Articles and related methods including markings

Abstract

The invention provides devices and related methods that reduce complications, such as reduced thrombus formation and / or other enhanced performance, when deployed in a patient. [Solution] A method comprising the steps of introducing fluid into a marked catheter using a marked catheter, the marked catheter having markings including a plurality of separate segments spaced apart along at least a portion of the catheter, wherein the mean shortest distance between each segment and its nearest adjacent segment is a first distance in a first configuration of the marked catheter, and inflating at least a portion of the marked catheter from a first configuration to a second configuration, wherein the mean shortest distance between each segment and its nearest adjacent segment in the second configuration is a second distance, and the ratio of the second distance to the first distance is 1.02:1 or greater and 2:1 or less.

Description

[Technical Field]

[0001] (Related applications) This application claims priority under jointly pending U.S. Provisional Application No. 63 / 046499, filed on June 30, 2020, under Section 19(e) of the U.S. Patent Act, which is incorporated herein by reference in its entirety.

[0002] The present invention generally relates to articles such as catheters, which include markings. The articles may be medical devices configured to be at least partially placed within a patient, such as articles and / or devices that include an elongated shaft configured to be placed within a blood vessel or other conduit of the patient. [Background technology]

[0003] Current catheters and other patient-implantable medical devices exhibit a variety of complications, including those associated with thrombus formation, when placed in the patient's bloodstream, such as when placed in the patient's veins, arteries, and / or heart. Thrombosis increases the risk of and / or causes infection, symptomatic deep vein thrombosis (DVT), pulmonary embolism (PE), asymptomatic thrombosis, vascular trauma, and / or vascular occlusion. Complications seen with such devices prolong hospital stays and increase morbidity and mortality rates.

[0004] When placed in a patient, there is a need for devices that reduce complications, such as reduced thrombus formation and / or other enhanced performance. [Overview of the project]

[0005] Methods and articles related to marked catheters are generally provided. In some embodiments, a series of methods are provided. In some embodiments, in the method, the marked catheter comprises a marking that includes a plurality of distinct segments spaced apart along at least a portion of the catheter, wherein the mean shortest distance between each segment and its nearest adjacent segment is a first distance in the first configuration of the marked catheter. The steps of introducing fluid into the marked catheter, and A step of expanding (or swelling) at least a portion of the marked catheter from a first configuration to a second configuration. This includes performing the following: The average shortest distance between each segment and its nearest adjacent segment in the second configuration is the second distance. The ratio of the second distance to the first distance (first distance:second distance) is between 1.02:1 and 2:1.

[0006] In some embodiments, the method includes a marking comprising a plurality of distinct segments spaced apart along at least a portion of the catheter, wherein the mean shortest distance between each segment and its nearest adjacent segment is a first distance in the first configuration of the marking catheter. The steps of introducing fluid into the marked catheter, and A step of expanding at least a portion of the marked catheter from a first configuration to a second configuration. This includes performing the following: The average shortest distance between each segment in the second configuration and its nearest adjacent segment becomes the second distance. The second distance is approximately 1 mm, approximately 10 mm, approximately 100 mm, approximately 1 cm, or approximately 10 cm.

[0007] In some embodiments, a series of articles are provided. In some embodiments, the article includes a catheter having a plurality of markings. The markings include a plurality of distinct segments spaced apart along at least a portion of the surface of the catheter. The article has a first configuration having a first water content (or moisture content) of 2 w / w% to 40 w / w%. The first distance is the average shortest distance between each segment in the first configuration and its nearest adjacent segment. The article has a second configuration having a second water content of 20 w / w% to 99 w / w%. The second distance is the average shortest distance between each segment in the second configuration and its nearest adjacent segment. The second water content is greater than the first water content. The ratio of the second distance to the first distance is 1.02:1 or greater.

[0008] In some embodiments, the article comprises a catheter having a plurality of markings. The markings include a plurality of distinct segments spaced apart along at least a portion of the surface of the catheter. The article has a first configuration having a first water content of 2 w / w% to 40 w / w%. The first distance is the mean shortest distance between each segment in the first configuration and its nearest adjacent segment. The article has a second configuration having a second water content of 20 w / w% to 99 w / w%. The second distance is the mean shortest distance between each segment in the second configuration and its nearest adjacent segment. The second water content is greater than the first water content. The second distance is equal to about 1 mm, about 10 mm, about 100 mm, about 1 cm, or about 10 cm.

[0009] In some embodiments, the article includes a catheter and markings. The markings include a plurality of distinct segments spaced apart along at least a portion of the surface of the catheter. At least a portion of the catheter does not include the markings. In some embodiments, the article has substantially no thrombus accumulation. The level of thrombus accumulation in the markings is within 50% of the level of thrombus accumulation in the portion of the catheter that does not include the markings.

[0010] In some embodiments, the article comprises a marking composition comprising a salt, a dye, and a first water-soluble polymer.

[0011] In some embodiments, the method includes the steps of placing a marking composition on a catheter, penetrating the marking composition into the catheter by at least 10 nm, and fixing (or locking) the marking composition to the catheter. The placement step includes automated inkjet deposition. The fixing step includes thermal annealing, heat treatment, moisture drying, freeze-drying, or a combination thereof.

[0012] In some embodiments, the article includes a catheter and markings. The markings include a number of distinct segments spaced apart along at least a portion of the surface of the catheter. At least a portion of the markings penetrates the catheter to a depth of 10 μm to 10 mm.

[0013] Other advantages and novel features of the present invention will become apparent from the following detailed description of various non-limiting embodiments of the invention, in conjunction with the accompanying drawings. In the event that there is any inconsistency and / or inconsistency between disclosures in this specification and those of documents incorporated by reference, the provisions of this specification shall prevail.

[0014] All publications, patents, and patent applications referenced herein are incorporated by reference to the same extent as if each individual publication, patent, or patent application were specifically and individually indicated by reference. [Brief explanation of the drawing]

[0015] Non-limiting embodiments of the present invention will be described by way of example with reference to the accompanying drawings, which are schematic and are not intended to be drawn to scale. In the figures, each identical or nearly identical component illustrated is typically represented by a single numeral. For purposes of clarity, not every component is labeled in every figure, nor is every component of each embodiment of the present invention shown where illustration is not necessary for those skilled in the art to understand the present invention. [Figure 1A] It shows a cross-sectional view of an exemplary device including markings according to one set of embodiments. [Figure 1B] It is a perspective view of a medical device and a schematic diagram of a system for manufacturing the medical device, consistent with some embodiments. [Figure 2] It shows data comparing normalized thrombus accumulation across different conduits, consistent with some embodiments. [Figure 3] It shows photographs of a dry catheter and a catheter after hydration with phosphate-buffered saline, consistent with some embodiments. [Figure 4] It shows photographs of a dry catheter and a catheter after hydration with phosphate-buffered saline, consistent with some embodiments. [Figure 5] It shows photographs of a dry catheter and a catheter after hydration with phosphate-buffered saline, consistent with some embodiments. [Figure 6] It shows photographs of a dry catheter and a catheter after hydration with phosphate-buffered saline, consistent with some embodiments. [Figure 7] It shows photographs of a dry catheter and a catheter after hydration with phosphate-buffered saline, consistent with some embodiments. [Figure 8] It is a diagram illustrating a method of manufacturing, fabricating, and inserting a medical device, consistent with some embodiments. [Figure 9] It is a perspective view of a medical device including an S-shaped conduit, consistent with some embodiments. [Figure 10A] Perspective and end views of clamps for fastening or securing conduits, consistent with several embodiments. [Figure 10B] Perspective and end views of clamps for fastening or securing conduits, consistent with several embodiments. [Figure 10C] Perspective and end views of clamps for fastening or securing conduits, consistent with several embodiments. [Figure 11A] A perspective view of a hydration device for hydrating a conduit, consistent with several embodiments, is shown. [Figure 11B] A perspective view of a hydration device for hydrating a conduit, consistent with several embodiments, is shown. [Figure 12] A flowchart of a method for manufacturing a conduit, consistent with several embodiments, is shown. [Figure 13] A method for batch processing polymer materials, consistent with several embodiments, is presented. [Figure 14] A method for extruding polymer materials, consistent with the concept of the present invention, is presented. [Figure 15] A method for hydrophilic treatment of a material, consistent with several embodiments, is presented. [Figure 16] A method for annealing a material, consistent with several embodiments, is shown. [Figure 17] This document describes a method for overmolding a material that is consistent with the concept of the present invention. [Figure 18] A method for humidifying a material, consistent with several embodiments, is shown. [Figure 19] This shows an article containing multiple holes, consistent with several embodiments. [Figure 20] This shows an article containing multiple holes, consistent with several embodiments. [Figure 21] This document shows an article comprising two components, consistent with several embodiments. [Figure 22] This document shows an article comprising two components, consistent with several embodiments. [Figure 23A]Photographs of exemplary marked catheters in several embodiments are shown. [Figure 23B] Photographs of exemplary marked catheters in several embodiments are shown. [Modes for carrying out the invention]

[0016] Next, we will refer in detail to embodiments of the technology illustrated in the accompanying drawings. Similar reference numerals may be used to refer to similar components. However, this description is not intended to limit the disclosure to any particular embodiment, but should be understood to include various modifications, equivalents, and / or substitutes of the embodiments described herein.

[0017] Articles such as catheters and related methods including markings are provided. Articles described herein may be configured to exhibit one or more desirable properties. For example, in some embodiments, an article comprises markings placed at known distances apart from one another. Such markings may be employed to assist the user of the article in measuring distances and / or identifying the article. In another example, an article may be configured to swell upon exposure to a fluid so that the markings placed on it do not crack or peel off. It is also possible that the article is configured to swell upon exposure to a fluid in a known, predictable, and / or uniform manner. This swelling may increase the spacing between the markings, and such increase may also be in a known, predictable, and / or uniform manner. If the fluid causing the article to swell is a bodily fluid, such as the fluid to which the article is exposed when implanted in a patient, and the article swells in the patient such that the markings are at known intervals, the markings may be advantageously employed to measure distances to the patient (e.g., the depth to which the article is inserted into the patient), and / or changes in the marking spacing may be employed to determine swelling of the article in the patient.

[0018] Another advantageous property that some articles described herein may exhibit is favorable (e.g., consistent with hydrophilic, non-thrombotic surfaces, such as those of the articles described herein) and / or consistent resistance to thrombus formation within the article. Resistance to thrombus formation consistent with hydrophilic, non-thrombotic surfaces is desirable because, when the article is placed in a patient, it can prevent thrombus formation and / or substantially reduce the rate at which thrombus formation occurs. A portion of an article implanted in a patient with relatively low resistance to thrombus formation may act as a nucleus for thrombi that may grow unfavorably across the article, even if placed in an article with relatively high overall resistance to thrombus formation. Therefore, uniform resistance to thrombus formation is particularly beneficial.

[0019] Methods and articles herein advantageously provide high-strength materials having a true porous structure and other useful properties such as an unexpectedly good combination of biocompatibility and mechanical properties. Embodiments of porous solid materials are provided having a combination of structural features independently selected from pore size, tensile strength, Young's modulus, solid concentration, type and degree of crosslinking, internal arrangement, hydrophilicity, and composition for the material, and further optionally, independently selected end-user devices or intermediate materials having a desired aspect ratio for molded shape, lumen, multiple lumen, tube with concentrically arranged lumen, or tolerance of thickness: each of these is described in further detail herein.

[0020] Advantageously, in some embodiments, the marking may be seamless with the catheter body. In some such embodiments, the marking may provide measurement (for example, for clinical insertion) without serving as an indicator of thrombus accumulation.

[0021] The methods and compositions described herein are useful for providing artwork, labels, product descriptions, brands, logos, etc., to various articles (e.g., catheters, suture wings, medical devices, polymer materials). For example, labels, markings, and / or identifiers may be provided to the articles described herein.

[0022] In a series of exemplary embodiments, the method includes swelling a conduit, including markings such as a marked catheter, from a first unswollen configuration to a second swollen configuration. The markings may take the form of a plurality of distinct segments spaced apart along at least a portion of the surface of the conduit. This swelling may increase the mean shortest distance between markings from a first mean shortest distance to a second mean shortest distance. For example, the method may include swelling the conduit such that the ratio of the first mean shortest distance to the second mean shortest distance is between 1.02:1 and 2:1. As another example, the method may include swelling the conduit such that the second mean shortest distance is equal to about 1 mm, about 1 cm, or about 10 cm.

[0023] In another exemplary set of embodiments, an article is provided. The article may include a conduit, such as a catheter, which includes a plurality of markings. The conduit may be configured to have a first unswollen configuration containing a relatively low amount of water (e.g., 2 w / w% to 40 w / w%) and a second swollen configuration containing a higher amount of water (e.g., 20 w / w% to 99 w / w%). The mean shortest distance between markings, which may take the form of a plurality of distinct segments spaced apart along at least a portion of the surface of the conduit, may be greater in the swollen configuration than in the unswollen configuration. In some embodiments, the ratio of the mean shortest distance between markings in the swollen configuration to the spacing between markings in the unswollen configuration is 1.02:1 or greater and 2:1 or less. In some embodiments, the mean shortest distance in the swollen conduit is equal to about 1 mm, about 1 cm, or about 10 cm.

[0024] In a third exemplary set of embodiments, an article is provided. The article may include a conduit, such as a catheter, which has markings in some parts and lacks markings in other parts. Both the markings and the conduit may be relatively resistant to thrombus formation. For example, the article as a whole may be substantially thrombus-free, and / or thrombus accumulation in the markings may be no more than 50% of the thrombus accumulation in the unmarked parts of the conduit.

[0025] A marking composition is provided in a fourth exemplary set of embodiments. The marking composition may be suitable for adhering to a conduit, such as a catheter, to form a marked conduit. The marking composition may comprise salts, dyes, and water-soluble polymers.

[0026] A fifth set of exemplary embodiments provides a method for forming an article. The method includes placing a marking composition on a conduit, such as a catheter, to form a marking thereon. In some embodiments, the marking composition may be adhered and then penetrated a distance within the conduit (e.g., at least 10 nanometers, at least 10 μm). The marking may then be fixed to the conduit. Affirming the marking may include preventing penetration into the catheter and / or chemically bonding to the conduit. This may be achieved by applying a stimulus, such as heat, to the conduit and / or the marking composition. Various suitable adhesion techniques may be employed, including automated inkjet adhesion and / or pad printing. In some embodiments, fixing includes heat treatment, moisture drying, freeze-drying, thermal annealing, or a combination thereof.

[0027] In some embodiments, the marking is applied to the surface of the article.

[0028] In a sixth set of exemplary embodiments, an article is provided comprising a conduit, such as a catheter, and a marking. At least a portion of the marking may penetrate into the interior of the conduit. The depth of penetration may be between 10 nanometers and 10 μm, or between 10 nanometers and 10 mm, or between 10 μm and 10 mm. The marking may take the form of a plurality of distinct segments spaced apart along the surface of the conduit.

[0029] For example, as shown in the cross-sectional view in Figure 1A, the device 100 includes a conduit 110 (e.g., a catheter) and markings 112 spaced apart along at least a portion of the conduit 110. In some embodiments, the conduit 110 may have a first configuration 110A (e.g., an unswollen configuration) and a second configuration 110B (e.g., a swollen configuration). In some embodiments, the markings have an average shortest distance 113 between them. For example, swelling between the first configuration 110A and the second configuration 110B results in an increase in the average shortest distance 113 between the markings.

[0030] Furthermore, some methods may involve implanting, at least partially, the articles described herein into a patient, some methods may involve fabricating the articles described herein, and some embodiments may relate to articles fabricated by the methods described herein.

[0031] One example of articles provided herein is a medical device such as a catheter, comprising a reinforcing material, such as a material configured to prevent thrombus formation or otherwise provide enhanced performance when placed in a patient. Methods for manufacturing these articles and / or medical devices are also provided. The reinforcing materials described herein can be used to create catheter shafts and / or other device components having a relatively high water content and / or a neutral surface charge (e.g., to minimize the body's foreign body reaction). These reinforcing materials can provide increased strength and improved lumen patency (e.g., for introduction into a blood vessel) while reducing trauma to the blood vessel into which the associated device is inserted. The reinforcing materials may include materials having hydrophilicity, high strength, improved flexibility, and / or a nanoporous structure. A medical device of the concept of the present invention may comprise a catheter that may be inserted into a patient's blood vessel without requiring an introducer (to reduce trauma to the associated blood vessel).

[0032] Furthermore, the devices described herein, and related techniques for placing markings on the devices, can also be performed on devices other than medical devices. For example, some embodiments relate to PVA films (such as those used in detergent pods), PVA membranes, and / or methods related to such devices.

[0033] Referring to Figure 1B, a perspective view of one example of an article is provided. It is a schematic diagram of a medical device including a conduit and a system for manufacturing the medical device. The system 10 shown in Figure 1B includes a medical device 100, as well as various components used to manufacture, package, and / or sterilize the device 100. The device 100 can be transported to a hospital, examination room, and / or other clinical environment ("clinical site") for placement of the device 100 in a patient. The device 100 can be implanted in a patient at an "implantation site" (e.g., by surgical procedure). Alternatively, the device 100 can be inserted into the patient by passing through the patient's skin at an "insertion site" (e.g., if the device 100 passes through the skin and enters the patient's blood vessels). The implantation or insertion (hereinafter "insertion") procedure may be performed in an operating room, catheterization laboratory, and / or other location where aseptic techniques can be performed ("operation site").

[0034] Device 100 may include a tube, conduit 101, which includes a proximal portion 104 having a proximal end 103, a distal portion 108 having a distal end 109, and a lumen 106 between them. The conduit 101 may include a wall 102 surrounding the lumen 106, the wall 102 including an inner surface (e.g., inside the conduit 101) and an outer surface (e.g., outside the conduit 101). The conduit 101 may be constructed from or otherwise fabricated from a polymer material 20 such as those described below. Device 100 may further include a mechanical interlock connector (e.g., a Luer connector), connector 120, which may be configured to operably attach Device 100 to another device (e.g., fluidly attach). System 10 may also include an extrusion device, extruder 500, which may be configured to produce one or more components of Device 100, such as the conduit 101 of Device 100. System 10 may further include various tools, containers, solutions, instruments, devices, and / or other components that can be used to manufacture, package, and / or store device 100 and / or its components (e.g., conduit 101).

[0035] In some embodiments, the device 100, the extruder 500, and / or other components of the system 10 have a similar structure and arrangement to similar components described in the applicant's concurrently pending applications.

[0036] Device 100 may comprise at least a portion of a medical device, such as a device configured to be implanted in a patient or otherwise inserted. In some embodiments, Device 100 includes a conduit 101 that can be attached to or attached to another medical device, for example, if Device 100 includes a catheter that can be attached to a pump, such as an implantable pump (e.g., an implantable pump configured to deliver drugs or other medications to locations in the patient's vascular system, the ventricles of the brain, the spaces of the spine (e.g., epidural or intrathecal space of the spine), and / or the gastrointestinal system of the patient (e.g., stomach or intestine). Device 100 may comprise a catheter selected from the group consisting of central venous catheters, peripheral central catheters, peripheral port catheters, central venous port catheters, midline catheters, peripheral catheters, tunnel catheters, dialysis access catheters, urethral catheters, nerve catheters, peritoneal catheters, intra-aortic balloon pump catheters, diagnostic catheters, interventional catheters, drug delivery catheters, drainage catheters, central nervous system catheters, hemodialysis catheters, and combinations thereof.

[0037] Furthermore, or alternatively, device 100 may comprise medical devices selected from the group consisting of shunts, wound drains such as external drains (e.g., ventricular, ventricular peritoneal, lumbar peritoneal), infusion ports, soft tissue patches, drug delivery devices such as insulin pumps, tubes, contraceptives, female hygiene devices, endoscopes, grafts, pacemakers, implantable cardioverter-defibrillators, cardiac resynchronization devices, cardiovascular device leads (conduit 101 may further include insulators for leads), ventricular assist devices, cochlear implants, endotracheal tubes, tracheostomy tubes; implantable sensor devices (e.g., intravascular, percutaneous, intracranial), ventilator pumps, ophthalmic devices such as ophthalmic drug delivery devices; and combinations thereof.

[0038] At least a portion of device 100 may be configured to come into contact with bodily fluids within the patient. For example, device 100 may include ex vivo (or in vitro) devices and / or in vivo (or intra vivo) devices, such as blood-contact implants.

[0039] At least a portion of device 100 may include a patient-implantable device, such as a percutaneously inserted device. At least a portion of device 100 may include a permanently implanted device. For example, device 100 may remain implanted in the patient for longer than 5 years. At least a portion of device 100 may include a temporarily implanted device. For example, device 100 may remain implanted in the patient for a period of 5 years or less, e.g., 1 year or less, e.g., 6 months or less, e.g., 3 months or less.

[0040] The conduit 101 may comprise one, two, or more nanoporous materials, microporous materials, and / or high-strength hydrogels. The conduit 101 is configured to prevent or otherwise reduce thrombus accumulation (e.g., compared to other conduits) when implanted in a patient. The conduit as a whole may have reduced thrombus accumulation and / or substantially no thrombus accumulation compared to polyurethane materials when placed in one or more relevant environments (e.g., body fluids, patient). For example, in some embodiments, the conduit may substantially exhibit (or not produce; exhibit) thrombus accumulation compared to other equivalent conduits formed from polyurethane. In some embodiments, the conduit 101 comprises one, two, or more polymer materials 20 configured to reduce thrombus accumulation. Such polymer materials may comprise water-soluble polymers described elsewhere herein as suitable for inclusion in the conduit. An exemplary method for determining thrombus accumulation (e.g., non-thrombogenicity) is described in Example 1.

[0041] The applicant conducted a study to evaluate the thrombotic resistance of one preferred type of conduit 101 (HydroPICC catheter) in an in vitro blood flow loop system, thereby evaluating thrombus formation and platelet adhesion to conduit 101 in the presence of blood. The blood flow loop system makes it possible to evaluate the intrinsic device thrombotic properties. Hematological parameters (e.g., hemodynamics, anticoagulation) in this in vitro model are more controlled than in the in vivo model, which is thought to allow for direct, semi-quantitative evaluation of thrombus formation. External dynamic parameters (e.g., vascular morphology, animal physiology, activity, fluctuating hemostasis, homeostasis, infection, etc.) that may interfere with in vivo evaluations can be eliminated in the in vitro blood loop model. This is thought to allow for focusing the evaluation of thrombolytic resistance on the surface properties and chemical properties of conduit 101, while keeping other parameters relatively constant. The in vitro blood loop model is thought to enable the isolated quantification of platelet adhesion. Since platelet adhesion is considered a fundamental and important step in thrombus formation, its quantification is considered a conservative indicator of thrombus accumulation.

[0042] For the study conducted by the applicant, the blood flow loop consisted of a polyvinyl chloride tube with an inner diameter of 1 / 4 inch. The conduit 101, containing the lumen 106, was hydrated with sterile saline for approximately 24 hours before insertion into the blood flow loop. The conduit 101 was then cut into a sample containing approximately 15 cm in length. The proximal opening of the lumen 106 was occluded with epoxy to simulate a "fixed" catheter. Fresh bovine blood was collected by cardioperfusion and heparin was added to a concentration of 0.75 U / mL. Autologous platelets were purified, marked with indium 111, and returned to the bovine blood. The conduit 101 was inserted into the blood flow loop and left in place for approximately 120 minutes. The bovine blood was maintained at a temperature of 37°C and pumped into the blood flow loop at a rate of 200 mL / min via a peristaltic pump, thereby simulating physiological blood flow across the conduit 101. Conduit 101 was evaluated for thrombus accumulation after 45 minutes and removed from the blood flow loop between 60 and 120 minutes. After removal from the blood flow loop, conduit 101 was washed with saline solution and placed in a gamma counter for analysis.

[0043] In addition to conduit 101, the applicant similarly evaluated two commercially available peripherally inserted central venous catheters (PICCs): Bard Access Systems' "PowerPICC®" and AngioDynamics' "BioFlo® PICC". Samples of "PowerPICC®" and "BioFlo® PICC" ​​were evaluated for thrombus accumulation according to the blood flow loop system described herein. The applicant observed considerable thrombus accumulation in the "PowerPICC®" and "BioFlo® PICC" ​​samples, while minimal thrombus accumulation was observed in conduit 101. Considering that there are hematological parameters that cannot be consistently controlled across experimental groups, the radiation counts of conduit 101 and "BioFlo® PICC" ​​samples were normalized to the radiation count of "PowerPICC®". Plots of normalized thrombus accumulation for "PowerPICC®", "BioFlo® PICC", and conduit 101 are shown in Figure 2.

[0044] Based on paired two-tailed t-tests, conduit 101 and "BioFlo® PICC" ​​showed a statistically significant reduction in thrombus formation compared to "PowerPICC®" (p-values ​​were 0.017 and 0.035, respectively). Conduit 101 was confirmed to show a statistically significant reduction in thrombus accumulation compared to "BioFlo® PICC" ​​(p-value 0.033). Compared to "PowerPICC®", "BioFlo® PICC" ​​showed a 71±30% reduction in thrombus accumulation, while conduit 101 showed a 97±2% reduction in thrombus accumulation.

[0045] The conduit 101 may include one, two, or more polymer materials 20 configured to limit dimensional changes relative to the device 100 (e.g., limiting dimensional changes relative to the conduit 101). In some embodiments, the included polymer materials are configured to limit dimensional changes (e.g., length, outer diameter, inner diameter) relative to the conduit 101 to less than 15%, e.g., less than 10%, e.g., less than 5%, when exposed to water, a solvent, a non-solvent, an aqueous solution, or a mixture thereof. The polymer material 20 may be configured to limit the dimensional changes of the conduit 101 to a minimum change in length (e.g., around 0%) and / or less than 10% of the outer diameter, so that the conduit 101 exhibits anisotropic swelling.

[0046] For example, in some embodiments, the ratio of inner diameter swelling to outer diameter swelling is 0.1 or greater, 0.2 or greater, 0.5 or greater, 0.8 or greater, 0.9 or greater, 1 or greater, 1.1 or greater, 1.2 or greater, 1.5 or greater, 2 or greater, 5 or greater, or 8 or greater. In some embodiments, the ratio of inner diameter swelling to outer diameter swelling is 10 or less, 8 or less, 5 or less, 2 or less, 1.5 or less, 1.2 or less, 1.1 or less, 1 or less, 0.9 or less, 0.8 or less, 0.5 or less, or 0.2 or less. Combinations of the above ranges are also possible (e.g., 0.1 or greater, 10 or less). Other ranges are also possible.

[0047] In some embodiments, the conduit 101 is configured to decrease in length when exposed to water, a solvent, a non-solvent, an aqueous solution, or a mixture thereof. The outer diameter of the conduit 101 may be configured to increase as the length decreases. Such embodiments can be employed in anatomical features (e.g., blood vessels) where widening may be required for support and / or further manipulation.

[0048] The conduit 101 and / or other parts of the device 100 may be configured to swell and / or deswell according to their water content. In addition or alternatively, the conduit 101 and / or other parts of the device 100 may, in some embodiments, be further configured to swell and / or deswell according to their sodium chloride content. In some embodiments, the device 100 may be configured with a sodium chloride content of 10% by weight, configured to reduce or otherwise limit its swelling capacity. The conduit may swell when exposed to a variety of suitable fluids such as water, body fluids, isotonic salt solutions (e.g., 1× phosphate buffered water, normal saline), Ringer's lactate solution (LRS), glucose (D5W), phosphate buffered water (PBS), and / or Hanks equilibrium salt solution (HBSS), normal saline, and / or physiological body fluids.

[0049] It is also possible that the conduit 101 and / or other parts of the device 100 dissolve and / or are configured to dissolve when exposed to the fluids described in the previous paragraph.

[0050] In some embodiments, when hydrated (e.g., with a high water content), the mandrel of system 10 (e.g., mandrel 614 described below) is slidably inserted into the lumen 106 of the conduit 101. The inserted mandrel 614 may have a diameter larger than the diameter of the lumen 106 when device 100 is dehydrated (e.g., with a low water content) to impart a radial expansion force to the conduit 101. In some embodiments, the diameter of the mandrel is less than or equal to the inner diameter of the hydrated conduit but greater than or equal to the inner diameter of the dehydrated conduit.

[0051] The conduit 101 and / or other parts of the device 100 can be dehydrated and annealed (either or both may be performed under vacuum or in the presence of one or more gases), such as when maintained at a temperature between 90°C and 180°C, for example between 130°C and 160°C, for example at 150°C (for example, when maintained within a specific temperature range by the components of system 10).

[0052] In some embodiments, and prior to annealing, one, two, or more shaping elements (not shown) may be inserted into at least a portion of the lumen 106 of the conduit 101. In some embodiments, and prior to annealing, one, two, or more shaping elements may slidably receive and surround at least a portion of the conduit 101. The shaping elements may be configured to encourage the conduit 101 to adopt a desired shape (e.g., curvature). Annealing the conduit 101 having the shaping elements in it may be configured to "fix" it in the desired shape. The shaping elements may include materials selected from the group consisting of steel, polypropylene, nylon, polysulfide, polysulfone, nickel-titanium alloy, and combinations thereof.

[0053] The dehydrated and annealed conduit 101 may be configured to compress around the inserted mandrel 614 to increase hydrogen bonding and / or polymer chain orientation within the conduit 101. Compression may occur around the mandrel during dehydration and diameter modification. This compression may induce chain orientation via hydrogen bonding radially, similar to how an extruder can be drawn linearly from a die. The increase in hydrogen bonding and / or polymer chain orientation may be performed (e.g., through dehydration of the conduit 101 on the mandrel 614) to increase the overall strength of the device 100 and / or reduce subsequent swelling of the device 100 if subsequently hydrated (e.g., to reduce the expansion of the device 100). In some embodiments, the annealing process may be repeated multiple times with hydration and drying steps between cycles to increase the degree of hydrogen bonding and / or polymer chain orientation. These mechanical properties (e.g., Young's modulus, peak tensile strength, yield stress, strain at fracture, tensile energy at fracture, elongation, etc.) can change when solvated in water above the glass transition temperature of the base polymer.

