WO2017084647A1

WO2017084647A1 - Coating for a medical instrument, method for the coating thereof, and medical instrument coated using said method

Info

Publication number: WO2017084647A1
Application number: PCT/DE2016/000397
Authority: WO
Inventors: Dirk Muscat; Johann Voit; Sophia Hefenbrock
Original assignee: Urotech Gmbh
Priority date: 2015-11-18
Filing date: 2016-11-15
Publication date: 2017-05-26
Also published as: CN108463257B; CN108463257A; DE102015014912A1; MA43264A; DE102015014912B4; EP3377127A1

Abstract

The invention relates to a coating for a medical instrument, which contains polyurethane on the surface thereof or consists entirely of same, and which, after being introduced into a human or animal body, comes into contact with the bodily fluid thereof, in particular urine, wherein the coating contains an adhesive cross-linking layer which is applied to the instrument and made of a chemical bonding agent and an alcohol cross-linked with same, as well as a layer which is made of copolymers containing at least one phosphorylcholine, and applied to the adhesive cross-linking layer and cross-linked on, and optionally with same.

Description

COATING FOR A MEDICAL INSTRUMENT, METHOD FOR THE COATING THEREOF, AND MEDICAL INSTRUMENT COATED WITH THIS METHOD

The present invention relates to a coating for a medical instrument which, after its introduction into a human or animal body, comes into contact with its body fluid, in particular with urine, comprising a material composition containing at least one polymer comprising phosphorylcholine. Furthermore, the present invention relates to a method for coating a medical instrument and a medical instrument coated with this method.

A medical instrument is understood here on the one hand to be a medical catheter which is to be introduced into a human or animal body and removed from it again after a certain period of time. In such a medical catheter, which, for example, comes into contact with urine in a human or animal body, it may in particular be a urether catheter, which is also referred to as a ureter rail. On the other hand, a medical instrument here means a medical implant which is to be introduced into a human or animal body or which is to be used as permanently as possible in it. However, with such implants, it can not be ruled out that they should be removed from the implant carrier after a certain period of time.

The carrier material of which medical instruments of the aforementioned type are made must generally be biocompatible. As such biocompatible carrier materials, various polyurethanes may be used, such as a polyester-based polyurethane or a polycarbonate-based polyurethane. The sliding properties of the respective carrier materials in body cavities or openings of human or animal bodies, however, sometimes do not satisfy requirements for so-called flooding, that is to say for virtually frictionless, but at least very low friction, displaceability of the medical instruments produced from these carrier materials. Therefore, such medical instruments are usually coated on their surface with a sliding layer. For the coating of medical instruments, the applicant has already tested at least one polymer comprising phosphorylcholine because, due to its hydrophilic or hydrophobic property, the sliding properties of the relevant medical instruments during their insertion into and out of body orifices or cavities of human or animal To improve bodies compared to those of the medical instruments forming or containing the support material.

In addition, on medical instruments coated in this way, there are no infiltrations of salts contained in liquids to which the instruments concerned are exposed. This also avoids the danger of infections associated with such incrustations.

The phosphorylcholine has the following structure:

There are already known polymeric material compositions for the surface coating of devices which come into contact with protein-containing or biological fluids (see the documents DE 692 31 450 T2, DE 692 33 378 T2, DE 699 07 686 T2, US 7 160 953). Phosphorylcholine-containing copolymers which are crosslinked are mainly used in these material compositions. According to published data (see document DE 692 31 450 T2), stable coatings are produced with the relevant material compositions on a wide variety of surfaces such as polyethylene, PVC, steel and poly (imid).

However, in the case of medical instruments containing or entirely consisting of polyurethane on their surface - hereinafter also referred to as PU instruments - such medical instruments, it has been shown in experiments that coatings containing the known material compositions in question only last for a relatively short time Liability periods on such medical instruments stick when exposed to a liquid, such as water or urine. Thus, in tests with such coatings in a liquid, such as water or urine, adhesion times of only a few hours to some reached in a few days. However, such liability periods are too short for a so-called long-term use of medical instruments in human or animal bodies. A long-term use is understood here to be a use of the medical instruments for a period of at least eight weeks. Within such a period of time, the particular medical instrument used in a human or animal body should remain unchanged in its nature and coating and need not be changed.

