Material binding compositions and related methods

Abstract

Articles and / or integrated articles are generally provided that include a body portion (e.g., a catheter) and a component (e.g., a cuff) that is physically integrated with the body portion. For example, materials, methods, and uses are set forth herein for forming a body portion comprising a first material that is physically integrated with a component comprising a second material, the second material being the same as or different from the first material. The disclosed compositions and devices are useful for administration to a subject (e.g., a patient). Advantageously, the compositions and / or devices described herein may be substantially thrombus-free, lubricious, and / or biocompatible. In some embodiments, the devices described herein may be used to deliver bioactive agents (e.g., therapeutic agents such as drugs) to a subject. Methods of forming such compositions and / or devices are also provided.

Description

(19) State Intellectual Property Office (12) Invention Patent Application (10) Application Publication Number (43) Application Publication Date (21) Application Number 202480024103.3 (22) Application Date 2024.03.08 (30) Priority Data 63 / 451,470 2023.03.10 US (85) PCT International Application Entering National Phase Date 2025.09.30 (86) PCT International Application Application Data PCT / US2024 / 019063 2024.03.08 (87) PCT International Application Publication Data WO2024 / 191800 EN 2024.09.19 (71) Applicant: Ases Vascular Co., Ltd. Address: USA (72) Inventors: Daniel T. Donahue, Nicholas Pipis, Mark Thomas Doherty (74) Patent Agency: Beijing J&J Intellectual Property Agency Co., Ltd. 11227 Patent Attorneys Zhang Fuyu and Wu Xiaojing (51) Int.Cl. C08J 9 / 00 (2006.01) C08J 5 / 04 (2006.01) A61L 29 / 12 (2006.01) (54) Title of Invention: Material Combining Compositions and Related Methods (57) Abstract: Articles and / or integrated articles generally provide a body portion (e.g., a catheter) and a component (e.g., a cuff) physically integrated with the body portion. For example, materials, methods, and uses for forming a body portion comprising a first material physically integrated with a component comprising a second material, which may be the same as or different from the first material, are described herein. The disclosed compositions and devices can be used on a subject (e.g., a patient). Advantageously, the compositions and / or devices described herein can be substantially non-thrombotic, lubricating, and / or biocompatible. In some embodiments, the devices described herein can be used to deliver a bioactive agent (e.g., a therapeutic agent such as a drug) to a subject. Methods for forming such compositions and / or devices are also provided.Claims 8 pages, Description 54 pages, Drawings 14 pages, CN 121195019 A 2025.12.23 CN 1 21 19 50 19 A 1. An article comprising: a body portion, wherein the body portion comprises a first material containing a water-soluble polymer; and a component physically integrated with the body portion, the component comprising a second material different from the first material, wherein one or more of the following are true: i) the first material has a Young's modulus greater than or equal to 500 MPa in a dehydrated state and a Young's modulus less than or equal to 300 MPa and greater than or equal to 5 MPa in an equilibrium water content state; ii) the first material is configured to expand from a dehydrated state to an equilibrium water content state in an amount greater than or equal to 5 w / w% and less than or equal to 50 w / w% in less than or equal to 60 minutes at 25°C; iii) the first material is free of covalent crosslinks between the water-soluble polymers forming the first material; and / or iv) the first material comprises pores, each pore having a diameter of 1 1. μm or smaller. 2. An article comprising: a hydrophilic porous polymer material containing a water-soluble polymer, the hydrophilic porous polymer material comprising a plurality of pores, wherein the hydrophilic porous polymer material is not covalently cross-linked between the water-soluble polymers; and a component physically integrated with the hydrophilic porous polymer material, the component comprising a second material different from the first material, wherein the component comprises a plurality of fibers, and wherein at least a portion of the plurality of fibers is embedded within the hydrophilic porous polymer material. 3. An article comprising: a body portion, wherein the body portion comprises a first material containing a water-soluble polymer, the first material comprising a plurality of pores; and a component physically integrated with the body portion such that at least a portion of the component is embedded within the body portion, the component comprising a second material different from the first material. 4. A method of forming an integrated article, comprising: using a polymer mixture comprising at least one water-soluble polymer and a solvent, said polymer mixture having at least 10% w / w of said at least one water-soluble polymer: heating said polymer mixture to a temperature above the melting point of said polymer mixture; extruding said polymer mixture as a body portion; and removing said solvent from the extruded body portion at a temperature above the freezing point of said solvent until said body portion is porous, wherein said body portion is a porous body portion comprising said at least one water-soluble polymer, and said porous body portion is prepared without using a covalent crosslinking agent that forms covalent crosslinks between the polymers extruded to prepare said porous body portion, wherein during the step of extruding said polymer mixture, a component is physically integrated with said body portion to form said integrated article, said component comprising a second material different from a first material.5. A method of forming an integrated article, comprising: exposing a body portion to a solvent; optionally, heating the body portion to a temperature less than or equal to 100°C, wherein the body portion comprises a first material containing a water-soluble polymer, such that the water-soluble polymer softens in the presence of the solvent; contacting the body portion with a component in the presence of the solvent, such that the component is physically integrated with the body portion to form the integrated article; and cooling the integrated article. 6. A method of forming an integrated article, comprising: exposing a body portion to a solvent, wherein the body portion comprises a first material containing a first water-soluble polymer, and wherein the solvent comprises water and a second water-soluble polymer; contacting the body portion with a component in the presence of the solvent, such that the component is physically integrated with the body portion to form the integrated article; and at least partially drying the integrated article. 7. An article comprising: a body portion, wherein the body portion comprises a first material containing a water-soluble polymer; a solution coating disposed on a portion of a surface of the body portion, wherein the solution coating comprises water and polyvinyl alcohol, the polyvinyl alcohol being present in the solvent in an amount greater than or equal to 0.1% by weight and less than or equal to 25% by weight; and a component in physical contact with the solution coating, such that the component is adhered to the body portion by the solution coating. 8. The article or method of any preceding claim, wherein the solvent comprises a water-soluble polymer, the concentration of the water-soluble polymer being lower than the concentration of a water-soluble polymer used to form the first material. 9. The article or method of any preceding claim, wherein the solvent comprises water and polyvinyl alcohol, the polyvinyl alcohol being present in the solvent in an amount greater than or equal to 0.1% by weight and less than or equal to 25% by weight. 10. The article or method of any preceding claim, wherein the hydrolysis level of the solvent is greater than or equal to 80%, such that the solvent comprises less than or equal to 20% acetate groups. 11. The article or method of any preceding claim, wherein the solvent comprises water. 12. The article or method according to any of the preceding claims, wherein the solvent comprises water and a water-soluble polymer. 13. The article according to any of the preceding claims, wherein the article comprises a lumen. 14. The article according to any of the preceding claims, wherein the article comprises a hemodialysis catheter, a peripherally inserted central venous catheter (PICC), a central venous catheter, a midline catheter, a peripheral catheter, a urinary catheter, a nerve catheter, a peritoneal catheter, and / or an infusion port.15. The article of any preceding claim, wherein the article is configured for use with a medical article, such as a catheter, balloon, shunt, wound drainage tube, infusion port, drug delivery article, tube, contraceptive article, feminine hygiene product, endoscope, graft, pacemaker, implantable cardioverter-defibrillator, cardiac resynchronization device, cardiovascular product lead, ventricular assist device, endotracheal tube, tracheostomy tube, implantable sensor, ventilator pump, and ophthalmic article. 16. The article or method of any preceding claim, wherein the polymer material is free of a covalent crosslinking agent. 17. The article or method of any preceding claim, wherein the polymer material has a Young's modulus of 5 to 100 MPa at equilibrium water content (EWC). 18. The article or method of any preceding claim, wherein the article comprises a plurality of interconnected pores. 19. The article or method of any preceding claim, wherein the component comprises a plurality of fibers. 20. The article or method of any preceding claim, wherein the component is a catheter cuff. 21. The article or method according to any preceding claim, wherein the body portion comprises a second material, the second material comprising a first water-soluble polymer at a concentration lower than the concentration of the first water-soluble polymer in the first material. Claims 2 / 8 Page 3 CN 121195019 A 22. The article or method according to any preceding claim, wherein the water-soluble polymer may entrain an insoluble compound selected from: therapeutic agents, bioactive compounds, woven textiles, metal meshes, color indicators, radiopaque agents, and reaction indicators. 23. The article or method according to any preceding claim, wherein the water-soluble polymer incorporates a conductive indicator to assist in the detection of the P wave on an electrocardiogram. 24. The article or method according to claim 23, wherein the conductive indicator comprises iron powder insoluble in physiological fluids entrained in the PVA. 25. The article or method according to any preceding claim, wherein the water-soluble polymer encapsulation is selected from woven textiles such as Dacron® (polyethylene terephthalate, also known as polyester), electrospun PVA, cotton, wool, polypropylene (random, syndiotactic, isotactic), and polyethylene (LLDPE, LDPE, HDPE). 26. The article or method according to any preceding claim, wherein the intended use of the article or method is selected from combining bandages, tissue growths, scaffolds, shunts, braided tubes, and wall supports with an additional PVA substrate. 27. The article or method according to any preceding claim, wherein the first water-soluble polymer is combined with a second water-soluble polymer to create a new geometry or to reinforce one or more components physically integrated with the body portion.28. The article or method of claim 27, wherein bonding comprises hydrating and heating the first and second water-soluble polymers to be bonded into an overlap joint. 29. The article or method of any preceding claim, wherein heating causes the first water-soluble polymer to flow into the second water-soluble polymer. 30. The article or method of any preceding claim, wherein heating causes the second water-soluble polymer to flow into the first water-soluble polymer. 31. The article or method of any preceding claim, wherein bonding further comprises cooling the first and second water-soluble polymers. 32. The article or method of any preceding claim, wherein cooling the polymers forms the integrated article. 33. The article or method of any preceding claim, wherein the water-soluble polymer is hydrated in a solution until an equilibrium hydration percentage is reached. 34. The article or method of any preceding claim, wherein the equilibrium hydration percentage is from about 0.1% to 100%. 35. The article or method of any preceding claim, wherein the solution comprises a phosphate-buffered saline solution with a concentration of about 0.1 M to 10 M. 36. The article or method according to any of the preceding claims, wherein the bonding is performed using a hot air press of a specific geometry, a split mold bonding machine, or an RF welding machine. 37. The article or method according to any of the preceding claims, wherein the bonding temperature is 60°C to 95°C. 38. The article or method according to any of the preceding claims, wherein the bonding time is 15 seconds to 5 minutes. 39. The article or method according to any of the preceding claims, wherein the bonding is performed using FEP heat shrink formed to a size and shape suitable for hot air treatment. 40. The article or method according to any of the preceding claims, wherein the bonding further includes pressing the bond to improve chain entanglement of the materials to be bonded.41. A method for reshaping a hydrophilic porous material, comprising: (Claims 3 / 8, page 4, CN 121195019 A) bending the hydrophilic porous material into a desired shape, the hydrophilic porous material comprising a cavity; heating the hydrophilic porous material in the bent configuration to a temperature greater than or equal to 90°C, wherein: a) the step of bending the hydrophilic porous material comprises pressing the hydrophilic porous material into a mold having a desired shape; and / or b) the step of bending the hydrophilic porous material comprises inserting material into the cavity of the hydrophilic porous material to provide a desired shape; and / or c) the step of bending the hydrophilic porous material comprises physically deforming the hydrophilic porous material and wherein, for any one of (a) to (c), one or more of the following are true: i) the hydrophilic porous material has a Young's modulus greater than or equal to 500 MPa in a dehydrated state and a Young's modulus less than or equal to 300 MPa in an equilibrium water content state. ii) The hydrophilic porous material is configured to expand from a dehydrated state to an equilibrium water content state in an amount greater than or equal to 5 w / w% and less than or equal to 50 w / w% within 60 minutes at 25°C; iii) The hydrophilic porous material is free from covalent crosslinking between the water-soluble polymers forming the hydrophilic porous material; and iv) The hydrophilic porous material comprises pores, each pore having a diameter of 1 μm or less. 42. An article comprising: an elongated tube, wherein the elongated tube comprises a first material containing a water-soluble polymer; the elongated tube comprising a first portion and a second portion, wherein, in a relaxed state, the radius of curvature of the first portion is different from the radius of curvature of the second portion, wherein one or more of the following are true: v) the first material has a Young's modulus greater than or equal to 500 MPa in a dehydrated state and a Young's modulus less than or equal to 300 MPa and greater than or equal to 5 MPa in an equilibrium water content state; vi) the first material is configured to expand from a dehydrated state to an equilibrium water content state in an amount greater than or equal to 5 w / w% and less than or equal to 50 w / w% over a period of less than or equal to 60 minutes at 25°C; vii) the first material is free from covalent crosslinking between the water-soluble polymers forming the first material; and viii) the first material comprises pores, each pore having a diameter of 1 μm or less.43. A dual-cavity article comprising: a first body portion comprising a first material containing a water-soluble polymer, the first body portion comprising a first cavity having a first inner diameter; and a second body portion comprising a second material different from the first material, the second body portion comprising a second cavity, wherein the outer diameter of the first portion of the second body portion is smaller than the first inner diameter of the first cavity, and the second inner diameter of the second portion of the second body portion is approximately equal to the first inner diameter, wherein the second body portion is at least partially disposed within the first body portion, wherein one or more of the following are true: x) the first material has a Young's modulus greater than or equal to 500 MPa in a dehydrated state and a Young's modulus less than or equal to 300 MPa and greater than or equal to 5 MPa in an equilibrium water content state; x) the first material is configured to expand from a dehydrated state to an equilibrium water content state in an amount greater than or equal to 5 w / w% and less than or equal to 50 w / w% in less than or equal to 60 minutes at 25°C; xi) The first material does not contain covalent crosslinks between the water-soluble polymers forming the first material; and xii) The first material contains pores, each pore having a diameter of 1 μm or less. 44. A method of forming a dual-cavity article, comprising: expanding a first body portion comprising a first material in a solvent, the first material comprising a water-soluble polymer, the first body portion comprising a first cavity having a first inner diameter; heating and / or mechanically deforming a second body portion comprising a second material different from the first material, such that the outer diameter of the second body portion is smaller than the first inner diameter of the first cavity; inserting the second body portion into the cavity of the first body portion to form a dual-cavity article; and drying the dual-cavity article such that the first body portion shrinks. 45. The article or method according to any preceding claim, further comprising one or more surface features (e.g., barbs, protrusions) at the interface between the first body portion and the second body portion, said one or more surface features being configured to mechanically reinforce the interface between the first body portion and the second body portion. 46. ​​The article or method according to any preceding claim, further comprising one or more surface features (e.g., barbs, protrusions) at the interface between the first body portion and the second body portion, said one or more surface features being configured to mechanically reinforce the interface between the first body portion and the second body portion. 47. The article or method according to any preceding claim, wherein the article is shaped using thermoforming. 48. The article or method according to any preceding claim, wherein thermoforming occurs at a temperature greater than 90°C.49. The article or method according to any preceding claim, wherein thermoforming includes inserting a wire into a cavity of the article, placing the article into a mold, and heating the mold into a designed shape. 50. The article or method according to any preceding claim, wherein the article shape is bent, straightened, compressed, or stretched by restricting the dimensions of an initial part to a desired shape. 51. The article or method according to any preceding claim, wherein the edges of the article are rounded to allow easy fluid flow, reduce abrasion, and reduce surface area, which can contribute to placement, catheter life, and patient comfort. 52. The article or method according to any preceding claim, wherein the solvent comprises water. 53. The article or method according to any preceding claim, wherein the solvent comprises water and a water-soluble polymer. 54. The article or method according to any preceding claim, wherein the solvent comprises a water-soluble polymer at a concentration lower than that used to form the first material. 55. The article or method according to any preceding claim, wherein the solvent comprises water and polyvinyl alcohol, wherein the polyvinyl alcohol is present in the solvent in an amount greater than or equal to 0.1% by weight and less than or equal to 25% by weight. 56. The article or method according to any of the preceding claims, wherein the hydrolysis level of the solvent is greater than or equal to 80%, such that the solvent contains less than or equal to 20% acetate groups. 57. The article according to any of the preceding claims, wherein the article comprises a lumen. 58. The article according to any of the preceding claims, wherein the article comprises a hemodialysis catheter, a peripherally inserted central venous catheter (PICC), a central venous catheter, a midline catheter, a peripheral catheter, a urinary catheter, a nerve catheter, a peritoneal catheter, and / or an infusion port. 59. The article of any preceding claim, wherein the article is configured for use with a medical article, such as a catheter, balloon, shunt, wound drainage tube, infusion port, drug delivery article, tube, contraceptive article, feminine hygiene article, endoscope, graft, pacemaker, implantable cardioverter defibrillator, cardiac resynchronization article, cardiovascular article lead, ventricular assist article, endotracheal tube, tracheostomy tube, implantable sensor, ventilator pump, and ophthalmic article. 60. The article or method of any preceding claim, wherein the polymer material is free of a covalent crosslinking agent. 61. The article or method of any preceding claim, wherein the polymer material has a Young's modulus of 5 to 100 MPa at equilibrium water content (EWC). 62. The article or method of any preceding claim, wherein the article comprises a plurality of interconnected pores. 63. The article or method of any preceding claim, wherein the component comprises a plurality of fibers.64. The article or method according to any preceding claim, wherein the component is a catheter cuff. 65. The article or method according to any preceding claim, wherein the body portion comprises a second material, the second material comprising a first water-soluble polymer at a concentration lower than that of a first water-soluble polymer in the first material. 66. The article or method according to any preceding claim, wherein the water-soluble polymer may entrain an insoluble compound selected from therapeutic agents, bioactive compounds, woven textiles, metal meshes, color indicators, radiopaque agents, and reaction indicators. 67. The article or method according to any preceding claim, wherein the water-soluble polymer incorporates a conductive indicator to assist in the detection of P waves on an electrocardiogram. 68. The article or method according to claim 23, wherein the conductive indicator comprises iron powder insoluble in physiological fluids entrained in the PVA. 69. The article or method according to any preceding claim, wherein the water-soluble polymer encapsulation is selected from woven textiles such as Dacron® (polyethylene terephthalate, also known as polyester), electrospun PVA, cotton, wool, polypropylene (random, syndiotactic, isotactic), and polyethylene (LLDPE, LDPE, HDPE). 70. The article or method according to any preceding claim, wherein the intended use of the article or method is selected from bonding bandages, tissue growths, scaffolds, shunts, braided tubes, and wall supports to an additional PVA substrate. 71. The article or method according to any preceding claim, wherein the first and second water-soluble polymers are combined to create a new geometry or to reinforce one or more components physically integrated with the body portion. 72. The article or method according to claim 27, wherein bonding comprises hydrating and heating the first and second water-soluble polymers to be bonded into an overlap. 73. The article or method according to any preceding claim, wherein heating causes the first water-soluble polymer to flow into the second water-soluble polymer. 74. The article or method according to any preceding claim, wherein heating causes the second water-soluble polymer to flow into the first water-soluble polymer. 75. The article or method according to any preceding claim, wherein the combination further includes cooling the first water-soluble polymer and the second water-soluble polymer. 76. The article or method according to any preceding claim, wherein cooling the polymer forms an integrated article. 77. The article or method according to any preceding claim, wherein the water-soluble polymer is hydrated in solution until an equilibrium hydration percentage is reached. 78. The article or method according to any preceding claim, wherein the equilibrium hydration percentage is from about 0.1% to 100%.79. The article or method according to any of the preceding claims, wherein the solution comprises a phosphate-buffered saline solution with a concentration of about 0.1 M to 10 M. 80. The article or method according to any of the preceding claims, wherein the bonding is performed using a hot air press of a specific geometry, a split-mold bonding machine, or an RF welding machine. 81. The article or method according to any of the preceding claims, wherein the bonding temperature is 60°C to 95°C. 82. The article or method according to any of the preceding claims, wherein the bonding time is 15 seconds to 5 minutes. 83. The article or method according to any of the preceding claims, wherein the bonding is performed using FEP heat shrinkable material shaped to a size and shape suitable for hot air treatment. 84. The article or method according to any of the preceding claims, wherein the bonding further includes pressing the bond to improve chain entanglement of the materials to be bonded. 85. An intravenous catheter comprising: a polymeric material comprising a first water-soluble polymer having a plurality of pores; a lumen; and a distal end comprising a tip geometry adapted for intravenous insertion into a subject; wherein the polymeric material has a water content of less than 5 w / w% and greater than or equal to 0.1 w / w% in a dehydrated state, and wherein the polymeric material is configured to expand from a dehydrated state to an equilibrium water content state in an amount of greater than or equal to 5 w / w% and less than or equal to 50 w / w% over a period of less than or equal to 60 minutes at 25°C. 86. A system comprising an intravenous catheter according to any preceding claim, and components configured for administering a therapeutic agent and / or fluid to a subject and / or aspirating bodily fluids from the subject. 87. A method comprising: inserting an intravenous catheter into a vein, the intravenous catheter comprising: a polymeric material comprising a first water-soluble polymer having a plurality of pores; a lumen; and a distal end comprising a tip geometry adapted for intravenous insertion into a subject; wherein, during the insertion step, the water content of the catheter is less than or equal to 5 w / w%; and the intravenous catheter is inflated to a water content greater than or equal to 5 w / w% and less than or equal to 50 w / w.88. A method comprising: inserting an intravenous catheter into a vein, the intravenous catheter comprising: a polymeric material containing a first water-soluble polymer having a plurality of pores, wherein the water content of the polymeric material is greater than or equal to 5 w / w% and less than or equal to 50 w / w%; a lumen; and a distal end comprising a tip geometry adapted for intravenous insertion into a subject; wherein one or more of the following are true: i) the polymeric material has a Young's modulus greater than or equal to 500 MPa in a dehydrated state and a Young's modulus less than or equal to 300 MPa and greater than or equal to 5 MPa in an equilibrium water content state; ii) the polymeric material is free of covalent crosslinking between the water-soluble polymers forming the polymeric material; and iii) the polymeric material comprises pores, each pore having a diameter of 1 μm or less. 89. The catheter or method according to any preceding claim, wherein the polymeric material is free of a covalent crosslinking agent. 90. The catheter or method according to any preceding claim, wherein the article comprises a plurality of interconnected pores. 91. The catheter or method according to any preceding claim, wherein the polymer material has a Young's modulus greater than or equal to 500 MPa in a dehydrated state and a Young's modulus less than or equal to 300 MPa and greater than or equal to 5 MPa in an equilibrium water content state. (Claims 7 / 8, page 8, CN 121195019 A) 92. The catheter or method according to any preceding claim, wherein the intravenous catheter is configured for insertion into a subject in a dehydrated state. 93. The catheter or method according to any preceding claim, wherein the intravenous catheter is configured for insertion into a subject in a at least partially hydrated state. 94. The catheter or method according to any preceding claim, further comprising administering fluid to the subject through the intravenous catheter. 95. The catheter or method according to any preceding claim, further comprising aspirating blood from the subject through the intravenous catheter. 96. The catheter or method according to any preceding claim, wherein the intravenous catheter exhibits a hemolysis rate of less than or equal to 10%. 97. The catheter or method according to any preceding claim, wherein the intravenous catheter softening rate is: for a 3-point ratio, the force in the insertion state to the final hydration state is reduced by at least 99%. 98. The catheter or method according to any preceding claim, wherein the distal end of the catheter is tip-treated. 99. The catheter or method according to any preceding claim, wherein the proximal end of the catheter has a hub design.Claims 8 / 8 Page 9 CN 121195019 A Material Binding Compositions and Related Methods Technical Field