[0054] In some embodiments, when the conduit 101 is hydrated after being annealed for one or more cycles at a temperature between 120°C and 180°C, the dimensions of the conduit 101 (e.g., outer and inner diameters) do not change by more than 5%. For example, a dehydrated conduit 101 may have an inner diameter of about 1.0 mm and an outer diameter of about 1.33 mm, while the same conduit 101 after hydration may have an inner diameter of about 1.2 mm and an outer diameter of about 1.5 mm. In this example, the inner diameter increases by about 0.83%, and the outer diameter increases by about 0.88%. Furthermore or alternatively, the total length of the conduit 101 does not change by more than 5% in some embodiments.

[0055] The polymer material 20 may include a polymer 21 which is a water-soluble polymer. In some embodiments, the water-soluble polymer 21 includes one, two, or more polymers selected from the group consisting of poly(vinyl alcohol), poly(acrylic acid), polyethylene glycol, poly(vinylpyrrolidone), poly(methacrylate sulfobetaine), poly(acrylic sulfobetaine), poly(methacrylate carboxybetaine), poly(acrylic carboxybetaine), povidone, polyacrylamide, poly(N-(2-hydroxypropyl)methacrylamide), polyoxazoline, polyphosphate, polyphosphazene, polyvinyl acetate, polypropylene glycol, poly(N-isopropylacrylamide), poly(2-hydroxymethyl methacrylate), and combinations thereof. In some embodiments, the polymer material includes copolymers of the water-soluble polymers described herein.

[0056] The polymer material 20 may contain one, two, or more radiopaque materials, which are agents 22. In some embodiments, the radiopaque agents 22 consist of one, two, or more agents selected from the group consisting of bismuth subcarbonate, barium sulfate, bismuth trioxide, bismuth oxychloride, tungsten, platinum, gold, titanium dioxide, tantalum, palladium, silver, and combinations thereof.

[0057] The polymer material 20 may contain a solution 23 which is one, two, or more phosphate solutions. In some embodiments, the phosphate solution 23 contains one, two, or more solutions selected from the group consisting of monobasic sodium phosphate, dibasic sodium phosphate, tribasic sodium phosphate, and combinations thereof.

[0058] The polymer material 20 may contain a plasticizer 29, which is one, two, or more plasticizers. In some embodiments, the plasticizer 29 includes materials selected from the group consisting of polyols, e.g., glycerol, propylene glycol, water, ethylene glycol, butylene glycol, erythritol, slaytol, arabitol, xylitol, ribitol, mannitol, sorbitol, galactit, fusitol, iditol, boretol, malitol, lactitol, maltotriitol, maltotetraitol, polyglycitol, and combinations thereof. In some embodiments, the polyol is included in the material 20 for plasticization and to function as a water-retaining agent to improve the hydration efficiency of the conduit 101. The polyol may be added to the material 20 in a secondary rehydration step before and / or after annealing. The plasticizer 29 may also be included to prevent cracking and / or shattering during storage of the conduit 101 when it is in a dry (e.g., unhydrated) state. The plasticizer 29 may be added in addition to the water-retaining agent to improve hydration performance.

[0059] In some embodiments, the conduit 101 is immersed in an immersion solution (aqueous or solvent-based) containing a plasticizer and / or water-retaining agent at a predetermined temperature (e.g., below the Tg of the base polymer material). The immersion solution may be stagnant or configured to flow across at least a portion of the conduit 101. After immersion, the conduit 101 may be dried and annealed (by ambient air, convection, vacuum, or dry gas purging, etc.). Furthermore, the conduit 101 may be immersed again after the drying and annealing process.

[0060] As used herein, a mixture comprising a water-soluble polymer 21, a radiopaque agent 22, a sodium phosphate solution 23, and / or a plasticizer 29 is generally referred to as the polymer material 20.

[0061] The proximal portion 104 and / or distal portion 108 of the conduit 101 may include a blunt end, a radial end, a chamfered end, a tapered shape, and / or other deformed ends (e.g., a deformed proximal portion 104 and / or a deformed distal portion 108). In some embodiments, radio frequency (RF) energy is applied to portions 104 and / or 108 (e.g., ends 103 and / or 109, respectively) to achieve the deformed end portions. In some embodiments, a tipping (or tip-forming; tipping) process (e.g., a melt tipping process) is applied to portions 104 and / or 108 to achieve the deformed end portions. In some embodiments, a solvent and / or solvent mixture is applied to portions 104 and / or 108 to achieve the deformed end portions.

[0062] In some embodiments, the conduit 101 includes markings 112, which are one, two, or more markings indicated along one or more portions of the conduit 101. It is also possible that one or more portions of the conduit 101 lack markings (e.g., in addition to other portions that do have markings). The markings 112 may be positioned relative to a point on the conduit 101. The markings may include multiple distinct segments. For example, some markings may be scaled (e.g., to indicate one or more distances). In some embodiments, the markings 112 are configured to provide a “ruler” to assist in determining the depth of insertion of the device 100 into the patient. The markings may also include text and / or words. For example, in some embodiments, the markings include numbers and / or phrases indicating distances (e.g., “5cm”). If the markings include sentences and / or words, the text and / or words may indicate distances from the distal end of the catheter and / or have numerical values ​​that increase from the distal end of the catheter to the proximal end of the catheter. Some conduits may include some markings in the form of segments and some markings in the form of text and / or words. As one example, a conduit may include markings that are closer together (e.g., every 1 cm) in the form of segments and markings that are not so close together (e.g., every 5 cm) that contain text and / or words. The markings containing text and / or words may further include segments. The markings in the form of segments may be positioned between the markings containing text and / or words.

[0063] In some embodiments, the marking 112 is configured to provide identification of features of the device 100, such as a model number or manufacturing date. In some embodiments, the marking is located on at least a portion of the surface of the conduit. For example, if the conduit is a catheter, the marking may be positioned along at least a portion of the surface of the catheter.

[0064] The markings may be formed from a variety of suitable materials. In some embodiments, the markings include polymers such as water-soluble polymers. Non-limiting examples of suitable water-soluble polymers include poly(vinyl alcohol), poly(acrylic acid), polyethylene glycol, poly(vinylpyrrolidone), poly(methacrylate sulfobetaine), poly(acrylic sulfobetaine), poly(acrylic carboxybetaine), povidone, polyacrylamide, poly(N-(2-hydroxypropyl)methacrylamide), polyoxazoline, polyphosphate, polyphosphazene, polyvinyl acetate, polypropylene glycol, poly(N-isopropylacrylamide), and / or poly(2-hydroxymethyl methacrylate). If both the conduit on which the markings are positioned and the markings contain one or more water-soluble polymers, the conduits and markings may have the same chemical composition or may have different chemical compositions in one or more respects. For example, the conduit and the markings on it may contain exclusively the same type of water-soluble polymer, may contain some common water-soluble polymers and some water-soluble polymers that differ between them, or each may contain water-soluble polymers that are not present in the other. Furthermore, the marking may also contain a water-insoluble polymer. In a series of exemplary embodiments, the marking is formed from a material selected from the group consisting of poly(vinyl alcohol) and poly(vinyl acetate). In some embodiments, the marking material contains 75% or more by weight of poly(vinyl alcohol) (solids content, e.g., 80% or more, 85% or more, 90% or more, 95% or more, or 98% or more by weight). In some embodiments, the marking material contains 100% or less by weight of poly(vinyl alcohol) (solids content, e.g., 99% or less, 98% or less, 95% or less, 90% or less, 85% or less, or 80% or less by weight) based on the total weight of the marking material. Combinations of the ranges mentioned above are also possible (e.g., 75% or more, 100% or less by weight). Other ranges are also possible.

[0065] The marking may also further include one or more additional species. For example, in some embodiments, the marking includes a dye such as a reactive dye. Non-limiting examples of suitable reactive dyes include: Tetrasodium; 4-amino-5-hydroxy-3,6-bis[[4-(2-sulfonatooxyethylsulfonyl)phenyl]diazenyl]naphthalene-2,7-disulfonic acid ("Reactive Black 5"), Copper; 33-[[4-(2-hydroxyethylsulfonyl)phenyl]sulfamoyl]-2,11,20,29,39,40-hexaaza-37,38-diazanidanonacyclo[28.6.1.1 3,10 .1 12,19 .1 21,28 .0 4,9 .0 13,18 .0 22,27 .0 31,36 Tetraconta-1,3(40),4(9),5,7,10,12(39),13(18),14,16,19,21,23,25,27,29,31(36),32,34-nonadecane-6,15,24-trisulfonic acid ("Reactive Blue 21"), 2-Naphthalenesulfonic acid, 7-(acetylamino)-4-hydroxy-3-[4-[2-(sulfoxy)ethyl]sulfonyl]phenyl]azo]-,2 sodium salt (9Cl) ("Reactive Orange 78"), "Reactive Yellow 15", Disodium; 1-amino-9,10-dioxo-4-[(3-{[2-(sulfonatooxy)ethyl]sulfonyl}phenyl)amino]-9,10-dihydro-2-anthracenesulfonic acid ("Reactive Blue 19"), 1-Amino-4-[3-(4,6-dichlorotriazine-2-ylamino)-4-sulfophenylamino]anthraquinone-2-sulfonic acid ("Reactive Blue 4"), "CI Reactive Red 11", 4-[2-(5-carbamoyl-1-ethyl-4-methyl-2,6-dioxopyridine-3-ylidene)hydrazinyl]-6-[(4,6-dichloro-1,3,5-triazine-2-yl)amino]benzene-1,3-disulfonic acid ("CI Reactive Yellow 86"), Tetrasodium; 6,13-dichloro-3,10-bis[[4-[(4,6-dichloro-1,3,5-triazine-2-yl)amino]sulfonatophenyl]amino]triphenodioxazine disulfonate ("CI Reactive Blue 163"), and / or Examples include 5-(benzoylamino)-4-hydroxy-3-[[1-sulfo-6-[[2-(sulfoxy)ethyl]sulfonyl]-2-naphthalenyl]azo]-, tetrasodium salt ("CI Reactive Red 180").

[0066] In some embodiments, the marking comprises a non-reactive dye, pigment, and / or radiosensitizer. The non-reactive dye, pigment, and / or radiosensitizer may enhance the contrast between the marking and other parts of the catheter (for example, when observing the catheter visually and / or under a microscope such as fluoroscopy). Non-limiting examples of suitable non-reactive dyes include phthalocyanine blue, phthalocyanine green, carbazole violet, and CI Vat Orange. 1", 2-[[2,5-diethoxy-4-[(4-methylphenyl)thiol]phenyl]azo]-1,3,5-benzenetriol, 16,23-dihydrodinaphtho[2,3-a:2',3'-i]naphtho[2',3':6,7]indro[2,3-c]carbazole-5,10,15,17,22,24-hexone, N,N'-(9,10-dihydro-9,10-dioxo-1,5-anthracenediyl)bisbenzamide, 7,16-dichloro-6,15-dihydro-5,9,14,18-anthrazinetetron, 16,17-dimethoxydinanaphtho[1,2,3- Examples of suitable non-reactive pigments include cd:3',2',1'-lm]perylene-5,10-dione, 4-[(2,4-dimethylphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazole-3-one, 6-ethoxy-2-(6-ethoxy-3-oxobenzo[b]thiene-2(3H)-ylidene)benzo[b]thiophene-3(2H)-one, 1-amino-4-[[4-[(2-bromo-1-oxoallyl)amino]-2-sulfonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulfonic acid disodium, and combinations thereof. Non-limiting examples of suitable non-reactive pigments include carbon black, modified carbon black, titanium dioxide, chromium-cobalt-aluminum oxide, chromium oxide green, iron oxides, mica-based pearlescent pigments, and combinations thereof. Non-exclusive examples of radiopaque dyes include platinum, palladium, bismuth oxychloride, bismuth carbonate, tantalum, barium sulfate, silver, gold, silver sulfadiazine, titanium dioxide, and iodine-based compounds such as "Omnipaque".In some embodiments, the marking comprises a fluorescent dye (e.g., fluorescein isothiocyanate (FIT-C), fluorescein-N-hydroxysuccinimide, eosin Y, etc.).

[0067] In some embodiments, the markings include salts. Non-limiting examples of suitable salts include phosphates (e.g., MSP, DSP, TSP), borates, sodium chloride, citrates, ethylenediaminetetraacetates, sulfites, sulfates, hyposulfites, metal oxides, selenium dioxide, selenium trioxide, selenite, selenic acid, nitrates, silicates, and vegetable salts.

[0068] In some embodiments, the marking includes TPU pad printing ink, such as Marabu's "Tampa® Pur 980 Black TPU" and / or "Tampa® Star 980 Black TPR".

[0069] Regardless of whether the marking has a similar (or identical) composition to the conduit or a different composition, when the conduit is placed in one or more environments (e.g., body fluids, patient), the portion of the conduit with the marking and (if any) the portion without the marking may show similar thrombus accumulation. In some embodiments, in one or more such environments, the level of thrombus accumulation relative to the marking is within 50%, 40%, 30%, 20%, 10%, 5%, 2%, or 1% of the level of thrombus accumulation in the portion of the conduit without the marking. In some embodiments, the marking is configured to show substantially no thrombus accumulation when the conduit is placed in a patient.

[0070] As described elsewhere in this specification, some embodiments involve swelling a conduit from an unswelled state (e.g., a first configuration) to a swollen state (e.g., a second configuration). In some embodiments, the swelling of the conduit may cause the markings to undergo a change in form. For example, in some embodiments, the distances between markings, which take the form of multiple segments spaced apart along the conduit, may change if the conduit swells (e.g., in the presence of a fluid, such as any fluid described elsewhere in this specification as capable of causing the conduit to swell). The markings may have a first mean shortest distance (e.g., the "first distance") between the nearest adjacent markings before the conduit swells, and a second different mean shortest distance (e.g., the "second distance") after the conduit swells. The second mean shortest distance may be greater than the first mean shortest distance. In some embodiments, the ratio of the second average shortest distance to the first average shortest distance is 1.02:1 or greater, 1.05:1 or greater, 1.075:1 or greater, 1.1:1 or greater, 1.2:1 or greater, 1.5:1 or greater, or 1.75:1 or greater. In some embodiments, the ratio of the second average shortest distance to the first average shortest distance is 2:1 or less, 1.75:1 or less, 1.5:1 or less, 1.2:1 or less, 1.1:1 or less, 1.075:1 or less, or 1.05:1 or less. Combinations of the above ranges are also possible (e.g., 1.02:1 or greater, 2:1 or less, or 1.05:1 or greater, 1.1:1 or less).

[0071] The shortest distance between two markings may be determined by identifying the shortest line segment connecting the two markings. Each marking may be considered to have a nearest adjacent marking, which is the marking with the smallest shortest distance. The average shortest distance between nearest adjacent markings for multiple markings may be determined by determining the shortest distance between each marking and its nearest adjacent marking, and then averaging these values.

[0072] In some embodiments, the swollen article (e.g., a conduit) may include markings having a particularly advantageous mean shortest distance between the nearest adjacent markings. The mean shortest distance between the nearest adjacent markings in the swollen conduit (e.g., a conduit in a second configuration) may be 1 mm or more, 5 mm or more, 10 mm or more, 50 mm or more, 0.1 cm or more, 0.2 cm or more, 0.5 cm or more, 0.75 cm or more, 0.5 cm or more, 75 cm or more, 1 cm or more, 1.25 cm or more, 1.5 cm or more, 2 cm or more, 2.5 cm or more, 3 cm or more, 4 cm or more, 5 cm or more, 7.5 cm or more, or 10 cm or more. The mean shortest distance between the nearest adjacent markings in a swollen conduit may be 20 cm or less, 10 cm or less, 7.5 cm or less, 5 cm or less, 4 cm or less, 3 cm or less, 2.5 cm or less, 2 cm or less, 1.5 cm or less, 1.25 cm or less, 1 cm or less, 0.75 cm or less, 0.5 cm or less, 0.2 cm or less, 0.1 cm or less, 50 mm or less, 10 mm or less, or 5 mm or less. Combinations of the above ranges are also possible (for example, 1 mm to 10 mm, 0.1 cm to 10 cm, or 0.5 cm to 5 cm). Other ranges are also possible.

[0073] In some embodiments, the article has an average shortest distance between the nearest adjacent markings in an unswollen state within one or more of the above ranges (e.g., 1 mm to 10 mm, 0.1 cm to 10 cm, or 0.5 cm to 5 cm). For example, the average shortest distance between the nearest adjacent markings in an unswollen conduit (e.g., a conduit in a second configuration) may be 1 mm or more, 5 mm or more, 10 mm or more, 50 mm or more, 0.1 cm or more, 0.2 cm or more, 0.5 cm or more, 0.75 cm or more, 1 cm or more, 1.25 cm or more, 1.5 cm or more, 2 cm or more, 2.5 cm or more, 3 cm or more, 4 cm or more, 5 cm or more, 7.5 cm or more, or 10 cm or more. The mean shortest distance between the nearest adjacent markings in an unswollen conduit may be 20 cm or less, 10 cm or less, 7.5 cm or less, 5 cm or less, 4 cm or less, 3 cm or less, 2.5 cm or less, 2 cm or less, 1.5 cm or less, 1.25 cm or less, 1 cm or less, 0.75 cm or less, 0.5 cm or less, 0.2 cm or less, 0.1 cm or less, 50 mm or less, 10 mm or less, or 5 mm or less. Other ranges are also possible.

[0074] In some embodiments, the above range may include a catheter gauge (e.g., a French scale). For example, the average shortest distance between the nearest adjacent markings may be 3Fr or greater, 5Fr or greater, 10Fr or greater, 15Fr or greater, 20Fr or greater, or 30Fr or greater. In some embodiments, the average shortest distance between the nearest adjacent markings may be 34Fr or less, 30Fr or less, 20Fr or less, 15Fr or less, 10Fr or less, or 5Fr or less. Combinations of the above ranges are also possible (e.g., 3Fr to 34Fr). Other ranges are also possible.

[0075] The values ​​in the previous paragraph may represent characteristics of conduits containing varying amounts of water. Typically, the amount of water in a conduit in a swollen and / or second configuration is greater than the amount of water in a conduit in an unswollen and / or first configuration. In some embodiments, the unswollen or first configuration conduit has a water content of 2 w / w% or more, 5 w / w% or more, 7.5 w / w% or more, 10 w / w% or more, 15 w / w% or more, 20 w / w% or more, 25 w / w% or more, 30 w / w% or more, or 35 w / w% or more. In some embodiments, the unswollen or first configuration conduit has a water content of 40 w / w% or less, 35 w / w% or less, 30 w / w% or less, 25 w / w% or less, 20 w / w% or less, 15 w / w% or less, 10 w / w% or less, 7.5 w / w% or less, or 5 w / w%. Combinations of the above ranges are also possible (for example, 2w / w% to 40w / w%, or 20w / w% to 40w / w%). Other ranges are also possible.

[0076] In some embodiments, the swollen or second-constituent conduit has a water content of 3 w / w% or more, 5 w / w% or more, 7.5 w / w% or more, 10 w / w% or more, 15 w / w% or more, 20 w / w% or more, 25 w / w% or more, 30 w / w% or more, 35 w / w% or more, 40 w / w% or more, 45 w / w% or more, 50 w / w% or more, 55 w / w% or more, 60 w / w% or more, 65 w / w% or more, 70 w / w% or more, 75 w / w% or more, 80 w / w% or more, 85 w / w% or more, 90 w / w% or more, 95 w / w% or more, 98 w / w% or more, or 99 w / w% or more. In some embodiments, the swollen or second-constituent conduit has a water content of 99.9 w / w% or less, 99 w / w% or less, 95 w / w% or less, 90 w / w% or less, 85 w / w% or less, 80 w / w% or less, 75 w / w% or less, 70 w / w% or less, 65 w / w% or less, 60 w / w% or less, 55 w / w% or less, 50 w / w% or less, 45 w / w% or less, 40 w / w% or less, 35 w / w% or less, 30 w / w% or less, 25 w / w% or less, 20 w / w% or less, 15 w / w% or less, 10 w / w% or less, 7.5 w / w% or less, or 5 w / w% or less. Combinations of the above ranges are also possible (for example, 3 w / w% to 99.5 w / w%, 3 w / w% to 80 w / w%, 40 w / w% to 80 w / w%). Other ranges are also possible. In some embodiments, the second state or swollen state contains an amount of water equivalent to the equilibrium water content of the conduit.

[0077] In some embodiments, the method comprises a marked catheter having markings comprising a plurality of distinct segments spaced apart along at least a portion of the catheter, wherein the mean shortest distance between each segment and its nearest adjacent segment is the first distance in the first configuration of the marked catheter, and the method comprises the steps of introducing fluid into the marked catheter and inflating at least a portion of the marked catheter from the first configuration to a second configuration, wherein the mean shortest distance between each segment and its nearest adjacent segment in the second configuration is the second distance, and the ratio of the second distance to the first distance is between 1.02:1 and 2:1.

[0078] In some embodiments, the method comprises the steps of introducing fluid into the marked catheter and inflating at least a portion of the marked catheter from the first configuration to a second configuration, wherein the mean shortest distance between each segment and its nearest adjacent segment is the first distance in the first configuration of the marked catheter, and the method comprises the steps of introducing fluid into the marked catheter and inflating at least a portion of the marked catheter from the first configuration to a second configuration, wherein the mean shortest distance between each segment and its nearest adjacent segment in the second configuration is the second distance, and the second distance is equal to about 1 mm, about 10 mm, about 100 mm, about 1 cm, or about 10 cm.

[0079] In some embodiments, the method includes swelling a polymer material (and / or catheter) to an equilibrium water content. In some embodiments, the method includes swelling a polymer material (and / or catheter) to an equilibrium water content over a period of time. In some embodiments, the period is 60 minutes or less (for example, 10 minutes or less, 5 minutes or less, 1 minute or less, 30 seconds or less, or 10 seconds or less).

[0080] In some embodiments, the method includes swelling a polymer material (and / or catheter) at a predetermined temperature. In some embodiments, the temperature is 4°C or higher, 10°C or higher, 16°C or higher, 20°C or higher, 25°C or higher, or 30°C or higher. In some embodiments, the temperature is 40°C or lower, 30°C or lower, 25°C or lower, 20°C or lower, 16°C or lower, or 10°C or lower. Combinations of these ranges are also possible (e.g., 20°C to 40°C).

[0081] In some embodiments, the method comprises swelling a polymer material (and / or catheter) such that the inner diameter and / or outer diameter increases at a rate greater than the rate of increase in length (as described herein). For example, in some embodiments, the method comprises swelling a polymer material such that the length increases by 0.1 to 19%, while the inner diameter and / or outer diameter increases by 1 to 20%.

[0082] In some embodiments, swelling occurs after administration. In some embodiments, swelling of the polymer material after administration to the subject's orifice closes the opening of the orifice. For example, in some embodiments, swelling of the polymer material results in a size increase to a dimension greater than the size of the orifice into which it is inserted. In some embodiments, the orifice is a wound. In some embodiments, swelling of the polymer material causes hemostasis. For example, in some embodiments, a subject (e.g., a human) may have a bleeding orifice (e.g., a wound) with a maximum cross-sectional diameter of A, and a device described herein having a maximum outer cross-sectional diameter smaller than A may be administered to the orifice. In some embodiments, the maximum outer cross-sectional diameter of the device may then swell to a dimension greater than or equal to A so that the orifice is closed. In some embodiments, this results in hemostasis.

[0083] In some embodiments, swelling occurs before administration. In some embodiments, swelling involves rehydrating the device for a period of time. In some embodiments, the period is 60 minutes or less (e.g., 10 minutes or less, 5 minutes or less, 1 minute or less, or 10 seconds or less). In some embodiments, rehydration of the device involves the use of a rehydration medium. In some embodiments, the rehydration medium consists of water, Ringer's lactate solution (LRS), glucose (D5W), phosphate-buffered saline (PBS), Hanks equilibrium salt solution (HBSS), and / or isotonic salt solution.

[0084] In some embodiments, any markings present in the conduit may not undergo cracking or delamination when the conduit expands from a first configuration to a second configuration. The presence of cracking or delamination may be assessed by visual inspection of the swollen conduit with an optical microscope. For example, delamination may not be observed when exposed to an alcohol / water disinfectant solution such as ethanol, isopropyl alcohol (70% / 30% water), povidone, or "Chloraprep" (see TD-082 reference).

[0085] The markings placed in the conduit may penetrate from its surface to various suitable depths. In some embodiments, the markings are 0.1 μm or larger, 0.2 μm or larger, 0.5 μm or larger, 0.75 μm or larger, 1 μm or larger, 2 μm or larger, 5 μm or larger, 7.5 μm or larger, 10 μm or larger, 20 μm or larger, 30 μm or larger, 40 μm or larger, 50 μm or larger, 60 μm or larger, 70 μm or larger, 80 μm or larger, 100 μm or larger, 125 μm or larger, 150 μm or larger, 175 μm or larger, 200 μm or larger, 250 μm or larger, 300 μm or larger, 400 μm or larger, 500 μm or larger, 750 μm or larger, 1 mm or larger, 2 mm or larger, 5 mm or larger, or 7.5 mm or larger in depth into the conduit. In some embodiments, the marking penetrates the conduit to a depth of 10 mm or less, 7.5 mm or less, 5 mm or less, 2 mm or less, 1 mm or less, 750 μm or less, 500 μm or less, 400 μm or less, 300 μm or less, 250 μm or less, 200 μm or less, 175 μm or less, 150 μm or less, 125 μm or less, 100 μm or less, 80 μm or less, 70 μm or less, 60 μm or less, 50 μm or less, 40 μm or less, 30 μm or less, 20 μm or less, 10 μm or less, 7.5 μm or less, 5 μm or less, 2 μm or less, 1 μm or less, 0.75 μm or less, 0.5 μm or less, or 0.2 μm or less. Combinations of the above ranges are also possible (for example, 0.1 μm to 10 mm, 10 μm to 200 μm, or 50 μm to 60 μm, etc.). Other ranges are also possible.

[0086] The marking 112 may be applied to at least a portion of the conduit 101 in various preferred ways. In some embodiments, the marking is formed by placing a marking composition on at least a portion of the surface of the conduit. Preferred marking compositions are described elsewhere in this specification. One preferred method for placing the marking on at least a portion of the surface of the conduit is inkjet printing, as described elsewhere in this specification. The marking may also be applied by liquid phase growth, pad printing, screen printing, electrostatic spraying, hot stamping, laser etching, and / or dip coating.

[0087] The markings described herein may have any preferred size and shape. In some embodiments, the markings include shapes, letters, numbers, combinations of letters and / or numbers, logos, and images. Non-limiting examples of preferred shapes include lines, zigzags, squares, rectangles, circles, ellipses, polygons (e.g., pentagons, hexagons, heptagons, octagons, nonagons, dodecagons, etc.), tubes, rings, stars or star shapes (e.g., triangular stars, quadrilateral stars, pentagonal stars, hexagonal stars, heptagonal stars, octagonal stars, etc.). In one exemplary set of embodiments, the markings include a combination of lines and numbers (e.g., defining a length along an article). In another exemplary set of embodiments, the markings include a logo and / or images (e.g., for identifying an article and / or the manufacturer of an article). Other markings are also possible.

[0088] Another example of a preferred method for applying markings to conduits is by pad printing. The applicant conducted a study to evaluate the durability of two one-component pad printing ink resins: "Tampa® Pur 980 Black TPU" and "Tampa® Star 980 Black TPR," both manufactured by Marabu. The applicant applied each ink to an extruded segment (e.g., conduit 101) containing a polymer material 20 comprising at least poly(vinyl alcohol) (PVA), after immersion in a non-solvent bath as described later with reference to STEP 1270 in Figure 14, and before immersion in a hydrophilic bath as described later with reference to STEP 1350 in Figure 15. The applicant observed that each ink adhered well to the extruded segment in a dry state. However, after hydration in 1× buffered saline (PBS) for about 15 minutes at a temperature of 20°C to 25°C (e.g., room temperature), the extruded segment swelled and the ink cracked, as shown in Figure 3.

[0089] The marking 112 may be applied to at least a portion of the conduit 101 by UV-curable pad printing. The applicant conducted a study to evaluate the durability of UV-curable pad printing ink: Deco Technology Group's "Series 747 PC (Lot# 747-8005)". The applicant applied each ink to an extruded segment (e.g., conduit 101) containing a polymer material 20 containing at least poly(vinyl alcohol) (PVA). Specifically, the applicant evaluated the durability of the UV-curable ink applied to the PVA-containing extruded segment and the PVA-containing extruded segment after immersion in a hydrophilic bath containing a polyacrylic acid solution (PAA), as described later with reference to STEP 1350 in Figure 15. The applicant dried the ink at a temperature between 20°C and 25°C (e.g., room temperature) for about 2 hours. The extruded segment was then transferred to a UV sterilizer and cured for about 4 hours. In some embodiments, the extruded segment was further annealed as described below with reference to Method 1400 in Figure 9. In other embodiments, the extruded segments were not annealed. The applicant examined each extruded segment in both dry and hydrated states, as shown in Figure 4. The applicant observed that the ink peeled off from the surface of each extruded segment after hydration in 1×PBS. Furthermore, the applicant observed that the extruded segments containing PAA also showed considerable discoloration after exposure to a UV-sterilizing agent.

[0090] The marking 112 may be applied to at least a portion of the conduit 101 by laser etching. The applicant conducted a study to evaluate the durability of uniaxial 355 nm diode-pumped solid-state laser etching. The applicant etched black band shapes and numbers onto the surface of an extruded segment (e.g., conduit 101) containing a polymer material 20 containing at least poly(vinyl alcohol) (PVA). Specifically, the applicant evaluated the durability of laser etching applied to the PVA-containing extruded segment and the PVA-containing extruded segment after immersion in a hydrophilic bath containing a polyacrylic acid solution (PAA), as described later with reference to STEP 1350 in Figure 8. The applicant dried the ink for about 2 hours at a temperature of 20°C to 25°C (e.g., room temperature). In some embodiments, the extruded segment was further annealed as described below with reference to Method 1400 in Figure 16. In other embodiments, the extruded segment was not annealed. The applicant examined each extruded segment in both dry and hydrated states, as shown in Figure 5. The applicant observed that after hydration in 1×PBS at 37°C for 24 hours, the laser etching peeled off from the surface of each extruded segment.

