CA2259073A1 - Bioactive and hydrophilic coating of polymeric substrates - Google Patents

Abstract

Disclosed is a process for forming a hydrophilic and bioactive coating on a surface of a polymer substrate, in which a hydrophilic or hydrophilized polymer substrate is treated with a polyalkyleneimine as a primer or with ammonia plasma, and a hydrophilic, bioactive coating polymer that contains (a) a carboxyl or carboxylate group, (b) a sulfonic acid or sulfonate group or (c) a sulfuric acid ester or sulfate group is applied to this pretreated substrate. The coated substrate can be used for technical, medico-technical, hygienic, or biotechnical purposes.

Description

Bioactive and Hydrophilic Coating of Polymer Substrates Field of Invention The present invention relates to a process for forming a hydrophilic and bioactive coating on a surface of a polymer substrate, to a product with a substrate coated in this way.
Prior Art Generally, colonization and proliferation of bacteria on surfaces is an unacceptable phenomenon that is frequently linked to detrimental consequences. Bacterial populations in drinking water and beverage-production equipment can lead to diminished quality that poses a threat to health. Bacteria in and on packaging frequently cause foodstuffs to spoil or even give rise to infections in consumers. In biotechnical systems that are to be operated so as to be sterile, bacteria that are foreign to the system pose a considerable risk from the standpoint of process technology. Such bacteria can be introduced with raw materials, or can remain in a11 parts of the system as a consequence of inadequate or improper sterilization. Some elements of the bacterial population can remain invulnerable to the exchange of liquids during flushing and cleaning processes because of adhesion, and then multiply within the system.
In addition, bacterial colonies can be found in water-treatment plants (used, for example, for desalination by membranes) or in tanks filled with dissolved or liquid, undiluted organic substances and provide good conditions for bacterial populations. Such microbial contents can lead to extensive blockages and/or corrosion damage in the plant.
Protection against bacterial adhesion is especially important in nutrition, nursing (particularly geriatric nursing), and medicine. In the case of large-scale food preparation or if large quantities of beverages are dispensed, there are considerable risks if, in order to reduce waste, disposable containers are not used, and reusable containers are insufficiently washed. The harmful spread of bacteria in hoses and pipes that convey foodstuffs is as well-known as the proliferation in storage tanks and in textiles, in a warm and moist environment, e.g., in baths. Such facilities are preferred living spaces for bacteria, as are certain surfaces in areas heavily used by the public, such as hospitals, telephone call boxes, schools and, in particular, public toilets.
As far as geriatric and sick nursing is concerned, the patients' resistance, which is frequently low, demands special measures to prevent infections, particularly in intensive care situations and in the case of home nursing.
Particular care is required when medical articles and equipment are used during medical examinations, treatments, and surgical procedures, particularly if such articles or equipment come into contact with living tissue or body fluids.
In the case of long-term or permanent contact, as seen, for example, in the case of implants, catheters, stems, cardiac valves, and cardiac pacemakers, bacterial contamination can become a life-threatening risk for the patients.
Many attempts have already been made to suppress surface

- 2 -colonization and proliferation of bacteria. S.E. Tebbs and T.S.J. Elliot, writing in J. Microbio. Chemoth, 31 (1993), pp.
261-271, describe lacquer-like coatings with quaternary ammonium salts as components with an antimicrobial action. It is a known fact that these salts are dissolved out of the coating material by water, aqueous or other polar media, and body fluids, and that they remain effective for only a limited time. This also applies to the incorporation of silver salts in coatings, as described in WO 92/18098.
T. Ouchi and Y. Ohya, writing in Progr. Polym. Sci., 20 (1995), 211 et seq., describe the immobilization of bactericides on polymer surfaces by covalent bonding or ionic interactions. In such cases, the germicidal effects are often significantly reduced vis-a-vis the pure substances. Hetero-polar compounds are frequently not sufficiently stable.
Furthermore, as a rule, killing the germs leads to undesirable deposits on the surfaces, and these mask the further bactericidal effect and form the basis for subsequent bacterial colonization.
W. Kohnen, et al. ( Zbl. Bakt. Suppl., 26, Gustav Fischer Verlag, Stuttgart-Jena-New York, l994, pp. 408-410) report that the adhesion of Staphylococcus epidermidis on a polyurethane film is reduced if the film is pretreated with a corona discharge in the presence of oxygen, and grafted with acrylic acid.
As discussed, it is important that when medical articles and equipment are used during medical examinations, treat-ments, and surgical procedures, any bacterial contamination of

- 3 -such articles and equipment be prevented. With many such articles and items of equipment, which come into contact with living tissue or body fluids over the mid-term or the long-term, any adhesion and proliferation of the bodies own cells is also highly undesirable. Thus, cellular colonies that occur with medium-term catheters that are applied intra corporally are just at injurious as long-term, implanted stem s or cardiac valves.
In addition, the transparency of intra ocular lenses can deteriorate continuously as a result of cellular colonization.
A number of procedures are intended to prevent cellular colonization by the incorporation of certain metals or metallic salts in the holders used for intraoccular lenses;
the effect achieved is in most instances incomplete and not lasting. WO 94/16648 describes a process intended to prevent cellular proliferation on the surfaces of intra occular lenses that are of polymer material.
EP 0 431 213 describes how cell-repellant properties are to be imparted to polymers by hyrophilising their surfaces with strong mineral acids. However, in most instances, the long-lasting chemical modification of polymer surfaces is not even. As a rule, there are places that are treated inadequately or not at a11, and these act as starting points for cellular colonization. In addition, the cell-repellant properties of the surfaces treated in this way are frequently not lasting.
On the other hand, for certain applications it is desirable to have objects that have bacterio-repellant

- 4 -surfaces but still encourage cellular colonization. This is so, for example, for a number of equipment types used for medical examinations, treatments, and surgical procedures, and similarly for many prostheses that are meant to become incorporated into the tissue within which they have been implanted. Such devices and prostheses as artificial hip joints or teeth are frequently of polymer-coated materials such a titanium.
Finally, materials used for devices and apparatuses that come into contact with body fluids such as blood or lymph, or with tissue, must be compatible with their alien environment.
Hemocompatibility is an important and highly desirable characteristic. To the highest degree possible, the materials must possess anti-thromboplastic properties.
Thus, there are different, and in some instances mutually exclusive, demands made on the bioactive characteristics of the surfaces of polymers used in medical applications. They must always be bacterio-repellant and compatible with body fluids and tissue, although--if so desired--they should either be cellulostatic or promote cellular proliferation.
It is attempted, according to the present invention, to develop an improved process for coating surfaces, so as to render a surface of an article permanently hydrophilic and bioactive, namely bacterio-repellant and hemocompatible (anti-thromboplastic), and compatible with body fluids and tissue, and be cellulostatic or else promote cellular proliferation, as may be desired, without any modification of the mechanical properties of article so treated or without causing any other

- 5 -disadvantages when this is done.
Summary of the Invention One aspect of the present invention provides a process for forming a hydrophilic and bioactive coating on a polymer surface of a substrate of an article, in which a hydrophilic or hydrophilized polymer substrate is treated with a polyalkyleneimine as a primer, and a hydrophilic, bioactive coating polymer that contains (a) a carboxyl or carboxylate group, (b) a sulfonic acid or sulfonate group or (c) acidic sulfuric acid ester or sulfuric acid ester sulfate group is applied to this pretreated substrate.
In one alternative version of the process, the polymer substrate may be treated with ammonia-plasma instead of the polyalkyleneimine, when the polymer substrate does not have to be hydrophilic or hydrophilized.
A feature common to both versions of the process is that base groups that enhance adhesion of the hydrophilic bioactive coating polymer are formed by treating the substrate.
Another aspect of the present invention provides the product (i.e., article), which comprises a polymer substrate having a surface that has been hydrophilically and bioactively coated by the process mentioned above.
The coating polymer must have at least one of the groups named above. All or some of the acid groups can be converted into salts by treatment with a base such as caustic soda. So, for example, a carboxyl or carboxylate group can be present alone or as a mixture. A group containing sulfur can be present in addition to the carboxyl or carboxylate group, or

