Abstract
The aspects of the disclosed embodiments relates to methods for optimization of the sliding properties of urinary catheters. The urinary catheters are first treated with a non-equilibrium gaseous plasma sustained in reactive gases or a mixture of a reactive gas with a noble gas. The first treatment enables a hydrophilic surface finish when oxygen is a reactive gas and an almost super-hydrophilic finish when the catheter is treated with hydrogen plasma followed by oxygen plasma. The hydrophilicity of the surface finish obtained upon the first plasma treatment is beneficial for adhering a layer of water solution of chitosan, which spreads uniformly on the entire outer surface of the catheter. The catheter with a layer of water solution of chitosan is dried and then treated with plasma containing an oxidative gas for better absorption of water by the dried chitosan film.
Claims
1. A method for preparation of chitosan-coated catheters comprising the following steps: a) treatment of a polymer catheter with a non-equilibrium gaseous plasma of molecular gases, b) application of a water solution or water suspension of chitosan on the plasma-treated polymer catheter prepared in step a), c) drying the catheter with the deposited solution or suspension of chitosan prepared in step b), and d) treatment of the chitosan-coated urinary catheter prepared in step c) with non-equilibrium gaseous plasma.
2. The method according to claim 1, wherein the concentration of chitosan in step b) is between 1 and 5% w/v, most optimally around 2 to 2.5% w/v.
3. The method according to claim 1, wherein the chitosan solution is applied by dipping, spraying, or any other suitable deposition method.
4. The method to claim 1, wherein drying is performed by any suitable method, preferably vacuum drying, fanning, or heating until the water evaporates.
5. The method according to claim 1, wherein step d) is shorter than the treatment in step a).
6. The method according to claim 5, wherein treatment in step d) is performed for 0.1 to 10 seconds, most preferably 1 to 3 seconds.
7. The method according to claim 5, wherein treatment in step d) is performed using oxygen plasma with the ratio between the ion density (O.sub.2.sup.+) and neutral oxygen atom (O) densities at most 10.sup.?5.
8. The method according to claim 1, wherein the molecular gas in plasma treatments in steps a) and d) is at least one gas selected in the group of reactive gases, noble gasses and mixtures thereof.
9. The method according to claim 7, wherein the reactive gas is selected in the group comprising water vapor, oxygen, ozone, nitrogen, carbon oxides, ammonia, and mixtures of these gases, including air.
10. The method according to claim 1, wherein plasma treatment is performed with two gases either in a single step or sequentially.
11. The method according to claim 10, wherein the first treatment with non-equilibrium gaseous plasma in step a) is performed using two different gases, for example, hydrogen or nitrogen or ammonia, followed by oxygen-comprising plasma.
12. The method according to claim 1, wherein the treatments with non-equilibrium gaseous plasma in steps a) and d) are performed with continuous and pulsed discharges, preferably at a discharge power density between 0.1 and 100 kW m.sup.?3 .
13. The method according to claim 1, wherein the treatments with non-equilibrium gaseous plasma in steps a) and d) are performed at a pressure between 0.1 and 1,000 Pa, preferably between 1 and 100 Pa.
14. A chitosan-coated catheter, wherein the chitosan layer on the catheter is highly wettable and the water contact angle is around 50? or lower, preferably 40??5? or lower.
15. The chitosan-coated catheter according to claim 14, wherein the cather comprises a medical-grade polyvinyl (PVC) blend or from thermoplastic elastomer (TPE) blend.