[0001] This technical field generally relates to porous biomaterials, including high-strength hydrophilic nanoporous biomaterials, such as porous biomaterials comprising conduits and / or polymer materials. Background Art

[0002] Biomaterials with high strength, low thrombotic properties and smooth surface properties can be used in the medical field. The porosity of biomaterials takes into account both the high-strength bulk material for medical devices and the channels that allow physical bonding with other materials. These properties can prevent or reduce biofilms, microbial colonization, infection, fibrin sheath formation, inflammation, pain and / or tumor growth, and / or can treat physiological conditions such as tumor reduction, fungal and bacterial infections, inflammation and pain. Complications observed with such devices prolong hospital stays and increase patient morbidity and mortality.

[0003] Therefore, there is a need for improved devices and methods. Summary of the Invention

[0004] Articles and / or integrated articles comprising a bulk portion (e.g., a conduit) are generally provided. In some aspects, material binding compositions and related methods are provided. In some aspects, methods for forming catheter tips are provided. In some aspects, intravenous catheters and related methods are provided.

[0005] For example, in some embodiments, materials, methods, and uses for forming a body portion comprising a first material that is physically integrated with a component comprising a second material are described herein, the second material being the same as or different from the first material. The disclosed compositions and devices can be used for administration to a subject (e.g., a patient). Advantageously, the compositions and / or devices described herein can be substantially non-thrombotic, lubricating, and / or biocompatible. In some embodiments, the devices described herein can be used to deliver bioactive agents (e.g., therapeutic agents such as drugs) to a subject. Methods for forming such compositions and / or devices are also provided.

[0006] Some aspects of this disclosure relate to articles comprising a body portion and a component physically integrated with said body portion, wherein said body portion comprises a first material containing a water-soluble polymer. In some embodiments, said component comprises a second material different from the first material.In some embodiments, one or more of the following are true: (i) the Young's modulus of the first material in the dehydrated state is greater than or equal to 500 MPa and in the equilibrium water content state is less than or equal to 300 MPa and greater than or equal to 5 MPa; (ii) the first material is configured to expand from the dehydrated state to the equilibrium water content state in an amount greater than or equal to 5 w / w% and less than or equal to 50 w / w% over a period of less than or equal to 60 minutes at 25°C; (iii) the first material is free of covalent crosslinks between the water-soluble polymers forming the first material; and / or (iv) the first material comprises pores, each pore having a diameter of 1 μm or less.

[0007] Some aspects of this disclosure relate to articles comprising a hydrophilic porous polymer material containing a water-soluble polymer. In some embodiments, the hydrophilic porous polymer material comprises a plurality of pores. In some embodiments, the hydrophilic porous polymer material is free of covalent crosslinks between the water-soluble polymers. In some embodiments, the component is physically integrated with the hydrophilic porous polymer material. In some embodiments, the component comprises a second material different from the first material. In some embodiments, the component comprises multiple fibers. In some embodiments, at least a portion of a large number of fibers is embedded within a hydrophilic porous polymer material. Specification 1 / 54 pages 10 CN 121195019 A

[0008] Some aspects of this disclosure relate to articles comprising a body portion, wherein the body portion comprises a first material containing a water-soluble polymer. In some embodiments, the first material comprises multiple pores, and the component is physically integrated with the body portion such that at least a portion of the component is embedded within the body portion. In some embodiments, the component comprises a second material different from the first material.

[0009] Some aspects of this disclosure relate to methods of forming integrated articles. In some embodiments, the method includes using a polymer mixture comprising at least one water-soluble polymer and a solvent, the polymer mixture having at least 10% w / w of the at least one water-soluble polymer, and performing the following steps: (i) heating the polymer mixture to a temperature above the melting point of the polymer mixture;

[0010] extruding the polymer mixture into a body portion; and (ii) removing the solvent from the extruded body portion at a temperature above the solidification point of the solvent until the body portion is porous. In some embodiments, the body portion is a porous body portion comprising at least one water-soluble polymer, and the porous body portion is prepared without a covalent crosslinking agent that forms covalent crosslinks between the polymers extruded to prepare the porous body portion. In some embodiments, during the step of extruding the polymer mixture, a component is physically integrated with the body portion to form an integrated article of articles, the component comprising a second material different from the first material.

[0011] Other aspects of this disclosure relate to a method of forming an integrated article, comprising exposing a body portion to a solvent; and optionally, heating the body portion to a temperature less than or equal to 100°C. In some embodiments, the body portion comprises a first material containing a water-soluble polymer, such that the water-soluble polymer softens in the presence of a solvent. In some embodiments, the method comprises contacting the body portion with a component in the presence of a solvent, such that the component and the body portion are physically integrated to form an integrated article. In some embodiments, the method comprises cooling the integrated article.

[0012] In some embodiments, the method comprises exposing the body portion to a solvent and contacting the body portion with a component in the presence of a solvent, such that the component and the body portion are physically integrated to form an integrated article. In some embodiments, the body portion comprises a first material containing a first water-soluble polymer. In some embodiments, the solvent comprises water and a second water-soluble polymer. In some embodiments, the method comprises at least partially drying the integrated article.

[0013] Other aspects of this disclosure relate to articles comprising a body portion, a solution coating disposed on a portion of the surface of the body portion, and a component physically in contact with the solution coating such that the component is adhered to the body portion by the solution coating. In some embodiments, the body portion comprises a first material containing a water-soluble polymer. In some embodiments, the solution coating comprises water and polyvinyl alcohol (PVA). In some embodiments, PVA is present in a solvent in an amount greater than or equal to 0.1% by weight and less than or equal to 25% by weight.

[0014] Other aspects of this disclosure relate to methods for reshaping hydrophilic porous materials. In some embodiments, the method includes bending the hydrophilic porous material into a desired shape, wherein the hydrophilic porous material comprises a cavity.In some embodiments, the method includes heating a hydrophilic porous material in a bent configuration to a temperature greater than or equal to 90 °C, wherein: (a) the step of bending the hydrophilic porous material includes pressing the hydrophilic porous material into a mold having a desired shape; and / or (b) the step of bending the hydrophilic porous material includes inserting material into a cavity of the hydrophilic porous material to provide a desired shape; and / or (c) the step of bending the hydrophilic porous material includes physically deforming the hydrophilic porous material, and wherein, for any of (a) to (c), one or more of the following are true: (i) the young's modulus of the hydrophilic porous material in a dehydrated state is greater than or equal to 500 MPa, and the young's modulus of the hydrophilic porous material in an equilibrium water content state is less than or equal to 300 MPa and greater than or equal to 5 MPa; (ii) the hydrophilic porous material is configured to be heated at 25 °C for less than or equal to 60 minutes at a temperature greater than or equal to 5 w / w% and less than or equal to 50 The amount of w / w% expands from the dehydrated state to the equilibrium water content state; (iii) the hydrophilic porous material is not covalently cross-linked between the water-soluble polymers forming the hydrophilic porous material; and (iv) the hydrophilic porous material contains pores, each pore having a diameter of 1 μm or less.