- 6 -in place thereof. Coating polymers that have only sulfuric acid ester sulfate groups (i.e., neutralized sulfuric acid ester groups) or those that contain carboxyl and/or carboxylate groups, as well as sulfonate groups, are examples.
If the hydrophilic or hydrophilized polymer substrate is pretreated with a polyalkyleneimine, its adhesion to the substrate is particularly strong if the substrate has acid groups, for example, carboxyl, sulfonic acid, or acid sulfuric acid ester groups. Very possibly, this strong adhesion can be attributed to ionic bonds that form between the polyalkylene-imine and the substrate. The acid groups in the polymer substrate may be contained in monomers that have been polymerized to produce the polymer, or they may have been created by surface treatment of standard polymers without polymerized acid groups. Such surface treatments, which have a simultaneous hyrophilising effect, are described below.
The coating of polymer substrates that contain hydrophilic or hydrophilized acid groups with polyalkyleneimine as a primer for the bioactive layer is a preferred embodiment of the process according to the present invention. The polyalkylene-imine itself adheres surprisingly strongly to the hydrophilic or hydrophilized polymer substrate if this has no acid groups.
If the hydrophilic, bioactive polymer coating layer contains acid groups, this layer is in its turn bonded sonically and thus especially strongly to the polymer substrate that has been treated with a polyalkyleneimine or with ammonia plasma. Even hydrophilic, bioactive coating polymers that contain only carboxylate, sulfonate, or acid sulfuric acid ester sulfate groups adhere remarkably strongly to the polymer substrate that has been pretreated with a polyalkyleneimine or ammonia plasma.
EP 0 603 987 A1 describes a hydrophilic-anionic or hydrophilic-cationic surface layer on a hydrophobic polymer, such as polysulfone, polyamide, or polyester, and a process for manufacturing this. The layer consists of a complex that results from one or more water-soluble cationic polymers and/or one or more water soluble cationically active surfactants, and one or more anionic polymers and/or one or more anionically active surfactants, the ratio of cationic to ionic groups in the complex being other than 1. The layer that is applied is described as being adsorptively adhesive.
The cationic polymers that are listed include polyethylene-imine. In addition, it is said that, as an option, ionic working substances can also be bonded. In contrast to the teachings of EP 0 603 987 A1, however, the process according to the present invention starts from hydrophilic or hydro-philized surfaces of substrates made of polymers. This process creates a coating layer that adheres much more strongly than a coating on a hydrophobic polymer substrate under otherwise equal conditions. The polyalkyleneimine that is applied preferably adheres sonically instead of absorp-tively, and thus particularly strongly, and a coating polymer that contains at least one of the cited groups is applied to the polyalkyleneimine; this, too, adheres sonically, and thus particularly strongly, provided that it contains acid groups.
_ g _ Advantages of the Invention The substrates coated according to the present invention display a remarkable combination of advantageous properties and outstanding physiological compatibility. They exhibit a high degree of hemocompatibility, and reduce the adhesion and proliferation of bacteria to a very great extent and over long time periods. Bacteria affected by this effect are, amongst others, Staphylococcus aureus, Staphylococcus epidermis, Streptococcus pyogenes, Klebsiella pneumoniae, Pseudomonas aeroginosa, and Escherichia coli. In many instances, cellular proliferation, for example of fibroblasts and endothelial cells such as human umbilical cells, is also inhibited. The special conditions under which a coating is bacterio-repellant and at the same time promotes the proliferation of cells, will be discussed below. Most polyalkyleneimines are non-toxic at the concentrations that are used, so that the coated substrates are also suitable for medical applications. The treatment of the polymer substrates with ammonia plasma entails no toxicological risk if any toxic monomers or dissolvable fragment molecules are removed by extraction after the coating process.
Description of Preferred Embodiments of the Invention 1. The polymer substrates In the embodiment of the process according to the present invention employing a polyalkyleneimine as a primer, surfaces of the substrates made of polymers should be hydrophilic, i.e, they contain hydrophilic groups in bulk from their production, or have been surface hydrophilized.
_ g _ In contrast to this, in the alternative embodiment, which involves pretreatment with ammonia plasma, the polymer substrates do not have to be hydrophilic or hydrophilized, and can be hydrophobic. Non-hydrophilic polymer substrates are, however, hydrophilized by the ammonia plasma pretreatment.
The polymer substrates can be of great variety, of geometric forms, for example, panels, foils, tubes or hoses, depending on the intended use of the particular article.
1.1 Hydrophilic polymer substrates In contrast to subsequently hydrophilized standard polymers, which will be discussed below, the hydrophilic polymers are special products, some of which are, however, available commercially. Suitable hydrophilic polymers are homopolymers from hydrophilic vinyl monomers that preferably have acid groups, or sufficiently hydrophilic copolymers that are made from hydrophilic vinyl monomers that preferably have acid groups and hydrophobic vinyl monomers. Preferred, amongst the hydrophobic vinyl monomers, are for example, vinyl chloride, ethylene, propylene, 1-butene, 1-octene, isoprene, styrene, a-methyl-styrene, 2- and 4-vinyl toluene, 2-ethyl-hexylacrylate, tetrafluorethylene, methylmethacrylate, methacrylamide, 1,3-butadiene, vinyl pyridine, vinylidene chloride, and vinyl acetate.
At 20~C, suitable hydrophilic vinyl monomers are at least 1%-wt, preferably at least 10%-wt, and in particular at least 40%-wt soluble in water, relative in each instance to the total amount of a solution. The acid groups that may be contained in the hydrophilic polymers are preferably carboxyl groups and sulfonic acid groups and their salts. The following are examples of suitable hydrophilic monomers:
acrylic acid and derivatives thereof, for example, acrylamide, N,N,-dimethylacrylamide, acrylonitrile, methacrylate, 2-hydroxyethylacrylate, 2-hydroxypropylacrylate, 2-methoxy-ethylacrylate, 2-ethoxyethylacrylate, 4-hydroxybutyl-acrylate, and 1,4-butanedioldiacrylate, as well as methacrylic acid and its corresponding derivatives; carboxylic acid vinyl derivatives such as vinyl acetate, N-vinylacetamide, and N-vinylpyrrolidone; vinyl sulfonic acids and their alkali salts, such as sodium vinyl sulfonate; alkenylarylsulfonic acids and their alkali salts, such as o- and p-styrenesulfonic acid and sodium styrenesulfonate, vinyl ethers such as vinyl methylether, vinyl ethylether, vinyl glycidylether, diethyleneglycoldivinylether, and vinyl-n-butylether; vinyl ketones, such as vinyl methylketone, vinyl ethylketone, and vinyl-n-propylketone; vinyl amines, such as N-vinyl-pyrrolidine; polyalkylene compounds with end-position allyl-, vinyl-, acryl-, or methacryl groups, such as ethoxy-tetraethoxyethyl acrylate or methacrylate, n-propoxydodeca-ethyleneethylvinylether, polyethyleneglycolmonoacrylates with molar weights from 600 or 1200, poly(ethylene/propylene)glycol-monomethacrylatess with molar weights from 400 and 800, as well as allyloxyoctapropylene-oxyethanol; sugar derivatives such as vinyl-substituted arabinoses or acryloylized hydroxypropyl cellulose; and functionalized polyalkyleneglycols, such as triethylene-glycoldiacrylate or tetraethyleneglycoldiallylether.

