Packaging for hydrated articles and related methods

Abstract

Packaging for hydrated articles is generally provided. In some embodiments, packaging articles are provided. For example, in some embodiments, a container contains an article such as a catheter and / or a polymeric material. The disclosed packaging articles are useful, for example, for providing controlled humidity conditions for contained items, maintaining a consistent hydration level of the packaged article, and / or for improved sterilization conditions. Advantageously, in some embodiments, the packaging articles described herein can create a minimal relative humidity environment for long-term storage of the catheter or polymeric material, extending the shelf life of the catheter or polymeric material, and / or facilitating hydration of the catheter, for example, so that the catheter hydrates to its intended dimensions within a specified time. Methods for manufacturing such packaging articles are also provided.

Description

Technical Field

[0001] This technical field generally relates to, for example, packaging articles including catheters and / or polymeric materials.

Background Art

[0002] Biomaterials having high strength, low thrombogenicity, lubricious surface properties, and including a biologically active agent are useful in medical technology. The porosity of the biomaterial (or porosity, or pore fraction, or void fraction; porosity) enables both high-strength bulk materials for medical devices and channels for controlled dissolution of biologically active agents. These biological activity properties can prevent or reduce biofilm, microbial colonization, infection, fibrin sheath formation, inflammation, pain, and / or tumor growth, and / or can treat physiological conditions such as tumor shrinkage, fungal and bacterial infections, inflammation, and pain. Complications seen in such devices lengthen the hospital stay and increase the patient's morbidity and mortality. Therefore, improved devices and methods are needed.

Summary of the Invention

[0003] Packaging for hydrated articles is generally disclosed herein.

[0004] In one aspect, a packaging article is provided.

[0005] In some embodiments, the packaging article includes a container (or receptacle, or container) including a foil material and a catheter including a polymeric material, the polymeric material having a water content of 2 mass% (or w / w%) or more and 40 mass% or less, the water content being less than the equilibrium water content of the polymeric material, and the polymeric material being configured to swell in an amount of 5 mass% or more relative to (or up to, or to) the state of the equilibrium water content.

[0006] In some embodiments, the packaged article comprises a container containing foil material and a polymer material containing poly(vinyl) alcohol, wherein the polymer material has a water content of 2% by mass or more and 40% by mass or less, the water content being less than the equilibrium water content of the polymer material, and the polymer material is configured to swell by an amount of 5% by mass or more relative to its equilibrium water content.

[0007] In another embodiment, a method is provided.

[0008] In some embodiments, the method includes sealing (or sealing, closing, or closing) a catheter in a first container containing a humidity control member (or component), removing the humidity control member from the first container, and sealing the catheter in a second container, the second container containing a foil material.

[0009] In some embodiments, the method comprises encapsulating a catheter in a first container containing a humidity control member, removing the humidity control member from the first container, and resealing the first container, the first container comprising a first part containing a foil material and a second part containing a gas (or vapor) permeable polymer.

[0010] 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 figures. In the event that this specification contains any conflicting and / or inconsistent disclosures between this specification and any documents incorporated by reference, this specification shall prevail. [Brief explanation of the drawing]

[0011] Non-limiting embodiments of the present invention are described illustratively with reference to the accompanying drawings, which are schematic and not intended to be drawn to scale. In the drawings, each identical or substantially identical component shown is typically represented by a single number. For clarity, not all components are shown in every drawing, nor are all components of each embodiment of the present invention shown where illustration is not necessary for those skilled in the art to understand the invention.

[0012] Figure 1A is a schematic cross-sectional view of an exemplary device according to a series of embodiments. Figure 1B is a schematic cross-sectional view of an exemplary device containing multiple holes according to a series of embodiments. Figure 1C is a schematic cross-sectional view of an exemplary device containing multiple holes according to a series of embodiments. Figure 1D is a schematic diagram of an exemplary extruder for forming a continuous form having a side cross-section of a bath, according to a series of embodiments. Figure 1E is an enlarged view of a part of the apparatus shown in Figure 1D, depicting the die head in a perspective view from outside the bath, according to a series of embodiments. Figure 1F is an enlarged view of a part of the apparatus shown in Figure 1D, depicting a die head positioned in a bath according to a series of embodiments. Figure 1G is a schematic cross-sectional view of an exemplary apparatus according to a series of embodiments. Figure 2 is a side view of a catheter illustrating the dimensional changes before and after swelling in one embodiment. Figure 3A is a schematic diagram of the process of bulk incorporation of polymers into porous solids according to a series of embodiments. Figure 3B is a cross-section of a portion of the tube taken along line 3B-3B in Figure 3A, according to a series of embodiments. Figure 4A is a process flowchart of an embodiment in which a surface polymer is bulk incorporated into a porous solid, and includes an extrusion step for creating a porous solid according to a series of embodiments. Figure 4B is a process flowchart for an embodiment of incorporating a biological agent and a polymer into a porous solid, according to a series of embodiments. Figure 5A is a schematic cross-sectional view of an exemplary packaged article including a device, according to a series of embodiments. Figure 5B is a schematic cross-sectional view of an exemplary packaged article including a device, according to a series of embodiments. Figure 6 is a photograph of an exemplary container according to a series of embodiments. Figure 7 is a photograph of an exemplary humidity control member according to a series of embodiments. Figure 8 shows plots of equilibrium water content of exemplary articles under various conditions according to a series of embodiments. Figure 9 is a flowchart illustrating an exemplary method for preparing packaged articles according to a series of embodiments. Figure 10 is a photograph of a tray and kit assembly used to house a catheter device according to a series of embodiments. Figure 11 is a photograph of Tyvek® pouches used to package trays and kit assemblies according to a series of embodiments. Figure 12 is a photograph of a foil pouch containing a sterilized product and a humidity chip, according to a series of embodiments. Figure 13A is a photograph of a sealed foil pouch with a Tyvek® header according to a series of embodiments. Figure 13B is a photograph of a sealed foil pouch with a Tyvek® header according to a series of embodiments. Figure 14A is a schematic diagram of a series of Tyvek® pouches for use in an IR (Interventional Radiation Therapy) kit. Figure 14B is a schematic diagram of a foil pouch for use in an IR kit according to a series of embodiments. Figure 15A is a schematic diagram of a series of foil pouches for use in nursing kits and / or Max Barrier kits, according to a series of embodiments. Figure 15B is a photograph of a series of foil pouches for use in nursing kits and / or Max Barrier kits, according to a series of embodiments. [Modes for carrying out the invention]

[0013] Packaging for hydration articles is generally provided. In some embodiments, packaged articles are provided. For example, in some embodiments, the container contains articles such as catheters and / or polymer materials. Disclosed packaged articles may be useful, for example, for providing controlled humidity conditions to contained components, for maintaining a consistent level of hydration of the packaged article, and / or for improved sterile conditions. Advantageously, in some embodiments, the packaged articles described herein can create an environment of minimum relative humidity for long-term storage of catheters or polymer materials, extend the shelf life of catheters or polymer materials, and / or promote the hydration of catheters, for example, so that the catheter hydrates to its intended dimensions within a specified time. Methods for preparing such packaged articles are also provided. Packaged articles may be useful, for example, for containing devices such as catheters and / or polymer materials (including other types of medical devices formed all or partially from polymer materials). Devices, catheters, and / or polymer materials may be designed and configured for administration to a subject (or subject, or test subject) (e.g., a patient). Such devices and / or polymer materials may be substantially non-thrombotic, lubricating, and / or biocompatible.

[0014] The devices described herein may be useful for a wide range of applications, for example, including the administration of biological agents. In some embodiments, therapeutic, antimicrobial, or antiseptic agents may be incorporated into the bulk material (e.g., polymer material) of the device so that the agent is released from the bulk material. In some such embodiments, the biological agents may advantageously prevent or reduce biofilm, microbial colonization, infection, fibrin sheath formation, inflammation, pain, and / or tumor growth, and / or treat physiological conditions such as tumor reduction, fungal and bacterial infections, inflammation, and pain. The devices described herein may, in some cases, be used to make blood-contact devices or devices that come into contact with bodily fluids, including ex vivo and / or in vivo devices such as blood-contact implants. Examples of drug delivery devices in which the devices described herein may be embodied or incorporated include medical tubes, wound dressings, contraceptives, feminine hygiene products, endoscopes, grafts (including, for example, those with a diameter of 6 mm or less), pacemakers, implantable cardiac defibrillators, cardiac resynchronization devices, cardiovascular device leads, ventricular assist devices, catheters (e.g., cochlear implants, endotracheal tubes, tracheostomy tubes, ports, shunts), implantable sensors (e.g., intravascular, percutaneous, intracranial), ventilation pumps, and ophthalmic devices such as drug delivery systems.

[0015] In some embodiments, the devices described herein include a body portion. For example, as illustrated in Figure 1A, the device 10 includes a body portion 20. In some embodiments, the body portion 20 is formed from and / or includes a polymer material. The polymer material may include a first water-soluble polymer. In some embodiments, a biological agent 50 is associated with the polymer material.

[0016] In some embodiments, one or more bioactive agents are present throughout the bulk of the polymeric material (e.g., distributed throughout the polymeric material matrix). For example, in some embodiments, a first arbitrary section 52 within the cross-section of the body part 20 contains a non-zero concentration of the bioactive agent. In some embodiments, a second arbitrary section 54 within the cross-section of the body part 20, which is different from the first arbitrary section 52, contains a non-zero concentration of the bioactive agent. One of ordinary skill in the art will understand, based on the teachings herein, that the presence of the bioactive agent within the bulk of the polymeric material (e.g., embedded within the polymer matrix of the polymeric material) is not meant to imply a coating of the polymeric material with the bioactive agent, but rather, is intended to mean a bioactive agent distributed throughout the bulk of the polymeric material. However, in some embodiments, a coating containing the bioactive agent may optionally be present. Examples of sections are described in more detail below.

[0017] The body part 20, section 52, and section 54 of FIG. 1A are depicted as circular, but one of ordinary skill in the art will understand, based on the teachings herein, that the body part and other sections in the embodiments disclosed herein need not be circular, and that other cross-sectional shapes (e.g., planar, rectangular, square, elliptical, oval, S-shaped, etc.) are also possible. For example, in some embodiments, the body part is S-shaped, which may, in some cases, provide ease of implantation into a subject, achieve a lower infiltration rate, and reduce the likelihood of dislodgement within the subject.

[0018] In some embodiments, as described in more detail below, the body portion (e.g., a polymeric material) may include a plurality of pores (or apertures). The polymeric material of the body portion may include a first water-soluble polymer as described herein. In some embodiments, the biologically active agent is distributed homogeneously or heterogeneously within the polymeric material (e.g., the first water-soluble polymer) within one of the above ranges, but not within the plurality of pores. That is, in some embodiments, the plurality of pores may be substantially free of the biologically active agent. In some embodiments, the plurality of pores may contain a second biologically active agent that is the same as or different from the (first) biologically active agent present in the polymeric material (e.g., the polymeric material including the first water-soluble polymer) that forms the bulk of the device. In still other embodiments, the biologically active agent is present only within the plurality of pores.

[0019] In an exemplary set of embodiments, the device is a catheter. In some embodiments, the catheter is configured for administration to a subject. For example, in some embodiments, the catheter is formed of a polymeric material, configured for administration to a subject, and the catheter includes a biologically active agent that is distributed (e.g., homogeneously distributed) within the polymeric material. In some embodiments, the catheter includes a body portion, and the body portion is formed of a polymeric material including a first water-soluble polymer as described herein.

[0020] In some aspects, a kit is described. The kit may include any suitable article described herein. In some embodiments, the kit includes a device (e.g., any embodiment of the devices described herein or a combination thereof).

[0021] In several embodiments, a packaged article is provided. The packaged article may comprise multiple components. For example, the packaged article may comprise a container and a device (e.g., a catheter) and / or polymer material contained within the container. For example, as shown in Figure 5A, the packaged article 500 comprises a container 510 (e.g., a pouch) and a device 520 (e.g., a catheter, polymer material) contained therein. While a catheter is generally depicted in Figure 5, those skilled in the art will understand, based on the teachings herein, that the container may comprise other articles. For example, in some embodiments, the container comprises a polymer material (or an article / device containing a polymer material) as described herein.

[0022] In some embodiments, the packaged article further includes a humidity control member, such as a humidity control sponge. For example, as shown in Figure 5A, the packaged article 500 further includes a humidity control member 530. The humidity control sponge may include a woven, nonwoven, porous, and / or solid material containing water and / or a hydration (or water supply, or hydration) medium. In some embodiments, the humidity control sponge is a porous cellulose nonwoven fabric swollen with water. In some embodiments, the humidity control sponge further includes a preservative or anti-infective agent (e.g., a bleach, sodium hypochlorite, peroxide, and / or peracetic acid).

[0023] In some embodiments, the humidity control member is a reservoir (or water reservoir) associated with a container. In some embodiments, the reservoir contains a hydrating medium. In some embodiments, the reservoir is in fluid communication with the humidity control member and / or device (e.g., a catheter) while the member is packaged in the container.

[0024] In some embodiments, the kit and / or packaged article further includes a hydration medium. Non-limiting examples of suitable hydration mediums include water, Ringer's lactate solution (LRS), glucose (D5W), phosphate-buffered saline (PBS), Hanks equilibrium salt solution (HBSS), and / or isotonic salt solutions. In some embodiments, the kit and / or packaged article contains a sufficient amount of hydration medium to adequately hydrate the device and / or polymer material to EWC. In some embodiments, the hydration medium is stored in a vessel (or container), fluid reservoir, tube, syringe, bag, fluid pump, and / or packet. In some embodiments, the hydration medium is sterilized. In some embodiments, the hydration medium is buffered at or near physiological pH (e.g., 6.8–7.8).

[0025] In some embodiments, the kit and / or packaging are sterile. In some embodiments, the kit is sealed. In some embodiments, the container is sealed.

[0026] In some embodiments, the kit and / or packaged article includes instructions for use. In some embodiments, the instructions for use describe the treatment methods described herein.

[0027] In some embodiments, the kit includes packaged articles.

[0028] In some embodiments, the packaged article includes a flexible container. In some embodiments, the flexible container includes fibers such as flash-spun high-density polyethylene fibers.

[0029] In some embodiments, the packaged article includes a tray into which a device can be positioned for shipment.

[0030] In an exemplary set of embodiments, the packaged article includes a container containing foil material and a catheter containing polymer material. In another exemplary set of embodiments, the packaged article includes a container containing foil material and polymer material (e.g., poly(vinyl) alcohol). The polymer material may be used to form all or part of a device as described herein. In some embodiments, the foil material is substantially impermeable to water. Any suitable material may be used for the foil material so that the foil material is substantially impermeable to water. In some embodiments, the foil material includes aluminum, polyethylene terephthalate, or a combination thereof.

[0031] In some embodiments, the container includes a gas-permeable polymer. In some embodiments, the gas-permeable polymer includes high-density polyethylene. A non-limiting example of a suitable gas-permeable polymer includes Tyvex®.

[0032] In some embodiments, the container comprises foil material and a gas-permeable polymer. In some embodiments, the container comprises a header portion. For example, as shown in Figure 5B, the packaged article 502 comprises a container 510 comprising a header portion 540 and a second portion 550. The header portion 540 may comprise a gas-permeable polymer, and the rest of the container may comprise foil material. In some embodiments, the header portion may be useful for sterilizing the contained article (e.g., via ethylene oxide sterilization). For example, the header portion may comprise a gas-permeable material so that the contents of the container can be sterilized.

[0033] Referring again to Figure 5B, in some embodiments, the humidity control member 530 is located within the header portion 540. In some embodiments, the humidity control member is located within the second portion.

[0034] In some embodiments, the header portion may be removed (or detached; remove) (for example, after sterilization of the packaged article and / or the device contained in the container). For example, upon completion of sterilization, in some embodiments, the header portion may be removed and / or sealed (for example, so that the container contains a substantially impermeable material and / or is substantially impermeable to gases). In some embodiments, the humidity control member is removed upon completion of sterilization. For example, the header portion and the humidity control member (for example, located within the header portion) are removed (for example, simultaneously) after sterilization of the container and / or the device contained within the container.

[0035] In some embodiments, the surface area of ​​the inner surface of the container contains a substantial amount of foil material. For example, in some embodiments, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% of the surface area of ​​the inner surface of the container is foil material. In some embodiments, 100% or less, 99% or less, 98% or less, 95% or less, 90% or less, or 85% or less of the surface area of ​​the inner surface of the container is foil material. Combinations of the above ranges are also possible (e.g., 80% or more, 100% or less). Other ranges are also possible.

[0036] In some embodiments, the polymer material, catheter, or other device is housed in a container in a state that is at least partially hydrated. For example, in some embodiments, the polymer material, catheter, or other device housed in a container has a water content of 2% by mass or more and 40% by mass or less (e.g., 2% by mass or more and 12% by mass or 6% by mass or more and 12% by mass or less). In some embodiments, the water content of the polymer material, catheter, or other device is less than the equilibrium water content of the polymer material, catheter, or other device. In some embodiments, the polymer material, catheter, or other device is configured to swell by an amount of 5% by mass or more relative to its equilibrium water content. Other polymer materials and water contents are also possible and are described herein.

[0037] In some embodiments, the polymer material, catheter, or other device is housed in a container in a fully hydrated state (e.g., at equilibrium water content).

[0038] The container may have any suitable size and / or shape. In some embodiments, the container is a pouch, bag, and / or vessel (e.g., a hot oven, chamber, bottle).

[0039] In some embodiments, the catheter, device, and / or polymer material may be removed from the packaged article. In some embodiments, after removal of the packaged article, the catheter, device, and / or polymer material may be (re)hydrated (e.g., to equilibrium water content) as described herein.

[0040] In some embodiments, the packaged article may be formed by encapsulating a catheter, device, and / or polymer material within a first container that includes a humidity control member. In some embodiments, the humidity control member may be removed from the first container (for example, during the assembly or formation of the packaged article and / or before the packaged article is used by the user).

[0041] In some embodiments, a second container (e.g., containing foil material) may be used to enclose the catheter, device, and / or polymer material. For example, upon removal of the humidity control member, the catheter, device, and / or polymer material may be enclosed within the second container containing the foil material. In some embodiments, upon removal of the humidity control member, the catheter, device, and / or polymer material may be resealed in the first container. In some such embodiments, the first container may comprise a first portion containing foil material and a second portion containing a gas-permeable polymer. For example, in some embodiments, the first container may comprise a header portion containing a gas-permeable polymer and a second portion containing foil material.

[0042] The humidity control member may be removed from the container (e.g., the first container) after any appropriate time has elapsed. For example, in some embodiments, the humidity control member may be removed after 0 hours or more, 1 hour or more, 2 hours or more, 5 hours or more, 10 hours or more, 24 hours or more, 30 hours or more, 48 hours or more, 70 hours or more, 90 hours or more, or 110 hours or more (e.g., after sealing the container (e.g., the first container)). In some embodiments, the humidity control member is removed after 120 hours or less, 110 hours or less, 90 hours or less, 70 hours or less, 48 ​​hours or less, 30 hours or less, 24 hours or less, 10 hours or less, 5 hours or less, or 2 hours or less after sealing the container (e.g., the first container). Combinations of the above ranges are also possible (e.g., 0 hours to 120 hours, 10 hours to 120 hours, 24 hours to 48 hours, etc.). Other ranges are also possible.

[0043] In some embodiments, the catheter may be sterilized (for example, in the first container). As described herein, in some embodiments, the container includes a gas-permeable material (e.g., a polymer) to facilitate sterilization within the container. For example, the gas-permeable material may be permeable to ethylene oxide so that the contents of the container (e.g., the catheter, polymer material, or other articles) are sterilized upon exposure to ethylene oxide. The gas-permeable material may be removed and / or the container may be resealed.

[0044] In some embodiments, the humidity control component is removed substantially immediately after sterilization. In some embodiments, the container is resealed substantially immediately after sterilization.

[0045] As described above, in some embodiments, the device includes a body portion. In some embodiments, the body portion includes a plurality of pores. In some embodiments, the plurality of pores (e.g., device 12 in Figure 1B, device 14 in Figure 1C) or a first water-soluble material (having a second water-soluble polymer optionally positioned in (or within; within) at least some of the pores) have a specific average pore diameter. In some embodiments, the average pore diameter of multiple 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, multiple pores have an average pore diameter 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 ranges mentioned above are also possible (e.g., 500 nm or less, 10 nm or more). Other ranges are also possible. The average pore size as described herein may be determined by mercury intrusion porosimetry of the material in a first configuration (e.g., a moisture content lower than the equilibrium moisture content state, such as a dehydrated state).