[0091] The marking 112 may be applied to at least a portion of the conduit 101 using a poly(vinyl alcohol)-based ink. The applicant conducted a study to evaluate the durability of two custom PVA-based inks: one containing 0.01 w / w% "Reactive Black 5" (CAS No. 17095-24-8) in a 15 w / w% mixture of 28-99 PVA in 1 × PBS, and another containing 0.01 w / w% "Pigment Green 7" (CAS No. 14832-14-5) in a 10 w / w% mixture of 28-99 PVA in 1 × PBS. The applicant applied each ink to an extruded segment (e.g., conduit 101) containing a polymer material 20 containing at least poly(vinyl alcohol) (PVA). Specifically, the applicant evaluated the durability of PVA-based inks applied to extruded segments containing PVA and PVA-containing extruded segments after immersion in a hydrophilic bath containing poly(acrylic acid) solution (PAA), as described later with reference to STEP 1350 in Figure 15. The applicant allowed the inks to dry under ambient conditions for about 1 hour. In some embodiments, the extruded segments were further annealed, as described below with reference to Method 1400 in Figure 16. In other embodiments, the extruded segments were not annealed. The applicant examined each extruded segment in both dry and hydrated states, as shown in Figure 6. The applicant observed that the ink adhered well to extruded segments without PAA, while it did not adhere well to extruded segments containing PAA and peeled off from the extruded segments. Furthermore, the applicant confirmed that the "Reactive Black 5" ink penetrated into the body of the extruded segments. Each extruded segment showed peeling after being hydrated in 1×PBS for about 24 hours.

[0092] The marking 112 may be applied to at least a portion of the conduit 101 by dye impregnation using an aqueous solution. The applicant conducted a study to evaluate the durability of a custom dye solution containing 0.01 w / w% "Reactive Black 5" (CAS No. 17095-24-8) in distilled water. The applicant applied each ink to an extruded segment (e.g., conduit 101) containing a polymer material 20 containing at least poly(vinyl alcohol) (PVA). Specifically, the applicant evaluated the durability of the dye applied to the PVA-containing extruded segment and the PVA-containing extruded segment after immersion in a hydrophilic bath containing a polyacrylic acid (PAA) solution, as described later with reference to STEP 1350 in Figure 15. The applicant dried the dye under ambient conditions. The applicant then transferred the extruded segments to a convection oven for drying at 150°C for 3 hours and annealing for 90 minutes. The applicant examined each extruded segment in two hydration states, as shown in Figure 7. The extruded segments were hydrated in 1×PBS at 37°C for 24 hours and in 1×PBS at 55°C for 2 weeks. The applicant observed the adhesion and penetration of the dye into the body of the extruded segments. Furthermore, the applicant observed that the dye was retained within the extruded segments after 2 weeks of hydration.

[0093] In some embodiments, the marking 112 may be applied to at least a portion of the conduit 101 by dye impregnation using a solvent solution. The applicant conducted a study to evaluate the durability of a custom dye solution containing 0.01 w / w% of "Reactive Black 5" (CAS No. 17095-24-8) in a "Carbopol®" (PAA) solution. The applicant applied each ink to an extruded segment (e.g., conduit 101) containing a polymer material 20 containing at least poly(vinyl alcohol) (PVA). Specifically, the applicant evaluated the durability of the dye applied to the PVA-containing extruded segment and the PVA-containing extruded segment after immersion in a hydrophilic bath containing a polyacrylic acid (PAA) solution, as described later with reference to STEP 1350 in Figure 15. The applicant dried the dye under ambient conditions. The applicant then transferred the extruded segment to a convection oven for drying at 150°C for 3 hours and annealing for 90 minutes. The extruded segments were hydrated in 1×PBS at 37°C for 24 hours. Similar to the results shown in Figure 7, the applicant observed the adhesion and penetration of the dye into the body of the extruded segments.

[0094] In some embodiments, the marking 112 may be applied to at least a portion of the conduit by hot stamping. The hot stamping method includes a die and, optionally, a hot stamping foil or pre-dried ink. For example, the die is heated and pressed onto the foil or pre-dried ink to transfer the ink to the conduit.

[0095] In some embodiments, the marking 112 may be applied to at least a portion of the conduit by inkjet printing. The applicant conducted studies using a custom dye solution containing poly(vinyl alcohol), copper phthalocyanine, and water. The applicant applied the custom dye to the extruded segment using a system capable of ejecting ink jets. This system ejects the ink using an electrically operated piezo-operated ejection valve. The system is pressurized with compressed air, and a program commands the opening time (Pulse) and the time between adhesions (Cycle) of the piezo ejection valve. This system is capable of ejecting ink over a wide range of shapes. The applicant placed the marking on the extruded segment using a Pulse of 0.30 milliseconds, a Cycle of 18.0–21.0 milliseconds, and a pressure of 3–15 psi. The marked extruded segment was then dried at 95°C for 6 hours. A friction test as specified in TD-082 Rev A was performed on the marked section of the extruded segment for 123 days. The research results concluded that this ink and application method are sufficient to place and adhere markings to the extruded sections of extruded materials. Exemplary marked catheters are shown in Figures 23A and 23B.

[0096] Device 100 may include one, two, or more patient fixation devices, such as the suture wing 160 shown. The conduit 101 and the suture wing 160 may have similar hardness and / or extensibility (or compliance). For example, the suture wing 160 may consist of 28-99% 42% poly(vinyl alcohol) and a deionized water slurry, which is injection molded into the shape of a suture wing (e.g., at 96°C) and then dried (e.g., at 55°C for 6 hours). The suture wing 160 may be dehydrated to cause a volume change of -52% (or approximately the water content of the initial injection-molded material) to match the hardness of the conduit 101. As another example, the suture wing 160 may comprise an 18% poly(vinyl alcohol) 28-99, 0.9% sodium chloride solution slurry that has been injection molded into a suture wing shape (e.g., at 96°C) and dried (e.g., at 55°C for 6 hours). Dehydration of the suture wing 160 can result in a volume change of -81% to match the hardness of the conduit 101. Similarly, the suture wing 160 may also undergo a volume change of -81% by heat treatment at 150°C for 90 minutes to match the hardness of the conduit 101. As yet another example, the suture wing 160 may comprise a thermoplastic or thermosetting material configured to not exhibit volume change upon exposure to an aqueous solution.

[0097] The device 100 may include one or more linear elements, the linear element 123 shown in the figure. The linear element 123 may include a needle, guidewire, stylet, or other elongated filament that is inserted into the lumen 106 of the conduit 101, such as to straighten the conduit 101 which is elastically biased in a nonlinear shape, as described below with reference to Figure 8.

[0098] Device 100 may include one or more accessories, such as accessory 170 shown in the figure. In some embodiments, accessory 170 includes a tube clamp, such as clamp 170a, which is described below with reference to Figures 4A to 4B.

[0099] The device 100 may include a package 180 in which other components of the device 100 (e.g., at least the conduit 101) are packaged, sterilized, and transported to the clinical site for insertion into a patient. The package 180 may include a flexible container made of flash-spun high-density polyethylene fibers. In some embodiments, the package 180 further includes a tray in which the device 100 is placed for transport.

[0100] Device 100 may include one or more sensors, transducers, and / or other functional elements, such as functional element 199 described below. Functional element 199 may include one or more functional elements positioned on and / or inside the conduit 101 (as shown), connector 120, band 122, suture wing 160, and / or another component of device 100. Functional element 199 may be connected to one or more wires, optical fibers, tubes (e.g., fluid delivery, hydraulic and / or pneumatic tubes), waveguides, and / or other conduits (not shown) that transport signals (e.g., information), energy, fluids, light, and / or sound from functional element 199 and / or another component (e.g., another component of system 10). In some embodiments, system 10 includes a functional device 999 configured to interface with functional element 199, as described below.

[0101] The extruder 500 may be configured and arranged to produce a conduit 101 containing polymer material 20, as described below. The extruder 500 may include a die head 502, an auger 504, and a screw 506. The extruder 500 may be configured to produce a conduit 101 having a fixed cross-sectional profile so that the polymer material 20 is extruded through a die head 502 having a desired cross-section. The die head 502 may include a disc having an opening configured and arranged to the size and shape of the intended cross-section of the conduit 101. The auger 504 may be configured to rotate adjacent to the extruder 500, for example, to move the polymer material 20 into the extruder 500 and toward the screw 506. The screw 506 may be configured to rotate within the extruder 500, for example, to move the polymer material 20 toward the die head 502 for extrusion molding.

[0102] In some embodiments, the extruder 500 includes a single-screw extruder such as one having a 3 / 4-inch diameter, an L / D ratio of 25:1, and a compression ratio of 1:1.

[0103] System 10 may further comprise one or more mixing devices, such as the illustrated device 602, configured to combine two or more substances to form an acceptable mixture of materials (e.g., a well-mixed combination of materials to form a polymer material 20). In some embodiments, the mixing device 602 comprises a high-speed double asymmetric centrifuge. In some embodiments, the mixture is heated to a temperature below the boiling point of the immersion liquid in a sealed or permeable jar and mixed in a double asymmetric centrifuge at a speed of 3500 rpm or less until homogeneously mixed. In some embodiments, the mixture is heated to a temperature below the boiling point of the immersion liquid and mixed in a stirrer, ribbon blender, paddle mixer, static mixer, emulsifier, homogenizer, and / or drum mixer until homogeneously mixed.

[0104] The system 10 may further include one or more tube extractors, such as the illustrated extractor 604, configured to assist in the advancement of a material (e.g., polymer material 20) through an extrusion device (e.g., an extruder 500). In some embodiments, the tube extractor 604 may have one or more conveyor belts positioned downstream of the die head 502 and be configured to move the conduit 101 away from the extruder 500 in a controlled manner. In some embodiments, the tube extractor 604 is configured to operate in a controlled manner to maintain a uniform outer diameter of the conduit 101 as it is being conveyed. In some embodiments, the tube extractor 604 is configured to selectively increase or decrease the outer diameter of one, two or more segments of the conduit 101. In some embodiments, the tube extractor 604 is configured to pull the conduit 101 at a speed configured to impart orientation to the polymer chains.

[0105] The system 10 may further comprise one or more containers, illustrated troughs (or tubs) 606, which have open tops and elongated containers into which an object (e.g., polymer material 20) may be at least partially immersed. The troughs 606 may be filled, or at least partially filled (hereinafter "filled"), with one or more fluids, solutions 630 (e.g., alcohol solutions, hydrophilic polymer solutions, hydrophobic polymer solutions). In some embodiments, the troughs 606 comprise a closed, elongated container containing one or more fluids (e.g., solutions 630) maintained under vacuum.

[0106] System 10 may further comprise one or more drying systems, such as the illustrated dryer 608, which include a manifold configured to apply a gas across the surface of an object (e.g., a polymer material 20). The dryer 608 may apply a gas configured to extract a solvent from the surface of the object. The dryer 608 can apply a gas selected from the group consisting of oxygen, nitrogen, argon, and combinations thereof. The dryer 608 may be configured to apply at least one of an ambient gas, a heating gas, and a cooling gas.

[0107] System 10 may further comprise one or more containers for immersing components, such as the illustrated chamber 618, in which an object (e.g., conduit 101) may be at least partially immersed in a fluid and / or semi-fluid, such as the solution 630 described herein. In some embodiments, the trough 606 comprises the chamber 618 (e.g., the trough 606 and chamber 618 constitute the same component of System 100).

[0108] As described herein with respect to trough 606 and chamber 618, system 10 may further include one or more solutions, solution 630 as shown herein. As used herein, one, two or more of solutions 631-635 are generally referred to as solution 630. Trough 606 and / or chamber 618 may be filled with solution 630 to expose, for example, one or more components of device 100 and / or system 10 to solution 630. Solution 630 may include a homogeneous mixture containing two or more substances. In some embodiments, trough 606 is filled with solution 630 containing a solution selected from the group consisting of water, ethanol, methanol, propanol, butanol, and combinations thereof.

[0109] In some embodiments, solution 630 further comprises a poly(acrylic acid) solution, solution 631.

[0110] In some embodiments, solution 630 further comprises a buffer, solution 632.

[0111] In some embodiments, solution 630 further comprises a polymer solution, solution 633. Solution 630 may also contain a hydrophilic and / or hydrophobic polymer solution 633 configured to penetrate the polymer material 20 to provide improved hydrophilicity and / or improved non-thrombogenicity. In some embodiments, the trough 606 is filled with solution 630 containing a hydrophilic polymer solution 633 selected from the group consisting of poly(vinyl alcohol), poly(acrylic acid), polyethylene glycol, poly(vinylpyrrolidone), poly(methacrylate sulfobetaine), poly(acrylic sulfobetaine), poly(methacrylate carboxybetaine), poly(acrylic carboxybetaine), povidone polyacrylamide, poly(N-(2-hydroxypropyl)methacrylamide), polyoxazoline, polyphosphate, polyphosphazene, polyvinyl acetate, polypropylene glycol, poly(N-isopropylacrylamide), poly(2-hydroxymethyl methacrylate), and combinations thereof. In some embodiments, the trough 606 is filled with a solution 630 containing a hydrophobic polymer solution 633 selected from the group consisting of polyurethane, silicone, polybutadiene, styrene-butadiene copolymer, natural rubber, and combinations thereof.

[0112] In some embodiments, solution 630 contains dye 634, which is a dye.

[0113] In some embodiments, solution 630 comprises a surfactant solution, solution 635. Solution 630 may also comprise a surfactant solution 635 containing a water-retaining agent. The water-retaining agent may comprise a nonionic surfactant (i.e., a surfactant having an uncharged hydrophilic head and a hydrophobic tail) or an amphoteric surfactant (i.e., a surfactant having a net uncharged hydrophilic head and a hydrophobic tail). In some embodiments, the water-retaining agent is a nonionic surfactant selected from the group consisting of poloxamer, triacetin, α-hydroxy acid, poly(ethylene glycol), poly(propylene glycol), glycerol, propylene glycol, ethylene glycol, butylene glycol, hexylene glycol, glycerol, erythritol, slythritol, arabitol, xylitol, ribitol, mannitol, sorbitol, galactitol, fusitol, iditol, inositol, boremitol, mariitol, lactitol, maltotriitol, maltotetraitol, polyglycitol, and combinations thereof. In some embodiments, the water-retaining agent comprises an oil such as vitamin E. Some water-retaining agents may also comprise one or more salts (e.g., sodium chloride, potassium chloride, and / or phosphocholine).

[0114] System 10 may further comprise a non-solvent bath 612 in which an object (e.g., conduit 101) is at least partially immersed in a non-solvent solution. The non-solvent bath 612 may contain a non-solvent solution selected from the group consisting of ethanol, methanol, propanol, butanol, pentanol, hexanol, heptanol, octanol, decanol, dodecanol, dimethyl sulfoxide, ethyl acetate, acetate, propionate, ether, dimethylformamide, dimethylacetamide, acetone, acetonitrile, ethylene glycol, propylene glycol, glycerol, air, and combinations thereof.

[0115] The system 10 may further comprise one or more mandrels, including the illustrated mandrel 614, which may be configured to be slidably inserted into an object having a lumen through which it passes (e.g., a conduit 101 via a lumen 106). In some embodiments, the mandrel 614 is made of a non-stick surface such as a polytetrafluoroethylene, parylene, and / or phenol-coated surface.

[0116] The mandrel 614 may be configured to impart one, two, or more geometric features to an object (e.g., conduit 101). In some embodiments, the mandrel 614 includes a taper. In some embodiments, the mandrel includes a non-linear shape, such as a curved or bent shape. In some embodiments, the mandrel 614 includes a non-cylindrical cross-section.

[0117] The mandrel 614 may include a textured surface. In some embodiments, the mandrel 614 imparts texture to the inner diameter of the object (e.g., the surface of the lumen). The textured surface may be configured to reduce the flow resistance within the object's lumen by inducing turbulence around a fluid film layer. The textured surface may be configured to reduce the resistance and pressure within the object's lumen from high-flow environments such as power injection, which involves flow rates between 3 mL / sec and 10 mL / sec.

[0118] The system 10 may further include one or more filaments, filament 608 shown in the figure, to which a material (e.g., polymer material 20) can be formed around or otherwise attached. In some embodiments, the mandrel 614 comprises the filament 608.

[0119] System 10 may further include one or more clamps, such as the illustrated clamp 200, configured to attach one component of System 10 to another. Clamp 200 may comprise one or more clamps as described below with reference to Figures 10A to 10C.

[0120] System 10 may further include a hydration apparatus, a hydration device 300. The hydration device 300 may include a tube or other container, an overtube 301, which can be at least partially filled ("filled" as herein) with a hydration medium, a fluid 365 as shown. The fluid 365 may include one or more materials (e.g., one or more solutions or other fluids) used to hydrate one or more portions of the device 100 (e.g., all or part of the conduit 101) placed inside the overtube 301 (before and / or after filling the overtube 301 with the fluid 365). In some embodiments, the fluid 365 includes several different fluids 365, such as the fluids 365a, 365b, and / or 365c shown. The hydration device 300 may further include one or more fluid reservoirs, a fluid reservoir 360, used to store one, two or more fluids 365 before the hydration treatment (e.g., before shipping the hydration device 300 to the clinical site). The fluid reservoir 360 may include one, two, or more fluid sources selected from the group consisting of syringes, gravity-driven fluid bags, fluid pumps (e.g., with reservoirs), and combinations thereof. In some embodiments, two or more fluid reservoirs 360 contain two or more different fluids 365.

[0121] The hydration devices 300 may be configured similarly to the hydration devices 300a and / or 300b described below with reference to Figures 11A and 11B, respectively.

[0122] The hydration fluid 365 may contain sterile material or material to be sterilized. The hydration fluid 365 may contain one, two, three or more materials selected from the group consisting of water-retaining agents, physiological saline, Ringer's lactate solution, glucose, water for injection (WFI), custom isotonic salt solutions, poloxamer, glycerol, sorbitol, xylitol, polyethylene glycol, starch, heparin, and combinations thereof. The fluid 365 may be supplied at a specific pH, temperature, and / or volume. In some embodiments, the hydration fluid 365 contains sterile normal physiological saline (isotonic) at body temperature (e.g., 37°C).

[0123] The hydration device 300 may be configured to provide the water content (e.g., hydration) of device 100 that is maintained during storage and / or transport.

[0124] In some embodiments, hydration may be performed with or without the use of a hydration device 300 to increase the size of the lumen 106 of the conduit 101. In some embodiments, the conduit 101 and the hydration device 300 are configured to increase the diameter of the lumen 106 between a dehydrated state and a rehydrated state by 0 to 25%.

[0125] In some embodiments, during the manufacturing process, one or more portions of the device 100 (e.g., all or part of the conduit 101) are dehydrated and / or annealed under stress to induce subsequent hydration or otherwise anisotropic swelling, which is carried out using the hydration device 300. In some embodiments, the conduit 101 and the hydration device 300 are configured to allow swelling of the conduit 101 only in the axial direction, such that the outer diameter and the diameter of the lumen 106 are maintained, in order to allow the physician to better match the size of the conduit 101 to the site for insertion. In some embodiments, the conduit 101 and the hydration device 300 are configured to allow radial swelling of the conduit 101 so that the length of the conduit 101 does not change, in order to allow precise placement of the proximal and / or distal ends of the conduit 101, and to seal the insertion site and / or reduce pressure loss across the conduit 101.

[0126] In some embodiments, during the manufacturing process, one or more portions of the device 100 (e.g., conduit 101) are freeze-dried while in a swollen state, so that the dimensions of the pores and / or other dimensions of the freeze-dried portion do not change significantly when subsequent hydration treatment is carried out (e.g., using a hydration device 300).

[0127] In some embodiments, one or more hydration devices 300 are used to perform multiple hydrations of the device 100, such as one or more hydrations performed during manufacturing and / or one or more hydrations performed at the treatment site immediately before insertion of the conduit 101 into the patient. In these embodiments, two or more hydrations may be performed using different fluids 365. In some embodiments, the hydration device 300 includes a fluid 365 configured to hyperswell (or hyperswell) the conduit 101, such as a low pH aqueous solution, a hypotonic solution, and / or a solution at a temperature above body temperature (e.g., 37°C) but below the Tg of the polymer material. A second hydration device 300 may include an isotonic solution at body temperature (e.g., 37°C) configured to neutralize the conduit 101 and maintain a desired level of swelling.

[0128] In some embodiments, the device 100 comprises one or more hydration devices 300. In these embodiments, the device 100 may be packaged together with the hydration devices 300, such as when all or part of the conduit 101 is placed inside the overtube 301 of the hydration devices 300 in a shipping container, package 180. This arrangement may simplify the hydration process performed at the treatment site. In some embodiments, the device 100 is shipped in a pouch or other storage container, package 180, and a reservoir 360 containing fluid 365 is also included in the storage container. In these embodiments, the reservoir 360 comprises a pouch or other container configured to burst or otherwise open while in package 180 (e.g., at the treatment site), allowing the fluid 365 to surround and hydrate the device 100 before the package 180 is opened.

[0129] In some embodiments, the hydration device 300 and system 10 are configured to perform a hydrophilic polymer introduction treatment at an elevated temperature, such as a temperature above body temperature (e.g., above 37°C). In these embodiments, the conduit 101 may be configured to "superhydrate" or "superswell," for example, to introduce further agents beyond the swelling observed at body temperature. In some embodiments, as described above, the hydration treatment at an elevated temperature is performed to introduce an agent containing one or more plasticizers, water-retaining agents, and / or hydrophilic polymers (e.g., one or more further plasticizers, water-retaining agents, and / or hydrophilic polymers).

[0130] Any hydration steps performed (e.g., initial hydration steps, subsequent hydration steps) may be performed for a duration that can be selected as desired. In some embodiments, the hydration steps are performed relatively quickly (e.g., in a time of 10 minutes or less).

[0131] The system 10 may further include an air blade 610 configured to blow away or otherwise remove solutions, solvents, volatiles, and / or other substances from the surface of an object (e.g., a conduit 101).

[0132] The system 10 may further comprise one or more holders, racks 622 for holding one or more conduits 101 and / or one or more components of conduits 101 (generally "conduits 101") in desired positions. The racks 622 may include an upper rack 622a (illustrated), a lower rack 622b (also illustrated), and / or other racks 622, each including a frame, base, or grid on which objects (e.g., conduits 101) are placed and / or mounted.

[0133] System 10 may further comprise one or more temperature-controlled environment chambers, including the illustrated oven 620. The oven 620 may comprise a thermally insulated chamber configured for heating and / or drying an object (e.g., conduit 101). In some embodiments, the oven 620 includes a convection oven. In some embodiments, the oven 620 is configured to extract or otherwise remove a material (e.g., solvent, water, etc.) from an object. In some embodiments, the oven 620 comprises a chamber capable of controlling both temperature and pressure. In some embodiments, the oven 620 comprises a chamber capable of controlling humidity as well. In some embodiments, the oven 620 comprises a chamber capable of purging a gas (e.g., air, nitrogen, argon, etc.).

[0134] Device 100 may include a circumferential (or partially circumferential) fixing element, such as the illustrated band 122, which may be configured to secure the connector 120 to the conduit 101. For example, the connector 120 may include a barbed or other elongated end portion that is inserted into the lumen 106 at the end of the conduit 101 (e.g., during a manufacturing process). The band 122 is positioned near the conduit 101 in a location that surrounds or at least closely (in this specification, “surrounds”) the inserted end portion of the connector 120, and can secure the connector 120 to the conduit 101. The band 122 may be configured to provide a fluid seal between the connector 120 and the conduit 101. The band 122 may include a material configured to shrink when heated, such as a heat-shrinkable tube, which is positioned to surround the conduit 101 and the inserted end portion of the connector 120 and is then heated to undergo radial shrinking to secure the connector 120 to the conduit 101. In some embodiments, the band 122 includes a heat-shrinkable tube configured to shrink at temperatures between 120°C and 350°C. The band 122 may include a material selected from the group consisting of polytetrafluoroethylene, fluorinated ethylene propylene, perfluoroalkoxy copolymer, ethylene tetrafluoroethylene, polyethylene terephthalate, polyether ether ketone, polyether block amide, poly(vinyl chloride), polyethylene, polyolefin, and combinations thereof. In some embodiments, the band 122 includes a material configured to be elastically stretched (e.g., radially expanded via a tool, increasing its diameter) and positioned near the end of the conduit 101. The band 122 is then transitioned to an elastically biased state with a smaller diameter, which is released and provides the desired attachment of the band 122 to the conduit 101. In some embodiments, the band 122 includes a material configured to be plastically deformed by radial compression, resulting in a reduced diameter configured to form a secure connection of the connector 120 to the conduit 101.In some embodiments, the band 122 comprises a material configured to swell radially upon exposure to a chemical (e.g., a solvent) and then be positioned near the conduit 101 at a location surrounding the insertion end portion of the connector 120. Removal of the chemical (e.g., by evaporation or other means) causes radial contraction of the band 122, providing the desired secure connection.

[0135] System 10 may further include one or more marking devices, such as the illustrated device 616. The marking devices may be employed to place markings on the surface of the conduit. In some embodiments, the marking device 616 comprises a laser, such as a solid-state laser. In some embodiments, the marking device 616 includes a pad printer. In some embodiments, the marking device 616 comprises an inkjet printer, such as a jetting valve printer. The inkjet printer may be configured to perform pressurized liquid deposition to deposit ink (e.g., liquid ink). These devices may operate in an automated manner (e.g., in a manner such that the marking device autonomously executes a set of commands pre-provided by an operator). In some embodiments, the marking device 616 includes a marking composition, such as ink 617, which is deposited on the conduit 101 in a dehydrated state (e.g., fully dehydrated or partially dehydrated) to allow the marking composition (e.g., ink 617) to be absorbed into the bulk of the conduit 101.

[0136] Subsequently, the marked conduit 101 may be dried and / or annealed. Drying and / or annealing of the conduit may lock the marking to the conduit, for example, by physically bonding and / or chemically crosslinking the marking composition (e.g., ink 617) to a portion of the conduit (e.g., a portion of the base polymer material 20). The marking device 616 may be configured to adhere the marking composition (e.g., ink 617) as droplets onto the dehydrated polymer material 20. The marking device 616 may be configured to apply the marking composition (e.g., ink 617) by spraying or jetting it in a liquid state. The marking device 161 may be configured to adhere the marking composition (e.g., ink 617) in a liquid state by pad printing, screen printing, or other ink transfer methods. The marking device 616 may be configured to inject the marking composition (e.g., ink 617) into the polymer material 20 in a dehydrated or partially hydrated state.

[0137] The marking device 616 may further include a post-processing element configured to bond the ink 617 to the polymer material 20 (e.g., physically, chemically, or ionically), such as an element selected from the group consisting of a heat treatment element, a chemical treatment element, an ultraviolet treatment element, a radiation treatment element, and a combination thereof.

[0138] When the marking composition is disposed on the surface of a conduit, it allows the marking composition to penetrate into the conduit to various suitable depths before being locked therein. In some embodiments, the marking composition allows penetration into the conduit to a depth of 10 µm or more, 20 µm or more, 30 µm or more, 40 µm or more, 50 µm or more, 60 µm or more, 70 µm or more, 80 µm or more, 100 µm or more, 125 µm or more, 150 µm or more, or 175 µm or more. In some embodiments, the marking composition allows penetration into the conduit to a depth of 200 µm or less, 175 µm or less, 150 µm or less, 125 µm or less, 100 µm or less, 80 µm or less, 70 µm or less, 60 µm or less, 50 µm or less, 40 µm or less, or 30 µm or less. Combinations of the above ranges are also possible (e.g., 10 µm or more and 200 µm or less, or 50 µm or more and 60 µm or less, etc.). Other ranges are also possible.

[0139] The system 10 may further comprise one or more marking compositions (such as printing ink and / or compositions comprising printing ink), the illustrated ink 617, which may be configured to physically bond and / or chemically crosslink to the polymer material 20. The marking composition (e.g., ink 617) may comprise a dye or a pigment. In some embodiments, the dye or pigment may be reactive. For example, tetrasodium 4-amino-5-hydroxy-3,6-bis[[4-(2-sulfonatooxyethylsulfonyl)phenyl]diazenyl]naphthalene-2,7-disulfonate ("Reactive Black 5"), copper 33-[[4-(2-hydroxyethylsulfonyl)phenyl]sulfamoyl]-2,11,20,29,39,40-hexaaza-37,38-diazanidanonacyclo[28.6.1.1 3,10 .1 12,19 .1 21,28 .0 4,9 .0 13,18 .0 22,27 .0 31,36Tetraconta-1,3(40),4(9),5,7,10,12(39),13(18),14,16,19,21,23,25,27,29,31(36),32,34-nonadecane-6,15,24-trisulfonic acid ("Reactive Blue 21"), 2-Naphthalenesulfonic acid, 7-(acetylamino)-4-hydroxy-3-[4-[2-(sulfoxy)ethyl]sulfonyl]phenyl]azo]-,2 sodium salt (9Cl) ("Reactive Orange 78"), "Reactive Yellow 15", Disodium; 1-amino-9,10-dioxo-4-[(3-{[2-(sulfonatooxy)ethyl]sulfonyl}phenyl)amino]-9,10-dihydro-2-anthracenesulfonic acid ("Reactive Blue 19"), 1-Amino-4-[3-(4,6-dichlorotriazine-2-ylamino)-4-sulfophenylamino]anthraquinone-2-sulfonic acid ("Reactive Blue 4"), "CI Reactive Red 11", 4-[2-(5-carbamoyl-1-ethyl-4-methyl-2,6-dioxopyridine-3-ylidene)hydrazinyl]-6-[(4,6-dichloro-1,3,5-triazine-2-yl)amino]benzene-1,3-disulfonic acid ("CI Reactive Yellow 86"), Tetrasodium; 6,13-dichloro-3,10-bis[[4-[(4,6-dichloro-1,3,5-triazine-2-yl)amino]sulfonatophenyl]amino]triphenodioxazine disulfonate ("CI Reactive Blue 163"), and / or 5-(benzoylamino)-4-hydroxy-3-[[1-sulfo-6-[[2-(sulfoxy)ethyl]sulfonyl]-2-naphthalenyl]azo]-, tetrasodium salt ("CI Reactive Red 180") It may be a dye or pigment selected from the group consisting of the following:

[0140] In some embodiments, the dye or pigment reacts with the marking polymer material. In exemplary embodiments, the reaction may occur with poly(acrylic acid) and PVA having a cationic salt. In another exemplary embodiment, the dye or pigment may be incorporated into (e.g., encapsulated) the polymer material matrix.