In order to manufacture hydrophilic copolymers from hydrophilic and hydrophobic comonomers, the hydrophilic vinyl monomers should at the least be used in a quantity such that the contact angle, measured at 25~C using the method described by R.J. Good, et al (which will be described below), is <40~, and advantageously <30~. Such a copolymer is considered to be hydrophilic in the sense of the present invention. Homo-polymers or copolymers that are built up exclusively from hydrophilic vinyl monomers, also satisfy this requirement. If necessary, the proportion of acid groups should be so large that the cationic primer is effectively bonded ionically, which is already the case at low concentrations. It is expedient that the molar proportion of vinyl monomers with acid groups in the copolymer amounts to at least 10 mol-%.
1.2 Hydrophilized polymer substrates A large number of options with respect to the mechanical and other properties of the polymer substrate are available as the hydrophobic standard polymers, which are available in large numbers. They are then hydrophilized. Suitable standard polymers include homopolymers and copolymers, for example polyolefines or polydienes such as polyethylene, polypropylene, polyisobutylene, polybutadiene, polyisoprene, natural rubbers and polyethylene-co-propylene; polymers that contain halogen, such as polyvinylchloride, polyvinylidene-chloride, polychloroprene, polytetrafluorethylene, and polyvinylidenefluoride; polymers and copolymers of vinylaromatic monomers, such as polystyrene, polyvinyltoluene, polystyrene-co-vinyltoluene, polystyrene-co-acrylonitrile, polystyrene-co-butadiene-co-acrylonitrile, polystyrene-co-ethylene-co-1-butene); poly(styrene-co-ethylene-co-2-butene), polycondensates, for example, polyesters such as polyethylene-t.erephthalate and polybutyleneterephthalate; polyamides, such as polycaprolactam, polylaurinlactam, and the polycondensate of adipinic acid and hexamethylenediamine; polyether block amides, for example, of laurinlactam and polyethyleneglycol with, on average, 8, 12, or 16 ethyleneoxy groups; in addition, poly-urethanes, polyethers, polycarbonates, polysulfones, polyether-ketones, polyesteramides and polyesterimides, polyacrylnitrile, polyacrylates and polymethacrylates, and silicones. Blends of two or more polymers or copolymers can also be hydrophilized using this process, as can combinations of different plastics that can be joined to each other by adhesion, welding, or smelting, including the transition areas.
The surfaces of the substrates can be hydrophilized by a number of methods, and in the majority of cases can be provided with acid groups at the same time. It is expedient that they first be cleansed of any oils, greases, or other impurities that may be adhering to them, by using a solvent.
The following hyrophilizing methods are known:
The hydrophilization of standard polymers without groups that are sensitive to W irradiation can best be effected by means of W irradiation, for example, in the wavelength range from 100 to 400 nm, preferably from 125 to 310 nm. Particularly good results have been obtained with largely monochromatic, continuous irradiation, such as that generated by excimer W

