Reactors for coating devices and related systems and methods

Abstract

A reactor for coating devices is provided herein. The reactor comprises a hollow body and a port. The hollow body supports the device. The port is in fluid communication with the hollow body for exchanging a coating fluid. During use, the device can be moved from a stacked orientation to a non-stacked orientation within the hollow body. Also provided herein are methods for coating the device and systems thereof.

Description

Technical Field

[0001] The present disclosure relates to reactors. In particular, the present disclosure relates to reactors for coating devices, and related processes and systems. Background Art

[0002] U.S. Patent No. 8,840,927 relates to a method for modifying the surface of a polymeric material with a polymer coating that can subsequently be treated to be lubricious and antimicrobial. The method comprises incubating a photoinitiator-coated polymeric material with an aqueous monomer capable of free radical polymerization, and exposing the incubated polymeric material to UV light to produce a modified surface on the polymeric material. The method may further comprise adding a silver component to the modified surface. The silver component may be provided as a silver salt coating or as a silver salt contained within a hydrogel that is bonded to the acrylate-modified polymeric material surface.

[0003] U.S. Patent No. 8,967,077 relates to a system and method for photo-grafting a coating polymer onto the surface of a medical device. The system includes a plurality of stations, each of which includes a novel grafting station. The system and method of the invention save both time and resources. The system includes a plurality of stations, each of which includes a dipping tank. The system allows the medical device to be automatically, semi-automatically, or manually dipped into the dipping tank in a specific order as needed, wherein at least one station is a grafting station for photo-grafting a coating polymer onto the surface of the medical device. The system is modular, which allows the required process to be modified according to the needs of the user. The system may include a plurality of stations for incorporating an antimicrobial agent into the coating, and / or for smoothing the coating. Summary of the Invention

[0004] According to one aspect, a reactor for coating a device is provided, the reactor comprising: a hollow body for supporting the device; and a port in fluid communication with the hollow body for exchanging a coating fluid.

[0005] In one aspect, the devices are movable from a stacked orientation to a non-stacked orientation within the hollow body.

[0006] In one aspect, the hollow body is longer than the device to allow the device to move substantially freely within the hollow body in the non-stacked orientation.

[0007] In one aspect, the hollow body is at least 50%, 60%, 70%, 80%, 90%, 100%, 110%, 120%, 130%, 140%, 150%, 160%, 170%, 180%, 190%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 550%, 600% longer than the device.

[0008] In one aspect, the hollow body has a cross-sectional area sufficiently similar to a cross-sectional area of ​​the stacked devices to constrain the devices to move substantially freely within the hollow body in the stacked orientation.

[0009] In one aspect, the hollow body has a diameter that is less than the length of the device to ensure that the device remains in a desired orientation in the non-stacked orientation.

[0010] In one aspect, the reactor further comprises a destacker to release the devices from the stacked orientation.

[0011] In one aspect, the destacker is movable along the length of the hollow body.

[0012] In one aspect, the destacker includes a destacker flange.

[0013] In one aspect, movement of the destacker flange disrupts the stacking orientation.

[0014] In one aspect, movement of the destacker flange provides a gap, optionally between a plurality of stacked devices, that disrupts the stacking orientation.

[0015] In one aspect, the destacker flange is porous and / or flexible.

[0016] In one aspect, the destacker further comprises a destacker rod coupled to the destacker flange for moving the destacker flange through the hollow body.

[0017] In one aspect, the decompressor rod extends axially through the hollow body.

[0018] In one aspect, the reactor further comprises a stopper for facilitating the stacking orientation.

[0019] In one aspect, the stop is movable along the length of the hollow body.

[0020] In one aspect, the stopper comprises a stopper flange.

[0021] In one aspect, movement of the retainer flange allows release of the device from the stacked orientation.

[0022] In one aspect, the stopper further comprises a stopper rod coupled to the stopper flange, the stopper rod being used to move the stopper flange through the hollow body.

[0023] In one aspect, the stopper rod extends axially through the hollow body.

[0024] In one aspect, the destacker rod extends axially through the stopper rod.

[0025] In one aspect, the destacker rod and the stopper rod move independently or in conjunction with each other.

[0026] In one aspect, the port is located at one end of the hollow body.

[0027] In one aspect, the port is located at the bottom end of the hollow body.

[0028] In one aspect, the port is located at the top end of the hollow body.

[0029] In one aspect, the ports are located at the top and bottom ends of the hollow body.

[0030] In one aspect, the reactor further comprises a plug located at the top end of the hollow body.

[0031] In one aspect, the port extends through the plug for fluid flow.

[0032] In one aspect, the plug defines a void having a convex shape to direct fluid to the port.

[0033] In one aspect, the convex shape is a frustoconical, conical, or parabolic shape.

[0034] In one aspect, the fluid is a gas.

[0035] In one aspect, the stopper rod and / or the destacker rod extends through the plug.

[0036] In one aspect, as the destacker rod and the stopper rod move through the plug, a washer coupled to the destacker rod slides into a washer coupled to the stopper rod, and the washer coupled to the destacker rod and the washer coupled to the stopper rod jointly abut a surface of the plug to restrict fluid flow through the plug in the destacker orientation.

[0037] In one aspect, the reactor further comprises a bottom plug.

[0038] In one aspect, the port extends through the bottom plug for exchanging the coating fluid.

[0039] In one aspect, the reactor further comprises an aerator.

[0040] In one aspect, the hollow body is cylindrical.

[0041] In one aspect, the hollow body is partially or fully transparent.

[0042] In one aspect, the hollow body is partially or fully UV transparent.

[0043] In one aspect, the hollow body comprises glass.

[0044] In one aspect, the glass is borosilicate or quartz.

[0045] In one aspect, the device is a medical device.

[0046] In one aspect, the device is selected from the group consisting of a heart valve, a dressing, a needle, a forceps, a clip, a syringe, a syringe attachment, a catheter, a drain, a stent, an implant, a tube, an eyepiece, and a delivery device thereof.

[0047] In one aspect, the device is a cannula.

[0048] In one aspect, the device is a catheter.

[0049] In one aspect, the device is a plurality of devices, optionally wherein each of the plurality of devices is substantially identical.

[0050] In one aspect, the plurality of devices remain in contact during the exchange of the coating fluid.

[0051] In one aspect, the plurality of devices contact each other when in the stacked orientation such that substantially no dead space exists.

[0052] In one aspect, the fluid exchange reduces air bubbles in and / or around the plurality of devices, optionally reducing air bubbles in individual lumens of the plurality of devices.

[0053] In one aspect, the reactor is movable between a substantially vertical position and a substantially horizontal position.

[0054] In one aspect, movement from the substantially vertical position to the substantially horizontal position facilitates the non-stacked orientation.

[0055] In one aspect, the non-stacked orientation and / or the substantially horizontal position promotes substantially uniform coverage of the device with the coating fluid.

[0056] In one aspect, the non-stacked orientation and / or the substantially horizontal position facilitates substantially uniform dispersion of the devices throughout the hollow body.

[0057] In one aspect, the plurality of devices are not exposed to air during or after the exchange of the coating fluid.

[0058] In one aspect, the coating fluid comprises a fluid selected from the group consisting of a photoinitiator, a monomer, water, an alcohol, and combinations thereof.

[0059] In one aspect, the photoinitiator is selected from the group consisting of esters, α-hydroxy ketones, benzyl ketones, benzoic acids, and derivatives and combinations thereof.

[0060] In one aspect, the photoinitiator is selected from the group consisting of 2,2-dimethoxy-2-phenyl-acetophenone (DPA), tert-butyl p-benzoylperbenzoate (BPB), tert-butyl peroxybenzoate (TBP), benzophenone (BP) and combinations thereof.

[0061] In one aspect, the photoinitiator comprises benzophenone and t-butyl perbenzoate.

[0062] In one aspect, the monomer solution is selected from the group consisting of acrylic acid, methacrylic acid, 2-carboxyethyl acrylate, 4-vinylbenzoic acid, itaconic acid, methyl acrylate, and combinations thereof.

[0063] In one aspect, the monomer solution comprises acrylic acid and methyl acrylate.

[0064] In one aspect, the monomer solution, water and / or alcohol are purged with an oxygen-scavenging gas.

[0065] In one aspect, the oxygen-scavenging gas is selected from the group consisting of nitrogen, argon, helium, and combinations thereof.

