CN108463257B

CN108463257B - Coating for medical devices, method for coating same and medical devices coated by said method

Info

Publication number: CN108463257B
Application number: CN201680078842.6A
Authority: CN
Inventors: D·马斯喀特; J·沃伊特; S·赫芬布罗克
Original assignee: Urotech Pty Ltd
Current assignee: Urotech Pty Ltd
Priority date: 2015-11-18
Filing date: 2016-11-15
Publication date: 2021-05-25
Anticipated expiration: 2036-11-15
Also published as: DE102015014912A1; MA43264A; CN108463257A; EP3377127A1; DE102015014912B4; WO2017084647A1

Abstract

Coating for a medical device comprising or consisting entirely of polyurethane on its surface, which medical device, after its introduction into the human or animal body, is in contact with its bodily fluids, in particular with urine, comprising an adherent crosslinked layer applied on the device and a layer consisting of at least one polymer comprising phosphorylcholine, applied on and crosslinked on the adherent crosslinked layer and optionally crosslinked with the adherent crosslinked layer.

Description

Coating for medical devices, method for coating same and medical devices coated by said method

Technical Field

The invention relates to a coating for a medical device which comes into contact with body fluids of the medical device after its introduction into the human or animal body, in particular with urine, comprising a material component which comprises at least one polymer containing choline phosphate. The invention also relates to a method for coating a medical device and to a medical device coated by the method.

Background

In one aspect, a medical instrument is understood here as a medical catheter which is introduced into a human or animal body and removed again after a period of time. Medical catheters which are in contact with urine, for example in the human or animal body, may in particular be urinary catheters, also known as ureteral catheters. On the other hand, a medical instrument is understood here as a medical implant which is introduced into or used in the human or animal body for as long as possible. But it cannot be excluded for such implants that they are removed again from the implant carrier after a period of time.

The carrier materials that make up medical devices of the type described above must generally be biocompatible. Different polyurethanes, for example polyester-based polyurethanes or polycarbonate-based polyurethanes, can be used as biocompatible carrier materials of this type. However, the sliding properties of the relevant carrier material in a body cavity or opening in a human or animal body do not meet the requirements of so-called "smoothness", i.e. practically frictionless, and medical devices made of this carrier material have at least a very low-friction movability. Therefore, such medical devices usually have a sliding layer on their surface.

For coating medical devices, the applicant has tested polymers comprising at least one phosphorylcholine, since, due to their hydrophilic or hydrophobic nature, the sliding characteristics of the relevant medical device during its insertion into and removal from a body orifice or cavity of a human or animal body can be improved compared to the carrier material formed or contained in the relevant medical device.

Furthermore, medical devices coated in this manner do not form scale from salts contained in the liquids to which the associated medical device is exposed. This also avoids the risk of infection associated with such fouling.

Phosphorylcholine has the following structure:

polymeric material components for surface coatings of devices which come into contact with protein-or biological-containing fluids are known (see documents DE 69231450T 2, DE 69233378T 2, DE 69907686T 2, US 7160953). In these material components, use is predominantly made of copolymers containing phosphorylcholine, which are crosslinked. According to published data (see document DE 69231450T 2), stable coatings are achieved on a wide variety of surfaces with relevant material components, such as polyethylene, PVC, steel and poly (imide).

However, in the case of medical devices which comprise polyurethane on their surface or consist entirely of polyurethane (such medical devices are also referred to below as PU devices), it has been shown in tests that, when a coating containing the relevant known material component is exposed to a liquid, for example water or urine, the material component remains attached to such medical devices only for a relatively short attachment time. Thus, in tests in which such coatings are made in liquids such as water or urine, adhesion times of only a few hours to a few days are achieved. However, such attachment times are too short for so-called long-term use of medical devices in the human or animal body. Long-term use is herein understood to mean a use period of the medical device of at least eight weeks. During this time, the properties and coatings of the corresponding medical device used in the human or animal body should remain unchanged and need not be changed.