Description
SUMMARY OF THE FIGURES
[0027] Embodiments and examples illustrating the methods of the aspects of the disclosed embodiments will now be discussed with reference to the accompanying figures, which show:
[0028] FIG. 1 a schematic of the method according to the aspects of the disclosed embodiments
[0029] FIG. 2 a device for the treatment of catheters with gaseous plasma
DETAILED DESCRIPTION
[0030] While the methods of the aspects of the disclosed embodiments may be used for all types of polymer catheters, the usefulness is demonstrated for two types of catheters, one made from a medical-grade polyvinyl (PVC) blend and the other one from a thermoplastic elastomer (TPE) blend. These materials exhibit appropriate properties and are standardly used for the synthesis of urinary catheters. Both materials are moderately hydrophobic with a water contact angle of approximately 98? and 100? for PVC and TPE, respectively. These materials do not swell upon wetting: a water droplet will dry rather than be absorbed by the PVC or TPE blends. If immersed in water or a water solution of chitosan and pulled from the water, some randomly distributed water droplets will remain on the surface of the catheters, but the vast surface will remain dry. This is a consequence of an imbalance between the surface energy of catheters and water. If catheters are dipped into a water solution of chitosan and pulled out and dried, chitosan will be scarce and non-evenly distributed on a catheter surface. Furthermore, when a catheter previously dipped in a chitosan solution and then dried is dipped into water, the chitosan deposited on the untreated catheter will dissolute in the water. The term untreated catheters here means that they were not pretreated by any means to improve their wettability or adhesion before immersion into a water solution of chitosan The untreated catheters are, thus, impractical for application because of the high friction due to the lack of a uniform chitosan coating.
[0031] The effect of the first step of the method, i.e., treatment with non-equilibrium oxygen plasma, is illustrated in FIG. 1. Untreated polymer catheter (1), whose surface may or may not be contaminated with impurities (2), is firstly treated with gaseous plasma (3). The gaseous plasma treatment (3) causes the removal of surface impurities (2) and causes the formation of dangling bonds on the surface of the untreated catheter (1); the dangling bonds will be occupied with oxidative species and form polar functional groups (4). The polar functional groups (4) will modify the surface wettabilitythe surface of the catheter treated with gaseous plasma will become polar so that the material will become hydrophilic. The water droplet will spread on the surface with a large concentration of polar functional groups (4) and assume a much lower contact angle than for the untreated catheters. The water contact angle after the first plasma treatment will depend on processing parameters and is disclosed in the examples below. The water contact angle is a simple and very reliable technique for measuring wettability. If the water contact angle is large, the wettability is poor, and vice versa. The best wettability is for an immeasurably low water contact angle.
[0032] In the second step (5), a water solution of chitosan is deposited on the catheter to form a layer (6) of water solution of chitosan, as the surface with polar functional groups (4) will attract water upon application of the water solution of chitosan (5). As a result, a thin layer of water solution of chitosan (6) will remain evenly distributed on the entire surface even after pulling the catheter out from the water solution of chitosan, as illustrated in FIG. 1. The catheter (1) with layer (6) is then dried (7), so that a solid layer of dry chitosan (8) stuck well on the surface of the catheter (1). Catheters with liquid films are not feasible for packaging, sterilization, storage, or transport, hence the drying step. The drying method is not particularly limited, but vacuum drying is preferred in one embodiment. As soon as products coated with a water-containing liquid are evacuated below the water vapor saturated pressure, the water starts boiling and desorbs from the surface, leaving a dry layer of the material initially dissolved in water, in this case, chitosan (8). The dry layer of chitosan (8) is continuous and sticks well to the surface functionalized with polar groups (4). In fact, the dry layer of chitosan (8) embraces the catheter.
[0033] The wettability of dry chitosan is sometimes inadequate, so the catheters with the solid layer of dry chitosan (8) are treated with the fourth step, i.e., with gaseous plasma (9). The properties of gaseous plasma (9) may differ from the properties of gaseous plasma (3) in the first step. Typically, the treatment time in the fourth step of plasma treatment (9) is shorter than in the first step of plasma treatment (3), preferably the second plasma treatment (9) is approximately 0.1 to 10 seconds long, which is about 10-times shorter than the first plasma treatment (3). The second plasma treatment (9) causes the formation of polar groups (10) on the surface of the solid layer of dry chitosan (8). The catheters with the solid layer of dry chitosan (8), functionalized with polar groups (10), are ready for packaging, sterilization, and transportation. The shelf time of catheters with a solid layer of dry chitosan (8) is very long, usually several years. Before application, the catheters with the solid layer of dry chitosan (8), functionalized with polar groups (10), are soaked (11) with water to form a lubricant layer (12) resembling chitosan gel.
