ceram Soc
77 1994; pp. 2401-7), trace elements are also present (
Biominerals
edited by F. Driessens and R. Verbeeck. Boston: CRC Press (1990). Calcium hydroxyapatite is but one of a number of calcium-phosphorous (Ca—P) compounds which are biocompatible. Others include octacalcium phosphate (Brown, W., M. Mathew and M. Tung.
Prog Crys Growth Charact
4 1981; pp. 59-87) and both phases of tricalcium phosphate (Ca
3
(PO
4
)
2
or &agr;-TCP/&bgr;-TCP) (Elliott
J. Structure and Chemistry of the Apatites and Other Calcium Orthophosphates
New York: Elsevier (1994). Compounds, particularly HA, may show differing degrees of stoichiometry with the Ca/P ratio ranging from 1.55 to 2.2 (Meyer, J. and B. Fowler.
Inorg Chem
21 1997; pp. 3029-35). Such materials can be artificially created by conventional high temperature ceramic processing (Santos, R. and R. Clayton.
American Mineralogist
80 1995; pp. 336-44) or by low temperature aqueous chemistry (Brown, P., N. Hocker and S. Hoyle.
J Am Ceram Soc
74(8) 1991; pp. 1848-54 and Brown, P. and M. Fulmer.
J Am Ceram Soc
74(5) 1991; pp. 934-40). Most of such artificial materials show good biocompatibility in that bone cells tolerate their presence with few deleterious effects, and indeed enhanced bone deposition may occur (Ito, K., Y. Ooi.
CRC Handbook of Bioactive Ceramics
edited by T. Yamamuro, L. Hench and J. Wilson. Boca Raton, Fla.: CRC Press, pp. 39-51 (1990) and Ohgushi, H., M. Okumura, S. Tamai, E. Shors and A. Caplan.
J Biomed Mater Res
24 1990; pp. 1563-70). Currently, the most recognized medical application of calcium phosphates is the coating of implantable prosthetic devices and components by thermal or plasma spray to render the surface osteoconductive. It has been noted that Ca—P ceramics which are stable in biological environments are often a mixture of individual compounds (LeGeros, R., G. Daculsi.
CRC Handbook of Bioactive Ceramics
edited by T. Yamamuro, L. Hench and J. Wilson. Boca Raton: CRC Press, (1990)). Howev
Langstaff Sarah Dorthea
Pugh Sydney M.
Sayer Michael
Smith Timothy J. N.
Alston & Bird LLP
Koslow C. Melissa
Millenium Biologix Inc.
LandOfFree
Synthetic biomaterial compound of calcium phosphate phases... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Synthetic biomaterial compound of calcium phosphate phases..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Synthetic biomaterial compound of calcium phosphate phases... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2618139