[0046] In some embodiments, at least a portion of the multiple pores may be characterized as nanopores, for example, pores having an average cross-sectional dimension of less than 1 micron. In some embodiments, at least a portion of the multiple pores may be characterized as micropores, for example, pores having an average cross-sectional dimension of less than 1 mm and 1 micron 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 multiple pores have a diameter of 1 micron or less, 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, 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 ranges mentioned above are also possible (for example, 1000 nm or less, 10 nm or more). Other ranges are also possible.

[0047] The compositions and devices described herein (for example, device 10 in Figure 1A, device 12 in Figure 1B, and device 14 in Figure 1C) may have a specific porosity in a first configuration (for example, a moisture content lower than the equilibrium moisture content state, such as a dehydrated state). In some embodiments, the device (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 first configuration (for example, a moisture content below the equilibrium moisture content state, such as a dehydrated state). In some embodiments, the device (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 first configuration (for example, a moisture content lower than the equilibrium moisture content state, such as a dehydrated state). Combinations of the above ranges are also possible (for example, 5% to 50% in the first configuration (e.g., a moisture content lower than the equilibrium moisture content state such as a dehydrated state)). Other ranges are also possible.

[0048] As described herein, in some embodiments, the devices, methods, catheters, or kits (or polymer materials) described herein are substantially non-thrombotic.

[0049] In some embodiments, the device (e.g., device 10 in Figure 1A, device 12 in Figure 1B, device 14 in Figure 1C) (or body portion (e.g., body portion 20 in Figures 1A-1B)) is hydrophilic. As used herein, the term “hydrophilic” is given its common meaning in the art and refers to a material surface having a water contact angle determined by goniometry of less than 90 degrees. In some embodiments, the polymer material (or its surface) (e.g., of the device) 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 moisture content. In some embodiments, the polymer material (or its surface) 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 moisture content. Combinations of the above ranges are also possible (for example, between 1 degree and 45 degrees). Other ranges are also possible.

[0050] As used herein, the equilibrium moisture state refers to the steady state of a device (or material) that does not increase (e.g., absorb) or lose bulk moisture content, as determined when submerged in water at 25°C without external mechanical stress. Those skilled in the art will understand that the steady state (or equilibrium moisture state) does not necessarily have to conform absolutely to the strict thermodynamic definition of such term, but rather to the extent possible to conform to the thermodynamic definition of such term for an object characterized in such a way, as would be understood by those most skilled in the art (e.g., by considering factors such as passive diffusion and / or Brownian motion).

[0051] In some embodiments, the equilibrium water content of the device (or polymer material) is 10% by mass or more, 20% by mass or more, 25% by mass or more, 30% by mass or more, 35% by mass or more, 40% by mass or more, 45% by mass or more, 50% by mass or more, 55% by mass or more, 60% by mass or more, 65% by mass or more, or 70% by mass or more. In some embodiments, the equilibrium water content of the device (or polymer material) is 80% by mass or less, 75% by mass or less, 70% by mass or less, 65% by mass or less, 60% by mass or less, 55% by mass or less, 50% by mass or less, 45% by mass or less, 40% by mass or less, 35% by mass or less, 30% by mass or less, 25% by mass or less, or 20% by mass or less. Combinations of these ranges are also possible (e.g., 10% by mass or more, 80% by mass or less). Other ranges are also possible.

[0052] In some embodiments, the devices (e.g., device 10 in Figure 1A, device 12 in Figure 1B, and device 14 in Figure 1C) are substantially lubricating at equilibrium moisture content. For example, in some embodiments, the devices (or the polymer material of the devices) have a surface roughness of 1000 nm (Ra) or less at equilibrium moisture content. In some embodiments, the devices (or the polymer material of the devices) have 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 moisture content. In some embodiments, the device (or the polymer material of the device) has a surface roughness (Ra) of 5 nm or more, 10 nm or more, 25 nm or more, 50 nm or more, 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 moisture content. Combinations of the above ranges are also possible (e.g., 5 nm or more, 1000 nm or less). Other ranges are also possible.

[0053] In some embodiments, the devices (e.g., device 10 in Figure 1A, device 12 in Figure 1B, device 14 in Figure 1C) have surfaces having a coefficient of friction of 0.10 or less at equilibrium moisture content. For example, the coefficient of friction of the surface of the device (or the polymer material of the device) is equal to 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 device (or the polymer material of the device) 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.

[0054] Advantageously, the compositions, devices, and apparatus described herein may have low sorption (or adsorption) of substances such as therapeutic agents (and / or proteins, for example) in the presence of a dynamic fluid containing such substances. Such devices and compositions may be useful for use in subjects where the presence of the device should not substantially reduce the availability and / or concentration of the therapeutic agent delivered (or delivered) to the subject (for example, via the apparatus). In some embodiments, administration of a therapeutic agent via a fluid flowing through a device described herein does not substantially reduce the concentration of the therapeutic agent in the fluid. In some embodiments, the device may not absorb and / or adsorb the therapeutic agent, for example, in flow or during use.

[0055] In some embodiments, 0.5% by mass or less of the therapeutic agent is absorbed onto the surface and / or bulk of the first water-soluble polymer, as determined by the equilibrium water content after the polymer is exposed to the therapeutic agent and washed with five times the volume of the device with an aqueous solution such as water or ordinary saline. In some embodiments, shrinkage of 0.5% by mass or less, 0.4% by mass or less, 0.3% by mass or less, 0.2% by mass or less, or 0.1% by mass or less of the therapeutic agent occurs onto the surface and / or bulk of the first water-soluble polymer. In some embodiments, 0.05% by mass or more, 0.1% by mass or more, 0.2% by mass or more, 0.3% by mass or more, or 0.4% by mass or more of the therapeutic agent is absorbed onto the surface and / or bulk of the first water-soluble polymer. Combinations of the above ranges are also possible (e.g., 0.5% by mass or less and 0.05% by mass or more). Other ranges are also possible.

[0056] Advantageously, the devices and compositions described herein may have desirable swelling properties (e.g., in water, saline solution, or the fluid environment of interest).

[0057] In some embodiments, the device (or polymer material) described herein has a first configuration (e.g., a water content below the equilibrium water content state, such as a dehydrated state) with a water content of 40% by mass or less, 30% by mass or less, 20% by mass or less, 10% by mass or less, 5% by mass or less, 4% by mass or less, 3% by mass or less, 2% by mass or less, 1% by mass or less, 0.8% by mass or less, 0.6% by mass or less, 0.4% by mass or less, or 0.2% by mass or less. In some embodiments, the device (or polymer material) described herein has a water content of 0.1% by mass or more, 0.2% by mass or more, 0.4% by mass or more, 0.6% by mass or more, 0.8% by mass or more, 1% by mass or more, 2% by mass or more, 3% by mass or more, 4% by mass or more, 5% by mass or more, 6% by mass or more, 7% by mass or more, or 8% by mass or more. The first composition has a water content of 9% by mass or more, 10% by mass or more, 15% by mass or more, 20% by mass or more, 25% by mass or more, 30% by mass or more, or 35% by mass or more (for example, a water content lower than the equilibrium water content state such as a dehydrated state). Combinations of the above ranges are also possible (for example, 0.1% by mass or more and 5% by mass or less, 2% by mass or more and 10% by mass or less, 2% by mass or more and 40% by mass or less, or 6% by mass or more and 40% by mass or less, etc.). Other ranges are also possible.

[0058] In some embodiments, the device (or polymer material) described herein has a first configuration (e.g., a moisture content lower than the equilibrium moisture content state, such as a dehydrated state). In some embodiments, the device (or polymer material) described herein swells from the first configuration (e.g., a moisture content lower than the equilibrium moisture content state, such as a dehydrated state) to a second configuration (e.g., the equilibrium moisture content state) in 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, the device (or polymer material) described herein swells from the first configuration (e.g., a moisture content below the equilibrium moisture content state, such as a dehydrated state) to a second configuration (e.g., the equilibrium moisture content state) at 25°C under ambient conditions.

[0059] In some embodiments, the device (or polymer material) described herein swells from, for example, a first configuration (e.g., a water content lower than the equilibrium water content state, such as a dehydrated state) to a second configuration (e.g., the equilibrium water content state) by an amount of 2% by mass or more, 3% by mass or more, 4% by mass or more, 5% by mass or more, 10% by mass or more and 15% by mass or more, 20% by mass or more, 25% by mass or more, 30% by mass or more, 35% by mass or more, 40% by mass or more, or 45% by mass or more. In some embodiments, the devices (or polymer materials) described herein swell from, for example, a first configuration (e.g., a water content lower than the equilibrium water content state, such as a dehydrated state) to a second configuration (e.g., the equilibrium water content state) by amounts of 50% by mass or less, 45% by mass or less, 40% by mass or less, 35% by mass or less, 30% by mass or less, 25% by mass or less, 20% by mass or less, 15% by mass or less, 10% by mass or less, 5% by mass or less, 4% by mass or less, or 3% by mass or less. Combinations of these ranges are also possible (e.g., greater than 5% by mass and 40% by mass or less).

[0060] In some embodiments, the devices described herein (for example, device 10 in Figure 1A, device 12 in Figure 1B, and device 14 in Figure 1C) have a first configuration (for example, a water content smaller than the equilibrium water content state, such as a dehydrated state). For example, in some embodiments, the devices (or polymer materials) described herein have a water content of 40% by mass or less, 30% by mass or less, 20% by mass or less, 10% by mass or less, 5% by mass or less, 4% by mass or less, 3% by mass or less, 2% by mass or less, 1% by mass or less, 0.8% by mass, 0.6% by mass or less, 0.4% by mass or less, or 0.2% by mass or less in the first configuration (for example, a water content smaller than the equilibrium water content state, such as a dehydrated state). In some embodiments, the devices (or polymer materials) described herein have a water content of 0.1% by mass or more, 0.2% by mass or more, 0.4% by mass or more, 0.6% by mass or more, 0.8% by mass or more, 1% by mass or more, 2% by mass or more, 3% by mass or more, or 4% by mass or more. Combinations of the above ranges are also possible (e.g., 0.1% by mass or more and 5% by mass or 2% by mass or more and 40% by mass or less). Other ranges are also possible. The dehydrated state described herein generally refers to a steady state determined under ambient conditions in which the device (or polymer material) does not experience a significant decrease in water content of less than 5% by mass over a 24-hour period. In some embodiments, the devices described herein may include a coating such as a moisture-retaining coating or unbound pologens, as described in more detail below.

[0061] Advantageously, the devices and compositions described herein are configured to swell rapidly in the presence of aqueous solutions such as water and / or saline solution. In some embodiments, a device (e.g., device 10 in Figure 1A, device 12 in Figure 1B, device 14 in Figure 1C) (or a body portion (e.g., body portion 20 in Figures 1A-1C) or polymer material) is configured to swell, for example, from a first configuration (e.g., a water content lower than the equilibrium water content state, such as a dehydrated state) to a second configuration (e.g., the equilibrium water content state) at 25°C, for example, over a specific time (e.g., 60 minutes or less, 10 minutes or less, 5 minutes or less, 1 minute or less, or 10 seconds or less) by an amount of 2% by mass or more, 5% by mass or more, 10% by mass or more, 15% by mass or more, 20% by mass or more, 25% by mass or more, 30% by mass or more, 35% by mass or more, 40% by mass or more, or 45% by mass or more, as described in more detail below. In some embodiments, the device or a part of the device (or body) swells, for example, from a first configuration (e.g., a water content lower than the equilibrium water content state, such as a dehydrated state) to a second configuration (e.g., the equilibrium water content state) at 25°C and over a specific time (e.g., 60 minutes or less, 10 minutes or less, 5 minutes or less, 1 minute or less, or 10 seconds or less) by amounts of 50% by mass or less, 45% by mass or less, 40% by mass or less, 35% by mass or less, 30% by mass or less, 25% by mass or less, 20% by mass or less, 15% by mass or less, or 10% by mass or less, as will be described in more detail below. Combinations of the above ranges are also possible (e.g., 5% by mass or more, 50% by mass or less). Other ranges are also possible.

[0062] In some embodiments, the device (for example, device 10 in Figure 1A, device 12 in Figure 1B, device 14 in Figure 1C) (or body portion (for example, body portion 20 in Figures 1A-1B)) swells by an amount of 2% by mass or more and 5% by mass or more, in a time of 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, 2 minutes or less, 1 minute or less, 30 seconds or less, or 10 seconds or less, from a first configuration (for example, a state with a moisture content lower than the equilibrium moisture content state, such as a dehydrated state) to a second configuration (for example, a state with an equilibrium moisture content) in a time of 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, 2 minutes or less, 1 minute or less, 30 seconds or less, or 10 seconds or less. In some embodiments, the device (or polymer material) swells from a first configuration (e.g., a water content lower than the equilibrium water content state, such as a dehydrated state) to a second configuration (e.g., a parallel swelling state) at 25°C under ambient conditions for 5 seconds or more, 15 seconds or more, 1 minute or more, 2 minutes or more, 5 minutes or more, 10 minutes or more, 20 minutes or more, 30 minutes or more, 40 minutes or more, or 50 minutes or more, by, for example, an amount of 5% by mass or more. Combinations of the above ranges are also possible (e.g., 60 minutes or less, 1 minute or more). Other ranges are also possible.

[0063] In exemplary embodiments, the device (for example, device 10 in Figure 1A, device 12 in Figure 1B, device 14 in Figure 1C) (or body portion (for example, body portion 20 in Figures 1A-1B)) is configured to swell in water from a first configuration (for example, a water content lower than the equilibrium water content state such as a dehydrated state) (for example, 5% by mass or less, or 2% by mass or more, and 40% by mass or less) to a parallel swelling state (for example, 5% by mass or more, or 20% by mass or more, and 80% by mass or less) in 60 minutes or less (for example, 10 minutes or less, 5 minutes or less, 1 minute or less, or 10 seconds or less). In some embodiments, the device (or polymer material) is configured to swell from a first configuration (e.g., a water content lower than the equilibrium water content state, such as a dehydrated state) (e.g., 5% by mass or less) to an equilibrium water content (e.g., 5% by mass or more, 20% by mass or more, or 80% by mass or less) in 60 minutes or less (e.g., 10 minutes or less, 5 minutes or less, 1 minute or less, or 10 seconds or less) in, for example, a standard normal physiological saline solution. In another exemplary embodiment, the device (or polymer material) is configured to swell from a first configuration (e.g., a water content lower than the equilibrium water content state, such as a dehydrated state) (e.g., 5% by mass or less) to an equilibrium water content state (e.g., 5% by mass or more, 20% by mass or more, or 80% by mass or less) in, for example, a normal physiological saline solution, in 60 minutes or less (e.g., 10 minutes or less, 5 minutes or less, 1 minute or less, or 10 seconds or less).

[0064] In some embodiments, a device (e.g., device 10 in Figure 1A, device 12 in Figure 1B, device 14 in Figure 1C) (or a body portion (e.g., body portion 20 in Figures 1A-1B)) has a specific length in a first configuration (e.g., a moisture content lower than the equilibrium moisture content state, such as a dehydrated state). In some embodiments, the overall length of the device (or polymer material) in the equilibrium moisture content state is increased by 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 its length in a first configuration (e.g., a moisture content lower than the equilibrium moisture content state, such as a dehydrated state). In some embodiments, the device (or polymer material) has an overall length at equilibrium moisture content that is significantly greater than or equal to 20%, 18%, 16%, 14%, 12%, 10%, 8%, 6%, 4%, 2%, 1%, or 0.5% compared to the length at a first configuration (e.g., a moisture content lower than the equilibrium moisture content, such as a dehydrated state). Combinations of the above ranges are also possible (e.g., 0.1% to 20%). Other ranges are also possible.

[0065] In some embodiments, the device (e.g., device 10 in Figure 1A, device 12 in Figure 1B, device 14 in Figure 1C) (or body portion (e.g., body portion 20 in Figures 1A-1B)) has a specific maximum outer cross-sectional dimension, such as the outer diameter of a cylindrical, elliptical, oblong, or rectangular tube. In embodiments in which the device includes multiple lumens (or bodies), the outer diameter refers to the maximum outer cross-sectional dimension of one or more of the lumens. For example, in some embodiments, only one lumen may have the outer diameter mentioned. In other embodiments, each and all lumens may independently have the outer diameter mentioned. In some embodiments, the device (or polymer material) has an increase in the maximum outer cross-sectional dimension (e.g., outer diameter) at equilibrium moisture 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) at first configurations (e.g., moisture content less than equilibrium moisture content states such as dehydrated state). In some embodiments, the device (or polymer material) has an increase in the maximum cross-sectional dimension (e.g., outer diameter) at equilibrium moisture 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) at first configurations (e.g., moisture content less than equilibrium moisture content states such as 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.

[0066] In some embodiments, the device (or body portion) has a specific inner diameter (for example, in embodiments where the device includes a hollow core) which is the maximum inner cross-sectional dimension, such as the inner diameter of a cylindrical or rectangular tube (or other non-circular device or body portion). In embodiments where the device (or body portion) includes multiple lumens, the inner diameter means the maximum inner cross-sectional dimension (i.e., the maximum inner cross-sectional dimension of the largest lumen). In some embodiments, the device (or body portion) has an increase in inner diameter at equilibrium moisture 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 inner diameter at a first configuration (for example, a moisture content lower than the equilibrium moisture content state, such as a dehydrated state). In some embodiments, the device (or body portion) has an increase in inner diameter at equilibrium moisture 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 inner diameter at a first configuration (e.g., a moisture content lower than the equilibrium moisture content state, such as a dehydrated state). Combinations of the above ranges are also possible (e.g., 0.1% or more, 20% or less). Other ranges are also possible.

[0067] In some embodiments, when the device (or polymer material) swells from a first configuration (e.g., a water content lower than the equilibrium water content, such as a dehydrated state) to a second configuration (e.g., a state with equilibrium water content), the device (or body portion) has a greater increase in overall length than in inner and / or outer diameter. For example, in some embodiments, the overall length may increase by 1-20% (e.g., 5-15%) while the inner and / or outer diameter may increase by 0.1-19% (e.g., 1-10%).

[0068] In some embodiments, the ratio of the increase in total length to the increase in inner and / or outer diameter when the device (or polymer material) swells from a first configuration (e.g., a moisture content lower than the equilibrium moisture content state, such as a dehydrated state) to a second configuration (e.g., the equilibrium moisture content state) is 1.1 or greater, 1.5 or greater, 2 or greater, 5 or greater, 7 or greater, or 10 or greater. In some embodiments, the ratio of the increase in total length to the increase in inner and / or outer diameter when the device (or polymer material) swells from a first configuration (e.g., a moisture content lower than the equilibrium moisture content state, such as a dehydrated state) to a second configuration (e.g., the equilibrium moisture content state) is 20 or less, 15 or less, 10 or less, 5 or less, or 2 or less. Combinations of these ranges are also possible (e.g., 1.1 to 20).

[0069] In some embodiments, when a device (or polymer material) swells from a first configuration (e.g., a moisture content lower than the equilibrium moisture content state, such as a dehydrated state), the device (or body portion) has a larger increase in inner diameter and / or outer diameter than in overall length. As a non-limiting example, in Figure 2, device 320 swells from a first configuration (e.g., a moisture content lower than the equilibrium moisture content state, such as a dehydrated state) to a second configuration (e.g., the equilibrium moisture content state) - device 340. According to some embodiments, in Figure 2, the outer diameter 302 and inner diameter 301 of device 320 increase to the outer diameter 305 and inner diameter 304 of device 340, respectively, while the overall length 300 increases to the overall length 303. According to some embodiments, in Figure 2, when device 320 swells to the equilibrium moisture content state - device 340, the inner diameter 301 and outer diameter 302 increase at a larger rate than the increase in overall length 300. In some embodiments, the inner and / or outer diameters may increase by 1-20% (e.g., 5-15%), while the overall length may increase by 0.1-19% (e.g., 1-10%).

[0070] In some embodiments, the ratio of the rate of increase in the inner diameter and / or outer diameter to the rate of increase in the total length when the device (or polymer material) swells from a first configuration (e.g., a moisture content lower than the equilibrium moisture content state, such as a dehydrated state) to a second configuration (e.g., the equilibrium moisture content state) is 1.1 or greater, 1.5 or greater, 2 or greater, 5 or greater, 7 or greater, or 10 or greater. In some embodiments, the ratio of the rate of increase in the inner diameter and / or outer diameter to the rate of increase in the total length when the device (or polymer material) swells from a first configuration (e.g., a moisture content lower than the equilibrium moisture content state, such as a dehydrated state) to a second configuration (e.g., the equilibrium moisture content state) is 20 or less, 10 or less, 5 or less, or 2 or less. Combinations of these ranges are also possible (e.g., 1.1 to 20).