In order to achieve the mentioned long-term use of medical PU devices, it has been investigated in further experiments whether the additive layer applied to the surface of the relevant PU device contains different chemical additives (so-called primer layers) and whether there is a possibility of consolidation on the surface of the relevant PU device during the so-called long term. However, tests carried out have shown that even such an extender layer adheres only a few hours to a few days to the applied medical PU device when the relevant device is exposed to a liquid, such as water or urine. Furthermore, similar results are achieved when another layer of choline phosphate-containing polymer is applied and crosslinked over the layer of the extender applied to the medical device (as will be explained in more detail below). Furthermore, in this case, a layer structure consisting of the two layers achieves only a relatively short attachment time if the medical PU device carrying the layer structure is exposed to liquids, such as water or urine.

The reason for the above-mentioned relatively poor adhesion of the copolymer comprising phosphorylcholine (or of the booster layer consisting of chemical booster on a medical PU appliance whose surface comprises polyurethane or consists entirely of polyurethane ) is that there is not sufficient bonding force between the surface of the PU appliance and the booster layer and between the booster layer and the layer consisting of copolymer comprising phosphorylcholine, due to covalent bonds or by dipole-dipole bonding or by hydrogen bonding between the material of the PU appliance and the chemical booster of the booster layer and between the booster layer and the layer consisting of copolymer comprising phosphorylcholine.

In this context, it must also be taken into account the known fact that, in general, dipole-dipole bonds and hydrogen bonds of different materials play a more pronounced role for water than between the relevant materials themselves. This is also possible because, when the PU appliance coated in this way is exposed to an aqueous environment, the additive layer consisting of the chemical additive and the layer consisting of the copolymer containing phosphorylcholine dissolve from the medical PU appliance relatively quickly again on its own or with the interposition of the additive layer, after successful application on the latter.

Disclosure of Invention

It is therefore an object of the present invention to show how it is possible to provide in a relatively simple, but effective manner, a way of such a coating for a medical device which, after its application to the relevant device, is firmly fixed to the device even after the above-mentioned prolonged use of the medical device, i.e. for a period of at least eight weeks.

Furthermore, it is an object of the present invention to provide a method for coating a medical device and a medical device coated by means of the method.

The above object is achieved according to the invention in a coating of the type mentioned at the outset in that the material component for a medical device comprising or consisting entirely of polyurethane on its surface is an adhesive crosslinking layer which can be applied to the medical device and which comprises a chemical enhancer and an alcohol which crosslinks thereto, at least one diol having two primary OH groups, and at least one polymer comprising phosphorylcholine, which is applied as a separate layer on the adhesive crosslinking layer and is crosslinked on the adhesive crosslinking layer and optionally crosslinked with the adhesive crosslinking layer.

An advantage of the coating according to the invention is that the coating, after application on a surface of a medical device comprising polyurethane or consisting entirely of polyurethane on its surface, remains attached to the surface during an attachment time of more than eight weeks during exposure of the relevant device to a liquid, such as water or urine, and rinsing. According to this knowledge, this relatively long attachment time is based on the double cross-linking achieved in the material component according to the invention; the first crosslinking results in the formation of an adhesive crosslinked layer composed of a chemical extender and an alcohol (to be precise at least one diol having two primary OH groups), and the second crosslinking possibility is achieved in that the layer composed of at least one copolymer comprising phosphorylcholine applied to the adhesive crosslinked layer formed is optionally crosslinkable with the adhesive crosslinked layer.

Thus, surprisingly, in this case (in contrast to the test mentioned at the outset), sufficient bonding forces (due to covalent bonds or by dipole-dipole bonding or by hydrogen bonding) are provided between the material of the PU appliance and the chemical extenders of the extender layer and between this extender layer and the layer composed of the copolymer comprising phosphorylcholine by crosslinking of the chemical extenders with the alcohol in the adhesive crosslinked layer. This binding force is based on the esterification of the alcohol with the chemical extenders and the resulting crosslinking in the layer of extenders to the surface of the PU appliance and the layer consisting of the copolymer containing phosphorylcholine.

Preferably, the polymer comprising choline phosphate is formed from a (2- (methacryloyloxyethyl) -2'- (trimethylammoniumethyl) phosphate, inner salt) - (hydroxypropyl methacrylate) - (3- (trimethoxysilyl) propyl methacrylate) copolymer and/or a (2- (methacryloyloxyethyl) 2' (trimethylammoniumethyl) phosphate, inner salt) - (n-dodecyl methacrylate) - (2-hydroxypropyl methacrylate) - (3- (methoxysilyl) propyl methacrylate) copolymer. The advantage is thereby obtained that phosphorylcholine can be used which is particularly effective for the intended attachment times of the material components according to the invention (at least eight weeks on PU instruments).