[0066] In one aspect, the oxygen-scavenging gas is nitrogen.

[0067] In one aspect, the water is deionized water.

[0068] In one aspect, the alcohol is a low surface tension alcohol solution.

[0069] In one aspect, the alcohol is selected from the group consisting of methanol, ethanol, isopropanol, and combinations.

[0070] In one aspect, the reactor is used to coat the device in a one-pot process with exchange of coating fluids.

[0071] In one aspect, the exchange of the coating fluid is fully automatic, semi-automatic or manual.

[0072] According to one aspect, a system is provided that includes a reactor stand for supporting a reactor as described herein and a rotation mechanism for changing the orientation of the reactor stand from a first orientation to a second orientation.

[0073] In one aspect, the first orientation is a substantially vertical orientation.

[0074] In one aspect, the first orientation is a vertical orientation.

[0075] In one aspect, the second orientation is a substantially horizontal orientation.

[0076] In one aspect, the second orientation is a horizontal orientation.

[0077] In one aspect, the system further comprises a lamp assembly attachable to the reactor holder for initiating polymerization within the reactor.

[0078] In one aspect, the lamp assembly includes a UV light source.

[0079] In one aspect, the UV light source has a wavelength between about 100 nm and about 400 nm.

[0080] In one aspect, the UV light source has a wavelength between about 300 nm and about 365 nm.

[0081] In one aspect, the system comprises one or more reactors described herein.

[0082] According to one aspect, a one-pot method for coating a device is provided, the method comprising: exchanging a coating fluid within a reactor; and coating the device with the coating fluid such that the coating fluid covers a surface of the device.

[0083] In one aspect, the device is continuously immersed in the coating fluid such that the device is not exposed to air.

[0084] In one aspect, the exchange coating fluid minimizes bubble formation inside and / or outside the device.

[0085] In one aspect, the method comprises immersing the device in alcohol to remove air bubbles and exchange subsequent fluids while maintaining the device submerged without substantially exposing the device to air.

[0086] According to one aspect, a one-pot method for treating a fluid device and reducing bubble formation includes immersing the device in alcohol and exchanging the alcohol with the fluid for treatment.

[0087] The novel features of the present invention will become apparent to those skilled in the art after studying the following detailed description of the present invention. However, it should be understood that the detailed description of the present invention and the specific examples presented, while indicating certain aspects of the present invention, are provided for illustrative purposes only, as various changes and modifications within the spirit and scope of the present invention will be apparent to those skilled in the art based on the detailed description of the present invention and the claims that follow. BRIEF DESCRIPTION OF THE DRAWINGS

[0088] The present invention will be further understood from the following description with reference to the accompanying drawings:

[0089] Figure 1 shows an exploded view of the components of a reactor according to the present invention;

[0090] Figure 2 Shown Figure 1 A perspective view of a reactor assembled and stacked with devices in a vertical direction;

[0091] Figure 3 Shown Figure 2 A perspective view of a reactor assembled and with the components not stacked in a horizontal orientation;

[0092] Figure 4 Shown Figure 1 A perspective view of a decompressor flange (A) and a stopper flange (B) of a reactor;

[0093] Figure 5 Shown Figure 4 Close-up view of the decompressor flange (A) and the stopper flange (B);

[0094] Figure 6 Shown Figure 2 a cross-sectional view of the assembled reactor;

[0095] Figure 7 Shown Figure 6 A close-up cross-sectional view of the top of the reactor (D);

[0096] Figure 8 Shown when the stopper and destacker are retracted Figure 1 a cross-sectional view of the top of the reactor;

[0097] Figure 9 shows an exploded view of the components of the system according to the present invention;

[0098] Figure 10 Shown Figure 9 A vertical perspective view of the system;

[0099] Figure 11 Shown Figure 9A horizontal perspective view of the system;

[0100] Figure 12 Shown Figure 11 A semi-exploded diagram of the system;

[0101] Figure 13 Shown is a diagram showing a reactor array Figure 9 A perspective front view of the system;

[0102] Figure 14 Shown Figure 13 A perspective rear view of the system;

[0103] Figure 15 Shown Figure 10 A perspective top view of the system; and

[0104] Figure 16 Shown Figure 10 Perspective side view of the system. DETAILED DESCRIPTION

[0105] This article describes an apparatus suitable for treating one or more devices with one or more fluids, such as a reactor. Typically, such devices are sequentially immersed in various fluid containers so that the coating is polymerized to the surface of the device. For example, U.S. Patents 6,808,738, 8,361,501, 8,746,168, 8,840,927, 8,877,256, 8,920,886, and 8,967,077, and U.S. Patent Application Publication 2018 / 0296737, which are incorporated herein by reference in their entirety, describe examples of these methods and coating compositions for these methods to describe various coating compositions, processes, and methods.

[0106] In some aspects, the reactors described herein are capable of sequentially treating devices with multiple fluids that are gradually exchanged with each other while substantially avoiding the introduction of bubbles into the process. When bubbles are on the surface of the device while the device is being coated with the fluid, these bubbles may interfere with the complete, uniform coating of the device. In addition, the reactors described herein are designed to maintain the devices in a regularly oriented "stacked" configuration during the first step in the coating process, and then to break the regularly oriented or "unstack" devices during the polymerization step of the process so that the coating can be polymerized substantially uniformly across the surface.

[0107] In some aspects, multiple devices are stacked on the bottom surface of the reactor and optionally held in place with restrictors that help maintain the orientation of the devices as fluids are exchanged and otherwise moved within the reactor. The fluid level is maintained above the level of the top of the devices so that the devices remain substantially submerged throughout the coating process. The gradual fluid exchange reduces the chance of bubbles forming in and / or on the devices.

[0108] Typically, an alcohol-based photoinitiator solution is first introduced into the reactor so that the device and stopper are completely submerged. A deoxygenating gas is typically introduced through the bottom of the reactor to remove dissolved oxygen from the surface of the fluid and device. After the airflow through the reactor stops, the low surface tension of the alcohol-based photoinitiator solution promotes the effective removal of bubbles from inside and around the device. This process removes air from the device and does not introduce any bubbles that would interfere with the subsequent coating process. All fluids thereafter, such as any washing solutions and monomers, are exchanged with the fluid in the reactor in a gradual manner so that the device remains submerged throughout the entire process. This avoids introducing any bubbles into the device.

[0109] The reactors described herein are suitable for scalable and high-throughput coating processes. Multiple devices can be coated in each reactor, and multiple reactors can be run in parallel.

[0110] definition

[0111] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Although any methods and materials similar or equivalent to those described herein can be used in the testing and implementation of the present invention, typical materials and methods are described herein. In describing and claiming the present invention, the following terminology will be used.

[0112] Relative terms are intended to aid understanding of the technology. For example, the term "top" is relative to the term "bottom," the term "above" is relative to the term "below," the term "upward" is relative to the term "downward," the term "rear" is relative to the term "front," and the term "horizontal" is relative to the term "vertical." Rotating a component changes the terminology without changing the meaning.

[0113] When introducing elements disclosed herein, the articles "a," "an," "the," and "said" are intended to mean that there may be one or more of the elements.

[0114] As used herein, the term "comprise" and its derivatives are intended to be open-ended terms that specify the presence of stated features, elements, components, groups, integers and / or steps, but do not preclude the presence of other unstated features, elements, components, groups, integers and / or steps. The foregoing also applies to words of similar meaning, such as the terms "comprises," "having" and their derivatives. It should be understood that any embodiment described as "comprising" certain components may also "consist of" or "consist essentially of" those components, where "consist of" has a closed or restrictive meaning, and "consisting essentially of" means including the specified components, but excluding other components other than materials present as impurities, unavoidable materials present as a result of the process used to provide the components, and components added for purposes other than achieving the technical effects described herein.

[0115] It should be understood that any component defined herein as included may be expressly excluded from the claimed invention by qualification or negative limitation, such as any specific coating fluid or process step implicitly or explicitly defined herein. For example, in some aspects, the coating method does not include an activation coating step for applying a therapeutic agent.

[0116] Furthermore, all ranges given herein include the ends of the ranges as well as any intermediate range points, whether expressly stated or not.

[0117] Terms of degree such as "substantially," "about," and "approximately" as used herein refer to a reasonable amount of deviation of the modified term such that the end result is not significantly changed. These terms of degree should be construed to include a deviation of at least ±5% of the modified term if such deviation would not negate the meaning of the word it modifies.