[0071] In some embodiments, the device (e.g., device 10 in Figure 1A, device 12 in Figure 1B, device 14 in Figure 1C) (or body portion (e.g., body portion 20 in Figures 1A-1B)) comprises a polymer material having desirable mechanical properties. For example, in some embodiments, the polymer material has a Young's modulus of 100 MPa or more, 250 MPa or more, 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 a first configuration (e.g., a water content less than 5% by mass) (e.g., water content less than 5% by mass). In some embodiments, the polymer material has a Young's modulus in a first configuration (e.g., a moisture content lower than the equilibrium moisture content state, such as a dehydrated state) (e.g., moisture content of 5% by mass or less) of 5000 MPa or less, 4000 MPa or less, 3500 MPa or less, 3000 MPa or less, 2500 MPa or less, 2000 MPa or less, 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, 600 MPa or less, 500 MPa or less, or 250 MPa or less. Combinations of the above ranges are also possible (e.g., 100 MPa or more, 5000 MPa or less, etc.). Other ranges are also possible.

[0072] In some embodiments, the polymer material has a Young's modulus at equilibrium moisture 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 a Young's modulus at equilibrium moisture 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, etc.). Other ranges are also possible.

[0073] In some embodiments, the device (e.g., device 10 in Figure 1A, device 12 in Figure 1B, device 14 in Figure 1C) (or body portion (e.g., body portion 20 in Figures 1A-1B)) includes an osmotic agent (or osmotic substance). For example, in some embodiments, the osmotic agent may be added during the formation of the device (e.g., to the prepolymer). In some embodiments, the osmotic agent is present in the polymer material (e.g., after the formation of the polymer material) in amounts of 0.05% by mass or more, 0.1% by mass or more, 0.2% by mass or more, 0.4% by mass or more, 0.6% by mass or more, 0.8% by mass or more, 1% by mass or more, 1.2% by mass or more, 1.4% by mass or more, 1.6% by mass or more, or 1.8% by mass or more, relative to the total weight of the device in a first configuration (e.g., dehydrated state) and / or a second configuration (e.g., equilibrium water content state). In some embodiments, the osmotic agent may be present in the polymer material (e.g., after the formation of the polymer material) in amounts of 2% by mass or less, 1.8% by mass or less, 1.6% by mass or less, 1.4% by mass or less, 1.2% by mass or less, 1.2% by mass or less, or 0.01% by mass or less, relative to the total weight of the device in a first configuration (e.g., dehydrated state) and / or a second configuration (e.g., equilibrium water content state). Combinations of the above ranges are also possible (e.g., greater than 0.05% by mass and 2% by mass or less). Other ranges are also possible.

[0074] Non-limiting examples of suitable osmotic agents include phosphates, borates, sodium chloride, citrates, ethylenediaminetetraacetates, sulfites, hyposulfites, metal oxides, selenium dioxide, selenium trioxide, selenite, selenous acid, nitrates, silicates, and peony salts (or botanic acids).

[0075] In some embodiments, the composition and / or the first water-soluble polymer (e.g., comprising or formed from a polymer material) does not include covalent crosslinking, as will be described in more detail below. However, in other embodiments, the composition and / or the first water-soluble polymer includes physical crosslinking (e.g., interpenetration networks, 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 polymerization material for the first water-soluble polymer, and / or the second water-soluble polymer.

[0076] The first water-soluble polymer may be present in the device (e.g., device 10 in Figure 1A, device 12 in Figure 1B, device 14 in Figure 1C) (or body portion (e.g., body portion 20 in Figures 1A-1B)) in any suitable amount. For example, in some embodiments, the first water-soluble polymer may be present in the device and / or body portion in equilibrium water content amounts of 20% by mass or more, 25% by mass or more, 30% by mass or more, 35% by mass or more, 40% by mass or more, 45% by mass or more, 50% by mass or more, 55% by mass or more, 60% by mass or more, 65% by mass or more, 70% by mass or more, 75% by mass or more, 80% by mass or more, 85% by mass or more, or 90% by mass or more. In some embodiments, the first water-soluble polymer is present in the device and / or body portion in amounts of 95% by mass or less, 90% by mass or less, 85% by mass or less, 80% by mass or less, 75% by mass or less, 70% by mass or less, 65% by mass or less, 60% by mass or less, 55% by mass or less, 50% by mass or less, 45% by mass or less, 40% by mass or less, 35% by mass or less, 30% by mass or less, or 25% by mass or less, in equilibrium water content. Combinations of the above ranges are also possible (e.g., 20% by mass or more, 95% by mass or less). Other ranges are also possible.

[0077] In some embodiments, the first water-soluble polymer includes or is 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 an exemplary series of embodiments, the first water-soluble polymer is poly(vinyl alcohol).

[0078] In some embodiments, the polymer material comprises a mixture containing a first water-soluble polymer and another (e.g., a third) water-soluble polymer. In some embodiments, the third water-soluble polymer includes, or is 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-hydroxymethylmethacrylic acid), and combinations thereof. The first and other (e.g., third) water-soluble polymers may have different chemical compositions.

[0079] In some embodiments, the total weight of the first water-soluble polymer and another (e.g., a third) water-soluble polymer in the device is 20% by mass or more, 25% by mass or more, 30% by mass or more, 35% by mass or more, 40% by mass or more, 45% by mass or more, 50% by mass or more, 55% by mass or more, 60% by mass or more, 20% by mass or more, 25% by mass or more, 35% by mass or more, 45% by mass or more, 50% by mass or more, 60% by mass or more, 65% by mass or more, 70% by mass or more, 75% by mass or more, 80% by mass or more, 85% by mass or more, 90% by mass or more, 95% by mass or more, 98% by mass or more, or 99% by mass or more, in the state of equilibrium water content. In some embodiments, the first water-soluble polymer and another (e.g., a third) water-soluble polymer are included in the device in amounts of 100% by mass or less, 90% by mass or less, 98% by mass or less, 95% by mass or less, 90% by mass or less, 85% by mass or less, 80% by mass or less, 75% by mass or less, 70% by mass or less, 65% by mass or less, 60% by mass or less, 55% by mass or less, 50% by mass or less, 45% by mass or less, 40% by mass or less, 35% by mass or less, 30% by mass or less, or 25% by mass or less. Combinations of the above ranges are also possible (e.g., 20% by mass or more, 100% by mass or less). Other ranges are also possible.

[0080] In some embodiments, the ratio of the first water-soluble polymer to the third water-soluble polymer present in the device 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 device 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.

[0081] As described above and herein, in some embodiments, the device (e.g., device 12 in Figure 1B, device 14 in Figure 1C) includes a second water-soluble polymer (e.g., a second water-soluble polymer 40) disposed within at least some of the pores (e.g., a plurality of pores 30) of a body portion (e.g., a body portion 20 formed from or containing a polymer material). In some embodiments, the second water-soluble polymer includes or is 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 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.

[0082] A second water-soluble polymer (e.g., second water-soluble polymer 40) may be present in the device in any suitable amount. For example, in some embodiments, the second water-soluble polymer is present in the device in amounts of 0.05% by mass or more, 0.1% by mass or more, 0.2% by mass or more, 0.5% by mass or more, 1.0% by mass or more, 2.0% by mass or more, 3.0% by mass or more, 4.0% by mass or more, 5.0% by mass or more, 10% by mass or more, 20% by mass or more, 30% by mass or more, 40% by mass or more, 50% by mass or more, 60% by mass or more, 70% by mass or more, 80% by mass or more, or 90% by mass or more, at equilibrium water content. In some embodiments, the second water-soluble polymer 40 is present in the device in amounts of 95% by mass or less, 90% by mass or less, 80% by mass or less, 70% by mass or less, 60% by mass or less, 50% by mass or less, 40% by mass or less, 30% by mass or less, 20% by mass or less, 10% by mass or less, 5.0% by mass, 4.0% by mass or less, 3.0% by mass or less, 2.0% by mass or less, 1.0% by mass or less, 0.5% by mass or less, 0.2% by mass or less, or 0.1% by mass or less, at equilibrium water content. In some embodiments, 0% by mass of the second water-soluble polymer is present. Combinations of the above ranges are also possible (for example, greater than 0.05% by mass and 95% by mass or less). Other ranges are also possible.

[0083] 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. It may be 900kDa or higher, 1000kDa or higher, 1500kDa or higher, 2000kDa or higher, 3000kDa or higher, or 4000kDa or higher. 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) may be 5000kDa or less, 4000kDa or less, 3000kDa or less, 2000kDa or less, 1500kDa or less, 1000kDa or less, 900kDa or less, 800kDa or less, 700kDa or less, 600kDa or less, 500kDa or less, 450kDa or less, 400kDa or less, 350kDa or less, 300kDa or less, 250kDa or less, 200kDa or less, 175kDa or less, 150kDa or less, 125kDa or less, 100kDa or less, 75kDa or less, or 50kDa 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.

[0084] In some embodiments, the devices described herein (e.g., device 10 in Figure 1A, device 12 in Figure 1B, device 14 in Figure 1C) 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 cardioverter-defibrillators, cardiac resynchronization devices, cardiovascular device leads, ventricular assist devices, endotracheal tubes, tracheostomy tubes, implantable sensors, ventilator pumps, and ophthalmic devices, or are intended to be used in conjunction with them. In some embodiments, the catheter is selected from the group consisting of central venous catheters, peripheral central catheters, midline catheters, peripheral catheters, tunnel catheters, dialysis access catheters, urinary catheters, nerve catheters, percutaneous transluminal angioplasty catheters, and / or peritoneal catheters. Other suitable applications are described in more detail below.

[0085] These materials can be manufactured as tough, high-strength materials with lubricating and biocompatible surfaces. This specification particularly describes nanoporous solids and microporous solids having high Young's modulus and tensile strength. Nanoporous materials are solids containing interconnected pores up to 100 nm in diameter. The manufacturing process for hydrogels is also described. Hydrophilic polymers can be used to create these various porous solids so that hydrophilic solids are obtained. The water content of nanoporous or microporous solids can be high, for example, 50% by mass at EWC. The water content of hydrogels may be higher, for example, up to 90% by mass 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 biocomponents to their surfaces is significantly reduced.

[0086] These or other porous materials may be processed to include polymers (or polymer-incorporated bulk) that are bulk-incorporated (or bulk, or internally, or largely) into the pores of the solid. Embodiments of materials are porous materials containing water-soluble polymers that are entrapped (or encapsulated, or captured, or contained) in the pores of the material. Polymers entrapped in this manner have been observed to reside within the pores and remain there even after repeated hydration and dehydration. The entrapped polymers provide a scratch-resistant, virtually permanent surface, and the entrapped polymers provide desirable properties beyond the outer surface of the material. In aqueous media, hydrophilic polymers entrapped in this manner hydrate and spread beyond the surface, improving biocompatibility and lubricity.

[0087] Processes for producing the material are described in international patent application publication numbers WO2018 / 237166 and WO2017 / 112878, which are incorporated herein by reference in their entirety. Processes for producing the material may include extrusion molding such that devices having a high aspect ratio can be fabricated. Embodiments of the process 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 can be performed while cooling the mixture and / or in the solvent-removal environment. Further polymers may be incorporated into the pores of the material.

[0088] Disclosed herein are forming processes, including extrusion, for producing high-strength porous solids. Guidance on processes and parameters for producing porous solids is disclosed, as well as on the porous solids themselves. Guidance on bulk incorporating polymers into porous solids is disclosed. It is disclosed that the porous solids have good properties and can be further improved by further incorporating bulk-incorporated polymers.

[0089] Herein are disclosed a novel process for providing extrusion molding of high-strength materials. Several embodiments of this process provide one or more of the following: removing the solvent from a hydrophilic polymer-solvent mixture when the material is extruded; extruding at a low temperature; extruding in a solvent-removal environment; and further removing the solvent for a period of time after extrusion. Furthermore, an annealing step and / or a bulk incorporation step for further polymers may also be included.

[0090] Figures 1D–1F depict one embodiment of an apparatus for manufacturing porous solid material. Device 100 as depicted includes a syringe pump 102 for receiving at least one syringe 104, an optional heating jacket (not shown) for heating the syringe, a die head 106, a heating element 108 and a power cable 109 for heating, providing heating to the die head 106 as needed (not shown in detail in Figure 1D), a dispensing spool 110 for a core tube 112, an intake spool 114 and a motor (not shown) for the core tube, and a bath (or bath; bath) 116 for the extruded material 117, depicted as a heat exchanger 118 including a heat exchange pipe 120 within the bath 116, the bath having temperature control for cooling or heating. The die head 106 receives the core tube 110 passing through the die head 106. A feed line 122 from the syringe to the die head 106 provides the feed to the device 100. The system according to this embodiment may further include a weighing station, a jacketed vessel for heating and mixing the solution to be filled into the syringe, and a solvent removal environment for further drying the tubes removed from the bath 116. The system may also optionally have a heating station for thermal annealing of the tubes or other extruded products. Core tubes made from wire, air, gas, non-solvent liquids or other materials, in addition to PTFE, may be used as the core.

[0091] For use, for example, the polymer is heated in a suitable solvent in a jacketed vessel and placed in syringe 104. One or more polymers may be present, and radiopaque agents or other additives may be added. One or more syringes may be used with the same mixture or different mixtures. The polymer syringe is heated to a predetermined temperature, e.g., 80-95°C or below, and degassed before extrusion. Syringe 104 is attached to a syringe pump 102 equipped with a wrap heater to maintain the temperature during extrusion. The core 112 is looped through a heated out-dwelling die head supplied to a die head 106, e.g., an extrusion bath 116, and then attached to a motor-driven intake spool 114. The bath temperature is controlled using a heat exchanger 118 such as a chiller; the extruded material may be extruded at temperatures in the range of -30°C to 75°C, or other temperatures may be used, with 0°C being a generally useful temperature setting for extrusion. 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 the following are available as upper or lower limits: -30, -25, -20, -15, -10, -5, 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75°C. The outer diameter gauge size around the core 112 can be adjusted by controlling the motor speed of the intake (e.g., puller) spool 114. Adjusting the die size, material supply rate, tube core diameter, and puller rate plays a role in adjusting the final tube gauge, for example, in embodiments in which catheters are manufactured. The polymer supply rate is adjustable, for example, by controlling the syringe pump 102 in this embodiment. The connector 122 connects one or more syringes to the die head 106. Many pumps and other tools are known for controllably supplying polymer solutions. Although alternative supply processes are available, the apparatus and method can be adapted to the stretching process.

[0092] In some embodiments, the composition (e.g., a prepolymer composition) may be provided before the formation of the polymer material (e.g., for extrusion). In some embodiments, the composition comprises an aqueous solution. The aqueous solution may contain an osmotic agent at a concentration of 0.01 M to 8 M, and the aqueous solution may contain a radiopaque agent in an amount of 0% to 50% by mass (e.g., 40% by mass or less). The composition may further contain a water-soluble polymer having a molecular weight of 40 kDa to 5000 kDa and present in the solution in an amount of 10% to 50% by mass.

[0093] In some embodiments, the composition forms a swellable polymer material upon extrusion.

[0094] In some embodiments, the osmotic agent is present in the solution at concentrations of 0.01 M or higher, 0.1 M or higher, 0.5 M or higher, 1 M or higher, 2 M or higher, 3 M or higher, 4 M or higher, 5 M or higher, or 6 M or higher. In some embodiments, the osmotic agent is present in the solution at concentrations of 8 M or lower, 6 M or lower, 4 M or lower, 2 M or lower, 1 M or lower, 0.5 M or lower, or 0.1 M or lower. Combinations of the above ranges are also possible (e.g., 0.01 M to 8 M). The osmotic agent is described in more detail herein.

[0095] In some embodiments, the radiopaque agent is present in the solution in amounts of 0% by mass or more, 5% by mass or more, 10% by mass or more, 15% by mass or more, 20% by mass or more, 25% by mass or more, 30% by mass or more, 35% by mass or more, 40% by mass or more, or 45% by mass or more. In some embodiments, the radiopaque agent is present in the solution in amounts of 50% by mass or less, 45% by mass or less, 40% by mass or less, 35% by mass or less, 30% by mass or less, 25% by mass or less, 20% by mass or less, 15% by mass or less, 10% by mass or less, or 5% by mass or less. Combinations of the above ranges are also possible (for example, 0% by mass or more, 50% by mass or less). Other ranges are also possible. The radiopaque agent will be described in more detail below.

[0096] In some embodiments, the water-soluble polymer is present in the solution in amounts of 10% by mass or more, 13% by mass or more, 15% by mass or more, 20% by mass or more, 25% by mass or more, 30% by mass or more, 35% by mass or more, 40% by mass or more, or 45% by mass or more. In some embodiments, the water-soluble polymer is present in the solution in amounts of 50% by mass or less, 45% by mass or less, 40% by mass or less, 35% by mass or less, 30% by mass or less, 25% by mass or less, 20% by mass or less, 15% by mass or less, or 13% by mass or less. Combinations of the above ranges are also possible (for example, 10% by mass or more, 50% by mass or less). In some embodiments, the water-soluble polymer is present in the solution in amounts greater than or equal to 13% by mass.

[0097] In some embodiments, as described above, the bioactive agent is present in a bulk polymer material formed as a layer within the device. For example, in some embodiments, the polymer material includes a first surface and a second surface, and the first surface and / or the second surface may be coated. In some embodiments, the first surface and / or the second surface are coated with a polymer, a second bioactive agent (same as or different from the bioactive agent present in the polymer material), or a combination thereof. In some embodiments, the device includes two or more layers of polymer material in a body portion. In some embodiments, each layer of polymer material may contain the same, different, or none of the bioactive agent. In an exemplary embodiment, the body portion of the device includes a first polymer material layer containing the first bioactive agent and a second polymer material layer disposed on the first polymer material layer and containing the second bioactive agent. Other combinations of layers are also possible.

[0098] In some embodiments, the biological activator is substantially homogeneously dispersed within the polymer material (of the body portion) and / or the first water-soluble polymer. For example, in some embodiments, the amount of the biological activator does not vary by more than 50% in any given section across the cross-sectional area of ​​the body portion and / or the first water-soluble polymer (e.g., sections 52 and 54 in Figure 1A) compared to the average amount of the biological activator in the body portion and / or the first water-soluble polymer.

[0099] In some embodiments, the biological activator is distributed heterogeneously within the polymer material (i.e., on one or more surfaces of the polymer material). For example, in some embodiments, the amount of the biological activator varies by more than 50% in a given arbitrary section across the cross-section of the body portion and / or the first water-soluble polymer (e.g., sections 52 and 54 in Figure 1A) compared to the average amount of the biological activator in the body portion and / or the first water-soluble polymer.

[0100] In some embodiments, the biological activator is distributed within the body portion (or polymer material of the body portion) and / or the first water-soluble polymer within an average loading (or filling) amount of the biological activator in the body portion (or polymer material) and / or the first water-soluble polymer, ranging from 0.1% or more, 1% or more, 2% or more, 5% or more, 10% or more, 15% or more, 20% or more, 25% or more, 30% or more, 35% or more, 40% or more, 45% or more, 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, 95% or more, or 98% or more. In some embodiments, the biological activator is distributed within the body portion (or polymer material of the body portion) and / or the first water-soluble polymer within the range of average filling amounts of the biological activator in the body portion (or polymer material) and / or the first water-soluble polymer, such as 99% or less, 98% or less, 95% or less, 90% or less, 80% or less, 70% or less, 60% or less, 50% or less, 45% or less, 40% or less, 35% or less, 30% or less, 25% or less, 20% or less, 15% or less, 10% or less, 5% or less, or 2% or less. Combinations of the above ranges are possible (e.g., 99% or less and 0.1% or more, 50% or less and 1% or more). Other ranges are also possible.