[0141] In some embodiments, the marking composition comprises a non-reactive dye, pigment, and / or radiosensitizer. Non-limiting examples of suitable non-reactive dyes include phthalocyanine blue, phthalocyanine green, carbazole violet, "Copper Phthalocyanine Blue," "Pigment Blue 15," "Pigment Green 7" having 0-15 halogenated groups, carbon black, modified carbon black, "Congo Red 17," "FD&C Blue 2," "FD&C Violet 2," "Carbazole Violet," "FD&C Yellow 8," "FD&C Yellow 10," "Chromium Cobalt" (see 21 CFR Part 73 Subpart D and 21 CFR Part 74 Subpart D), and "CI Vat Orange." 1", 2-[[2,5-diethoxy-4-[(4-methylphenyl)thiol]phenyl]azo]-1,3,5-benzenetriol, 16,23-dihydrodinaphtho[2,3-a:2',3'-i]naphtho[2',3':6,7]indro[2,3-c]carbazole-5,10,15,17,22,24-hexone, N,N'-(9,10-dihydro-9,10-dioxo-1,5-anthracenediyl)bisbenzamide, 7,16-dichloro-6,15-dihydro-5,9,14,18-anthrazinetetron, 16,17-dimethoxydinanaphtho[1,2,3- Examples include cd:3',2',1'-lm]perylene-5,10-dione, 4-[(2,4-dimethylphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazole-3-one, 6-ethoxy-2-(6-ethoxy-3-oxobenzo[b]thiene-2(3H)-ylidene)benzo[b]thiophene-3(2H)-one, 1-amino-4-[[4-[(2-bromo-1-oxoallyl)amino]-2-sulfonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulfonate disodium, and combinations thereof.Non-limiting examples of suitable non-reactive pigments include carbon black, modified carbon black, titanium dioxide, chromium-cobalt-aluminum oxide, chromium oxide green, iron oxides, mica-based pearlescent pigments, and combinations thereof.

[0142] Dyes or pigments (e.g., reactive dyes or pigments, non-reactive dyes or pigments) may constitute various suitable amounts of the marking composition. In some embodiments, the dye may constitute 0.001 w / w% or more, 0.002 w / w% or more, 0.005 w / w% or more, 0.0075 w / w% or more, 0.01 w / w% or more, 0.02 w / w% or more, 0.05 w / w% or more, 0.075 w / w% or more, 0.1 w / w% or more, 0.2 w / w% or more, 0.5 w / w% or more, or 0.75 w / w% or more of the marking composition. In some embodiments, the dye constitutes 1 w / w% or less, 0.75 w / w% or less, 0.5 w / w% or less, 0.2 w / w% or less, 0.1 w / w% or less, 0.075 w / w% or less, 0.05 w / w% or less, 0.02 w / w% or less, 0.01 w / w% or less, 0.0075 w / w% or less, 0.005 w / w% or less, or 0.002 w / w% or less of the marking composition. Combinations of the above ranges are also possible (for example, 0.001 w / w% to 1 w / w% or 0.01 w / w% to 0.05 w / w%). Other ranges are also possible.

[0143] If a marking composition contains two or more dyes and / or pigments, each dye or pigment may independently constitute an amount of one or more marking compositions within the above range, and / or all of the dyes and pigments together may constitute an amount of one or more marking compositions within the above range.

[0144] The marking composition (e.g., Ink 617) may further contain a dye or pigment comprising a solvent suspension or solution containing a water-soluble polymer selected from the group consisting of poly(vinyl alcohol), poly(acrylic acid), polyethylene glycol, or poly(vinylpyrrolidone), poly(methacrylate sulfobetaine), poly(acrylic sulfobetaine), poly(methacrylate carboxybetaine), poly(acrylic carboxybetaine), poly(methacrylate sulfobetaine), poly(methacrylate carboxybetaine), povidone polyacrylamide, poly(N-(2-hydroxypropyl)methacrylamide), polyoxazoline, polyphosphate, polyphosphazene, polyvinyl acetate, polypropylene glycol, poly(N-isopropylacrylamide), poly(2-hydroxymethyl methacrylate), and combinations thereof.

[0145] The water-soluble polymer may constitute various suitable amounts of the marking composition. In some embodiments, the water-soluble polymer constitutes 10 w / w% or more, or 12.5 w / w% or more. In some embodiments, the water-soluble polymer constitutes 15 w / w% or less, or 12.5 w / w% or less. Combinations of the above ranges are also possible (e.g., 10 w / w% or more, 15 w / w% or less). Other ranges are also possible.

[0146] In some embodiments, the solvent suspension and / or solution further comprises water and / or salt. Non-limiting examples of suitable salts include phosphates (e.g., MSP, DSP, TSP), borates, sodium chloride, citrates, ethylenediaminetetraacetates, sulfites, hyposulfites, metal oxides, selenium dioxide, selenium trioxide, selenite, selenic acid, nitrates, silicates, and vegetable salts.

[0147] In some embodiments, the ink 617 may be configured to diffuse into the polymer material 20 to create colored markings within the bulk of the polymer material 20.

[0148] The system 10 may further comprise one or more pressure chambers, chamber 640 shown in the figure, which may be configured to generate and / or maintain a specific pressure (e.g., a pressure above or below the room pressure) within the chamber. In some embodiments, the pressurizing device 640 includes a low-pressure source, such as a low-pressure oven. In some embodiments, the pressurizing device 640 includes a high-pressure source, such as a chamber having a high-pressure fan. In some embodiments, the chamber 640 includes a chamber that can control both pressure and temperature. In some embodiments, the chamber 640 constitutes a chamber that can also control humidity.

[0149] The system 10 may further include one or more stretching devices, such as the illustrated stretcher 650, which may be configured to apply axial tension to an object (e.g., a conduit 101).

[0150] System 10 may further comprise one or more molding machines, such as the illustrated molding machine 660, which may be configured to form or otherwise apply an overmolding material (e.g., material 665 described below) onto an object (e.g., conduit 101). In some embodiments, the overmolding material 665 includes thermoplastic polyurethane (TPU) which includes thermoplastic materials selected from the group consisting of aromatic polyethers, aromatic polyesters, aliphatic polyethers, aliphatic polyesters, polycarbonates, silicones, polypropylenes, polyethylenes, poly(vinyl chloride), polyetheretherketones, polyamides, liquid crystal polymers, polystyrenes, nylons, and combinations thereof. In some embodiments, the overmolding material 665 includes silicones such as silicone-urethane copolymers. Overmolding of first and second water-soluble polymers is also possible.

[0151] In some embodiments, one or more core pins, pin 661 in the illustration, are configured to be slidably inserted into an object (e.g., conduit 101) to which the molding machine 660 applies the overmolding material 665.

[0152] System 10 may further comprise one or more tipping (or tip-forming) devices, such as a tipper 670 shown in the figure, which may be configured to form tips on the conduit 101, such as a distal tip and / or a proximal tip. The tipper 670 may be configured to deliver an energy source selected from the group consisting of heat, solvent, laser, radio frequency, ultrasound, and combinations thereof. The tipper 670 may be configured to form tips including shapes selected from the group consisting of flat (e.g., vertical), chamfered (e.g., oblique), obtuse (e.g., radial), tapered, flared, and combinations thereof. In some embodiments, the tips are formed before annealing of the conduit 101 (as described later with reference to method 1400 in Figure 16). In some embodiments, the tips are formed after annealing of the conduit 101 in a dehydrated state and before the incorporation of a water-retaining agent (as described later with reference to method 1600 in Figure 18). In some embodiments, the tip is formed after annealing and after the incorporation of the water-retaining agent.

[0153] System 10 may include one or more sensors, transducers, and / or other functional elements, such as the functional element 99 described below. The functional element 99 may include a functional element 99a located on, in, and / or otherwise in close proximity to, the extruder 500, a functional element 99b located in close proximity to the hydration device 300 (as shown in the figure), and / or other functional elements 99 (e.g., located in close proximity to one or more other components of System 10). The functional element 99 may be operably connected to one or more wires, optical fibers, tubes (e.g., fluid delivery, hydraulic, and / or pneumatic tubes), waveguides, and / or other conduits (not shown) that transport signals (e.g., information), energy, fluids, light, and / or sound between the functional element 199 and / or other components (e.g., other components of System 10). In some embodiments, System 10 includes a functional device 999 configured to interface with the functional element 199, as described below.

[0154] In some embodiments, the functional elements 99 and / or 199 comprise one or more sensors, one or more transducers, and / or one or more other functional elements.

[0155] The system 10 may include a functional device 999 configured to operably interact with one or more of the functional elements 99 and / or 199.

[0156] Referring here to Figure 8, a method for inserting an article, such as a device described elsewhere in this specification, which comprises a conduit (e.g., a catheter device), into a patient is illustrated. Method 2000 of Figure 8 will be described with reference to the device 100 and other components of system 10 in Figure 1. As described herein, the device 100 may comprise an article that is a catheter device, such as a nanoporous hydrophilic catheter, which can be inserted into the patient's vascular system by an over-the-wire (OTW) method with vasodilation (e.g., venous dilation) without the use of a sheath introducer.

[0157] In STEP 2010 shown in Figure 8, the device 100 is manufactured as described herein, including, for example, if the device 100 includes at least a conduit 101 (e.g., sealed) placed within a package 180. The device 100 may be assembled, sterilized, and finally shipped to the customer for insertion into a patient (e.g., insertion of the distal portion of the conduit 101 into the patient's vein, artery, and / or other internal conduit at a skin location ("insertion location")). In some embodiments, step 2010 includes the complete or partial hydration of at least a portion of the device 100 (e.g., hydration of at least a portion of the conduit 101 using a hydration device 300 before sterilization). For example, a partial hydration treatment may be performed in which the device 100 is packaged at a high equilibrium weight content (EWC). The hydration treatment may be limited in time (e.g., limited to less than 10 minutes) in order to achieve a desired level of hydration. In some embodiments, multiple hydration treatments are performed (e.g., using similar or dissimilar solutions 365). In some embodiments, the device 100 is packaged and shipped without any specific hydration treatment (for example, in a dehydrated state).

[0158] As used herein, dehydration can be defined as having a total water content of less than 5 w / w%. As used herein, partial hydration can be defined as having a water content of 5 to 90 w / w% of the equilibrium water content (EWC), for example, 30 to 40 w / w%. As used herein, complete hydration can be defined as having a water content of 90 to 100% of the EWC, or within 10% of the EWC.

[0159] In STEP2020 shown in Figure 8, the device 100, still containing package 180, is shipped to the clinical site where the conduit 101 is inserted into the patient. At the site where the insertion procedure is performed ("procedure site"), package 180 is opened using standard sterile techniques, and the remaining components of device 100 (hereinafter referred to as device 100) are removed. STEP2020 may include a complete or partial hydration procedure performed on one or more parts of device 100, as detailed below. The hydration procedure may be time-limited, as described herein.

[0160] As shown in Figure 8, in STEP 2030, the conduit 101 of the device 100 is inserted into the patient, for example, by inserting it through the skin into the patient's vein or artery using a modified “Seldinger” technique. The distal end of the conduit 101 can be advanced (e.g., on a guidewire) to one or more locations within the patient, such as one or more locations within the patient's cardiovascular system, such as within the patient's heart or at least close to the heart.

[0161] In some embodiments where device 100 is shipped fully hydrated, patient insertion in STEP 2030 occurs as soon as package 180 is opened in STEP 2020.

[0162] In some embodiments where device 100 is shipped in a partially hydrated state, device 100 may be further hydrated in STEP 2020 and then inserted into the patient. Alternatively, device 100 may be inserted into the patient in a partially hydrated state (e.g., the hydrated state of the shipped device 101 configured to be sufficiently hydrated to allow safe and easy insertion of the conduit 101 into the patient). This provides additional column stiffness (or column rigidity) within the conduit 101 while still exhibiting substantial lubricity.

[0163] In embodiments in which device 100 is shipped in a dehydrated state, device 100 can be partially or completely hydrated at the treatment site before insertion into the patient. As described herein, partial hydration of device 100 can increase column stiffness (compared to complete hydration) while achieving sufficient hydration to allow safe insertion.

[0164] (For example, from partial hydration treatment performed before sterilization and / or at the treatment site) The device 100, which is inserted into the patient in a partially hydrated state, may be configured to continue to hydrate (e.g., continue to swell) after insertion into the patient. Post-insertion swelling (e.g., of the conduit 101) may be configured to cause hemostasis at the insertion site.

[0165] Hydration of one or more parts of device 100 can be performed using the hydration device 300 described herein. Hydration at the treatment site is performed using sterile techniques.

[0166] Referring here to Figure 9, a perspective view of an article which is a medical device including an S-shaped conduit is shown. As with other articles and / or medical devices described herein, the article shown in Figure 9 may be a catheter and / or may include a catheter. Device 100 may include an S-shaped conduit 101' configured to facilitate implantation into a patient, achieve a lower infiltration rate, and reduce the likelihood of dislodgement within the patient. The conduit 101' may include a first curved portion 114 and a second curved portion 118. The portions 114 and 118 may have similar or different radii of curvature. In some embodiments, the first portion 114 includes a relatively small radius (e.g., sharp curvature) and the second portion 118 includes a relatively large radius (e.g., wide curvature). The distance between portions 114 and 118, distance D1, may include a distance of 1 mm to 200 mm, e.g., 2 mm to 20 mm, e.g., 10 mm. The radius of curvature of parts 114 and / or 118 may include radii greater than 1 mm, for example between 2 mm and 50 mm, for example 10 mm.

[0167] In some embodiments, once the device 100 is implanted in a patient, the first portion 114 may be configured to remain on the dermis, while the second portion 118 may be configured to remain within the dermis and / or within blood vessels (e.g., veins).

[0168] In some embodiments, as described below with reference to Figure 16, the conduit 101 may be annealed with a mandrel 614, which is an S-shaped mandrel, or otherwise processed to form an S-shaped conduit 101'. After removing the S-shaped mandrel 614, the conduit 101' can maintain its S-shape (for example, the material of the conduit 101' may be made elastically biased or otherwise possess shape memory properties). In some embodiments, the device 100 slidably receives a linear element 123 (e.g., a needle) to give the conduit 101' a relatively linear shape, such as a straight shape, which may be desired during storage, transport, and / or insertion by the patient. After removing the linear element 123, the device 100 (e.g., conduit 101') can take on an S-shape created by annealing or other manufacturing methods.

[0169] Referring here to Figures 10A to 10C, perspective and end views of clamps for fastening or securing conduits are shown. The clamp 200 may comprise a pair of elongated members 220, 240 that are hinged together by a biasing assembly 210 (similar to the structure and arrangement of a clothespin, for example) or otherwise pivot. The clamp 200 may be used to secure conduit 101 and / or another component of system 10 to a device or other distinct component of system 10, such as those described later with reference to Figures 15 and 16. In some embodiments, one or more clamps 200 are included and used to secure conduit 101 and / or another component of system 10. The biasing assembly 210 may comprise a biasing element 211 configured to rotate about an axis 215. The biasing element 211 may comprise a spring with two arms 214a, 214b such that arm 214a engages with elongated member 220 and arm 214b engages with elongated member 240. The clamp 200 may be configured to move between an open position (as shown in Figure 10A) and a closed position (as shown in Figure 10B). In some embodiments, the biasing assembly 210 is configured to bias the clamp 200 to the closed position. The clamp 200 and the biasing assembly 210 may include high heat-resistant materials selected from the group consisting of metal, stainless steel, nitinol, polyetheretherketone, liquid crystal polymer, polyoxymethylene, polyamide, polysulfone, polyethersulfone, polyphenylenesulfone, polyamideimide, polyetherimide, polyimide, and combinations thereof.

[0170] The elongated member 220 includes a first portion 223 and a second portion 227, with an intermediate portion 225 in between. In some embodiments, the first portion 223 and / or the second portion 227 are linearly offset from the intermediate portion 225 (for example, the first portion 223, the second portion 227, and the intermediate portion 225 are not linearly aligned). The first portion 223 may have an inner surface 224 with one, two, or more longitudinal recesses 226. The recesses 226 may slidably receive at least a portion of a conduit, such as a conduit 101 of the device 100 (for example, a conduit 101 having a proximal portion 104 and a distal portion 108). The second portion 227 may be configured and positioned to have a cavity 228 that can receive or otherwise engage a bar of a rack (for example, a drying rack, an oven rack, etc.).

[0171] The elongated member 240 includes a first portion 243 and a second portion 247, with an intermediate portion 245 in between. In some embodiments, the first portion 243 and / or the second portion 247 are linearly offset from the intermediate portion 245 (for example, the first portion 243, the second portion 247, and the intermediate portion 245 are not linearly aligned). The first portion 243 may have an inner surface 244 with one, two, or more longitudinal recesses 246. The recesses 246 may slidably receive at least a portion of a conduit, such as a conduit 101 of the device 100 (e.g., a conduit 101 having a proximal portion 104 and a distal portion 108). The second portion 247 may have a cavity 248 that can receive or otherwise engage a bar of a rack (e.g., a drying rack, an oven rack, etc.).

[0172] The inner surface 224 of the first portion 223 may be configured to frictionally engage with the inner surface 244 of the first portion 243, so that recesses 226, 246 align to define one, two, or more lumens 260 (three as shown in Figure 10C). The lumens 260 may include a diameter D1 configured to surround and fix at least a portion of a conduit, such as the conduit 101 of the device 100. In some embodiments, the lumens 260 surround and fix a portion of the conduit 101 (e.g., a proximal portion 104 or a distal portion 108). The lumens 260 may include a cross-section having a shape selected from the group consisting of circular, elliptical, polygonal, triangular, hexagonal, pentagonal, rectangular, square, and / or trapezoidal. In some embodiments, the lumens 260 include a cross-section equal to the cross-section of the proximal portion 104 and / or distal portion 108 of the conduit 101 of the device 100.

[0173] Referring here to Figure 11A, a perspective view of a hydration device for hydrating a conduit, consistent with the concept of the present invention, is shown. As shown, the system 10 includes a device 100 and a hydration device 300a. The hydration device 300a in Figure 11A may include similar components (e.g., an overtube 301, a fluid reservoir 360, and / or fluid 365) and / or may have a similar structure and arrangement to the hydration device 300 described herein with reference to Figure 1. The hydration device 300a may include an overtube 301 configured to surround at least a portion of the medical device to be hydrated, such as surrounding the conduit 101 of the device 100, as shown. The overtube 301 may have a length greater than or equal to the length of the conduit 101 and / or device 100, for example, to hydrate a large portion of the length of the conduit 101 and / or device 100.

[0174] The overtube 301 may have a proximal end 303 and a distal end, with a lumen 306 in between. The proximal end 303 and the lumen 306 may be sized and configured to slidably receive a portion of the medical device (e.g., all of the medical device to be hydrated), such as slidably receiving the conduit 101 (e.g., substantially the entirety of the device to be hydrated is contained within the lumen 306 of the overtube 301). The proximal end 303 is further sized and configured such that, once inserted, the proximal end of the device 100 or at least the proximal portion forms a seal with the proximal end 303 of the overtube 301 in order to prevent or at least limit ("prevent" as used herein) the presence of fluid between the proximal portion of the device 100 and the proximal end 303. In some embodiments, the device 100 includes a suture wing 160, the distal portion of which forms a seal with the proximal end 303, as shown, for example, in Figure 11A.

[0175] Once the device 100 is placed inside the overtube 301, an operator (e.g., a clinician, nurse, manufacturer's employee, and / or other qualified operator) may fill the lumen 306 of the overtube 301 with fluid 365 (e.g., after passing through the lumen 106 of the conduit 101). The device 100 and / or hydration device 300a are configured such that the portion of the device 100 to be hydrated reaches a desired hydration level (e.g., a desired water content for storage, transport, and / or insertion into a patient).

[0176] The hydration device 300a may include a syringe or other fluid reservoir, a fluid reservoir 360 as shown in the figure, which may contain fluid 365. Fluid 365 may contain one or more solutions or other fluids as described herein with reference to Figure 1. The fluid reservoir 360 is configured to be fluidly attached to the device inserted into the overtube 301, for example, if the fluid reservoir 360 is fluidly attachable to the connector 120 of the device 100 as shown in the figure (for example, if the connector 120 includes a luer or other connector configured to fluidly attach to the mating connector of the fluid reservoir 360).

[0177] The hydration device 300a may include a flow limiter, restrictor 340, located at the distal end of the overtube 301, for example, to restrict the fluid from leaving the overtube 301 (e.g., to provide back pressure to restrict the fluid 365 introduced by the fluid reservoir 360 from leaving). In the hydration procedure, the fluid 365 may be introduced into the conduit 101 (via the fluid reservoir 360 and connector 120), and the lumen 106 may be filled so that the fluid 365 is in contact with the inner surface of the conduit 101, after which the fluid 365 may exit the distal end 109 of the conduit 101. The size and structure of the restrictor 340 may be determined so that a portion of the fluid 365 exiting the conduit 101 moves proximal within the overtube 301 toward the proximal end 303 (e.g. toward the suture wing 160) so that the fluid 365 is in contact with the outer surface of the conduit 101. In some embodiments, the clamp 170a is activated (e.g., clamped) after the fluid 365 has been forcefully flowed through the conduit 101 (after flushing) to prevent backflow.

[0178] Referring here to Figure 4B, a perspective view of a hydration device including a closed end for hydrating a conduit is shown, consistent with the concept of the present invention. The hydration device 300b shown in Figure 11B may include components similar to those of the hydration device 300 described herein with reference to Figure 1B, and / or the hydration device 300a described herein with reference to Figure 11A, and / or similar structures and arrangements. In the embodiment of Figure 11A, the distal end 309' of the overtube 301 is closed (e.g., sealed) to prevent, for example, fluid from escaping from the closed distal end 309'. In some embodiments, a hydration procedure using the hydration device 300b involves introducing fluid 365 into the conduit 101 (via a fluid reservoir 360 and a connector 120), filling the lumen 106 so that the fluid 365 is in contact with the inner surface of the conduit 101, and then the fluid 365 exits the distal end 109 of the conduit 101. The closed distal end 309' may direct the fluid 365 that has exited the conduit 101 in the overtube 301 toward the proximal end 303 (e.g., toward the suture wing 160) so that the fluid 365 contacts the outer surface of the conduit 101. The overtube 301 may include an opening located near the proximal end 303, the illustrated port 305, so that a continuous flow of fluid 365 can exit through the port 305. In some embodiments, the port 305 includes a valve such as a pressure threshold valve and / or a one-way valve. In some embodiments, a clamp 170a is activated (e.g., clamped) after the fluid 365 has flowed forcefully through the conduit 101 to prevent backflow.

[0179] Referring here to Figure 5, a flowchart of a method for manufacturing conduits, consistent with the concept of the present invention, is shown. Method 1000 shown in Figure 5 comprises a series of sub-methods, Methods 1100, 1200, 1300, 1400, 1500, and 1600, respectively, as will be described later with reference to Figures 13 to 18. Method 1100 may include a method for batch processing polymers. Method 1200 may include a method for extruding the polymer produced in Method 1100. Method 1300 may include a method for hydrophilizing the material produced in Method 1200. Method 1400 may include a method for annealing the material produced in Method 1300. Method 1500 may include a method for overmolding the material produced in Method 1400. Method 1600 may include a method for humidifying the material produced in Method 1500. Methods 1100-1600 may be employed to produce a single device 100 containing a single conduit 101 from a batch of polymer material, as will be described later with reference to Figures 13-18. However, these methods 1100-1600 may similarly be used to produce two, three, or more conduits 101 contained in one, two, three, or more devices 100. Multiple conduits 101 and / or devices 100 can be produced simultaneously (e.g., in batch mode) by modifying the method to utilize multiple tools and / or devices of system 10 (e.g., mandrel 614, filament 608, clamp 200, etc.) to produce multiple conduits 101 and / or devices 100 from one or more batches of polymer material.

[0180] Referring now to Figure 13, an example of a method 1100 for batch processing polymer materials, consistent with the concept of the present invention, is shown.

[0181] In STEP 1110 shown in Figure 13, a water-soluble polymer 21, a radiopaque agent 22, and / or a sodium phosphate solution 23 are combined in a container (this combination of materials is referred to herein as "polymer material 20"). Polymer material 20 may have a water-soluble polymer 21 concentration of at least 10 w / w%, for example, at least 20 w / w%, or for example, at least 30 w / w%. For example, the water-soluble polymer 21 may have a total mass between 10 g and 150 g, for example, between 25 g and 120 g, or for example, about 78 g. Polymer material 20 may have a radiopaque agent 22 concentration of at least 1 w / w%, for example, at least 10 w / w%, or for example, at least 20 w / w%. For example, the radiopaque agent 22 may have a total mass between 0.15 g and 100 g, for example, between 30 g and 60 g, or for example, about 43 g. The polymer material 20 may have a sodium phosphate solution concentration of at least 20 w / w%, for example, at least 40 w / w%, or for example, at least 50 w / w%. For example, the sodium phosphate solution 23 may have a total mass between 100 g and 300 g, for example, between 150 g and 200 g, for example, about 179 g.

[0182] In STEP 1120 shown in Figure 13, a cover is placed on the container and the polymer material 20 is preheated to a temperature above the softening point of the polymer material. In some embodiments, the polymer material 20 is preheated to a temperature between 50°C and 120°C, for example between 60°C and 95°C, for example to about 65°C.

[0183] In STEP 1130 shown in Figure 13, the polymer material 20 is mixed into a homogeneous mixture. The polymer material 20 may be mixed using a mixing device such as a high-speed double asymmetric centrifuge (e.g., the mixing device 602 described herein). In some embodiments, the polymer material 20 is centrifuged at 2000 rpm for 10 minutes. During centrifugation, the polymer material 20 may be heated, for example to a temperature between 50°C and 120°C, for example to a temperature between 80°C and 100°C, for example to about 95°C. In STEP 1140 shown in Figure 13, the polymer material 20 is cooled, for example to a temperature between 16°C and 24°C (e.g., to room temperature).

[0184] In STEP 1150 shown in Figure 13, the polymer material 20 is cut into two or more segments (hereinafter referred to as "segments") or otherwise divided. The two or more segments may have similar or dissimilar sizes and / or shapes. In some embodiments, the segments include cubes of about 1 cm.

[0185] Referring here to Figure 14, a method 1200 for extruding a polymer is shown, which is consistent with the concept of the present invention. Method 1200 may be configured to extrude a polymer material produced by the aforementioned method 1100, referring here to Figure 13.

[0186] In STEP 1210 shown in Figure 14, the extruder (for example, the extruder 500 as described herein) is positioned perpendicular to the tube extractor (for example, the tube extractor 604 as described herein).

[0187] In STEP 1220 shown in Figure 14, a fluid trough (e.g., trough 606 as described herein) is positioned close to the surface of the extruder die head 502. In some embodiments, the trough 606 is positioned about 15 cm away from the extruder die head 502. The trough 606 may contain (e.g., at least partially filled) an alcohol solution for introduction into the polymer material 20. The alcohol solution may be cooled to a temperature between -20°C and 20°C, for example between 0°C and 15°C, for example 10°C. In some embodiments, the alcohol solution is configured to solidify the polymer material 20.

[0188] The trough 606 may further contain hydrophilic and / or hydrophobic polymer solutions for introduction into the polymer material 20. In some embodiments, the hydrophilic polymer solution may be configured to swell or otherwise expand the polymer material 20 so that the polymer material 20 can introduce further polymer solutions (e.g., hydrophilic, hydrophobic polymer solutions).

[0189] In some embodiments, a second trough 606 is positioned adjacent to the first trough 606 described herein. The second trough 606 may contain a hydrophilic and / or hydrophobic polymer solution for introduction into the polymer material 20. In some embodiments, a third trough 606 is positioned adjacent to the second trough 606 described herein. The third trough 606 may contain an alcohol solution for incorporation into the polymer material 20. The alcohol solution may be cooled to a temperature between -20°C and 20°C, for example, between 0°C and 15°C, such as when cooled to a temperature of about 10°C. In some embodiments, the alcohol solution is configured to dewell the polymer material in order to "lock in," for example, the hydrophilic and / or hydrophobic polymer solution.

[0190] In STEP 1230 shown in Figure 14, one, two, or more zones of the extruder 500 are set to one, two, or more temperature profiles. For example, the extruder 500 can consist of four zones, the first zone can provide a temperature of approximately 80°C, the second zone can provide a temperature of approximately 95°C, the third zone can provide a temperature of approximately 95°C, and the fourth zone can provide a temperature of approximately 40°C. In some embodiments, at least one zone constitutes the die head 502 of the extruder 500.

[0191] In STEP 1240 shown in Figure 14, the segment from STEP 1114 is supplied to the extruder 500. The extruder 500 (e.g., the auger 504 of the extruder 500) may be configured to operate at a rotational speed between 1 rpm and 100 rpm, for example between 2 rpm and 40 rpm, or for example, about 10 rpm. The extruder 500 (e.g., the screw 506 of the extruder 500) may be configured to operate at a rotational speed between 5 rpm and 120 rpm, for example between 20 rpm and 80 rpm, or for example, about 60 rpm. The extruder 500 may be configured to maintain the pressure at the tip of the screw 506 between 20 psi and 2000 psi, for example between 100 psi and 200 psi. The extruder 500 may be configured to have a melting temperature at the tip of the extruder screw 506 between 70°C and 110°C, for example between 80°C and 85°C.

[0192] In STEP 1250 shown in Figure 14, the polymer material 20 is drawn out through the extruder die head 502 and trough 606 to form an extruded tube, such as a hollow extruded tube (e.g., a tube with walls surrounding one, two, or more lumens) or a solid extruded tube (e.g., a tube without lumens). The extruded material may be drawn out through the extruder die head 502 and trough 606 at a speed of 0.25 m / min to 10 m / min, for example, 1 m / min to 4 m / min, for example, about 2 m / min.

[0193] As used herein, unless otherwise indicated, “extruded tube,” “extruded material,” and “extruded segment” refer to a hollow tube containing a single lumen. Method 1200 is understood to be modifiable to produce a solid extruded tube (avoiding, for example, the insertion of mandrels 614, filaments 608, etc.). Furthermore, Method 1200 is understood to be modifiable to produce a hollow extruded tube containing multiple lumens (with, for example, the insertion of multiple mandrels 614, filaments 608, etc.).