[0118] The abbreviation "eg" is derived from the Latin exempli gratia and is used herein to indicate a non-limiting example. Thus, the abbreviation "eg" is synonymous with the term "for example." Unless the context clearly indicates otherwise, the word "or" is intended to include "and."

[0119] The phrase "at least one" is understood to mean one or more. If not explicitly listed, the phrase "at least one of ... and ..." should be understood to mean at least one of the listed elements or a combination thereof. For example, "at least one of A, B, and C" should be understood to mean A alone, or B alone, or C alone, or a combination of A and B, or a combination of A and C, or a combination of B and C, or a combination of A, B, and C.

[0120] Reactors for coating devices

[0121] The reactor is now described with reference to the accompanying drawings. Generally, a reactor 10 for coating devices 12 is described herein, and the coating device is typically a plurality of devices 12. In typical aspects, the reactor 10 allows the devices 12 to be coated in a "one-pot process". "One-pot process" means that the exchange of all coating fluids can be carried out in the reactor 10 itself, without the need for additional reactors (e.g., additional equipment containing fluids), and the exchange of all coating fluids within the reactor 10 is continuous. In this way, the coating fluid can be injected into the reactor 10 and continuously replaced so that the devices 12 remain immersed in the coating fluid throughout the process when they are in the reactor 10. This reduces the exposure of the devices 12 contained therein to air and / or reduces the generation of bubbles on the inner cavity and / or outer surface of the devices 12 during the coating process. Typically, the device 12 coated using this process is a cannula, such as a catheter.

[0122] Figure 1-8 The reactor 10 is shown in an assembled configuration, a disassembled configuration, and in different orientations during its use. Figure 1 The reactor 10 is shown in exploded form, Figure 2 The reactor 10 is shown in its assembled configuration. As shown, the reactor 10 includes a hollow body 14 for supporting a device 12 or a plurality of devices 12, and a port 16 in fluid communication with the hollow body 14. In this way, when a coating fluid is introduced into the hollow body 14 through the port 16, the coating fluid can be exchanged within the hollow body 14. The hollow body 14 is generally transparent so that it allows UV light to be transmitted therethrough during the coating process to initiate and propagate the polymerization reaction. The hollow body 14 is generally made of glass, such as borosilicate or quartz, however, it should be understood that the hollow body 14 can be made of any material that is capable of transmitting UV light.

[0123] In a typical aspect, the devices 12 are movable within the hollow body 14 so that they can appear as Figure 2 and 3 Different orientations are best shown, as described in more detail below, such as the stacked orientation (see Figure 2 ) or unstacked orientation (see Figure 3 ). By stacked orientation, it is meant that the devices 12 are in close contact with one another and that there is substantially no dead space between the devices 12. For example, the devices 12 form an array in which the devices 12 are in contact with one another. In a typical aspect, when the devices 12 are in the stacked orientation, the devices 12 remain in contact during the exchange of the coating fluid. The stacked orientation facilitates uniform, substantially bubble-free coating of the devices 12 with, for example, a polymeric solution and one or more washing solutions.

[0124] By non-stacked orientation, it is meant that the devices 12 are not in close contact with each other, and that there is space between the devices 12. Typically, the devices are loosely contained and freely movable within the coating fluid contained within the hollow body 14. The non-stacked orientation ensures that the devices 12 are completely coated with, for example, a monomer solution, and facilitates exposure of all surfaces of the devices 12 to UV light during the polymerization reaction, thereby producing a substantially complete and uniform coating on the surfaces of the devices 12. Typically, the diameter of the reactor is smaller than the length of the devices to prevent the devices from falling sideways after unstacking.

[0125] Multiple components are arranged within the hollow body 14 to facilitate stacking and unstacking of the devices 12 during the coating process. Figure 1 As shown, the reactor 10 also includes an unstacker 18 for releasing the devices 12 from the stacked orientation. In some aspects, the unstacker 18 can be moved along the length of the hollow body 14 to release the devices 12 from the stacked orientation to a non-stacked orientation, thereby allowing, for example, the devices 12 to move freely within the hollow body 14.

[0126] In a typical aspect, the destacker 18 includes a destacker flange 20 that is disposed near the bottom of the hollow body below the device 12 when the device 12 is in a stacked orientation. When the destacker 18 is pulled out along the length of the hollow body 14, the destacker flange 20 moves with the destacker 18, thereby destroying the stacking orientation by removing one or more devices 12 from the core portion of the stack. This creates a gap in the device 12, providing enough space for the device 12 to release from the stacking orientation and assume a non-stacked orientation. In a typical aspect, the destacker flange 20 is sufficiently rigid to maintain its shape while removing one or more devices 12 from the core portion of the stack as described above. In an additional or optional aspect, the destacker flange 20 is porous, thereby allowing the coating fluid in the hollow body 14 to flow through. In this way, the coating fluid contained in the hollow body 14 will not be blocked by the destacker flange 20.

[0127] In a typical aspect, the decompressor 18 also includes a decompressor rod 22. In a typical aspect, the decompressor flange 20 is connected to the decompressor rod 22 so that the decompressor rod 22 and the decompressor flange 20 can move axially through the hollow body 14. In a typical aspect, the decompressor rod 22 extends axially through the hollow body 14 and, typically, the decompressor rod 22 protrudes outside the hollow body 14 to facilitate its axial movement.

[0128] In a typical aspect, the reactor 10 further includes a stopper 24. The stopper 24 is biased against the devices 12 and urges the devices 12 to remain in a stacked orientation. In this manner, the stopper 24 limits movement of the stacked devices 12 when the coating fluid is introduced and / or exchanged within the hollow body 14, as well as during bubbling of the deoxygenated gas within the hollow body 14. In addition, the stopper 24 can knock the devices 12 out of contact with, and restore contact with, the devices 12 by moving the stopper up and down to facilitate the discharge of any bubbles from the stacked devices 12.

[0129] In typical aspects, the stopper 24 is movable along the length of the hollow body 14. In some aspects, the stopper 24 protrudes outside the hollow body 14 as the stopper 24 moves axially through the hollow body 14 (see FIG. Figure 9 ), so that the stopper 24 moves away from the device 12. In this way, the device 12 can assume the non-stacked orientation described herein. In a typical aspect, the stopper 24 extends within the hollow body 14 (see Figure 2 ), for holding the devices 12 in the stacked orientation. In a typical aspect, the stopper 24 includes a porous stopper flange 26 that is configured to abut a surface of the device 12 to limit movement of the device 12 and hold the device 12 in the stacked orientation. It should be understood that movement of the stopper flange 26 allows the device 12 to be released from the stacked orientation to the non-stacked orientation, thereby facilitating coating of the device 12. When porous, the stopper flange 26 allows the coating fluid within the hollow body 14 to flow therethrough.

[0130] In a typical aspect, the stopper 24 further includes a stopper rod 28 that extends axially through the hollow body 14 and is movable through the hollow body 14. In some aspects, the stopper rod 28 is connected to the stopper flange 26 for movement through the hollow body 14. Movement of the stopper flange 26 and / or the stopper rod 28 through the hollow body 14 facilitates movement of the devices 12 from the non-stacked orientation to the stacked orientation. In addition, the stopper flange 26 can be used to partially restack the devices 12 as needed, for example, during a wash step.

[0131] In typical aspects, the stopper rod 28 is hollow and can receive the destacker rod 22 axially therethrough. In various aspects, the stopper rod 28 and the destacker rod 22 move independently of each other. For example, the stopper rod 28 can move axially along the length of the hollow body 14 while the destacker rod 22 remains in its starting position in the hollow body 14, or the destacker rod 22 can move axially through the hollow body 14 in the stopper rod 28 while the stopper rod 28 remains in its starting position in the hollow body 14. In other aspects, the stopper rod 28 moves through the hollow body 14, followed by the destacker rod 22, or vice versa. In other aspects, the stopper rod 28 and the destacker rod 22 can move together, so that the stopper rod 28 and the destacker rod 22, for example, move through the hollow body 14 substantially simultaneously, and allow, for example, to release the devices 12 stacked in the hollow body 14 so that the devices 12 become non-stacked.