radiators (Heraeus Co., Kleinostheim, Germany), for example with F2, Xe2, ArF, XeCl, KrCl, and KrF as the lamp medium.
But other sources of radiation, such as mercury vapour lamps with wide-spectrum radiation and radiation bands in the visible range are suitable, providing they emit a considerable proportion of radiation in the cited radiation ranges. It has been shown that the presence of a small quantities of oxygen is advantageous. The preferred oxygen partial pressure is between 2x10-5 and 2x10-2 bar. One can work, for example, in a vacuum of 10-4 to 10-1 bar, or using an inert gas such as helium, nitrogen, or argon, with an oxygen content of 0.02 to per mille. The optimal duration of radiation will depend on the polymer substrate, the composition of the ambient gas medium, the wavelength of the radiation, and the power of the radiation source, and can be ascertained without difficulty by prior testing. In general, the substrate is irradiated for a period of 0.1 seconds to 20 minutes, in particular for 1 second to 10 minutes. Given these brief periods of irradiation, the polymer substrate will only heat up a little, 20 and no undesirable reactions, which could result in damage to the exposed surfaces, occur even with irradiation with wavelengths at the hard end of the cited additional range at irradiation times that are correspondingly brief.
(2) The hydrophilization can also be carried out by high-frequency or microwave plasma ( e.g., Hexagon*, Techics Plasma, 85551 Kirchheim, Germany) in an air, oxygen, nitrogen or argon atmosphere. In general, exposure times range from 30 * Trade-mark seconds to 30 minutes, preferably 2 to 10 minutes. The energy input is between 100 W to 500 W, preferably between 200 W and 300 W, for laboratory equipment.
(3) In addition, corona equipment (SOFTAL, Hamburg, Germany) can also be used for hydrophilization. In this case, the exposure times range from 1 second to 10 minutes, preferably from 1 to 60 seconds.
(4) Hydrophilization by electron or gamma rays (e.g., from a cobalt-60 source) permits short exposure times that generally amount to 0.1 to 60 seconds.
(5) Flame treatments of the surfaces also result in hyrophil-ization. Suitable apparatuses, in particular those with a barrier flame front, can be built quite simply, or can be obtained, for example, from ARCOTEC, 71297 Monsheim, Germany.
They can be operated with hydrocarbons or hydrogen as the combustion gas. In each case, it is essential to avoid harmful overheating of the substrate; this can be achieved by close contact with a cooled metal surface on the substrate surface that is remote from the flaming side.
hydrophilization is accordingly restricted to relatively thin, flat substrates. Exposure times generally run from 0.1 seconds to 1 minute, and preferably from 0.5 to 2 seconds.
Without exception, this is done with roaring flames, with distances to the substrate of 0.2 to 5 cm, preferably of 0.5 to 2 cm.
(6) Substrate surfaces can also be hydrophilized by treating them with strong acids or bases. Suitable acids are sulfuric acid, nitric acid, and hydrochloric acid. As an example, polyamides can be treated for 5 seconds to 1 minute with concentrated sulfuric acid at room temperature. Alkali metal hydroxides in water or an organic solvent are suitable strong bases. As an example, one can allow diluted caustic soda to act on the substrates for 1 to 60 minutes at 20 to 80~C. As an alternative, polyamides can be activated if one allows 2%
KOH in tetrahydrofurane to act on the substrate surface for 1 to 30 minutes. Of course, after being hydrophilized with a strong base, the polymer substrate has no acid groups, although it can be acidified by treating it with an acid.
In many instances, e.g., in the case of extremely hydrophobic polymers, it may be advisable to activate the substrate surface by a combination of two or more of the methods described above. The preferred method of hydro-philization is with UV irradiation as described in (1) above.
Regardless of what occurs in detail at the molecular level during the treatments that are described, the result is still clear. Hydrophilization can be proved by the change in the angle of contact which, if determined by the method used by R.J. Goods et al. as described above, should be <40~, and preferably <30~, at 25~C. The resulting acid groups are detectable by titration with alkaline lye.
1.3 Non-hydrophilic (or hydrophobic) substrates Using R.J. Good's method described above, such substrates exhibit a contact angle of >40~. They can be used according to the present invention when the pretreatment with ammonia plasm is selected. The standard polymers discussed in Chapter 1.2 above are amongst the suitable polymers. They may be homopolymers or copolymers, namely polyolefins or polydienes, polymers that contain halogens, polymers and copolymers of vinyl aromatic monomers. As has already been discussed, the non-hydrophilic polymer substrates are hydrophilized, and the adhesion of the hydrophilic, bioactive coating polymer on the treated polymer substrate is improved, by treating them with ammonia plasma.
2 Polyalkyleneimine as primer Polyalkyleneimines are produced by polymerization of the monomer alkyleneimine (or aziridines) and contain primary, secondary, and tertiary amino groups in variable proportions, as well as straight chain, branched chain, and cross-linked components. The best-known polyalkyleneimine is polyethylene-imine, that is commercially available as an approximate 50%-wt aqueous solution or as a product that is water-free for all practical purposes. Also suitable for the present invention are polypropyleneimine and poly(co-ethyleneimine-co-propyleneimine). The polyalkyleneimines may have number average molecular weights of up to several millions (i.e., close to 1 x 107). In the interests of good adhesion, the molecular weight should be at least about l0,000, and preferably between 10,000 and 2,000,000. It is advantageous that the hydrophilic or hydrophilized polymer substrate be treated with a 0.5 to 20%-wt solution of the polyethyleneimine for approximately 30 seconds at room temperature or at a moderately higher temperature of up to approximately 60~C.
The preferred solvent is water, if necessary with smaller parts of a lower alcohol such as methanol or ethanol. After treatment, the polymer substrate may first be dried.
Alternatively, without drying, the hydrophilic, bioactive layer may be applied immediately.
3 Treatment of the polymer substrate with ammonia plasma The embodiment of the process that uses ammonia plasma to generate basis groups that act as a primer layer entails the advantage that no hydrophilic or hydrophilized polymer substrates are required. Rather, non-hydrophilic (which is to say, hydrophobic) standard polymers may be used as starting materials. Of course, the hydrophilic or hydrophilized polymers discussed above can be used, in which case even better adhesion of the hydrophilic bioactive coating is frequently achieved.
Both high-frequency plasma (in the kiloherz range) and microwave plasma (in the gigaherz range) are suitable for treatment with ammonia. The treatment chamber is evacuated and a specific ammonia pressure, for example from 10 to 500 Pa, preferably from 20 to 180 Pa, is set up. The plasma generator can operate within a broad power spectrum, for example, from a few hundred watts such as 200 watts to a few kilowatts, e.g., 10 kilowatts. The duration of the treatment can also vary within wide limits, and can range from 10 seconds to 30 minutes, for example. Once the treatment has ended, the ammonia gas is pumped out or displaced by air; it is preferred that the treatment chamber be flushed out with air. As an alternative, the ammonia plasma can be generated in a flow of ammonia gas, when one feeds ammonia in and removes it continuously, regulating the pressure within the required range when so doing. An optimal combination of frequency, power, treatment time, and ammonia pressure can be determined very easily for a giving coating job by way of test runs.
Reactive groups, in particular amino groups, are formed on the polymer surface by plasma treatment. If oxygen is present, reactive groups that contain oxygen, possibly hydroxyl, carboxyl, and/or hydroperoxy groups, are also formed. However, the amino groups may be the most important for the adhesion of the subsequent coating, since--as is known--amino groups react with isocyanate groups more easily than the known reactive groups that contain oxygen. In the case of nitrogen-free substrates, the amino groups can be indicated by means of ESCA, and in the case of a11 substrates, by acid titration.
4 Hydrophilic bioactive coating The hydrophilic bioactive coating adheres ionically to the polymer substrate that has been treated with a polyalkyleneimine or ammonia plasma, namely by the formation of ammonium/ carboxylate, ammonium/sulfonate, or ammonium/sulfate structures, since the coating polymer contains carboxyl, sulfonic acid, or acid sulfuric acid ester groups or their salts. The sulfonic acid group has the formula -503H; the acid sulfuric acid ester group has the formula -OS03H; the sulfonate group is represented by the formula -503M; and the sulfuric acid sulfate group has the formula -OS03M, where M is one equivalent of a cation such as Na+ and 1/2 C2+. The coating can be applied by allowing a solution, preferably an aqueous solution, of an appropriate hydrophilic bioactive coating polymer to act on the treated polymer substrate that contains the groups referred to. The acid groups that may be present have a double function, in that--on the one hand--they bring about the ionic bonding of the hydrophilic bioactive coating on the basic groups of the polyalkyleneimine primer or of the polymer substrate that has been treated with ammonia plasma and--on the other hand--they initiate a biological effect, if applicable after neutralization, i.e., with caustic soda.
The coating polymers can be homopolymers or copolymers of hydrophilic vinylmonomers or copolymers of hydrophilic and hydrophobic vinylmonomers. Examples of suitable hydrophilic and hydrophobic vinylmonomers are those listed above, in Chapter 1. In the sense of the present invention, a coating polymer is considered to be hydrophilic if its contact angle according to R.J. Goods et al. is less than 35~, preferably less than 25~ at 25~C. Coating (co)polymers that are built up exclusively from hydrophilic monomers satisfy this requirement in every case. If a coating copolymer contains hydrophobic vinyl monomers, the proportion of them may be only so high that the contact angle corresponds to the above condition. The coating (co)polymers are produced by the usual processes, e.g., by radical-initiated solution or emulsion polymerization in an aqueous medium. Frequently, the coating polymers that are to be used according to the present invention are so hydrophilic that it is no longer possible to measure a contact angle because the water droplets spread over the surface.
The following are examples of suitable hydrophilic bioactive coating (co)polymers:
(i) Poly(meth)acrylic acid, as well as hydrophilic copolymers of acrylic, methacrylic acid or malefic acid with another unsaturated carboxylic acid or neutral, hydrophilic or hydrophobic comonomers. It is possible to neutralize the carboxyl groups partially in the monomers or subsequently, partially or completely, in the polymer. These polymers contain no sulfonic acid and/or sulfonate groups. Suitable other unsaturated carboxylic acids or neutral, hydrophilic or hydrophobic comonomers are, for example, those described above in Chapter 1.
(ii) Other suitable hydrophilic bioactive coating polymers are copolymers of olefinically unsaturated carboxylic acids or their anhydrides, and olefinically unsaturated sulfonic acids and, if applicable, other neutral and hydrophilic or hydrophobic comonomers. Here, too, the acid groups can in part be neutralized in the monomers, or subsequently, completely or in part, in the polymers. Of the olefinically unsaturated carboxylic acids, the following can be cited:
acrylic acid, methacrylic acid, crotonic acid, malefic acid and malefic acid anhydride (which usually hydrolyzes under the conditions of the reaction), vinylsalicylic acid, itaconid acid, vinylacetic acid, phenyl acrylic acid, 4-vinylbenzoic acid, 2-vinylbenzoic acid, sorbic acid, chlorogenic acid, methylmaleic acid, isocrotonic acid, fumaric acid, methylfumaric acid, dimethylfumaric acid, dihydroxymaleic acid, and allylacetic acid, as well as their sodium salts.
Examples of suitable olefinically unsaturated sulfonic acids are vinylsulfonic acid, 2- and 4-styrenesulfonic acid, allylsulfuric acid, methallylsulfuric acid, methallylsulfonic acid, vinyltoluene-sulfonic acid, and their sodium salts.
Examples of suitable copolymers of this kind are described in Published Canadian Patent Application No. 2,226,129.
(iii) Other suitable coating polymers are the heparin-like copolymers that are described in Published Canadian Patent l0 Application No. 2,237,480. These contain repeating units of the formulae:

R2 3 4 - CRl- CHR 5 (H-C-R-R )n (~ and R2 i COOR6 H
in which, independently in each instance, R1 stands for hydrogen or methyl; R2 stands for a divalent organic radical, for example, an aliphatic, cycloaliphatic or aromatic radical with up to 10 carbon atoms (such as o-phenylene, m-phenylene, and p-phenylene), or a bond; R3 stands for -0- or -NH-; R4 stands for hydrogen or -S03 -Na+, R5 stands for hydrogen, methyl or -R2-COOR6; R6 stands for hydrogen or Na, and n = 4 20 or 5; provided that at least one of the R4 substituents is -S03 -Na+. It is advantageous that, in at least some of the groups, R6 stands for hydrogen. The blocks I originate from vinylmonomers of the general formula (III):

- CR1=CHR 1 C R3 R4)n i H
in which R1, R2, R3, R4, and n have the above-cited values.
Examples of suitable vinyl monomers (III) are O-sulfated 1-hydroxy-1-desoxy-1-(4-vinylphenyl)-D-gluco(or D-manno)-pentitol (Ia) and N-and O-sulfated 1-amino-1-desoxy-1-(4-vinylphenyl)-D-gluco(or D-manno)-pentitol (Ib) or the sodium salts thereof. Both monomers are obtained by a multi-stage synthesis that proceeds from D-glucono-1,5-lactone, as described in the above-quoted Published Canadian Patent to Application. This also describes the production of 4-vinylbenzoic acid, whose sodium salt is a suitable monomer (II) .
(iv) Other suitable coating polymers are the homopolymers or copolymers which contain a repeating unit of the formula (IV):

I~
R
I
A
in which Rl has the same values as in the formula (I), R~ is a bridging member, and A stands for a sulfated polyol, polyamine, or (poly)-amine-(poly)ol radical, optionally containing one or more acetylized or aminalized carbonyl groups. The bridging member R7 may be of an inorganic or organic nature, and preferably stands for 0, S, SO, 502, NR', (where R' indicates hydrogen or a hydrocarbon radical with 1 to 12 carbon atoms), a divalent organic radical, in particular an aliphatic, cycloaliphatic or aromatic hydrocarbon radical with 1 to 10 carbon atoms, -O-CO-, -NR'-CO- or -O-CO-NR'-(where R' having the above quoted value), or a chemical bond.
The homopolymers or copolymers may be those described in Published Canadian Patent Application No. 2,237,480.
Preferred repeating units (IV) with acetylized or aminalized carbonyl function correspond to the formula (V):

R~
~_ ~C R3 R 4)n i H
wherein R1, R3, R4, R7, and n have the values as given for the formula (I), provided that:
(1) at least one, but preferably one or two per molecule, of the H and -R3-R4 combinations attached to the same carbon atom, with this carbon atom, form a C=O carbonyl function that is acetylized or aminalized, respectively, by an hydroxyl or amino function in the 3rd position, relative to the carbonyl function, while forming a tetrahydrofuran or pyrrolidine ring, or by a hydroxyl or amino function in the 4th position, relative to the carbonyl function, while forming a pyran or pentamethyl-eneimine ring; and (2) at least one of the R4 substituents is -S03-Na+.
Monomers of the following formula (Va) correspond to the repeating units (V) in the (co)polymer:
~1-~ 1 R~
(H_~C-R3 R4)n (Va) i H
wherein R1, R3, R4, R7 and n have the values as in formula (V), including the same quantitative conditions.
Examples of suitable (Va) monomers are the O-sulfated 1-(4-vinylphenyl)-D-manno(or D-gluco)-hexulo-2,6-pyranoses to (VaA) as well as the 0-sulfated 6-(4-vinylphenyl)-D-glycero(or L-glycero)-a-D-galactorpyranoses (VaB). Production of these monomers is also described in Published Canadian Patent Application No. 2,237,480.
In order to coat the hydrophilic or hydrophilized polymer substrates that have been pretreated with the primer, the coating polymer, preferably in a 1 to 20%-wt solution, preferably an aqueous solution, is allowed to act for 0.1 to minutes on the polymer substrates, generally at 25 to 50~C.
The substrate is then dried. Any acid groups that are still 2o present can be converted either wholly or in part to carboxylate and/or sulfate groups at the surface by treatment with a base, for example, sodium hydroxide. The layer structure of primer and hydrophilic bioactive polymer then adheres firmly to the polymer substrate and cannot be loosened by the effects of water at 60~C.
Repetitive coatinct For many applications, it is recommended that the coating process be repeated, including the treatment with polyalkyleneimine or with ammonia plasma if appropriate, in order to achieve complete coverage of the hydrophilic or hydrophilized polymer substrate with the hydrophilic bioactive coating. In the case of treatment with a polyalkyleneimine, it is useful that there be carboxyl and optionally sulfonic acid groups present in the hydrophilic bioactive coating agent that is first applied, so that the primer can be sonically bonded. The acid groups of the coating agent may have been neutralized, at most in part, with a base such as sodium hydroxide prior to being applied to the substrate. After application, they can be completely neutralized, as discussed above. For the remainder, the description provided above also applies analogously to the repetitive coating processes (treatment with polyalkyleneimine or ammonia plasma and the application of the coating polymer).
6 Bioactive properties of the coated substrates The substrates coated according to the present invention are hydrophilic and bacterio-repellant. In addition, when wet, the coatings of coating polymer 4 (iii) and 4 (iv) are distinguished by particularly low coefficients of friction. In coating polymers that have carboxyl and/or carboxylate groups, as well as sulfonic acid and/or sulfonate groups, the molar ratios of this groups can vary within very wide limits. In addition to their hydrophilic and bacterio-repellant character, the bioactively coated polymer substrates display outstanding cellulostatic properties when the cited molar ratio is 0.2 to 3, and in particular from 0.4 to 2. The coated surfaces exhibit bacterio-repellant but cellulo-proliferating characteristics to a notable degree when the molar ratio is 2 to 10, preferably 3 to 10, and in particular 3 to 5. A coating is considered to promote cellular proliferation [be celluloproliferating] when, as compared to uncoated surfaces, the adhesion and proliferation of mammalian cells is either improved or at any rate impaired to a lesser degree.
Coating polymers 4 (iii) and 4 (iv) exhibit pronounced effectiveness that is analogous to heparin, as described in greater detail in Published Canadian Patent Application No. 2,237,480.

7 Products and the use thereof Products (= articles) with a surface coated according to the present invention can be used for technical, medico-technical, hygienic, or biotechnical purposes, as has been described above. If it is important that substrates that are coated hydrophilically by the process according to the present invention be free of monomers when they are used, it is recommended that the residual monomers be extracted from the polymer hydrophilic coating. This can be done with water, and then with an organic solvent, for example, with hydrocarbons such as hexane or cyclohexane, and/or with an alcohol with 1 to 4 carbon atoms, such as ethanol and n-propanol. Well suited for the second extraction is a mixture of n-hexane and ethanol with 65 to 85 %-vol hexane.
Examples of products for technical, medico-technical, hygienic, or biotechnical purposes are catheters, tubes, stents, membranes, blood bags, wound dressings, oxygenators, elastic gloves for medical purposes, and condoms.

5. Examples Materials and Processes Table 1 - Substrates foils (F) and substrate tubes (Sch) used Foil/tube Plastic Source Production Number method F1 Polyamide 12 VESTMID~ Huls Extrusion AG

Sch 2 Polyurethane TECOFLEX~ Extrusion THERMEDIX GmbH

Sch 3 Polyether- VESTAMID~ Extrusion esteramide Hiils AG

F 4 Polyurethane PELLETHANE~ Extrusion 2363-A .