[0034] FIG. 2 shows a device useful for the treatment of catheters with gaseous plasma. The vacuum chamber (21) is hermetically tight and of vertical dimension larger than the length of catheters. The vacuum chamber (21) is pumped with one or more vacuum pumps (22). In one embodiment, the vacuum pumps (22) were roots pumps backed with a dry mechanical pump. The application of dry pumps is preferred because pumps lubricated with oil may release organic vapors, which may contaminate any product assembled into the vacuum chamber (21). The vacuum chamber (21) is equipped with one or more ports for introducing the desired gas during pumping with pumps (22). In a preferred embodiment, several ports were found useful for the proper distribution of gaseous species in the vacuum chamber (21). The ports are terminated with gas flow controllers (23), which may be replaced with needle valves. One or more gases are introduced into the vacuum chamber (21) through the flow controllers (23), for example, a noble gas, oxygen, hydrogen, nitrogen, or air. The catheters (24) are mounted on a holder (25). The catheters (24) may be evenly placed on the holder (25). Several holders (25) may be positioned in lines so that the distance between neighboring catheters is similar. In FIG. 2, only one holder (24) is shown with four catheters (25) for the sake of clarity. In one embodiment, there are several holders (24) holding several catheters (25) in the vacuum chamber (21). In a preferred embodiment, there are 10 holders (24), each holding 10 catheters, so a batch contains 100 catheters. There is at least one powered electrode (26) in the vacuum chamber (21). Two electrodes (26) are shown in the illustration in FIG. 2. The vacuum chamber (21) is grounded, and the electrodes (26) are powered with a voltage supply (27). The distance between the grounded chamber (21) and the electrode (26) is shorter than the Paschen minimum so that gaseous plasma (not shown in FIG. 2) spreads uniformly in the entire volume of the vacuum chamber (21) except within gaps between the electrode (26) and the grounded chamber (21). In a preferred embodiment, the electrodes (26) are powered with a DC pulsed power supply operating at the voltage just above the Paschen minimum. Alternatively, a radiofrequency generator may be used for sustaining plasma.
EXAMPLES
[0035] The methods of the aspects of the disclosed embodiments are further disclosed in the following examples. In all examples, a catheter or a bunch of catheters were assembled into the system shown schematically in FIG. 2. The vacuum chamber (21) was evacuated to the ultimate pressure using a roots vacuum pump backed with a dry mechanical fore pump. The nominal pumping speed of the roots pump was 600 m.sup.3/h. The fore pump was a scroll pump with a nominal pumping speed of 20 m.sup.3/h. Gases were introduced into the vacuum chamber (21) during continuous pumping with the pumps (22). The treatments caused increased wettability. The water contact angle of untreated PVC and TPE was 98??2?, and 100??2?, respectively. After the first plasma treatment, the catheters were dipped in the 2% w/w water solution of chitosan and dried. The second plasma treatment was performed according to step 3 shown in FIG. 1. The second plasma treatment was always performed using oxygen plasma with the ratio between the ion density (O.sub.2.sup.30) and neutral oxygen atom (O) densities of at most 10.sup.?5, usually approximately 10.sup.?6. Such a small ratio that is not commonly used was unexpectedly found beneficial for rapid hydrophilization of the chitosan coating.