[0132] In some aspects, the port 16 is in fluid communication with the hollow body 14 through the top end 32 or the bottom end 34 of the hollow body 14, or both. As is understood in the art, there is no limitation on the location of the port 16 relative to the hollow body 14, nor is there a limitation on the number of ports 16 that can be in fluid communication with the hollow body 14. For example, the reactor can include a single port 16 for fluid inflow and outflow, or it can have two ports 16 at the bottom end 34 of the hollow body 14, one for fluid inflow and the other for fluid outflow. Alternatively or additionally, the reactor can include one or more ports 16 at the top end 32 of the hollow body 14 for inflow and / or outflow.

[0133] In some aspects, the port 16 at the top end of the hollow body is particularly useful for the outflow of gaseous fluids, such as in a purification process as described herein. In additional or alternative aspects, the reactor is rotatable, so that when the reactor 10 is rotated or inverted, the presence of the outflow port 16 at the top end of the reactor is particularly useful for the outflow of coating fluids.

[0134] In typical aspects, at least one port 16 is located at or near the bottom end 34 of the hollow body 14 for introducing coating fluid into the hollow body 14 and at least one other port 16 is located at or near the top 32 of the hollow body 14 for removing coating fluid, or vice versa.

[0135] Fluid flow into and out of port 16 may be initiated, controlled, and / or substantially or completely restricted by any arrangement of upstream or downstream valves, pumps, reservoirs, mixers, purge chambers, etc. It will be appreciated that some solutions, such as monomer, alcohol, and / or water washes, may be purged with a monomer solution as desired.

[0136] Figure 6-8A cross-section of the top end 32 of the hollow body 14 is shown. In some aspects, the reactor 10 further comprises a top stopper 30 located at the top end 32 of the hollow body 14. In typical aspects, the top stopper 30 defines a void 36 that facilitates the flow of a fluid (e.g., a gas) toward the port 16. In some aspects, the port 16 passes through the stopper 30 such that the port 16 allows the fluid to flow therefrom. In typical aspects, the void 36 has a convex shape for directing the fluid to the port 16. The convex shape is shown as a frustoconical shape, however, it should be understood that other shapes are also contemplated, such as conical, parabolic, etc.

[0137] like Figure 6-8 As shown, the stopper rod 28 and the destacker rod 22 extend generally axially through the plug 30. Thus, when the stopper rod 28 and the destacker rod 22 move axially through the hollow body 14 and thus through the plug 30, the stopper flange 26 and the destacker flange 20 abut against the plug 30.

[0138] like Figure 4 and 5 As shown, the stopper 24 and the destacker 18 also include washers. In some aspects, the destacker 18 also includes a destacker washer 40, and the stopper 24 also includes a stopper washer 42. In a typical aspect, the destacker washer 40 is connected to the destacker rod 22, and in a typical aspect, the stopper washer 42 is connected to the stopper rod 28. Thus, when the stopper rod 28 and the destacker rod 22 are axially retracted through and / or from the hollow body 14, the destacker washer 40 and the stopper washer 42 jointly abut the surface of the rod insertion hole 38 in the plug 30 ( Figure 7 ) so as to substantially or completely restrict the flow of fluid through the rod insertion hole 38. When the flow of fluid through the port 16 is substantially or completely restricted by the external valve system, the simultaneous abutment of the destacker gasket 40 and the stopper gasket 42 with the surface of the rod insertion hole 38 can substantially or completely restrict the flow of fluid through the plug 30. It should be understood that the gaskets 40 and 42 act as a seal against the plug 30, and the flanges 20 and 26 do not need to abut the surface of the plug 30 to achieve this seal. In addition, although the flanges 20 and 26 are shown as abutting the surface of the plug 30, this is only to maximize the volume of the hollow body. It will be understood that these components can be constructed differently depending on the desired end use and the volume capacity of the hollow body.

[0139] In a typical aspect, the reactor 10 further includes a bottom plug 44 that engages the bottom end 34 of the hollow body 14 to form, for example, a tight seal therewith. The bottom plug 44 typically defines one or more apertures through which corresponding ports 16 extend to allow, for example, a coating fluid to flow into and / or out of the hollow body 14.

[0140] In some aspects, reactor 10 further includes an aerator 46. In typical aspects, aerator 46 is in communication with port 16 and, when assembled within hollow body 14, is generally below stacked devices 12. The aerator helps to evenly disperse fluids introduced into the hollow body, particularly gaseous fluids such as nitrogen, which may be introduced during the purge step of the methods described herein.

[0141] In a typical aspect, the reactor 10 is movable about an axis between a substantially vertical orientation and a substantially horizontal orientation. Movement between these orientations helps untie the stacked devices 12 by breaking up the stack due to gravity. For example, when the devices 12 are moved from a stacked orientation ( Figure 2 ) moves to a non-stacked orientation ( Figure 3 ), by retraction of the stopper flange 26 and / or the destacker flange 20 and rotation of the hollow body, the devices 12 are then loosely accommodated and substantially evenly dispersed within the hollow body 14 to achieve effective and uniform polymerization of the coating fluid.

[0142] The stopper rod 28 and / or the destacker rod 22 can be a single solid rod, or can be two separate rods, for example, which are telescopically engaged to operate independently or in series, or can be two separate rods that are not connected to each other and operate independently or in series. The stopper rod 28 and / or the destacker rod 22 can be made of any suitable material as long as the material does not hinder the function of the stopper rod 28 and / or the destacker rod 22 (for example, by axial movement of the hollow body 14 and / or sliding engagement between the stopper rod 28 and / or the destacker rod 22).

[0143] Hollow body 14 has been described above as being cylindrical, however, it will be appreciated that it may have any suitable shape, which may be determined at least in part by the shape and number of desired devices to be coated.

[0144] In this regard, the reactor 10 is used to coat any device 12 on which a coating can be polymerized. Typically, the device is made of a polymeric material such as polyurethane, polyamide, polyester, polyether, polyorganosiloxane, polysulfone, polytetrafluoroethylene, polysiloxane, organosilicon material, poly(dimethylsiloxane)-based polymers, and combinations thereof. Such polymers are commonly used in the clinic for a variety of medical devices, including inpatient medical devices and general equipment, including but not limited to heart valves, dressings, needles, clips, clamps, syringes and accessories, catheters, drains, stents, implants, tubes, etc. Coatings of devices such as eyepieces and / or their delivery devices are also contemplated herein.

[0145] The top plug 30 and / or the bottom plug 44 may be made of any material capable of forming a sealing engagement with the hollow body 14. Typically, the top plug 30 and / or the bottom plug 44 are made of rubber or silicone.

[0146] The coating fluid used in the coating process includes, for example, a photoinitiator, a monomer, water, alcohol, an oxygen scavenging gas and a combination thereof. Suitable photoinitiators for the photoinitiator solution include, but are not limited to, peresters, α-hydroxyketones, benzyl ketals, benzoins and their derivatives and mixtures thereof. Specifically, suitable photoinitiators can be selected from 2,2-dimethoxy-2-phenyl-acetophenone (DPA), p-benzoyl tert-butylperbenzoate (BPB), benzophenone (BP) and mixtures thereof. Typically, photoinitiators include benzophenone and tert-butylperoxybenzoate. Those skilled in the art will readily understand the types of photoinitiators that can be used in the methods described herein.

[0147] It will be appreciated that the photoinitiator is typically in an alcohol-based solvent (eg, methanol, ethanol, isopropanol, or a combination thereof), which allows the solution to have a low surface tension and thus facilitates more efficient removal of bubbles from the surface of the device.

[0148] The monomer is a polymerizable component within a polymerizable solution that can be photografted onto the surface of device 12. Suitable monomers for the polymerizable solution include, but are not limited to, monomers that are sensitive to the presence of free radicals, i.e., monomers that can be free radically polymerized, such as acrylic acid, methacrylic acid, 2-carboxyethyl acrylate, 4-vinylbenzoic acid, itaconic acid, and mixtures thereof. Typically, the monomer is a combination of acrylic acid and methyl acrylate.

[0149] In typical aspects, the alcohol is a low surface tension alcohol, such as methanol, ethanol, isopropanol, and combinations thereof.

[0150] Typically, the methods described herein include the step of purging the liquid component with an oxygen-scavenging gas to reduce bubbles and dissolved oxygen in the liquid. The oxygen-scavenging gas is, for example, nitrogen, argon, helium, or a combination thereof. In typical aspects, the oxygen-scavenging gas is nitrogen.