Suitably, the chemical extender is formed from a copolymer of ethylene and maleic anhydride. This has the advantage that particularly effective chemical additives can be used according to the invention on PU instruments with regard to the adhesion capability of the material components.

According to the invention, the above object is also achieved by a method for coating a medical device, which is in contact with its body fluids, in particular with urine, after its introduction into the human or animal body, with a material composition having a polymer comprising phosphorylcholine, by applying a first layer formed from a chemical enhancer and an alcohol, at least one diol having two primary OH groups, onto a medical device, the surface of which comprises or consists entirely of polyurethane, crosslinking the chemical enhancer and the alcohol in the first layer to form a crosslinked layer, and then applying a second layer comprising phosphorylcholine onto the crosslinked layer, the second layer having at least one polymer comprising phosphorylcholine, and likewise crosslinking the second layer.

The advantage is thereby obtained that, according to the invention, in two successive coating processes, each comprising a cross-linking process, the material component can be applied as a long-term coating on the surface of the PU appliance, which coating remains attached to the surface of the PU appliance for an attachment time of more than eight weeks, when the PU appliance is continuously exposed to a liquid, such as water or urine, for example by being stored in this liquid for a long time or being rinsed with this liquid.

Preferably, as the polymer comprising choline phosphate in the second layer is selected (2- (methacryloyloxyethyl) -2'- (trimethylammoniumethyl) phosphate, an inner salt) - (hydroxypropyl methacrylate) - (3- (trimethoxysilyl) propyl methacrylate) copolymer and/or (2- (methacryloyloxyethyl) -2' - (trimethylammoniumethyl) phosphate, an inner salt) - (n-dodecyl methacrylate) - (2-hydroxypropyl methacrylate) 3- (trimethoxysilyl) propyl methacrylate copolymer. The advantage is thereby obtained that a particularly effective phosphorylcholine is used for the intended attachment time of the material component according to the invention (at least eight weeks on PU instruments).

Suitably, a copolymer of ethylene and maleic anhydride is selected as the chemical extender in the first layer. This has the advantage that particularly effective chemical additives can be used according to the invention on PU instruments with regard to the adhesion capability of the material components.

In order to achieve a significant adhesion effect by the method according to the invention, the cross-linking of the chemical enhancer of the first layer with the alcohol and the cross-linking of the polymer comprising phosphorylcholine of the second layer are carried out at a temperature of about 60 ℃ to about 140 ℃, preferably about 80 ℃ to 120 ℃, respectively. This has the advantage that it is possible to work at crosslinking temperatures which can be achieved relatively easily.

Preferably, the corresponding crosslinking duration is from about 15 minutes to 1 day, preferably from about 45 minutes to about 2 hours. An acceptable length of time is thereby achieved in an advantageous manner, i.e. the length of time is not too long for the corresponding crosslinking.

The above object is also achieved by a medical device comprising or consisting entirely of polyurethane on its surface and which is intended for use in an area of the human or animal body where it is in contact with body fluids thereof, in particular with urine, comprising a material component applied on its device surface, which material component is manufactured and cross-linked according to the method of the invention.

The advantage is thereby obtained that a medical PU device is provided on the surface of which the material component layer remains attached during the attachment time of more than eight weeks that is pursued when the relevant device is continuously exposed to liquids such as water or urine.

Drawings

The invention is explained in detail below with reference to the drawings. In the drawings, there is shown in the drawings,

FIG. 1 shows a diagram showing the weight change over time of a coating stored in a test solution, which without the use of the invention had previously been formed on two PU instrument specimens each from an adhesive crosslinking layer and a copolymer containing phosphorylcholine located thereon, and

fig. 2 shows a diagram which shows the weight change over time of the coating deposited in the test solution, which coating was previously formed according to the invention on two PU instrument specimens in each case from an adherent crosslinked layer and a copolymer containing phosphorylcholine located thereon.

Detailed Description

Before elaborating on the graphs of fig. 1 and 2, it should be noted here that the graphs are based on tests in a test fluid, for which H is used₂And O. However, the specific test results can be transferred without problems, at least in terms of quantity, to other liquids, in particular urine; because of water (H)₂O) only has a stronger dissolving capacity for the coating material of the PU instrument sample referred to below than for urine.