[0194] In some embodiments, the polymer material 20 is drawn through an extruder die head 502 that forms a hollow tube arranged around a solid filament (e.g., the filament 608 described herein). The solid filament 608 may include a material selected from the group consisting of acetal, silicone, polytetrafluoroethylene, fluorinated ethylene propylene copolymer, polyether ether ketone, polyamide, stainless steel, nitinol, silver, copper, and combinations thereof.

[0195] In some embodiments, the extruded material is further pulled through an air blade (e.g., the air blade 610 described herein) configured to remove the alcohol solution from the surface of the extruded material (e.g., the alcohol solution in the trough 606 described herein). In some embodiments, the extruded material is further pulled through a tube extractor 604 as described herein. For example, the extruded material may be pulled through the extruder die head 502, through the trough 606, through the air blade 610, and then through the tube extractor 604.

[0196] In some embodiments, various drawing and forming techniques are applied to the extruded material during the extrusion process. The drawing and forming techniques may be configured to provide the extruded material with anisotropic mechanical compliance.

[0197] In STEP 1260 shown in Figure 14, the extruded material is cut or otherwise divided (hereinafter referred to as “extruded segment”). In some embodiments, the extruded segment has a length of about 90 cm.

[0198] In STEP 1270 shown in Figure 14, the extruded segment is placed in an alcohol bath (e.g., the alcohol bath 612 described herein) for a period of 10 minutes to 48 hours, for example, 3 hours to 24 hours, for example, for a duration of about 16 hours. The alcohol bath 612 may be a room temperature bath.

[0199] Referring here to Figure 15, a method 1300 for hydrophilic treatment of a polymer material is shown, consistent with the concept of the present invention. Method 1300 may be configured to hydrophilic treat an extruded material produced by Method 1200 described herein, with reference to Figure 14.

[0200] In STEP 1310 of Figure 15, the filament 608 (if present within the extrusion segment) is removed from the extrusion segment so that the associated extrusion segment includes the lumen through which it passes.

[0201] In STEP 1320 of Figure 15, a mandrel (e.g., the mandrel 614 described herein) is slidably positioned within the extrusion segment. A mechanical interlock connector (e.g., the connector 120 described herein) may be inserted into one end of the extrusion segment (e.g., positioned at the proximal end of the conduit 101 and configured to fluidly attach to a syringe, infusion line, or other fluid delivery device or conduit).

[0202] In STEP 1330 of Figure 15, the extruded segment is dried in a convection oven (e.g., oven 620 as described herein). In some embodiments, the extruded segment is dried in a convection oven 620 for a period of 1 to 24 hours at a temperature between 20°C and 100°C, for example, 55°C for 3 hours.

[0203] In some embodiments, as described above herein with reference to Figures 10A to 10C, a first clamp 200 secures a first end of the extruded segment, and a second clamp 200 secures a second end of the extruded segment. The first clamp 200 (e.g., cavities 228, 248) can engage with the inner bars of the upper drying rack (e.g., the upper rack 622a described herein), and the second clamp 200 (cavities 228, 248) can engage with the inner bars of the lower drying rack (e.g., the lower rack 622b described herein), so that the extruded segment extends from the upper drying rack 622a to the lower drying rack 622b. In this embodiment, the clamps 200 are used in combination to prevent twisting or other axial deformation of the extruded segment during this process (e.g., the clamps 200 are used in combination to straighten the extruded segment during this process).

[0204] In STEP 1340 of Figure 15, the external thermal shrinkage (e.g., the band 122 described herein) is positioned on or around the interface between the mechanical interlock connector 120 and the extruded segment. In some embodiments, and before proceeding to STEP 1350, the mandrel 614 is slidably removed from the extruded segment.

[0205] In some embodiments, one, two, or more markings (e.g., the markings 112 described herein) are formed along the length of the extruded segment. The markings 112 may be configured to expand and contract in conjunction with the expansion and contraction (e.g., swelling and de-swelling) of the extruded segment. The markings 112 can be positioned relative to a point on the extruded segment. For example, a solid-state laser (e.g., the laser 616 described herein) may be configured to apply one, two, or more dashes, dots, or other markings 112 (e.g., markings 112 placed at regular intervals to provide a “ruler” to assist in the depth of device insertion into a patient) along the length of the extruded segment.

[0206] In STEP 1350 of Figure 15, the extruded segment is placed in a hydrophilic immersion chamber (e.g., the immersion chamber 618 described herein). The hydrophilic immersion chamber may be configured to facilitate the introduction of a hydrophilic polymer into at least a portion of the extruded segment. In some embodiments, the hydrophilic immersion chamber 618 contains a poly(acrylic acid) solution (e.g., the solution 631 described herein) so that the acrylic acid solution is introduced into the extruded segment. For example, the hydrophilic immersion chamber 618 may contain a 1 w / w% solution of poly(acrylic acid) in 5x concentrated phosphate-buffered saline. In some embodiments, and before proceeding to STEP 1360, the extruded segment is slidably received by a mandrel 614.

[0207] In STEP 1360 of Figure 15, the poly(acrylic acid) solution passes through the extrusion segment and circulates around it. In some embodiments, the poly(acrylic acid) solution is circulated at a temperature of approximately 37°C for a period of 16 to 20 hours.

[0208] In some embodiments, one, two, or more agents are introduced into the extrusion segment. The agents may be configured to provide the extrusion segment with dual or more functionalities. The agents may be configured to act, function, and interact with patient tissue, for example, to promote at least one of tissue adhesion, ingrowth, and coagulation. In some embodiments, the agents are configured to bind to at least one of collagen and albumin. In some embodiments, the agents are configured as precursors configured to bind to specific proteins. Furthermore, or alternatively, the agents may be configured to reduce thrombosis along at least a portion of the extrusion segment. Each of the agents may be introduced along a specific length, portion, and / or region of the extrusion segment.

[0209] A first method for introducing the agent may include treating the hydrophilic polymer described herein with reference to STEP 1350 and 1360, and then exfoliating the first hydrophilic polymer from at least a portion of the extruded segment. In some embodiments, STEP 1350 and 1360 are repeated with the agent so that the agent is introduced to the portion from which the first hydrophilic polymer has been exfoliated. Additional agents may be introduced in the same manner (e.g., the first agent is exfoliated from at least a portion of the extruded segment). In other embodiments, the agent is applied in particular to at least a portion of the extruded segment from which the hydrophilic polymer has been exfoliated. Further agents may be introduced in the same manner (e.g., applied in particular to at least a portion of the extruded segment that does not contain the hydrophilic polymer and / or the first agent).

[0210] A second method for introducing the agent may include treating the hydrophilic polymer as described herein with reference to STEP 1350 and 1360, with one or more portions of the extruded segment excluded from the treatment or otherwise shielded, so that the hydrophilic polymer is not introduced into the excluded portions. In some embodiments, STEP 1350 and 1360 are repeated with the agent so that the agent is introduced into the excluded portions. Additional agents may be introduced in the same manner (e.g., one or more portions of the extruded segment are excluded from the first agent or otherwise shielded). In other embodiments, the agent is applied specifically to the excluded portions. Additional agents may be introduced in the same manner (e.g., specifically to the excluded portions that do not contain the hydrophilic polymer and / or the first agent).

[0211] As a non-limiting example, the first hydrophilic polymer may be introduced along at least a portion of the interior (e.g., lumen) of the outer segment and configured to reduce thrombosis. The second hydrophilic polymer may be introduced along at least a portion of the exterior of the extruded segment and configured to promote tissue adhesion and / or inward growth. In this example, the interior of the extruded segment is configured to be non-thrombotic, while the exterior is configured to interact with the surrounding tissue.

[0212] Referring here to Figure 16, a method 1400 for annealing a material is shown, which is consistent with the concept of the present invention. Method 1400 may be configured to anneal a material produced in the aforementioned method 1300, referring here to Figure 15.

[0213] In STEP 1410 of Figure 16, the extruded segment is removed from the hydrophilic immersion chamber 618.

[0214] In some embodiments, one, two, or more plasticizers (e.g., the plasticizer 29 described herein) are introduced into the extruded segment. The plasticizer 29 may be configured to prevent, or otherwise reduce, cracking and / or shattering of the extruded segment.

[0215] In STEP 1420 of Figure 16, a mandrel (e.g., mandrel 614 as described herein) is slidably positioned within the extrusion segment. In some embodiments, the mandrel includes a non-stick surface such as a PTFE coating. In some embodiments, the mandrel includes a nickel-titanium alloy. The mandrel may include any designated shape to produce a shape-memory shape that conforms to the extrusion segment. In some embodiments, the mandrel has a non-cylindrical and / or non-circular cross-section such that the lumen of the associated extrusion segment is configured to assume the non-cylindrical and / or non-circular shape of the mandrel. In some embodiments, the mandrel has a diameter that varies along the length of the mandrel. In some embodiments, the mandrel has a non-linear shape (e.g., a curved shape, a bent shape, or other composite shape) such that the associated extrusion segment is configured to assume the non-linear shape of the mandrel. For example, the mandrel may have a relative "S" shape as described herein with reference to Figure 9. In some embodiments, the mandrel includes an oversized mandrel (e.g., a mandrel having an outer diameter larger than the lumen diameter of the segment) configured to stretch or otherwise expand the diameter of the wall of the associated extruded segment. This stretching of the wall of the extruded segment may be configured to provide anisotropic mechanical compliance to the extruded segment and / or to provide other effects described later herein in relation to applying a pressure difference across the entire wall of the extruded segment.

[0216] Furthermore, or alternatively, a pressure difference (a pressure difference between the inner and outer surfaces of the wall) can be applied across the entire wall of the extruded segment (e.g., an increased pressure applied into the lumen and / or a decreased pressure applied to the outside of the extruded segment) to expand the wall of the extruded segment radially (e.g., similar to the expansion caused by the insertion of the mandrel 614 described herein, so that the insertion of the mandrel is not required to produce the desired effect). The pressure difference may be configured to allow for an increase in crystallinity that is significantly formed during the compression of the polymer material 20 as bound water is removed. The increase in crystallinity may correlate with an increase in strength and / or a decrease in equilibrium water content. The pressure difference may be applied by a pressurizing device (e.g., the pressurizing device 640 described herein). In some embodiments, a higher pressure is applied to the lumen of the extruded segment and a lower pressure is applied to the outer surface of the extruded segment. Furthermore, or alternatively, the pressure difference can be increased by locking (or confining) one, two or more fluids into the lumen of the extruded segment. To lock the fluid into the lumen, each end of the extruded segment may be sealed or otherwise closed. The locking fluid may be configured to swell in response to an increase in temperature. The locking fluid may include a fluid selected from the group consisting of dimethylacetamide, dimethyl sulfoxide, silicone oil, mineral oil, air, nitrogen, argon, and combinations thereof. The locking fluid may include a non-solvent having a phase transition temperature below 0°C. The locking fluid may include a non-solvent having a phase transition temperature greater than 180°C.

[0217] In STEP 1430 of Figure 16, the extruded segment is dried and / or annealed. Drying and / or annealing may be performed thermally, for example, in a convection oven 620. The drying time may generally be selected as desired, for example, 30 minutes or longer. In some embodiments, the extruded segment is dried in a convection oven 620 at a temperature of 30°C to 100°C for 1 to 24 hours, for example, 55°C for 3 hours. Annealing may also be performed at a higher temperature (e.g., above 100°C). Annealing may be performed at atmospheric pressure.

[0218] In some embodiments, as described above herein with reference to Figures 10A to 10C, a first clamp 200 secures a first end of the extruded segment, and a second clamp 200 secures a second end of the extruded segment. The first clamp 200 (e.g., cavities 228, 248) can engage with the inner bars of the upper drying rack (e.g., the upper rack 622a described herein), and the second clamp 200 (cavities 228, 248) can engage with the inner bars of the lower drying rack (e.g., the lower rack 622b described herein), allowing the extruded segment to extend from the upper drying rack 622a to the lower drying rack 622b. In this embodiment, the clamps 200 are used in combination to prevent twisting or other axial deformation of the extruded segment during the process (e.g., the clamps 200 are used in combination to straighten the extruded segment during the process).

[0219] In some embodiments, one, two, or more markings (e.g., marking 112 as described herein) are formed along the length of the extruded segment. The marking 112 may be configured to expand and contract with the expansion and contraction (e.g., swelling and de-swelling) of the extruded segment. For example, one, two, or more droplets of a dye solution (e.g., solution 634 as described herein) can be deposited along the length of the extruded segment. The dye solution may be configured to penetrate the extruded segment to a depth between 10 μm and 200 μm, for example between 50 μm and 60 μm. The dye solution may contain 0.01 w / w% to 5.0 w / w% of "Reactive Black 5" in USP water, for example, 0.2 w / w% of "Reactive Black 5" in USP water, and may be deposited by a blunt (or non-pointed) needle, such as a 24-gauge needle. In some embodiments, the dye solution is configured to dry under ambient conditions for at least 10 minutes, for example, about 2 hours, before proceeding to STEP 1440. In some embodiments, the dye solution may contain 0.01 w / w% to 5.0 w / w% of "Reactive Black 5" in the poly(acrylic acid) solution from STEP 1350 or 1360.

[0220] In STEP 1440 of Figure 16, the extruded segment is annealed in a convection oven (e.g., oven 620 as described herein). In some embodiments, the extruded segment is annealed in a convection oven 620 for about 90 minutes at a temperature between 120°C and 200°C, for example, about 150°C, for a period of 30 minutes to 24 hours.

[0221] In some embodiments, as described above herein with reference to Figures 10A to 10C, a first clamp 200 secures a first end of the extruded segment, and a second clamp 200 secures a second end of the extruded segment. The first clamp 200 (e.g., cavities 228, 248) can engage with the inner bars of the upper drying rack (e.g., the upper rack 622a described herein), and the second clamp 200 (cavities 228, 248) can engage with the inner bars of the lower drying rack (e.g., the lower rack 622b described herein), allowing the extruded segment to extend from the upper drying rack 622a to the lower drying rack 622b. In this embodiment, the clamps 200 are used in combination to prevent twisting or other axial deformation of the extruded segment during this process (e.g., the clamps 200 are used to tension the extruded segment during this process).

[0222] In some embodiments, the extruded segments are annealed using selective or gradient heating. The gradient heating may be configured to provide differential mechanical properties (e.g., compliance) along the length of the extruded segment. In some embodiments, the gradient may be generated by a convection heating element directed towards a portion of the extruded segment. In some embodiments, the extruded segments may be placed inside the oven 620 such that a portion of the extruded segment is outside the oven 620. In some embodiments, the extruded segments are annealed using selective or gradient solvent exposure and / or extraction of solvent components (e.g., salts, additives, secondary hydrophilic polymers, etc.). The selective or gradient exposure and / or extraction may be configured to provide differential mechanical properties (e.g., compliance) along the length of the extruded segment.

[0223] In some embodiments, the extruded segments are subsequently exposed to a hydrophilic polymer solution (e.g., solution 633 as described herein). The hydrophilic polymer solution may include aqueous solutions selected from the group consisting of polyvinyl alcohol, polyvinylpyrrolidone, polyethylene glycol, polyacrylic acid, polyacrylamide, hydroxypropyl methacrylamide, polyoxazoline, polyphosphate, polyphosphazene, poly(vinyl acetate), polypropylene glycol, poly(N-isopropylacrylamide), polysaccharides, sulfonated hydrophilic polymers, such as sulfonated polyphenylene oxide, sulfonated tetrafluoroethylene, sulfobetaine methacrylate, and combinations thereof. In some embodiments, the aqueous solution further contains iodine. The hydrophilic polymer solution may have a temperature of at least 45°C, for example, about 70°C. In some embodiments, the extruded segments undergo a second drying in a convection oven (e.g., oven 620 as described herein). The extruded segments may be dried in a convection oven at a temperature of about 55°C for about 3 hours. In some embodiments, the extruded segment undergoes a second annealing in a convection oven 620. This second annealing may be configured to increase the overall strength of the extruded segment (compared to the first annealing). The extruded segment may undergo the second annealing in the convection oven 620 at a temperature of at least 120°C for about 90 minutes. The second annealing temperature may be at least 30°C higher than the temperature of the first annealing performed in STEP 1440.

[0224] In some embodiments, an axial stretching device (e.g., the stretching device 650 described herein) is configured to apply axial tension to the extruded segment during annealing. Applying axial tension to the extruded segment may be configured to provide the extruded segment with anisotropic mechanical compliance.

[0225] In STEP 1450 of Figure 16, the extruded segment is placed in a buffer solution (e.g., solution 632 as described herein). The buffer solution may include a solution at room temperature. In some embodiments, the extruded segment remains in the buffer for about 60 minutes. The buffer solution may include a solution selected from the group consisting of PBS, physiological saline, monosodium phosphate, disodium phosphate, trisodium phosphate, Ringer's lactate injection, and combinations thereof.

[0226] In STEP 1460 of Figure 16, the extruded segment is dried in a convection oven (e.g., oven 620 as described herein). In some embodiments, the extruded segment is dried in the convection oven 620 at approximately 55°C for approximately 3 hours.

[0227] In some embodiments, as described above herein with reference to Figures 10A to 10C, a first clamp 200 secures a first end of the extruded segment, and a second clamp 200 secures a second end of the extruded segment. The first clamp 200 (e.g., cavities 228, 248) can engage with the inner bars of the upper drying rack (e.g., the upper rack 622a described herein), and the second clamp 200 (cavities 228, 248) can engage with the inner bars of the lower drying rack (e.g., the lower rack 622b described herein), allowing the extruded segment to extend from the upper drying rack 622a to the lower drying rack 622b. In this embodiment, the clamps 200 are used in combination to prevent twisting or other axial deformation of the extruded segment during this process (e.g., the clamps 200 are used in combination to straighten the extruded segment during this process).

[0228] In STEP 1470 of Figure 16, the extruded segment is removed from the mandrel 614.

[0229] Referring here to Figure 17, a method 1500 for overmolding a material is shown, which is consistent with the concept of the present invention. Method 1500 may be configured to overmolde a material produced by the aforementioned method 1400, referring here to Figure 16.

[0230] In STEP 1510 of Figure 17, the molded core-pin (e.g., the pin 661 described herein) is slidably positioned within the extruded segment (the combined pin 661 and extruded segment are referred to herein as the “overmolded assembly”). In some embodiments, the molded core-pin 661 includes an extension tube and a Luer connector.

[0231] In STEP 1520 of Figure 17, the overmolding assembly is placed in a molding machine (e.g., the molding machine 660 described herein). In some embodiments, the molding machine 660 comprises a reciprocating screw injection molding machine. The molding machine 660 may be configured to apply the overmolding material 665 onto the overmolding assembly.

[0232] In STEP 1530 of Figure 17, the overmolded assembly is removed from the molding machine 660. Furthermore, the core-pin 661 is removed from the extrusion segment.

[0233] In some embodiments, one, two, or more markings (e.g., the markings 112 described herein) are formed along the length of the extruded segment. The markings 112 may be configured to expand and contract in conjunction with the expansion and contraction (e.g., swelling and de-swelling) of the extruded segment. The markings 112 can be positioned relative to a point on the extruded segment. For example, a solid-state laser (e.g., the laser 616 described herein) may be configured to apply one, two, or more dashes, dots, and / or other markings 112 (e.g., markings 112 arranged at regular intervals to provide a “ruler” to assist in the depth of device insertion into the patient) along the length of the extruded segment.

[0234] Figures 23A and 23B show photographs of exemplary marked catheters in one embodiment.

[0235] Referring here to Figure 18, an example of method 1600 for humidifying a material, consistent with the concept of the present invention, is illustrated. Method 1600 may be configured to humidify a material produced by method 1500 described herein with reference to Figure 17.

[0236] In STEP 1610 of Figure 18, the extruded segment is placed in a surfactant solution (e.g., the surfactant solution 635 described herein). In some embodiments, the extruded segment remains in the surfactant solution for about 3 hours. The surfactant solution 635 may include a solution containing 10 w / w% poloxamer 407 in 1x concentration (1×)PBS, or a solution containing 30 w / w% glycerol in 1x concentration PBS. In some embodiments, the surfactant solution 635 is maintained at a temperature between 20°C and 70°C, for example between 37°C and 55°C, for example around 45°C.

[0237] In STEP 1620 of Figure 18, the extruded segment is removed from the surfactant solution.

[0238] In STEP 1630 of Figure 18, the mandrel (e.g., mandrel 614 as described herein) is slidably positioned within the extrusion segment. In some embodiments, the mandrel 614 includes a non-stick surface such as a PTFE coating.

[0239] In STEP 1640 of Figure 18, the extruded segment is dried in a convection oven (e.g., oven 620 as described herein). In some embodiments, the extruded segment is dried in the convection oven 620 at approximately 30°C for approximately 3 hours.

[0240] In some embodiments, as described above with reference to Figures 10A to 10C, a first clamp 200 secures a first end of the extruded segment, and a second clamp 200 secures a second end of the extruded segment. The first clamp 200 (e.g., cavities 228, 248) can engage with the inner bars of the upper drying rack (e.g., the upper rack 622a described herein), and the second clamp 200 (cavities 228, 248) can engage with the inner bars of the lower drying rack (e.g., the lower rack 622b described herein), allowing the extruded segment to extend from the upper drying rack 622a to the lower drying rack 622b. In this embodiment, the clamps 200 are used in combination to prevent twisting or other axial deformation of the extruded segment during this process (e.g., the clamps 200 are used in combination to straighten the extruded segment during this process).

[0241] In STEP 1650 of Figure 18, the extruded segment is removed from the mandrel 614.

[0242] In some embodiments, the extruded segments are freeze-dried. Freeze-drying may be configured to prevent, or otherwise reduce, swelling of the extruded segments during subsequent rehydration (e.g., when a fluid comes into contact with the extruded segments). In some embodiments, the extruded segments from STEP 1650 are frozen at a temperature below 0°C, then drawn into a vacuum of less than 5 torr, such as less than 500 mtorr, and the extruded segments are heated to a temperature above 0°C, such as about 25°C, to allow the sublimation of ice from the extruded segments.

[0243] In STEP 1660 of Figure 18, the extruded segment (e.g., conduit 101) is placed in a protective sleeve for packaging. The extruded segment may be sterilized prior to placement in the protective sleeve. In some embodiments, the extruded segment is sterilized by ethylene oxide exposure, peroxide exposure, peracetic acid exposure, gamma ray, X-ray radiation, or electron beam radiation. Alternatively, the extruded segment may be hydrated before placement in the protective sleeve. In some embodiments, the extruded segment is hydrated by a hydration device 300 as described above in this specification with reference to Figures 1, 4A and / or 4B.

[0244] While the conduit 101 has been described primarily in the context of device 100, including catheter devices (e.g., elongated tubes having a lumen), it will be further understood that the conduit 101 using the manufacturing, hydration, and other methods described herein may include a variety of tubular (e.g., hollow or solid) and non-tubular shapes.

[0245] The embodiments described herein should be understood to be for illustrative purposes only, and further embodiments are conceivable. Any feature described herein in relation to any one embodiment may be used alone or in combination with other features described herein, or in combination with any one or more other features of the embodiment, or any other combination of features of the embodiment. Furthermore, equivalents and modifications not described above may also be adopted without departing from the scope of the invention as defined in the appended claims.

[0246] In some embodiments, the compositions and articles described herein (e.g., article 1710 in Figure 19, article 1712 in Figure 20) include a polymer material comprising a first water-soluble polymer having a plurality of pores and a second water-soluble polymer, which is the same as or different from the first water-soluble polymer, disposed within at least a portion of the plurality of pores. While not wishing to be bound by theory, in some embodiments, the presence of the second water-soluble polymer disposed within at least a portion of the plurality of pores of the first water-soluble polymer may reduce the thrombogenicity of the article and / or increase its lubricity compared to an article without the second water-soluble polymer disposed within the pores (e.g., article 1710 in Figure 19, article 1712 in Figure 20) (all other factors equal). In an exemplary set of embodiments, the first water-soluble polymer is polyvinyl alcohol. In another exemplary set of embodiments, the second water-soluble polymer is polyacrylic acid. Other water-soluble polymers are also possible, as described herein.

[0247] In some embodiments, the articles and compositions described herein are administered to a subject. In some embodiments, the articles may be administered orally, rectally, vaginally, nasally, intravenously, subcutaneously, or urethrally. In some embodiments, the articles may be administered into the subject's cavity (e.g., venous system), epidural space, and / or abscess.

[0248] As described herein, in some embodiments, the compositions and articles described herein include a polymer material comprising a first water-soluble polymer having a plurality of pores. For example, as shown in Figure 19, article 1710 comprises a polymer material having a plurality of pores 1730, comprising a first water-soluble polymer 1720. In some embodiments, a second water-soluble polymer 40 is located within at least a portion of the plurality of pores (e.g., at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98%, at least 99%, at least 99.99%). In some embodiments, the second water-soluble polymer 1740 is located within 100%, 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20%, or 10% of the plurality of pores 30. Combinations of the above ranges are also possible.

[0249] In some embodiments, the second water-soluble polymer is located within the bulk of the first water-soluble polymer (e.g., within the pores and / or gaps of the first water-soluble polymer). In some embodiments, as shown in Figure 20, the second water-soluble polymer 1740 may be present as a coating 1745 on at least a portion of the surface of the polymer material 1720. Although Figure 20 shows the second water-soluble polymer as a coating on the first water-soluble polymer and within the pores of the first water-soluble polymer, it should be understood that in some embodiments, only the coating 1745 is present, and the pores 1730 are not substantially filled with the second water-soluble polymer 1740. Other configurations are also possible.

[0250] In some embodiments, article 1710 and / or article 1712 may be hollow (e.g., including a hollow core 1725). However, although Figures 19 and 20 are shown with a hollow core, those skilled in the art will understand from the teachings herein that such a hollow core may not be present. That is, in some cases, the core 1725 of the article may be a bulk material without a hollow core 1725.

[0251] In some embodiments, the plurality of pores (e.g., pores in an article, or pores in a first water-soluble material, optionally having a second water-soluble polymer disposed within at least a portion of the pores) have a specific average pore size. In some embodiments, the average pore size of the plurality of pores is 500 nm or less, 450 nm or less, 400 nm or less, 350 nm or less, 300 nm or less, 250 nm or less, 200 nm or less, 150 nm or less, 100 nm or less, 75 nm or less, 50 nm or less, 25 nm or less, 20 nm or less, or 15 nm or less. In some embodiments, the plurality of pores have an average pore size of 10 nm or more, 15 nm or more, 20 nm or more, 25 nm or more, 50 nm or more, 75 nm or more, 100 nm or more, 150 nm or more, 200 nm or more, 250 nm or more, 300 nm or more, 350 nm or more, 400 nm or more, or 450 nm or more. Combinations of the above ranges are also possible (e.g., less than 500 nm, greater than 10 nm). Other ranges are also possible. The average pore size described herein may be determined by mercury intrusion porosimetry of a dehydrated material (i.e., having less than 5 w / w% water).

[0252] In some embodiments, at least a portion of the plurality of pores may be characterized as nanopores, for example, pores having an average cross-sectional dimension of less than 1 μm. In some embodiments, at least a portion of the plurality of pores may be characterized as micropores, for example, pores having an average cross-sectional dimension of less than 1 mm and 1 μm or more. In some embodiments, at least 50% (e.g., at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98%, at least 99%, at least 99.9%) of the plurality of pores have a diameter of less than 1 μm, 800 nm or less, 600 nm or less, 500 nm or less, 450 nm or less, 400 nm or less, 350 nm or less, 300 nm or less, 250 nm or less, 200 nm or less, 150 nm or less, 100 nm or less, 75 nm or less, 50 nm or less, 25 nm or less, 20 nm or less, or 15 nm or less. In some embodiments, at least 50% of the multiple pores have diameters of 10 nm or more, 15 nm or more, 20 nm or more, 25 nm or more, 50 nm or more, 75 nm or more, 100 nm or more, 150 nm or more, 200 nm or more, 250 nm or more, 300 nm or more, 350 nm or more, 400 nm or more, 450 nm or more, 500 nm or more, 600 nm or more, or 800 nm or more. Combinations of the above ranges are also possible (e.g., 1000 nm or less, 10 nm or more). Other ranges are also possible.

[0253] The compositions and articles described herein may have a specific porosity, for example, a porosity in a dehydrated state. In some embodiments, the article (or polymer material) has a porosity of 5% or more, 10% or more, 15% or more, 20% or more, 25% or more, 30% or more, 35% or more, 40% or more, or 45% or more in a dehydrated state. In some embodiments, the article (or polymer material) has a porosity of 50% or less, 45% or less, 40% or less, 35% or less, 30% or less, 25% or less, 20% or less, 15% or less, or 10% or less in a dehydrated state. Combinations of the above ranges are also possible (for example, 5% or more, 50% or less in a dehydrated state). Other ranges are also possible.

[0254] As described herein, in some embodiments, the article (or polymer material) is substantially non-thrombogenic.

[0255] In some embodiments, the article (or polymer material (e.g., polymer material 1720 in Figures 19-20)) is hydrophilic. As used herein, the term “hydrophilic” is given its common meaning in the art and means a material surface having a water contact angle less than 90 degrees, as determined by an angle measurement method (or goniometry). In some embodiments, the surface of the polymer material of the article has a water contact angle of 45 degrees or less, 40 degrees or less, 35 degrees or less, 30 degrees or less, 25 degrees or less, 20 degrees or less, 15 degrees or less, 10 degrees or less, 5 degrees or less, or 2 degrees or less at equilibrium water content. In some embodiments, the surface of the polymer material has a water contact angle of 1 degree or more, 2 degrees or more, 5 degrees or more, 10 degrees or more, 15 degrees or more, 20 degrees or more, 25 degrees or more, 30 degrees or more, 35 degrees or more, or 40 degrees or more at equilibrium water content. Combinations of the above ranges are also possible (e.g., 1 degree or more, 45 degrees or less). Other ranges are also possible.