[0151] The reactor 10 is typically assembled by placing the destacker rod 22 within the retainer rod 28 so that the retainer flange 26 and the destacker flange 20 are spatially separated from each other and can hold the device 12 therebetween. Figure 1 ). The assembly can be placed in the hollow tube 14. When ready for use, the device 12 is placed in the hollow tube 14, wherein the destacker flange 20 is placed on the top of the aerator 46, and the device 12 is placed on the destacker 18, for example, the device 12 is placed around the destacker rod 22 so that the destacker rod 22 passes through the middle of the stacked devices 12. The stopper flange 26 is then placed on the top of the device 12 to prevent the device 12 from lifting during, for example, a nitrogen purge. Once the reactor 10 is assembled, the coating fluid can be introduced and exchanged in the hollow body 14 for coating the device 12. The assembled reactor 10 can be placed in the system 100 described below so that the array of reactors 10 can be rotated between substantially vertical and horizontal directions to achieve destacking of the device 12, and therefore achieve coating of the device 12 by the method described herein. A more detailed description of the process and system 100 is provided below, so for the sake of brevity, it is not repeated here.

[0152] Systems for coating devices

[0153] Typically, the reactor 10 can be incorporated into a system 100 for coating devices 12. The system 100 allows multiple reactors 10 containing multiple devices 12 to coat the devices 12 simultaneously. In this way, a large number of devices 12 can be coated in parallel quickly and efficiently. The system 100 includes a reactor stand 102 for supporting the reactor 10 and a rotation mechanism 106, such as a rotating rack (rotating stand), for changing the orientation of the reactor 10. Figure 9-16 The orientation of the reactor 10 can be changed from a first orientation ( Figure 10 ) changes to the second orientation ( Figure 11 The change in orientation of the reactor 10 facilitates coating of the devices 12 by allowing the devices 12 to de-stack in the second orientation.

[0154] In typical aspects, the first orientation is substantially vertical, such as Figure 2 and Figure 10 In typical aspects, the second orientation is substantially horizontal, as shown. Figure 3 and Figure 11As shown. In a typical aspect, the reactor holder 102 includes slots for accommodating the array 104 of reactors 10. The reactors 10 can be slidably and fixably connected to the reactor holder 102, so that the system 100 can change the orientation of the array 104 of reactors 10 via the rotation mechanism 106. In this manner, the reactor holder 102 can accommodate multiple reactors 10 (e.g., multiple reactors 10) for timely and efficient coating of the devices 12. It is also contemplated that the rotation mechanism 106 can allow for full rotation of the reactor holder 102. In this manner, the rotation mechanism 106 is not limited to only substantially horizontal and vertical orientations.

[0155] In an exemplary aspect, system 100 further includes a lamp assembly 108 for initiating polymerization. Lamp assembly 108 can be connected to reactor holder 102. Lamp assembly 108 includes a housing 107 that houses a UV light source, such as an array of bulbs 110, for polymerization. When assembled in reactor holder 102, each reactor 10 is flanked by lamp assembly 108, which directs UV light through hollow body 14 and into the interior of reactor 10 via bulbs 110. In an exemplary aspect, housing 107 of lamp assembly 108 can be connected to reactor holder 102 via slots 112 connected to reactor holder 102 and pins 114 connected to housing 107. In this manner, slots 112 can matingly receive pins 114, thereby connecting housing 107 to reactor holder 102. It will be appreciated that housing 107 and reactor holder 102 can be connected to each other in various other ways, such as screws and bolts, nails, snap-fits, snap-fits, and the like.

[0156] In typical aspects, once the reactor holder 102 is coupled to the rotation mechanism 106, such as a stand, and the housing 107 is coupled to the reactor holder 102, the coating fluid exchange process can begin to coat the device 12. In alternative aspects, the coating fluid exchange process can begin before and / or after the reactor holder 102 has been oriented to a substantially or completely horizontal orientation (respectively). Figure 10 and Figure 11 ) Attach the shell 107 to the reactor holder 102. In this way, when the shell 107 is connected to the reactor holder 102 after the reactor 10 is positioned in a horizontal direction, the coating fluid exchange process can be observed before the polymerization reaction begins. The system 100 allows for a small footprint, so that multiple systems 100 can be set up in a workspace area for simultaneous coating of multiple devices 12.

[0157] Process for coating devices

[0158] Typically, reactor 10 is used to coat devices 12 in a "one-pot process." In this manner, the process and corresponding apparatus allow for the simultaneous coating of a large number of devices 12 in an efficient and cost-effective manner. Advantageously, the coating fluid is exchanged within reactor 10 such that devices 12 remain submerged throughout the process and the devices 12 are not exposed to air. In this manner, devices 12 are continuously immersed in the coating fluid, thereby avoiding the formation of bubbles in or around devices 12 during the coating process. The one-pot process for coating devices 12 includes exchanging the coating fluid within reactor 10 and coating devices 12 with the coating fluid such that the coating fluid covers the surface of devices 12.

[0159] The exchange of coating fluids typically includes exchanging coating fluids in a continuous and sequential manner, starting with the photoinitiator and oxygen scavenging gas, followed by a pre-polymerization wash, then the addition of monomer, then polymerization, followed by a post-polymerization wash, and a final wash. In other aspects, the exchange of coating fluids also includes using additional coating fluids, such as coating activation washes, or solutions containing therapeutic agents for applying the therapeutic agent to the surface of the device 12. It should be understood that this sequence can be modified, expanded, or reduced as needed, for example, if a coating activation wash is included in the method, it can be performed before the final wash. Once the reactor 10 is assembled, the exchange of coating fluids to coat the device 12 can begin.

[0160] Photoinitiator:

[0161] In a typical aspect, the process of exchanging the coating fluid begins with the introduction of a photoinitiator. In a typical aspect, the photoinitiator is introduced into the hollow body 14 so that the device 12 is immersed in the photoinitiator. In a typical aspect, when the device 12 is introduced into the hollow body 14, the device 12 is completely immersed in the photoinitiator. At this time, the device 12 and the photoinitiator are purged with an oxygen-scavenging gas (e.g., nitrogen) for a period of time. For example, the period of time is about 5 minutes, about 6 minutes, about 7 minutes, about 8 minutes, or about 9 minutes. In a typical aspect, the period of time is about 6 minutes. Those skilled in the art will understand that the period of time depends on the time required to eliminate surface oxygen from the device 12.

[0162] Typically, after the oxygen-scavenging gas purge, the device 12 remains immersed in the photoinitiator for an additional period of time. For example, the period of time can be in the range of 1 minute to 10 minutes, such as about 1 minute, about 2 minutes, about 5 minutes, about 6 minutes, about 7 minutes, about 9 minutes, or about 10 minutes. In a typical aspect, the period of time is about 6 minutes. Those skilled in the art will understand that the period of time depends on the time required to allow bubbles to evacuate from the device 12 due to, for example, the lower surface tension of the alcohol-based photoinitiator solution. In additional or alternative aspects, those skilled in the art will understand that the period of time depends on the time required to introduce a sufficient concentration of photoinitiator to the surface of the device 12.

[0163] Prepolymer washing:

[0164] In a typical aspect, after immersion in the photoinitiator, a pre-polymerization wash solution (e.g., 70% alcohol, 30% deionized water, optionally pre-purged with nitrogen) is introduced into the hollow body 14 of the reactor 10 by exchanging the fluid and maintaining each device immersed. The pre-polymerization wash solution is used to wash out excess photoinitiator residue that may remain on the surface of the reactor. In a typical aspect, the wash comprises about 2 times, about 3 times, or about 4 times the volume of the hollow body 14 so as to thoroughly wash the reactor without substantially removing photoinitiator absorbed on the surface of the device 12. In a typical aspect, the wash comprises about 3 times the volume of the hollow body 14.

[0165] Typically, after the alcohol wash step, deionized water, typically pre-purged with nitrogen, is introduced into the hollow body 14 by fluid exchange while keeping the device submerged to wash away residual alcohol. In typical aspects, the wash comprises washing the hollow body 14 using about 2, about 3, or about 4 times the volume of the hollow body 14. In typical aspects, the wash comprises about 3 times the volume of the hollow body 14.