Example 1: A Catheter Made from PVC Blend, the First Step Using Oxygen Plasmas
[0036] PVC catheters were mounted in a plasma reactor, shown schematically in FIG. 2. The reactor was pumped down to the ultimate pressure, and the pumping time was 60 s. After achieving the ultimate pressure, oxygen was introduced into the plasma reactor to achieve the pressure of 30 Pa. Plasma was sustained at the discharge power density of 6 kW m.sup.?3. The plasma treatment time in the first step was 60 s. The wettability improved after the plasma treatment in the first step because the water contact angle dropped to 52??4?. Such a moderately low water contact angle was observed on the entire surface of the catheter. After dipping in the water solution of chitosan and drying, a layer of chitosan was embracing the PVC catheter, which was proved by XPS and FTIR analyses. The water contact angle on the chitosan layer embracing the PVC catheter was 90??2?. The chitosan-coated catheters were placed in the reactor in FIG. 2 again and treated with oxygen plasma at the discharge power density of 6 kW m.sup.?3 and pressure 30 Pa for 1 s, and the water contact angle was 40??5?.
Example 2: A Catheter Made from PVC Blend, the First Step Using Subsequent Treatment with Hydrogen and Oxygen Plasmas
[0037] PVC catheters were mounted in a plasma reactor, shown schematically in FIG. 2. The reactor was pumped down to the ultimate pressure, and the pumping time was 60 s. After achieving the ultimate pressure, hydrogen was introduced into the plasma reactor to achieve the pressure of 10 Pa. Hydrogen plasma was sustained at the discharge power density of 15 kW m.sup.?3. The hydrogen plasma treatment time in the first step was 30 s. After hydrogen plasma treatment, oxygen was introduced into the reactor. Oxygen plasma was sustained at the discharge power density of 5 kW m.sup.?3. The treatment time with oxygen plasma at 30 Pa was 2 s. The wettability improved after the hydrogen and plasma treatments because the water contact angle was 34?4?, indicating a very hydrophilic surface finish. Such a finish was observed on the entire surface of the catheter. After dipping in the water solution of chitosan and drying, a layer of chitosan was embracing the PVC catheter, which was proved by XPS and FTIR analyses. The water contact angle on the chitosan layer embracing the PVC catheter was 82??6?. The catheters were placed in the reactor in FIG. 2 again and treated with oxygen plasma at the discharge power density of 6 kW m.sup.?3 and pressure 30 Pa for 1 s, and the water contact angle was 37??9?.
Example 3: A Catheter Made from PVC Blend, the First Step Using Subsequent Treatment with Nitrogen and Oxygen Plasmas
[0038] PVC catheters were mounted in a plasma reactor, shown schematically in FIG. 2. The reactor was pumped down to the ultimate pressure, and the pumping time was 60 s. After achieving the ultimate pressure, nitrogen was introduced into the plasma reactor to achieve the pressure of 20 Pa. Nitrogen plasma was sustained at the discharge power density of 15 kW m.sup.?3. The nitrogen plasma treatment time in the first step was 30 s. After nitrogen plasma treatment, oxygen was introduced into the reactor. Oxygen plasma was sustained at the discharge power density of 5 kW m.sup.?3. The treatment time with oxygen plasma at 30 Pa was 2 s. The wettability improved after the nitrogen and plasma treatments because the water contact angle was 32??6?. Such a finish was observed on the entire surface of the catheter. After dipping in the water solution of chitosan and drying, a layer of chitosan was embracing the PVC catheter, which was proved by XPS and FTIR analyses. The water contact angle on the chitosan layer embracing the PVC catheter was 88??3?. The catheters were placed in the reactor in FIG. 2 again and treated with oxygen plasma at the discharge power density of 6 kW m.sup.?3 and pressure 30 Pa for 1 s, and the water contact angle was 41??5?.