To construct the diagram of fig. 1, a coating consisting of two layers was applied without the invention on two PU instrument samples (referred to as sample 1 and sample 2). To construct the diagram of FIG. 1 and to construct the diagram of FIG. 2, a tubular or hose-shaped PU sample having an outer diameter of about 2.3mm to 2.5mm, respectively, having a length of about 100 to 150mm was used as the PU instrument sample.

Polyester-based polyurethane sold under the name Tecoflex by the manufacturer Lubrizol Advanced Materials, Inc. (Ohio, USA) was used as the polyurethane material for the PU instrument samples. It is noted here that instead of Tecoflex material, polycarbonate-based polyurethane sold by the same manufacturer under the trade name Carbothane can also be used.

The coating concerned here consists of a first extender layer and a second layer situated thereon, the second layer consisting of a copolymer comprising phosphorylcholine. It should also be noted with respect to the coating quantity that, at 100mm²An amount of 5mg on the area of (a) corresponds to 1g/cm³Assumed material density and average coating thickness of 5 μm.

As the chemical extender, a chemical extender (hereinafter and in the drawings simply referred to as ZeMac) commercially available under the trade name ZeMac400 manufactured by the manufacturer Vertellus Specialties, Inc. The chemical additive is a copolymer of ethylene and maleic anhydride.

For this, 1150mg of powder ZeMac were first dissolved in 23ml of acetone for about 2 hours. The two PU instrument samples 1 and 2 were then coated with the chemical extender material during immersion and then subjected to a heat treatment at about 100 ℃ for about one hour, thereby crosslinking the chemical extender.

Subsequently, a layer of a copolymer containing phosphorylcholine is applied to the thus formed extender layer of the chemical extender ZeMac. As copolymer comprising phosphorylcholine a copolymer provided under the name PC2118 by the manufacturer Vertellus Specialities, Inc (indianapolis, usa) is used here. The material PC2118 is a choline phosphate containing terpolymer — (2- (methacryloyloxyethyl) -2' - (trimethylammoniumethyl) phosphate, inner salt) - (hydroxypropyl methacrylate) - (3- (trimethoxysilyl) propyl methacrylate) copolymer. Thus, the materials involved comprise three different monomers; two of which are hydrophilic and one of which is hydrophobic.

From which three monomers can be seen, i.e.

a → poly (2- (methacryloyloxyethyl) -2' - (trimethylammonioethyl) phosphate, inner salt

b → hydroxypropyl methacrylate

c → - (3- (trimethoxysilyl) propyl methacrylate)

The corresponding structural formula is given below:

in order to apply a layer composed of a copolymer containing phosphorylcholine onto the crosslinked extender layer of the two PU device samples 1 and 2, the two PU device samples were then coated in a dipping process in a solution composed of 2300mg of PC2118 and 23ml of ethanol and then subjected to a heat treatment at a temperature of about 100 ℃ for a duration of about 1 hour, and at the same time likewise crosslinked.

FIG. 1 now shows the samples involved on two PU instrument samples 1 and 2 in the test liquid H₂Shelf-time-dependent weight change of the coating amount in O. To this end, inThe percentage of the remaining portion of the corresponding PU instrument sample in relation to the total coating material applied thereon is plotted in the ordinate direction, and the storage time in weeks (test time) of the PU instrument sample with the two crosslinked layers, i.e. the adhesive crosslinked layer and the PC-2118 layer, is plotted in the abscissa direction.

The percentage of the remaining portion on the corresponding PU instrument specimen in relation to the total coating material applied thereon was calculated on the basis of gravimetric determination on an analytical balance. For this purpose, first only the weight G1 of the instrument sample is determined, and then the weight G2 of the instrument sample coated with the coating material is determined. After the instrument sample coated with the coating material has been stored in the test solution, the weight G3 of the relevant instrument sample at the determined point in time is then determined. The percentage A can then be calculated from the relation

Samples 1 and 2 thus coated with a chemical extender ZeMac and a copolymer PC2118 comprising phosphorylcholine are described in H₂The storage in the test solution of O in both samples already showed a significant loss of coating material after about three weeks, which had dissolved in the test solution of both PU instrument samples. Sample 1 also contained only about 10% of the amount of coating initially applied thereto after about three weeks of storage in the test fluid, while sample 2 even contained only about 5% of the amount of coating initially applied thereto after about three weeks of storage in the test fluid. After about ten weeks of storage in the test solution, the entire coating of the two test specimens 1 and 2 disappeared, and the coating material of the PU instrument specimen had virtually completely dissolved in the test solution.