[0166] monomer:

[0167] In a typical aspect, after washing the devices 12 with water, the monomer solution is introduced into the hollow body 14 by gradual fluid exchange while keeping the devices submerged. In a typical aspect, when the monomer substantially or completely replaces the previous coating fluid, the destacker 18 is retracted into the hollow body 14 and the reactor is rotated to a substantially horizontal position. The retraction and rotation can occur simultaneously or sequentially in any order, whereby the retraction can occur first or the rotation can occur first, followed by the rotation or retraction, respectively. The retraction of the destacker 18 displaces the central portion of the stacked devices 12, thereby creating a gap that allows further destacking and movement. The rotation of the reactor can include, for example, rotating the reactor back and forth to promote a substantially uniform dispersion of the devices 12 in the hollow body 14.

[0168] polymerization:

[0169] In a typical aspect, once the devices 12 described herein are substantially evenly dispersed within the hollow body 14, the hollow body 14 is maintained or locked in a substantially horizontal orientation, and the devices are exposed to a UV light source to initiate polymerization. In other embodiments, the hollow body 14 is continuously rotated between a substantially horizontal orientation and a substantially vertical orientation, or at various points therebetween, for the duration of the polymerization step to ensure that all devices are equally exposed to the UV light. In a typical aspect, the UV light source has a wavelength between approximately 100 nm and approximately 400 nm, for example, between approximately 100 nm and approximately 200 nm, or between approximately 100 nm and approximately 300 nm, or between approximately 200 nm and approximately 300 nm, or between approximately 200 nm and approximately 400 nm, or between approximately 300 nm and approximately 400 nm. Typically, the UV light source has a wavelength between approximately 300 nm and approximately 365 nm. The devices 12 are exposed to the UV light source for a period of time. For example, the period of time is approximately 5 minutes, approximately 6 minutes, approximately 7 minutes, or approximately 8 minutes. Typically, the period of time is approximately 6 minutes. Those skilled in the art will appreciate that the polymerization time depends on, for example, the device 12 and the photoinitiator or monomer concentration used in the polymerization reaction.

[0170] Post-polymerization washing:

[0171] After polymerization, the devices are typically restacked by rotating the reactor back to a substantially vertical orientation and tapping the device with a stopper. Complete stacking of the devices is not required in this step, and typically the devices exhibit a compact but semi-random orientation. The presence of a hydrophilic coating (grafted onto the surface of the device in a previous step) alleviates the need for perfect stacking and alignment, as subsequent solutions can more easily penetrate the coated device at this stage.

[0172] In a typical aspect, after polymerization, the monomer described herein is replaced with another alcohol wash solution. It should be understood that once polymerization is complete, subsequent fluid wash steps can be performed by fluid exchange, keeping the device submerged as described above, or by removing the monomer or wash solution and subsequently replacing it with the next solution. Typically, gradual fluid exchange is performed continuously during these steps. In a typical aspect, the alcohol comprises approximately 2 times, 3 times, or 4 times the volume of the hollow body 14. In a typical aspect, the alcohol wash to remove the monomer described herein comprises approximately 2 times the volume of the hollow body 14. In some aspects, when the monomer has been completely replaced by the alcohol, the drain is closed and the device 12 is allowed to remain in the alcohol for a period of time. For example, the period of time is approximately 5 minutes, approximately 6 minutes, approximately 7 minutes, or approximately 8 minutes, while the hollow body 14 is gently turned back and forth. Typically, the period of time is approximately 6 minutes. It should be understood that the period of time depends on the time required to ensure that unreacted photoinitiator and monomer molecules are washed out of the device 12 described herein.

[0173] Final Wash:

[0174] In a typical aspect, after completing the steps of the coating process described above, the process ends with a deionized water rinse of the device 12 described herein. Typically, the deionized water rinse rinses any excess alcohol wash solution from the device 12 described herein.

[0175] Coating activation:

[0176] In some aspects, and if desired by the user, after the aforementioned post-polymerization wash, the alcohol solution is replaced with an activation solution, which prepares the coating for incorporation of the active agent. In typical aspects, the activation solution is an alkaline solution, such as TRIS base (Tris(hydroxymethyl)aminomethane), at a concentration of 1-100 mM (typically 10-50 mM), which deprotonates acidic groups within the coating on the surface of device 12. When used, the activation solution is typically delivered to the hollow body 14, as described above. In typical aspects, the activation solution is introduced into the hollow body 14 at a volume of approximately 2, 3, or 4 times the volume of the hollow body 14. Typically, the amount of activation solution used is approximately 2 times the volume of the hollow body 14. In some aspects, when the alcohol solution has been completely replaced by the activation solution, the drain is closed and the device 12 is allowed to remain in the activation solution for a period of time. For example, the period of time is approximately 5 minutes, approximately 6 minutes, approximately 7 minutes, or approximately 8 minutes, while the hollow body 14 is gently inverted. Typically, the time period is about 6 minutes. As mentioned above, once the coating surface of device 12 is suitably activated, a solution containing therapeutic agent is introduced into hollow body 14. Typically, therapeutic agent is, for example, an antimicrobial (e.g., antibacterial, antifungal, antiviral, innate immune peptide or protein, silver ion, preservative), antiproliferative, antitumor, analgesic or anti-inflammatory agent. It should be understood that any suitable reagent can be incorporated into apparatus and methods as herein described. When the surface of device 12 comprises an antimicrobial, device 12 can be used for treating or preventing an infection that may damage a patient by using device 12. As will be understood, the contact time between the therapeutic agent described herein and the device 12 of coating depends on the desired concentration of the medicament on device 12, and typically can be in any range of the coating time from a few seconds to a few minutes.

[0177] The coating process described herein can be fully automated, semi-automated, or manual. The process described herein reduces the occurrence of trapped bubbles in and / or on the device during the coating process, compared to, for example, a method that includes sequentially immersing the device in various solutions. Because the method described herein is a "wet process," the product is not dried between each step. This allows for faster operation and coating methods compared to methods that require drying between steps, and also limits exposure to air / bubble formation in and / or on the device 12 as described herein. In addition, the process described herein allows all fluid exchanges to be performed in a single reactor 10, rather than in several separate stations, thereby eliminating the need for additional equipment / machinery to complete the coating process.

[0178] The foregoing disclosure generally describes the present invention. A more complete understanding may be obtained by reference to the following specific examples. These examples are described for illustrative purposes only and are not intended to limit the scope of the present invention. Variations in form and substitutions of equivalents are contemplated as circumstances may suggest or provide convenience. Although specific terms are used herein, these terms are intended to be descriptive and not for purposes of limitation.

[0179] Example

[0180] Example 1: Lubricious polyurethane extrusions

[0181] The general coating method described above was specifically applied to a 55 mm long tubular polyurethane extrudate having an inner diameter (ID) of approximately 0.76 mm and an outer diameter (OD) of approximately 1 mm. The purpose of the coating was to smooth the extrudate. As part of the method, a coating-specific dye was applied to the coated device 12 to facilitate visual inspection of the coating consistency on both the inner and outer surfaces of the tubular device. The method was performed as follows:

[0182] 1. Use a 50 cm long hollow borosilicate glass tube with an ID of 2.5 cm as the hollow body 14

[0183] 2. Approximately 400 devices 12 are stacked in the hollow body 14

[0184] 3. Assemble the reactor 10 according to the general coating process described above and rotate it to a vertical orientation.

[0185] 4. A volume of photoinitiator solution (400 mM benzophenone and 400 mM tert-butylperoxybenzoate dissolved in isopropyl alcohol) sufficient to completely immerse the device 12 is introduced into the reactor 10 through the top port 16 .

[0186] 5. A constant flow of nitrogen is introduced through the bottom port 16 for 6 minutes. The top port 16 is opened to the atmosphere to serve as an outlet for the nitrogen.

[0187] 6. After stopping the nitrogen flow, the device 12 is incubated in the photoinitiator solution for another 3 minutes. During this period, the stopper 24 is moved up and down several times to gently tap the stack of devices 12 to remove any remaining bubbles.

[0188] 7. A 70% isopropyl alcohol washing solution (7 parts isopropyl alcohol, 3 parts water, pre-purged with nitrogen for at least 10 minutes) approximately 3 times the volume of the hollow body 14 is introduced from the top port 16 while the fluid mixture in the reactor 10 is discharged from the bottom port 16. The flow rate in and out of the reactor 10 is adjusted to ensure that the stack of devices 12 is always immersed in the fluid.

