Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Implant or insert
Reexamination Certificate
2000-09-29
2004-02-03
Naff, David M. (Department: 1651)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Implant or insert
C424S444000, C424S094100, C435S182000, C514S002600, C530S817000
Reexamination Certificate
active
06685957
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to a fibrous polymer loaded with one or more bioactive agents and to a process for preparing the fibrous polymer loaded with the bioactive agent or agents. The invention further relates to the use of the polymer loaded with the bioactive agent or agents as a scaffold for tissue engineering.
2. Description of the Related Art
The development of biological substitutes, that can restore or improve tissue function, is a rapidly evolving interdisciplinary field in science. New tissues can be engineered from living cells and three dimensional scaffolds. The function of the scaffold is to provide structural integrity and space for growing tissue, and to guide tissue formation. For this purpose, scaffolds are needed with a high porosity and a high surface area. Ideally, the scaffold delivers bioactive factors which modulate cellular behavior such as proliferation, migration and adhesion. For example, it has been shown that release of bone morphogenetic protein (rhBMP-2) from biodegradable porous scaffolds stimulated growth of bone into the scaffolds in vivo (see K. Whang et al., J. Biomed. Mater. Res. 42 (1998) 491-499).
Macroporous scaffolds for tissue engineering have been fabricated by various techniques, including fiber bonding (see A. G. Mikos et al., J. Biomed. Mater. Res. 27 (1993) 183-189), solvent casting/salt-leaching (see A. G. Mikos et al., Biomaterials 14 (1993) 323-330), phase separation (see H. Lo et al., J. Biomed. Mater. Res. 30 (1996) 475-484) and emulsion freeze-drying (see K. Whang et al., Polymer 36 (1995) 837-842). Often, the methods used to prepare macroporous structures are not suitable for incorporation of labile proteins and other bioactive compounds, due to the high temperatures used, exposure to organic solvents, or the need for removal of the porogens.
Recently, Whang et al. (see J. Biomed. Mater. Res. 42 (1998) 491-499) developed an emulsion freeze-drying process to overcome these drawbacks in the incorporation of proteins into porous matrices. This method consists of creating an emulsion from a poly(lactide-co-glycolide) (PLG) solution in methylene chloride and an aqueous protein solution. Subsequently, the emulsion is quenched in liquid nitrogen, and methylene chloride and water are removed by freeze-drying. The large pores in the resulting matrices are formed by the dispersed water phase and since the proteins are also dissolved in the water phase, this implies that the proteins are located within the large interconnected pores. This might limit the possibilities to obtain slow release of proteins. Furthermore, it appeared that the type of protein influenced the ultimate structure of the pores. In case of bovine serum albumin (BSA) loaded scaffolds, the median pore size was 65 &mgr;m, while incorporation of rhBMP-2 resulted in a median pore size of only 9 &mgr;m, which is probably too small for optimal bone-ingrowth.
The present invention aims to provide a method for preparing a fibrous polymer loaded with one or more bioactive agents. Further, in particular in view of the application of polymers as scaffold for tissue engineering, it is often desired to be able to incorporate (bioactive) additives in a solid body that constitutes the scaffold. For instance, the presence of growth factors may be very much desired in order to enhance cell growth or differentiation. As many of these bioactive additives are very sensitive compounds, the need for working under mild conditions becomes even more important. It is particularly desired that the method can be performed under such mild conditions that the biologic activity of the bioactive agent is essentially not deteriorated during the carrying out of the method. Further, it is desired that the bioactive agent can be homogeneously distributed throughout the polymer.
SUMMARY OF THE INVENTION
Surprisingly, it has now been found that a wet spinning technique is highly suitable for achieving the above goals. Accordingly, the invention specifically relates to a process for preparing a polymer loaded with one or more bioactive agents comprising the steps of:
a) providing a solution of the polymer in a suitable first solvent;
b) adding an aqueous solution of the bioactive agent or agents to the polymer solution to obtain a water-in-oil emulsion;
c) immersing the water-in-oil emulsion in a suitable second solvent by injecting the emulsion through a nozzle into the second solvent;
d) allowing the first solvent to migrate into the second solvent to obtain a solid, fibrous polymer loaded with the bioactive agent or agents.
REFERENCES:
patent: 4576817 (1986-03-01), Montgomery et al.
patent: 5096585 (1992-03-01), Nguyen
patent: 5151227 (1992-09-01), Nguyen et al.
patent: 0 830 859 (1998-03-01), None
patent: 0 891 783 (1999-01-01), None
van de Witte et al., “Formation of porous membranes for drug delivery systems,”J. Controlled Release, 24:61-78 (1993).
Bezemer Jeroen Mattijs
Feijen Jan
Grijpma Dirk Wybe
van Blitterswijk Clemens Antoni
Banner & Witcoff , Ltd.
Chienna B.V.
Naff David M.
LandOfFree
Preparation of fibrous polymer implant containing bioactive... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Preparation of fibrous polymer implant containing bioactive..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Preparation of fibrous polymer implant containing bioactive... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3338506