In order to achieve the mentioned long-term use of medical PU instruments, it has been investigated in further experiments whether adhesion promoter layers applied to the surface of the relevant PU instruments and containing various chemical adhesion promoters (so-called primers) on this surface of the relevant PU instruments could be anchored during the mentioned long term. However, the tests carried out showed that even such primer layers would only adhere to the medical PU instruments to which they were applied for a few hours to a few days, when the respective instruments were exposed to a liquid, such as water or urine. Incidentally, a similar result was also obtained, as will be explained in more detail below, when an additional layer of phosphorylcholine-containing polymers was applied to a primer layer which had been applied to a medical instrument and crosslinked. In this case, too, only a relatively short duration of adhesion of the layer structure consisting of these two layers could be achieved if the medical PU instrument carrying this layer structure was exposed to a liquid, such as water or urine.

As a cause for the above-mentioned relatively poor adhesion of the

Phosphorylcholine comprising copolymers either alone or with the involvement of a primer layer of a chemical adhesion promoter on a medical PU instrument whose surface contains polyurethane or entirely consists of that is that neither between the surface of the PU instrument and the adhesive layer still between This bonding agent layer and the layer of the copolymers comprising phosphorylcholine sufficient binding forces exist, whether due to covalent bond or by dipole-dipole bond or by hydrogen bonding both between the material of the PU instrument and the chemical coupling agent of the adhesive layer and between this adhesive layer and the layer of the copolymers comprising phosphorylcholine. In this context, the well-known fact that dipole-dipole bonds and hydrogen bonds are often more effective from different materials towards water than between the respective materials themselves must also be taken into account. This may also be the reason why both the adhesion promoter layer a chemical adhesion promoter as well as the layer of the copolymers comprising phosphorylcholine either alone or with the interposition of the adhesive layer after application to a medical PU instrument of this again relatively quickly solved when the thus coated PU instrument was exposed to a respective water environment.

The present invention is therefore based on the object to show a way how to provide in a relatively simple, yet effective way, such a coating for medical instruments, which, after it has been applied to the relevant instruments, on this even during the Duration of the above-mentioned long-term use of medical instruments, that is firmly anchored for a period of at least eight weeks.

In addition, it is an object of the present invention to provide a method for coating a medical instrument and a medical instrument coated with this method.

The above object is achieved with a coating of the aforementioned type according to the invention in that the material composition for a medical instrument containing polyurethane on its surface or consisting entirely of it, an attachable to the medical instrument adhesion network layer of a chemical adhesion promoter and a with this crosslinked alcohol, at least one dihydric alcohol having two primary OH groups, and containing at least one phosphorylcholine polymer, which is applied to the Haftungsvernetzungsschicht as a separate layer and on this and optionally crosslinked with this.

The coating according to the present invention is characterized by the advantage that, after being applied to the surface of a medical instrument which contains polyurethane on its surface or which consists entirely of polyurethane, it has an adhesion time of more than eight weeks adherence when the instrument in question is exposed to a fluid, such as water or urine, by continuous irrigation. According to the present state of knowledge, this relatively long liability period is based on the material composition tion according to the present invention enabled dual crosslinking; the first crosslinking results in the formation of an adhesion-crosslinking layer of a chemical coupling agent and an alcohol, at least one dihydric alcohol having two primary OH groups, and the second crosslinking capability is provided by a layer of the at least one phosphorylcholine applied to the formed adhesion-crosslinking layer comprehensive copolymer optionally crosslinkable with the Haftungsvernetzungsschicht.

As a result of the crosslinking of the chemical adhesion promoter with the alcohol in the adhesion crosslinking layer, there are surprisingly sufficient bonding forces-whether due to covalent bonding or by dipole-dipole bonding or by hydrogen bonding-in contrast to the experiments described at the outset the material of the PU instrument and the chemical adhesion promoter of the adhesion promoter layer as well as between this adhesion promoter layer and the layer of the copolymers comprising phosphorylcholine. These binding forces are believed to be based on esterification of the alcohol with the chemical coupling agent and the resulting crosslinks in the primer layer to the surface of the PU instrument and in the layer of the copolymers comprising phosphorylcholine.