[0015] Some aspects of this disclosure relate to articles comprising elongated tubes, wherein the elongated tubes comprise a first material containing a water-soluble polymer; the elongated tubes comprise a first portion and a second portion, wherein, in a relaxed state, the radius of curvature of the first portion is different from that of the second portion, wherein one or more of the following are true: (i) the first material has a Young's modulus greater than or equal to 500 MPa in a dehydrated state and a Young's modulus less than or equal to 300 MPa and greater than or equal to 5 MPa in an equilibrium water content state; (ii) the first material is configured to expand from a dehydrated state to an equilibrium water content state in an amount greater than or equal to 5 w / w% and less than or equal to 50 w / w% over a period of less than or equal to 60 minutes at 25°C; (iii) the first material is free of covalent crosslinks between the water-soluble polymers forming the first material; and (iv) the first material comprises pores, each pore having a diameter of 1 μm or less.

[0016] Some aspects of this disclosure relate to dual-cavity articles.In some embodiments, a dual-cavity article comprises a first body portion and a second body portion, the first body portion comprising a first material containing a water-soluble polymer and comprising a first cavity having a first inner diameter; the second body portion comprising a second material different from the first material and comprising a second cavity, wherein the outer diameter of the first portion of the second body portion is smaller than the first inner diameter of the first cavity, and the second inner diameter of the second portion of the second body portion is approximately equal to the first inner diameter, wherein the second body portion is at least partially disposed within the first body portion, wherein one or more of the following are true: (i) the first material has a Young's modulus greater than or equal to 500 MPa in a dehydrated state and a Young's modulus less than or equal to 300 MPa and greater than or equal to 5 MPa in an equilibrium water content state; (ii) the first material is configured to expand from a dehydrated state to an equilibrium water content state in an amount greater than or equal to 5 w / w% and less than or equal to 50 w / w% over a period of less than or equal to 60 minutes at 25°C; (iii) the first material is free of covalent crosslinks between the water-soluble polymers forming the first material; and (iv) the first material comprises pores, each pore having a diameter of 1 mm. μm or smaller.

[0017] Some aspects of this disclosure also relate to methods of forming a dual-cavity article. In some embodiments, the method includes swelling a first body portion in a solvent, the first body portion comprising a first material containing a water-soluble polymer, the first body portion comprising a first cavity having a first inner diameter; heating and / or mechanically deforming a second body portion, the second body portion comprising a second material different from the first material, such that the outer diameter of the second body portion is smaller than the first inner diameter of the first cavity; inserting the second body portion into the cavity of the first body portion to form a dual-cavity article; and drying the dual-cavity article such that the first body portion shrinks.

[0018] Other aspects of this disclosure relate to intravenous catheters. In some embodiments, the intravenous catheter comprises a polymeric material comprising a first water-soluble polymer having a plurality of pores; a lumen; and a distal end comprising a tip geometry adapted for intravenous insertion into a subject; wherein the polymeric material has a water content of less than 5 w / w% and greater than or equal to 0.1 w / w% in a dehydrated state, and wherein the polymeric material is configured to expand from a dehydrated state to an equilibrium water content state in an amount of greater than or equal to 5 w / w% and less than or equal to 50 w / w% over a period of less than or equal to 60 minutes at 25°C.

[0019] Other aspects of this disclosure relate to systems comprising intravenous catheters and components configured for administering therapeutic agents and / or fluids to a subject, and / or aspirating bodily fluids from a subject.

[0020] Some aspects of this disclosure also relate to methods of inserting an intravenous catheter into a subject in which such insertion is desired.In some embodiments, the method includes intravenous insertion of an intravenous catheter comprising: a polymeric material having a first water-soluble polymer having a plurality of pores; a lumen; and a distal end having a tip geometry adapted for intravenous insertion into a subject; wherein, during the insertion step, the water content of the catheter is less than or equal to 5 w / w%; and the intravenous catheter is inflated to a water content greater than or equal to 5 w / w% and less than or equal to 50 w / w. Specification 3 / 54 pages 12 CN 121195019 A

[0021] In some embodiments, the method includes intravenous insertion of an intravenous catheter, the intravenous catheter comprising: a polymeric material containing a first water-soluble polymer having a plurality of pores, wherein the water content of the polymeric material is greater than or equal to 5 w / w% and less than or equal to 50 w / w%; a lumen; and a distal end comprising a tip geometry adapted for intravenous insertion into a subject; wherein one or more of the following are true: (i) the polymeric material has a Young's modulus greater than or equal to 500 MPa in a dehydrated state and a Young's modulus less than or equal to 300 MPa and greater than or equal to 5 MPa in an equilibrium water content state; (ii) the polymeric material is free of covalent crosslinks between the water-soluble polymers forming the polymeric material; and (iii) the polymeric material comprises pores, each pore having a diameter of 1 μm or less.

[0022] Other advantages and novel features of the invention will become apparent from the following detailed description of several non-limiting embodiments of the invention when considered in conjunction with the accompanying drawings. In the event of conflicting and / or inconsistent disclosures in this specification and documents incorporated by reference, this specification shall prevail. Brief Description of the Drawings

[0023] Non-limiting embodiments of the invention will be described by way of example 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 generally represented by a single number. For clarity, not every component is labeled in each figure, nor is every component of every embodiment of the invention shown, where illustration is not required to allow those skilled in the art to understand the invention.In the accompanying drawings:

[0024] FIG1 is a schematic diagram of an exemplary article of an embodiment comprising a body portion having a plurality of holes and a component physically integrated with the body portion;

[0025] FIG2 is a schematic diagram of an exemplary article of an embodiment comprising a body portion having a plurality of holes and a component having a plurality of fibers, wherein the fibers of the component are wound within the holes of the body portion;

[0026] FIG3 is a schematic diagram of two materials physically integrated with each other according to an embodiment;

[0027] FIG4 is a schematic diagram of two materials physically integrated with each other using a solution coating according to an embodiment;

[0028] FIG5A is a schematic diagram of a shaped conduit comprising an elongated tube according to an embodiment;

[0029] FIG5B is a schematic cross-section of the shaped conduit shown in FIG5A according to an embodiment;

[0030] FIG6A is a schematic horizontal cross-section of an exemplary dual-cavity article of an embodiment;

[0031] FIG6B is a schematic vertical cross-section of the dual-cavity article shown in FIG6A according to an embodiment;

[0032] Figure 7 is a schematic diagram of an exemplary intravenous catheter according to one embodiment, the intravenous catheter including a distal end having a tip geometry suitable for intravenous insertion;

[0033] Figure 8A is a schematic diagram of an exemplary catheter including an expandable cuff according to one embodiment;

[0034] Figure 8B is a cross-sectional schematic diagram of the catheter shown in Figure 8A in collapsed and expanded views according to one embodiment;

[0035] Figure 9A is a schematic diagram of an extrusion device for forming a continuous morphology according to one embodiment, with a cross-sectional view of the side of the bath;

[0036] Figure 9B is an enlarged view of a portion of the device of Figure 9A according to one embodiment, showing the die head in a perspective view when viewed from outside the bath;

[0037] Figure 9C is an enlarged view of a portion of the device of Figure 9A according to one embodiment, showing the die head arranged in the bath;

[0038] Figure 10 is a longitudinal section of a portion of a continuous porous solid formed using the device of Figures 9A to 9C according to one embodiment; Specification 4 / 54 pages 13 CN 121195019 A

[0039] FIG11A is a schematic diagram of a process for incorporating a polymer bulk into a porous solid according to one embodiment;

[0040] FIG11B is a cross-section of a portion of a tube taken along line 3B-3B of FIG11A according to one embodiment;

[0041] FIG12 is a process flow diagram of an embodiment for incorporating a surface polymer bulk into a porous solid according to one embodiment, and includes an extrusion process for preparing the porous solid; and

[0042] FIG13 is a graph depicting the stress-strain curve of a polymer material according to one embodiment.

[0043] Figures 14A to 14C are photographs of exemplary shaped conduits according to some embodiments. Figure 14A is a photograph of a partially hydrated straight conduit. Figure 14B is a photograph of a partially hydrated straight conduit (in 2.2% sodium chloride) on a shaped mandrel. Figure 14C (top) shows the shaped mandrel. Figure 14C (bottom) is a photograph of an exemplary conduit that has been dried at 95°C for 90 minutes, annealed at 150°C for 90 minutes, and rehydrated in 1x phosphate-buffered saline at 37°C, with the mandrel removed.

[0044] Figures 15A to 15C are exemplary photographs of a lumen reshaped from a circular to a D-shape according to one set of embodiments. Figure 15A shows room temperature / 20°C (no change); Figure 15B shows a mandrel aspect ratio of 65% at 70°C; and Figure 15C shows a mandrel aspect ratio of 87% at 95°C. Detailed Description

[0045] Articles and / or integrated articles are generally provided comprising a body portion (e.g., a catheter) and a component (e.g., a cuff) physically integrated with the body portion. For example, materials, methods, and uses for forming a body portion comprising a first material physically integrated with a component comprising a second material, which may be the same as or different from the first material, are described herein. The disclosed compositions and devices can be used for administration to a subject (e.g., a patient). Advantageously, the compositions and / or devices described herein can be substantially non-thrombotic, lubricating, and / or biocompatible. In some embodiments, the devices described herein can be used to deliver bioactive agents (e.g., therapeutic agents such as drugs) to a subject. Methods for forming such compositions and / or devices are also provided.

[0046] The articles described herein can be used in a wide variety of applications, including, for example, the preparation of blood-contact devices or devices that contact body fluids, including ex vivo and / or in vivo devices, such as blood-contact implants. Examples of drug delivery devices into which the articles described herein may be embedded or incorporated include, but are not limited to, medical tubing, wound dressings, contraceptive devices, feminine hygiene products, endoscopes, implants (e.g., including those with a small diameter of 6 mm or less), pacemakers, implantable cardioverter-defibrillators, cardiac resynchronization devices, cardiovascular device leads, ventricular assist devices, catheters (e.g., including cochlear implants, endotracheal tubes, tracheostomy tubes, ports, shunts), implantable sensors (e.g., intravascular, percutaneous, intracranial), ventilator pumps, and ophthalmic devices incorporating drug delivery systems.

[0047] In one set of embodiments, physically integrated articles are provided. In some embodiments, the article comprises a body portion and components physically integrated with the body portion. Methods for forming physically integrated articles are also provided. For example, in some embodiments, extrusion, thermal bonding, and / or solvent bonding are used to form the integrated article.

[0048] In another set of embodiments, shaped articles are provided.In some embodiments, the shaped article includes an elongated tube, wherein at least a portion of the elongated tube has a specific radius of curvature. Methods for forming the shaped article are also provided. For example, in some embodiments, thermoforming can be used to shape the article, for example, by placing a wire (Nitinol, steel, etc.) into the cavity and heating the article to mold it into a desired shape. The shaped article can have any suitable shape, including but not limited to straight, arcuate, curved, zigzag, spiral, annular, twisted spiral, wavy, irregular, and twisted shapes, etc.

[0049] In another set of embodiments, a dual-cavity article is provided. In some embodiments, the dual-cavity article includes a first body portion and a second body portion, the second body portion being at least partially disposed within the first body portion. Methods for forming a dual-cavity article for use in specification page 5 / 54 14 CN 121195019 A are also provided. For example, in some embodiments, the dual-cavity article can be formed by expanding the first body portion in a solvent until the first body portion is deformable and inserting the second body portion into the cavity of the first body portion. In some cases, the second body portion may also be deformable using heat and / or mechanical force.

[0050] In another set of embodiments, an intravenous catheter is provided. In some embodiments, the intravenous catheter comprises a body portion containing a first water-soluble polymer (e.g., a polymeric material). In some embodiments, the polymeric material has multiple pores. In some embodiments, the intravenous catheter comprises a lumen and a distal end comprising a tip geometry adapted for intravenous insertion into a subject (e.g., a beveled tip needle). Methods for inserting an intravenous catheter into a subject in need are also provided. For example, in some embodiments, the intravenous catheter is inserted in a dehydrated state (e.g., percutaneous insertion) and becomes hydrated after insertion; in some embodiments, the catheter is inserted in a hydrated state. In some embodiments, the hydrated intravenous catheter is more flexible and does not cause the discomfort associated with conventional polymer catheters.

[0051] Some of the above embodiments utilize solvents. For example, in some embodiments, the solvent is used to dissolve at least a portion of the polymer in the first and / or second material. In some embodiments, the solvent is used to expand the material, making it deformable (e.g., bending the catheter into a specific shape or stretching the inner diameter of the lumen). In another set of embodiments, the solvent is used to indirectly bond the first material to the second material (e.g., the first material is bonded to the solvent, and the solvent is bonded to the second material).

[0052] In some embodiments, the solvent comprises a water-soluble polymer (e.g., polyvinyl alcohol) dissolved in an aqueous solvent. In some embodiments, the solvent comprises an aqueous solution (e.g., without a water-soluble polymer). In some embodiments, the solvent comprises a water-miscible organic compound (e.g., DMSO).

[0053] FIG1 illustrates an exemplary embodiment of an integrated article comprising a body portion and components. For example, integrated article 100 comprises a body portion 110 and a component 130 physically integrated with the body portion. In some embodiments, the body portion 120 is formed of a first material and comprises a polymeric material. The polymeric material may comprise a first water-soluble polymer. In some embodiments, the component 130 is formed of a second material different from the first material. In some embodiments, the body portion comprises a plurality of pores 120 (e.g., the average pore size of the plurality of pores is 1 micrometer or less).

[0054] Although the body portion 110 in FIG1 is shown as a rectangle, those skilled in the art will understand, based on the teachings of this specification, that the body portion and other cross-sections in the embodiments disclosed herein need not be rectangular, and other cross-sectional shapes (e.g., planar, circular, square, elliptical, rectangular, S-shaped, etc.) are also possible. For example, in some embodiments, the body portion is S-shaped, which in some cases can provide ease of implantation in an object, achieve lower permeability, and reduce the likelihood of displacement within the object.

[0055] FIG2 illustrates an integrated article 200 comprising a body portion 210 (e.g., a polymeric material) that includes one or more components 230 (e.g., catheter sheaths) physically integrated with the body portion 210. In some cases, the body portion 210 comprises a first material containing a hydrophilic, water-soluble polymer. In some embodiments, the components 230 comprise a second material comprising a plurality of fibers 235 at least partially embedded within the body portion (e.g., a first hydrophilic porous material). Although the components 230 in FIG2 are depicted as fibers 235, those skilled in the art will understand that, based on the teachings of this specification, the components and other cross-sections in the embodiments disclosed herein need not be fibers and other textiles (e.g., nets, porous foam cavities, meshes, etc.) are also possible.

[0056] As described herein, in some aspects, at least a portion of the article may be physically integrated. The term “physical integration” has its typical meaning in the art and generally refers to the physical connection of two or more components (e.g., layers, articles, surfaces) such that they are adhered together. In some embodiments, two or more components that are physically integrated with each other are typically inseparable, otherwise irreversible damage to at least a portion of one or more of the two or more components would occur (e.g., by fracture, mechanical failure, and / or dissolution of chemical bonds). For example, two or more physically integrated components share at least one surface described in specification 6 / 54 page 15 CN 121195019 A, on which the two or more components are adhered to each other (e.g., fused together).Those skilled in the art will understand that the phrases “physical integration” and “fused together” do not mean that the components simply come into contact with each other on one or more surfaces, but rather that at least a portion of the original surface of each individual component is no longer distinguishable from another component (e.g., forming an intermediate layer comprising at least a portion of the first component and at least a portion of the second component). In some embodiments, two or more components are physically integrated by bonding, entanglement, pore filling, etc.