Thus, samples 1 and 2 lose their initially good sliding properties after having been stored in the test solution for about three weeks, so that their coatings are not usable for the long-term use described at the outset.

In fig. 2, the weight change of the coating quantities of the coatings formed according to the invention on the two PU device samples 3 and 4 as a function of the storage time of the samples 3, 4 in question in the test solution can be seen.In this case, as in fig. 1, the percentage of the remaining portion of the corresponding PU instrument sample in relation to the total coating material applied thereon is plotted in the ordinate direction, and the storage time in weeks (═ test time) of the PU instrument samples 3, 4 coated according to the invention is plotted in the abscissa direction in a test liquid, here also H₂O。

The percentage of the remaining portion of the corresponding PU instrument specimen in the total coating material applied thereon was determined by calculation on the basis of gravimetric determination by means of an analytical balance, as described with reference to fig. 1. Furthermore, the steps for applying an adhesion promoter layer and a layer made of a copolymer containing phosphorylcholine to a PU instrument sample corresponding to the steps described in connection with fig. 1 were carried out here, but differ from the following description of the adhesion promoter layer.

As polyurethane material for the PU instrument sample, polyester-based polyurethane described with respect to fig. 1 and sold under the name Tecoflex by the manufacturer Lubrizol Advanced Materials, Inc (ohio, usa) was also used herein. It is also noted here that instead of Tecoflex material, polycarbonate-based polyurethane sold by the same manufacturer under the trade name Carbothane can also be used.

In contrast to the procedure described with reference to fig. 1, the adhesive crosslinking layer according to the invention is composed of a chemical extender (here again ZeMac400, abbreviated to ZeMac) and an alcohol which is at least a diol (a diol having two primary OH groups) and the triol glycerol is used here as alcohol. In this case, a solution was first made from 1150mg of ZeMac, 80mg of glycerol and 23ml of dry acetone, in which two PU instrument samples 3 and 4 were subjected to an immersion process after a dissolution time of about two hours. The adhesive crosslinked layer was crosslinked at a temperature of about 100 ℃ for a long period of 1 hour after it was applied to samples 3 and 4.

It should be noted here that, instead of glycerol (propane-1, 2, 3-triol) as a triol, it is also possible to use any other alcohol, wherein an alcohol is understood here to be at least one diol having at least two primary OH groups. As other alcohols, there may be used ethylene-1, 2-diol (ethylene glycol, 1, 2-ethylene glycol), propylene-1, 2-diol (propylene glycol), propylene-1, 3-diol (1, 3-propylene glycol), butane-1, 4-diol (1, 4-butanediol), pentane-1, 5-diol (1, 5-pentanediol), hexane-1, 6-diol (1, 6-hexanediol), octane-1, 8-diol (1, 8-octanediol), nonane-1, 9-diol (1, 9-nonanediol), and decane-1, 10-diol (1, 10-decanediol).

During the above crosslinking, the maleic anhydride group of the extender ZeMac enters into bonding with the hydroxyl group of glycerol through esterification reaction. In this exothermic reaction step, the OH group of glycerol reacts with maleic anhydride ring opening. The possible esterification reactions are shown in the following diagram:

this reaction gives rise to further hydroxyl groups which themselves react with the maleic anhydride groups of the adjacent extender chain and thus cause crosslinking. As a result, as will be seen, a practically permanent anchoring of the extenders on the surface of the PU appliance is achieved, the extenders being applied together with the alcohol and being crosslinked.

As a result of the esterification, molecules are generated in the booster layer for the purpose of reinforcing the connection to the PU material molecules on the surface of the medical PU appliance, so that here not only a bonding force exists due to dipole-dipole bonding or through hydrogen bonding between the PU material of the PU appliance and the booster layer, but also a bonding force exists due to covalent bonding between the relevant materials or layers.

