Synthetic resins or natural rubbers -- part of the class 520 ser – Synthetic resins – Processes of preparing a desired or intentional composition...
Reexamination Certificate
1998-01-05
2001-06-19
Low, Christopher S. F. (Department: 1653)
Synthetic resins or natural rubbers -- part of the class 520 ser
Synthetic resins
Processes of preparing a desired or intentional composition...
C522S149000, C523S407000, C524S068000, C525S063000, C525S071000
Reexamination Certificate
active
06248811
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a process for coating surfaces, preferably polymer substrates, with coating polymers, which owing to the presence of specific functional groups, are fixed bioactively and covalently, i.e., permanently, on the surfaces. The coatings are anti-bacterial and can, moreover, be formulated so as to inhibit or promote cell proliferation thereon. The invention also relates to articles having surfaces coated in this way for, inter alia, medical or biotechnical purposes.
2. Description of the Background
The colonization and multiplication of bacteria on surfaces is a phenomenon which is in general unwanted and is frequently associated with disadvantageous consequences. For instance, in the drinking water and beverage industry bacterial populations may lead to health hazards. Bacteria on or in packaging frequently cause food contamination, or even infections in the consumer. In biotechnical plants that are to be operated under sterile conditions, bacteria alien to the system constitute a considerable processing risk. Such bacteria may be introduced with raw materials or may remain in all parts of the plant if sterilization is inadequate. By means of adhesion, sections of the bacterial population may escape the normal liquid exchange entailed in rinsing and cleaning and can multiply within the system.
Bacterial colonies are also known in water treatment plants (for example for membrane desalination) or else in containers which are filled with dissolved or liquid undiluted organic substances and which have advantageous conditions for bacterial populations. Such microbial colonization can, to a considerable extent, lead to the blocking and/or corrosive destruction of the plant.
Particular importance is attached to protecting against bacterial adhesion and propagation in nutrition, in human care, especially in the care of the elderly, and in medicine. In the case of large-scale outlets serving food or drinks there are considerable risks especially when, rather than using disposable tableware with its attendant problem of waste, reusable tableware is employed that is not adequately cleaned. Also known is the harmful propagation of bacteria in hoses and pipes which conduct foods, as is their multiplication in storage containers and in textiles in a hot and damp environment, for example in swimming baths. Facilities of this kind are preferred habitats for bacteria, as are certain surfaces in areas through which many people pass, for example in public transport vehicles, hospitals, telephone boxes and schools and, especially, in public toilets.
In the care of the sick and elderly, the often reduced defenses of the those affected necessitate careful measures to counter infections, especially in intensive care wards and in the case of care at home.
Particular care is required in the use of medical articles and instruments in the case of medical investigations, treatments and interventions, especially when such instruments or articles come into contact with living tissue or with body fluids. In the case of long-term or permanent contact, especially in the case of implants, catheters, stents, cardiac valves and pacemakers, bacterial contamination can become a life-threatening risk to the patient.
Diverse attempts have already been made to suppress the colonization and propagation of bacteria on surfaces. In J. Microbiol. Chemoth. 31 (1993), 261-271 S. E. Tebbs and T. S. J. Elliot describe paint-like coatings with quaternary ammonium salts as antimicrobial components. It is known that these salts are dissolved out of the coating material by water, by aqueous or other polar media and by body fluids, and that their action is therefore short-lived. This applies equally to the incorporation of silver salts in coatings, as described in WO 92/18098.
T. Ouchi and Y. Ohya in Progr. Polym. Sci. 20 (1995), 211 ff., describe the immobilization of bactericidal active substances on polymer surfaces by means of covalent bonding or ionic interaction. In such cases, the microbicidal actions are frequently reduced markedly relative to the pure active substance. Heteropolar bonds often prove to be of insufficient stability. Furthermore, the killing of the microbes leads in general to unwanted deposits on the surfaces, which mask the subsequent bactericidal action and form the basis for a subsequent bacterial colonization.
W. Kohnen et al. in ZB1. Bakt. Suppl. 26, Gustav Fischer Verlag, Stuttgart-Jena-New York, 1994, pages 408 to 410, report that the adhesion of
Streptococcus epidermidis
on a polyurethane film is reduced if the film is pretreated by glow discharge in the presence of oxygen and is then grafted with acrylic acid.
In many medical applications it is not only important that the surfaces be kept free from bacteria; rather, colonization with cells also has a part to play. In modern medicine frequent use is made of exogenous articles in such a way that they come into medium- or long-term contact with tissue or body fluids. Examples are implants, such as pacemakers, stents and prostheses, and also suture materials, drainage hoses and catheters. Such articles may consist, inter alia, of metals, ceramic and/or polymers. These materials must be biocompatible, i.e., compatible with the tissue and/or with the tissue fluids with which they are in contact. Numerous processes have been disclosed which are intended to make polymers biocompatible or to improve their biocompatibility. One of these methods is the colonization of the polymer surfaces with human cells.
On the other hand, there are medical applications where colonization of the surface of such exogenous articles with human cells is extremely undesirable. For instance, cell colonization in the case of catheters applied intracorporally in the medium term (indwelling catheters) is just as harmful as in the case of cardiac valves or stents which are implanted for the long term. WO 94/16648 describes a process by means of which it is intended to prevent the adhesion and proliferation of cells on the surface of implanted eye lenses made from polymer material. According to EP 0 431 213, polymers are equipped with cell-repelling properties by rendering their surface hydrophilic using strong mineral acids. This leads to a reduction in the cell adhesion.
The subsequent chemical modification of polymer surfaces, however, is usually not uniform. In many cases there remain areas which have not been treated, or not sufficiently treated, which form starting points for cell colonization. Furthermore, the cell-repelling properties of the treated surfaces are in many cases not persistent.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide an improved process for the bioactive coating of surfaces by means of which surfaces can be kept substantially and persistently free from bacteria, for example cocci, in a physiologically compatible manner without thereby altering the mechanical properties of the treated materials or giving rise to any other of the disadvantages of the methods described above.
It is another object of the present invention to provide a process by means of which the antibacterial coatings may be formulated to additionally either inhibit or promote cell proliferation.
It has surprisingly been found that antibacterial, covalently fixed coatings may be prepared advantageously on the surface of substrates, especially polymer substrates, by grafting to a surface of a substrate a coating polymer which comprises, in copolymerized form,
(i) at least one monomer of the general formula (I):
R—(A)
a
in which R is a mono- or diolefinically unsaturated organic radical having the valence a,
A is a carboxyl group (—COOH), sulfuric acid group (—OSO
2
OH), sulfonic acid group (—SO
3
H), phosphoric acid group (—OPO(OH)
2
), phosphonic acid group (—PO(OH)
2
), phosphorous acid group (—OP(OH)
2
), a phenolic hydroxyl group, or a salt of one of these groups, and
a is 1, 2 or 3; and
(ii) at least one monomer which is sensitive to UV radiation.
A more complete appreciati
Helary Gerard
Jozefowicz Marcel
Mensing Britta
Migonney Veronique
Ottersbach Peter
Huels Aktiengesellschaft
Low Christopher S. F.
Lukton David
Oblon & Spivak, McClelland, Maier & Neustadt P.C.
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