[0057] In some embodiments, the first component is physically integrated with the second component (e.g., the body portion) by embedding at least a portion of the first component into the second component. In some embodiments, the first component is physically integrated with the second component (e.g., the body portion) by embedding at least a portion of the second component into the first component. In some embodiments, the first component is physically integrated with the second component by forming bonds (e.g., ionic bonds, covalent bonds, hydrogen bonds, van der Waals interactions, etc.). Covalent bonds can be, for example, carbon-carbon, carbon-oxygen, oxygen-silicon, sulfur-sulfur, phosphorus-nitrogen, carbon-nitrogen, metal-oxygen, or other covalent bonds. Hydrogen bonds can be between, for example, hydroxyl, amine, carboxyl, thiol, and / or similar functional groups. In some embodiments, the first component is physically integrated with the second component by chain entanglement (e.g., between polymer chains of the first component and polymer chains of the second component).

[0058] In one set of exemplary embodiments, physical integration includes the physical entanglement of hydrophilic polymer chains of the first material within the pores of the second material. In another set of exemplary embodiments, the hydrophilic polymers of the first material may be entangled within the polymer chains of the second material. In yet another set of exemplary embodiments, physical integration includes the entanglement of the second material (e.g., multiple fibers, webs, porous foam cavities, meshes, or other structures) within the pores and / or body of the first material (e.g., hydrogel).

[0059] FIG3 illustrates an example of two components, component 310 and component 320, which are physically integrated with each other (e.g., in the presence of one or more solvents disclosed herein) to form an integrated article 300. In some embodiments, the integrated article 300 includes at least a portion of component 310, at least a portion of component 320, and a physically integrated region 330 (e.g., which includes the material of component 310 and the material of component 320).

[0060] In some embodiments, a solution coating is used to physically integrate the body portion with the component. For example, as shown in FIG. 4, a solution coating 440 is added to a first surface of a body portion 410 and positioned to physically contact a component 420 to produce an integrated article 400. In some embodiments, the solution coating comprises a water-soluble polymer configured to be wound around pores and / or polymer chains within the first material of the body portion. According to some embodiments, the solution coating may also be wound around or embedded in pores and / or polymer chains within a second material of the component.In this way, the component is adhered to the body portion by a solution coating (e.g., the body portion is physically integrated with the solution coating, which is physically integrated with the component).

[0061] In some embodiments, the first component is adjacent to the second component. In some embodiments, an intermediate layer may exist between the first and second components, the intermediate layer comprising the solution coating.

[0062] Other aspects of this disclosure relate to articles such as shaped conduits. For example, as shown in FIG5A, a shaped conduit may comprise an elongated tube 510 comprising a first portion 520 and a second portion 530. In some embodiments, the radius of curvature of the first portion 520 is different from the radius of curvature of the second portion 530 (e.g., the conduit has a “hook” shape). FIG5B shows a cross-section of an exemplary conduit 500. In some embodiments, the elongated tube 510 comprises a lumen 540 and a shell, the shell comprising a first material 550 containing a water-soluble polymer. In some embodiments, the first material comprises a plurality of pores with an average diameter of 1 micrometer or less.

[0063] In some embodiments, the article is a dual-lumen article. Exemplary embodiments are shown in FIG6. FIG6A shows a longitudinal cross-section of a dual-lumen article comprising a first body 610 and a second body 630, the first body 610 comprising a first lumen 620 having a first inner diameter, and the second body 630 comprising a second material containing a second lumen 640. In some embodiments, the second body 630 comprises a first portion 650 having an outer diameter smaller than the first inner diameter 670 of the first lumen 620; in some embodiments, a second portion 660 of the second body 630 has a second inner diameter 680, which is approximately equal to the first inner diameter of the first lumen 620. Specification 7 / 54 pages 16 CN 121195019 A

[0064] Additionally, in some embodiments, the article may comprise an intravascular catheter. For example, as shown in FIG7, an intravenous catheter may comprise a polymer material 710, a lumen 720, and a distal end 730, the polymer material 710 comprising a first water-soluble polymer (e.g., a first body) having a plurality of pores, and the distal end 730 comprising a tip geometry adapted for venous insertion into an object.

[0065] In one set of exemplary embodiments, the article comprises a catheter that includes a cuff, for example, to secure the catheter within a body cavity (e.g., a urinary cavity) of an object. For example, as shown in FIG8, the catheter 800 may include a first material 810 containing a first water-soluble polymer having a plurality of pores, a second material 820 (e.g., a balloon or cuff), a first lumen 830 connected to a first opening 840, a second lumen 850 connected to a second opening 860, and a distal end including a tip geometry adapted to the desired application (e.g., a blunt tip for urinary applications and a pointed tip for intravascular applications).In some embodiments, the second material is physically integrated with the first material along its periphery such that the center of the second material is located above the first opening. In some embodiments, the second material is configured to expand radially when gas 870 (e.g., air) is introduced into the first cavity (e.g., via a syringe).

[0066] Some embodiments of this application utilize a solvent (e.g., to combine the first material with the second material). In some embodiments, the solvent comprises water. In some embodiments, the solvent comprises a water-soluble polymer (e.g., a second water-soluble polymer). In some embodiments, the solvent comprises a water-soluble organic compound (e.g., DMSO).

[0067] It is not desired to be bound by any particular theory that contacting the body portion with the component in the presence of a solvent (e.g., water) causes the first water-soluble polymer of the body portion to interdiffuse into the second material of the component, thereby forming an integrated article of articles. In some embodiments, the method causes the second material to interdiffuse into the first material of the body portion (e.g., when the second material is the same as the first material). Combinations are also possible. For example, in some embodiments, the first material may diffuse into the second material, and the second material may also diffuse into the first material.

[0068] In some embodiments, a solvent comprising water and a second water-soluble polymer can be used to physically integrate a component comprising a second material with a body portion comprising a first material. Similarly, it is not desirable to be bound by any particular theory that contacting the body portion with the component in the presence of a solvent results in the second water-soluble polymer interdiffusion into the first material of the body portion and the second material of the component, thereby forming an integrated article. In other words, the solvent can act as a polymer bridge, becoming physically integrated with both the body portion and the component, thus physically integrating the body portion and the component. For example, in some embodiments, the second water-soluble polymer (e.g., poly(vinyl alcohol)) can be embedded within the body portion and one or more components (e.g., Dacron® (polyethylene terephthalate, also known as polyester), electrospun PVA, cotton, wool, polypropylene (randomized, syndiotactic, isotactic), and polyethylene (LLDPE, LDPE, HDPE)).

[0069] As described above and herein, in some embodiments, the solvent can interact with more than one element of the body portion or component. For example, in some cases, the solvent can physically integrate the body portion and the component by wrapping it around the surface of the body portion, the body and / or the orifice, and the surface of the component, the body and / or the orifice.

[0070] In some embodiments, the solvent includes a homogeneous solvent (e.g., water, DMSO, etc.) or a heterogeneous mixture (e.g., a co-solvent). Exemplary embodiments of the solvent include, but are not limited to, water and DMSO.For example, in some embodiments, the solvent is a heterogeneous mixture of water / DMSO in a ratio of about 0:1, 0.1:0.9, 0.2:0.8, 0.3:0.7, 0.4:0.6, 0.5:0.5, 0.6:0.4, 0.7:0.3, 0.8:0.2, 0.9:0.1, 1:0 (or combinations thereof or ranges thereof).

[0071] In some embodiments, the solvent comprises a polymer. The polymer may be the same as or different from the first material (e.g., a second water-soluble polymer). For example, in some embodiments, the solvent comprises a water-soluble polymer (e.g., a second water-soluble polymer) containing or selected from the following: poly(vinyl alcohol), poly(acrylic acid), polyethylene glycol, poly(vinylpyrrolidone), poly(sulfonated betaine methacrylate), poly(sulfonated betaine acrylate), poly(carboxylated betaine methacrylate), poly(carboxylated betaine acrylate), povidone-polyacrylamide, poly(N-(2-hydroxypropyl)methacrylamide), polyazoline, polyphosphate ester, polyphosphazene, polyvinyl acetate, polypropylene glycol, poly(N-isopropylacrylamide), poly(2-hydroxymethyl methacrylate), and combinations thereof. In a set of preferred embodiments, the solvent comprises poly(vinyl alcohol).

[0072] In some embodiments, the concentration of the water-soluble polymer in the solvent is lower than the concentration of the water-soluble polymer used to form the first material. For example, in some embodiments, the water-soluble polymer is present in the solvent in amounts of the following in equilibrium water content: greater than or equal to 20 w / w%, greater than or equal to 25 w / w%, greater than or equal to 30 w / w%, greater than or equal to 35 w / w%, greater than or equal to 40 w / w%, greater than or equal to 45 w / w%, greater than or equal to 50 w / w%, greater than or equal to 55 w / w%, greater than or equal to 60 w / w%, greater than or equal to 65 w / w%, greater than or equal to 70 w / w%, greater than or equal to 75 w / w%, greater than or equal to 80 w / w%, greater than or equal to 85 w / w%, or greater than or equal to 90 w / w. In some embodiments, the water-soluble polymer is present in the solvent in amounts of the following in equilibrium water content: less than or equal to 95 w / w%, less than or equal to 90 w / w%, less than or equal to 85 w / w%, less than or equal to 80 w / w%, less than or equal to 75 w / w%, less than or equal to 70 w / w%, less than or equal to 65 w / w%, less than or equal to 60 w / w%, less than or equal to 55 w / w%, less than or equal to 50 w / w%, less than or equal to 45 w / w%, less than or equal to 40 w / w%, less than or equal to 35 w / w%, less than or equal to 30 w / w%, or less than or equal to 25 w / w.Combinations of the above ranges are also possible (e.g., greater than or equal to 20 w / w% and less than or equal to 95 w / w%). Other ranges are also possible.

[0073] In some embodiments, the solvent comprises water and poly(vinyl alcohol) present in the solvent in an amount greater than or equal to 0.1 wt% and less than or equal to 25 wt%. For example, in some embodiments, the solvent contains greater than or equal to 0.1 wt%, greater than or equal to 0.5 wt%, greater than or equal to 1.0 wt%, greater than or equal to 2.0 wt%, greater than or equal to 4.0 wt%, greater than or equal to 8.0 wt%, greater than or equal to 10 wt%, greater than or equal to 12 wt%, greater than or equal to 14 wt%, greater than or equal to 16 wt%, greater than or equal to 18 wt%, greater than or equal to 20 wt%, or greater than or equal to 25 wt% of poly(vinyl alcohol) at equilibrium water content. In some embodiments, the solvent, at equilibrium water content, comprises less than or equal to 25 wt%, less than or equal to 20 wt%, less than or equal to 18 wt%, less than or equal to 16 wt%, less than or equal to 14 wt%, less than or equal to 12 wt%, less than or equal to 10 wt%, less than or equal to 8.0 wt%, less than or equal to 4.0 wt%, less than or equal to 2.0 wt%, less than or equal to 1.0 wt%, less than or equal to 0.5 wt%, or less than or equal to 0.1 wt% of poly(vinyl alcohol). Combinations of the above ranges are also possible (e.g., greater than or equal to 0.1 w / w% and less than or equal to 25 w / w%). Other ranges are also possible.

[0074] In some embodiments, the solvent comprises a polymer containing poly(vinyl alcohol). Poly(vinyl alcohol) can be purchased from commercial suppliers (e.g., MilliPore Sigma) and / or synthesized by those skilled in the art, for example, by hydrolyzing polyvinyl acetate (or other vinyl ester-derived polymers having formate or chloroacetate groups instead of acetate). In some embodiments, the hydrolysis reaction is less than 100%, producing a polymer having a mixture of hydroxyl and acetate groups. In some embodiments, the degree of hydrolysis is greater than or equal to 20% and less than or equal to 99%. For example, in some embodiments, the degree of hydrolysis is greater than or equal to 20%, greater than or equal to 30%, greater than or equal to 40%, greater than or equal to 50%, greater than or equal to 60%, greater than or equal to 70%, greater than or equal to 80%, greater than or equal to 90%, greater than or equal to 95%, or greater than or equal to 99%. In some embodiments, the degree of hydrolysis is less than or equal to 99%, less than or equal to 95%, less than or equal to 90%, less than or equal to 80%, less than or equal to 70%, less than or equal to 60%, less than or equal to 50%, less than or equal to 40%, less than or equal to 30%, or less than or equal to 20%.In some embodiments, the solvent comprises 80% hydrolyzed poly(vinyl alcohol) polymer, corresponding to about 20% acetate groups and about 80% hydroxyl groups.

[0075] The solvent can be applied to the material (e.g., the body portion) using any technique known to those skilled in the art. Exemplary embodiments include, but are not limited to: (1) a brushing method, wherein the solvent is brushed onto the surfaces to be joined, followed by pressure, until full bond strength is formed after the solvent has completely evaporated; (2) a capillary action method, which utilizes capillary action to draw a solvent wick into the gap formed at the joint between the two parts to be joined; (3) a dip-dab method, which immerses the surfaces to be joined in a solvent tank for a set period of time before mating with the desired parts; and (4) a solvent dispenser method, wherein a dispenser is used to precisely control the amount of solvent applied to each surface to be joined.

[0076] Other applications of the solvent are also considered. For example, in some embodiments, the solvent can be used to expand and bend the article into any desired shape. As a supplement or alternative, the solvent can be used to entrain or trap insoluble compounds such as therapeutic agents, bioactive compounds, textiles, metal meshes, color indicators, radiopaque agents, and active indicators onto the outer surface of the integrated article. In some cases, the solvent can be used to incorporate conductive indicators to aid in the detection of P waves on an electrocardiogram. For example, iron powder insoluble in physiological fluids entrained in a second water-soluble polymer (e.g., poly(vinyl alcohol)) can provide an embedded ECG probe (e.g., when placed at the tip of a catheter).

[0077] In some embodiments, a solvent can be used to bind one or more materials to a first water-soluble polymer (e.g., poly(vinyl alcohol). For example, in some cases, a solvent can be used to bind bandages, tissues, scaffolds, shunts, braided tubes, and / or wall scaffolds to one or more materials that also contain a water-soluble polymer (e.g., poly(vinyl alcohol)).

[0078] In some embodiments, the solvent can be used in combination with other techniques such as heating. For example, as described herein and above, binding can be achieved by applying a solvent to a first and a second material to be bound together (e.g., in an overlap joint), and heating the first and / or the second material to allow the polymer chains of the first material to flow into the bulk of the second material, and vice versa. After cooling, the first and second materials become physically integrated to form a single cohesive material.

[0079] Some aspects of this disclosure generally relate to methods for producing the integrated article described herein. In some embodiments, the method includes heating a polymer mixture comprising a water-soluble polymer and a solvent, and extruding the mixture as a body portion while simultaneously bringing the body portion into physical contact with a component, thereby physically integrating the body portion with the component.

[0080] In some embodiments, the method includes exposing a body portion to a solvent, and optionally, heating the body portion to a temperature less than or equal to 100°C, contacting the body portion with a component in the presence of the solvent to form an integrated article, and cooling the integrated article.

[0081] In some embodiments, the method includes exposing the body portion to a solvent to soften a first material of the body portion, contacting the body portion with a component in the presence of the solvent such that the component and the body portion are physically integrated to form an integrated article, and at least partially drying the article.

