Bioactive sol-gel compositions and methods

Compositions: ceramic – Ceramic compositions – Glass compositions – compositions containing glass other than...

Reexamination Certificate

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C501S039000, C501S057000, C501S058000, C501S063000, C106S035000, C623S016110

Reexamination Certificate

active

06171986

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to bioactive glass compositions, for example, used for filling bone defects, and bioactive compositions produced by a sol-gel process. The present invention also relates to various methods for making sol-gel bioactive glasses and methods of treatment using bioactive glasses.
BACKGROUND OF THE INVENTION
Sol-gel processes for making, bioactive glass using sol-gel technology are generally known. For example, U.S. Pat. No. 5,074,916 (the “'916 patent”), the subject matter of which is incorporated herein by reference, discloses sol-gel processing techniques used to produce alkali-free bioactive glass compositions based on SiO
2
, CaO and P
2
O
5
. The '916 patent discloses that by varying, the SiO
2
content, a range of hydroxyapatite production rates can be obtained. Also, varying the time of exposure to actual or simulated in vivo solutions permits use of a range of allowable proportions of SiO
2
. The sol-gel derived compositions disclosed in the '916 patent can be chosen to achieve target values for a thermal expansion coefficient, elastic modulus and volume electrical resistivity.
The processes and compositions described in U.S. Pat. No. 5,074,916 have certain disadvantages. For example, the process of the '916 patent does not provide for bioactive glasses having large pore sizes. This results in a relatively low rate of hydroxycarbonate apatite (“HCA”) development when the glasses are exposed to biological fluids and tissues. See “Effect of Texture on the Rate of Hydroxyapatite Formation on Gel-Silica Interface”, J. Am. Ceram. Soc., 78[9] 2463-68 (1995), the subject matter of which is herein incorporated by reference. Moreover, the resultant product lacks homogeneity, stability and can only be heated to a limited extent during preparation. Also, the resultant product lacks an acceptable level of resorbability.
Other examples of sol-gel processes can be found in Thomas, “Multicomponent Glasses From the Sol-Gel Process”, Noyes Publications edited by Lisa C. Klein of the Center for Ceramics Research, College of Engineering, Rutgers, Piscataway, New Jersey and “Sol-Gel Science—The Physics and Chemistry of Sol-Gel processing, Brinker et al., Academic Press Inc. These publication are also incorporated by reference.
Previous methods for preparing monoliths of bioactive glasses have also proven unsatisfactory. Earlier methods required the use of various toxic chemicals in an effort to avoid cracking of the monolith during drying. U.S. Pat. No. 4,849,378 (“the 378 patent”), incorporated herein by reference discloses a method of fabricating an ultraporous silicon dioxide containing gel monolith having a predetermined mean pore size by controlling temperature, duration and other conditions of aging. The '378 patent discloses that the use of a drying control chemical additive is important and formamide is the additive of choice. Similarly, U.S. Pat. No. 4,851,150 (“the '150 patent”) addresses drying control chemical additives for rapid production of large sol-gel derived monoliths. The '150 patent also discloses drying in a methanolic atmosphere. Both of these methods are unsatisfactory because they require the use of chemical additives.
Other early work in U.S. Pat. No. 5,076,980 (incorporated by reference) used drying under humidity environment and sintering under some gas atmosphere to make a sol-gel monolith. However, the focus of such procedures was the fabrication of crack-free and fully dense silica glass and the pore texture of the monolith was not mentioned. Moreover, this patent does not address the preparation of a bioactive glass.
Accordingly, it is an object of the present invention to provide a sol-gel process, particle and monolith that yield bioactive glasses used for bone grafting and filling osseous defects, having larger pore size at a given level of silicon dioxide in the final composition, faster HCA formation, better resorbability, and better homogeneity. It is further an object of the present invention to provide for precise control of rates of resorbtion.
SUMMARY OF THE INVENTION
The present invention is directed to a process for making bioactive glasses used, for example, for bone grafting including; preparing a reaction mixture (sol) capable of forming a gel, aging the reaction mixture, near equilibrium drying a gel resulting from the reaction mixture, and heating the near equilibrium-dried gel. The present invention is also directed to dried bioactive glass compositions and monolithic bioactive compositions having improved resorbability. The present invention is further directed to materials suitable for bone grafting, repairing of tissue defects and other orthopedic uses.


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Brinker, C. Jeffrey and Scherer W. Scherer. “Drying.”Sol-Gel Science, the Physics and Chemistry of sol-Gel Processing.pp. 500-503.
Brinker, C. Jeffrey and Schemer W. Schemer. “Hydrolysis and Condensation.”Sol-Gel Science, The Physics and Chemistry of Sol-Gel Processing,pp. 116-119.
Hoellrich, R. G., Chamberland, D. L., Stokes, K. E., McLoughling, S. W., and Wheeler, D. L. “In Vivo Evaluation of sol-Gel Bioglass.” (Part II: Mechanical Compression Strength at 4 Weeks).
Kokubo, T. et al., “Solutions able to reproduce in vivo surface-structure changes in bioactive glass-ceramic A-W3”,J. of Bio. Matls. Res.,v.24, pp. 721-734, 1990.
Pereira, Marivalda M., and Clark, Authur E., and Hench, Larry L. “Effect of Texture on the Rate of Hydroxyapatite Formation on Gel-Silica Surface,”J. Am. Ceram. Soc.,v78(9): pp. 2463-2468(1995).
Thomas, Ian M. “Multicomponent Glasses from the Sol-Gel Process,”Sol-Gel Technology for Thin Films, Fibers, Preforms, electronics, and specialty Shapes.pp. 1-15. (Rutgers-The State University of New Jersey). edited by Lisa C. Klein.
Wheeler, D. L. and Stokes, K. E. “In View Evaluation of Sol-Gel Bioglass.” (Part I: Histological Findings).

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