[0101] The amount of bioactive substance packed in can be determined by extraction and liquid chromatography after the body portion (or polymer material) has been cut out. For example, an article formed from a body portion (e.g., article 10 in Figure 1A) may be cut along the cross-sectional dimensions passing through its central axis and flattened. Three or more sections of the flattened body portion (e.g., upper section, middle section, and lower section) may be sliced ​​along the length and / or width of the body portion, and the bioactive substance is extracted from each section. The amount of bioactive substance present in each section may be determined by liquid chromatography. The highest amount of variation between the measured sections (compared to the average packing) constitutes the variation of the molded article or device. For example, if the bioactive substance is distributed within the body portion at dispersion levels of 5% of the average packing from the upper section, 15% from the middle section, and 10% from the lower section, the molded article / device containing the body portion will have a dispersion of 15% of the average packing. Such articles / devices can be said to have biological activators distributed within the body portion (or polymer material of the body portion) within a range of 15% or less of the average load of biological activators in the body portion (or polymer material), and the biological activators can be considered to be substantially homogeneously dispersed within the body portion. In contrast, and for illustrative purposes only, an article including a coating of biological activators deposited on the external surface of the body portion (e.g., a coated catheter) where there are no biological activators in the bulk polymer material of the body portion cannot be considered to have biological activators dispersed within the body portion within a range of 15% or less of the average filling, and the filling amount in the first section (e.g., the upper section including the coating) varies by more than 15% from the average filling of biological activators in the body portion (or polymer material).Thus, a person skilled in the art will understand, based on the teachings herein, that an article or apparatus comprising a coating of a biological agent, in which the biological agent is not present in the bulk polymer material of the body portion, does not have the biological agent distributed substantially homogeneously (e.g., within 50% of the average fill weight) within the polymer material (of the body portion).

[0102] In embodiments in which one or more layers of polymer material are present within the device, each layer of polymer material may contain a biological activator distributed homogeneously or heterogeneously throughout each polymer material within one or more of the above-described ranges.

[0103] In some embodiments, the amount of the biological activator does not vary by more than 50% (or any combination of the above percentages) in any of at least 2, 4, 6, 8, 10, 20, or 30 sections of the body portion. In some embodiments, the sections are randomly selected across the length and / or width of the polymer material forming the body portion.

[0104] If one or more biological activators are present (for example, a first and second biological activator present in the polymer material that forms the majority of the body portion), it should be understood that each biological activator may be independently distributed within the polymer material in one or more of the above-mentioned ranges.

[0105] Suitable biological agents are described in more detail below and include, for example, pharmaceutical agents (e.g., drugs), calcium salts (e.g., calcium chloride), iron salts (e.g., ferrous sulfate), starch, modified silica, cellulose, etc. As used herein, the term “biological agent” generally refers to an agent that, when administered to a subject, has a physiologically significant effect on at least a portion of the subject’s body. In some embodiments, the compositions and devices described herein (e.g., device 10 in Figure 1A, device 12 in Figure 1B, device 14 in Figure 1C) include a body portion having a plurality of pores. The body portion may be formed of a polymer material comprising a first water-soluble polymer. In some embodiments, the body portion further comprises a second water-soluble polymer, which is the same as or different from the first water-soluble polymer. For example, in some embodiments, the second water-soluble polymer, which is the same as or different from the first water-soluble polymer, may be located within at least a portion of the plurality of pores. In some embodiments, the second water-soluble polymer may be located within the bulk of the first water-soluble polymer. In some embodiments, the second water-soluble polymer is substantially homogeneously dispersed within the bulk of the first water-soluble polymer. In some embodiments, the second water-soluble polymer is substantially heterogeneously dispersed within the bulk of the first water-soluble polymer. The embodiments described below generally refer to devices comprising a second water-soluble polymer positioned within a plurality of pores, but those skilled in the art will understand, based on the teachings herein, that the presence of the second water-soluble polymer is not necessarily required. While we do not wish to be bound by theory, in some embodiments, the presence of a second water-soluble polymer positioned within a body portion or within at least a portion of the plurality of pores of the first water-soluble polymer can reduce thrombotic properties and / or increase lubricity of a device (e.g., device 12 in Figure 1B, device 14 in Figure 1C) compared to a device without a second water-soluble polymer positioned within the pores (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.

[0106] In some embodiments, if both the first water-soluble polymer and the second water-soluble polymer are polymers of the same monomer but have different monomer numbers and / or molecular weights and other properties, the second water-soluble polymer may be considered the same as the first water-soluble polymer.

[0107] In some embodiments, the devices and compositions described herein (e.g., device 10 in Figure 1A, device 12 in Figure 1B, device 14 in Figure 1C) are administered to a subject. In some embodiments, the devices may be administered orally, rectally, vaginally, nasally, intravenously, subcutaneously, or urethrally. In some cases, the devices may be administered to cavities, epidural spaces, veins, arteries, openings, external openings, and / or abscesses of the subject. Non-limiting examples of openings include wounds. Non-limiting examples of wounds include wound orifices (or openings, or mouths, or holes; orifices) created for venous access through the skin (e.g., created as insertion sites).

[0108] As described herein, in some embodiments, compositions, devices, and devices described herein include a polymer material comprising a first water-soluble polymer having a plurality of pores, or is formed from a polymer material comprising a first water-soluble polymer having a plurality of pores. For example, as shown in Figure 1B, device 12 includes a body portion 20 formed from a polymer material comprising a first water-soluble polymer and having a plurality of pores 30, or from a polymer material comprising a first water-soluble polymer and having a plurality of pores 30. In some embodiments, a second water-soluble polymer 40 is located in 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 40 is distributed within 100%, 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20%, or 10% of the pores (for example, at least 10% and 100% of the pores). Combinations of the above ranges are also possible.

[0109] In some embodiments, the second water-soluble polymer is placed (e.g., dispersed) within the bulk of the first water-soluble polymer (e.g., within the pores and / or voids of the first water-soluble polymer). In some embodiments, as shown in Figure 1C, the second water-soluble polymer 40 may be present as a coating 45 on at least a portion of the surface of the body portion 20. Although Figure 1C 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 45 is present, and the pores 30 are not substantially filled with the second water-soluble polymer 40. Other configurations are also possible.

[0110] In some embodiments, the devices and / or the devices described herein may be hollow (e.g., having a hollow core). For example, device 10 and / or device 12 may be hollow (e.g., including a hollow core 25). However, although Figures 1A-1C are depicted as having a hollow core, those skilled in the art will understand from the teachings herein that such a hollow core is not required. That is, in some cases, the core 25 of the device (e.g., device 10 in Figure 1A, device 12 in Figure 1B, device 14 in Figure 1C) may be a bulk material (e.g., a solid core) that does not have a hollow core 25.

[0111] As described above, in some embodiments, one or more biological activators may be dispersed within the body portion 20 and / or a plurality of pores 30 (Figures 1B-1C). In some embodiments, the biological activator is a therapeutic agent. As used herein, the term “therapeutic agent” or “drug” also means a drug administered to a subject for the treatment, alleviation, delay, improvement and / or prevention of a disease, disorder or other clinically recognized condition, or for preventive purposes, and in some embodiments, a drug having a clinically significant effect on the subject’s body for the treatment, alleviation, delay, improvement and / or prevention of a disease, disorder or condition. Therapeutic drugs include, but are not limited to, drugs listed in the United States Pharmacopeia (USP), The Pharmacological Basis of Therapeutics, 10th Ed, McGraw Hill, 2001 by Goodman and Gilman; Basic and Clinical Pharmacology, McGraw-Hill / Appleton & Lange; 8th edition (September 21, 2000); Physician's Desk Reference (Thomson Publishing), and / or The Merck Manual of Diagnosis and Therapy, 17th ed. (1999) or its subsequent 18th ed (2006), Mark H. Beers and Robert Berkow (eds), Merck Publishing Group, and in the case of animals, drugs listed in The Merck Veterinary Manual, 9th ed., Kahn, CA (ed.), Merck Publishing Group, 2005. In some embodiments, therapeutic agents may be selected from the “Approved Drug Products with Therapeutic Equivalence and Evaluations” (the “Orange Book”) published by the U.S. Food and Drug Administration (FDA).In some cases, the therapeutic agent may have already been determined by the appropriate government agency or regulatory body to be safe and effective for use in humans or animals. For example, drugs approved for use in humans are listed by the FDA under Sections 330.5, 331 to 361, and 440 to 460 of 21 Code of Federal Regulations, which are incorporated herein by reference, and veterinary drugs are listed by the FDA under Sections 500 to 589 of 21 Code of Federal Regulations, which are incorporated herein by reference. All listed drugs are considered permissible for use in accordance with the present invention. In some embodiments, the therapeutic agent is a small molecule. Examples of drug types include, but are not limited to, analgesics, anti-analgesics, anti-inflammatory drugs, antipyretics, antidepressants, antiepileptic drugs, antipsychotics, neuroprotective drugs, antiproliferative agents, anticancer drugs (e.g., taxane drugs such as paclitaxel and docetaxel; cisplatin, doxorubicin, methotrexate, etc.), antihistamines, antibacterial agents, anticancer drugs, etc. This includes antihistamines, anti-migraine drugs, hormones, prostaglandins, antibacterial agents (including antibiotics, antifungals, antivirals, and antiparasitic agents), antimuscarinic agents, anxiolytics, bacteriostatic agents, immunosuppressants, sedatives, hypnotics, antipsychotics, bronchodilators, anti-asthmatics, cardiovascular drugs, anesthetics, anticoagulants, enzyme inhibitors, steroids, steroids or non-steroidal anti-inflammatory drugs, corticosteroids, dopamine agonists, electrolytes, gastrointestinal drugs, muscle relaxants, nutritional supplements, vitamins, parasympathomimetic agents, stimulants, analgesics, and anti-narcolepsy agents. Nutritional supplements may also be included. These may be vitamins, supplements such as calcium and biotin, or natural ingredients such as plant extracts and plant hormones.

[0112] In some embodiments, the biological activator is an anti-inflammatory agent. Non-limiting examples of suitable anti-inflammatory agents include betamethasone, beclomethasone, budesonide, ciclesonide, dexamethasone, desoxymethasone, fluocinolone acetonide, fluocinonide, flunisolide, fluticasone, icometasone, lorofreponide, triamcinolone acetonide, fluocortin butyl, hydrocortisone aceponate, hydrocortisone buteplate, hydroxycortisone 17-butyrate, prednicarbate, 6-methylprednisolone aceponate, mometasone furoate, elastane, prostaglandins, leukotrienes, and bradykinin antagonists.

[0113] In some embodiments, the biological activator is an anesthetic. Non-limiting examples of suitable anesthetics include bupivacaine, lidocaine, procaine, and tetracaine.

[0114] In some embodiments, the biological activator is an antiplatelet agent. Non-limiting examples of suitable antiplatelet agents include clopidogrel, prasugrel, ticagrelor, ticlopidine, cilostazol, borapaxer, absiximab, eptifivatide, tyrofiban, dipyridamole, and tertroban.

[0115] In some embodiments, the biological activator is an analgesic. Non-limiting examples of suitable analgesics include paclitaxel, clopidogrel, prasugrel, ticagrelor, aspirin, ibuprofen, naproxen (and other NSAIDs), warfarin, heparin, apixaban, dabigatran, rivaroxaban, and statins.

[0116] In some embodiments, the biological activator is an anti-cancer agent. Non-limiting examples of suitable anti-cancer agents include paclitaxel, oxaliplatin, fluorouracil (5-FU), docetaxel, methotrexate, doxorubicin, mitoxantrone, teniposide, etoposide, nobiosin, melbaron, and acralubicin.

[0117] In some embodiments, the biological activator is a preservative. Non-limiting examples of suitable preservatives include chlorhexidine, alexidine, iodine, povidone, octenidine, polybiguanide, cetrimide, biphenylole, chlorophene, triclosan, copper, silver, nanosilver, gold, selenium, gallium, tauroridine, cyclotauroridine, N-chlorotaurine, alcohol, lauroyl arginine ethyl, myrisramidopropyl dimethylamine (MAPD), and oleamidopropyl dimethylamine (OAPD).

[0118] In some embodiments, the biological agent is an antimicrobial agent. Non-limiting examples of suitable antimicrobial agents include penicillins: benzylpenicillins (e.g., penicillin G-sodium, cremizolepenicillin, benzathinepenicillin G); phenoxypenicillins (e.g., penicillin V, propicillin); aminobenzylpenicillins (e.g., ampicillin, amoxicillin, bacampicillin); acylaminepenicillins (e.g., azurocillin, mezurocillin, piperacillin, aparcillin); carboxypenicillins (e.g., carbenicillin, ticarcillin, tetraquinol). Mocillin), isoxazolyl penicillin (e.g., oxacillin, cloxacillin, dicloxacillin, flucloxacillin), amidine penicillin (e.g., mesillinnum), cephalosporins, e.g.: cefazolin (e.g., cefazolin, cefazedone); cefuroxime (e.g., celfoxime, cephamandol, cefotiam); cefoxitin (e.g., cefoxitin, cefotetan, latamxef, flomoxef); cefotaxime (e.g., cefotaxime, ceftriaxine) Son, ceftizoxime, cefmenoxime); ceftazidime (e.g., ceftazidime, cefpirome, cefpime); cephalexin (e.g., cephalexin, cefacrol, cefadroxil, cefradin, loracalbeff, cefprodil); cefixime (e.g., cefixime, cefpodoxime proxetil, cefuroxime axetil, cefetamet pivoxil, cefotiam hexetil), carbapenems; imipenem; cilastatin; meropenem; biapenem monobactam; Ziller X-inhibitors include ciprofloxacin, gatifloxacin, norfloxacin, ofloxacin, levofloxacin, pefloxacin, lomefloxacin, freloxacin, clinafloxacin, sitafloxacin, gemifloxacin, balofloxacin, trovafloxacin, moxifloxacin, rifampicin, sitafloxacin, minocycline, tetracycline, erythromycin, roxithromycin, azithromycin, clarithromycin, sulfonamides, and aminoglycosides, and combinations thereof.

[0119] In some embodiments, the biological activator is a coagulant. Non-limiting examples of suitable coagulants include cellulose, oxidized cellulose, tranexamic acid, aprotinin, epsilon-aminocaproic acid, aminomethylbenzoic acid, fibrinogen, and calcium salts.

[0120] In some embodiments, the biological activator is a biological entity (or biological being). Non-limiting examples of suitable biological entities include peptides and peptide oligomers. These include insulin, adrenocorticotropic hormone, calcitonin, oxytocin, vasopressin, octreotide, leuprorelin, exenatide, carfilzomib, bortezomib, lixyrenatide, voclosporine, daptomycin, glatiramer, lindopepimut, dulaglutide, trevananib, lutetium, romiplostim, liraglutide, peginesatide, zoptarelin, tesamorelin, lucinactant, pasireotide, linaclotide, teduglutide, albiglutide, dulaglutide, afmeranotide, etelcalcetide, precanatide, and checkpoint. PD-1 inhibitors: PD-1, CTLA-4, PD-L1; immunotherapy: tumor-infiltrating lymphocytes (TILs), chimeric antigen receptors (CARs), tisagenlecroucyl, axicabutagensiloleucel; antibody therapy: trastuzumab, rituximab, octamumab, alemtuzumab, adtrastuzumab emtansine, brentuximab vedotin, brinatomab; therapeutic vaccines: cypreucel T, tarimogen laherbeck; and immunomodulators: cytokines, bacilscalmateguerane (BCG), thalidomide, lenalidomide, pomalidomide, imiquimod.

[0121] In some embodiments, the biological activator includes natural and / or synthetic cannabinoids or derivatives thereof.

[0122] It should be understood that if one or more biological activators are present (for example, a first biological activator present in the polymer material forming the bulk of the body portion, or a second biological activator present in the pores of the body portion), each biological activator may independently be one of the above activators.

[0123] The biological activators (e.g., first and second biological activators) are distributed within the body portion and / or polymer material and may be present in the device in any appropriate amount. In some embodiments, the biological activators are present in the body portion or polymer material of the device in an amount ranging from about 0.01% to about 50% by mass relative to the total weight of the device in a device with a first configuration (e.g., a water content lower than the equilibrium water content state, such as a dehydrated state). In some embodiments, the biological activators are present in the body portion of the device in an amount ranging from at least about 0.01% by mass, at least about 0.05% by mass, at least about 0.1% by mass, at least about 0.5% by mass, at least about 1% by mass, at least about 2% by mass, at least about 3% by mass, at least about 5% by mass, at least about 10% by mass, at least about 20% by mass, at least about 30% by mass, and at least about 40% by mass relative to the total weight of the device in a device with a first configuration (e.g., a water content lower than the equilibrium water content state, such as a dehydrated state). In some embodiments, the biological activator is present in the device body portion or polymer material in amounts of about 50% by mass or less, about 40% by mass or less, about 30% by mass or less, about 20% by mass or less, about 10% by mass or less, about 5% by mass or less, about 3% by mass or less, about 2% by mass or less, about 1% by mass or less, about 0.5% by mass or less, about 0.1% by mass or less, or about 0.05% by mass or less. Combinations of the above ranges are also possible (e.g., about 0.01% by mass or more and about 50% by mass or less). Other ranges are also possible. If one or more biological activators are present (e.g., a first biological activator present in the polymer material forming the bulk of the body portion, or a second biological activator present in the pores of the body portion), it should be understood that each biological activator may be present independently in amounts within one or more of the above ranges.

[0124] The devices, catheters, kits, and methods described herein may be administered to any suitable subject. As used herein, the term “subject” refers to an individual organism, such as a human or an animal. In some embodiments, subjects are mammals (e.g., humans, non-human primates, or non-human mammals), vertebrates, laboratory animals, livestock animals, agricultural animals, or companion animals. Non-limiting examples of subjects include humans, non-human primates, cattle, horses, pigs, sheep, goats, dogs, cats, or rodents such as mice, rats, and hamsters, birds, fish, or guinea pigs. Generally, the present invention is directed toward human use. In some embodiments, subjects may demonstrate health benefits, for example, upon administration of the device.

[0125] Advantageously, the devices described herein may allow for the incorporation of higher concentrations (by weight percent) of activators, such as biological activators, compared to certain other devices (e.g., certain devices comprising only a coating of a biological activator). In some embodiments, the biological activator is associated with a first water-soluble polymer and / or a second water-soluble polymer. In some embodiments, the biological activator is dispersed within the first water-soluble polymer and / or the second water-soluble polymer. In addition, or alternatively, the devices described herein may allow for the extended release of one or more biological activators compared to certain other devices (e.g., certain devices comprising only a coating of a biological activator).

[0126] In some embodiments, the biological activator may be released from the body portion of the device by any suitable means. In some embodiments, the biological activator is released by diffusion from the body portion (e.g., the polymer material of the body portion). In some embodiments, the biological activator is released by the decomposition of at least a portion of the body portion (e.g., biodegradation, enzymatic degradation, hydrolysis of the polymer material forming the body portion, or hydrolysis of the polymer material in the pores of the body portion). In some embodiments, the active substance is released from the device at a specific rate. Those skilled in the art will understand that, in some embodiments, the release rate may depend on the solubility of the biological activator in the medium to which the device is exposed, such as a physiological fluid such as blood. In some embodiments, the release rate may depend on the crosslinking density, porosity, pore size distribution, pore interconnectivity (e.g., labyrinthiness), crystallinity, and / or the number of biological activator-containing layers within the device (e.g., the body portion of the device).

[0127] In some embodiments, the device may be configured to release one or more biological agents using a combination of burst (or rupture, or sudden) release and controlled release. In an exemplary example, the biologically active agent may be released by controlled release following a first burst release in any of the above amounts, average rates, and / or time. In another exemplary example, the first biological agent may be released by burst release, and the second biological agent may be released at a specific average rate as described above. In some embodiments, the first and second biological agents may begin release substantially simultaneously. In some embodiments, the first and second biological agents may be released at different times.

[0128] The biological activator may be released at a substantially constant average rate (e.g., substantially zero-order average release rate) over a period of at least about 24 hours. In some embodiments, the biological activator is released at a primary release rate (e.g., the release rate of the biological activator is roughly proportional to the concentration of the biological activator) over a period of at least about 24 hours.

[0129] In some embodiments, a method for forming the polymer material and / or device described herein includes providing a mixture comprising a first water-soluble polymer and an osmotic agent such as a salt. In some embodiments, the mixture is extruded. In some embodiments, the extruded mixture is extruded onto a core material to form a polymer material placed on the core material. In some embodiments, the formed polymer material is exposed to a non-solvent of the polymer material. In some embodiments, a solution comprising a second water-soluble polymer different from the first water-soluble polymer and optionally an osmotic agent is introduced into the polymer material. In some embodiments, the polymer material (e.g., after the solution has been introduced into the osmotic agent) is heated. In some embodiments, the solution is flowed over the polymer material. In some embodiments, the polymer material may be dried.