[0082] Other methods relate to forming articles. For example, in some embodiments, the method includes bending a hydrophilic porous material (e.g., a body portion) containing a cavity into a desired shape, and heating the material in the bent configuration to a temperature greater than or equal to 90°C.

[0083] In some embodiments, the method relates to forming a dual-cavity article. In some embodiments, the method includes swelling a first body portion containing a first cavity with a first inner diameter in a solvent to soften the first body portion. In some embodiments, the method further includes heating and / or mechanically deforming the second body portion such that the outer diameter of the second body portion is smaller than the first inner diameter of the first lumen. The method also includes inserting the second body portion into the lumen of the first body portion to form a double-lumen article.

[0084] Other methods also involve inserting an article (e.g., a catheter) into an object where this is desired. In some embodiments, the article is an intravenous catheter comprising a porous polymeric material containing a first water-soluble polymer, a lumen, and a distal end containing a tip geometry suitable for intravenous insertion into the object. In some embodiments, the article is inserted in a dehydrated state (e.g., the water content of the catheter is less than or equal to 5% wt / wt) and hydrated after placement into the object (e.g., the catheter swells to a water content greater than or equal to 5% wt / wt and less than or equal to 50% wt / wt). Specification 10 / 54 pages 19 CN 121195019 A

[0085] In some embodiments, the intravenous catheter is hydrated before insertion into the subject (e.g., by swelling the catheter to a water content greater than or equal to 5% wt / wt and less than or equal to 50% wt / wt).

[0086] Other embodiments are also contemplated herein. Systems comprising a catheter and components configured to deliver therapeutic agents and / or aspirate bodily fluids from the subject are also disclosed.

[0087] Some aspects of this disclosure generally relate to compositions, articles, and devices comprising a body portion and components physically integrated with the body portion. The body portion may be formed of a first material comprising, for example, a first water-soluble polymer (e.g., polyvinyl alcohol). In some embodiments, the first material comprises non-covalently cross-linked polymer chains. In some cases, the first material comprises pores.In some cases, the first material comprises a combination of non-covalently cross-linked polymer chains and pores.

[0088] In some cases, the body portion may also include a component containing a second material that can be physically integrated with the body portion. In some embodiments, the second material may be the same as or different from the first material. In some embodiments, the second material comprises a polymer (e.g., a second polymer). In some cases, the polymer comprises a second water-soluble polymer such as polyvinyl alcohol (e.g., PVA). In some embodiments, the polymer comprises a partially water-soluble polymer; and in some cases, the polymer may comprise a water-insoluble polymer.

[0089] In some embodiments, the article comprises a body portion containing a first material, which comprises a water-soluble polymer (e.g., PVA). As described elsewhere herein, the body portion may comprise any water-soluble polymer known to those skilled in the art. Some exemplary embodiments include, but are not limited to, poly(vinyl alcohol), poly(acrylic acid), polyethylene glycol, poly(vinylpyrrolidone), poly(sulfonated betaine methacrylate), poly(sulfonated betaine acrylate), poly(carboxylated betaine methacrylate), poly(carboxylated betaine acrylate), povidone, polyacrylamide, poly(N-(2-hydroxypropyl)methacrylamide), polyazoline, polyphosphate, polyphosphazene, polyvinyl acetate, polypropylene glycol, poly(N-isopropylacrylamide), poly(2-hydroxymethyl methacrylate), and combinations thereof. In one set of exemplary embodiments, the first material is poly(vinyl alcohol).

[0090] In some embodiments, the first material of the body portion has a Young's modulus greater than or equal to 500 MPa in a dehydrated state and a Young's modulus less than or equal to 300 MPa and greater than or equal to 5 MPa in an equilibrium water content state. In some cases, the first material is configured to swell from a dehydrated state to an equilibrium water content state in an amount greater than or equal to 5 w / w% and less than or equal to 50 w / w% over 60 minutes at 25°C. In some embodiments, the first material is free of covalent crosslinks between the water-soluble polymers forming the first material, and / or the first material contains pores, each with a diameter of 1 μm or less. Other diameters, Young's modulus and swelling percentages are also contemplated elsewhere herein (see the Body Section section).

[0091] According to some embodiments, the body portion may comprise a hydrophilic porous polymer material containing a water-soluble polymer. In some cases, the hydrophilic porous polymer material may contain a plurality of pores. In some embodiments, the hydrophilic porous polymer material is free of covalent crosslinks between the water-soluble polymer chains, and / or contains a plurality of pores (e.g., pores with a diameter of 1 μm or less).

[0092] According to another embodiment, the article may also comprise a component. In some embodiments, the component comprises a second material that is different from or the same as the first material.In one set of exemplary embodiments, the second material is different from the first material. In another set of exemplary embodiments, the second material is the same as the first material. In some embodiments, the body portion comprises a second material (e.g., a component) containing a first water-soluble polymer at a concentration less than that of the first water-soluble polymer in the first material.

[0093] In some embodiments, the component comprises a second material that is different from or the same as the first material. In some cases, the second material comprises a medical-grade polymer, a metal, or a ceramic. The second material can be processed into multiple structures using any techniques known to those skilled in the art, including but not limited to multiple pores, multiple fibers, porous foam cavities, meshes, reticulates, and / or other structures (e.g., body material). For example, in some embodiments, the component can be processed into yarns and fabrics using techniques known to those skilled in the art to produce complex three-dimensional shapes (e.g., tubular geometries with tapered angles, etc.). In some embodiments, the second material can be a porous structure; in some embodiments, the second material can be a woven structure in which two sets of polymer yarns are interwoven at right angles. In some embodiments, the second material may be a knitted structure in which the loops of polymer yarns are entangled with each other; and in some cases, according to other embodiments, the second material may be braided in which three or more polymer yarns cross each other in a diagonal pattern.

[0094] In some embodiments, the article comprises a component physically integrated with a body portion. In some embodiments, the article comprises a component physically integrated with a hydrophilic porous polymer material. In some cases, the component is physically integrated with the body portion such that at least a portion of the component is embedded within the body portion.

[0095] In some embodiments, the article comprises a solution coating disposed on a portion of the surface of the body portion, the solution coating being configured to physically integrate the body portion with the component to form an integrated article. In some embodiments, the solution coating comprises water and poly(vinyl alcohol) (e.g., PVA) at a concentration greater than or equal to 0.1% by weight and less than or equal to 25% by weight. In some embodiments, the PVA concentration is greater than or equal to 0.1 wt%, greater than or equal to 0.5 wt%, greater than or equal to 1 wt%, greater than or equal to 5 wt%, greater than or equal to 10 wt%, greater than or equal to 15 wt%, greater than or equal to 20 wt%, or greater than or equal to 25 wt%. In some embodiments, the PVA concentration is less than or equal to 25 wt%, less than or equal to 20 wt%, less than or equal to 15 wt%, less than or equal to 10 wt%, less than or equal to 5 wt%, less than or equal to 1 wt%, less than or equal to 0.5 wt%, or less than or equal to 0.1 wt%. Combinations of the above ranges are also possible (e.g., greater than or equal to 0.1 wt% and less than or equal to 25 wt%).

[0096] In some embodiments, the solution coating comprises a UV-curable adhesive (e.g., a UV-curable adhesive capable of reacting with poly(vinyl alcohol)) such that the UV-curable adhesive reduces the equilibrium water content, for example, so that delamination due to hydrophobic bonding does not occur upon exposure to water, saline, blood, or other physiological fluids.

[0097] In some embodiments, the solution coating comprises a crosslinkable adhesive (e.g., to generate covalent crosslinks resistant to hydrolysis), for example by etherification, diurea, thiocyanate, and carbonyl cyanate, and / or using the hydroxyl portion from poly(vinyl alcohol). Some non-limiting examples of suitable (e.g., hydrolysis-resistant) crosslinkers include cyanates (e.g., diisocyanates, triisocyanates, diisothiocyanates) and ureas (e.g., isobutylene diurea, vinylidene diurea, propylene diurea), etc. Unwilling to be bound by theory, etherification can be achieved at relatively low pH using, for example, sulfuric acid and mixtures of polyethylene glycol, poly(tetrahydrofuran), poly(phenyl ether), etc.

[0098] In some embodiments, and unwilling to be bound by theory, esterification can occur in PVA-based solution coatings when polycarboxylic acids react to bridge two or more PVA molecules together. Esterification is generally readily hydrolyzed (e.g., especially in the presence of alkaline (high pH) environments). Thus, in some embodiments, esterification can provide an advantage for the biodegradable release of the adhesive mechanism, for example, to release two non-hydrolyzable devices from each other. In some embodiments, esterification can be advantageously used when a feature is temporarily required on a PVA-based device, such as a sharp tip for inserting the device into a vein (e.g., then rapidly or slowly decomposing in the vascular system). Some non-limiting examples of suitable crosslinking agents include oxalic acid, maleic acid, malonic acid, fumaric acid, malic acid, ascorbic acid, succinic acid, adipic acid, glutaric acid, tartaric acid, citric acid, poly(acrylic acid), poly(methacrylic acid), poly(caprolactone), poly(lactic acid), and poly(glycolic acid). Without wishing to be bound by theory, rigid covalent crosslinking structures can occur where two or more carboxylic acid groups are linked by carbon-carbon bonded segments. In some embodiments, such dicarboxylic acid groups can be useful (e.g., as useful hydrolyzable crosslinking bonds) and can be manufactured under low pH conditions.

[0099] In some embodiments, the body portion comprises a first material, and the component comprises a second material that is the same as or different from the first material. In a set of preferred embodiments, the first and / or second materials comprise polymers.Without wishing to be bound by any particular theory, it is generally understood that a bulk polymer material comprises surface polymer chains (hereinafter referred to as surface polymers) (e.g., polymer chains within 1 to 100 micrometers of the air-surface interface) and bulk polymer chains (hereinafter referred to as bulk polymers) (e.g., polymer chains more than 100 micrometers from the air-surface interface). In some embodiments, the first and / or second materials may contain pores. Combinations are also possible. For example, the first and / or second materials may comprise surface polymers, bulk polymers, and / or pores.

[0100] Thus, the surface polymers, bulk polymers, and / or pores of the first material (e.g., the body portion) may be integrated with the corresponding surface polymers, bulk polymers, and / or pores of the second material. The term “integration” as used herein means that the polymer chains of the first and / or second materials become physically entangled with the polymer chains and / or pores of the corresponding materials (e.g., the surface polymer of the first material may become entangled with the bulk polymer of the second material). In some cases, the entanglement may also create one or more non-covalent bonds between the polymer chains of the first and / or second materials. Some non-limiting examples include electrostatic interactions (e.g., ionic bonding, hydrogen bonding, halogen bonding), van der Waals forces (e.g., dipole-dipole interactions, dipole-induced dipole interactions, and London dispersion forces), π interactions (e.g., π-π interactions, cation-π and anion-π interactions, and polar-π interactions), and hydrophobic interactions. In some cases, the presence of one or more non-covalent bonds improves the mechanical properties of the integrated article (e.g., the body portion containing the component).

[0101] In some embodiments, the surface polymer interacts with at least a portion of the bulk polymer and at least a portion of the pores within the polymer body. In some embodiments, the surface polymer does not interact with at least a portion of the bulk polymer and at least a portion of the pores within the polymer body.

[0102] In some embodiments, the component (e.g., the second water-soluble polymer) is located within the body of the first material (e.g., the first water-soluble polymer). In some embodiments, the component (e.g., the second water-soluble polymer) is substantially uniformly distributed within the body of the first material (e.g., the first water-soluble polymer), and the first material is substantially uniformly distributed within the body of the second material. In some embodiments, the component (e.g., the second water-soluble polymer) is substantially non-uniformly distributed within the bulk of the first material (e.g., the first water-soluble polymer), and vice versa.

[0103] In some embodiments, the surface polymer of the first material is physically integrated with the surface polymer, bulk material, and / or pores of the second material. In some embodiments, the surface polymer of the second material is physically integrated with the surface polymer, bulk material, and / or pores of the first material.

[0104] In some embodiments, the bulk material of the first material is physically integrated with the surface polymer, bulk material, and / or pores of the second material. In some embodiments, the bulk material of the second material is physically integrated with the surface polymer, bulk material, and / or pores of the first material.

[0105] In some embodiments, the pores of the first material are physically integrated with the surface polymer and / or bulk material of the second material. In some embodiments, the pores of the second material are physically integrated with the surface polymer and / or bulk material of the first material.

[0106] In some embodiments, an adhesive may be present. In some embodiments, the adhesive may be physically integrated with the first component and / or the second component.

[0107] In some embodiments, the article may comprise a body portion containing an elongated tube (e.g., a conduit shaft). In some cases, the elongated tube may comprise a first material containing a water-soluble polymer (e.g., PVA). As described elsewhere herein, the water-soluble first material is a hydrophilic porous polymer material that can be processed in a dehydrated state (e.g., tensioned) or a hydrated state (e.g., relaxed). According to some embodiments, the elongated tube may further comprise a first portion (e.g., a proximal end) and a second portion (e.g., a distal end). In some embodiments, when the elongated tube is in a relaxed state (e.g., a hydrated and swollen state), the radius of curvature of the first portion (see page 13 / 54 of CN 121195019 A) differs from that of the second portion. In some embodiments, when the elongated tube is in a relaxed state, the radius of curvature of the first portion is greater than that of the second portion; while in other embodiments, when the elongated tube is in a relaxed state, the radius of curvature of the first portion is smaller than that of the second portion.

[0108] In some embodiments, the radius of curvature of the second portion (e.g., the distal portion) relative to the first portion (e.g., the proximal portion) is greater than or equal to 1 degree, greater than or equal to 2 degrees, greater than or equal to 4 degrees, greater than or equal to 5 degrees, greater than or equal to 10 degrees, greater than or equal to 15 degrees, greater than or equal to 20 degrees, greater than or equal to 40 degrees, greater than or equal to 80 degrees, greater than or equal to 100 degrees, greater than or equal to 120 degrees, greater than or equal to 140 degrees, or greater than or equal to 180 degrees. In some embodiments, the radius of curvature of the second portion (e.g., the distal portion) relative to the first portion is less than or equal to 180 degrees, less than or equal to 140 degrees, less than or equal to 120 degrees, less than or equal to 100 degrees, less than or equal to 80 degrees, less than or equal to 40 degrees, less than or equal to 20 degrees, less than or equal to 15 degrees, less than or equal to 10 degrees, less than or equal to 5 degrees, less than or equal to 4 degrees, less than or equal to 2 degrees, or less than or equal to 1 degree.

[0109] In some embodiments, the present invention describes a dual-cavity article comprising a first body portion comprising a first material containing a water-soluble polymer (e.g., PVA).The first body portion may include a first cavity (e.g., an elongated tube) having a first inner diameter. In some cases, the first body portion includes a first part and a second part. In some embodiments, the inner diameter of the first part is greater than, less than, or equal to the inner diameter of the second part. In a preferred embodiment, the first body portion includes a first cavity (e.g., an elongated tube) of a constant size (e.g., the inner diameter of the first part is equal to the inner diameter of the second part).

[0110] In some embodiments, the dual-cavity article further includes a second body portion containing a second material different from the first material, the second body portion including a second cavity (e.g., a second elongated tube) having a second inner diameter. In some cases, the second body portion includes a first part and a second part. In some embodiments, the inner diameter of the first part is greater than, less than, or equal to the inner diameter of the second part (e.g., the second body portion may taper towards one end).