[0256] As used herein, equilibrium water content state means the steady state of an article (or material) whose bulk water content does not increase (e.g., absorb) or decrease, as determined when submerged in water at 25°C without any externally applied mechanical stress. Those skilled in the art will understand that a steady state (or equilibrium water content state) does not require absolute conformity to the strict thermodynamic definition of such term, but rather demonstrates conformity to the thermodynamic definition of such term to the extent possible with respect to a subject characterized in a manner that is most understandable to those skilled in the art (e.g., by considering factors such as passive diffusion and / or Brownian motion).

[0257] In some embodiments, the article is substantially lubricating at equilibrium water content. For example, in some embodiments, the article (or polymer material of the article) has a surface roughness (Ra) of 1000 nm or less at equilibrium water content. In some embodiments, the article (or polymer material of the article) has a surface roughness (Ra) of 500 nm or less, 400 nm or less, 300 nm or less, 250 nm or less, 200 nm or less, 150 nm or less, 100 nm or less, 50 nm or less, 25 nm or less, 10 nm or less, or 5 nm or less at equilibrium water content. In some embodiments, the article (or polymer material of the article) has a surface roughness (Ra) of 5 nm or more, 10 nm or more, 25 nm or more, 50 nm or more at equilibrium water content. In some embodiments, the article (or polymer material of the article) has a surface roughness (Ra) of 100 nm or more, 150 nm or more, 200 nm or more, 250 nm or more, 300 nm or more, 400 nm or more, or 500 nm or more at equilibrium water content. Combinations of the above ranges are also possible (for example, 5nm or more, 1000nm or less). Other ranges are also possible.

[0258] In some embodiments, the article has a surface having a coefficient of friction of 0.10 or less in an equilibrium water content state. For example, the coefficient of friction of the surface of the article (or the polymer material of the article) is 0.1 or less, 0.09 or less, 0.08 or less, 0.07 or less, 0.06 or less, 0.05 or less, 0.04 or less, 0.03 or less, or 0.02 or less. In some embodiments, the coefficient of friction of the surface of the article (or the polymer material of the article) is 0.01 or more, 0.02 or more, 0.03 or more, 0.04 or more, 0.05 or more, 0.06 or more, 0.07 or more, 0.08 or more, or 0.09 or more. Combinations of the above ranges are also possible (e.g., 0.1 or less, 0.01 or more). Other ranges are also possible.

[0259] Advantageously, the compositions and articles described herein may exhibit low sorption of substances such as therapeutic agents (and / or proteins, for example) in the presence of dynamic fluids containing such substances. Such articles and compositions may be useful, for example, for use in a subject where the presence of the article should not substantially reduce the availability and / or concentration of the therapeutic agent delivered to the subject (e.g., by the article). In some embodiments, administration of a therapeutic agent via a fluid flowed into an article described herein does not substantially reduce the concentration of the therapeutic agent in the fluid. In some aspects, the article may not absorb and / or adsorb the therapeutic agent, for example, during flow or use.

[0260] In some embodiments, no more than 0.5 w / w% of the therapeutic agent sorbs to the surface and / or bulk of the first water-soluble polymer, as determined by equilibrium water content after exposing the polymer to the therapeutic agent and vigorously flushing with 5 times the volume of the article of an aqueous solution, such as water or physiological saline. In some embodiments, no more than 0.5 w / w%, no more than 0.4 w / w%, no more than 0.3 w / w%, no more than 0.2 w / w%, or no more than 0.1 w / w% of the therapeutic agent sorbs to the surface and / or bulk of the first water-soluble polymer. In some embodiments, at least 0.05 w / w%, at least 0.1 w / w%, at least 0.2 w / w%, at least 0.3 w / w%, or at least 0.4 w / w% of the therapeutic agent sorbs to the surface and / or bulk of the first water-soluble polymer. Combinations of the above ranges are also possible (for example, 0.5 w / w% or less, and 0.05 w / w% or more). Other ranges are also possible.

[0261] Advantageously, the articles and compositions described herein may have desirable swelling properties (e.g., in water, physiological saline, or the fluid environment of a subject).

[0262] In some embodiments, the articles described herein are in a dehydrated state. For example, in some embodiments, the articles (or polymer materials) described herein have a water content of 5 w / w% or less, 4 w / w% or less, 3 w / w% or less, 2 w / w% or less, 1 w / w% or less, 0.8 w / w% or less, 0.6 w / w% or less, 0.4 w / w% or less, or 0.2 w / w% or less in a dehydrated state. In some embodiments, the articles (or polymer materials) described herein have a water content of 0.1 w / w% or more, 0.2 w / w% or more, 0.4 w / w% or more, 0.6 w / w% or more, 0.8 w / w% or more, 1 w / w% or more, 2 w / w% or more, 3 w / w% or more, or 4 w / w%. Combinations of the above ranges are also possible (e.g., less than 5 w / w%, 0.1 w / w% or more). Other ranges are also possible. As described herein, a dehydrated state generally refers to a steady state determined under ambient conditions in which the article (or polymer material) does not experience a significant decrease in water content of less than 5 w / w% over a 24-hour period. In some embodiments, the articles described herein may include coatings such as water-retaining coatings or unbound pologens, as described in more detail below.

[0263] Advantageously, the articles and compositions described herein may be configured to swell rapidly in the presence of an aqueous solution such as water and / or physiological saline. In some embodiments, the article (or polymer material, e.g., polymer material 1720 of FIGS. 19-20) swells from a dehydrated state to an equilibrium water content state at 25°C in an amount of at least 5 w / w%, at least 10 w / w%, at least 15 w / w%, at least 20 w / w%, at least 25 w / w%, at least 30 w / w%, at least 35 w / w%, at least 40 w / w%, or at least 45 w / w%, for example within a specific period of time (e.g., 60 minutes or less), as described in more detail below. In some embodiments, the article (or polymer material) is configured to swell from a dehydrated state to an equilibrium water content state at 25°C in an amount of at most 50 w / w%, at most 45 w / w%, at most 40 w / w%, at most 35 w / w%, at most 30 w / w%, at most 25 w / w%, at most 20 w / w%, at most 15 w / w%, or at most 10 w / w%, for example within a specific period of time (e.g., 60 minutes or less), as described in further detail below. Combinations of the above ranges are also possible (e.g., at least 5 w / w% and at most 50 w / w%). Other ranges are also possible.

[0264] In some embodiments, the article (or polymer material, e.g., polymer material 1720 of FIGS. 19-20) is configured to swell from a dehydrated state to an equilibrium water content state in an amount of at least 5 w / w% within 60 minutes or less, 50 minutes or less, 40 minutes or less, 30 minutes or less, 20 minutes or less, 10 minutes or less, 5 minutes or less, or 2 minutes or less at 25°C. In some embodiments, the article (or polymer material) is configured to swell from a dehydrated state to an equilibrium water content state in an amount of at least 5 w / w% over at least 1 minute, at least 2 minutes, at least 5 minutes, at least 10 minutes, at least 20 minutes, at least 30 minutes, at least 40 minutes, or at least 50 minutes at 25°C. Combinations of the above ranges are also possible (e.g., 60 minutes or less and at least 1 minute). Other ranges are also possible.

[0265] In exemplary embodiments, the article (or polymer material (e.g., polymer material 20 in Figures 19-20)) is configured to swell in water from a dehydrated state (e.g., less than 5 w / w%) to an equilibrium water content (e.g., 5 w / w%) in 60 minutes or less. In some embodiments, the article (or polymer material) is configured to swell in standard physiological saline from a dehydrated state (e.g., less than 5 w / w%) to an equilibrium water content (e.g., 5 w / w%) in 60 minutes or less. In another exemplary embodiment, the article (or polymer material) is configured to swell in normal physiological saline from a dehydrated state (e.g., less than 5 w / w%) to an equilibrium water content (e.g., 5 w / w%) in 60 minutes or less.

[0266] In some embodiments, the article (or polymer (e.g., polymer 1720 in Figures 19-20)) has a specific length in a dehydrated state. In some embodiments, the article (or polymer material) has an increase in overall length at an equilibrium water content of 0.1% or more, 0.5% or more, 1% or more, 2% or more, 4% or more, 6% or more, 8% or more, 10% or more, 12% or more, 14% or more, 16% or more, or 18% or more compared to the length in a dehydrated state. In some cases, the article (or polymer material) has an increase in overall length at an equilibrium water content of 20% or less, 18% or less, 16% or less, 14% or less, 12% or less, 10% or less, 8% or less, 6% or less, 4% or less, 2% or less, 1% or less, or 0.5% or less compared to the length in a dehydrated state. Combinations of the above ranges are also possible (e.g., 0.1% to 20%). Other ranges are also possible.

[0267] In some embodiments, the article (or polymer material (e.g., polymer material 1720 in Figures 19-20)) has a specific maximum outer cross-sectional dimension, such as the outer diameter, in a dehydrated state. In some embodiments, the article (or polymer material) has an increase in the maximum outer cross-sectional dimension (e.g., outer diameter) at equilibrium water content states of 0.1% or more, 0.5% or more, 1% or more, 2% or more, 4% or more, 6% or more, 8% or more, 10% or more, 12% or more, 14% or more, 16% or more, or 18% or more compared to the maximum cross-sectional dimension (e.g., outer diameter) in a dehydrated state. In some cases, the article (or polymer material) has an increase in the maximum cross-sectional dimension (e.g., outer diameter) at equilibrium water content states of 20% or less, 18% or less, 16% or less, 14% or less, 12% or less, 10% or less, 8% or less, 6% or less, 4% or less, 2% or less, 1% or less, or 0.5% or less compared to the maximum cross-sectional dimension (e.g., outer diameter) in a dehydrated state. Combinations of the above ranges are also possible (for example, 0.1% to 20%, 0.1% to 10%). Other ranges are also possible.

[0268] In some embodiments, the article (or polymer material) has a specific inner diameter in a dehydrated state (e.g., in embodiments where the article has a hollow core). In some embodiments, the article (or polymer material) has an increase in inner diameter at equilibrium water content of 0.1% or more, 0.5% or more, 1% or more, 2% or more, 4% or more, 6% or more, 8% or more, 10% or more, 12% or more, 14% or more, 16% or more, or 18% or more compared to the inner diameter in a dehydrated state. In some cases, the article (or polymer material) has an increase in inner diameter at equilibrium water content of 20% or less, 18% or less, 16% or less, 14% or less, 12% or less, 10% or less, 8% or less, 6% or less, 4% or less, 2% or less, 1% or less, or 0.5% or less compared to the inner diameter in a dehydrated state. Combinations of the above ranges are also possible (e.g., 0.1% to 20%). Other ranges are also possible.

[0269] In some embodiments, the article comprises a polymer material having desirable mechanical properties. For example, in some embodiments, the polymer material has a Young's modulus in a dehydrated state (e.g., with a water content of less than 5 w / w%) of 500 MPa or more, 600 MPa or more, 750 MPa or more, 800 MPa or more, 900 MPa or more, 1000 MPa or more, 1250 MPa or more, 1500 MPa or more, 1750 MPa or more, 2000 MPa or more, 2500 MPa or more, 3000 MPa or more, 3500 MPa or more, or 4000 MPa or more. In some embodiments, the polymer material has a Young's modulus of 5000 MPa or less, 4000 MPa or less, 3500 MPa or less, 3000 MPa or less, 2500 MPa or less, or 2000 MPa or less. It has a Young's modulus at a dehydrated state (e.g., water content less than 5 w / w%) of 1750 MPa or less, 1500 MPa or less, 1250 MPa or less, 1000 MPa or less, 900 MPa or less, 800 MPa or less, 750 MPa or less, or 600 MPa or less. Combinations of the above ranges are also possible (e.g., 500 MPa or more, 5000 MPa or less). Other ranges are also possible.

[0270] In some embodiments, the polymer material has Young's elasticity at equilibrium water content of 300 MPa or less, 250 MPa or less, 200 MPa or less, 150 MPa or less, 100 MPa or less, 75 MPa or less, 50 MPa or less, 25 MPa or less, 20 MPa or less, or 10 MPa or less. In some embodiments, the polymer material has Young's elasticity at equilibrium water content of 5 MPa or more, 10 MPa or more, 20 MPa or more, 25 MPa or more, 50 MPa or more, 75 MPa or more, 100 MPa or more, 150 MPa or more, 200 MPa or more, or 250 MPa or more. Combinations of the above ranges are also possible (e.g., 300 MPa or less, 5 MPa or more). Other ranges are also possible.

[0271] In some embodiments, the article comprises a penetrating agent. For example, in some embodiments, the penetrating agent may be added during the formation of the article (e.g., to a prepolymer). In some embodiments, the penetrating agent is present in the polymer material (e.g., after the formation of the polymer) in an amount of 0.05 w / w% or more, 0.1 w / w% or more, 0.2 w / w% or more, 0.4 w / w% or more, 0.6 w / w% or more, 0.8 w / w% or more, 1 w / w% or more, 1.2 w / w% or more, 1.4 w / w% or more, 1.6 w / w% or more, or 1.8 w / w% or more. In some cases, the penetrating agent may be present in the polymer material (for example, after the formation of the polymer material) in amounts of 2 w / w% or less, 1.8 w / w% or less, 1.6 w / w% or less, 1.4 w / w% or less, 1.4 w / w% or less, 1.2 w / w% or less, 1 w / w% or less, 0.8 w / w% or less, 0.6 w / w% or less, 0.4 w / w% or less, 0.2 w / w% or less, or 0.01 w / w% or less. Combinations of the above ranges are also possible (for example, 0.05 w / w% or more, 2 w / w% or less). Other ranges are also possible.

[0272] Non-limiting examples of suitable penetrants include phosphates, borates, sodium chloride, citrates, ethylenediaminetetraacetates, sulfites, hyposulfites, metal oxides, selenium dioxide, selenium trioxide, selenic acid, nitrates, silicates, and butanoic acid (or botanic acid).

[0273] In some embodiments, the composition (e.g., including a polymer material) does not include covalent crosslinking, as will be described in more detail below. However, in other embodiments, the composition includes physical crosslinking (e.g., interpenetration networks, molecular chain entanglement, and / or one or more bonds such as covalent bonds, ionic bonds, and / or hydrogen bonds). In a particular set of embodiments, no covalent crosslinking agent is used to form the polymer material, the first water-soluble polymer of the polymer material, and / or the second water-soluble polymer.

[0274] The first water-soluble polymer may be present in the article in any suitable amount. For example, in some embodiments, the first water-soluble polymer is present in the article in an equilibrium water content of 20 w / w% or more, 25 w / w% or more, 30 w / w% or more, 35 w / w% or more, 40 w / w% or more, 45 w / w% or more, 50 w / w% or more, 55 w / w% or more, 60 w / w% or more, 65 w / w% or more, 70 w / w% or more, 75 w / w% or more, 80 w / w% or more, 85 w / w% or more, or 90 w / w% or more. In some embodiments, the first water-soluble polymer is present in the article in amounts of 95 w / w% or less, 90 w / w% or less, 85 w / w% or less, 80 w / w% or less, 75 w / w% or less, 70 w / w% or less, 65 w / w% or less, 60 w / w% or less, 55 w / w% or less, 50 w / w% or less, 45 w / w% or less, 40 w / w% or less, 35 w / w% or less, 30 w / w% or less, or 25 w / w% or less at equilibrium water content. Combinations of the above ranges are also possible (e.g., 20 w / w% or more, 95 w / w% or less). Other ranges are also possible.

[0275] In some embodiments, the first water-soluble polymer is selected from the group comprising or consisting of poly(vinyl alcohol), poly(acrylic acid), polyethylene glycol, poly(vinylpyrrolidone), poly(methacrylate sulfobetaine), poly(acrylic sulfobetaine), poly(methacrylate carboxybetaine), poly(acrylic carboxybetaine), povidone, polyacrylamide, poly(N-(2-hydroxypropyl)methacrylamide), polyoxazoline, polyphosphate, polyphosphazene, polyvinyl acetate, polypropylene glycol, poly(N-isopropylacrylamide), poly(2-hydroxymethyl methacrylate), and combinations thereof. In an exemplary set of embodiments, the first water-soluble polymer is poly(vinyl alcohol).

[0276] In some embodiments, the polymer material comprises a mixture of a first water-soluble polymer and another (e.g., a third) water-soluble polymer. In some embodiments, the third water-soluble polymer is selected from the group comprising or consisting of poly(vinyl alcohol), poly(acrylic acid), polyethylene glycol, poly(vinylpyrrolidone), poly(methacrylate sulfobetaine), poly(acrylic sulfobetaine), poly(methacrylate carboxybetaine), poly(acrylic carboxybetaine), povidone, polyacrylamide, poly(N-(2-hydroxypropyl)methacrylamide), polyoxazoline, polyphosphate, polyphosphazene, polyvinyl acetate, polypropylene glycol, poly(N-isopropylacrylamide), poly(2-hydroxymethyl methacrylate), and combinations thereof. The first and other (e.g., third) water-soluble polymers may have different chemical compositions.

[0277] In some embodiments, the total weight of the first water-soluble polymer and another (e.g., a third) water-soluble polymer in the article is 20 w / w% or more, 25 w / w% or more, 30 w / w% or more, 35 w / w% or more, 40 w / w% or more, 45 w / w% or more, 50 w / w% or more, 55 w / w% or more, 60 w / w% or more, 65 w / w% or more, 70 w / w% or more, 75 w / w% or more, 80 w / w% or more, 85 w / w% or more, 90 w / w% or more, 95 w / w% or more, 98 w / w% or more, or 99 w / w% or more, in equilibrium water content. In some embodiments, the total weight of the first water-soluble polymer and another (e.g., a third) water-soluble polymer in the article is, in equilibrium water content, 100 w / w% or less, 99 w / w% or less, 98 w / w% or less, 95 w / w% or less, 90 w / w% or less, 85 w / w% or less, 80 w / w% or less, 75 w / w% or less, 70 w / w% or less, 65 w / w% or less, 60 w / w% or less, 55 w / w% or less, 50 w / w% or less, 45 w / w% or less, 40 w / w% or less, 35 w / w% or less, 30 w / w% or less, or 25 w / w% or less. Combinations of the above ranges are also possible (e.g., 20 w / w% or more, 100 w / w% or less). Other ranges are also possible.

[0278] In some embodiments, the ratio of the first water-soluble polymer to the third water-soluble polymer present in the article (first:third) is 100:0 or less, 99:1 or less, 95:5 or less, 90:10 or less, 80:20 or less, 70:30 or less, 60:40 or less, or 55:45 or less. In some embodiments, the ratio of the first water-soluble polymer to the third water-soluble polymer present in the article is 50:50 or more, 60:40 or more, 70:30 or more, 80:20 or more, 90:10 or more, 95:5 or more, or 99:1 or more. Combinations of the above ranges are also possible (e.g., 100:0 or less, 50:50 or more). Other ranges are also possible.

[0279] As described above and herein, in some embodiments, the article comprises a second water-soluble polymer (e.g., second water-soluble polymer 1740) disposed within at least some of the pores (e.g., multiple pores 1730) of a polymer material (e.g., polymer material 1720). In some embodiments, the second water-soluble polymer is selected from the group comprising or consisting of poly(vinyl alcohol), poly(acrylic acid), polyethylene glycol, poly(vinylpyrrolidone), poly(methacrylate sulfobetaine), poly(acrylic sulfobetaine), poly(methacrylate carboxybetaine), poly(acrylic carboxybetaine), povidone, polyacrylamide, poly(N-(2-hydroxypropyl)methacrylamide), polyoxazoline, polyphosphate, polyphosphazene, polyvinyl acetate, polypropylene glycol, poly(N-isopropylacrylamide), poly(2-hydroxymethyl methacrylate), and combinations thereof. In some embodiments, the second water-soluble polymer is poly(acrylic acid). The second water-soluble polymer may have a different chemical composition from the first (and optionally third) water-soluble polymer.

[0280] A second water-soluble polymer (e.g., second water-soluble polymer 1740) may be present in the article in any suitable amount. For example, in some embodiments, the second water-soluble polymer is present in the article in an amount of 0.05 w / w% or more, 0.1 w / w% or more, 0.2 w / w% or more, 0.5 w / w% or more, 1.0 w / w% or more, 2.0 w / w% or more, 3.0 w / w% or more, 4.0 w / w%, 5.0 w / w% or more, 10 w / w% or more, 20 w / w% or more, 30 w / w% or more, 40 w / w% or more, 50 w / w% or more, 60 w / w% or more, 70 w / w% or more, 80 w / w% or more, or 90 w / w% or more at equilibrium water content. In some embodiments, the second water-soluble polymer 40 is present in the article in amounts of 95 w / w% or less, 90 w / w% or less, 80 w / w% or less, 70 w / w% or less, 60 w / w% or less, 50 w / w% or less, 40 w / w% or less, 30 w / w% or less, 20 w / w% or less, 10 w / w% or less, 5.0 w / w%, 4.0 w / w% or less, 3.0 w / w% or less, 2.0 w / w% or less, 1.0 w / w% or less, 0.5 w / w% or less, 0.2 w / w% or less, or 0.1 w / w% or less, in equilibrium water content. In some embodiments, 0 w / w% of the second water-soluble polymer is present. Combinations of the above ranges are also possible (e.g., 0.05 w / w% or more, 95 w / w% or less). Other ranges are also possible.

[0281] In some embodiments, the water-soluble polymers (e.g., the first water-soluble polymer, the second water-soluble polymer, and the third water-soluble polymer) have specific molecular weights. In some embodiments, the molecular weights of the water-soluble polymers (e.g., independently, the first water-soluble polymer, the second water-soluble polymer, or the third water-soluble polymer) are 40 kDa or more, 50 kDa or more, 75 kDa or more, 100 kDa or more, 125 kDa or more, 150 kDa or more, 175 kDa or more, 200 kDa or more, 250 kDa or more, 300 kDa or more, 350 kDa or more, 400 kDa or more, 450 kDa or more, 500 kDa or more, 600 kDa or more, 700 kDa or more, and 800 kDa or more. The molecular weight may be 900 kDa or more, 1000 kDa or more, 1500 kDa or more, 2000 kDa or more, 3000 kDa or more, or 4000 kDa or more. In some embodiments, the molecular weight of the water-soluble polymer (for example, independently, the first water-soluble polymer, the second water-soluble polymer, or the third water-soluble polymer) is 5000 kDa or less, 4000 kDa or less, 3000 kDa or less, 2000 kDa or less, 1500 kDa or less, 1000 kDa or less, 900 kDa or less, 800 kDa or less, 700 kDa or less, 600 kDa or less, 500 kDa or less, 450 kDa or less, 400 kDa or less, 350 kDa or less, 300 kDa or less, or 250 kDa or less. The molecular weight may be 200 kDa or less, 175 kDa or less, 150 kDa or less, 125 kDa or less, 100 kDa or less, 75 kDa or less, or 50 kDa or less. Combinations of the above ranges are also possible (for example, molecular weights between 40 kDa and 5000 kDa). Other ranges are also possible.

[0282] In some embodiments, the articles (and / or polymer materials) described herein are medical devices such as catheters, balloons, shunts, wound drains, infusion ports, drug delivery devices, tubes, contraceptive devices, female hygiene devices, endoscopes, grafts, pacemakers, implantable cardiac defibrillators, cardiac resynchronization devices, cardiovascular device leads, ventricular assist devices, endotracheal tubes, tracheostomy tubes, implantable sensors, ventilator pumps, and ophthalmic devices, or are configured for use with such devices. In some embodiments, catheters are selected from the group consisting of central venous catheters, peripheral central catheters, midline catheters, peripheral catheters, peripheral port catheters, central venous port catheters, tunnel catheters, dialysis access catheters, urinary catheters, nerve catheters, epidural catheters, percutaneous transluminal angioplasty catheters, and / or peritoneal catheters. Some catheters may be suitable for drainage (or drainage, pus drainage), urination, and / or dialysis applications. Other suitable applications are described in more detail below.

[0283] In some embodiments, the article comprises a first component comprising a polymer material (e.g., comprising a water-soluble polymer), and a second component adjacent to the first component. For example, in some cases, the second component is mechanically coupled to the first component. In some such embodiments, the second component may comprise a plurality of surface features configured to mechanically retain the second component within or on the first component. In some embodiments, as shown in FIGS. 21-22, the article 3300 comprises a first component 3310 (e.g., an article such as article 1710 of FIG. 19 or article 1712 of FIG. 20) and a second component 3320 (e.g., an extension, a connector, a luer lock, a suture wing, a second article such as article 1710 of FIG. 19 or article 1712 of FIG. 20) adjacent to the first component 3310. In some embodiments, a first thermoplastic layer 3330 is disposed between the first component 3310 and the second component 3320. In some embodiments, an optional second thermoplastic layer 3340 is adjacent to the first component 3310 (e.g., in contact with an outer surface of the first component). In some cases, the second component 3320 may comprise a plurality of surface features 3350 associated with the first component 3310 such that the second component is mechanically retained (e.g., within, on, adjacent to) the first component 3310.

[0284] In some embodiments, the second component may be a connector (e.g., to a medical component and / or a medical device). In some embodiments, the second component may be selected from the group consisting of an extender, a connector, a luer lock, and a suture wing. In some embodiments, the second component may be another article such as an article described herein that comprises a polymer material.

[0285] In some embodiments, the article includes a first thermoplastic layer positioned between a first component and a second component (for example, to assist in mechanical retention between the first and second components). In some cases, the second thermoplastic layer may be in contact with the outer surface of the first component. For example, the second thermoplastic layer may cover both a portion of the second component and a portion of the first component. Each thermoplastic layer may contain a suitable thermoplastic material. In some embodiments, the first thermoplastic material and / or the second thermoplastic material may independently be polyurethane elastomers, silicone elastomers, silicone-polyurethane copolymers, polyethylene, polypropylene, styrene-isoprene butadiene copolymers, vinyl acetate homopolymers and copolymers such as ethylene vinyl acetate copolymers, polyvinyl chloride, acrylate and methacrylate homopolymers and copolymers, polyvinylpyrrolidone, 2-pyrrolidone, polyacrylonitrile butadiene, polycarbonate, and polyamide. The materials include, or are selected from, polyether block amides, fluoropolymers (including homopolymers and copolymers of polytetrafluoroethylene and polyvinyl fluoride), fluoroethylene propylene, polystyrene, homopolymers and copolymers of styrene acrylonitrile, homopolymers and copolymers of styrene butadiene, cellulose acetate, homopolymers and copolymers of acrylonitrile butadiene styrene, polymethylpentene, polysulfone, polyester, polyimide, polyisobutylene, polymethylstyrene, polyoxymethylene, and homopolymers and copolymers of polylactic acid, polyglycolic acid, and poly(caprolactone). In some embodiments, the first thermoplastic material and / or the second thermoplastic material swell at least partially in water at 25°C.

[0286] In some embodiments, the second component is thermally bonded to the first component. In some embodiments, the second component is solvent-bonded to the first thermoplastic material. In some embodiments, the solvent may be selected based on its ability to solvate both the first and / or second components. Non-limiting examples of suitable solvents include tetrahydrofuran, toluene, N,N-dimethylformamide, N,N-dimethylacetamide, chloroform, dichloromethane, ethyl acetate, acetone, acetonitrile, dimethyl sulfoxide, nitromethane, propylene carbonate, diethyl ether, 1,4-dioxane, benzene, cyclohexane, hexane, cyclopentane, pentane, formic acid, n-butanol, isopropyl alcohol, ethanol, methanol, acetic acid, hexafluoroisopropanol, trifluoroacetic acid, water, and combinations thereof. In an exemplary embodiment, a water-swellable polyurethane is solvent-bonded to a hydrophobic polyurethane using tetrahydrofuran.

[0287] In some embodiments, the second component has a Young's modulus greater than that of the first component in the dehydrated state and / or equilibrium water content state. In some embodiments, the second component has a Young's modulus greater than that of the first component in the equilibrium water content state, but less than that of the first component in the dehydrated state.

[0288] In some embodiments, the second component includes a plurality of surface features, such as protrusions or spikes. The surface features may be present at the interface between the first and second components to mechanically maintain a connection between the two components. In some embodiments, the plurality of surface features include rounded edges. In some embodiments, the plurality of surface features include rounded edges, sharp edges, blunt edges, flares, bulges, and / or raised features. In some embodiments, the plurality of surface features consist of a plurality of barbs (or spikes) and / or bulges (or raised features). Other surface features are also possible.

[0289] In some embodiments, the multiple surface features may have a specific radius of curvature (for example, on a surface adjacent to the first component). For example, in some cases, at least some of the multiple surface features have a radius of curvature of 0.1 times, 0.2 times, 0.3 times, 0.5 times, 0.7 times, 0.9 times, 1 time, 1.1 times, 1.2 times, 1.5 times, 2 times, 2.5 times, 3 times, 3.5 times, 4 times, or 4.5 times or more the radius of curvature of the inner surface of the article (for example, the hollow part of the article). In some embodiments, at least some of the surface features have a radius of curvature of 5 times or less, 4.5 times or less, 4 times or less, 3.5 times or less, 3 times or less, 2.5 times or less, 2 times or less, 1.5 times or less, 1.2 times or less, 1.1 times or less, 1 time or less, 0.9 times or less, 0.7 times or less, 0.5 times or less, 0.3 times or less, or 0.2 times or less than the radius of curvature of the inner surface of the article (e.g., the hollow part of the article). Combinations of the above ranges are also possible (e.g., 0.1 times or more, 5 times or less). Other ranges are also possible.

[0290] In some embodiments, the joint strength between the first and second components (for example, at the interface between the first and second components) is 10N or greater, 15N or greater, 20N or greater, 25N or greater, 30N or greater, 40N or greater, 50N or greater, 60N or greater, 70N or greater, or 75N or greater. In some embodiments, the joint strength is 100N or less, 75N or less, 70N or less, 60N or less, 50N or less, 40N or less, 30N or less, 25N or less, 20N or less, or 15N or less. Combinations of the above ranges are also possible (for example, 10N or greater, 100N or less). Other ranges are also possible. The joint strength may be determined by determining the maximum load at fracture using an INSTRON tensile testing machine (Model 3343, 500N load cell) with a pneumatic grip of 40 psi and a grip strength of 1 kN. The components are pulled at a rate of 400 mm / min, starting with a gap distance of 20 mm.