Example 4: A Catheter Made from TPE Blend, the First Step Using Oxygen Plasmas
[0039] TPE catheters were mounted in a plasma reactor, shown schematically in FIG. 2. The reactor was pumped down to the ultimate pressure, and the pumping time was 60 s. After achieving the ultimate pressure, oxygen was introduced into the plasma reactor to achieve the pressure of 30 Pa. Plasma was sustained at the discharge power density of 6 KW m.sup.?3. The plasma treatment time in the first step was 60 s. The wettability improved after the plasma treatment in the first step because the water contact angle dropped to 48??4?. Such a moderately low water contact angle was observed on the entire surface of the catheter. After dipping in the water solution of chitosan and drying, a layer of chitosan was embracing the TPE catheter, which was proved by XPS and FTIR analyses. The water contact angle on the chitosan layer embracing the TPE catheter was 97??3?. The catheters were placed in the reactor in FIG. 2 again and treated with oxygen plasma at the discharge power density of 6 kW m.sup.?3 and pressure 30 Pa for 1 s, and the water contact angle was 34??5?.
Example 5: A Catheter Made from TPE Blend, the First Step Using Subsequent Treatment with Hydrogen and Oxygen Plasmas
[0040] TPE catheters were mounted in a plasma reactor, shown schematically in FIG. 2. The reactor was pumped down to the ultimate pressure, and the pumping time was 60 s. After achieving the ultimate pressure, hydrogen was introduced into the plasma reactor to achieve the pressure of 10 Pa. Hydrogen plasma was sustained at the discharge power density of 15 kW m.sup.?3. The hydrogen plasma treatment time in the first step was 30 s. After hydrogen plasma treatment, oxygen was introduced into the reactor. Oxygen plasma was sustained at the discharge power density of 5 KW m.sup.?3. The treatment time with oxygen plasma at 30 Pa was 2 s. The wettability improved after the hydrogen and plasma treatments because the water contact angle was 11??3?, indicating almost a super-hydrophilic surface finish. Such a finish was observed on the entire surface of the catheter. After dipping in the water solution of chitosan and drying, a layer of chitosan was embracing the TPE catheter, which was proved by XPS and FTIR analyses. The water contact angle on the chitosan layer embracing the TPE catheter was 69??3?. The catheters were placed in the reactor in FIG. 2 again and treated with oxygen plasma at the discharge power density of 6 KW m.sup.?3 and pressure 30 Pa for 1 s, and the water contact angle was 39??7?.
[0041] Example 6: A Catheter Made from TPE Blend, the First Step Using Subsequent Treatment with Nitrogen and Oxygen Plasmas
[0042] TPE catheters were mounted in a plasma reactor, shown schematically in FIG. 2. The reactor was pumped down to the ultimate pressure, and the pumping time was 60 s. After achieving the ultimate pressure, nitrogen was introduced into the plasma reactor to achieve the pressure of 20 Pa. Nitrogen plasma was sustained at the discharge power density of 15 KW m.sup.?3. The nitrogen plasma treatment time in the first step was 20 s. After nitrogen plasma treatment, oxygen was introduced into the reactor. Oxygen plasma was sustained at the discharge power density of 5 KW m.sup.?3. The treatment time with oxygen plasma at 30 Pa was 1 s. The wettability improved after the nitrogen and plasma treatments because the water contact angle was 39??14?. After dipping in the water solution of chitosan and drying, a layer of chitosan was embracing the TPE catheter, which was proved by XPS and FTIR analyses. The water contact angle on the chitosan layer embracing the TPE catheter was 83??2?. The catheters were placed in the reactor in FIG. 2 again and treated with oxygen plasma at the discharge power density of 6 KW m.sup.?3 and pressure 30 Pa for 1 s, and the water contact angle was 39??5?.
[0043] The examples are provided just as a few embodiments. A skilled person will be able to use other embodiments. For example, treatment times and discharge power densities could be altered. The gas pressures could also be different from those disclosed in the examples. The reactive gases could be mixed with one or more noble gases to benefit from plasma uniformity. Other reactive gases may be used in different embodiments. The concentration of chitosan in the water solution may be varied, too.