DOW CHEMICAL CO

F 5 Polyethylene VESTOLEN ~ A Extrusion VESTOLEN GmbH

F 6 Polypropylene VESTOLEN ~ P Extrusion VESTOLEN GmbH

F 7 Polyorgano- NG 37-52 Doctor knife siloxane Silicon GmbH spread coat-Niinchri t z ing F 8 Polyvinyl- VESTOLIT~+Di- Brabendering chloride ethylhexylphth-alate VESTOLIT GmbH

F 9 PTFE HOSTAFLON~ Extrusion HOECHST AG

F 10 Polystyrene VESTYRON~ Pressing i HLTLS AG

Sch 11 Polyethylene VESTOLEN ~ A Extrusion VESTOLEN GmbH

Sch 12 Polyurethane TECOFLEX~ Extrusion THERMEDIX GmbH

Table 1 (cont) Foil/tube Plastic Source Production Number Method Sch 13 Polyurethane PELLETHANE~ Extrusion DOW CHEMICAL CO

Sch 14 Polyether- PEBAX~ 5S33 Extrusion esteramide ATOCHEM S.A.

Sch 15 Polyvinyl- VESTOLIT~+Di- Extrusion chloride ethylhexylphth-alate VESTOLIT GmbH

Mainly, the foils or tubes are first activated, i.e., hydrophilized and, insofar as hydrophilization is effected with ammonia plasma, they are simultaneously treated according to the present invention. Activation is effected selectively, using the processes and conditions set out in Table 2.
Table 2 - Activation methods Activation Activation process Conditions No A 1 W excimer radiation 1 - 20 min, 1 mbar s (172 nm) 4 distance cm A 2 Microwave plasma 1 - 30 min, 1 mbar s (argon) A 3 High-frequency plasma 1 - 30 min, 6 mbar s (argon A 4 Corona 0.1 s - 60 s, 2 distance mm A S Flaming CH4:air =
1:10 4 distance cm A 6 NaOH solution 1~, 5 min; 60C

Activation No Activation process Conditions A 7 Microwave plasma (NH,) 10 s - 3 min;

- 35 - 150 Pa A 8 High-frequency plasma 10 s - 3 min;

(NH,) 35 - 150 Pa Table 3 - Polyalkyleneimines used Designator Product features P 1 Polyethyleneimine with an average molecular weight of 7S0,000 (as determined by the light-dispersal method) in the form of an approximate 50~-wt aqueous solution with a pH of 10-12 in a 1~ aqueous solution (LUPASOL~P, BASF AG) diluted with water to 2.5~-wt solids P 2 Polyethyleneimine with an average molecular weight of 25,000 (as determined by the light-dispersal method), with a solids content of 99~, with a pH
of 10-12 in a 1~ aqueous solution (LUPASOL~WF, BASF

AG) diluted with water to 1~-wt solids P2a or 5~-wt solids (P2b).

Table 4 - Coating polymers Designator~~- Product features B 1 Polyacrylic acid with an average gm/molecular weight Mw of 2000, 5~-wt aqueous solution B2 Terpolymer of 0-sulfated 1-hydroxy-1-desoxy-1-(4-vinylphenyl)-D-gluco(D-manno)-pentitol, - and O-sulfated 1-(4-vinylphenyl)-D-gluco(D-manno)-penti-tol and sodium-4-vinylbenzoate in a molar ratio 1:1:1, Mn approx. 229,000, produced as per Patent Application 192 20 369.8 (O.Z. 5195) as 5~-wt aqueous solution B3 Polyacrylic acid with an average gm/molecular weight Mw of 450,000, S~-wt aqueous solution B3 -[CH-CH2-CH-CHZ]" - Copolymer (1:1), gm/mol weight Mn approx. 231,000 sulfating p-C6H,, p-CoHa degree 3.35 radicals -SO3Na/

molecule, produced by Patent CHOR COONa appl'n 198 O1 040.0(0.Z. 5281) OR used as 5~-wt aqueous solution RO

OR

OR

OR

R = H, -S03Na; p-C6H4 = p-phenylene B4 -(CH=CH,]n- - Homopolymer, gm/mol weight (Mn) approx. 126,000 sulfating p-C6Ha degree 3.35 radicals -SO,Na/

molecule, produced by Patent CHOR appl'n 198 O1 040.0(0.Z. S281) OR used as 5~-wt aqueous solution RO

OR

OR

OR

R = H, -S03Na; p-CbH4 = p-phenylene B6 Poly(sodiumstyrenesulfonate-co-malefic acid), 10~-wt in water, Mw approx. 70,000, produced from the monomers (1:1) by conventional solution polymeri-sation in Hz0 Treatment with polyethyleneimine The foils or tubes were immersed in the polyethyleneimine solution at 25~C, slowly withdrawn within 20 sec, and dried for 5 minutes at 60~C, immersed in the solution of coating polymer at 25~C, slowly withdrawn within 20 sec, and once again dried for 5 minutes at 60~C. This cycle was repeated several times as necessary, as shown in Table 5.
Treatment with ammonia plasma The samples to be treated were either cemented to a glass carrier or mounted on a glass apparatus so that their position in the plasma chamber remained unchanged when a partial vacuum was applied. The pressure was then reduced to 5 to 20 Pa and ammonia so metered in and withdrawn that a pressure of 10 to 500 Pa and preferably 30 to 180 Pa was set up and maintained. The plasma was ignited after a 20-second homogenisation period for the gas. The optimal power per unit area of the substrate depends on the size of the plasma chamber, and can be determined very simply by tests. The duration of the treatment can amount to 1 second to 30 minutes, depending on the substrate and the desired extent to which basis groups are generated. The plasma chamber is then flushed with air for approximately 1 minute. If required, a vacuum can be reapplied in order to remove the final traces of ammonia gas.
Measurement and testing methods Molecular weights A11 molecular weights Mn were determined by membrane-osmometry; a11 molecular weights Mw were determined by the light dispersal method.
Determination of COOK and S on the coating The oxygen content on the surface, which was elevated compared to the untreated sample, was determined by ESCA; this could be attributed to the carboxyl and/or carboxylate, sulfonic acid and/or sulfonate and/or acid sulfuric acid ester and/or sulfate groups. The groups of the coating polymer that contain sulfur were identified by measuring the sulfur as a surface element.
Determination of contact angle A measure for the hydrophilic nature of the surface is the change in the contact angle of the water droplets that are applied to the surface. Such a procedure is described in R.J. Good et al., Techniques of Measuring Contact Angles in Surface and Colloid Science, (Published by R.J. Good), Vol.
II, Plenum Press, New York, N.Y., 1979). In the examples, the contact angle was measured according to this method at 25~C.
The contact angle can no longer be measured in the case of strongly hydrophilic substrates because the liquid disperses into a thin layer on the substrate. This is referred to as spreading in Table 6.
Determination of the coefficient of friction The coefficient of friction ~, was determined by the inclined-plane method. To this end, the coated substrate foil was cemented to a round, metal disk and then kept in water or in a 0.9%-wt NaCl solution for various lengths of time (in Table 4 "Water minutes"). The metal disk was then placed--foil down--on a flat plate coated with the uncoated polymer, and this was then wetted down with distilled water. The angle subtended by the plate and the horizontal was then gradually increased.
The angle at which the metal disk began to slide was recorded.
The tangent of this angle is the coefficient of friction Determination of primary bacterial adhesion under static conditions An overnight culture of the bacterial strain Klebsiella pneumoniae in yeast extract-peptone-glucose nutrient [1%+1%+1%] was centrifuged off and reabsorbed in phosphate-buffered saline (=PBS; 0.05m KH2P04, pH 7,2 + 0.9%
NaCl). The PBS buffer is diluted to a cellular concentration of l08 cells/ml. The suspended bacteria are brought into contact with the foil sample to be tested for a period of 3 hours. To this end, round pieces of foil, coated on both sides, diameter 1.6 cm (=4.02 cm2) are impaled on a preparation needle and agitated with the cellular suspension.
Foils coated on one side, in the form of a round, flat disk, 4.5 cm diameter and with a supporting membrane of 2 - 3 cm thick soft PVC are installed in a membrane filter apparatus.
The cellular suspension is applied to the uppermost side that has the coating that is to be tested, and agitated for 3 hours. The membrane filter apparatus must be tightly closed, i.e., no cellular suspension is to be allowed to flow through unsealed cells.
Once the contact time has expired, the bacterial suspension is drawn off with a water-jet pump and the pieces of foil are agitated with 20 ml of sterile PBS solution in a 100-ml beaker for 2 minutes in order to wash them. The pieces of foil are one again immersed in sterile PBS solution, and then extracted for 2 minutes in 10 ml of heated TRIS/EDTA
(0.1M tris-hydroxyethylaminomethane, 4mM ethylenediamine-tetraacetic acid, adjusted to pH 7.8 with HC1) in a boiling-water bath.
Small Eppendorf cups are filled with the extraction solution and then frozen immediately at -20~C until the bioluminescence of the extracted adenosine triphosphate (ATP) was determined. This determination was effected as follows:
100 ~.1 of reagent mixture (Biolumineszenz-Test CLS II, BOEHRINGER MANNHEIM GmbH) was added to a transparent capillary tube and the light pulses were integrated for a period of 10 seconds in a LUMAT light-pulse measuring device (Laboratorien Prof. Berthold GmbH, 75323 Bad Wildbad, Germany). Then a 100 ~l sample was added, and the measurements repeated. The relative light units (RLU) were obtained by subtracting the light pulses in the reagent mix from the number of measured light pulses in the complete batch. This number is related to the number of the bacteria adhering to the foil. The conversion factor between the RLU value and the bacteria count is determined in that an aliquot of 0.1 ml of the bacterial suspension with l08 cells /ml is extracted in 10 ml hot TRIS/EDTA and then the ATP content is determined. In Table 6, the bacterial adhesion on the untreated substrates is set at 100% (= 0% reduction of the bacterial adhesion).
Tests conducted with other bacterial strains such as staphylococcus aureus, Staphylococcus epidermis, Streptococcus pyogenes, Pseudomonas aeroginosa, and Escherichia coli proceed in the same way, and provide similar results.
Test results Examples 1 to 30.
The test conditions and the results obtained are set out in the following Table 5.