A copolymer layer comprising phosphorylcholine, available from the manufacturer Vertellus Specialties, Inc (indianapolis, usa), under the trade name PC2118, is then applied on the adhesive cross-linked layer, which may be a splint, of the medical PU device 3 and 4. The PC2118 layer was then crosslinked at a temperature of about 100 ℃ for a duration of about 1 hour. The material PC2118 relates to the above-mentioned choline phosphate-containing terpolymer — (2- (methacryloyloxyethyl) -2' - (trimethylammoniumethyl) phosphate, inner salt) - (hydroxypropyl methacrylate) - (3- (trimethoxysilyl) propyl methacrylate) copolymer. Thus, the materials involved comprise three different monomers; two of which are hydrophilic and one of which is hydrophobic.

As can be seen from fig. 2, the percentage portion of the amount of coating left on the medical PU devices 3 and 4 by the material used to form the two crosslinked layers after about 2.5 weeks from storage in water was about 85% or 79% of the amount of initial coating material applied on the two PU device samples 3 and 4. The relevant coating amount was then further reduced over the storage duration and after about 10 weeks was 80% or 73% of the initial coating material amount applied on the two PU device samples 3 and 4. In PU Instrument samples 3 and 4 in test solution H₂After 20 weeks in O, this PU device sample always contained either 77% or 71% of the amount of initial coating material on the two PU device samples 3 and 4, respectively.

It can therefore be seen from fig. 2 that after 8 weeks, i.e. after a prolonged period of use, the crosslinked layer and the adhesive crosslinked layer lying thereunder, which has the copolymer comprising phosphorylcholine, respectively, remain attached to the greatest extent and are not washed or rinsed away.

The crosslinked layer with the phosphorylcholine-containing copolymer and the adhesive crosslinked layer lying thereunder on the surface of the corresponding PU device sample are therefore suitable in an advantageous manner for the long-term use of such PU device samples mentioned in body cavities or body orifices of the human or animal body, in which the PU device is subjected to body fluids and in particular urine.

The relatively large adhesion properties of the above-mentioned layer consisting of the copolymer comprising phosphorylcholine on the adhesive crosslinked layer may be based on the above-mentioned esterification. By esterification, the molecules in the adhesive crosslinking layer also serve to strengthen the bond with the molecules of the copolymer comprising phosphorylcholine, so that here not only bonding forces are present due to dipole-dipole bonding or hydrogen bonding between the material of the adhesive crosslinking layer and the copolymer comprising phosphorylcholine, but also bonding forces are present due to covalent bonding between the material of the adhesive crosslinking layer and the polymer.

Finally, it should also be noted that the method steps described above with reference to fig. 1 and 2 can be used not only for the tests carried out, but at the same time also in the actually carried out coatings of medical PU devices. In this connection, it is considered to use the same mechanism of action between the PU material and the adhesive crosslinking layer of the medical PU device, and between the adhesive crosslinking layer and the at least one copolymer comprising phosphorylcholine as in the tests described according to fig. 1 and 2.

Furthermore, instead of the chemical extenders and phosphocholine-containing copolymers described in connection with fig. 1 and 2, other materials may be used.

Thus, instead of the chemical extenders described in connection with FIGS. 1 and 2, for example, an extender manufactured by Sigma-Aldrich Sigma-Aldrich (Missouri, USA) and applied below may be used.

Bis-2-hydroxyethyl-3-aminopropyltriethoxysilane

(65% in ethanol), HE-APTES for short)

Structural formula of HE-APTES

Bis [3- (trimethoxysilyl) propyl ] amine, abbreviated TMSPA

Structural formula of TMSPA

3- (triethoxysilyl) propyl isocyanate, abbreviated NCO

Structural formula of NCO

3-Aminopropyltriethoxysilane, abbreviated APTES

Structural formula of APTES

3-mercaptopropyltrimethoxysilane, abbreviated MPTMS

Structural formula of MPTMS

Trimethoxy [3- (methylamino) propyl ] silane, abbreviated TM-MAPS

Structural formula of TM-MAPS

Furthermore, instead of or in addition to the phosphorylcholine-containing terpolymer described in connection with fig. 1 and 2, (2- (methacryloyloxyethyl) -2' - (trimethylammoniumethyl) phosphate, inner salt) - (n-dodecyl methacrylate) - (2-hydroxypropyl methacrylate) - (3- (trimethoxysilyl) propyl methacrylate) copolymers containing four monomers may be used. This material is available under the name PC 1036 from the above-mentioned manufacturer Vertellus Specialties, Inc. The structural formula of PC 1036 is given below:

as can be seen from a comparison of the structural formulae PC2118 and PC 1036, the three monomers a, b and c of PC2118 correspond to the three monomers a, c and d of PC 1036; monomer b in PC 1036 is thus additionally engaged between monomers a and b of PC 2118.