[0291] In some embodiments, the interface between the first and second components is fluidically sealed. For example, in some embodiments, the interface between the first and second components is configured to withstand injection pressures of 50 psi or more, 75 psi or more, 100 psi or more, 125 psi or more, 150 psi or more, 175 psi or more, 200 psi or more, 225 psi or more, 250 psi or more, 300 psi or more, or 350 psi or more (injection of fluid through the first component into the second component which is fluidically connected to the first component). In some embodiments, the interface between the first and second components is configured to withstand injection pressures of 500 psi or less, 400 psi or less, 350 psi or less, 300 psi or less, 250 psi or less, 225 psi or less, 200 psi or less, 175 psi or less, 150 psi or less, 125 psi or less, 100 psi or less, or 75 psi or less. Combinations of the above ranges are also possible (for example, 50 psi or more, 500 psi or less). Other ranges are also possible.

[0292] As described herein, in some embodiments, the article includes at least one first thermoplastic layer positioned between a first component and a second component. In some embodiments, the second component is positioned on or adjacent to the first component before the sorption of the second water-soluble polymer. In some embodiments, the second component is positioned on or adjacent to the first component after the sorption of the second water-soluble polymer and after the second water-soluble polymer has been re-extracted with a solvent. In some embodiments, the article comprises a first component including a water-soluble polymer and a plurality of pores; a second component including a first thermoplastic material positioned within at least a portion of the plurality of pores; and a third component including a second thermoplastic material relative to (e.g., adjacent, directly adjacent to, or on) the second component.

[0293] These materials can be manufactured as tough, high-strength materials with lubricating and biocompatible surfaces. Nanoporous and microporous solids, particularly those with high Young's modulus and tensile strength, are described herein. Nanoporous materials are solids containing interconnected pores with a diameter of 100 nm or less. Methods for manufacturing hydrogels are also described. Hydrophilic polymers may be used to manufacture these various porous solids so that hydrophilic solids are obtained. The water content of nanoporous or microporous solids may be high, for example, 50 w / w% EWC. The water content of hydrogels may be even higher, for example, 90 w / w% or less in principle. Porous solid materials can be used in the manufacture of various devices such as medical catheters and implants, where the adsorption and / or adhesion of biomolecules to their surface is significantly reduced.

[0294] These or other porous materials may be treated to include polymers that are bulk-incorporated into the pores of the solid. One embodiment of the material is a porous material containing water-soluble polymers incorporated into the pores of the material. Polymers incorporated in this way have been observed to reside within the pores and remain there even after repeated hydration and dehydration. The incorporated polymers provide a scratch-resistant, virtually permanent surface, and the incorporated polymers provide desirable properties beyond the outer surface of the material. In aqueous media, hydrophilic polymers incorporated in this way hydrate and spread beyond the surface, improving biocompatibility and lubricity.

[0295] Methods for producing the material may include extrusion molding so that high aspect ratio devices may be created. Embodiments of methods for producing the material include heating a mixture comprising at least one water-soluble polymer and a solvent to a temperature above the melting point of the polymer solution forming the mixture in a solvent-removal environment resulting in a crosslinked matrix, and continuing to remove the solvent until the crosslinked matrix becomes a microporous or nanoporous solid material. Crosslinking may be carried out while cooling the mixture and / or in a solvent-removal environment. Further polymers may be incorporated into the pores of the material.

[0296] Articles described herein (e.g., catheters) may be manufactured using any preferred method. Exemplary methods for manufacturing such catheters are described, for example, in U.S. Patent Application Publication No. 2018 / 0369454, entitled "High Strength Porous Materials Incorporating Water Soluble Polymers," and U.S. Patent Publication No. 2020 / 0230295, entitled "High Strength Porous Materials for Controlled Release," which are incorporated herein by reference for all purposes.

[0297] Those skilled in the art who read this disclosure can adapt the principles in light of what is known about extrusion or other molding techniques to produce alternative methods and devices that achieve the same end products as described herein. Scaled-up embodiments of this method can be adapted, for example, for use in a multi-zone screw extruder, where the solvent mixture is supplied by a suitable injector or hopper, and the zones are controlled to supply low-temperature extruders. Mechanisms such as syringe pumps can be replaced by suitably metered liquid or solid polymer supply systems.

[0298] In some embodiments, the methods described herein are free of freeze-thaw steps and / or freezing steps and / or thawing steps. Furthermore, the methods may be used to produce solid porous materials that swell little to no, even in the absence of a covalent crosslinking agent, for example, having a swelling of 0 to 100 w / w% in EWC. Those skilled in the art will immediately understand that all ranges and values ​​between the specified boundaries are intended, for example, any of 0, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 95, and 100 w / w% can be used as upper or lower limits, and swelling is % swelling = 100 × (Gross weight in EWC - Dry weight) / Dry weight (In the formula, dry weight is the weight of the material excluding water.) It is measured as follows.

[0299] In some embodiments, the extruded sample has a horizontal polymer chain orientation and arrangement along the length of the sample (extrusion direction). The polymer chain orientation is formed by the extrusion process. While we do not wish to be constrained by theory, in some embodiments, this horizontal chain orientation and arrangement along the length of the sample is thought to contribute to an increase in inner and / or outer diameter at a rate greater than the increase in length when the sample swells.

[0300] In some embodiments, it is useful to have one or more combinations of extrusion of the hydrophilic polymer in a solvent, cold extrusion, and extrusion into a bath to rapidly remove the solvent from the extruded material. Furthermore, in some embodiments, additional solvent removal and / or annealing treatments provide further utility for producing a desired porous solid.

[0301] In some embodiments, the requirements for nanoporous materials include high polymer concentrations exceeding about 10 w / w% in the polymer-solvent mixture with a high level of crosslinking. Those skilled in the art will immediately understand that all ranges and values ​​between the expressed boundaries are contemplated, and that any of 10, 12, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 80, 90, 95, or 99 w / w% of the polymer in the total weight of the polymer-solvent mixture is available as an upper or lower limit. In some embodiments, the polymer is substantially solvated, i.e., a true solution, meaning that at least half of the polymer is dissolved and the remainder is at least suspended. In some embodiments, the solvation of the polymer contributes to the arrangement of polymer chains in extrusion and to crosslinking between polymers. Without being bound by any particular theory, it is considered that high concentrations of the starting polymer-solvent mixture can assist in this. Furthermore, according to some embodiments, the stochastic chain arrangement of the material as it passes through the die is thought to further promote intrapolymer and interpolymer crosslinking. In some embodiments, the extruded material or mixture formed by other means entering a solvent-removal environment, whether gaseous or liquid, is thought to further break down the pore structure before the densely concentrated polymer is fully crosslinked, thereby improving chain proximity and promoting a higher crosslinking density. Directly adhering the extruded material or material formed by other means to a solvent-removal environment is useful in some embodiments. In some embodiments, further solvent removal may be continued to break down the material until a desired endpoint in structure and / or properties is reached. Annealing treatment may further contribute to strength in some embodiments.

[0302] On the other hand, the freezing method improves strength by creating ultra-concentrated microregions that also achieve chain proximity and enhance crosslinking density, while forcing the retention of macroporosity due to the presence of ice crystals in the overall gel structure. Desolvent removal forces the formation of ultra-concentrated microregions, but these do not form macropores. On the other hand, gels pre-formed before dehydration or freezing will form macropores due to the nature of the method. Furthermore, our research has shown that such nanoporous solids have greater strength than macroporous materials.

[0303] Hydrogels may also be manufactured by using lower polymer concentrations in the polymer-solvent mixture, generally less than 10 w / w% of the polymer in the polymer-solvent mixture. Those skilled in the art will immediately understand that all ranges and values ​​between the specified boundaries are contemplated, and that, for example, any of 2, 5, 7, 8, 9, or 10 w / w% of the polymer in the total weight of the polymer-solvent mixture is available as an upper or lower limit. Furthermore, or alternatively, the polymer-solvent mixture is not extruded into a solvent removal environment.

[0304] Microporous materials may be manufactured using intermediate process conditions between those for nanoporous solids and hydrogels. One embodiment involves manufacturing the material using conditions equivalent to those for manufacturing nanoporous materials, but stopping the solvent removal before it reaches a nanoporous solid structure.

[0305] Extruding hydrophilic polymers in a solvent is useful for creating high-strength materials. Using solvents as starting materials in extrusion molding is, at least, not common. Generally, extrusion molding uses solid materials that have been heated to a flowable temperature, extruded, and then cooled in various ways. For example, thermoplastic extrusion of pure PVA is considered possible. However, such extrusions lack the polymer structure necessary to create porous solids and instead exhibit properties closer to conventional thermoplastic materials. According to the theory of operation, extrusion of pure PVA lacks the quality of hydrogen bonding that occurs in an aqueous ionic solvent state. At temperatures suitable for making PVA fluid in extrusion molding, poorly cohesive material is produced in the die head, and continuous shapes cannot be formed. Furthermore, it is difficult to form high aspect ratio shapes, such as tubes, from extruded PVA, making it unsuitable for extrusion molding. PVA and other hydrophilic polymers have high viscosity and are difficult to dissolve. In particular, a narrow working temperature range, such as 85-95°C, has been observed to be effective. Below approximately 85°C, PVA cannot truly melt and therefore cannot become completely amorphous for extrusion molding. Above 95°C, losses due to boiling and evaporation rendered this method ineffective. While these temperature ranges can be compensated for by increasing the pressure above atmospheric pressure, the use and expansion of pressurized systems are difficult. This method is most effective when implemented at temperatures below the boiling points of the polymer and solvent materials.

[0306] The cohesive force of the flowing polymer-solvent mixture was weak when exiting the die. To maintain its shape in the die, it is effective to use a core to support the mixture in the die. This condition is in contrast to typical core extrusion, which is used, for example, as a coating method for coating wires for mobile phone chargers. Typical methods that avoid the use of solvents or solvents with high concentrations have relatively high cohesive force when exiting the die, which makes it easier to hold the tube in place, and do not rely on active bonds such as hydrogen bonds of hydrophilic polymers to form a cohesive shape when exiting the die.

[0307] It has been effective to pass the formed polymer-solvent mixture through a solvent-removal environment. In most extrusion processes, bath temperatures below room temperature are not used. Furthermore, the use of a solvent-removal bath is atypical compared to conventional methods, where the bath or other solvent-removal environment helps to sufficiently solidify the extruded material and keep it stable and concentrically in the core, otherwise the molten material would be teardrop-shaped. Attempting to recover it at the end of extrusion would result in destruction because it is still molten. Also, in conventional water-containing baths, PVA or similar hydrophilic polymer materials would lose their shape due to swelling, dissolution, or both. A molding process involving the preparation of a polymer-solvent mixture formed in a mold and then treated in a solvent-removal environment does not have the advantages of chain arrangement observed in extrusion. However, with suitably controlled temperature and solvent removal, it is possible to obtain a material with high strength and a controlled porosity structure.

[0308] This porous solid is highly lubricated, can be used in a hydrated state, and can readily bond with other materials. In the case of catheters, for example, extensions, Luer locks, and suture wings are useful. In some embodiments, copolymer extrusion is useful in the range where the second polymer is 0.1% to 10 w / w% or less of the first polymer, and also less than 5 w / w%. Those skilled in the art will immediately understand that all ranges and values ​​between the specified boundaries are intended, and that any of, for example, 0.1, 0.2, 0.4, 0.5, 0.8, 1, 2, 3, 4, 5, 6, 8, and 10 w / w% are available as upper or lower limits.

[0309] In some embodiments, salts are useful for manipulating the strength of materials. Without being limited to any particular theory, salts are considered to be part of physical crosslinking and essentially act as low molecular weight crosslinking agents between polymer chains.

[0310] Several embodiments relating to polymer blends include at least one first hydrophilic polymer and at least one second hydrophilic polymer in a solvent extruded as described herein. Examples include one or more combinations of PVA, PAA, PEG, PVP, polyalkylene glycol, hydrophilic polymers, and combinations thereof. Examples of concentrations include at least one second hydrophilic polymer present in amounts from 1 to 10,000 parts of the first hydrophilic polymer. Those skilled in the art will immediately understand that all ranges and values ​​between the indicated boundaries are intended, and that any of, for example, 1, 2, 10, 100, 1,000, 1,500, 2,000, 2,500, 3,000, 4,000, 5,000, 6,000, 7,000, 8,000, 9,000, and 10,000 parts are available as upper or lower limits. An example of polymer concentrations in a polymer-solvent mixture includes a first polymer present at a first concentration and one or more further polymers present at a second concentration, where the first polymer concentration and the further polymer concentrations are independently selected from 0.1 to 99%, for example, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 33, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 w / w%. Furthermore, nonhydrophilic polymers and / or nonhydrophilic blocks may be present in the block polymer, with concentrations of such polymers and / or such blocks generally less than about 10 w / w%, for example, 0.1, 0.2, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 w / w%.

[0311] Some embodiments include a porous matrix conditioned with a water-soluble polymer that loses 20–90 w / w% or more of the water-soluble polymer under comparable conditions, and those skilled in the art will readily understand that all ranges and values ​​between the explicitly stated boundaries, e.g., 20, 25, 30, 33, 40, 50, 60, 70, 80, 90 w / w%, are intended.

[0312] In some embodiments, the bulk-incorporated material may form a monolayer on the surface. The term monolayer means a layer having the thickness of a single molecule. The monolayer does not rely on intermolecular cohesive forces to remain stably present on the surface. At least one water-soluble polymer forms the monolayer. In contrast, even a thin polymer coating that is crosslinked itself has a thickness equivalent to the thickness of the network structure (or mesh) formed by the crosslinked polymer. For example, it may be possible to form a crosslinked PVA coating on a surface, but such a coating relies on the intermolecular interconnections of PVA and inevitably forms a crosslinked network structure. Thus, embodiments include water-soluble polymers present on the surface of a porous solid without covalent bonding to the surface and without the polymer being part of a network structure.

[0313] In some embodiments, bulk-incorporation polymers are introduced continuously. In contrast, a layer of water-soluble material simply adsorbed onto a sublayer material, for example, applied by dip coating or spraying, may be essentially removed from the hydrophilic substrate in most or all environments, meaning that at least 90 w / w% of the material may be separated from the sublayer material in an aqueous solution, such as physiological saline, at 90°C for 24 hours. Covalently bonded materials are not removed under these conditions, and physically crosslinked networks of water-soluble polymers may also not be removed, but such networks are undesirable compared to bulk-incorporation polymers and may result in increased thrombosis or reduced durability, for example. Covalent bonding involves using chemically reactive portions that can be avoided by the bulk incorporation process.

[0314] This specification provides methods for creating biocompatible porous solids, such as microporous or nanoporous solid materials having low protein adsorption properties, and for providing a basis for non-bioadherent devices. Modifications to the starting polymer concentration, molecular weight, solvent removal, formation method, and curing / annealing treatment may be used to provide surface properties with reduced protein adsorption and other properties. Some embodiments involve the formation of various continuous shapes by extruding polymer mixtures. The mixtures may be further cured and annealed. These steps may be used to create tough and highly lubricated materials. Embodiments include polymer mixtures extruded into shapes having one or more lumens and having various diameters and wall thicknesses.

[0315] Embodiments of a method for producing nanoporous solid materials include heating a mixture containing a polymer and a solvent (polymer mixture), extruding the mixture into a solvent-removal environment, and removing the solvent from the crosslinked matrix until a nanoporous solid material is formed. Depending on the method, one or more of these actions may be combined. Furthermore, cooling the mixture as it passes through the die is useful. Without being bound by a specific operational theory, crosslinking the polymer while it passes through the die initially appears to form a porous matrix, but since there are spaces between the polymer strands but no pore structure, it cannot be called a true nanoporous solid material. When the solvent is removed under favorable conditions, the crosslinked structure becomes a nanoporous solid. Crosslinking is initiated by extruding the polymer mixture from the die and cooling it. Crosslinking may also continue while the solvent is being removed. The transition to forming the nanoporous material occurs when the solvent is removed and is generally considered to be completed or essentially completed (meaning 90% or more) at this stage. The resulting material may be further processed by annealing, in or without the presence of additional solvents or plasticizers. This method, and other extrusion or other forming methods and / or materials specified herein, including bulk incorporation methods, may not contain one or more of the following: covalent crosslinking agents, agents that promote covalent crosslinking, radiation that crosslinks polymer chains, freezing, thawing, freeze-thaw cycles, one or more freeze-thaw cycles, ice crystal formation, foaming agents, surfactants, hydrophobic polymers, hydrophobic polymer segments, reinforcing materials, wires, blades, non-porous solids, and fibers.

[0316] Porous materials may be manufactured by an extrusion process that involves passing a polymer mixture through a die into a cooling environment. The cooling environment may further be an environment that removes the solvent. If the solvent is water, it is a dehydrated environment. The die may have a core through which the polymer mixture passes, so that it may form around the core. Further solvent removal environments and / or annealing environments may be used.

[0317] The extrusion process of the polymer-solvent mixture may be carried out as cold extrusion. Cold extrusion means a process that involves passing the polymer-solvent mixture through a die, and does not require heating the polymer-solvent mixture above its boiling point during the entire process of preparing and extruding the polymer-solvent mixture. Therefore, in cold extrusion molding, the die head is kept below the boiling point of the polymer-solvent mixture. Many solvents can be used, but water is often a useful solvent when the die head is kept below 100°C, and as mentioned above, even lower temperatures may be useful.

[0318] The term polymer mixture refers to a polymer in a solution dissolved or suspended in a solvent. The solvent may be, for example, water, an aqueous solution, an organic solvent, or a combination thereof. Heating a polymer mixture may involve heating the mixture to a temperature above the melting point of the polymer. Generally, when a solution reaches its melting point, it transitions from a cloudy state to a clear state. An aqueous solution may contain, for example, 10–100% (w / w or v / v) of liquid as water, and those skilled in the art will immediately understand that all ranges and values ​​between the indicated boundaries, e.g., 10, 20, 30, 40, 50, 60, 70, 80, or 90% or at least one of them, are intended.

[0319] Extrusion is a useful method for forming materials. Other forming methods, such as molding, casting, or thermoforming of polymer-solvent mixtures, may also be used. Generally, polymer-solvent mixtures are prepared without boiling and formed into shapes that are exposed to controlled solvent removal conditions to produce nanoporous or microporous materials using the guidelines provided herein. An annealing step may be included. Hydrogels that are not microporous or nanoporous materials can also be produced.

[0320] The heated polymer mixture may be molded, or otherwise formed while cooled, or immediately after molding / forming. Molding is a broad term referring to the transition of a material from an amorphous molten state to a final product or an intermediate shape for further processing. Molding includes casting, lamination, coating, injection molding, stretching, and extrusion. Molding can be performed by injection molding, where the mold consists of a thermally conductive material that is easily heated to increase the fluidity of the injected polymer mixture and rapidly cooled in a cooling environment. In other embodiments, the molding process may be achieved by extruding the polymer mixture through a die to form a continuous material.

[0321] Cooling a polymer mixture may include, for example, cooling an extruded material, such as when passing a polymer material through a die. Embodiments for cooling include temperatures at least 20°C below the boiling point of the polymer mixture, or alternatively temperatures below the boiling point Tm of the polymer mixture, e.g., 20, 30, 40, 50, 60, 70, 80, 90, 100, 110°C below the boiling point Tm of the polymer mixture, or alternatively, the bath or other environment being at a temperature of -50 to 30°C, and those skilled in the art will immediately understand that all ranges and values ​​between the clearly stated boundaries are intended, e.g., -50, -45, -25, -20, -10, -5, -4, 0, 15, 20, 25, 30°C, which are available as upper or lower limits. Cooling may be carried out in an environment with the solvent removed. Freezing temperatures may be avoided. Without being bound by a specific operational theory, the polymer chains are cooled to a point where intermolecular hydrogen bonding is promoted and the chain movement is fixed. This process may be carried out at a temperature of around 30°C, or even higher if time permits. The bath may be aqueous, and may be adjusted with salts or other penetrating agents to provide a penetrating value for solvent removal to aqueous materials with relatively low penetrating values ​​due to osmotic pressure and diffusion. Alternatively, the bath may be another solvent that freezes at a lower temperature than water, and it is also possible to use temperatures below 0°C without freezing the solvent or materials. When hydrophilic copolymers are used in combination with PVA, for example, crosslinking and chain immobilization occur at higher temperatures, so temperatures above 20°C may be used.

[0322] A solvent removal environment is an environment that significantly accelerates solvent removal compared to drying under ambient conditions. Such an environment may be unheated and not above ambient temperature, for example, not above 20°C. Such an environment may be a vacuum, such as a vacuum chamber, a salt bath, or a bath for removing solvent from a polymer mixture. For example, an aqueous polymer mixture may be introduced into an ethanol bath so that the ethanol is replaced by water. The ethanol may then be removed. The salt bath may be, for example, a high-salt concentration bath (1M to 6M). The processing time in the solvent removal environment and / or cooling step may be independently selected to be between 1 and 240 hours, and those skilled in the art will immediately understand that all ranges and values ​​between the specified boundaries are intended, and that any of, for example, 1, 2, 5, 10, 24 hours, or 1, 2, 5, 7, 10 days are available as upper or lower limits. The salt may be a salt that dissociates into monovalent, divalent, or trivalent ions.

[0323] An environment for removing one or more solvents may be used, or one environment may be controlled with respect to temperature. Thus, a cooling bath may be used, and then the solvent may be removed in an oven or vacuum oven. Before or after cooling or solvent removal, a washing step may be performed, for example, by immersion in a series of solvents of different concentrations, different salt solutions, different proportions of ethanol or other solvents.

[0324] The embodiment is an extruded material that has undergone a solvent removal process including exposure to a salt bath, wherein the material is immersed in a series of H2O baths (new or replaced baths) for a set period of time (e.g., 2 to 48 hours, 4 to 24 hours) to remove excess salt from the casting material or end-user device. The material is removed from the washing process and dehydrated to remove excess water. Dehydration may be carried out using a temperature in the range of 20 to 95°C, for example. Dehydration is generally carried out at 37°C for 24 hours or more.

[0325] The embodiment is a polymer mixture formed by extrusion, or otherwise by subsequent exposure to a high-concentration salt bath (1M to 6M) for a time inversely correlated with the salt concentration, where high salt concentration shortens the immersion time, for example, immersion in a 6M NaCl solution for 16 to 24 hours. After immersion, the salt solution is washed away. This makes the material tough, allowing it to be removed from mold pieces carried over from the initial formation. Alternatively, after the salt bath, the material may be immersed in a water bath to dehydrate and remove excess water. Dehydration may be carried out using a temperature in the range of 20 to 95°C. Dehydration may be carried out at 37°C for 4 hours or more, 24 hours or more, or in the range of 2 to 150 hours. A person skilled in the art will immediately understand that all ranges and values ​​between the specified boundaries are intended, and that any of the following can be used as upper or lower limits: for example, 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 16 hours, 24 hours, 48 ​​hours, 72 hours, 96 hours, 120 hours, 144 hours, or 150 hours. For example, dehydration at 40°C for 6 to 24 hours has been observed to be useful.

[0326] In another embodiment, NaCl is introduced into the starting polymer solution at a concentration ranging from 0.1 to 3 M by the volume of the final polymer mixture. The polymer is dissolved in a heated solution under stirring, and then heated above its melting point. To this solution, dry NaCl is slowly added while stirring until completely dissolved. The slightly cloudy solution is drawn into a feed for the purpose of forming a shape by injection molding, casting, extrusion and / or stretching. Quenching is performed at the end of each step to rapidly lower the temperature and form a solid material. In this embodiment, further salt soaking is not required. After the material has cured, if necessary, the material is removed from the molded part, washed to remove salt and dehydrated.

[0327] In the context of semicrystalline polymers or solid porous materials, the term annealing refers to a heat treatment at an annealing temperature comparable to the melting point of the polymer in the polymer or related material. This temperature is typically lower than the melting temperature on an absolute temperature scale, within approximately 0-15% of the melting temperature. Plasticizers or other additives can affect the melting temperature, usually by lowering it. For example, in the case of pure PVA, the annealing temperature is within approximately 10% of the melting point of PVA, and in the presence of other materials, the annealing temperature is usually lower. The operating theory of annealing is that it is a process of stress relaxation combined with an increase in the size of the crystalline regions of the material being annealed. Unlike metals, annealing increases the strength of the annealed material. Annealing may be performed in one or more of the following conditions: in air, in gas, in an oxygen-free state, in a water-free state, e.g., in nitrogen, in vacuum nitrogen, under argon, with the use of oxygen scavengers, etc. For example, experiments have been conducted to anneal dehydrated PVA nanoporous material. Annealing is used to increase the crystallinity of the PVA network structure, further reduce the pore size of the PVA network structure, and decrease the adsorption properties of the final gel surface. Annealing may be carried out at a temperature in the range of 100-200°C, for example, and in a preferred embodiment, this step is carried out by immersing the dehydrated gel in a bath of mineral oil. Bulk incorporation of polymers into porous solids may also include an annealing step as already described for porous solids. Annealing may be carried out after exposing the desolvented porous solid to a mixture having a polymer to be bulk incorporated. The Tg of the material may increase or decrease depending on the residual solvent content and / or the presence of a second hydrophilic polymer bulk incorporated. As already described, the annealing conditions can therefore be adapted to depend on the temperature, time, ramp rate, and cooling rate of the substrate.

[0328] Annealing may be performed in a gas or liquid at ambient pressure, rising pressure, or low (vacuum) pressure. The liquid may be a low molecular weight polymer (less than 2000 Da) or other material (e.g., mineral oil). Examples of low molecular weight polymers include silicone oil, glycerin, polyols, and polyethylene glycol with less than 500 Da. A useful embodiment is, for example, annealing in a glycerin bath at 140°C for 1 to 3 hours, where the glycerin acts to further reduce the contaminant properties of the gel through interaction and neutralization of the free hydroxyl terminal groups of the PVA network structure. The annealed nanoporous material is cooled, removed from the annealing bath, and washed without the bath medium using a series of long immersions. The product is then dehydrated and prepared for final sterilization.

[0329] Various types of dies may be used, for example, vertical, angular, horizontal, and spiral extrusion heads, as well as single-polymer extrusion heads used for extruding a single polymer and multi-layer extrusion heads used for the simultaneous extrusion of multiple polymer layers or other layers. Continuous heads may also be used, as well as circulating heads. Various materials, such as reinforcing materials, fibers, wires, braided materials, braided wires, and braided plastics, may be incorporated into or as layers. Similarly, such materials may be excluded. Furthermore, porous solids may have certain properties that are known and therefore measurable, apart from various other materials, such as Young's modulus, tensile strength, solids content, polymer composition, porous structure, or solvent content. Accordingly, embodiments include materials disclosed herein, described in terms of material properties, regardless of various other incorporated materials. For example, nanoporous solids have a certain known Young's modulus, even if the material has reinforcing wires that contribute further strength.

[0330] The core may be used with an extrusion die. The core may be air, water, liquid, solid, non-solvent, or gas. Those skilled in the art who read this disclosure will understand that various extrusion methods using these various types of cores may be used. Cores made of polytetrafluoroethylene (PTFE) tubing are useful. In some embodiments, the core is a wire.

[0331] Multi-lumen tubes have multiple channels running through their profile. These extrudes can be custom designed to match the device design. Multi-lumen tubes have a variable outer diameter (OD), numerous custom inner diameters (ID), and various wall thicknesses. These tubes are available in a variety of shapes, including circular, elliptical, triangular, square, semicircular, and crescent shapes. These lumens can be used in a variety of applications, such as guide wires, fluids, gases, and wires. The number of lumens in a multi-lumen tube is limited only by the size of the OD. In some embodiments, the OD can be as large as 0.5 inches, the ID as small as 0.002 inches, and the web and wall thickness can be as thin as 0.002 inches. Tight tolerances can be maintained down to ±0.0005 inches. A person skilled in the art will immediately understand that all ranges and values ​​between the indicated boundaries are intended, and that any of 0.002, 0.003, 0.004, 0.007, 0.01, 0.02, 0.03, 0.04, 0.05, 0.1, 0.2, 0.3, 0.4, and 0.5 inches are available as upper or lower limits for OD and / or ID. The tolerance may be, for example, 0.0005 to 0.1 inches. A person skilled in the art will immediately understand that all ranges and values ​​between the indicated boundaries are intended, and that any of 0.0005, 0.001, 0.002, 0.003, 0.006, 0.01, 0.02, 0.03, 0.06, 0.8, 0.9, and 1 inch are available as upper or lower limits.

[0332] Braided (or bladed) reinforced tubing can be formed in various configurations. For example, it can be braided using 0.001-inch round or flat wire, single-ended or double-ended wire. Braided reinforced tubing can be formed from a variety of materials, including stainless steel, beryllium copper, silver, and monofilament polymers. The braid can be wrapped around many thermoplastic substrates, such as nylon or polyurethane, at various picks per inch. The advantages of braided catheter shafts are high torque performance and kink resistance. Furthermore, the properties of the tubing can be modified to meet required performance by changing several elements during the braiding process. After the braiding is complete, a secondary extrusion process may be performed on the braided tubing to encase the braid and give it a smooth finish. In the case of braided reinforced tubing, a wall thickness of 0.007 inches is possible.

[0333] Porous solids such as nanoporous materials, microporous materials, and strong hydrogels may be used to form catheters or medical fibers. These may be formed from bulk-incorporated polymers and may have the various characteristics described therein. Examples of catheters include central venous catheters, peripheral central catheters, midline catheters, peripheral catheters, tunnel catheters, dialysis access catheters, urinary catheters, nerve catheters, peritoneal catheters, intra-aortic balloon pump catheters, diagnostic catheters, intervention catheters, drug delivery catheters, shunts, wound drains (external drains such as ventricular, ventricular peritoneal, and lumbar peritoneal), and infusion ports. Porous solids may also be used to make implantable devices, including permanent and temporary, fully implantable and percutaneously implanted devices. Porous solid materials may also be used to make blood-contact devices or devices that come into contact with bodily fluids (including ex vivo and / or in vivo devices, including blood-contact implants). Examples of such devices include drug delivery devices (e.g., insulin pumps), tubing, contraceptives, feminine hygiene devices, endoscopes, grafts (including small diameters <6 mm), pacemakers, implantable cardioverter-defibrillators, cardiac resynchronization devices, cardiovascular device leads, ventricular assist devices, catheters (cochlear implants, endotracheal tubes, tracheostomy tubes, drug delivery ports and tubes), implantable sensors (intravascular, percutaneous, intracranial), ventilator pumps, and ophthalmic devices such as drug delivery systems. Catheters are also used with other devices. The material may include a tubular nanoporous material having fasteners for cooperation, such as Luer fasteners or fittings. Radiopaque agents may be added to the material, fiber, or device. The term radiopaque agent refers to agents commonly used in the medical device industry to impart radiopaqueness to materials, such as barium sulfate, bismuth, or tungsten. The RO agent (radiopaque agent) may be introduced, for example, at 5 to 50 w / w% of the total solids weight, for example, 5, 10, 20, 30, 40, or 50%.