Ex. Foil/ Acti- Polymin CoatingDip ESCA CoeFf. Red'n No. Tube nation SolutionPolymercycles(atom-%)Frictionbacterial (%_~) O S ~ adhesion Waters min 1 Foil A 1, P I B 2 3 - - 5 0.36 89%

5 min (2.5lo) LO 0.31 bilateral 2 Foil A l P 1 B l 1 - - l 0.31 97%

5 min (2.5%) 5 0.Z9 bilateral l0 D.29 3 Tube A 1 P 1 B 2 1 - - - 73"0 40 s (2.5%) @

40 rpm 4 Tube A 2 P 1 B 2 l - - - 93%

60 s (2.5%) Tube A l P t B 2 3 _ _ _ _ 95%

4U s (2.5%) C.~

40 rpm 6 Tube A t P I B 1 l _ _ _ _ 95%

40 s (2.5%) @

40 rpm 7 Tube A 1 P 1 B l 3 - - - - 86%

40 s (2.5%) @

40 rpm

8 Foil A 1 P l B 2 1 - - l 0.04 82%

5 min (2.5%) 5 0.0:l once 10 0.03 0.03

9 Foil A 1 P I B 2 3 - - 1 0.06 95%
l 5 min (2.5%) 5 U.05 once 10 0.l5 l5 0.21 Foil4 A 6 P 1 B 3 3 2-l.a 1 0.25 94%
-Q2.5%) 5 0.27 t 0.28 ll FoilS r1 -t P l B -4 l 3?.0 1 0.04 9l%
7.0 (2.5%) 5 d.04 t o 0.04 12 Foil6 A 5 P 1 B 4 3 34.0 1 0.05 93%
6.8 (2.p%a) 5 0.05

10 0.05 Table 5 (cont) Ex. FoiU Acti- Polymin CoatingDip ESCA Coetf. Red'n No. Tube vation Solution Polymercycles(atom-%)Frictionbacterial (%-wt) O S Waters adhesion ,cc min 13 Foil7 - P 1 B ~ 3 - - 84%

(2.~%) 14 Foil A 6 P 1 B 2 1 - - 88'7 (2.5%) 15 Foil A 1 P I B 4 1 - - - 75%

3 min (?.~%) 16 Foil A 4 P 1 B ~ 3 - - 1 0.09 96%

(2.5%) 5 0.1l 10 0.15 17 Foil A I P 1 B -1 3 36.l 1 0.03 93%
i 6.9 min (2.6%) ~ 0.04 once IO 0.04 18 Foil A 1 P ? B 6 ~ I9.9 - 93%
1 4.0 5 min ( I %) once 19 Tube A 1 P 2 H 6 3 l8.1 - 67%
2 2.7 40 s (5%) @

40 rpm 20* Foil 6.9 1 0.36 0%
l -5 0.36 10 0.36 21 * Tube 6.5 0%

22* Foil 1 1. I 0.36 0%
-l f -5 0.36 10 0.36 23* Iuil 2 - l 0.36 0%
~

5 0.36 l0 0.36 24* Foil I - 1 0.36 0%
~

5 0.36 10 0.36 Table 5 (conclusion) Ex. Foil/ Acti- Polymin CoatingDip ESCA Coeff. Red'n No. Tube vation SolutionPolymercycles(atom-%)Frictionbacterial (%-wt) O S Ec adhesion Watecs min 25 Foil A 8 - B 4 l 25.9 1 0.07 62%
1 1.7 3 min - 5 0.07 10 0.05 26 Tube A l P 2 B -1 1 - - l 0.05 30%

11 30 sec (2.5%) 27 Tube A 8 - B -4 l 24.0 - ~5%

12 2.2 t min 28 Tube A 7 B -1~ l3 23.7 67%
l3 3.
I

l min -29 Tube: A 1 P 1 B -t 1 - - 1 0.04 -t-l 30 sec (2.5%) 5 0.04 once t0 0.04 30 Tube A 7 - B -1 t 23.3 - 43%
15 =4.3 l0 min once Comparitive example It was impossible to measure a contact angle in Examples 1 to 19 and 25 to 30.