[0130] In an exemplary series of embodiments, a method for forming a polymer material and / or device described herein comprises providing a mixture comprising a first water-soluble polymer and an osmotic agent (e.g., a salt), wherein the first water-soluble polymer is present in the mixture at a concentration of 10% by mass or more (e.g., 13% by mass or more, or 13% by mass or more and 50% by mass or less) relative to the total weight of the mixture, and performing the following steps: extruding the mixture at atmospheric pressure at a temperature of 65°C or higher (e.g., 65°C or higher and 100°C or less) to form a polymer material (e.g., a solid rod or a gas) placed in a core material, and heating the polymer material at a temperature of 28°C or lower (e.g., 28°C or higher). The process includes exposing the polymer material to a non-solvent at a temperature of -20°C or lower for 15 minutes or more (e.g., 1 hour or more, 240 hours or less), introducing a biological activator and / or a second water-soluble polymer different from the first water-soluble polymer, and / or an osmotic agent (e.g., a salt) into the polymer material, heating the polymer material and solution to a temperature of 25°C or higher (e.g., 30°C or higher, or 30°C or higher, 65°C or lower), running the solution adjacent to the polymer material for 1 hour or more (e.g., 1 hour or more, 48 hours or 3 hours or more, 48 hours or less), and drying the polymer material. In some embodiments, the biological activator is substantially homogeneously distributed within the polymer material, within a range of 50% or less of the average filling of the polymer material. In some embodiments, the biological activator is heterogeneously distributed within the polymer material (i.e., on one or more surfaces of the polymer material).

[0131] In some embodiments, the second water-soluble polymer is placed in at least one pore (or more pores) of the first water-soluble polymer, as described herein.

[0132] In some embodiments, the non-solvent includes alcohols. In some embodiments, the non-solvent is ethanol, methanol, propanol, butanol, pentanol, hexanol, heptanol, octanol, decanol, dodecanol, dimethyl sulfoxide, ethyl acetate, acetate, propionic acid, ether, dimethylformamide, dimethylacetamide, acetone, acetonitrile, ethylene glycol, propylene glycol, glycerol, air, vacuum, or a combination thereof. Other non-solvents are also possible (e.g., solvents that have high solubility in water but lower solubility in water-soluble polymers compared to their solubility in water).

[0133] In some embodiments, the core material may be air, water, a non-solvent liquid, a solid, or a gas. In some cases, the core material may be removed after the polymer material has been formed on the core material. In some cases, the core material may be physically removed and / or dissolved.

[0134] In some embodiments, the polymer materials and / or devices described herein may be exposed to and / or contain a humectant (or wetting agent). For example, in some embodiments, device 10 contains a humectant 70, as illustrated in Figure 1G. In some embodiments, at least a portion of the humectant is disposed on the surface (e.g., lumen and / or lumen surface) of the polymer material and / or device (e.g., body portion). For example, in some embodiments, a portion of the humectant 70 is disposed on the surface of device 10. In some embodiments, 30% or more, 40% or more, 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, or all of the humectant is disposed on the surface of the polymer material and / or device (e.g., body portion). In some embodiments, 100% or less, 90% or less, 80% or less, 70% or less, 60% or less, 50% or less, or 40% or less of the humectant is disposed on the surface of the polymer material and / or device (e.g., body portion). Combinations of these ranges are also possible (for example, 40-100%).

[0135] In some embodiments, at least a portion of the humectant is located inside the polymer material and / or device (e.g., body portion). In some embodiments, at least a portion of the humectant is located inside the polymer material and / or device (e.g., body portion). For example, in some embodiments, a portion of the humectant 70 is located inside the device 10 (e.g., absorbed into the bulk of the device). In some embodiments, 30% or more, 40% or more, 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, or all of the humectant is located inside the polymer material and / or device (e.g., body portion). In some embodiments, 100% or less, 90% or less, 80% or less, 70% or less, 60% or less, 50% or less, or 40% or less of the humectant is located inside the polymer material and / or device (e.g., body portion). Combinations of these ranges are also possible (e.g., 30-100%).

[0136] In some embodiments, the humectant is a nonionic surfactant (i.e., a surfactant having an uncharged hydrophilic head and a hydrophobic tail) or a zwitterionic (i.e., a surfactant having a purely uncharged hydrophilic head and a hydrophobic tail). In some embodiments, the humectant is a nonionic surfactant selected from the group consisting of sugar alcohols, poloxamers, triacetins, α-hydroxy acids, polyethylene glycol, polypropylene glycol, ethylene glycol, propylene glycol, hexylene glycol, butylene glycol, glycerol, sorbitol, mannitol, xylitol, maltitol, erythritol, slayitol, arabitol, ribitol, galactitol, futitol, isitol, inositol, boretol, malitol, lactitol, maltotriitol, maltotetraitol, polyglycitol and combinations thereof. In some embodiments, the humectant contains an oil such as vitamin E. In some embodiments, the humectant contains a salt such as sodium chloride, potassium chloride, and / or phosphocholine.

[0137] In some embodiments, the polymer materials and / or devices described herein are exposed to and / or contain 0.1% by mass or more of a humectant, 0.5% by mass or more of a humectant, 1% by mass or more of a humectant, 5% by mass or more of a humectant, 10% by mass or more of a humectant, or 20% by mass or more of a humectant. In some embodiments, the polymer materials and / or devices described herein are exposed to and / or contain 30% by mass or less of a humectant, 25% by mass or less of a humectant, 20% by mass or less of a humectant, 15% by mass or less of a humectant, 10% by mass or less of a humectant, 5% by mass or less of a humectant, or 1% by mass or less of a humectant. Combinations of these ranges are also possible (e.g., 0.1 to 30% by mass of a humectant or 1 to 10% by mass of a humectant). Porous solids (e.g., manufactured by the apparatus of Figures 1D to 1F) may be annealed. Furthermore, porous solids with or without prior annealing may be processed to further contain a polymer-incorporated bulk. In Figure 3A, a material 210 containing a porous solid matrix 212 is desolvated (or desolvated) and exposed to a mixture containing a polymer in a solvent to be resolvated, and resolvated in the mixture to form a material 212 having a bulk 214 into which the polymer is incorporated. A cross-section of the matrix 212 (Figure 3B) reveals the outermost zone 216 in which the pores of the matrix 212 are filled, an intermediate zone 218 with a low density of polymer in the pores, less filling, and / or less pore occupation, and an inner zone 220 in which the polymer has not permeated. The matrix may be solvated and / or desolvated before exposure to the mixture, provided that it is desolvated when exposed to the mixture so that water-soluble polymers can migrate into the matrix.

[0138] In some embodiments, a method for wetting a device and / or polymer material includes placing (or arranging) an extruded segment in a solution containing a humectant (e.g., glycerol or poloxamer). In some embodiments, the solution contains 1% by mass or more, 5% by mass or more, 10% by mass or more, 15% by mass or more, 20% by mass or more, or 25% by mass or more of the humectant. In some embodiments, the solution contains 35% by mass or less, 30% by mass or less, 25% by mass or less, 20% by mass or less, 15% by mass or less, 10% by mass or less, or 5% by mass or less of the humectant. Combinations of these ranges are also possible (e.g., 1 to 35% by mass). In some embodiments, the solution contains a surfactant. In some embodiments, the solution contains PBS.

[0139] In some embodiments, the extruded segments are placed in a solution for a certain period of time. In some embodiments, this period is 1 hour or more, 2 hours or more, or 3 hours or more. In some embodiments, the period is 4 hours or less, 3 hours or less, or 2 hours or less. Combinations of these ranges are also possible (e.g., 3 hours, or 1 to 4 hours).

[0140] In some embodiments, the solution is maintained at a certain temperature during the exposure of the extruded segments to the solution. In some embodiments, the temperature is 20°C or higher, 30°C or higher, 37°C or higher, 40°C or higher, 50°C or higher, or 60°C or higher. In some embodiments, the temperature is 70°C or lower, 60°C or lower, 55°C or lower, 50°C or lower, 40°C or lower, 37°C or lower, or 30°C or lower. Combinations of these ranges are also possible (e.g., 20-70°C, 37-55°C, or 45°C).

[0141] In some embodiments, after removing the extruded segments from the solution, the extruded segments can be dried (for example, in a convection oven). In some embodiments, the extruded segments are dried at a certain temperature. In some embodiments, the temperature is 20°C or higher, 30°C or higher, or 40°C or higher. In some embodiments, the temperature is 50°C or lower, 40°C or lower, or 30°C or lower. Combinations of these ranges are also possible (e.g., 30°C, or 20-50°C). In some embodiments, the extruded segments are dried for a certain period of time. In some embodiments, the period may be 1 hour or more, 2 hours or more, or 3 hours or more. In some embodiments, the period of time may be 4 hours or less, 3 hours or less, or 2 hours or less. Combinations of these ranges are also possible (e.g., 3 hours, or 1-4 hours).

[0142] The biological activator may be incorporated into the devices and / or devices described herein by any suitable method. For example, in some embodiments, the first water-soluble polymer may be mixed with water (e.g., via a solution formulation method (or compounding) in mass ratios of 0.1–99.9, 1–99, 5–95, 10–90, 20–80, 30–70, 33–67, 37–63, 40–60, 42–58, 45–55, 47–53, 50–50 of the water-soluble polymer). In some embodiments, the biological activator may be suspended or solubilized in water before solution formulation. When the biological activator is formulated into a solution containing the water-soluble polymer and water, it may optionally be pulverized, aggregated, and / or untreated. In some embodiments, the biological activator may be mixed with the water-soluble polymer and water before heating the solution as described herein. In some embodiments, the biological activator may be added while lowering the temperature during cooling after bulk assembly of the polymer as described herein.

[0143] In some embodiments, crosslinking of the third water-soluble polymer can be achieved before micronization by UV crosslinking, chemical crosslinking (e.g., glutaraldehyde, bis(hydroxyethyl) sulfone, maleic acid, etc.), and / or radiation crosslinking (e.g., gamma). In some embodiments, the polymer may be micronized to less than 50 microns using conventional encapsulation methods and / or used, for example, through in situ oil-in-water emulsions or water-in-oil emulsions or cavity molding to extend controlled release from the fine particles or nanoparticles.

[0144] In some embodiments, particles containing biological activators can be produced in situ using fully polymerized polymers, prepolymers having crosslinking agents or initiators, monomers and initiators, or two or more self-polymerizing monomers, or combinations thereof.

[0145] As described herein, in some embodiments, the biological activator may be present in multiple pores of the device body portion (e.g., Figures 1B-1C). In some such embodiments, the biological activator may be released, for example, during hydration and / or swelling / extension of the device. Incorporation of the biological activator into the multiple pores may be done using any suitable method. For example, in some embodiments, the biological activator may be mixed with a second water-soluble polymer as described herein, so that the biological activator is placed in the multiple pores. In some embodiments, the biological activator may be adsorbed / absorbed into the multiple pores.

[0146] In some embodiments, a biological activator may be solubilized and injected (or filled or impregnated; infuse) into the body portion through a channel in the device (e.g., the hollow core 25 in Figures 1A-1C). Such a device may be useful as a delayed-release (e.g., long-term release) and / or refillable device.

[0147] In some embodiments, a bioactive agent having a water-soluble polymer is co-extruded as a central layer between an outer layer and an inner layer containing a non-pharmaceutical bulk polymer (e.g., PVA). In exemplary embodiments, the bioactive agent is compatible with the bulk polymer and adheres well without peeling. In some embodiments, the bioactive agent layer is located away from the surface, allowing the binding polymer to be adsorbed and absorbed into their surface layers.

[0148] Figure 4A shows an illustrative flowchart of a process for producing a porous solid containing bulk-integrated polymers. This process includes an extrusion step where a radiopaque (RO) agent is used. A heated hydrophilic polymer solution refers to the polymer that is bulk-integrated into the pores of the extruded porous solid.

[0149] Another exemplary flowchart of a process for producing porous solids containing bulk-integrated polymers and biological activators is shown in Figure 4B. In this process, post-processing is included in the extrusion step after drying the extrusion on a steel mandrel.

[0150] Those skilled in the art who read this disclosure will be able to adapt the principles in light of what is known about extrusion or other molding techniques to create alternative processes and apparatus that achieve the same end products as described herein. Scaled-up embodiments of this process can, for example, be adapted for use in a multi-zone screw extruder, where the solvent mixture is supplied via a suitable injector or hopper, and the zones (or areas, or regions) are controlled to provide low-temperature extrusion. Functions such as syringe pumps can be replaced by appropriately metered and controlled liquid or solid polymer supply systems.

[0151] Fukumori et al. (2013), Open J. Organic Polymer Materials 3:110-116, reported a freeze-thaw process for producing poly(vinyl alcohol) (PVA) materials with a Young's modulus of approximately 5 MPa or higher and 181 MPa, requiring at least approximately 3 cycles in the tested samples. Multiple freeze-thaw cycles were necessary in the production of these gels. Since the obtained materials were tested in a dry state, they cannot be compared to strengths measured by EWC. Fukumori et al. reported that the crystal content in the material increased with increasing freeze-thaw cycles, and attributed the material's strength to the formation of larger crystals as the freeze-thaw cycles progressed, which formed excellent crosslinks and increased the material's Tg. Such a process results in a dry material. Furthermore, as will be discussed later, the freeze-thaw process generates macropores.

[0152] In some embodiments, the processes described herein are freeze-thaw processes and / or freeze-thaw processes. Furthermore, the processes can 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% by mass at EWC. Those skilled in the art will immediately understand that all ranges and values ​​between the explicitly stated boundaries, e.g., 0, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 95, and 100% by mass, are intended, and that swelling is measured as % swelling = 100 × (gross weight at EWC - dry weight) / dry weight, where dry weight is the weight of the material without water.

[0153] In some embodiments, the extruded sample has a horizontal orientation and alignment (or arrangement, or alignment) of polymer chains along the length of the sample (extrusion direction). This is the polymer chain orientation produced by the extrusion molding process. While we do not wish to be bound by theory, in some embodiments, this horizontal orientation and alignment of chains 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.

[0154] Various types of dies may be used, for example, longitudinal, angular, transverse, and helical 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 as well as circulating heads may also be used. Various materials may be incorporated into or as layers: for example, reinforcing materials, fibers, wires, braided (or braided) materials, braided wires, braided plastic fibers, etc. Similarly, such materials may be excluded. Furthermore, porous solids may be made of which specific properties, such as Young's modulus, tensile strength, solids content, polymer composition, porous structure, or solvent content, are known and therefore measurable, apart from various other materials. Thus, embodiments include materials disclosed herein, described in terms of material properties, regardless of various other incorporated materials. For example, nanoporous solids have a known specific Young's modulus, even if the material has reinforcing wires that contribute to further strength.

[0155] 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 processes 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.

[0156] Multi-lumen tubes have multiple channels running through their profile. These extruded parts can be custom designed to match the device design. Multi-lumen tubes have a variable outer diameter (OD), numerous custom inner diameters (ID), and a variety of wall thicknesses. The tubes are available in a variety of shapes, including circular, elliptical, triangular, square, semicircular, crescent, etc. These lumens can be used in a variety of applications, such as guide wires, liquids, 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. It is possible to maintain tight tolerances down to + / - 0.0005 inches. Those skilled in the art will immediately understand that all ranges and values ​​between the specified boundaries are intended. For example, any of the following are available as upper or lower limits for OD and / or ID: 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. The tolerance may be, for example, 0.0005 to 0.1 inches. Those skilled in the art will immediately understand that all ranges and values ​​between explicit boundaries are assumed. For example, any of the following are available as upper or lower limits: 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.

[0157] Braided reinforced tubing can be manufactured in various configurations. For example, it is possible to braid using small round or flat wires of 0.001 inches, with one or both ends. Braided reinforced tubing can be made using various materials such as stainless steel, beryllium copper, silver, and monofilament polymers. It can also be wrapped around a thermoplastic base material such as nylon or polyurethane with various PICs per inch. The advantages of this catheter shaft are its high torque performance and kink resistance. Furthermore, by changing several elements in the braiding process, the characteristics of the tubing can be obtained to match the required performance. 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, it is possible to make it as thin as 0.007 inches.

[0158] Porous material, microporous material, nanoporous material The term "porous solid," used herein in a broad sense, refers to a material having a solid phase containing open space (or void), and is used to describe true porous materials and hydrogels having an open matrix structure. Several terms related to porosity are used somewhat loosely in the scientific literature, and it is useful to provide a certain definition herein. The term nanoporous material or nanoporous solid is used herein, in particular, to refer to a solid made of interconnected pores having pore sizes up to about 100 nm in diameter. The term diameter, as is customary in these arts, broadly encompasses pores of any shape. The term microporous solid or microporous material is similarly used herein, in particular, to refer to a solid made of interconnected pores having pore sizes up to about 10 μm in diameter. These nano or microporous materials are characterized by their interconnected porous structure.

[0159] Hydrogels, sometimes called hydrogel sponges by those skilled in the art, are true porous materials having a continuous, rigid network of material filled with voids, where voids are holes. However, the open matrix structure found in many hydrogels is not a true porous structure, and while it is convenient to refer to them as porous materials or to use the analogy of pores when characterizing their diffusivity or other properties, such hydrogels are not nanoporous or microporous solids as those terms are used herein. The spaces between strands in open-matrix hydrogels, and the strands of the matrix, are not interconnected pores. Hydrogels are crosslinked, insoluble in solvents, and possess significant mechanical strength, so it is convenient to refer to them generally as solids in this specification and in these arts, but they are crosslinked gels that have solid-like properties even if they are not true solids. Hydrogels can have a high water content, for example, 25% by mass or more at EWC. Those skilled in the field of hydrogel technology may use the term porous to characterize the cleavage of net molecular weight or to refer to the spacing between strands in an open hydrogel matrix, but in this case the hydrogel does not have a truly porous structure and these terms are not nanoporous or microporous materials as used herein. The definitions of nanoporous and microporous materials used herein are also in contrast to the sometimes-following convention that describes microporous materials as having a pore diameter of less than 2 nm, macroporous materials as having a pore diameter of more than 50 nm, and the mesoporous category as being in between.

[0160] Extrusion molding offers several advantages as a method for manufacturing the material of the present invention. Extrusion molding has been shown to orient polymers in parallel, resulting in high tensile strength. By extruding and stretching, the polymer molecules align in the direction of the tube or fiber. Strong intermolecular forces suppress the tendency to return to a random orientation. Furthermore, it is possible to create materials and devices with high aspect ratios compared to molding processes such as injection molding. In addition, extrusion molding allows for control of wall thickness, lumen arrangement, etc., thus enabling good dimensional control. Using a high concentration of polymer above the melting point in the solvent was effective in enabling extrusion molding. It is important to note that other attempts to create high-strength materials using similar polymers have relied on other techniques that do not enable extrusion molding, are inefficient, and are often unsuitable for the manufacture of actual end-user products.

[0161] For example, poly(vinyl alcohol) (PVA) was used herein to create nanoporous materials with superior properties compared to conventionally used PVA medical materials. In fact, PVA is widely used in the medical device industry and has a proven track record of biocompatibility. PVA is a linear molecule and has a long history as a biocompatible biomaterial. PVA hydrogels and membranes have been developed for biomedical applications such as contact lenses, artificial pancreases, hemodialysis, and synthetic vitreous humors, as well as for implantation medical materials to replace cartilage and meniscus tissue. Compared to other hydrogels, it has high biocompatibility and low protein adsorption, resulting in low cell adhesion, making it an attractive material for these applications.

[0162] Attempts have also been made to improve the properties of PVA for biomedical purposes. For example, some have experimented with freeze / thaw processes. Hydrogel formation techniques from PVA, such as "salting-out" gelation, have been shown to form useful polymer hydrogels using different molecular weights and concentrations. Manipulation of Flory interactions has also been studied in the formation of PVA gels by combining two solutions for the use of PVA as an injectable in situ forming gel for intervertebral disc repair (see US7,845,670, US8,637,063, US7,619,009). In general, prior processes for producing tough PVA materials have been studied in US8,541,484. Methods that do not use radiation or chemical crosslinking agents have also been studied previously, as shown in US6,231,605. None of these other PVA-related studies have led to the inventions described herein. Some of these other materials were useful in terms of tensile strength, but nevertheless were essentially macroporous.

[0163] In contrast, the processes described herein provide high-strength materials with a true porous structure and other useful properties such as an unexpectedly good combination of biocompatibility and mechanical properties. Embodiments of porous solid materials have a combination of structural features independently selected from pore size, tensile strength, Young's modulus, solid concentration, crosslinking type and degree, internal alignment, hydrophilicity, and composition, and further optionally, end-user devices or intermediate materials having a molded shape, lumen, multiple lumens, a tube with concentrically arranged lumens, or a tolerance for thickness, or a desired aspect ratio for a particular medical device: each of these is further detailed herein.

