Synthetic resins or natural rubbers -- part of the class 520 ser – Synthetic resins – Polymers from only ethylenic monomers or processes of...
Reexamination Certificate
1997-12-30
2002-04-02
Henderson, Christopher (Department: 1713)
Synthetic resins or natural rubbers -- part of the class 520 ser
Synthetic resins
Polymers from only ethylenic monomers or processes of...
Reexamination Certificate
active
06365692
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to water-insoluble polymers which promote cell proliferation and to a process for their preparation. The invention furthermore relates to the use of the water-insoluble polymers which promote cell proliferation for the production of products having a surface which promotes cell proliferation and for the production of products having a coating, of the polymer, which promotes cell proliferation. The invention moreover relates to products having a surface which promotes cell proliferation and products having a coating, of the polymer, which promotes cell proliferation. For numerous medical applications of materials such as polymers, ceramics and metals, for example as suture materials, stems, implants or prostheses, good compatibilities with the immune and complement system and the blood must be ensured. This property, which is often called biocompatibility, includes avoidance of degradation phenomena of the materials by physiological components, such as enzymes and macrophages.
2. Description of the Prior Art
An improved biocompatibility of substitute materials employed medically can be achieved in principle by colonization with human cells. The process described in EP 0 290 642 initially requires covalent bonding of an intermediate layer of so-called copolymers onto polymer surfaces functionalized by carboxyl, amino and hydroxyl groups. The biocompatibility sought in the material is then achieved by careful, extracorporeal colonization of the intermediate layer with endothelial cells.
WO 90/02145 describes, with the same aim, a process in which acrylic acid is grafted onto fluorine-containing polymer substrates by irradiation with a
60
Co source or a laser. After a series of chemical processes on the surface, controlled absorption of proteins takes place, which is followed by colonization with endothelial cells to establish the biocompatibility.
These processes are extremely time-consuming and cost-intensive and require the greatest care for a medical application, so that the endothelial cell layers applied extracorporeally are not damaged. It is furthermore not possible to allow the cell colonization and cell growth (cell proliferation) to be carried out by the body itself in vivo, since an undesirable thrombic reaction starts before the cell colonization.
Subsequent chemical modification of surfaces of polymeric materials with the known RGD sequence method (arginine-glycine-aspartic acid) is usually not uniform and/or standard. Untreated areas often remain, which are no longer available as starting points for cell colonization of the surface (G. Muller, Angewandte Chemie, 104 (1992) 341 et seq.).
From another technical field, according to U.S. Pat. No. 5,278,200, polymers which contain carboxylate and sulfonate groups in a ratio comparable to that of naturally occurring heparin are known. These polymers have anticoagulating properties with respect to platelets in the blood.
SUMMARY OF THE INVENTION
The present invention is therefore based on the object of improving cell proliferation on the surfaces of polymers. It has now been found, surprisingly, that water-insoluble polymers which contain carboxylate and sulfonate groups and are obtainable by free radical copolymerization of
one or more aliphatically unsaturated monomers containing carboxylate groups, or the correspondingly functionalized derivatives of the monomers, as component I with
one or more aliphatically unsaturated monomers containing sulfonate groups, or the correspondingly functionalized derivatives of the monomers, as component II and
a component III which comprises an aliphatically unsaturated monomer or several aliphatically unsaturated monomers, the correspondingly functionalized derivatives being converted into carboxylate and sulfonate groups after the copolymerization, are capable of promoting cell proliferation.
The adhesion and the growth of cells is thus improved in a physiologically tolerated manner on the polymers according to the invention.
The polymers according to the invention are thus particularly suitable for the production of implants in which growth of endogenous or non-differentiated cells is desired.
The present invention therefore relates to water-insoluble polymers which promote cell proliferation, contain carboxylate and sulfonate groups and are obtainable by free radical copolymerization of
one or more aliphatically unsaturated monomers containing carboxylate groups, or the correspondingly functionalized derivatives of the monomers, as component I with
one or more aliphatically unsaturated monomers containing sulfonate groups, or the correspondingly functionalized derivatives of the monomers, as component II and
a component III which comprises an aliphatically unsaturated monomer or several aliphatically unsaturated monomers,
the correspondingly functionalized derivatives being converted into carboxylate and sulfonate groups after the copolymerization.
The present invention furthermore relates to a process for the preparation of water-insoluble polymers, which promote cell proliferation and contain carboxylate and sulfonate groups, which comprises obtaining the polymers by free radical copolymerization of one or more aliphatically unsaturated monomers containing carboxylate groups, or the correspondingly functionalized derivatives of the monomers, as component I with one or more aliphatically unsaturated monomers containing sulfonate groups, or the correspondingly functionalized derivatives of the monomers, as component II and a component III which comprises an aliphatically unsaturated monomer or several aliphatically unsaturated monomers, the correspondingly functionalized derivatives being converted into carboxylate and sulfonate groups after the copolymerization.
The present invention moreover relates to the use of the water-insoluble polymers, which promote cell proliferation and contain carboxylate and sulfonate groups, for the production of products having a surface which promotes cell proliferation, and to the use of the water-insoluble polymers, which promote cell proliferation and contain carboxylate and sulfonate groups, for the production of products having a coating, of the polymer, which promotes cell proliferation.
The present invention furthermore relates to the use of the water-insoluble polymers, which promote cell proliferation and contain carboxylate and sulfonate groups, for the production of medical articles, in particular artificial blood vessels, having a surface which promotes cell proliferation.
The present invention moreover relates to the use of the water-insoluble polymers, which promote cell proliferation and contain carboxylate and sulfonate groups, for the production of medical articles of plastics, ceramics or metals having a coating, of the polymer, which promotes cell proliferation.
The present invention furthermore relates to the use of the water-insoluble polymers, which promote cell proliferation and contain carboxylate and sulfonate groups, for the production of artificial blood vessels having a coating, of the polymer, which promotes cell proliferation.
The present invention also relates to products having a surface, which promotes cell proliferation, of water-insoluble polymers, which promote cell proliferation and contain carboxylate and sulfonate groups.
Such products according to the invention are preferably medical articles, particularly preferably artificial blood vessels.
The present invention also relates to products having a coating, which promotes cell proliferation, of water-insoluble polymers, which promote cell proliferation and contain carboxylate and sulfonate groups.
Products having a coating, of the polymer according to the invention, which promotes cell proliferation are preferably medical articles, particularly preferably medical articles of plastics, ceramics or metals. Medical articles having a coating, of the polymer according to the invention, which promotes cell proliferation are preferably artificial blood vessels.
DESCRIPTION OF OF THE PREFERRED
Djavid Graciella
Hill Frank
Hill Friedrich Frank
Hill Henning Hinrich
Hilless by Regina Luise
Alston & Bird LLP
Henderson Christopher
Hill Friedrich Frank
Hill Henning Hinrich
Hilless by Regina Luise
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