Preferably, the polymer comprising phosphorylcholine is poly (2- (methacrylooxyethyl) -2 '- (trimethylammonium ethyl phosphate, inner salt) -co- (hydroxypropyl methacrylate) -co- (3- (trimethoxysilyl) propyl methacrylate and / or poly (2 - (methacryloyloxethyl) -2 '- (trimethylammoniumethyl) phosphate, inner salt) -co- (n-dodecylmethacrylate) -co- (2-hydroxypropylmethacrylate) -co- (3-

(Methoxysilyl) propyl methacrylate formed. This results in the advantage that a phosphorylcholine which is particularly effective for the desired adhesion time (at least eight weeks on a PU instrument) of the material composition according to the present invention can be used.

Conveniently, the chemical coupling agent is formed by a copolymer of ethene and maleic anhydride. This has the advantage that a chemical coupling agent which is particularly effective with respect to the adhesion of the material composition according to the present invention to a PU instrument can be used.

The above object is further achieved by a method for coating a medical instrument, which after its introduction into a human Chen or animal body with its body fluid, in particular comes into contact with urine, with a material composition containing at least one polymer comprising phosphorylcholine, according to the invention characterized in that on the surface of its polyurethane-containing or entirely existing medical instrument a first layer of a chemical coupling agent and an alcohol, at least one dihydric alcohol having two primary OH groups is applied,

that the chemical adhesion promoter and the alcohol in said first layer are crosslinked to form a crosslinking layer,

that then a phosphorylcholine-containing second layer comprising the polymer comprising at least one phosphorylcholine is applied to the crosslinking layer,

and that the second layer is also crosslinked. This results in the advantage that in two successive coating operations, each comprising a crosslinking process, the material composition can be applied as a long-term coating according to the invention on the surface of a PU instrument, on the surface of this coating during a liability time of more than sticks for eight weeks, when the PU instrument of a liquid, such as water or urine is also constantly exposed, for example, by storage in or purging with this liquid.

Preferably, as the phosphorylcholine-comprising polymer in the second layer, poly (2- (methacryloyloxyethyl) -2 '- (trimethylammonium ethyl phosphate, inner salt) -co- (hydroxypropyl methacrylate) -co- (3- (trimethoxysilyl) propyl methacrylate and / or poly ( 2- (methacryloyloxyethyl) -2 '- (trimethylammoniumethyl) phosphate, inner salt) -co- (n-dodecylmethacrylate) -co- (2-hydroxypropylmethacrylate) -co- (3- (trimethoxysilyl) propylmethacrylate and / or poly (2- (methacryloyloxyethyl) -2'- (trimethylammoniumethyl) phosphate, inner salt) -co- (n-dodecylmethacrylate) -co- (2-hydroxypropylmethacrylate) -co- (3- (trimethoxysilyl) propylmethacrylate.) This has the advantage that A phosphorylcholine which is particularly effective for the intended period of adhesion (at least eight weeks on a PU instrument) of the material composition according to the present invention is expediently used as chemical adhesion promoter in the first layer, a copolymer of ethene and maleic anhydride id selected. This brings with it the advantage that one in terms of the adhesion of the material composition according to the present invention on a PU instrument particularly effective chemical coupling agent is used.

In order to obtain an excellent adhesion result by the method according to the invention, the crosslinking of the chemical coupling agent and the alcohol of the first layer and the crosslinking of the phosphorylcholine comprising polymer of the second layer are in each case in a temperature range between about 60 ° C and about 140 ° C, preferably between about 80 ° C and 120 ° C performed. This has the advantage that it is possible to work with relatively easily realizable crosslinking temperatures.

Preferably, the particular crosslinking is carried out for a period between about 15 minutes and 1 day, preferably between about 45 minutes and about 2 hours. This advantageously achieves an acceptable period of time, that is to say not too long a time span for the respective crosslinking.

The above-mentioned object is also achieved by a medical instrument which contains or entirely consists of polyurethane on its surface and which is intended to be inserted in a region of a human or animal body in which it reacts with its body fluid, in particular with Urine comes into contact containing a deposited on its instrument surface material composition, which is prepared and crosslinked by a method according to the invention. This has the advantage that a medical PU instrument is available, on the surface of which the material composition layer remains adhered for the intended adherence time of more than eight weeks, when the instrument concerned is also exposed to a liquid, such as water or urine, by continuous flushing ,

With reference to drawings, the invention will be explained in more detail below. In the drawings show

Fig. 1 is a diagram showing the temporal weight development of in a

Test liquid stored coatings previously on two PU

Instrument samples without application of the invention have each been formed from a adhesion-crosslinking layer and copolymers comprising phosphorylcholine applied thereto, and Fig. 2 is a diagram showing the time evolution of weight in a

Test liquid stored coatings shows that have been previously formed according to the invention on two PU instrument samples each of a Haftungsvemet- tion layer and applied thereon comprising phosphorylcholine copolymers.