[0189] 8. Water (pre-purged with nitrogen for at least 10 minutes) approximately three times the volume of the hollow body 14 is introduced from the top port 16 while the fluid mixture in the reactor 10 is discharged from the bottom port 16. The flow rates in and out of the reactor 10 are adjusted to ensure that the stack of devices 12 always remains immersed in the fluid.

[0190] 9. The hollow body 14 is filled with a monomer solution (300 mM acrylic acid, 50 mM methyl acrylate dissolved in water, pre-purged with nitrogen for at least 10 minutes) through the bottom port 16. The top port 16 is open to the atmosphere to serve as an outlet for the gas. When the hollow body 14 is filled with the monomer solution, the stopper 24 and the destacker 18 are retracted so that the destacker gasket 40, the stopper gasket 42 and the top plug 30 form a tight seal. The retraction of the destacker also achieves the destacking of the device 12.

[0191] 10. The reactor 10 is rotated between vertical and horizontal directions to further achieve destacking of the device 12

[0192] 11. Rotate the reactor 10 to a horizontal orientation and expose to UV radiation for 8 minutes

[0193] 12. Rotate the reactor 10 to a vertical orientation, allowing the devices 12 to settle at the bottom of the hollow body 14. Move the stopper 24 up and down several times to facilitate restacking of the devices 12.

[0194] 13. The monomer solution was drained from the reactor 10 through the bottom port 16 and a volume of isopropyl alcohol sufficient to completely immerse the device 12 was introduced into the reactor 10 through the top port 16. The device 12 was incubated in the isopropyl alcohol for 6 minutes.

[0195] 14. Drain the isopropyl alcohol from the reactor 10 through the bottom port 16 and introduce a volume of activating alkaline solution 1 (50 mM Tris(hydroxymethyl)aminomethane) sufficient to completely immerse the device 12 into the reactor 10 through the top port 16. Incubate the device 12 in the activating alkaline solution 1 for 6 minutes.

[0196] 15. The activated alkaline solution 1 is drained from the reactor 10 through the bottom port 16, and a volume of coating-specific dye solution (160 μM Brilliant Green, 10 mM Silver Acetate, 10 mM Pyroglutamic acid dissolved in water) sufficient to completely immerse the device 12 is introduced into the reactor 10 through the top port 16. The device 12 is incubated in the coating-specific dye solution for 6 minutes.

[0197] 16. The coating dye solution was drained from the reactor 10 through the bottom port 16, and a volume of activated alkaline solution 2 (10 mM tris(hydroxymethyl)aminomethane) sufficient to completely immerse the device 12 was introduced into the reactor 10 through the top port 16. The device 12 was incubated in the activated alkaline solution 2 for 6 minutes.

[0198] 17. Drain the activated alkaline solution 2 from the reactor 10 through the bottom port 16 and introduce a volume of water sufficient to completely immerse the device 12 into the reactor 10 through the top port 16. Incubate the device 12 in water for 6 minutes.

[0199] 18. Remove the device 12 from the reactor 10, unfold it and dry it at ambient temperature for at least 12 hours.

[0200] 19. Visually inspect each device for inconsistencies (pores) in the coating by the absence of coating specific staining in significant portions of the device.

[0201] To compare the performance of the present invention (one-pot process) with a more conventional coating process (multi-station approach), the following process was performed:

[0202] 1. Incubate approximately 400 devices 12 in a photoinitiator solution (400 mM benzophenone and 400 mM t-butyl peroxybenzoate dissolved in isopropyl alcohol) for 9 minutes.

[0203] 2. Incubate the device 12 in a 70% isopropyl alcohol cleaning solution for 1 minute

[0204] 3. Incubate the device 12 in the water washing station for 1 minute

[0205] 4. Move the device 12 to a 50 cm long hollow borosilicate glass tube (monomer station) with an ID of 2.5 cm filled with a monomer solution (300 mM acrylic acid, 50 mM methyl acrylate dissolved in water). A constant flow of nitrogen was introduced into the monomer solution for 6 minutes, after which the device 12 in the monomer station was exposed to UV irradiation for 8 minutes.

[0206] 5. Incubate the device 12 in an isopropyl alcohol wash station for 6 minutes

[0207] 6. Incubate the device 12 in an activated alkaline solution 1 (50 mM tris(hydroxymethyl)aminomethane) for 6 minutes

[0208] 7. Incubate the device 12 in a coating-specific dye solution (160 μM Brilliant Green, 10 mM Silver Acetate, 10 mM Pyroglutamic Acid dissolved in water) for 6 minutes

[0209] 8. Incubate the device 12 in the activated alkaline solution 2 (10 mM tris(hydroxymethyl)aminomethane) for 6 minutes

[0210] 9. Incubate the device 12 in the washing station for 1 minute

[0211] 10. Remove the device 12 from the washing station, unfold it and dry it at ambient temperature for at least 12 hours

[0212] 11. Visually inspect each device for inconsistencies (pores) in the coating by the absence of coating specific staining in significant portions of the device.

[0213] The consistency of the coatings produced by the two methods described above was compared based on the proportion of devices with significant inconsistencies (voids) in the coatings and the results are summarized in the table below.

[0214] Coating method No coating inconsistencies Minor coating inconsistencies Severe coating inconsistency One-pot method 74％ 26％ 0％ Multi-station method 0.5％ 4％ 95.5％

[0215] The above disclosure generally describes the present invention. Although specific terms are employed herein, these terms are intended in a descriptive sense only and not for purposes of limitation.

[0216] Patent applications, patents, and publications are cited herein to aid in understanding the embodiments. All of these references cited herein are incorporated herein by reference in their entirety and are incorporated herein for all purposes to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated as being incorporated herein by reference in its entirety for all purposes. To the extent that publications, patents, or patent applications incorporated by reference conflict with the disclosure contained in the specification, the specification is intended to supersede and / or take precedence over any such conflicting material.

[0217] While specific embodiments of the present invention have been described in detail herein, those skilled in the art will recognize that changes can be made thereto without departing from the spirit of the invention or the scope of the appended claims.

[0218] It should be understood that some of the above-described structures, functions, and operations of the above-described embodiments are not necessary for practicing the present invention and are included in the description only for the sake of completeness of one or more exemplary embodiments. In addition, it should be understood that the specific structures, functions, and operations set forth in the above-referenced patents and publications can be implemented in conjunction with the present invention, but they are not necessary for its practice. Therefore, it should be understood that the present invention can be implemented in a manner different from that specifically described without departing from the spirit and scope of the present invention as defined by the appended claims.

Claims

1. A reactor for coating a plurality of devices, characterized in that The reactor comprises: a hollow body for supporting the plurality of devices; a port in fluid communication with the hollow body for exchanging a coating fluid; A retainer for facilitating a stacked orientation of the plurality of devices, wherein the retainer is movable along a length of the hollow body, and wherein the retainer includes a retainer flange.

2. The reactor according to claim 1, characterized in that The plurality of devices are movable within the hollow body from the stacked orientation to a non-stacked orientation.

3. The reactor according to claim 2, characterized in that The hollow body is longer than the plurality of devices to allow the plurality of devices to move substantially freely within the hollow body in the non-stacked orientation.

4. The reactor according to claim 3, characterized in that The hollow body is at least 50%, 60%, 70%, 80%, 90%, 100%, 110%, 120%, 130%, 140%, 150%, 160%, 170%, 180%, 190%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 550%, 600% longer than the plurality of devices.

5. The reactor according to claim 2, characterized in that The hollow body has a cross-sectional area sufficiently similar to a cross-sectional area of ​​the plurality of devices in the stacked orientation to constrain the plurality of devices to move substantially freely within the hollow body in the stacked orientation.

6. The reactor according to claim 2, characterized in that The hollow body has a diameter that is less than a length of the plurality of devices to ensure that the plurality of devices remain in a desired orientation in the non-stacked orientation.

7. The reactor according to claim 2, characterized in that The reactor also includes a destacker that releases the plurality of devices from the stacked orientation.

8. The reactor according to claim 7, characterized in that The destacker is movable along the length of the hollow body.

9. The reactor according to claim 7 or 8, characterized in that The decompressor includes a decompressor flange.

10. The reactor according to claim 9, characterized in that Movement of the destacker flange disrupts the stacking orientation.

11. The reactor according to claim 10, characterized in that Movement of the destacker flange provides a gap that disrupts the stacking orientation.