[0164] The embodiments include nanoporous materials having pore diameters of 100 nm or less, or in the range of 10 to 100 nm; those skilled in the art will immediately understand that all ranges and values ​​between the specified boundaries are contemplated, and that any of the following can be used as upper or lower limits, for example: 1, 2, 3, 4, 5, 10, 20, 50, 60, 70, 80, 90, 100 nm.

[0165] Embodiments include nanoporous or microporous materials having a tensile strength at break of at least about 50 MPa or 1 to 300 MPa as measured by EWC. Those skilled in the art will immediately understand that all ranges and values ​​between the specified boundaries are intended, and that any of the following are available as upper or lower limits, for example: 10, 20, 30, 40, 50, 60, 70, 100, 200, 300 MPa.

[0166] Embodiments include nanoporous or microporous materials having a Young's modulus strength of at least about 1 MPa or 1 to 200 MPa as measured by EWC. Those skilled in the art will immediately understand that all ranges and values ​​between the specified boundaries are intended, and that any of the following are available as upper or lower limits, for example: 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 120, 140, 160, 180, 200 MPa.

[0167] Embodiments include nanoporous materials or microporous materials or hydrogels having a fracture elongation of at least about 100% or 50–1500% as measured by EWC. 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 the following are available as upper or lower limits: 50, 60, 70, 80, 90, 100, 200, 300, 400, 450, or 500% (e.g., greater than or equal to 50%).

[0168] Embodiments include nanoporous materials or microporous materials or hydrogels having at least 20% solids or 20–90% solids by mass as measured in EWC; those skilled in the art will immediately understand that all ranges and values ​​between the explicitly stated boundaries are contemplated, and that, for example, any of the following can be used as upper or lower limits: 5, 10, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 80, 90% solids by mass. The solids content is measured by comparing the total weight in EWC with the dry weight.

[0169] The values ​​of tensile strength, modulus of elasticity, and elongation may be combined within the range derived by this disclosure to produce a variety of materials.

[0170] Embodiments include nanoporous materials or microporous materials or hydrogels having physical crosslinks or covalent crosslinks or a combination thereof. Physical crosslinks are non-covalent, and for example, physical crosslinks are ionic bonds, hydrogen bonds, electrostatic bonds, van der Waals forces, or hydrophobic packing. The material may be free from covalent crosslinks, covalent crosslinking agents, and their chemical products. As is known in the art of polymerization, chemicals can be added during processing to create covalent crosslinks. Alternatively, the process and material may not use such chemicals.

[0171] Embodiments include nanoporous materials or microporous materials or hydrogels having an internal alignment of polymer structures. The alignment can be visualized using SEM images of a cross-section taken along the extrusion direction, i.e., longitudinally in the case of a tube. The alignment here refers to the orientation of mostly horizontal chains along the longitudinal direction (extrusion direction) of the sample.

[0172] Embodiments include nanoporous materials or microporous materials or hydrogels having hydrophilic surfaces and / or materials. Materials made of water-soluble polymers are hydrophilic. Water-soluble polymers are polymers that dissolve in water at a concentration of at least 1 g / 100 ml at 20°C. Water-soluble polymers are hydrophilic. A surface is hydrophilic if the contact angle with respect to a water droplet on the surface is 90 degrees or less (the contact angle is defined as the angle passing through the interior of the water droplet). Embodiments include hydrophilic surfaces with contact angles between 90 and 0 degrees; those skilled in the art will immediately understand that all ranges and values ​​between the expressed boundaries are intended, and for example, any of the following can be used as upper or lower limits: 90 degrees, 80 degrees, 70 degrees, 60 degrees, 50 degrees, 40 degrees, 30 degrees, 20 degrees, 10 degrees, 5 degrees, 2 degrees, 0 degrees. The matrix of a material is hydrophilic with respect to a solvent if the matrix is ​​hydrophilic and the contact angle of a solvent droplet on the surface is less than 90 degrees.

[0173] Materials for use in processes and / or biomaterials may include polymers. Hydrophilic polymers are useful, and for example, one or more polymers may be selected from polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), polyacrylic acid (PAA), polyacrylamide, hydroxypropyl methacrylamide, polyoxazoline, polyphosphate, polyphosphazene, poly(vinyl acetate), polypropylene glycol, poly(N-isopropylacrylamide) (PNIPAM), polysaccharides, sulfonated hydrophilic polymers (e.g., sulfonated polyphenylene oxide, Nafion®, sulfobetaine methacrylate), and iodine-added variants (e.g., PVA-I, PVP-I), or variants having further pendant groups, copolymers of these, and combinations thereof. Two or more hydrophilic polymers may be mixed with each other to form nanoporous materials. The molecular weight of the polymer can affect the properties of the biomaterial. Higher molecular weights tend to increase strength, decrease pore size, and reduce protein adsorption. Accordingly, the embodiments include polymers or hydrophilic polymers having molecular weights of 40 kDa to 5000 kDa; those skilled in the art will immediately understand that all ranges and values ​​between the specified boundaries are contemplated, and that any of the following can be used as upper or lower limits, for example: molecular weights of 40 kDa, 50 kDa, 100 kDa, 125 kDa, 150 kDa, 250 kDa, 400 kDa, 500 kDa, 600 kDa, 750 kDa, 800 kDa, 900 kDa, 1 million, 1.5 million, 2.5 million, and 3 million.

[0174] The term PEG refers to all polyethylene oxides, regardless of molecular weight or whether the polymer is hydroxyl-terminated. Similarly, the terms PVA, PVP, and PAA are used without limitation in terms of terminal chemical sites or MW range. References to polymers described herein include all forms of polymers, including linear polymers, branched polymers, non-derivative polymers, and derivative polymers. Branched polymers are a term that has a linear backbone and at least one branch, and therefore encompasses star-shaped, brush-shaped, comb-shaped, and combinations thereof. Derivative polymers have a backbone that includes repeating units and one or more substituents or pendant groups, collectively called derivatization sites. A substituent is the substitution of one atom with another. A pendant group is a chemical part added to a polymer, which may be the same part as the polymer repeating unit or a different part. Thus, polymers include highly derivatized polymers and also polymers in which the derivatization sites are 0.01 to 20% by mass or less, calculated as the total MW of such sites compared to the total weight of the polymer. A person skilled in the art will immediately understand that all ranges and values ​​between the specified boundaries are contemplated, and that any of the following can be used as upper or lower limits, for example: 0.01, 0.05, 0.1, 0.2, 0.3, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20% mass.

[0175] Porous solids may be formed as monolithic materials, as layers on another material, device, or surface, as multiple layers, or as one or more layers of a nanoporous material or a material containing nanoporous materials. For example, multiple layers can be extruded, and the layers can be independently selected to form one or more of the following: nanoporous materials, microporous materials, hydrogels, single polymer materials, materials having two or more polymers, and non-nanoporous materials.

[0176] Furthermore, the manufacturing process of the material may affect the material properties, such as the polymer concentration in the polymer mixture passing through the die. The initial concentration of PVA or other hydrophilic polymer may be, for example, in the range of 5 to 70% by weight-volume (mass%) in water; generally, about 10 to 30% (mass%) is preferred; those skilled in the art will immediately understand that all ranges and values ​​between the explicitly stated boundaries are intended, and that, for example, any of the following can be used as upper or lower limits: 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70%.

[0177] The processes specified herein may be truncated before the polymer is crosslinked and processed to become a true nanoporous material, or they may be otherwise adapted to avoid the nanoporous structure. Generally, such materials have low strength and toughness and low solids content. Such materials are generally hydrogels when hydrophilic polymers are used in relatively low solids content. Thus, such materials, and even hydrogels, can produce materials that are somewhat inferior in properties to the nanoporous materials intended herein, but still superior to conventional processes and materials using the same polymers. Similarly, as a general rule, microporous solids will have properties that approach those of nanoporous materials and will have better strength than hydrogels.

[0178] Those skilled in the art commonly practice the quantification of pore size distribution in materials. Nanoporous, microporous, and microporous materials are disclosed herein, and the control of pore size in such materials is demonstrated. Accordingly, embodiments include materials having a specific amount or distribution of pore size. These can be measured at the surface, at depth from the surface in a cross-sectional sample, or with respect to the bulk of the material. For example, the pore diameter of a material at a surface, at a depth from the surface, or in the bulk may be within the range of 1 nm to 20 μm, or 50 to 100% of the pore diameters that fall above or below a certain value; those skilled in the art will immediately understand that all ranges and values ​​between the explicitly stated boundaries, e.g., 10, 20, 30, 40, 50, 60, 65, 70, 75, 80, 90, 95, 98, 99, 99.9 or 100%, and between 1, 10, 20, 30, 40, 50, 100, 200, 400, 500, 1000, 2000, 3000, 5000, 10000, 15000 or 20000 nm. An example of quantification for depth is, for example, a depth in the range of at least, or 1 to 5000 μm; a person skilled in the art will immediately understand that all ranges and values ​​between the indicated boundaries are intended to be 1, 2, 3, 4, 5, 10, 20, 50, 100, 250, 500, 750, 1000, 2000, 3000, 4000, or 5000 μm. For example, a surface may have a certain proportion of pores not exceeding a certain diameter, and a depth or depth range may have a certain proportion of pores not exceeding a certain diameter.

[0179] The embodiments include a process for producing a polymer material, comprising heating a mixture containing a water-soluble polymer and a solvent to a temperature above the melting point of the polymer, extruding the mixture, cooling the mixture while removing the solvent, and / or cooling the mixture while crosslinking. When multiple polymers are present in the solvent, with or without other additives, the melting points of the bound polymers in the solvent can be readily determined by those skilled in the art, for example, by observing the mixture as it is heated and changes from a cloudy appearance to a noticeably translucent appearance. Furthermore, some or all of the solvent can be removed from the mixture after or as part of a forming process using the mixture, while cooling is taking place. The embodiments include removing at least 50% by mass of the solvent in less than 60 minutes (or less than 1, 2, 5, or 10 minutes). The embodiments include removing at least 90% by mass (or at least 70% by mass or at least 80% by mass) of the solvent in less than 60 minutes (or less than 1, 2, 5, 10, or 30 minutes).

[0180] Bulk incorporation of polymers into porous solids During desolvation of a porous matrix, the porous material can be exposed to a mixture containing a solvating polymer (for bulk-integrated polymers) to draw it into its pores. The solvent in the mixture has an affinity for the matrix, and when the matrix absorbs the solvent, it is drawn in. The solvent in the mixture with the bulk-integrated polymer can be selected to have an affinity for the matrix so that it is absorbed into the desolvated matrix, but it does not need to be the same as the solvent in the matrix. In general, the hydrophilic solvent in the mixture is at least partially desolvated and adsorbed onto the hydrophilic porous matrix containing the hydrophilic solvent, and those skilled in the art can adjust various solvents as needed to create suitable conditions when bulk integration is intended.

[0181] A hydrophilic solvent is a solvent that is freely miscible with water at 20°C, or a solvent present in a mixture that is freely miscible with water at a certain concentration.

[0182] Solvation means that the matrix is ​​solvent-free, for example, completely dry, or less than or equal to the EWC of the matrix with respect to the solvent it contains. If the solvent in the matrix is ​​not water, the EWC can be calculated for the material based on measurements in the solvent, i.e., the term EWC can be used for non-water solvents in the appropriate context. For example, a hydrophilic matrix may be solvated in an aqueous solution of alcohol and will have an EWC of 1 to 100 of porous solids, and those skilled in the art will immediately understand that all ranges and values ​​between the specified boundaries are intended, for example, 1, 5, 10, 15, 20, 33, 40, 50, 60, 70, 80, 90, 95, 99, and 100% mass mean the total weight of solvent that can be removed.

[0183] Without being bound by any particular theory, it is believed that porous materials can be redissolved by desolvating them (dehydrating them if water is the solvent for the porous material) and exposing them to a polymer in solution, so that the polymer can be drawn into the pores. The polymer then forms physical bonds with the matrix material defining the pores, and by at least partially filling the pores and by physical bonding with the matrix, it is practically permanently incorporated into the bulk of the material. Alternatively or additionally, the polymer may have a hydrodynamic radius that presents a diameter exceeding the pore opening diameter, especially when the material is to be used in water or physiological solutions, so that the polymer can be permanently incorporated into the pores of the material. Generally, when a bulk-incorporated polymer is solvated with a polymer that wets the pores of a porous solid, the polymer can be drawn into the pores of the matrix during solvation. If the hydrophilic porous matrix is ​​below the EWC of the matrix, the mixture containing the bulk-incorporated polymer will be drawn in because the solvent of the polymer is compatible with the matrix material, for example, because it wets the pores of the material. For example, a hydrophilic solvent will typically wet the pores of a hydrophilic matrix.

[0184] Materials comprising a porous matrix of polymers bonded by non-covalent bonds are preferred embodiments because these materials can be produced with a high degree of control over pore size and material properties, including the selection of nanoporous, microporous, or other characteristic pore sizes. The matrix may contain physically crosslinked water-soluble polymers that define the pores. The solids content concentration of these water-soluble polymers may be at least 33% by mass of the matrix at the equilibrium water content (EWC) of the matrix, but other concentrations may also be used.

[0185] Accordingly, embodiments of the process for incorporating polymers into porous materials include providing a material having a porous, hydrophilic matrix comprising one or more water-soluble polymers (also referred herein as matrix polymers) crosslinked with each other to form a matrix. The material having the matrix is ​​exposed to a mixture comprising one or more polymers dissolved in a solvent (also referred to as bulk-integrated polymers, preferably the polymers being water-soluble, and the mixture also referred to as a conditioning (or conditioning) mixture or bulk-integrated mixture), wherein the matrix is ​​below EWC and affinity for the solvent before exposure to the mixture. The material before exposure to the mixture having the bulk-integrated polymers is desolvated.

[0186] In some embodiments, the bulk incorporation process creates an outer zone where pores are filled, an intermediate zone where most or most of the pores are filled, and an inner zone where there is little or no polymer incorporation. Bulk incorporation modifies not only the surface pores but also pores below the surface, for example, in the range of at least or 1 to 5000 μm; those skilled in the art will immediately understand that all ranges and values ​​between the explicitly stated boundaries, e.g., 1, 2, 3, 4, 5, 10, 20, 30, 40, 50, 75, 100, 250, 500, 750, 1000, 2000, 3000, 4000, or 5000 μm, are intended. The percentage of pores having polymer is assayed as already described, and the incorporation may be graded by a percentage cutoff, for example, a first zone with 100% pore filling, a second zone with 50% filling, a third zone with 0% filling.

[0187] The bulk incorporation process is preferably carried out using a porous matrix made from a water-soluble polymer, which does not need to contain hydrophobic domains in the polymer; for example, the matrix may be made of PVA alone. The polymer may form the matrix by physical crosslinking. Thus, embodiments include materials that contain a matrix made using a water-soluble polymer that does not contain hydrophobic domains or that does not contain hydrophobic domains. However, some hydrophobic domains may be acceptable when a hydrophilic matrix is ​​made using a water-soluble polymer with physical crosslinking without destroying the matrix formed thereby. Embodiments of the present invention include the hydrophobic content of the polymer forming the porous matrix being 0, 1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 12, or 15% by mass.

[0188] A porous matrix consisting essentially of water-soluble polymers means that the content of polymers crosslinked to form the matrix is ​​up to 3% by mass. RO agents such as salts are not polymers that crosslink to form the matrix. A porous matrix consisting essentially of physically crosslinked polymers means a matrix that does not contain agents that create covalent bonds between polymers, or is crosslinked with such agents in small amounts so as not to exceed about 6% of the polymers (referring to the number of polymers), for example, such that the stoichiometric ratio of polymer number to bifunctional crosslinker is at least 100:3. Similarly, a matrix that is essentially free of covalent bonds is made using polymers that are crosslinked in a way that about 6% or less of the polymers (in number) are not covalently crosslinked. The number of covalent bonds in the matrix may also be limited to stoichiometric ratios of 100:3 to 100:100, for example, the ratio of 100 to any of 3, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, or 100 in number. For example, hydrogels produced by free radical polymerization typically have 100% polymers bonded to each other by covalent bonds, which is a stoichiometric ratio of polymer:covalent bonds of 100:100.

[0189] As otherwise stated, porous solids can be made within a controlled range of pore diameters, and may be made to provide a matrix that does not have pores larger than a certain diameter. The diameter may be measured in an appropriate context, for example, by EWC in distilled water. Thus, embodiments include polymers encapsulated in a porous matrix that does not have pores larger than 1 to 5000 μm; those skilled in the art will immediately understand that all ranges and values ​​between the expressed boundaries, e.g., 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 50, 100, 200, 250, 300, 400, 500, 750, 1000, 2000, 3000, 4000, or 5000 μm are intended.

[0190] Porous solids may have other materials present as described elsewhere herein, such as radiopaque (RO) agents that are added to the matrix but are not part of it. RO agents typically contribute little to the crosslinking that provides strength to the matrix. Similarly, other materials may be present in the matrix even if they are not part of it, such as wires and reinforcing materials. A matrix made by physical crosslinking is one type of matrix that can be made of a material that defines pores of a certain diameter, and can be seen as in contrast to a hydrogel, which has polymer chains that are spaced apart from each other and connected in a mesh network structure, such as those generally formed using free radical polymerization or by monomer / polymer reactions in solution. Such a mesh network would generally not be expected to stably incorporate polymers into its pores without covalent bonding using a polymer-in-being process. Porous materials are described in detail herein and can be freely selected for use with bulk-incorporated polymers as led by the disclosure herein. Porous materials may be selected to have bulk properties such as those described herein.

[0191] The bulk incorporated polymer may be a polymer described elsewhere in this specification for porous solids. Examples include water-soluble polymers. Water-soluble polymers may include, for example, polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), polyacrylic acid (PAA), polyacrylamide, hydroxypropyl methacrylamide polyoxazoline, polyphosphates, polyphosphazene, poly(vinyl acetate), polypropylene glycol, poly(N-isopropylacrylamide) (PNIPAM), polysaccharides, sulfonated hydrophilic polymers (e.g., sulfonated polyphenylene oxide, Nafion®, sulfobetaine methacrylate), and iodine-added variations (e.g., PVA-I, PVP-I), or variations having further pendant groups, copolymers of the same, and mixtures of the same, which may contain one or more polymers meaning polymers with different chemical compositions, such as PVA and PEG. Polymer means one or more polymers.

[0192] The solubility of water-soluble polymers for porous matrices or bulk incorporation may be selected, for example, as at least 1, 2, 5, or 10 g / 100 ml in water at 20°C. The polymers may be selected to be linear or branched. Embodiments include, for example, polymers having molecular weights of 40 k to 5000 k Daltons or hydrophilic polymers; those skilled in the art will immediately understand that all ranges and values ​​between the specified boundaries are intended, and that, for example, any of the following are available as upper or lower limits: polymers having molecular weights of 40 k, 50 k, 100 k, 125 k, 150 k, 250 k, 400 k, 500 k, 600 k, 750 k, 800, 900 k, 1 million, 1.5 million, 2.5 million, and 3 million. The molecular weight of the polymer can be selected considering the size of the pores available in the porous solid. Nanoporous or microporous materials are preferred.

[0193] The bulk incorporated polymer may be the same as the polymer forming the porous matrix, the same as at least one of the polymers constituting the matrix, or different from it.

[0194] It should be noted that the concentration of the bulk incorporated polymer in the mixture may be any concentration at which the polymer is dissolved, with reference to the mixture at the start of the process, and that polymers that are not dissolved, or other insoluble materials, are not destined to enter the pores. In some embodiments, the concentration is 1 to 50% by mass; those skilled in the art will immediately understand that all ranges and values ​​between the specified boundaries, e.g., 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 33, 35, 40, and 50% by mass are intended.

[0195] The solvent for the mixture is appropriately selected to solvate the polymer and to provide a solvent that is absorbed by the porous solid. For hydrophilic matrices, hydrophilic solvents are generally preferred. The solvent may be water, organic, or aqueous, or the same, for example, without organic solvents. In some embodiments, the concentration of water is 0 to 99, for example, 0, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 95, or 99% by mass.

[0196] The temperature of the conditioning mixture should not exceed the melting temperature of the porous solid matrix. The temperature range may be, for example, 10 to 100°C, or for example, 10, 20, 30, 37, 40, 50, 60, 70, 80, or 90°C.