[0111] In a set of preferred embodiments, the dual-cavity article includes a second body portion located inside the first body portion (e.g., a dual-cavity configuration). For example, in some embodiments, the outer diameter of the first part of the second body is smaller than the first inner diameter of the first cavity, and the second inner diameter of the second part of the second body is approximately equal to the first inner diameter. In other words, the dual-lumen article comprises a second tube having a proximal end with a first diameter and a distal end with a second diameter, the second tube being placed within a first tube of constant diameter (having a size similar to the proximal end of the second tube). Other configurations are also possible.

[0112] In some embodiments, the dual-lumen article comprises one or more surface features (e.g., barbs, bulges, etc.) at the interface between the first body portion and the second body portion. It is not desirable to be bound by any particular theory, but it is generally considered that such surface features mechanically reinforce the interface between the first body portion and the second body portion. In some embodiments, one or more surface features may be located on the first body portion and / or the second body portion.

[0113] In some embodiments, the article comprises an intravenous catheter. In some embodiments, the intravenous catheter comprises a polymeric material containing a first water-soluble polymer having a plurality of pores. As described elsewhere in this document, the preferred polymeric material comprises a first water-soluble polymer containing poly(vinyl alcohol), said polymeric material being processed into a porous material free of covalent crosslinking agents, having a water content in a dehydrated state of less than 5 w / w% and greater than or equal to 0.1 w / w%, and being configured to swell from a dehydrated state to an equilibrium water content state in an amount of greater than or equal to 5 w / w% and less than or equal to 50 w / w% over a period of less than or equal to 60 minutes at 25°C.

[0114] In some embodiments, the polymer material is processed to have a water content in the dehydrated state greater than or equal to 0.1 w / w%, greater than or equal to 0.5 w / w%, greater than or equal to 1 w / w%, greater than or equal to 2 w / w%, greater than or equal to 3 w / w%, greater than or equal to 4 w / w%, or greater than or equal to 5 w / w%. In some embodiments, the polymer material is processed to have a water content less than or equal to 5 w / w%, less than or equal to 4 w / w%, less than or equal to 3 w / w%, less than or equal to 2 w / w%, less than or equal to 1 w / w%, less than or equal to 0.5 w / w%, or less than or equal to 0.1 w / w.

[0115] In some embodiments, the polymer material is configured to swell in amounts greater than or equal to 5 w / w%, greater than or equal to 10 w / w%, greater than or equal to 15 w / w%, greater than or equal to 20 w / w%, greater than or equal to 25 w / w%, greater than or equal to 30 w / w%, greater than or equal to 35 w / w%, greater than or equal to 40 w / w%, greater than or equal to 45 w / w%, or greater than or equal to 50 w / w%. In some embodiments, the polymer material is configured to swell in amounts less than or equal to 50 w / w%, less than or equal to 45 w / w%, less than or equal to 40 w / w%, less than or equal to 35 w / w%, less than or equal to 30 w / w%, less than or equal to 25 w / w%, less than or equal to 20 w / w%, less than or equal to 15 w / w%, less than or equal to 10 w / w%, or less than or equal to 5 w / w.

[0116] In some embodiments, the polymer material is configured to swell from a dehydrated state to an equilibrium water content state within 60 minutes or less, 50 minutes or less, 40 minutes or less, 30 minutes or less, or 15 minutes.

[0117] In some embodiments, the intravenous catheter may be configured to be inserted into the object in a dehydrated, partially hydrated, or hydrated state. In some embodiments, the catheter may be at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, or at least 50% hydrated before insertion. In some embodiments, the catheter may be less than or equal to 50%, less than or equal to 40%, less than or equal to 30%, less than or equal to 20%, or less than or equal to 10% hydrated before insertion. Combinations of the above ranges are also possible.

[0118] In some cases, the intravenous catheter also includes a lumen and a distal end having a tip geometry adapted for intravenous insertion into the object. The lumen of the intravenous catheter may be of any size known to those skilled in the art. For example, in some cases, the lumen size can be selected to correspond to the standard peripheral venous catheter size.Without wishing to be bound by any particular theory, those skilled in the art will recognize that catheters are typically sized by specifications (e.g., 14G, 16G, 18G, 20G, 22G, 24G, 26G, and 30G, etc.), with each specification having a standardized outer diameter and length. For example, a standard 14G catheter typically has an outer diameter of 2.1 mm, while a 26G catheter has an outer diameter of 0.6 mm.

[0119] In some embodiments, intravenous catheters may include a tip geometry, for example, to improve insertion into a vein of the recipient. Any tip geometry known to those skilled in the art may be used. Some non-limiting embodiments include a bevel tip needle stylet, a bevel tip needle cannula, a lancet point needle stylet, a back bevel needle stylet, a back bevel needle cannula, a trocar tip needle stylet, a Franseen tip needle cannula, or a conical tip needle stylet. In some embodiments, the tip comprises a symmetrical geometry; however, in some embodiments, the tip comprises an asymmetrical geometry.

[0120] Some aspects of this disclosure generally relate to catheter systems comprising the catheters and components described herein, said components being configured for administering therapeutic agents and / or fluids (e.g., saline, Plasma Lyte, etc.) to a subject and / or aspirating bodily fluids (e.g., blood) from a subject.

[0121] In some embodiments, the catheter system is configured for obtaining venous access. The system may include peripheral devices such as peripheral intravenous lines (e.g., PIV, for short-term access, e.g., up to 96 hours) and / or midline catheters, or central devices such as PICC (e.g., for medium-term access, approximately 6 months, and especially for antibiotics, TPN, chemotherapy, transfusions, and frequent blood sampling), non-tunneled central catheters (e.g., for short-term access when PIV is unsuitable, and especially for resuscitation and central venous pressure monitoring), tunneled central catheters (e.g., for frequent long-term access, and especially for TPN, transfusions, and frequent blood sampling. Can be used when a PICC line is contraindicated or not feasible), or implantable ports (e.g., for long-term infrequent access, or when lifestyle issues make one of the other options less attractive).

[0122] In some embodiments, the catheter system is configured to provide urinary access. Those skilled in the art will understand that current catheter systems include intermittent catheters, indwelling catheters, and suprapubic catheters. Intermittent catheters are the most common and are inserted into the bladder several times a day to empty it and are subsequently removed from the body. Indwelling catheters are held in the bladder by a water-filled balloon to prevent dislodgement (often referred to as Foley catheters). Urine is drained through a tube connected to a collection bag. In some cases, indwelling catheters may include a valve that can be opened to allow urine to drain and closed to allow the bladder to fill with urine until it is convenient to drain. Suprapubic catheters are left in place for long-term use. The catheter is not inserted through the urethra but through a hole in the abdomen and placed directly in the bladder. Suprapubic catheters are typically used when the urethra is damaged or obstructed (e.g., due to cancer). Like indwelling catheters, suprapubic catheters may include a valve to allow intermittent drainage.

[0123] Therefore, the systems described herein may include any number of components other than the catheter itself. Some exemplary embodiments include, but are not limited to, collection bags, drainage tubes, drainage ports, catheter cuffs and / or catheter balloons, hubs and wings, valves, injection port caps, needle grips, flashback chambers, Luer lock plugs, and optional needles.

[0124] In some embodiments, the articles of the present invention comprise a first material (e.g., a water-soluble polymer, a hydrophilic porous material, etc.). The following is a non-limiting description of several embodiments contemplated with respect to the first material as described elsewhere herein.

[0125] Some aspects of this disclosure generally relate to articles (e.g., devices) comprising a body portion containing a first porous material. In some embodiments, the plurality of pores have a specific average pore size. In some embodiments, the average pore size of the plurality of pores is less than or equal to 500 nm, less than or equal to 450 nm, less than or equal to 400 nm, less than or equal to 350 nm, less than or equal to 300 nm, less than or equal to 250 nm, less than or equal to 200 nm, less than or equal to 150 nm, less than or equal to 100 nm, less than or equal to 75 nm, less than or equal to 50 nm, less than or equal to 25 nm, less than or equal to 20 nm, or less than or equal to 15 nm.In some embodiments, the average pore size of the plurality of pores is greater than or equal to 10 nm, greater than or equal to 15 nm, greater than or equal to 20 nm, greater than or equal to 25 nm, greater than or equal to 50 nm, greater than or equal to 75 nm, greater than or equal to 100 nm, greater than or equal to 150 nm, greater than or equal to 200 nm, greater than or equal to 250 nm, greater than or equal to 300 nm, greater than or equal to 350 nm, greater than or equal to 400 nm, or greater than or equal to 450 nm. Combinations of the above ranges are also possible (e.g., less than or equal to 500 nm and greater than or equal to 10 nm). Other ranges are also possible. As described herein, the average pore size can be determined by mercury intrusion porosimetry of the material in a first configuration (e.g., a water content less than the equilibrium water content state, such as a dehydrated state). In some embodiments, the pores are interconnected.

[0126] In some embodiments, at least a portion of the plurality of pores can be characterized as nanopores, for example, pores with an average cross-sectional size of less than 1 micrometer. In some embodiments, at least a portion of the plurality of pores may be characterized as micropores, for example, pores with an average cross-sectional size of less than 1 mm and greater than or equal to 1 micrometer. In some embodiments, at least 50% (e.g., at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98%, at least 99%, at least 99.9%) of the plurality of pores have diameters less than or equal to 1 micrometer, less than or equal to 800 nm, less than or equal to 600 nm, less than or equal to 500 nm, less than or equal to 450 nm, less than or equal to 400 nm, less than or equal to 350 nm, less than or equal to 300 nm, less than or equal to 250 nm, less than or equal to 200 nm, less than or equal to 150 nm, less than or equal to 100 nm, less than or equal to 75 nm, less than or equal to 50 nm, less than or equal to 25 nm, less than or equal to 20 nm, or less than or equal to 15 nm. In some cases, at least 50% of the diameters of multiple holes are greater than or equal to 10 nm, greater than or equal to 15 nm, greater than or equal to 20 nm, greater than or equal to 25 nm, greater than or equal to 50 nm, greater than or equal to 75 nm, greater than or equal to 100 nm, greater than or equal to 150 nm, greater than or equal to 200 nm, greater than or equal to 250 nm, greater than or equal to 300 nm, greater than or equal to 350 nm, greater than or equal to 400 nm, greater than or equal to 450 nm, greater than or equal to 500 nm, greater than or equal to 600 nm, or greater than or equal to 800 nm.Combinations of the above ranges are also possible (e.g., less than or equal to 1000 nm and greater than or equal to 10 nm). Other ranges are also possible. In some embodiments, the pores are interconnected.

[0127] The first material described herein may have a specific porosity, for example, in a first configuration (e.g., a water content less than the equilibrium water content state, such as a dehydrated state). In some embodiments, the device (first water-soluble polymer) has a porosity greater than or equal to 5%, greater than or equal to 10%, greater than or equal to 15%, greater than or equal to 20%, greater than or equal to 25%, greater than or equal to 30%, greater than or equal to 35%, greater than or equal to 40%, or greater than or equal to 45% in the first configuration (e.g., a water content less than the equilibrium water content state, such as a dehydrated state). In some embodiments, the porosity of the device (first water-soluble polymer) in a first configuration (e.g., water content less than equilibrium water content, e.g., dehydrated state) is less than or equal to 50%, less than or equal to 45%, less than or equal to 40%, less than or equal to 35%, less than or equal to 30%, less than or equal to 25%, less than or equal to 20%, less than or equal to 15%, or less than or equal to 10%. Combinations of the above ranges are also possible (e.g., greater than or equal to 5% and less than or equal to 50% in the first configuration (e.g., water content less than equilibrium water content, e.g., dehydrated state)). Other ranges are also possible.

[0128] In some embodiments, the first material (e.g., first water-soluble polymer) is hydrophilic. The term “hydrophilic” as used herein is given its common meaning in the art and refers to a material surface having a water contact angle of less than 90 degrees as determined by goniometrics. In some embodiments, the polymer material (or its surface) (e.g., the polymer material of the device) has a water contact angle in an equilibrium water content state that is less than or equal to 45 degrees, less than or equal to 40 degrees, less than or equal to 35 degrees, less than or equal to 30 degrees, less than or equal to 25 degrees, less than or equal to 20 degrees, less than or equal to 15 degrees, less than or equal to 10 degrees, less than or equal to 5 degrees, or less than or equal to 2 degrees. In some embodiments, the polymer material (or its surface) has a water contact angle in an equilibrium water content state that is greater than or equal to 1 degree, greater than or equal to 2 degrees, greater than or equal to 5 degrees, greater than or equal to 10 degrees, greater than or equal to 15 degrees, greater than or equal to 20 degrees, greater than or equal to 25 degrees, greater than or equal to 30 degrees, greater than or equal to 35 degrees, or greater than or equal to 40 degrees. Combinations of the above ranges are also possible (e.g., greater than or equal to 1 degree and less than or equal to 45 degrees). Other ranges are also possible.

[0129] As used herein, equilibrium water content state refers to the steady state of a device (or material) that does not increase (e.g., absorb) or lose its bulk water content when immersed in water at 25°C without externally applied mechanical stress.Those skilled in the art will understand that a steady state (or equilibrium water content state) should be understood not to require absolute conformity to the strict thermodynamic definition of such a term, but rather to indicate conformity to the thermodynamic definition of such a term to the extent that the subject matter being characterized can be understood by those skilled in the art most closely related to such subject matter (e.g., taking into account factors such as passive diffusion and / or Brownian motion).

[0130] In some embodiments, the equilibrium water content state of the first water-soluble polymer is greater than or equal to 10 w / w%, greater than or equal to 20 w / w%, greater than or equal to 25 w / w%, greater than or equal to 30 w / w%, greater than or equal to 35 w / w%, greater than or equal to 40 w / w%, greater than or equal to 45 w / w%, greater than or equal to 50 w / w%, greater than or equal to 55 w / w%, greater than or equal to 60 w / w%, greater than or equal to 65 w / w%, or greater than or equal to 70 w / w. In some embodiments, the equilibrium water content of the first water-soluble polymer is less than or equal to 80 w / w%, less than or equal to 75 w / w%, less than or equal to 70 w / w%, less than or equal to 65 w / w%, less than or equal to 60 w / w%, less than or equal to 55 w / w%, less than or equal to 50 w / w%, less than or equal to 45 w / w%, less than or equal to 40 w / w%, less than or equal to 35 w / w%, less than or equal to 30 w / w%, less than or equal to 25 w / w%, or less than or equal to 20 w / w%. Combinations of these ranges are also possible (e.g., greater than or equal to 10% w / w and less than or equal to 80% w / w). Other ranges are also possible.

[0131] In some embodiments, the first material is substantially smooth in the equilibrium water content state. For example, in some embodiments, the surface roughness (Ra) of the first material (e.g., the first water-soluble polymer) in the equilibrium water content state is less than or equal to 1000 nm. In some embodiments, the surface roughness (Ra) of the first material (e.g., the first water-soluble polymer) in the equilibrium water content state is less than or equal to 500 nm, less than or equal to 400 nm, less than or equal to 300 nm, less than or equal to 250 nm, less than or equal to 200 nm, less than or equal to 150 nm, less than or equal to 100 nm, less than or equal to 50 nm, less than or equal to 25 nm, less than or equal to 10 nm, or less than or equal to 5 nm.In some embodiments, the surface roughness (Ra) of the first material (or the polymer material of the device) in the equilibrium water content state is greater than or equal to 5 nm, and the surface roughness (Ra) in the equilibrium water content state is greater than or equal to 10 nm, greater than or equal to 25 nm, greater than or equal to 50 nm, greater than or equal to 100 nm, greater than or equal to 150 nm, greater than or equal to 200 nm, greater than or equal to 250 nm, greater than or equal to 300 nm, greater than or equal to 400 nm, or greater than or equal to 500 nm. Combinations of the above ranges are also possible (e.g., greater than or equal to 5 nm and less than or equal to 1000 nm). Other ranges are also possible.