12. The reactor according to claim 10 or 11, characterized in that The decompressor flange is porous and / or flexible.

13. The reactor according to claim 9, characterized in that The destacker further includes a destacker rod coupled to the destacker flange for moving the destacker flange through the hollow body.

14. The reactor according to claim 13, characterized in that The decompressor rod extends axially through the hollow body.

15. The reactor according to claim 14, characterized in that Movement of the retainer flange allows the plurality of devices to be released from the stacked orientation.

16. The reactor according to claim 15, characterized in that The stopper further includes a stopper rod coupled to the stopper flange for moving the stopper flange through the hollow body.

17. The reactor according to claim 16, characterized in that The stopper rod extends axially through the hollow body.

18. The reactor according to claim 16 or 17, characterized in that The destacker rod extends axially through the stopper rod.

19. The reactor according to claim 16, characterized in that The destacker rod and the stopper rod move independently of each other or together.

20. The reactor according to claim 19, characterized in that The port is located at one end of the hollow body.

21. The reactor according to claim 19, characterized in that The port is located at the bottom end of the hollow body.

22. The reactor according to claim 19, characterized in that The port is located at the top end of the hollow body.

23. The reactor according to claim 19, characterized in that The ports are located at the top and bottom ends of the hollow body.

24. The reactor according to claim 23, characterized in that The reactor further includes a plug located at a top end of the hollow body.

25. The reactor according to claim 24, characterized in that The port extends through the plug for fluid flow.

26. The reactor according to claim 24 or 25, characterized in that The plug defines a void having a convex shape to direct fluid to the port.

27. The reactor according to claim 26, characterized in that The convex shape is a frustoconical, conical, or parabolic shape.

28. The reactor according to claim 25, characterized in that The fluid is a gas.

29. The reactor according to claim 25, characterized in that The stopper rod and / or the destacker rod extend through the plug.

30. The reactor according to claim 25, characterized in that When the destacker rod and the stopper rod move through the plug, a washer coupled to the destacker rod slides into a washer coupled to the stopper rod, and the washer coupled to the destacker rod and the washer coupled to the stopper rod jointly abut a surface of the plug to restrict fluid flow through the plug in the non-stacked orientation.

31. The reactor according to claim 30, characterized in that The reactor also includes a bottom plug.

32. The reactor according to claim 31, characterized in that The port extends through the bottom plug for exchanging the coating fluid.

33. The reactor according to claim 32, characterized in that The reactor also includes an aerator.

34. The reactor according to claim 33, characterized in that The hollow body is cylindrical.

35. The reactor according to claim 34, characterized in that The hollow body is partially or completely transparent.

36. The reactor according to claim 35, characterized in that The hollow body is partially or completely UV-transparent.

37. The reactor according to claim 36, characterized in that The hollow body comprises glass.

38. The reactor according to claim 37, characterized in that The glass is borosilicate or quartz.

39. The reactor according to claim 38, characterized in that The plurality of devices is a plurality of medical devices.

40. The reactor according to claim 39, characterized in that The plurality of devices are selected from the group consisting of heart valves, dressings, needles, forceps, clips, syringes, syringe accessories, catheters, drains, stents, implants, eyepieces, and delivery devices thereof.

41. The reactor according to claim 39, characterized in that The plurality of devices are bushings.

42. The reactor according to claim 41, characterized in that The plurality of devices are catheters.

43. The reactor according to claim 40, characterized in that Each of the plurality of devices is identical.

44. The reactor according to claim 43, characterized in that During the exchange of the coating fluid, the plurality of devices remain in contact.

45. The reactor according to claim 43 or 44, characterized in that The plurality of devices contact each other when in the stacked orientation such that no dead space exists.

46. ​​The reactor according to claim 44, characterized in that The fluid exchange reduces air bubbles in and / or around the plurality of devices.

47. The reactor according to claim 46, characterized in that The reactor is movable between a vertical position and a horizontal position.

48. The reactor according to claim 47, characterized in that Movement from the vertical position to the horizontal position facilitates the non-stacked orientation.

49. The reactor according to claim 47 or 48, characterized in that The non-stacked orientation and / or the horizontal position promotes substantially uniform coverage of the device with the coating fluid.

50. The reactor according to claim 49, characterized in that The non-stacked orientation and / or the horizontal position facilitates substantially uniform dispersion of the devices throughout the hollow body.

51. The reactor according to claim 44, characterized in that The plurality of devices are not exposed to air during or after the exchange of the coating fluid.

52. The reactor according to claim 51, characterized in that The coating fluid includes a fluid selected from the group consisting of a photoinitiator, a monomer, water, alcohol, and combinations thereof.

53. The reactor according to claim 52, characterized in that The photoinitiator is selected from the group consisting of esters, α-hydroxy ketones, benzyl ketones, benzoic acids and derivatives and combinations thereof.

54. The reactor according to claim 52, characterized in that The photoinitiator is selected from the group consisting of 2,2-dimethoxy-2-phenyl-acetophenone (DPA), tert-butyl p-benzoylperbenzoate (BPB), tert-butyl peroxybenzoate (TBP), benzophenone (BP) and combinations thereof.

55. The reactor according to claim 52, characterized in that The photoinitiators include benzophenone and t-butyl perbenzoate.

56. The reactor according to claim 52, characterized in that The monomer is selected from the group consisting of acrylic acid, methacrylic acid, 2-carboxyethyl acrylate, 4-vinylbenzoic acid, itaconic acid, methyl acrylate, and combinations thereof.

57. The reactor according to claim 56, characterized in that The monomers include acrylic acid and methyl acrylate.

58. The reactor according to claim 52, characterized in that The monomer, water and / or alcohol are purged with an oxygen-scavenging gas.

59. The reactor according to claim 58, characterized in that The oxygen-scavenging gas is selected from the group consisting of nitrogen, argon, helium and combinations thereof.

60. The reactor according to claim 59, characterized in that The oxygen-scavenging gas is nitrogen.

61. The reactor according to claim 52, characterized in that The water is deionized water.

62. The reactor according to claim 52, characterized in that The alcohol is a low surface tension alcohol solution.

63. The reactor according to claim 62, characterized in that The alcohol is selected from the group consisting of methanol, ethanol, isopropyl alcohol and combinations thereof.

64. The reactor according to claim 1, characterized in that The reactor is used to coat the device in a one-pot process with exchange of coating fluids.

65. The reactor according to claim 64, characterized in that The exchange of the coating fluid is fully automatic, semi-automatic or manual.

66. A system, characterized in that comprising a reactor stand for supporting a reactor according to any one of claims 1 to 65 and a rotation mechanism for changing the orientation of the reactor stand from a first orientation to a second orientation.

67. The system according to claim 66, characterized in that The first orientation is a vertical orientation.

68. The system according to claim 67, wherein: The second orientation is a horizontal orientation.

69. The system according to claim 68, characterized in that The system also includes a lamp assembly attachable to the reactor support for initiating a polymerization reaction within the reactor.

70. The system according to claim 69, wherein: The lamp assembly includes a UV light source.

71. The system according to claim 70, wherein: The UV light source has a wavelength between 100 nm and 400 nm.

72. The system according to claim 71, characterized in that The UV light source has a wavelength between 300 nm and 365 nm.

73. The system according to any one of claims 66 to 72, characterized in that The system comprises one or more reactors according to any one of claims 1 to 65.

74. A one-pot method for coating a device, characterized in that The method comprises: exchanging coating fluids within a reactor according to any one of claims 1 to 65; and The plurality of devices are coated with the coating fluid such that the coating fluid covers surfaces of the plurality of devices.

75. The method according to claim 74, wherein The plurality of devices are continuously immersed in the coating fluid such that the plurality of devices are not exposed to air.

76. The method according to claim 74, characterized in that The exchanging coating fluids minimizes bubble formation within and / or outside the plurality of devices.

77. The method according to claim 74, characterized in that The method includes immersing the plurality of devices in alcohol to remove air bubbles and exchange subsequent fluids while maintaining the plurality of devices submerged without substantially exposing the plurality of devices to air.

78. A one-pot process for fluid processing a plurality of devices coated with a reactor according to any one of claims 1 to 65 and reducing bubble formation, characterized in that The method includes immersing the plurality of devices in alcohol and exchanging the alcohol with the fluid for processing.

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