[0197] The exposure time is preferably a certain period of time (or a certain number of minutes or hours) required for the porous solid to reach EWC in the mixture. The duration may include 2, 4, 6, 8, 10, 12, 16, 20, 24, and 48 hours in some embodiments. Stirring and temperature may be manipulated to affect the exposure time, for example, to accelerate the achievement of EWC or to control the viscosity of the mixture. Salt and / or osmotic content may be adjusted to be useful, for example, for solubility, viscosity, and / or EWC.

[0198] The examples provide guidance on salt concentrations in conditioning mixtures. Examples of salt concentrations are 0.1–2% by mass. Generally, single-charged cations with smaller atomic radii have greater penetration into the depth of porous solids, while larger cations reduce penetration. Examples of salts include single-cation, divalent cation, or other cations, such as sodium, potassium, lithium, copper, and quaternary ammonium (NR4). + Here, R is a salt of hydrogen, alkyl, or aryl group, magnesium, calcium, copper, iron, or zinc. Generally, a physiological pH with a buffer has been useful for the mixture. The pH may be adjusted to increase or decrease osmosis into the matrix, and the solvent may or may not contain a buffer salt. Examples of pH ranges are 4 to 10, e.g., 4, 5, 6, 7, 8, 9, or 10.

[0199] The viscosity of a conditioning mixture, which refers to a water-soluble polymer and a solvent, is influenced by pH (higher pH results in higher viscosity), polymer concentration and / or molecular weight, and polymer branching, with increases in any of these generally leading to higher viscosity. Generally, higher viscosity reduces the penetration of bulk-incorporated polymers into porous solids. Embodiments are porous materials comprising water-soluble polymers incorporated into the pores of a porous matrix. The matrix may comprise physically crosslinked water-soluble polymers that are crosslinked with each other to form the matrix and define the pores. The matrix may have features such as those disclosed herein, e.g., polymer content, weight percentage of polymer, strength, Young's modulus, degree of coverage, pore size, etc.

[0200] The surface coating of the water-soluble polymer in the porous matrix may be complete. Complete coating, where the pores of the substrate surface are not visible under SEM conditions, indicates coating in EWC. The degree of coating may be less than 100%, for example, 50-100%; those skilled in the art will immediately understand that all ranges and values ​​between the indicated boundaries, e.g., 50, 60, 70, 80, 90, 95, 98, 99, 99.9, or 100%, are intended.

[0201] The incorporation of bulk polymers can degrade the physical properties of porous solids. Embodiments therefore include porous solids having 1–20% less Young's modulus and / or tensile strength as a result of being modified with water-soluble polymers compared to the same material not modified with water-soluble polymers, e.g., as disclosed herein; those skilled in the art will immediately understand that all ranges and values ​​between the explicitly stated boundaries, e.g., 1, 2, 3, 4, 5, 7, 9, 10, 12, 15 or 20%, are intended. A test for the stable incorporation of water-soluble polymers is as follows: The test device is immersed in a physiologically representative liquid (i.e., PBS) under body temperature conditions and subjected to a circulating peristaltic loop with the test device placed directly on the head of a pump at a flow rate of 10–12 mL / sec at 150 rpm for 24 hours and 0.1225 cm 3 *s -1 *cm-2 The volume flux rate (or flux, or flow rate) is used to approximate 500,000 mechanical sample compressions. While the test revealed a loss of as much as 25%, other test criteria may be used, for example, a loss of 0–50% mass, e.g., 1, 5, 10, 15, 20, 25, 30, 40, or 50% mass. Alternatively, other tests may be proposed, for example, a loss of 0–5% mass with 1–52 weeks of static exposure to excessive PBS, e.g., a loss of 1, 2, 3, 4, 5, 10, 20, 30, 40, 50, or 52 weeks.

[0202] product With reference to the materials described herein, including nanoporous materials, microporous materials, and hydrogels, end-users or intermediate products, or products containing materials, having a desired aspect ratio, for example, at least 3:1. The aspect ratio increases as the length of the device increases and the width decreases. Those skilled in the art will immediately understand that all ranges and values ​​between the indicated boundaries are contemplated, and that, for example, any of the following are available as upper or lower limits: 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 50:1, 100:1, 1000:1. High aspect ratios are very advantageous for certain devices, for example, many types of catheters. In principle, thin tubes can be continuously extruded without limitation in terms of length. Such devices include, for example, tubes, rods, cylinders, and cross-sections having square, polygonal, or circular profiles. Two or more lumens may be provided in any one of them. The device may be made of a single material, essentially a single material, or multiple materials including various layers as already described, or reinforcing materials, fibers, wires, braided materials, braided wires, braided plastic fibers.

[0203] In particular, the extrusion process provides a concentric arrangement of lumens. Concentricity is in contrast to eccentricity, which means that the lumens are off-center. In the case of multiple lumens, the lumens may be arranged symmetrically: symmetry is in contrast to eccentric arrangement of lumens, which is a result of an inadequately controlled process. Embodiments include the aforementioned devices having an aspect ratio of at least 3:1, with lumens arranged without eccentricity, or with one lumen concentric with the longitudinal axis of the device.

[0204] Porous solids such as nanoporous materials, microporous materials, and tough hydrogels may be used to fabricate catheters or medical fibers. These may be made from polymers with incorporated bulk and may have the various characteristics described for the same. Examples of catheters include central veins, peripheral insertion centers, midline, peripheral, tunnel type, dialysis access, hemodialysis, vascular access ports, peritoneal dialysis, urinary tract, nerve, peritoneum, intra-aortic balloon pumps, diagnostic, intervention, drug delivery, etc.), shunts, wound drains (external, including ventricles, ventricular peritoneum, lumboperitoneum), inlet ports, etc. Porous solids may be used to fabricate implantable devices, including fully implantable and percutaneously implanted, permanent or temporary. Porous solid materials may be used to fabricate blood-contact devices or devices that come into contact with body fluids (including extracorporeal and / or intracorporeal 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 those with a diameter of <6 mm), pacemakers, implantable cardioverter-defibrillators, cardiac resynchronization devices, cardiovascular device leads, ventricular assist devices, catheters (including 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 may include tubular nanoporous materials with fasteners, such as Luer fasteners or connectors, for working with other devices. Radiopaque agents may be added to materials, fibers, or devices. 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. RO agents can be incorporated, for example, in an amount of 5 to 50% by mass relative to the total solid weight, such as 5, 10, 20, 30, 40, or 50%.

[0205] Medical fibers using porous solid materials include applications such as sutures, threads, medical fabrics, braids, meshes, knitted or woven meshes, nonwovens, and devices using these materials. The fibers are strong and flexible. Materials may be manufactured using these fibers to be resistant to fatigue and abrasion.

[0206] In exemplary embodiments, the method involves administering a device comprising a body portion to an external (or external, or outside) orifice of a target, wherein the body portion comprises a polymer material comprising a water-soluble polymer and a biological activator associated with the polymer material. In some embodiments, the device has an aspect ratio of 3:1 or greater. In some embodiments, the biological activator is substantially homogeneously distributed within the polymer material. In some embodiments, the biological activator is heterogeneously distributed within the polymer material (i.e., on one or more surfaces of the polymer material). In some embodiments, the administration of the device (e.g., device 10 in Figure 1A, device 12 in Figure 1B, device 14 in Figure 1C) does not involve the use of a sheath introducer. The polymer material is substantially non-thrombotic, and has a water content of less than 5% by mass and 0.1% by mass or more in a first configuration (e.g., a water content below the equilibrium water content state, such as a dehydrated state), and is configured to swell from the first configuration by amounts of 5% by mass or more and 50% by mass or less (e.g., a water content lower than the equilibrium water content state, such as a dehydrated state) to a second configuration (e.g., the equilibrium water content state) in 60 minutes or less (e.g., 10 minutes or less, 5 minutes or less, 1 minute or less, or 10 seconds or less).

[0207] Treatment method In some embodiments, methods for treating a subject are described. In some embodiments, the method involves administering the device described herein (e.g., any embodiment of the device described herein or a combination thereof) to the orifice of the subject.

[0208] In some embodiments, the method includes swelling a polymer material as described herein. For example, in some embodiments, the method includes swelling a device and / or polymer material from, for example, a first configuration (e.g., a water content lower than an equilibrium water content state such as a dehydrated state) to a second configuration (e.g., an equilibrium water content state) by an amount of 2% by mass or more, 3% by mass or more, 4% by mass or more, 5% by mass or more, 10% by mass or more and 15% by mass or more, 20% by mass or more, 25% by mass or more, 30% by mass or more, 35% by mass or more, 40% by mass or more, or 45% by mass or more. In some embodiments, the method includes swelling the device and / or polymer material from, for example, a first configuration (e.g., a state with a moisture content lower than the equilibrium moisture content state, such as a dehydrated state) to a second configuration (e.g., the equilibrium moisture content state) by amounts of 50% by mass or less, 45% by mass or less, 40% by mass or less, 35% by mass or less, 30% by mass or less, 25% by mass or less, 20% by mass or less, 15% by mass or less, or 10% by mass or less. Combinations of these ranges are also possible (e.g., greater than 5% by mass and 40% by mass or less).

[0209] In some embodiments, the method includes swelling a polymer material to an equilibrium water content. In some embodiments, the method includes swelling a polymer material 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).

[0210] In some embodiments, the method includes swelling a polymer material 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).

[0211] In some embodiments, the method involves swelling a polymer material 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 involves swelling a polymer material such that the inner diameter and / or outer diameter increases by 1 to 20%, while the length increases by 0.1 to 19%.

[0212] In some embodiments, swelling occurs after administration. In some embodiments, swelling of the polymer material after administration to the orifice of the subject closes (or 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 or equal to the size of the orifice into which the polymer material 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, the 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 may result in hemostasis.

[0213] 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, rehydrating the device involves using 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 saline (HBSS), and / or isotonic salt solutions.

[0214] Further definition The term "medically acceptable" refers to a material that is highly purified to be free of contaminants and non-toxic. In the context of biomaterials or medical devices, the term "essentially composed" means a material or device that does not contain more than 3% by mass of other materials or components, such that the 3% does not render the device unsuitable for its intended medical use. Equilibrium water content (EWC) refers to the water content at which the wet weight of a material becomes constant before the material degrades (or decomposes). Generally, materials with a high solids content are observed to reach equilibrium water content in 24–48 hours. Distilled water is used to measure EWC unless otherwise specified.

[0215] The term w / v refers to weight per volume, such as g / L and mg / mL. The terms biomaterials and biomedical materials are used interchangeably herein and include biomedically acceptable materials for use in biomedical technologies such as implants, catheters, blood contact materials, tissue contact materials, diagnostic assays, medical kits, tissue sample processing, or other medical purposes. Furthermore, materials suitable for biomedical applications are not limited to those described herein and can also be created as general-purpose materials. Physiological saline is a phosphate buffer solution with a pH of 7-7.4 at 37°C and the physiological osmotic pressure of humans.

[0216] Molecular weight (MW) is measured in units of 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 it is crosslinked. If the distance between crosslinks is specified, it means the weight-average MW between crosslinks unless otherwise specified. k represents thousands, M represents millions, and G represents billions; 50 kMW means 50,000 MW. Dalton is also a unit of MW, and similarly, when used for polymers, it means the weight-average.

[0217] The publications, journal devices, patents, and patent applications referenced herein are incorporated herein for all purposes, and in the event of any conflict, the specification shall prevail. The features of the embodiments described herein may be mixed and adapted as guided by the need to produce an operable process or product.

[0218] As used herein, the terms “therapeutic” or “drug” mean 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 in the subject’s body to treat and / or prevent the disease, disorder, or condition.

[0219] As used herein, when a component is referred to as “adjacent” to another component, it may be directly adjacent to (e.g., in contact with) that component, or it may also have one or more intervening components. A component that is “directly adjacent” to another component means that there are no intervening components.

[0220] "Subject" refers to any animal, such as a mammal (e.g., 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, or guinea pigs. Generally, the present invention is directed toward use in humans. In some embodiments, subjects may exhibit health benefits, for example, upon administration of a self-righting device.

[0221] As used herein, “fluid” is given in its ordinary sense, i.e., a liquid or a gas. A fluid cannot maintain a defined shape and will flow during an observable time frame to fill the container in which it is placed. Thus, a fluid may have any suitable viscosity that allows for flow. If two or more fluids are present, each fluid may be independently selected by those skilled in the art from essentially any fluid (liquid, gas, etc.).

[0222] Examples The following examples are intended to illustrate some embodiments described herein, including some aspects of the present invention, but are not intended to represent the entire scope of the invention.

[0223] Example 1: Packaged article containing a catheter The following describes exemplary packaging articles according to some embodiments described herein.

[0224] The first configuration incorporates glycerol as a humectant (hydration aid) and a foil pouch (13-inch x 19-inch foil pouch, manufactured by Stephen Gould Associates, Shannon Packaging Inc, PFP400) on the outside of the Tyvek catheter kit. The foil pouch creates an environment with minimal relative humidity for the catheter during storage. The foil, in some cases, minimizes moisture transport from the catheter to the fluctuating external environment, facilitating catheter hydration and thus generally ensuring that the catheter can be hydrated to its intended dimensions within a given time.

[0225] In one sample, packaging was performed that included a humidity chip (HUMIDIChip, Anderson Product, AN-1071) in a foil pouch to further assist in achieving appropriate relative humidity. Functional testing revealed that the hydration requirements could be met, for example, by reconditioning (or readjusting) the catheter in a Tyvek pouch for 24 hours after sterilization. The reconditioning step is performed by placing the catheter with the Tyvek pouch into the foil packaging along with the humidity chip. The humidity chip is discarded after the reconditioning period, and the catheter is then resealed in foil and prepared for final packaging to be delivered to the end user. Removing the chip from the final packaging eliminates the potential risk of the chip falling from the packaging into a sterile field. Therefore, the reconditioning step can, in some cases, be incorporated as part of the manufacturing process, rather than as part of the final product.

[0226] Exemplary foil pouches and humidity chips are shown in Figures 6 and 7, respectively.

[0227] Example 2: Moisture content The following examples illustrate the moisture content of exemplary articles under various packaging conditions.

[0228] Figure 8 is a plot showing moisture content as a function of pouch / humidity control (e.g., tip). The moisture content test method used an automated moisture analyzer with a halogen lamp heat source to gravimetrically measure the moisture content of the sample. The data showed that reconditioning the product maintained the moisture content within the catheter over the long term. The data also showed that prolonged exposure to a humid tip in a sealed environment increased the equilibrium moisture content.

[0229] Example 3: Composition of the packaged article The following examples illustrate exemplary configurations of the packaged articles described herein.

[0230] 1) Sterilize the product in a foil pouch with a Tyvek header. This generally allows ethylene oxide (EtO) sterilizer to enter and exit the pouch (through the Tyvek), after which the foil is sealed and the Tyvek portion is separated. Provide the customer with a single outer packaging rather than placing a foil pouch inside a Tyvek pouch.

[0231] 2) Sterilizing the product in a foil pouch while it is still hydrated eliminates preparation time, allowing for immediate catheter insertion. Sterilization methods such as EO (electrolysis) and radiation (e-beam, gamma, etc.) can be used.

[0232] Example 4: Packaging of polymer materials to maintain moisture content The following examples illustrate exemplary methods for packaging polymer materials and / or devices according to some embodiments described herein.

[0233] Device packaging in porous Tyvek pouches may be useful for sterilization with ethylene oxide (EtO) gas. EtO sterilization processes generally utilize humidity and pressure / vacuum cycles to function properly. During testing, it was found that the hydration level of the device could be affected by the sterilization cycle, thus impacting the device's hydration time. Furthermore, additional testing revealed that storage temperature and humidity cycles also affect the hydration level and potentially impact the device's hydration time. A method for maintaining a consistent hydration level within the packaging is desirable.

[0234] In this example, the catheter device is packaged in a Tyvek pouch and sterilized by EtO. After sterilization, the Tyvek pouch is packaged in a second non-sterile, water-impermeable pouch containing a humidity chip. The humidity chip releases water into the pouch, re-humidifying the catheter. The humidity chip can be a commercially available product (e.g., AnPro Humidichip) or a custom device made of cellulose or sponge-like material absorbed with sterile water, typical saline solution, or other aqueous media. The humidity control component (i.e., the chip) may also contain an anti-growth agent or bacteriostatic agent such as alcohol, sodium hypochlorite, iodine, peroxide, or phenol. A schematic flowchart of this exemplary method is shown in Figure 9.

[0235] Example 5: Packaging of catheters and related components into trays and kit assemblies The following examples illustrate exemplary methods for packaging catheter devices in trays and kit assemblies according to some embodiments described herein.

[0236] In this example, the catheter device was packaged in a tray (10.75 inches × 8.90 inches × 1.38 inches) containing white HIPS material (shown in Figure 10). The catheter was first inserted into the catheter hoop, and then the catheter and peripheral components were placed in the tray. The tray had a transparent lid (9.42 inches × 7.57 inches × 0.93 inches) containing PET. The catheter hoop (outer diameter 0.150 inches × inner diameter 0.100 inches × 30.0 inches) contained polyethylene or a mixture of low-density polyethylene (LDPE) and high-density polyethylene (HDPE). A two-channel catheter clip with a 0.145-inch ID channel containing polypropylene was also used in the process of packaging the catheter device in the tray.

[0237] Example 6: Packaging of trays and kits into Tyvek pouches The following examples illustrate exemplary methods for packaging trays and kit assemblies (as shown in Figure 10) into containers (Tyvek pouches) according to some embodiments described herein.

[0238] In this example, the trays and kits (e.g., the trays and kits in Figure 10) were further packaged in containers such as Tyvek pouches and properly sealed. The sealed Tyvek pouches were then packed into shippers (or carriers) such as cardboard boxes. The packed shippers were then sterilized in a PCS using a valid (or authorized or validated) cycle. Figure 10 is a photograph of the trays and kits packaged in a sealed Tyvek pouch (18.0 inches x 12.0 inches) with clear poly / Tyvek and a three-sided chevron seal. Note that the containers (e.g., Tyvek pouches) may have any of the various dimensions described elsewhere in this specification.

[0239] Example 7: Packaging of sterilized products into foil pouches The following examples demonstrate exemplary methods for packaging sterilized products in containers such as foil pouches, according to some embodiments described herein.

[0240] The sterile products were received via AVI and subsequently placed in a container such as a foil pouch (as shown in Figure 12) along with a humidity chip. The sterile products were conditioned for 24 hours, after which the foil pouch was opened and the humidity chip was discarded. The conditioned sterile products were then placed in a new foil pouch and properly sealed. An example of a sterile product is shown in Figure 11, which is a photograph of a Tyvek pouch containing the tray and kit assembly that make up the catheter device. The foil pouch can have any of the appropriate dimensions. For example, as shown in Figure 12, the foil pouch had dimensions of 19.0 inches × 13.0 inches, a thickness of 4 mils, and contained PET / foil / polybarrier film. The humidity chip had dimensions of 2 inches x 2 inches and included a Humidichip RH Stabilizer.

[0241] Example 8: Container with Tyvek header The following examples illustrate exemplary packaging containers, including a header portion, according to several embodiments.

[0242] The catheter device may be sealed in a container containing foil material (e.g., a foil pouch) with a header (e.g., a Tyvek header). The pouch may then be sterilized and sealed just above the header. The header may then be cut from the container, and the sealed container may be inserted into a finished product box. For example, as shown in Figure 13A, the container contained a foil pouch with a Tyvek / poly header and had dimensions of 9.5 inches x 9.0 inches. Note that the container may have any suitable dimensions and is not so limited. For example, Figure 13B shows photographs of two containers, each having dimensions of 18 inches x 8.125 inches and containing a Tyvek header (5.125 inches x 8.125 inches) and a foil pouch (13.375 inches x 8.125 inches). Any suitable finished product box can be used, such as 20Pt C1S SBS White Paperboard.

[0243] Example 9: Container used in the IR kit The following examples illustrate exemplary designs of containers for use in IR kits, according to several embodiments.

[0244] The IR kit is first assembled by placing a Tyvek pouch containing accessories (Figure 14A) into a foil pouch containing the catheter device (Figure 14B), after which the two pouches can be folded and placed in a carton. The pouches can have any dimensions suitable for use with IR. For example, Figure 14A shows a Tyvek pouch (6.5 inches x 9 inches) and a foil pouch (8.125 inches x 9 inches) used in an IR kit. The carton can have any suitable size. For example, the pouches shown in Figure 14A may be placed in a carton having dimensions of 8.25 inches x 9.25 inches x 1.25 inches. Each carton (containing the sealed pouches) may have any suitable weight (e.g., approximately 121 g for the IR kit). The carton may then be placed in an over-shipper of any suitable size. For example, an overshipper with dimensions of 8.25 inches x 9.25 inches x 6.25 inches can be used to accommodate five identical cartons, each with dimensions of 8.25 inches x 9.25 inches x 1.25 inches.