[0132] In some embodiments, the first material has a surface with a coefficient of friction less than or equal to 0.10 in the equilibrium water content state. For example, the coefficient of friction of the surface of the device (or the polymer material of the device) is less than or equal to 0.1, less than or equal to 0.09, less than or equal to 0.08, less than or equal to 0.07, less than or equal to 0.06, less than or equal to 0.05, less than or equal to 0.04, less than or equal to 0.03, or less than or equal to 0.02. In some embodiments, the coefficient of friction of the surface of the body portion (or the polymer material of the device) is greater than or equal to 0.01, greater than or equal to 0.02, greater than or equal to 0.03, greater than or equal to 0.04, greater than or equal to 0.05, greater than or equal to 0.06, greater than or equal to 0.07, greater than or equal to 0.08, or greater than or equal to 0.09. Combinations of the above ranges are also possible (e.g., less than or equal to 0.1 and greater than or equal to 0.01). Other ranges are also possible.

[0133] Advantageously, the first material described herein (e.g., the first water-soluble polymer) can have low adsorption to such substances in the presence of a dynamic fluid containing substances such as therapeutic agents (and / or, for example, proteins). Such devices and compositions can be used in objects in which, for example, the presence of the device should substantially not reduce the availability and / or concentration of the therapeutic agent delivered (e.g., via the device) to the object. In some embodiments, application of the therapeutic agent via a fluid flowing within the device described herein does not substantially reduce the concentration of the therapeutic agent within the fluid. In some cases, the device may not absorb and / or adsorb the therapeutic agent, for example, during flow or use.

[0134] In some embodiments, as determined at the equilibrium water content after exposing the polymer to the therapeutic agent and rinsing with an aqueous solution (e.g., water or saline) of 5 times the device volume, adsorption of the therapeutic agent by the surface and / or bulk of the first material (e.g., the first water-soluble polymer) is less than or equal to 0.5 w / w.In some embodiments, the adsorption of the therapeutic agent on the surface and / or bulk of the first water-soluble polymer is less than or equal to 0.5 w / w%, less than or equal to 0.4 w / w%, less than or equal to 0.3 w / w%, less than or equal to 0.2 w / w%, or less than or equal to 0.1 w / w%. In some embodiments, the adsorption of the therapeutic agent on the surface and / or bulk of the first water-soluble polymer is greater than or equal to 0.05 w / w%, greater than or equal to 0.1 w / w%, greater than or equal to 0.2 w / w%, greater than or equal to 0.3 w / w%, or greater than or equal to 0.4 w / w%. Combinations of the above ranges are also possible (e.g., less than or equal to 0.5 w / w% and greater than or equal to 0.05 w / w%). Other ranges are also possible.

[0135] Advantageously, the first material described herein may have desired swelling properties (e.g., in water, in salt water, in the fluid environment of the object).

[0136] In some embodiments, the first material described herein (e.g., a first water-soluble polymer) has a first configuration with a water content of the following (e.g., a water content less than the equilibrium water content state, such as a dehydrated state): less than or equal to 40 w / w%, less than or equal to 30 w / w%, less than or equal to 20 w / w%, less than or equal to 10 w / w%, less than or equal to 5 w / w%, less than or equal to 4 w / w%, less than or equal to 3 w / w%, less than or equal to 2 w / w%, less than or equal to 1 w / w%, less than or equal to 0.8 w / w%, less than or equal to 0.6 w / w%, less than or equal to 0.4 w / w%, or less than or equal to 0.2 w / w. In some embodiments, the first material described herein has a first configuration with a water content of the following (e.g., a water content less than the equilibrium water content state, such as a dehydrated state): greater than or equal to 0.1 w / w%, greater than or equal to 0.2 w / w%, greater than or equal to 0.4 w / w%, greater than or equal to 0.6 w / w%, greater than or equal to 0.8 w / w%, greater than or equal to 1 w / w%, greater than or equal to 2 w / w%, greater than or equal to 3 w / w%, greater than or equal to 4 w / w%, greater than or equal to 5 w / w%, greater than or equal to 6 w / w%, greater than or equal to 7 w / w%, greater than or equal to 8 w / w%, greater than or equal to 9 w / w%, greater than or equal to 10 w / w%, greater than or equal to 15 w / w, greater than or equal to 20 w / w%, greater than or equal to 25 w / w%, greater than or equal to 30 w / w%, or greater than or equal to 35 w / w.Combinations of the above ranges are also possible (e.g., greater than or equal to 0.1 w / w% and less than 5 w / w%, greater than or equal to 2 w / w% and less than or equal to 10 w / w%, greater than or equal to 2 w / w% and less than or equal to 40 w / w%, or greater than or equal to 6 w / w% and less than or equal to 40 w / w%). Other ranges are also possible.

[0137] In some embodiments, the first material described herein has a first configuration (e.g., a water content less than the equilibrium water content state, such as a dehydrated state). In some embodiments, the first material (or polymer material) described herein swells from the first configuration (e.g., a water content less than the equilibrium water content state, such as a dehydrated state) to a second configuration (e.g., an equilibrium water content state) in less than or equal to 60 minutes (e.g., less than or equal to 10 minutes, less than or equal to 5 minutes, less than or equal to 1 minute, or less than or equal to 10 seconds). In some embodiments, the first material (or polymeric material) described herein swells from a first configuration (e.g., a state with less water content than equilibrium water content, e.g., a dehydrated state) to a second configuration (e.g., a state with equilibrium water content) at 25°C.

[0138] In some embodiments, the first material described herein swells from the first configuration (e.g., a state with less water content than equilibrium water content, e.g., a dehydrated state) to a second configuration (e.g., a state with equilibrium water content) in amounts such as: greater than or equal to 2 w / w%, greater than or equal to 3 w / w%, greater than or equal to 4 w / w%, greater than or equal to 5 w / w%, greater than or equal to 10 w / w%, greater than or equal to 15 w / w%, greater than or equal to 20 w / w%, greater than or equal to 25 w / w%, greater than or equal to 30 w / w%, greater than or equal to 35 w / w%, greater than or equal to 40 w / w%, or greater than or equal to 45 w / w. In some embodiments, the first material (or polymeric material) described herein swells from a first configuration (e.g., a water content less than the equilibrium water content state, e.g., a dehydrated state) to a second configuration (e.g., an equilibrium water content state) in amounts such as: less than or equal to 50 w / w%, less than or equal to 45 w / w%, less than or equal to 40 w / w%, less than or equal to 35 w / w%, less than or equal to 30 w / w%, less than or equal to 25 w / w%, less than or equal to 20 w / w%, less than or equal to 15 w / w%, less than or equal to 10 w / w%, less than or equal to 5 w / w%, less than or equal to 4 w / w%, or less than or equal to 3 w / w%. Combinations of these ranges are also possible (e.g., greater than or equal to 5% w / w and less than or equal to 40% w / w).

[0139] In some embodiments, the first material described herein is in a first configuration (e.g., a water content less than the equilibrium water content state, e.g., a dehydrated state).For example, in some embodiments, the first material described herein (e.g., the first water-soluble polymer) has a water content of less than or equal to 40 w / w%, less than or equal to 30 w / w%, less than or equal to 20 w / w%, less than or equal to 10 w / w%, less than or equal to 5 w / w%, less than or equal to 4 w / w%, less than or equal to 3 w / w%, less than or equal to 2 w / w%, less than or equal to 1 w / w%, less than or equal to 0.8 w / w%, less than or equal to 0.6 w / w%, less than or equal to 0.4 w / w%, or less than or equal to 0.2 w / w in a first configuration (e.g., a water content less than the equilibrium water content state, such as a dehydrated state). In some embodiments, the water content of the first material described herein (e.g., the first water-soluble polymer) is greater than or equal to 0.1 w / w%, greater than or equal to 0.2 w / w%, greater than or equal to 0.4 w / w%, greater than or equal to 0.6 w / w%, greater than or equal to 0.8 w / w%, greater than or equal to 1 w / w%, greater than or equal to 2 w / w%, greater than or equal to 3 w / w%, or greater than or equal to 4 w / w%. Combinations of the above ranges are also possible (e.g., greater than or equal to 0.1 w / w% and less than 5 w / w%, or greater than or equal to 2 w / w% and less than or equal to 40 w / w%). Other ranges are also possible. The dehydration state described herein generally refers to a stable state determined under environmental conditions, wherein the water content of the device (first water-soluble polymer) does not decrease significantly (less than 5 w / w%) within 24 hours. In some embodiments, the device described herein may include a coating or an unbonded pore-forming agent, such as a humectant coating, as described in more detail below.

[0140] Advantageously, the first material (e.g., a first water-soluble polymer) and composition described herein may be configured to swell rapidly in the presence of an aqueous solution (e.g., water and / or brine). In some embodiments, the first material is configured to swell, for example, at 25°C for a specific time period (e.g., less than or equal to 60 minutes, less than or equal to 10 minutes, less than or equal to 5 minutes, less than or equal to 1 minute, or less than or equal to 10 seconds) from a first configuration (e.g., a state with water content less than the equilibrium water content, such as a dehydrated state) to a second configuration (e.g., a state with equilibrium water content) in the following amounts: greater than or equal to 2 w / w%, greater than or equal to 5 w / w%, greater than or equal to 10 w / w%, greater than or equal to 15 w / w%, greater than or equal to 20 w / w%, greater than or equal to 25 w / w%, greater than or equal to 30 w / w%, greater than or equal to 35 w / w%, greater than or equal to 40 w / w%, or greater than or equal to 45 w / w, as described in more detail below.In some embodiments, the first material is configured to swell, for example, at 25°C for a specific time period (e.g., less than or equal to 60 minutes, less than or equal to 10 minutes, less than or equal to 5 minutes, less than or equal to 1 minute, or less than or equal to 10 seconds) from a first configuration (e.g., a water content less than the equilibrium water content state, such as a dehydrated state) to a second configuration (e.g., an equilibrium water content state) in the following amounts: less than or equal to 50 w / w%, less than or equal to 45 w / w%, less than or equal to 40 w / w%, less than or equal to 35 w / w%, less than or equal to 30 w / w%, less than or equal to 25 w / w%, less than or equal to 20 w / w%, less than or equal to 15 w / w%, or less than or equal to 10 w / w, as described in more detail below. Combinations of the above ranges are also possible (e.g., greater than or equal to 5 w / w% and less than or equal to 50 w / w%). Other ranges are also possible.

[0141] In one exemplary embodiment, the first material is configured to swell in water in a first configuration (e.g., a water content less than the equilibrium water content state, such as a dehydrated state) (e.g., less than 5 w / w% or greater than or equal to 10 minutes, 5 minutes, 1 minute, or 10 seconds) to an equilibrium water content state (e.g., greater than or equal to 5 w / w% or greater than or equal to 20 w / w% and less than or equal to 80 w / w%) within 60 minutes (e.g., less than 10 minutes, 5 minutes, 1 minute, or 10 seconds). In some embodiments, the first material is configured to swell in standard physiological saline from, for example, a first configuration (e.g., a water content less than the equilibrium water content state, such as a dehydrated state) to an equilibrium water content (e.g., greater than or equal to 5 w / w% or greater than or equal to 20 w / w% and less than or equal to 80 w / w%) within 60 minutes (e.g., less than or equal to 10 minutes, 5 minutes, 1 minute, or 10 seconds) for less than or equal to 60 minutes (e.g., less than or equal to 10 minutes, 5 minutes, 1 minute, or 10 seconds). In another exemplary embodiment, the first material (e.g., a first water-soluble polymer) is configured to swell in physiological saline from, for example, a first configuration (e.g., a water content less than the equilibrium water content state, such as a dehydrated state) (e.g., less than 5 w / w%) to an equilibrium water content (e.g., greater than or equal to 5 w / w%) or greater than or equal to 20 w / w% and less than or equal to 80 w / w%) within 60 minutes (e.g., less than or equal to 10 minutes, 5 minutes, 1 minute, or 10 seconds) for less than or equal to 60 minutes (e.g., less than or equal to 10 minutes, 5 minutes, 1 minute, or 10 seconds).

[0142] In some embodiments, the first material has a specific length in the first configuration (e.g., a water content less than the equilibrium water content state, such as a dehydrated state).In some embodiments, compared to the length of the device (first water-soluble polymer) in the first configuration (e.g., with a water content less than the equilibrium water content state, such as the dehydrated state), its total length in the equilibrium water content state increases by greater than or equal to 0.1%, greater than or equal to 0.5%, greater than or equal to 1%, greater than or equal to 2%, greater than or equal to 4%, greater than or equal to 6%, greater than or equal to 8%, greater than or equal to 10%, greater than or equal to 12%, greater than or equal to 14%, greater than or equal to 16%, or greater than or equal to 18%. In some cases, the total length of the first material (first water-soluble polymer) in the first configuration (e.g., with a water content less than the equilibrium water content state, such as a dehydrated state) increases by less than or equal to 20%, less than or equal to 18%, less than or equal to 16%, less than or equal to 14%, less than or equal to 12%, less than or equal to 10%, less than or equal to 8%, less than or equal to 6%, less than or equal to 4%, less than or equal to 2%, less than or equal to 1%, or less than or equal to 0.5% compared to the length of the first material (first water-soluble polymer) in the first configuration (e.g., with a water content less than the equilibrium water content state, such as a dehydrated state). Combinations of the above ranges are also possible (e.g., greater than or equal to 0.1% and less than or equal to 20%). Other ranges are also possible.

[0143] In some embodiments, the first material has a specific maximum external cross-sectional dimension, such as the outer diameter of a cylindrical tube, an elliptical tube, a rectangular tube, or a square tube. In some embodiments in which the device comprises multiple cavities, the outer diameter refers to the maximum external cross-sectional dimension of one or more cavities. For example, in some embodiments, only one cavity may have the listed outer diameter. In other embodiments, each and every cavity may have the listed outer diameter independently. In some embodiments, compared to the maximum cross-sectional dimension (e.g., outer diameter) of the first material (e.g., the first water-soluble polymer) in the first configuration (e.g., the water content is less than the equilibrium water content state, such as the dehydrated state), the maximum external cross-sectional dimension (e.g., outer diameter) of the first material (e.g., the first water-soluble polymer) in the equilibrium water content state is increased by greater than or equal to 0.1%, greater than or equal to 0.5%, greater than or equal to 1%, greater than or equal to 2%, greater than or equal to 4%, greater than or equal to 6%, greater than or equal to 8%, greater than or equal to 10%, greater than or equal to 12%, greater than or equal to 14%, greater than or equal to 16%, or greater than or equal to 18%.In some cases, compared to the maximum cross-sectional size (e.g., outer diameter) of the first material (e.g., the first water-soluble polymer) in the first configuration (e.g., the water content is less than the equilibrium water content state, such as the dehydrated state), the increase in the maximum cross-sectional size (e.g., outer diameter) of the first material (e.g., the first water-soluble polymer) in the equilibrium water content state is less than or equal to 20%, less than or equal to 18%, less than or equal to 16%, less than or equal to 14%, less than or equal to 12%, less than or equal to 10%, less than or equal to 8%, less than or equal to 6%, less than or equal to 4%, less than or equal to 2%, less than or equal to 1%, or less than or equal to 0.5%. Combinations of the above ranges are also possible (e.g., greater than or equal to 0.1% and less than or equal to 20%, greater than or equal to 0.1% and less than or equal to 10%). Other ranges are also possible.