Example 31 A polyamide 12-foil (L2101F, Huls AG) was irradiated for 5 minutes at 1 Torr, using a 172 nm excimer lamp, and then immersed in a 2.5%-wt solution of Lupasol P (BASF
Aktiengesell-schaft) (P 1 in Table 3) and dried for 5 minutes at 60~C. The dried foil is immersed for 20 seconds in a 5%-wt solution of the coating polymer B 5 and then dried for 72 hours at 60~C. The coefficient of friction ~, was between 0.07 and 0.1, as compared to 0.36 for the uncoated material. The angle of contact could not be measured because the droplets spread.
Example 32 A foil of an thermoplastic elastomer was dipped 3 times for 10 seconds on each occasion in acetone for hydrophilization, dried at room temperature, and then immersed for 30 seconds in a 2.5%-wt aqueous solution of Lupasol P
(BASF AG) (P 1 in Table 3). It was then dried for 5 minutes at room temperature and for 30 minutes in a drying cabinet at 60~C. The dried foil was then immersed for 30 seconds in the solution of a sugar polymer of formula - [CH-CH2-CH- CH2]n _ 4 p-06H4 CHOR COONa RO OR
OR
OR
OR

R = H, -S03Na; p-C H4 = p-phenylene (copolymer 1:1, gm~molecular weight Mn = 570,000, degree of sulfation 3.09 radicals -S03Na/molecule, produced as described in Patent Application 195 20 369.8 (O.Z. 5195), used as a 5%-wt aqueous solution) and dried for 5 minutes at room temperature and for 30 minutes in a drying cabinet at 60~C.
The coefficient of friction was 0.02. It was not possible to measure an angle of contact because the water droplets spread.
In a finger test, abrasion of the coating was perceptible after 58 strokes.
Example 33 As in Example 32, although instead of an acetone wash, the foil was irradiated for 10 seconds at 1 Torr, using an 172 nm excimer radiator. In a finger test, the coating could be abraded after 120 strokes.

Claims (24)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. A process for producing an article having a hydrophilic and bioactive coating surface layer, which comprises:
(A) treating a polymer surface of a substrate of the article with a polyalkyleneimine as a primer or with ammonia plasma, provided that the polymer surface is hydrophilic or hydrophilized when the polyalkyleneimine as a primer is employed; and (B) then forming, on the so treated surface, a hydrophilic and bioactive coating layer of a polymer that contains at least one group member selected from the class consisting of (a) a carboxyl group and a carboxylate group, (b) a sulfonic acid group and a sulfonate group and (c) an acid sulfuric acid ester group and a sulfuric acid sulfate group.

2. A process as defined in claim 1, wherein the polymer surface of the substrate is hydrophilic or has been hydrophilized prior to the step (A); and the polymer surface of the substrate is treated with the polyalkyleneimine as a primer in the step (A).

3. A process as defined in claim 2, wherein the hydrophilic or hydrophilized polymer surface of the substrate contains an acid group.

4. A process as defined in claim 3, wherein the acid group is selected from the class consisting of a carboxyl group, a sulfonic acid group, salts thereof and mixtures thereof.

5. A process as defined in claim 2, 3 or 4, wherein the hydrophilic or hydrophilized polymer surface of the substrate shows an angle of contact of more than 40° at 25°C.

6. A process as defined in claim 5, wherein the hydrophilic or hydrophilized polymer surface of the substrate shows an angle of contact of more than 30° at 25°C.

7. A process as defined in any one of claims 2 to 6, wherein the polyalkyleneimine is applied to the polymer surface of the substrate as an aqueous solution containing 0.5 to 20% by weight of the polyalkyleneimine.

8. A process as defined in any one of claims 2 to 7, wherein the polyalkyleneimine is polyethyleneimine.

9. A process as defined in any one of claims 2 to 8, wherein, the polyalkyleneimine has a number average molecular weight of from 10,000 to 2,000,000.

10. A process as defined in claim 1, wherein the polymer surface of the substrate is treated with ammonia plasma in the step (A), whereby an amino group is formed on the polymer surface.

11. A process as defined in claim 10, wherein the polymer surface is hydrophobic.

12. A process as defined in claim 10 or 11, wherein the treatment with ammonia plasma is conducted in a treatment chamber at an ammonia pressure of 10 to 500 Pa using a plasma generator capable of operating at a power of 200 watts to 10 kilowatts for 10 seconds to 30 minutes.

13. A process as defined in any one of claims 1 to 12, wherein the polymer of the hydrophilic and bioactive coating layer contains a carboxyl, sulfonic acid or acid sulfuric acid ester group.

14. A process as defined in any one of claims 1 to 13, wherein in the step (B), a solution of the polymer of the hydrophilic and bioactive coating layer is allowed to act on the polymer surface of the substrate treated with the polyalkyleneimine or the ammonia plasma.

15. A process as defined in claim 14, wherein the polymer of the hydrophilic and bioactive coating layer is polyacrylic acid or a copolymer of acrylic acid, methacrylic acid or malefic acid with another unsaturated carboxylic acid or neutral hydrophilic or hydrophobic comonomers.

16. A process as defined in claim 14, wherein the polymer of the hydrophilic and bioactive coating layer is a copolymer of an olefinically unsaturated carboxylic acid or anhydride thereof, with an olefinically unsaturated sulfonic acid and optionally a neutral hydrophilic or hydrophobic comonomer.

17. A process as defined in claim 14, wherein the polymer of the hydrophilic and bioactive coating layer is a copolymer that contains repeating units of the formulae:
and (wherein R1 stands for hydrogen or methyl; R2 stands for a bivalent organic radical or a bond; R3 stands for -O- or -NH-;
R4 stands for hydrogen or -SO3 -Na+; R5 stands for hydrogen, methyl or -R2-COOR6; R6 stands for hydrogen or Na, and n = 4 or 5; provided that at least one of the R4 substituents is -SO3-Na+).

18. A process as defined in claim 14, wherein the polymer of the hydrophilic and bioactive coating layer is a homopolymer or a copolymer, of a repeating unit of the formula (IV) (in which R1 is hydrogen or methyl; R7 is a bridging member, and A stands for a sulfated polyol, polyamine or (poly)-amine-(poly)ol radical, optionally containing one or more acetylized or aminalized carbonyl groups).

19. A process as defined in claim 18, wherein R7 is O, S, SO, SO2, NR , a divalent aliphatic, cycloaliphatic or aromatic hydrocarbon radical with 1 to 10 carbon atoms, -O-CO-, -NR'-CO-, -O-CO-NR'- or a chemical bond and R'is hydrogen or a hydrocarbon radical with 1 to 12 carbon atoms.

20. A process as defined in claim 19, wherein the repeating unit (IV) is a repeating unit having an acetylized or aminalized carboxyl function of the formula (V):
(in which R1 is as defined in claim 18; R7 is as defined in claim 19; R3 is -O- or -NH-; R4 is hydrogen or -SO3-Na+; and n is 4 or 5, provided that:

(1) at least one, of a combination of H and -R3-R4 substituents attached to the same carbon atom, together with this carbon atom, form a C=O carbonyl function that is acetylized or aminalized, respectively, by an hydroxyl or amino function in the 3rd position, relative to the carbonyl function, forming a tetrahydrofuran or pyrrolidine ring , or by a hydroxyl or amino function in the 4th position, relative to the carbonyl function, forming a pyran or pentamethyleneimine ring; and (2) at least one of the R4 substituents is -SO3-Na+.

21. A process as defined in any one of the claims 15 to 20, wherein acid groups in the polymer of the hydrophilic and bioactive coating layer are partially or wholly neutralized.

22. An article comprising a substrate having a polymer surface, wherein the polymer surface has been treated with a polyalkyleneimine as a primer or with ammonia plasma and has been coated to form thereon a hydrophilic and bacterio-repellant coating layer by the process according to any one of the claims 1 to 21.

23. The article as defined in claim 22, which is adapted to be used for a technical, medico-technical, hygienic, or biotechnical purpose.

24. The article as defined in claim 22, which is a catheter, a tube, a stent, a membrane, a wound dressing, an oxgenator, an elastic glove for medical purpose or a condom.