[0245] Example 10: Container for use in a nursing kit The following examples illustrate exemplary designs of containers for use in nursing kits, according to several embodiments.

[0246] A container containing a catheter device placed inside a foil material (e.g., a foil pouch) may be used in a nursing kit. For example, in figures 15A-15B, a foil pouch having any suitable dimensions (e.g., 8.125 inches x 13 inches) suitable for use in a nursing kit may be used to house the catheter device. The foil pouch may be placed in a nursing tray (3 inches x 7 inches x 13 inches) which can then be placed in an over-shipper. Each nursing tray and its contents may have any suitable weight (e.g., about 456 g) suitable for use. Any suitable number of nursing trays (e.g., about 5 trays) can be packed into the over-shipper.

[0247] Example 11: Container for use in the Max Barrier Kit The following examples demonstrate exemplary designs of containers for use with Max Barrier Kits, according to several embodiments.

[0248] A container containing foil material (e.g., a foil pouch) with a catheter device placed inside may be used in a Max Barrier kit. For example, in figures 15A-15B, a foil pouch having dimensions suitable for use in a Max Barrier kit (e.g., 8.125 inches x 13 inches) may be used to house the catheter device. The foil pouch may be placed in a nursing tray (3 inches x 7 inches x 13 inches) and then in an over-shipper. Each Max Barrier tray and its enclosed contents may have any suitable weight for use (e.g., about 1031 g). Any suitable number of Max Barrier trays (e.g., about 5 trays) may be packaged in an over-shipper.

[0249] While several embodiments of the present invention have been described and illustrated herein, those skilled in the art will readily conceive of various other means and / or structures for performing the functions described herein and / or obtaining the results and / or one or more advantages, and each of such variations and / or modifications will be considered within the scope of the present invention. More generally, those skilled in the art will 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 use or application in which the teachings of the present invention are used. Those skilled in the art will be able to recognize or confirm many equivalents to specific embodiments of the present invention described herein without using anything more than routine experimentation. Thus, the embodiments described herein are presented only as examples, and it will be understood that within the scope of the appended claims and their equivalents, the present invention may be carried out in ways different from those specifically described and claimed. The present invention is directed toward the individual features, systems, devices, materials, kits, and / or methods described herein. Furthermore, any combination of two or more such features, systems, devices, materials, kits, and / or methods is within the scope of the present invention, provided that they are not mutually inconsistent.

[0250] As used herein and in the claims, the indefinite devices “a” and “an” should be understood to mean “at least one” unless explicitly indicated otherwise.

[0251] As used herein and in the claims, the phrase “and / or” should be understood to mean “either or both” of the elements thus combined, i.e., elements that are contingent in some cases and contingent in others. The other elements may be present, in addition to those specifically identified by the “and / or” clause, whether related to or unrelated to the specifically identified elements, unless explicitly indicated otherwise. Thus, as a non-restrictive example, a reference to “A and / or B” when used in combination with open-ended language such as “including” may, in one embodiment, refer to A without B (optionally including elements other than B); in another embodiment, refer to B without A (optionally including elements other than A); in yet another embodiment, refer to both A and B (optionally including other elements); and so on.

[0252] As used herein and in the 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” shall be interpreted as inclusive, that is, including at least one of the number of elements or the list, but also including one or more, and optionally including items not in the additional list. Only terms that are clearly indicated in the opposite way, such as “one only” or “exactly one,” or, as used in the claims, “consisting of,” shall mean including the number of elements or exactly one element of the list. In general, the term “or” as used herein shall be interpreted as indicating an exclusive choice (i.e., “one or the other, but not both”) only when preceded by terms of exclusivity such as “either,” “one or the other,” “one or the other,” or “exactly one.” As used in the claims, “consisting essentially of” shall have its usual meaning as used in the field of patent law.

[0253] When used herein and in the claims, the phrase “at least one” referring to a list of one or more elements should be understood to mean at least one element selected from any one or more elements in the list of elements, but not necessarily having to include at least one of each and all of the elements specifically listed in the list of elements, nor excluding any combination of elements in the list of elements. This definition also allows for the presence of elements other than those specifically identified in the list of elements referred to by the phrase “at least one,” whether or not they relate to the specifically identified elements. Thus, as a non-restrictive example, “at least one of A and B” (or equivalently, “at least one of A or B,” or equivalently, “at least one of A and / or B”) could, in one embodiment, refer to at least one, optionally more than one A, in which B is absent (and optionally includes elements other than B). In another embodiment, this may refer to at least one which includes one or more B, where A is absent (and optionally includes elements other than A); in yet another embodiment, at least one which includes one or more A, and optionally one or more B (and optionally includes other elements); and so on.

[0254] In the claims, as in the specification above, all transitional phrases such as “comprising,” “including,” “carrying,” “having,” “containing,” “involving,” and “holding” shall be understood to be open-ended, meaning they include but are not limited to including. Only the transitional phrases “consisting of” and “consisting essentially of” must be closed or semi-closed transitional phrases, respectively, as provided for in Section 211.03 of the U.S. Patent and Trademark Office's “Manual for Patent Examination Procedure.”

[0255] Any terms used herein relating to the shape, orientation, arrangement, and / or geometric relationships between 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 subject to characterization by such terms, are defined by these terms. Unless otherwise specifically defined or indicated, absolute conformity to the mathematical definition of such terms is not required; rather, conformity to the mathematical definition of these terms is understood to the extent possible with respect to the thus characterized subject, as would be understood by those skilled in the art most relevant to such subject matter. Examples of terms relating to shape, orientation, and / or geometric relationships include, but are not limited to, terms describing the following: Shape—round, square, rhombus, circle / round, rectangle / rectangle, triangle / triangle, cylinder / cylinder, ellipse / ellipse, (n) polygon / (n) polygon, etc.; Angular direction—perpendicular, orthogonal, parallel, vertical, horizontal, parallel, etc.; Contour and / or locus—contour, locus, or trajectory, or geometric direction, etc. (e.g., perpendicular to the vertical, not perpendicular, etc.); Contour and / or locus—plane / plane, coplane, hemisphere, hemisphere, straight line / straight line, hyperbola, monoline, 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—for example, smooth, reflective, transparent, clear, opaque, rigid, impermeable, uniform (ly), inert, non-wetting, insoluble, stable, immutable, constant, homogeneous, etc.; and many others that will be obvious to a person familiar with the relevant art. As an example, a fabricated device that will be described herein as a “square” does not need to be perfectly planar or linear and have faces or sides that intersect at exactly 90-degree angles (in fact, such a device A may exist only as a mathematical abstraction), but rather the shape of such a device should be interpreted as approximating a “square” as will be understood by a person skilled in the art, or as mathematically defined to the extent that it is typically achievable and feasible for the fabrication techniques described in particular.As another example, two or more manufactured devices described herein as “aligned” do not need to have faces or sides that are perfectly aligned (in fact, such devices may exist only as mathematical abstractions), but rather, as understood by those skilled in the art, the arrangement of such devices should be understood as approximating a mathematically defined “alignment” to the extent that it is typically achievable and would be achievable for the manufacturing techniques mentioned, as understood by those skilled in the art or as specifically described.

Claims

1. Container containing foil material, Catheters containing polymer materials, and A packaging article including a humidity control member, wherein the polymer material has a water content of 2% by mass or more and 40% by mass or less. The humidity control member includes a humidity control sponge. The water content is less than the equilibrium water content of the polymer material, and A packaging article wherein the polymer material swells to an amount of 5% by mass or more relative to the equilibrium water content state.

2. Container containing foil material, Polymer materials containing polyvinyl alcohol, and A packaging article including a humidity control member, wherein the polymer material has a water content of 2% by mass or more and 40% by mass or less. The humidity control member includes a humidity control sponge. The water content is less than the equilibrium water content of the polymer material, and A packaging article wherein the polymer material swells to an amount of 5% by mass or more relative to the equilibrium water content state.

3. The packaging article according to claim 1 or 2, wherein the foil material is substantially impermeable to water.

4. The packaged article according to any one of claims 1 to 3, wherein the container is a pouch.

5. The packaging article according to claim 1, wherein the container further comprises a gas-permeable polymer.

6. The packaging article according to claim 5, wherein the gas-permeable polymer includes high-density polyethylene.

7. A packaged article according to any one of claims 1 to 6, including a header portion.

8. The packaging article according to claim 7, wherein the header portion is removed after sterilization of the catheter.

9. The packaged article according to claim 8, wherein the header portion contains a gas-permeable polymer.

10. The packaged article according to claim 9, wherein the humidity control member includes a fluid reservoir.

11. The packaged article according to claim 7, wherein the humidity control member is disposed within the header portion.

12. The packaging article according to any one of claims 1 to 11, wherein the foil material comprises aluminum, polyethylene terephthalate, or a combination thereof.

13. The packaging article according to any one of claims 1 to 12, wherein the polymer material has a water content of 2% by mass or more and 12% by mass or less.

14. The packaging article according to any one of claims 1 to 13, wherein at least 80% of the inner surface area of ​​the container is the foil material.

15. The polymer material has a water content of 2% by mass or more and 20% by mass or less. A packaged article according to any one of claims 1 to 14, optionally having a water content of 5% by mass or more and 10% by mass or less.

16. The packaging article according to any one of claims 1 to 15, wherein the polymer material 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.

17. A method comprising removing a catheter from a packaged article according to any one of claims 1 to 16, and rehydrating the catheter to an equilibrium water content.

18. A method for manufacturing a packaged article, wherein the manufacturing method is: A catheter containing a polymer material is enclosed in a first container including a humidity control member. Removing the humidity control member from the first container, and a) Enclosing the catheter in a second container, wherein the second container contains foil material, or b) Resealing the first container, wherein the first container comprises a first portion containing the foil material and a second portion containing a gas-permeable polymer. The humidity control member includes a humidity control sponge. The polymer material has a water content of 2% by mass or more and 40% by mass or less. The water content is less than the equilibrium water content of the polymer material, and A method for manufacturing a packaged article, wherein the polymer material swells to an amount of 5% by mass or more relative to the equilibrium water content state.

19. The method according to claim 18, wherein the removal of the catheter occurs between 0 hours and 120 hours after the catheter has been sealed.

20. The method according to claim 18 or 19, wherein the first container comprises high-density polyethylene fibers.

21. The method according to any one of claims 18 to 20, further comprising sterilizing the catheter in the first container.

22. The method according to any one of claims 18 to 21, wherein the packaged article includes a header portion, and the humidity control member is disposed within the header portion.

23. The packaging article according to any one of claims 1 to 16, wherein the polymer material swells by an amount of 5% by weight or more relative to the equilibrium water content state.

24. The packaging article according to any one of claims 1 to 16 or 23, wherein the polymer material swells to the equilibrium water content state in a time of 60 minutes or less at 25°C.

25. The packaged article according to any one of claims 1 to 16, 23, or 24, wherein the catheter contains a humectant.

26. The catheter has an inner diameter, an outer diameter, and a length, and The packaging article according to any one of claims 1 to 16, 23 to 25, wherein the polymer material swells such that the inner diameter and / or outer diameter increase at a rate greater than the rate of increase in length.

27. The packaged article according to any one of claims 1 to 16, 23 to 26, wherein the catheter has a plurality of holes.

28. A packaged article according to any one of claims 1 to 16, 23 to 27, further comprising a biological activator.

29. The packaged article according to claim 28, wherein the biological activator is present in the catheter in an amount of 0.01% by weight or more relative to the total weight of the catheter.

30. The packaging article according to any one of claims 1 to 16, 23 to 29, wherein the polymer material has a water content of less than 5% by weight and 0.1% by weight or more in a dehydrated state, and the polymer material swells from a dehydrated state to an equilibrium water content state by an amount of 5% by weight or more and 50% by weight or less in 60 minutes or less.

31. The packaged article according to claim 24, wherein the aforementioned time is 10 minutes or less.

32. The packaged article according to claim 24, wherein the aforementioned time is 5 minutes or less.

33. The packaged article according to claim 24, wherein the aforementioned time is 1 minute or less.

34. The packaged article according to claim 24, wherein the aforementioned time is 30 seconds or less.

35. The packaged article according to claim 24, wherein the aforementioned time is 10 seconds or less.

36. The packaging article according to claim 25, wherein the humectant comprises a sugar alcohol and / or poloxamer.

37. The packaging article according to claim 25, wherein the humectant comprises poloxamer, polyethylene glycol, glycerol, propylene glycol, ethylene glycol, butylene glycol, erythritol, treitol, arabitol, xylitol, ribitol, mannitol, sorbitol, galactitol, fusitol, iditol, inositol, boremitol, mariitol, lactitol, maltotriitol, maltotetriitol, and / or polyglycitol.

38. The packaging article according to claim 25, wherein the humectant comprises poloxamer, sorbitol, mannitol, glycerol, ethylene glycol, and / or xylitol.

39. The packaging article according to claim 25, wherein the humectant comprises glycerol.

40. The packaged article according to claim 25, comprising 0.1 to 30% by mass of a humectant.

41. The packaged article according to claim 25, comprising 1 to 10% by mass of a humectant.

42. The packaging article according to claim 25, wherein at least a portion of the humectant is disposed on the surface of the catheter.

43. The packaging article according to claim 25, wherein at least a portion of the humectant is located inside the bulk of the catheter.

44. The packaged article according to claim 26, wherein the inner diameter and / or outer diameter are increased by 1 to 20%, and the length is increased by 0.1 to 19%.

45. The packaged article according to any one of claims 1 to 16, 23 to 44, wherein the equilibrium moisture content is 20% by mass or more and 80% by mass or less.

46. The packaged article according to any one of claims 1 to 16, 23 to 45, wherein the moisture content is 6% by weight or more and 40% by mass or less.

47. The packaged article according to any one of claims 1 to 16, 23 to 46, wherein the moisture content is 2% by weight or more and 10% by mass or less.

48. The packaging article according to claim 27, wherein the polymer material comprises a first water-soluble polymer, and the catheter is positioned in at least some of the plurality of holes and further comprises a second water-soluble polymer that is the same as or different from the first water-soluble polymer.

49. The packaging article according to any one of claims 1 to 16, 23 to 48, wherein the polymer material has a Young's modulus of 500 MPa or more in a dehydrated state and a Young's modulus of 300 MPa or less and 5 MPa or more in an equilibrium moisture content state.

50. The packaging article according to any one of claims 1 to 16, 23 to 49, wherein the polymer material has a water content of less than 5% by mass and 0.1% by mass or more in a dehydrated state, and the polymer material swells from a dehydrated state to an equilibrium water content state by an amount of 5% by mass or more and 50% by mass or less at 25°C for 60 minutes or less.

51. The packaging article according to claim 27, wherein the plurality of pores have an average pore diameter of 10 nm or more and less than or equal to 500 nm.

52. The packaging article according to claim 27, wherein at least 50% of the plurality of holes have a diameter of 1 μm or less.

53. The packaged article according to any one of claims 1 to 16, 23 to 52, wherein the catheter swells to an equilibrium water content by an amount of 5% by mass or more and 50% by mass or less from a dehydrated state to an equilibrium water content state.

54. The packaged article according to any one of claims 1 to 16, 23 to 53, wherein the catheter has a coefficient of friction of 0.10 or less in a state of equilibrium water content.

55. The packaged article according to any one of claims 1 to 16, 23 to 54, wherein the catheter contains an osmotic agent present in the polymer material in an amount of 0.05% by mass or more and 2% by mass or less based on the total weight of the catheter.

56. The packaged article according to claim 55, wherein the osmotic agent is selected from the group consisting of phosphates, borates, sodium chloride, citrates, ethylenediaminetetraacetates, sulfites, hyposulfites, metal oxides, selenium dioxide, selenium trioxide, selenite, selenic acid, nitrates, silicates, and peony acid.

57. The packaging article according to any one of claims 1 to 16, 23 to 56, wherein the polymer material has a water contact angle of 45 degrees or less in a state of equilibrium water content.

58. The packaging article according to claim 48, wherein the first water-soluble polymer does not contain a covalent crosslinking agent.

59. The first water-soluble polymer is poly(vinyl alcohol), poly(acrylic acid), polyethylene glycol, poly(vinylpyrrolidone), poly(methacrylate sulfobetaine), poly(acrylic sulfobetaine), poly(methacrylate carboxybetaine), poly(acrylic carboxybetaine), povidone, polyacrylamide, The packaging article according to claim 48, selected from the group consisting of poly(N-(2-hydroxypropyl)methacrylamide), polyoxazoline, polyphosphate, polyphosphazene, polyvinyl acetate, polypropylene glycol, poly(N-isopropylacrylamide), poly(2-hydroxymethyl methacrylate), and combinations thereof.

60. The packaging article according to claim 48, wherein the second water-soluble polymer is 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), povidone, polyacrylamide, poly(N-(2-hydroxypropyl)methacrylamide), polyoxazoline, polyphosphate, polyphosphazene, polyvinyl acetate, polypropylene glycol, poly(N-isopropylacrylamide), poly(2-hydroxymethyl methacrylate) and combinations thereof.

61. The packaged article according to any one of claims 1 to 16, 23 to 60, 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 tunnel catheter, a dialysis access catheter, a urinary catheter, a nerve catheter, a percutaneous transluminal angioplasty catheter, and a peritoneal catheter.

62. The packaged article according to claim 48, wherein the second water-soluble polymer is disposed in bulk with the first water-soluble polymer.

63. The packaged article according to claim 48, wherein, after washing five times the volume of the catheter with water or physiological saline, sorption of less than 0.5% by mass of the therapeutic agent of the first water-soluble polymer onto the bulk occurs at an equilibrium water content.

64. The packaged article according to any one of claims 1 to 16, 23 to 63, wherein the catheter and / or polymer material is substantially non-thrombotic.

65. A packaging article according to any one of claims 1 to 16, 23 to 64, further comprising a humidity control sponge.

66. A packaged article according to any one of claims 1 to 16, 23 to 65, further comprising a hydration medium.

67. The packaged article according to claim 66, wherein the hydration medium comprises water, Ringer's lactate solution (LRS), glucose (D5W), phosphate-buffered saline (PBS), and / or Hanks equilibrium saline (HBSS).

68. The packaged article according to claim 66 or 67, wherein the hydrated medium contains an isotonic salt solution.

69. The packaged article according to any one of claims 1 to 16, 23 to 68, wherein the packaged article is sterilized.

70. A packaged article according to any one of claims 1 to 16 or 23 to 69, further comprising instructions for use.

71. The method according to claim 17, comprising rehydrating the polymer material in an amount of 5% by mass or more until it reaches an equilibrium water content.

72. The method according to claim 17 or 71, wherein the rehydration occurs after administration of the catheter to the target.

73. The method according to claim 17, 71, or 72, wherein the rehydration of the polymer material increases in size to a dimension greater than or equal to the size of the orifice into which the polymer material is inserted, thereby closing the opening of the orifice.

74. The method according to any one of claims 17, 71 to 73, wherein the rehydration of the polymer material brings hemostasis.

75. The method according to claim 73, wherein the orifice is a scratch.

76. The method according to any one of claims 17, 71 to 75, wherein the rehydration occurs before the administration of the catheter.

77. The method according to any one of claims 17, 71 to 76, wherein the rehydration comprises rehydrating the catheter for a certain period of time.

78. The method according to claim 77, wherein rehydrating the catheter involves using a rehydration medium comprising water, Ringer's lactate solution (LRS), glucose (D5W), phosphate-buffered saline (PBS), and / or Hanks equilibrium saline (HBSS).

79. The method according to any one of claims 17, 71 to 78, wherein rehydrating the catheter involves using a rehydration medium containing an isotonic salt solution.

80. The method according to claim 77, wherein the aforementioned period is 10 minutes or less.

81. The method according to claim 77, wherein the aforementioned period is 5 minutes or less.

82. The method according to claim 77, wherein the aforementioned period is 1 minute or less.

83. The method according to claim 77, wherein the aforementioned period is 30 seconds or less.

84. The method according to claim 77, wherein the aforementioned period is 10 seconds or less.

85. The method according to any one of claims 17, 71 to 84, wherein the rehydration of the polymer material is such that the inner diameter and / or outer diameter increase at a rate greater than the rate of increase in length.

86. The method according to any one of claims 18, 71 to 85, wherein the inner diameter and / or outer diameter is increased by 1 to 20 percent and the length is increased by 0.1 to 19 percent.

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