Before discussing the diagrams according to FIGS. 1 and 2, it should be noted here that these diagrams are based on tests in test liquids for which H ₂ O has been used. However, the test results obtained are at least qualitatively readily transferable to other fluids, especially urine; In fact, water (H ₂ O) alone has a greater ability to dissolve or dissolve in urine compared to the coating materials of PU instrument samples considered below. To produce the diagram of FIG. 1, a coating of two layers has been applied to two PU instrument samples - referred to as sample 1 and sample 2 - without the present invention. As PU instrument samples, tube-shaped or tubular PU specimens having an outer diameter of about 2.3 mm to 2, in each case about 100 to 150 mm in length, are both for the production of the diagram of FIG. 1 and of FIG. 5mm used.

As the polyurethane material of the PU instrument samples, a polyester-based polyurethane sold by the manufacturer Lubrizol Advanced Materials, Inc., Ohio, U.S.A. under the name Tecoflex has been used. It should be noted at this point that, instead of the Tecoflex material, it would also be possible to use a polycarbonate-based polyurethane from the same manufacturer, marketed under the trade name Carbosane.

The coating in question consists here of a first adhesion promoter layer and of a second layer of phosphorylcholine-containing copolymers applied thereto. To the coating quantities should also be noted that an amount of 5 mg in an area of 100 mm ² of a material density of 1 g / cm ^3, and thus adopted a mean coating thickness of 5pm corresponds. As a chemical adhesion promoter here is a commercially available from the manufacturer Vertellus Specialties, Inc., Indianapolis, USA under the name ZeMac 400 chemical adhesion promoter - in the following and in the drawings only briefly as ZeMac be draws - has been used. This chemical coupling agent is a copolymer of ethene and maleic anhydride.

First, 1150 mg of ZeMac were dissolved as a powder in 23 ml of acetone for about 2 hours. Thereafter, the two PU instrument samples 1 and 2 were coated with this chemical primer material in a dipping operation and then subjected to heat treatment at about 100 ° C for about one hour, whereby the chemical coupling agent was crosslinked. Subsequently, a layer of copolymers containing phosphorylcholine has been applied to the adhesion promoter layer of the chemical adhesion promoter ZeMac thus formed. As the copolymers containing phosphorylcholine, copolymers available from the manufacturer Vertellus Specialties, Inc., Indianapolis, U.S.A., under the name PC 2118, have been used. Material PC 2118 is the three copolymers comprising poly (2- (methacryloyl-oxyethyl) -2 '- (trimethylammoniumethyl) phosphate, inner salt) -co- (hydroxypropylmethacrylate) -co- (3- (3-phosphorylcholine) trimethoxysilyl) propyl methacrylate, so the material in question comprises three different monomers, two of which are hydrophilic and one is hydrophobic.

From this, the three monomers can be seen, namely

a -> Poly (2- (methacryloyloxyethyl) -2 '- (trimethylammoniumethyl) phosphate, inner salt

b-hydroxypropyl methacrylate

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

The corresponding structural formula is given below:

To apply the layer of phosphorylcholine-containing copolymers on the crosslinked adhesion promoter layer of the two PU instrument samples 1 and 2, these were then coated in a dipping process in a solution of 2300 mg of PC 21 18 and 23 ml of ethanol and then a heat treatment at a temperature of about 100 ° C during a period of about 1 h subjected and also networked.

1 shows the weight development of the coating amounts of the two PU instrument samples 1 and 2 as a function of the storage time of the respective samples in a test liquid H ₂ 0. Here, in the ordinate direction, the percentage of the portion remaining on the respective PU instrument sample of the total applied to this coating material, and in the abscissa the storage time (= examination time) of the two crosslinked layers, so the Haftungsvernetzungsschicht and the PC-21 18-layer bearing PU instrument samples applied in weeks.

The determination of the percentage of the remaining on the respective PU instrument sample portion of the total applied to this coating material is done here arithmetically on the basis of gravimetric weight determinations by means of analytical balance. For this purpose, first the weight G1 of the instrument sample alone and then the weight G2 of the instrument sample coated with the coating material have been determined. On the incorporation of the coated with the coating material instrument sample in a test liquid then the weight G3 of the relevant instrument sample has been determined at certain times. The mentioned percentage A can then be deduced from the relationship

A = ^{G3 ~ G1} - 100 [%]

G2 - G \

calculate.