[0334] Medical fibers made from porous solid materials have applications in sutures, threads, medical fabrics, braids, meshes, woven meshes, nonwoven fabrics, and devices using them. These fibers are strong and flexible. Materials may be manufactured using these fibers to be resistant to fatigue and abrasion.

[0335] In exemplary embodiments, the method comprises administering a polymer material comprising a water-soluble polymer and having an aspect ratio of 3:1 or greater to an external orifice of a subject, wherein the administration of the article does not involve the use of a sheath introducer. The polymer material is substantially non-thrombogenic, has a water content of less than 5 w / w% and 0.1 w / w% or greater in a dehydrated state, and is configured to swell from a dehydrated state to an equilibrium water content state by an amount of 5 w / w% or greater and 50 w / w% or less in 60 minutes or less. [Examples]

[0336] Example 1 A sample of PVA extruded material was prepared by heating 200g of distilled water in a jacketed reaction vessel at 95°C. To this, 40g of PVA (Sigma, 146k-186k) was added over 5 minutes while mixing at 200 RPM. The polymer was mixed at 300 RPM for 1.5 hours. The polymer was degassed at 90°C for less than 2 hours. The polymer was then extruded into ethanol at -23°C and stored in ethanol in a freezer at -25°C for 24 hours. The sample was dried for 6 hours.

[0337] After drying, the sample was immersed in glycerol at 120°C for 17 hours. After annealing, the sample was removed, cooled, rinsed with ethanol, and the core was removed. The sample was dried at 50°C for 12 hours.

[0338] A sample of PVA containing barium sulfate was prepared by heating 50 g of water to 90°C in a jacketed reaction vessel. 4 g of barium sulfate and 50 g of water were placed in a side container and homogenized at 11 k RPM for 15 minutes, then added to the jacketed container. This was stirred and heated for 10 minutes. After heating, 16 g of PVA (Sigma, 146 k~186 k) was added and mixed at 360 RPM for approximately 2 hours.

[0339] A PVA-RO polymer mixture was heated to 90°C and extruded into ethanol at -16°C. The extruded material was dehydrated at -25°C for 24 hours. The core was removed, and the sample was dried in a 50°C incubator for approximately 6 hours. After drying, the sample was immersed in glycerol (Sigma) at 120°C for 17 hours. After annealing, the sample was removed, cooled, and washed with distilled water. The sample was dried at 50°C for 12 hours and packaged for testing.

[0340] The samples were evaluated for non-thrombotic resistance testing at Thrombodyne, Inc. (Salt Lake City, Utah). Each sample was cut to a length of 15 cm, with N=5 per sample group. Prior to testing, the samples were sterilized by ethylene oxide treatment for 12 hours. The samples were subjected to hydrostatic testing with distilled water for approximately 48 hours, simulating clinical use.

[0341] 111 Fresh bovine blood, heparinized and containing indium-labeled platelets, was divided into test and control samples for evaluation. The samples were inserted into an in vitro blood flow loop in a 0.25-inch inner diameter polyvinyl chloride tube for approximately 120 minutes. The blood was maintained at 98°C and pumped into the blood loop using a peristaltic pump during the experiment. The samples were initially checked for thrombus after 45 minutes in the blood flow loop and then removed after 120 minutes. At the end of the experiment, the device was removed from the tube, washed with saline, and placed in a gamma counter for thrombus quantification. Experimental parameters are shown in Table 1. Each experiment consisted of an independent flow system for each circulating blood sample from the same animal, allowing for simultaneous comparison without crossover effects.

[0342] The samples were measured for radioactivity and qualitatively evaluated for specific types of thrombus accumulation (i.e., adhesion or fibrin accumulation). The thrombosis rate was calculated by comparing it to the average total thrombosis rate observed in all test and control groups for each animal in which blood was circulated.

[0343] Further definition "Medically acceptable" means a non-toxic material that is highly purified to be free of contaminants. "Essentially composed" is a term used in the context of biomaterials or medical devices, meaning that other materials or components make up 3% (w / w) or less of the material or device, and that 3% does not render the device unsuitable for its intended medical use. Equilibrium moisture content (EWC) is the moisture content of a material before it degrades, when its wet weight becomes constant. Generally, materials with a high solids content are known to reach equilibrium moisture content in 24 to 48 hours. Distilled water is used to measure EWC unless otherwise specified.

[0344] The term w / v means weight per volume, e.g., g / L or mg / mL. The terms biomaterial and biomedical material are used interchangeably herein and encompass, for example, biologically acceptable materials intended for use in biomedical art for purposes such as implants, catheters, materials in contact with blood, materials in contact with tissue, diagnostic assays, medical kits, tissue sample preparation, or other medical purposes. Furthermore, materials suitable for biomedical applications are not limited to them and can also be created as general-purpose materials. Physiological saline refers to a phosphate buffer solution with a pH of 7-7.4 at 37°C and the physiological osmotic pressure of humans.

[0345] Molecular weight (MW) is measured in g / mol. For polymers, MW refers to the weight-average MW unless otherwise specified. If the polymer is part of a porous solid, the term MW refers to the polymer before crosslinking. If the distance between crosslinks is specified, it refers to the weight-average MW between crosslinks unless otherwise specified. k is an abbreviation for thousands, M for ten thousand, and G for billions; 50 kMW means 50,000 MW. Dalton is also a unit of MW and, similarly, refers to the weight-average when used for polymers.

[0346] Publications, journal articles, patents, and patent applications referenced herein are incorporated herein by reference for all purposes, and in the event of any conflict, herein shall prevail. Features of embodiments described herein may be mixed and combined as guided by the need to create a working method or product.

[0347] In this specification, the terms “therapeutic agent” or “medicine” refer to a drug administered to a subject for the treatment or prevention of a disease, disorder or other clinically recognized condition, and which has a clinically significant effect on the subject’s body to treat and / or prevent the disease, disorder or condition.

[0348] In this specification, when a component is referred to as “adjacent” to another component, it may mean that it is directly adjacent to (e.g., in contact with) that component, or that there are one or more intervening components. A component that is “directly adjacent” to another component means that there are no intervening components.

[0349] The term "subject" refers to any animal, such as a mammal (e.g., a human). Non-limiting examples of subjects include humans, non-human primates, cattle, horses, pigs, sheep, goats, dogs, cats, or rodents such as mice, rats, hamsters, birds, fish, and guinea pigs. Generally, the present invention is directed toward human use. In some embodiments, the subject may exhibit health benefits, for example, upon administration of the self-correcting article.

[0350] In this specification, “fluid” means in its ordinary sense, i.e., a liquid or a gas. A fluid cannot maintain a defined shape and flows during an observable time frame, filling the container in which it is placed. Thus, a fluid can have any suitable viscosity that allows it to flow. If two or more fluids are present, each fluid can be independently selected by a person skilled in the art from essentially any fluid (liquid, gas, etc.).

[0351] While several aspects of the present invention are described and illustrated herein, those skilled in the art will readily anticipate a variety of other means and / or structures for performing the function and / or obtaining the results and / or one or more advantages described herein, and such variations and / or improvements will each be considered within the scope of the present invention. More generally, those skilled in the art will readily understand that all parameters, dimensions, materials and configurations described herein are illustrative, and that actual parameters, dimensions, materials and / or configurations will depend on the specific application for which the teachings of the present invention are used. Those skilled in the art can recognize or confirm many equivalents to some aspects of the present invention described herein by means of routine experimentation alone. Accordingly, it should be understood that the aspects described herein are shown for illustrative purposes only and, within the scope of the appended claims and their equivalents, the present invention can be carried out in ways other than those specifically described and described in the claims. The present invention relates to individual features, systems, articles, materials, kits and / or methods described herein. Furthermore, combinations of two or more such features, systems, articles, materials, kits, and / or methods are included within the scope of the present invention, provided that such features, systems, articles, materials, kits, and / or methods do not conflict with each other.

[0352] As used in the specification and claims, the indefinite articles "a" and "an" should be understood to mean "at least one" unless explicitly stated otherwise.

[0353] As used in the specification and claims, the phrase “and / or” should be understood to mean “either or both” of the combined elements, i.e., elements that exist together in some cases and separately in the other. Unless explicitly stated, other elements may optionally exist in addition to those specifically identified by the “and / or” phrase, whether related to or unrelated to those specifically identified elements. Thus, as a non-restrictive example, when used in conjunction with an open-ended phrase such as “including ~”, it means, in one embodiment, A without B (optionally including elements other than B), in another embodiment, B without A (optionally including elements other than A), in yet another embodiment, both A and B (optionally including other elements), and so on.

[0354] As used in the specification and claims, “or” should be understood to have the same meaning as “and / or” as defined above. For example, when separating items in a list, “or” or “and / or” is inclusive, i.e., It should be interpreted that a number of elements or a list of elements includes at least one, including more than one, and optionally, any further items not listed. Only clearly indicated items, such as "only one of ~" or "exactly one of ~," or "consisting of ~" as used in claims, mean to include exactly one of a number of elements or a list of elements. In general, the term "or" as used herein should be interpreted only as indicating an exclusive choice (i.e., "one or both, but the other") when preceded by an exclusive term such as "either," "one of ~," "only one of ~," or "exactly one of ~." "Essentially consisting of ~" as used in claims has its usual meaning as it is used in the field of patent law.

[0355] As used in the specification and claims, the phrase “at least one” relating to a single list of one or more elements should be understood to mean at least one element selected from one or more elements in the list of elements, but not necessarily including at least one of each element specifically listed in the list of elements, nor necessarily excluding combinations of elements in the list of elements. This definition also allows for the possibility that there may be elements other than those specifically identified in the list of elements, meaning whether or not they are related to those specifically identified elements. Therefore, as a non-restrictive example, “at least one of A and B” (equivalently, “at least one of A or B,” or equivalently, “at least one of A and / or B”) can mean, in one embodiment, at least one including any more than one, A without B (including any elements other than B); in another embodiment, at least one including any more than one, B without A (including any elements other than A); and in yet another embodiment, at least one including any more than one, A and at least one including any more than one, B (including any other elements), and so on.

[0356] In the claims as well as in the specification, all such transitional clauses as “comprising,” “including,” “carrying,” “having,” “containing,” “involving,” and “holding” are understood to be open-ended, meaning they include but are not limited to them. Only the transitional clauses “consisting of” and “essentially consisting of” are closed or semi-closed transitional clauses, as described in the United States Patent Office Manual of Patent Examining Procedures, Section 2111.03.

[0357] The terms used herein relate, for example, to the shape, orientation, alignment, and / or geometric relationships of one or more devices, structures, forces, fields, flows, directions / trajectories, and / or their sub-components, and / or combinations thereof, and / or other tangible or intangible elements not described above that are characterized by such terms. Unless otherwise defined or indicated, absolute conformity to the mathematical definitions of such terms is not required, but rather it is understood that conformity to the mathematical definitions of such terms is to the extent possible with respect to the characterized requirements, as understood by those skilled in the art in the most relevant field. Examples of terms relating to shape, direction, and / or geometric relationships include, but are not limited to, terms describing the following: shape—e.g., circle, square, rubber box, circle / circle, rectangle / rectangle, triangle / triangle, cylinder / cylinder, ellipse / ellipse, (n) polygon / (n) polygonal body, etc.; angular direction—e.g., perpendicular, orthogonal, parallel, vertical, horizontal, collinear, etc.; contour and / or trajectory—e.g., perpendicular, orthogonal, parallel, vertical, horizontal, collinear, etc.; contour and / or trajectory (plane, coplane, hemisphere, semi-hemisphere, line, straight line, hyperbola, parabola, plane, curve, straight line, arc, sine wave, tangent / tangent, etc.); direction (north, south, east, west, etc.). The properties of the surface and / or bulk material and / or the spatial / temporal resolution and / or distribution (such as smoothness, reflectivity, transparency, clarity, opacity, rigidity, impermeability, uniformity, inertness, non-wettability, insolubility, stability, invariance, constant, homogeneity, etc.), as well as many others that are obvious to those skilled in the art. As one example, a manufactured device described herein as “square” does not require that such a device be a perfect plane or straight line and have faces or sides intersecting at exactly 90-degree angles (in fact, such a device may exist only as a mathematical abstraction), but rather the shape of such a device should be understood as approximating a “square” as mathematically defined, to the extent that it is typically achievable and attainable for the described manufacturing art, as understood by those skilled in the art or as specifically described.As another example, two or more manufactured devices described herein as “aligned” do not need to have perfectly aligned faces or sides (in fact, such devices exist only as mathematical abstractions), but rather the arrangement of such devices should be understood as approximating “aligned” as mathematically defined, to the extent that is typically achievable in the described manufacturing techniques, as understood by those skilled in the art or as specifically described. [Explanation of Symbols]

[0358] 10… System 20, 1720 ... Polymer materials 29… Plasticizer 40, 1740 ... Water-soluble polymer 99…Functional elements 100…devices 101, 110 … Conduit 101' … S-shaped conduit 102... Wall 103, 303 ... Proximal end 104 ... Proximal portion 106 … lumen 108 … Distal portion 109 … Distal end 110A ... First configuration 110B… Second configuration 112… Marking 113 ... Average shortest distance between markings 120… Connector 122… Band 160... Sutured wing 180… Package 200… Clamp 210 … biasing assembly 214 ... Arm 215 ... axis 220, 240 ... elongated members 223, 243... Part 1 224, 244... inner 225, 245 … middle part 226, 246… recessed 227, 247... Part 2 228, 248 ... Cavity 248 … hollow 260, 306 … lumen 300… Hydration devices 301... Overtube 301… Port 340 … restrictor 360 ... Fluid reservoir 365 … fluid 407... Poloxamer 500 ... Extruder 502… Extruder die head 504... Auger 506… Screw 604 … Pipe extractor 606... Trough 608… Filament 610 ... Air blade 612… Alcohol bath 614 ... Mandrel 616… Marking device (laser) 617… Ink 618... Immersion Chamber 620 ... Oven 622... rack 635 ... Surfactant solution 640 ... Chamber 650 ... Stretching machine (device) 660 … Molding machine 661… pin 665 ... Overmolding material 670… Tipper 670… Tipper 999… Functional device 1710, 1712 … Goods 1725 ... Hollow core 1745 ... Coating 2000 … Method 2010…Process 3310 … First component 3320 … Second component 3330 … First thermoplastic layer 3340 … Second thermoplastic layer 3350 … Surface features

Claims

1. A marked catheter comprising a marking that includes a plurality of distinct segments spaced apart along at least a portion of the catheter, wherein the mean shortest distance between each segment and its nearest adjacent segment is a first distance in the first configuration of the marked catheter, The steps of introducing fluid into the marked catheter, and A step of expanding at least a portion of the marked catheter from a first configuration to a second configuration. This includes performing the following: The average shortest distance between each segment and its nearest adjacent segment in the second configuration becomes the second distance. A method wherein the ratio of the second distance to the first distance is 1.02:1 or greater and 2:1 or less.

2. A marked catheter comprising a marking that includes a plurality of distinct segments spaced apart along at least a portion of the catheter, wherein the mean shortest distance between each segment and its nearest adjacent segment is a first distance in the first configuration of the marked catheter, The steps of introducing fluid into the marked catheter, and A step of expanding at least a portion of the marked catheter from a first configuration to a second configuration. This includes performing the following: The average shortest distance between each segment and its nearest adjacent segment in the second configuration becomes the second distance. The method wherein the second distance is approximately 1 mm, approximately 10 mm, approximately 100 mm, approximately 1 cm, or approximately 10 cm.

3. The method according to claim 2, wherein the second configuration is the equilibrium water content of the catheter.

4. The method according to claim 1, wherein the second distance is 0.5 cm or more and 5 cm or less.

5. The method according to any one of claims 1 to 3, wherein the fluid comprises water, Ringer's lactate solution (LRS), glucose (D5W), phosphate-buffered saline (PBS), and / or Hanks equilibrium salt solution (HBSS), saline, and physiological body fluids.

6. The method according to any one of claims 1 to 5, wherein the fluid comprises an isotonic salt solution.

7. The method according to any one of claims 1 to 6, wherein the catheter comprises a first water-soluble polymer.

8. The method according to any one of claims 1 to 7, wherein the marking comprises a second water-soluble polymer and a dye.

9. The method according to claim 8, wherein the first water-soluble polymer and the second water-soluble polymer are different.

10. The method according to claim 8, wherein the first water-soluble polymer and the second water-soluble polymer are the same.

11. An article comprising a catheter having multiple markings, The marking includes a plurality of separate segments spaced apart along at least a portion of the surface of the catheter, The article has a first structure having a first water content of 2 w / w% or more and 40 w / w% or less, and the average shortest distance between each segment in the first structure and its nearest adjacent segment is a first distance. The article has a second structure having a second water content of 20 w / w% or more and 99 w / w% or less, and the average shortest distance between each segment in the second structure and its nearest adjacent segment is the second distance. The second water content is greater than the first water content. An item in which the ratio of the second distance to the first distance is 1.02:1 or greater.

12. An article comprising a catheter having multiple markings, The marking includes a plurality of separate segments spaced apart along at least a portion of the surface of the catheter, The article has a first structure having a first water content of 2 w / w% or more and 40 w / w% or less, and the average shortest distance between each segment in the first structure and its nearest adjacent segment is a first distance. The article has a second structure having a second water content of 20 w / w% or more and 99 w / w% or less, and the average shortest distance between each segment in the second structure and its nearest adjacent segment is the second distance. The second water content is greater than the first water content. The second distance is equal to approximately 1 mm, approximately 10 mm, approximately 100 mm, approximately 1 cm, or approximately 10 cm for the articles.

13. The article according to claim 11, wherein the second configuration is the equilibrium water content of the catheter.

14. The article according to any one of claims 11 to 13, wherein the catheter comprises a first water-soluble polymer.

15. The article according to any one of claims 11 to 14, wherein the marking comprises a second water-soluble polymer and a dye.

16. The article according to claim 15, wherein the first water-soluble polymer and the second water-soluble polymer are different.

17. The article according to claim 15, wherein the first water-soluble polymer and the second water-soluble polymer are the same.

18. Articles including catheters and markings, The marking includes a plurality of separate segments spaced apart along at least a portion of the surface of the catheter, At least a portion of the catheter does not include markings. The aforementioned article does not substantially accumulate thrombi, An article wherein the level of thrombus accumulation in the marking is within 50% of the level of thrombus accumulation in the portion of the catheter that does not include the marking.

19. The article according to claim 18, wherein the catheter comprises a first water-soluble polymer.

20. The article according to claim 18 or 19, wherein the marking comprises a second water-soluble polymer and a dye.

21. The article according to claim 20, wherein the first water-soluble polymer and the second water-soluble polymer are different.

22. The article according to claim 21, wherein the first water-soluble polymer and the second water-soluble polymer are the same.

23. The aforementioned dye Tetrasodium; 4-amino-5-hydroxy-3,6-bis[[4-(2-sulfonatooxyethylsulfonyl)phenyl]diazenyl]naphthalene-2,7-disulfonic acid ("Reactive Black 5") Copper; 33-[[4-(2-hydroxyethylsulfonyl)phenyl]sulfamoyl]-2,11,20,29,39,40-hexaaza-37,38-diazanidanonacyclo[28.6.1.1 ３，１０ 1. １２，１９ 1. ２１，２８ . 0 ４，９ . 0 １３，１８ . 0 ２２，２７ . 0 ３１，３６ Tetraconta-1,3(40),4(9),5,7,10,12(39),13(18),14,16,19,21,23,25,27,29,31(36),32,34-nonadecane-6,15,24-trisulfonic acid ("Reactive Blue 21") 2-Naphthalenesulfonic acid, 7-(acetylamino)-4-hydroxy-3-[4-[2-(sulfoxy)ethyl]sulfonyl]phenyl]azo]-, disodium salt (9Cl) ("Reactive Orange 78") "Reactive Yellow 15", Disodium; 1-amino-9,10-dioxo-4-[(3-{[2-(sulfonatooxy)ethyl]sulfonyl}phenyl)amino]-9,10-dihydro-2-anthracenesulfonic acid ("Reactive Blue 19"), 1-Amino-4-[3-(4,6-dichlorotriazine-2-ylamino)-4-sulfophenylamino]anthraquinone-2-sulfonic acid ("Reactive Blue 4") "CI Reactive Red 11", 4-[2-(5-carbamoyl-1-ethyl-4-methyl-2,6-dioxopyridine-3-ylidene)hydrazinyl]-6-[(4,6-dichloro-1,3,5-triazine-2-yl)amino]benzene-1,3-disulfonic acid ("CI Reactive Yellow 86"), Tetrasodium; 6,13-dichloro-3,10-bis[[4-[(4,6-dichloro-1,3,5-triazine-2-yl)amino]sulfonatophenyl]amino]triphenodioxazine disulfonate ("CI Reactive Blue 163"), and / or The article according to any one of claims 18 to 22, comprising a compound selected from the group consisting of 5-(benzoylamino)-4-hydroxy-3-[[1-sulfo-6-[[2-(sulfoxy)ethyl]sulfonyl]-2-naphthalenyl]azo]-, tetrasodium salt ("CI Reactive Red 180").

24. The article according to any one of claims 18 to 23, wherein the marking further comprises a salt.

25. An article comprising a marking composition containing a salt, a dye, and a first water-soluble polymer.

26. The article according to claim 25, further comprising a catheter, wherein the marking composition is disposed on at least a portion of the surface of the catheter.

27. The article according to claim 26, wherein the catheter comprises a second water-soluble polymer.

28. The article according to claim 27, wherein the second water-soluble polymer includes poly(vinyl alcohol), poly(acrylic acid), polyethylene glycol, poly(vinylpyrrolidone), poly(methacrylate sulfobetaine), poly(acrylic sulfobetaine), poly(methacrylate carboxybetaine), poly(acrylic carboxybetaine), povidone, polyacrylamide, poly(N-(2-hydroxypropyl)methacrylamide), polyoxazoline, polyphosphate, polyphosphazene, polyvinyl acetate, polypropylene glycol, poly(N-isopropylacrylamide), poly(2-hydroxymethyl methacrylate), and combinations thereof.

29. The article according to claim 27, wherein the second water-soluble polymer comprises PVA.

30. The article according to any one of claims 25 to 29, wherein the first water-soluble polymer comprises poly(vinyl alcohol), poly(acrylic acid), polyethylene glycol, poly(vinylpyrrolidone), poly(methacrylate sulfobetaine), poly(acrylic sulfobetaine), poly(methacrylate carboxybetaine), poly(acrylic carboxybetaine), povidone, polyacrylamide, poly(N-(2-hydroxypropyl)methacrylamide), polyoxazoline, polyphosphate, polyphosphazene, polyvinyl acetate, polypropylene glycol, poly(N-isopropylacrylamide), poly(2-hydroxymethyl methacrylate), and combinations thereof.

31. The article according to any one of claims 25 to 30, wherein the first water-soluble polymer comprises PAA.

32. The article according to any one of claims 25 to 31, wherein the dye comprises "Reactive Black 5", "Reactive Blue 21", "Reactive Orange 78", "Reactive Yellow 15", "Reactive Blue 19", "Reactive Blue 4", "CI Reactive Red 11", "CI Reactive Yellow 86", "CI Reactive Blue 163", and / or "CI Reactive Red 180".

33. The article according to any one of claims 25 to 32, wherein the salt comprises an agent selected from the group consisting of phosphates (e.g., MSP, DSP, TSP), borates, sodium chloride, citrates, ethylenediaminetetraacetic acid, sulfites, sulfates, hyposulfites, metal oxides, selenium dioxide, selenium trioxide, selenite, selenic acid, nitrates, silicates, and butanoic acid.

34. The article according to any one of claims 25 to 33, wherein the marking composition further comprises water.

35. A step of placing a marking composition on a catheter, The steps include: attaching the marking composition to the catheter at least 10 nm in length, and Step of fixing the marking composition to the catheter. Includes, The aforementioned placement process includes automatic inkjet application. A method wherein the fixing step includes thermal annealing, heat treatment, moisture drying, freeze-drying, or a combination thereof.

36. The method according to claim 35, wherein the marking composition contains water.

37. The method according to claim 35 or 36, wherein the marking composition comprises a water-soluble polymer.

38. The method according to any one of claims 35 to 37, wherein the marking composition comprises a dye.

39. The method according to any one of claims 35 to 38, wherein the marking composition comprises a salt.

40. Articles including catheters and markings, The marking includes a plurality of separate segments spaced apart along at least a portion of the surface of the catheter, An article in which at least a portion of the marking penetrates the catheter to a depth of 10 μm to 10 mm.

41. The article according to claim 40, wherein the marking penetrates the catheter to a depth of 0.1 mm to 10 mm.

42. The article according to claim 40, wherein the catheter comprises a first water-soluble polymer.

43. The article according to any one of claims 40 to 42, wherein the marking comprises a second water-soluble polymer and a dye.

44. The article according to claim 43, wherein the first water-soluble polymer and the second water-soluble polymer are different.

45. The article according to claim 43, wherein the first water-soluble polymer and the second water-soluble polymer are the same.

46. The article or method according to any one of claims 1 to 45, wherein the second distance is equal to approximately 1 cm.

47. The article or method according to any one of claims 1 to 46, wherein the second distance is 1 mm or more.

48. The article or method according to any one of claims 1 to 47, wherein the second distance is 10 cm or more.

49. The article or method according to any one of claims 1 to 48, wherein the catheter is selected from the group consisting of a central venous catheter, a peripheral central catheter, a midline catheter, a peripheral catheter, a peripheral port catheter, a central venous port catheter, a tunnel catheter, a dialysis access catheter, a urethral catheter, a nerve catheter, a percutaneous transluminal angioplasty catheter, and a peritoneal catheter.

50. The article or method according to any one of claims 1 to 49, wherein the catheter is a venous catheter.

51. The article or method according to any one of claims 1 to 50, wherein the catheter is a catheter for the nervous system or an epidural catheter.

52. The article or method according to any one of claims 1 to 51, wherein the catheter is configured to be used for drainage, urination, and / or dialysis purposes.

53. The article or method according to any one of claims 1 to 52, wherein the marking does not crack or peel off when the marked catheter is expanded from the first configuration to the second configuration.

54. The article or method according to any one of claims 1 to 53, wherein the marking is configured such that it does not substantially indicate the accumulation of thrombus when the catheter is placed in a patient.

55. The article or method according to any one of claims 1 to 54, wherein the catheter is configured such that it does not substantially exhibit thrombus accumulation when placed in a patient.

56. The article or method according to any one of claims 1 to 55, wherein the level of thrombus accumulation relative to the marking is within 50% of the level of thrombus accumulation relative to the portion of the catheter that does not include the marking.

57. The article or method according to any one of claims 1 to 56, wherein the marking adheres to the catheter or penetrates into the catheter by a distance of 0.1 μm or more and 200 μm or less.

58. The article or method according to any one of claims 1 to 57, wherein the marking adheres to the catheter or penetrates into the catheter by 1 μm or more.

59. The article or method according to any one of claims 1 to 58, wherein the dye or pigment constitutes 0.001 w / w% or more and 1 w / w% or less of the marking.

60. The article or method according to any one of claims 1 to 59, wherein the dye or pigment constitutes 0.001 w / w% or more and 0.1 w / w% or less of the marking.

61. The article according to any one of claims 11 to 34 and 40 to 60, wherein the dye comprises a non-reactive dye.

62. The article or method according to any one of claims 1 to 61, wherein the marking is placed on a catheter by an inkjet deposition method, liquid phase growth method, pad printing method, screen printing method, electrostatic spray method, hot stamping, laser etching, and / or dip coating method.

63. The article or method according to claim 62, wherein the inkjet deposition method includes pressurized liquid deposition.

64. The article or method according to any one of claims 1 to 63, wherein the catheter is annealed.

65. The article or method according to claim 64, wherein the annealing includes thermal annealing or moisture drying.

66. The article or method according to claim 65, wherein the thermal annealing is carried out at a temperature of 90°C or higher for a period of 30 minutes or more at atmospheric pressure or lower.

67. The article or method according to any one of claims 1 to 66, wherein the first configuration has a water content of 20 w / w% or more and 40 w / w% or less.

68. The article or method according to any one of claims 1 to 67, wherein the second configuration has a water content of 3 w / w% or more and 80 w / w% or less.

69. The article or method according to any one of claims 1 to 68, wherein the ratio of the first distance to the second distance is 1.02:1 or more and 2:1 or less.

70. The article or method according to any one of claims 1 to 69, wherein the ratio of the first distance to the second distance is 1.05:1 or more and 1.10:1 or less.

71. The article or method according to any one of claims 1 to 70, wherein the catheter contains a water-retaining agent.

72. The article or method according to claim 71, wherein the water-retaining agent comprises glycerol.

73. The article or method according to any one of claims 1 to 72, wherein the catheter is rehydrated.

74. The article or method according to claim 73, wherein the catheter is hydrated with a fluid comprising water, Ringer's lactate solution (LRS), glucose (D5W), phosphate-buffered saline (PBS), and / or Hanks equilibrium salt solution (HBSS), saline, or physiological body fluid.

75. The article or method according to claim 73 or 74, wherein the hydration is carried out for 10 minutes or less.

76. The article or method according to any one of claims 1 to 75, wherein the expansion of the catheter is anisotropic with respect to the length, inner diameter, outer diameter, and / or total mass of the catheter.

77. A method comprising implanting an article according to any one of claims 11 to 34 and 40 to 76 into a patient.

78. A method comprising preparing an article according to any one of claims 11 to 34 and 40 to 77 by placing a marking composition on a catheter.

79. An article manufactured by any one of claims 1 to 10, 35 to 39, 46 to 60, and 62 to 78.

80. An article according to any one of claims 11 to 34, 40 to 76, and 79, including a tapered portion.

81. The article according to claim 61, wherein the non-reactive dye enhances the contrast between the markings on the catheter and other parts.

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