Claims

1. A coating for a medical device which is to be brought into contact with body fluids of a human or animal body after introduction of the medical device, the coating comprising a material component comprising at least one polymer comprising phosphorylcholine,

characterized in that the material component for the medical device is an adhesive cross-linked layer which can be applied to the medical device, which comprises or consists entirely of polyurethane on its surface, which comprises a chemical enhancer and an alcohol cross-linked thereto, at least one diol having two primary OH groups, and which comprises the at least one polymer comprising phosphorylcholine, which is applied as a separate layer on the adhesive cross-linked layer and is cross-linked on the adhesive cross-linked layer and optionally cross-linked with the adhesive cross-linked layer.

2. The coating of claim 1, wherein the medical device is contacted with urine after its introduction into a human or animal body.

3. The coating according to claim 1 or 2, characterized in that the polymer comprising choline phosphate is formed from a (2- (methacryloyloxyethyl) -2'- (trimethylammoniumethyl) phosphate, an inner salt) - (hydroxypropyl methacrylate) - (3- (trimethoxysilyl) propyl methacrylate) copolymer and/or a (2- (methacryloyloxyethyl) -2' - (trimethylammoniumethyl) phosphate, an inner salt) - (n-dodecyl methacrylate) - (2-hydroxypropyl methacrylate) - (3- (trimethoxysilyl) propyl methacrylate) copolymer.

4. A coating according to claim 1 or 2, wherein the chemical extender is formed from a copolymer of ethylene and maleic anhydride.

5. A method for coating a medical device which is brought into contact with its body fluid after its introduction into the human or animal body with a material composition comprising at least one monomer or polymer comprising phosphorylcholine, characterized in that a first layer is applied to a medical device comprising polyurethane on its surface or consisting entirely of polyurethane, the first layer being formed from a chemical booster and an alcohol, at least one diol having two primary OH groups, the chemical booster and the alcohol in the first layer being crosslinked to form a crosslinked layer, and then a second layer comprising phosphorylcholine is applied on the crosslinked layer, the second layer having at least one polymer comprising phosphorylcholine, and the second layer also being crosslinked.

6. The method of claim 5, wherein the medical device is contacted with urine after its introduction into the human or animal body.

7. The method according to claim 5 or 6, characterized in that (2- (methacryloyloxyethyl) -2'- (trimethylammoniumethyl) phosphate, an inner salt) - (hydroxypropyl methacrylate) - (3- (trimethoxysilyl) propyl methacrylate) copolymer and/or (2- (methacryloyloxyethyl) -2' -trimethylammoniumethyl) phosphate, an inner salt) - (n-dodecyl methacrylate) - (2-hydroxypropyl methacrylate) - (3- (trimethoxysilyl) propyl methacrylate) copolymer are selected as the polymer comprising choline phosphate in the second layer.

8. A method according to claim 5 or 6, characterized in that a copolymer of ethylene and maleic anhydride is selected as chemical enhancer in the first layer.

9. The method according to claim 5 or 6, wherein the cross-linking of the chemical enhancer and the alcohol of the first layer and the cross-linking of the at least one polymer comprising phosphorylcholine of the second layer are each performed at a temperature in the range of 60 ℃ to 140 ℃.

10. The method according to claim 5 or 6, characterized in that the cross-linking of the chemical enhancer and the alcohol of the first layer and the cross-linking of the at least one polymer comprising phosphorylcholine of the second layer are carried out at a temperature ranging from 80 ℃ to 120 ℃ respectively.

11. The method according to claim 5 or 6, characterized in that the respective crosslinking duration is 15 minutes to 1 day.

12. The method according to claim 5 or 6, characterized in that the respective crosslinking duration is 45 minutes to 2 hours.

13. A medical device comprising or entirely consisting of polyurethane on its surface and intended for use in an area of a human or animal body where it is in contact with its bodily fluids, the medical device comprising a coating applied on its device surface, the coating being manufactured and cross-linked according to the method of any one of claims 5 to 12.

14. The medical device of claim 13, wherein said medical device is in contact with urine in said region.