The storage of the samples 1 and 2 in the H ₂ O-containing test liquid thus coated with the chemical adhesion promoter ZeMac and the phosphorylcholine copolymers PC 2118 showed a significant loss of coating material in both samples after only about three weeks Test liquid from both PU instrument samples had solved. After about three weeks of storage in the test liquid, sample 1 contained only about 10% of the coating amount originally applied to it, and sample 2 even contained only about 5% of the coating amount after this three-week storage in the test liquid that was originally applied to them. To After approximately ten weeks of storage in the test liquid, the entire coating of both Samples 1 and 2 had disappeared - the coating material had almost completely dissolved from the PU instrument samples in the test liquid. Thus, after approximately three weeks of storage in the test liquid, samples 1 and 2 have already lost their initial good sliding properties to such an extent that their coatings are not suitable for the long-term use mentioned in the beginning.

FIG. 2 illustrates the weight development of the coating amount of a coating formed according to the invention on two PU instrument samples 3 and 4 as a function of the storage duration of the respective samples 3, 4 in a test liquid. Here, as in Fig. 1, in the ordinate direction, the percentage of the remaining portion of the respective PU instrument sample is plotted from the total coating material applied thereto, and in the abscissa direction, the storage period is weeks (= examination time) of the PU coated according to the invention Instrument samples 3, 4 applied in the test liquid, which is also given here by H2O.

Again, the determination of the percentage of the remaining on the respective PU instrument sample portion of the total applied to this coating material is calculated on the basis of gravimetric weight determinations by means of analytical balance, as has been explained with reference to FIG. In addition, here corresponding steps are carried out for the steps illustrated in connection with FIG. 1 for applying a primer layer and a layer of phosphorylcholine-containing polymers to PU instrument samples, but with the deviation explained below for the adhesion promoter layer.

As the polyurethane material of the PU instrument samples, the polyester-based polyurethane mentioned in connection with Fig. 1 and sold by the manufacturer Lubrizol Advanced Materials, Inc., Ohio, U.S.A. under the name Tecoflex has also been used herein. It should also be noted at this point that, instead of the Tecoflex material, it would also be possible to use a polycarbonate-based polyurethane of the same manufacturer marketed under the trade name Carbothane.

In contrast to the steps explained with reference to FIG. 1, the adhesion-crosslinking layer according to the invention consisted of a chemical adhesion promoter (here again ZeMac 400 - abbreviated to ZeMac) and an alcohol containing at least one is dihydric alcohol (a diol having two primary OH groups) and as which here the trihydric alcohol glycerol has been used. In the present case, a solution of 1150 mg of ZeMac, 80 mg of glycerol and 23 ml of acetone, dried, was first prepared in which after about two hours of solution time the two PU instrument samples 3 and 4 were coated in a dipping process. This adhesion-curing layer was crosslinked after its application to Samples 3 and 4 for about 1 hour at a temperature of about 100 ° C.

It should be noted here that instead of glycerol (propane-1, 2,3-triol) as trivalent alcohol, any other alcohol can be used, wherein an alcohol here is understood to mean at least one diol having at least two primary OH groups. As such other alcohols are ethane-1, 2-diol (ethylene glycol, 1, 2-glycol), propane-1, 2-diol (propylene glycol), propane-1, 3-diol (trimethylene glycol), butane-1, 4, diol (tetramethylene glycol), pentane-1,5-diol (pentamethylene glycol), hexane-1,6-diol (hexamethylene glycol), octane-1,8-diol (octamethylene glycol), nonane-1, 9-diol (nonamethylene glycol) , Decane-1, 10-diol (decamethylene glycol) in question.

In the crosslinking considered above, the maleic anhydride groups of the adhesion promoter ZeMac enter into a bond with the hydroxyl groups of the glycerol by means of a esterification reaction. In this exothermic reaction step, the OH groups of the glycerol react with the maleic anhydride with ring opening. A possible esterification reaction shows the following representation:

By this reaction, further hydroxyl groups are available, which in turn can react with maleic anhydride groups of adjacent adhesion promoter chains and thus bring about crosslinking. As a result, as will be seen, a practically permanent anchoring of the coupling agent on the surface of the PU instrument was achieved, to which it was applied and crosslinked together with the alcohol. Due to the esterification, molecules are available in the adhesion promoter layer for a strong connection with molecules of the PU material on the surface of the medical PU instrument, so that binding forces are not only due to dipole-dipole bonding or hydrogen bonding between the surface PU material of the PU instrument and the adhesive layer exist, but also due to covalent bonding between the respective materials or

Layers.

A layer of phosphorylcholine copolymers available from Vertellus Specialties, Inc., Indianapolis, USA, under the designation PC 2118, was then applied to this adhesion-crosslinking layer of the medical grade PU instrumental samples 3 and 4, which may be urethane splints , Then, this PC-2118 layer was also crosslinked at a temperature of about 100 ° C for about 1 hour. Material PC 2118 is the above-mentioned phosphorylcholine comprising three copolymers poly (2- (methacryloyloxyethyl) -2 '- (trimethylammoniumethyl) phosphate, inner salt) -co- (hydroxypropyl methacrylate) -co- (3 (trimethoxysilyl) propyl methacrylate Thus, the material in question comprises three different monomers, two of which are hydrophilic and one is hydrophobic.

As can be seen in Figure 2, the percentages of coating amount remaining on the PU medical instrument samples 3 and 4 out of the total material used to form the two crosslinking layers remained in water after approximately 2.5 weeks of storage were about 85% and 79%, respectively, of the amount of coating originally applied to the two PU instrument samples 3 and 4. The respective coating amounts then further decreased over the period of storage and amounted to about 80% or 73% of the amount of coating originally applied to the two samples 3 and 4 after about 10 weeks. After 20 weeks of storage of the PU instrument samples 3 and 4 in the test liquid H2O, they still contained about 77% and 71% respectively of the original amount of coating material applied to the two PU instrument samples 3 and 4.

It can thus be seen from FIG. 2 that the crosslinking layer comprising phosphorylcholine comprising copolymers and the adhesion-crosslinking layer below it have largely adhered to the surface of the respective PU instrument sample even after 8 weeks, that is to say after the duration considered for long-term use, and not had been washed off or rinsed off. The crosslinking layer comprising phosphorylcholine-comprising copolymers and the layer of adhesion crosslinking thereunder on the surface of the respective PU instrument sample are therefore excellently suitable for the long-term use mentioned of such PU instrument samples in body cavities or orifices of human or animal bodies in which they contain body fluids and especially urine are exposed.

Also, the above-explained relatively strong adhesion of the layer of the copolymers comprising phosphorylcholine on the adhesion-crosslinking layer may be based on the above-mentioned esterification. As a result of this esterification, molecules in the adhesive crosslinking layer also have a strong bond with molecules of the

Also, bonding forces exist not only due to dipole-dipole bonding or hydrogen bonding between the material of the adhesion crosslinking layer and the phosphorylcholine copolymers, but also due to covalent bonding between the material of the adhesion crosslinking layer and the mentioned polymers.

Finally, it should be noted that the method steps explained above with reference to FIGS. 1 and 2 not only apply to the tests that have been carried out, but can equally be applied to the coating of medical PU instruments carried out in practice. In this case, the same mechanisms of action occur between the PU material of the medical PU instruments and the adhesive crosslinking layer and between the adhesion crosslinking layer and the fewest copolymers comprising a phosphorylcholine, as demonstrated in connection with the investigations explained with reference to FIGS. 1 and 2 are.

In addition, other materials may be used in place of the chemical coupling agent and the copolymers comprising phosphorylcholine, which have been described in connection with FIGS. 1 and 2.

Thus, instead of the chemical coupling agent mentioned in connection with FIGS. 1 and 2, for example, the adhesion promoters listed below from the manufacturer Sigma-Aldrich Sigma-Aldrich Corporatiom, Missouri, U.S.A. may be used.

Bis-2-hydroxyethyl-3-Aminopropyltrieethoxysilan

(65% in ethanol), abbreviated HE-APTES)

Structural formula HE-APTES

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

Structural formula TMSPA 3- (triethoxysilyl) propyl isocyanate, abbreviated to NCO

Structural formula NCO

3-aminopropyltriethoxysilane, abbreviated APTES

Structural formula APTES

3-mercaptopropyltrimethoxysilane, abbreviated MPTMS

OCH3

Si-OCH ₃

OCH3

Structural formula MPTMS

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

N H

Structural Formula TM-MAPS Further, instead of or in addition to the phosphorylcholine mentioned in connection with Figures 1 and 2, the three copolymers (n) may contain the four-monomer-containing poly (2- (methacryloyloxyethyl) -2 '- (trimethylammoniumethyl) phosphate, inner Salt) -co- (n-dodecylmethacrylate) -co- (2-hydroxypropylmethacrylate) -co- (3- (trimethoxysilyl) propylmethacrylate) This material is from Vertellus Specialties, Inc., Indianapolis, USA mentioned above available under the designation PC 1036. The structural formula of PC 1036 is given below:

As can be seen from a comparison of the structural formulas of PC 2118 and PC 1036, the three monomers a, b and c of PC 2118 correspond to the three monomers a, c and d, respectively, of PC 1036; the monomer b in PC 1036 is thus additionally inserted between the monomers a and b of PC 2118.

Claims

claims

A coating for a medical instrument which, after its introduction into a human or animal body, comes into contact with its body fluid, in particular with urine, comprising a material composition containing at least one polymer comprising phosphorylcholine,

characterized in that the composition of matter for a medical instrument containing polyurethane on its surface, or consisting entirely of it, comprises a bonding layer of a chemical coupling agent and a cross-linked alcohol, at least one dihydric alcohol having two primary ones, which can be applied to the medical instrument OH groups, and containing at least one phosphorylcholine polymer, which is applied to the Haftungsvernetzungsschicht as a separate layer and on this and optionally crosslinked with this.

2. Coating according to claim 1,

characterized in that the polymer comprising phosphorylcholine is poly (2- (methacryloyloxyethyl) -2 '- (trimethylammonium ethyl phosphate, inner salt) -co- (hydroxypropyl methacrylate) -co- (3- (trimethoxysilyl) propyl methacrylate and / or poly (2 - (methacryloyloxyethyl) -2 ^, - (trimethylammoniumethyl) phosphate, inner salt) -co- (n-dodecylmethacrylate) -co- (2-hydroxypropylmethacrylate) -co- (3- (trimethoxysilyl) propylmethacrylate.

3. Coating according to claim 1 or 2,

characterized in that the chemical adhesion promoter is formed by a copolymer of ethene and maleic anhydride.

4. A method for coating a medical instrument, which, after its introduction into a human or animal body, comes into contact with its body fluid, in particular urine, with a material composition containing at least one mono- or polymer comprising phosphorylcholine, characterized in that a first layer of a chemical adhesion promoter and an alcohol, at least one dihydric alcohol having two primary OH groups, is applied to the surface of the polyurethane containing or wholly existing medical instrument,

that the chemical adhesion promoter and the alcohol in said first layer are crosslinked to form a crosslinking layer, that then a phosphorylcholine-containing second layer comprising the polymer comprising at least one phosphorylcholine is applied to the crosslinking layer,

and that the second layer is also crosslinked.

5. The method according to claim 4,

characterized in that the polymer comprising phosphorylcholine in the second layer comprises poly (2- (methacryloyloxyethyl) -2'-

(trimethylammoniumethylphosphate, inner salt) -co- (hydroxypropylmethacrylate) -co- (3- (trimethoxysilyl) propylmethacrylate and / or poly (2- (methacryloyloxyethyl) -2'- (trimethylammoniumethyl) phosphate, inner salt) -co- ( n-dodecyl methacrylate) -co- (2-hydroxypropyl methacrylate) -co- (3- (trimethoxysilyl) propyl methacrylate.

6. The method according to claim 4 or 5,

characterized in that a copolymer of ethene and maleic anhydride is selected as the chemical adhesion promoter in the first layer.

7. The method according to any one of claims 4 to 6,

characterized in that the crosslinking of the chemical adhesion promoter and the alcohol of the first layer and the crosslinking of the phosphorylcholine comprising at least one polymer of the second layer each in a temperature range between about 60 ° C and about 140 ° C, preferably between about 80 ° C. and 120 ° C is performed.

8. The method according to claim 6 or 7,

characterized in that the respective crosslinking is carried out for a duration of between about 15 minutes and 1 day, preferably between about 45 minutes and about 2 hours.

9. A medical instrument containing on its surface polyurethane or consisting entirely of it and which is intended for insertion in a region of a human or animal body, in which it comes into contact with the body fluid, in particular with urine containing one of his Surface-applied coating prepared and crosslinked according to any one of claims 4 to 8.