[0144] In some embodiments, the first material (e.g., the first water-soluble polymer) has a specific inner diameter as the maximum internal cross-sectional size (e.g., in one embodiment where the device includes a hollow core), such as the inner diameter of a cylindrical or square tube (or other non-cylindrical device or body portion). In some embodiments where the first material (e.g., the first water-soluble polymer) includes multiple cavities, the inner diameter refers to the maximum internal cross-sectional size (i.e., the maximum internal cross-sectional size of the maximum cavity). In some embodiments, the inner diameter of the first material (e.g., the first water-soluble polymer) in the equilibrium water content state increases by greater than or equal to 0.1%, greater than or equal to 0.5%, greater than or equal to 1%, greater than or equal to 2%, greater than or equal to 4%, greater than or equal to 6%, greater than or equal to 8%, greater than or equal to 10%, greater than or equal to 12%, greater than or equal to 14%, greater than or equal to 16%, or greater than or equal to 18%, compared to the inner diameter of the first material (e.g., the first water-soluble polymer) in the first configuration (e.g., a water content less than the equilibrium water content state, e.g., a dehydrated state). In some cases, compared to the inner diameter of the first material (e.g., the first water-soluble polymer) in the first configuration (e.g., with a water content less than the equilibrium water content state, such as a dehydrated state), the increase in the inner diameter of the first material (e.g., the first water-soluble polymer) in the equilibrium water content state is less than or equal to 20%, less than or equal to 18%, less than or equal to 16%, less than or equal to 14%, less than or equal to 12%, less than or equal to 10%, less than or equal to 8%, less than or equal to 6%, less than or equal to 4%, less than or equal to 2%, less than or equal to 1%, or less than or equal to 0.5%. Combinations of the above ranges are also possible (e.g., greater than or equal to 0.1% and less than or equal to 20%). Other ranges are also possible.

[0145] In some embodiments, when the first material (e.g., the first water-soluble polymer) swells from a first configuration (e.g., a state with less water content than the equilibrium water content, such as a dehydrated state) to a second configuration (e.g., a state with the equilibrium water content), the percentage increase in the total length of the material (e.g., the first water-soluble polymer) is greater than the percentage increase in the inner diameter and / or outer diameter. For example, in some embodiments, the total length may increase by 1% to 20% (e.g., 5% to 15%), while the inner diameter and / or outer diameter increases by 0.1% to 19% (e.g., 1% to 10%).

[0146] In some embodiments, when the first material (e.g., the first water-soluble polymer) swells from a first configuration (e.g., a state with less water content than the equilibrium water content, such as a dehydrated state) to a second configuration (e.g., a state with equilibrium water content), the ratio of the percentage increase in total length to the percentage increase in inner diameter and / or outer diameter is greater than or equal to 1.1, greater than or equal to 1.5, greater than or equal to 2, greater than or equal to 5, greater than or equal to 7, or greater than or equal to 10. In some embodiments, when the first material (e.g., the first water-soluble polymer) swells from a first configuration (e.g., a state with less water content than the equilibrium water content, such as a dehydrated state) to a second configuration (e.g., a state with equilibrium water content), the ratio of the percentage increase in total length to the percentage increase in inner diameter and / or outer diameter is less than or equal to 20, less than or equal to 15, less than or equal to 10, less than or equal to 5, or less than or equal to 2. Combinations of these ranges are also possible (e.g., 1.1 to 20).

[0147] In some embodiments, when the first material (e.g., the first water-soluble polymer) swells from a first configuration (e.g., a state with less water content than the equilibrium water content, such as a dehydrated state), the percentage increase in the inner diameter and / or outer diameter of the first material (e.g., the first water-soluble polymer) is greater than the percentage increase in the total length.

[0148] In some embodiments, when the first material (e.g., the first water-soluble polymer) swells from a first configuration (e.g., a state with less water content than the equilibrium water content, such as a dehydrated state) to a second configuration (e.g., a state with equilibrium water content), the ratio of the percentage increase in the inner diameter and / or outer diameter to the percentage increase in the total length is greater than or equal to 1.1, greater than or equal to 1.5, greater than or equal to 2, greater than or equal to 5, greater than or equal to 7, or greater than or equal to 10. In some embodiments, when the first material (e.g., the first water-soluble polymer) swells from a first configuration (e.g., a state with less water content than the equilibrium water content, such as a dehydrated state) to a second configuration (e.g., a state with equilibrium water content), the percentage increase in the inner diameter and / or outer diameter relative to the percentage increase in the total length is less than or equal to 20, less than or equal to 10, less than or equal to 5, or less than or equal to 2.Combinations of these ranges are also possible (e.g., 1.1 to 20).

[0149] In some embodiments, the first material comprises one or more polymers having the desired mechanical properties. For example, in some embodiments, the first material has a Young's modulus greater than or equal to 100 MPa, greater than or equal to 250 MPa, greater than or equal to 500 MPa, greater than or equal to 600 MPa, greater than or equal to 750 MPa, greater than or equal to 800 MPa, greater than or equal to 900 MPa, greater than or equal to 1000 MPa, greater than or equal to 1250 MPa, greater than or equal to 1500 MPa, greater than or equal to 1750 MPa, greater than or equal to 2000 MPa, greater than or equal to 2500 MPa, greater than or equal to 3000 MPa, greater than or equal to 3500 MPa, or greater than or equal to 4000 MPa in a first configuration (e.g., water content less than equilibrium water content, e.g., dehydrated state) (e.g., less than 5 w / w% water content). In some embodiments, the Young's modulus of the first and / or second materials in a first configuration (e.g., a water content less than the equilibrium water content state, such as a dehydrated state) (e.g., less than 5 w / w% water content) is less than or equal to 5000 MPa, less than or equal to 4000 MPa, less than or equal to 3500 MPa, less than or equal to 3000 MPa, less than or equal to 2500 MPa, less than or equal to 2000 MPa, less than or equal to 1750 MPa, less than or equal to 1500 MPa, less than or equal to 1250 MPa, less than or equal to 1000 MPa, less than or equal to 900 MPa, less than or equal to 800 MPa, less than or equal to 750 MPa, less than or equal to 600 MPa, less than or equal to 500 MPa, or less than or equal to 250 MPa. Combinations of the above ranges are also possible (e.g., greater than or equal to 100 MPa and less than or equal to 5000 MPa). Other ranges are also possible.

[0150] In some embodiments, the Young's modulus of the first material in the equilibrium water content state is less than or equal to 300 MPa, less than or equal to 250 MPa, less than or equal to 200 MPa, less than or equal to 150 MPa, less than or equal to 100 MPa, less than or equal to 75 MPa, less than or equal to 50 MPa, less than or equal to 25 MPa, less than or equal to 20 MPa, or less than or equal to 10 MPa, as specified on page 22 / 54 of the specification (CN 121195019 A).In some embodiments, the Young's modulus of the first material in the equilibrium water content state is greater than or equal to 5 MPa, greater than or equal to 10 MPa, greater than or equal to 20 MPa, greater than or equal to 25 MPa, greater than or equal to 50 MPa, greater than or equal to 75 MPa, greater than or equal to 100 MPa, greater than or equal to 150 MPa, greater than or equal to 200 MPa, or greater than or equal to 250 MPa. Combinations of the above ranges are also possible (e.g., less than or equal to 300 MPa and greater than or equal to 5 MPa). Other ranges are also possible.

[0151] In a set of preferred embodiments, the Young's modulus of the first material in the dehydrated state is greater than or equal to 500 MPa, greater than or equal to 600 MPa, greater than or equal to 700 MPa, greater than or equal to 800 MPa, greater than or equal to 900 MPa, or greater than or equal to 1000 MPa. In some embodiments, the Young's modulus of the first material in the dehydrated state is less than or equal to 1000 MPa, less than or equal to 900 MPa, less than or equal to 800 MPa, less than or equal to 700 MPa, less than or equal to 600 MPa, or less than or equal to 500 MPa.

[0152] In another set of preferred embodiments, the Young's modulus of the first material in the equilibrium water content state is less than or equal to 300 MPa and greater than or equal to 5 MPa. In some cases, the Young's modulus of the first material in the dehydrated state may be greater than or equal to 500 MPa, and the Young's modulus in the equilibrium water content state may be less than or equal to 300 MPa and greater than or equal to 5 MPa.

[0153] In some embodiments, the Young's modulus of the polymer material in the equilibrium water content state is less than or equal to 100 MPa and greater than or equal to 5 MPa.

[0154] In a set of preferred embodiments, the devices / articles described herein (e.g., intravascular catheters) include mechanical properties (e.g., stiffness) (e.g., to prevent bending or lumen collapse) or intended use (e.g., to draw blood from the subject) that support insertion into a vein of a subject via percutaneous injection. As a complement or alternative, the device / article acquires appropriate flexibility after insertion to allow for longer indwelling times.

[0155] In some embodiments, the composition of the first material (e.g., a first water-soluble polymer material) (e.g., comprising or formed of a polymer material) does not contain covalent crosslinks, as described in more detail below. However, in other embodiments, the composition (e.g., the first material) contains physical crosslinks (e.g., interpenetrating networks, chain entanglements, and / or one or more bonds, such as covalent bonds, ionic bonds, and / or hydrogen bonds). In a set of specific embodiments, covalent crosslinking agents are not used to form the body portion (e.g., the first material and / or the second material).

[0156] The first material may be present in the device in any suitable amount. For example, in some embodiments, the first material (e.g., a first water-soluble polymer) is present in the device and / or body portion in the following amounts at equilibrium water content: greater than or equal to 20 w / w%, greater than or equal to 25 w / w%, greater than or equal to 30 w / w%, greater than or equal to 35 w / w%, greater than or equal to 40 w / w%, greater than or equal to 45 w / w%, greater than or equal to 50 w / w%, greater than or equal to 55 w / w%, greater than or equal to 60 w / w%, greater than or equal to 65 w / w%, greater than or equal to 70 w / w%, greater than or equal to 75 w / w%, greater than or equal to 80 w / w%, greater than or equal to 85 w / w%, or greater than or equal to 90 w / w. In some embodiments, the first material and / or the second material (e.g., the first water-soluble polymer and / or the second water-soluble polymer) are present in the device and / or body portion in the following amounts under equilibrium water content conditions: less than or equal to 95 w / w%, less than or equal to 90 w / w%, less than or equal to 85 w / w%, less than or equal to 80 w / w%, less than or equal to 75 w / w%, less than or equal to 70 w / w%, less than or equal to 65 w / w%, less than or equal to 60 w / w%, less than or equal to 55 w / w%, less than or equal to 50 w / w%, less than or equal to 45 w / w%, less than or equal to 40 w / w%, less than or equal to 35 w / w%, less than or equal to 30 w / w%, or less than or equal to 25 w / w%. Combinations of the above ranges are also possible (e.g., greater than or equal to 20 w / w% and less than or equal to 95 w / w%). Other ranges are also possible.

[0157] In some embodiments, the first material (e.g., a water-soluble polymer material) comprises or is selected from the following: polyvinyl alcohol, poly(acrylic acid), polyethylene glycol, poly(vinylpyrrolidone), poly(sulfonated betaine methacrylate), poly(sulfonated betaine acrylate), poly(carboxylated betaine methacrylate), poly(carboxylated betaine acrylate), povidone, polyacrylamide, poly(N-(2-hydroxypropyl)methacrylamide), polyazoline, polyphosphate, polyphosphazene, polyvinyl acetate, polypropylene glycol, poly(N-isopropylacrylamide), poly(2-hydroxymethyl methacrylate), and combinations thereof. In one set of exemplary embodiments, the first material is poly(vinyl alcohol).

[0158] In some embodiments, the first material (e.g., a first water-soluble 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 comprises or is selected from the following: poly(vinyl alcohol), poly(acrylic acid), polyethylene glycol, poly(vinylpyrrolidone), poly(sulfonated betaine methacrylate), poly(sulfonated betaine acrylate), poly(carboxylated betaine methacrylate), poly(carboxylated betaine acrylate), povidone, polyacrylamide, poly(N-(2-hydroxypropyl)methacrylamide), polyazoline, polyphosphate, polyphosphazene, polyvinyl acetate, polypropylene glycol, poly(N-isopropylacrylamide), poly(2-hydroxymethyl methacrylate), and combinations thereof. The first water-soluble polymer and the additional (e.g., the third) water-soluble polymer may have different chemical compositions.

[0159] In some embodiments, the total weight of the first material (e.g., the first polymer and / or the third polymer) in the device is greater than or equal to 20 w / w%, greater than or equal to 25 w / w%, greater than or equal to 30 w / w%, greater than or equal to 35 w / w%, greater than or equal to 40 w / w%, greater than or equal to 45 w / w%, greater than or equal to 50 w / w%, greater than or equal to 55 w / w%, greater than or equal to 60 w / w%, greater than or equal to 65 w / w%, greater than or equal to 70 w / w%, greater than or equal to 75 w / w%, greater than or equal to 80 w / w%, greater than or equal to 85 w / w%, greater than or equal to 90 w / w%, greater than or equal to 95 w / w%, greater than or equal to 98 w / w%, or greater than or equal to 99 w / w. In some embodiments, the total weight of the first water-soluble polymer and the additional (e.g., third) water-soluble polymer in the device, under equilibrium water content conditions, is in the following amounts: less than or equal to 100 w / w%, less than or equal to 90 w / w%, less than or equal to 98 w / w%, less than or equal to 95 w / w%, less than or equal to 90 w / w%, less than or equal to 85 w / w%, less than or equal to 80 w / w%, less than or equal to 75 w / w%, less than or equal to 70 w / w%, less than or equal to 65 w / w%, less than or equal to 60 w / w%, less than or equal to 55 w / w%, less than or equal to 50 w / w%, less than or equal to 45 w / w%, less than or equal to 40 w / w%, less than or equal to 35 w / w%, less than or equal to 30 w / w%, or less than or equal to 25 w / w%. Combinations of the above ranges are also possible (e.g., greater than or equal to 20 w / w% and less than or equal to 100 w / w%). Other ranges are also possible.

[0160] In some embodiments, the ratio of the first water-soluble polymer to the third water-soluble polymer present in the device is less than or equal to 100:0, less than or equal to 99:1, less than or equal to 95:5, less than or equal to 90:10, less than or equal to 80:20, less than or equal to 70:30, less than or equal to 60:40, or less than or equal to 55:45. In some embodiments, the ratio of the first water-soluble polymer to the third water-soluble polymer present in the device is greater than or equal to 50:50, greater than or equal to 60:40, greater than or equal to 70:30, greater than or equal to 80:20, greater than or equal to 90:10, greater than or equal to 95:5, or greater than or equal to 99:1. Combinations of the above ranges are also possible (e.g., less than or equal to 100:0 and greater than or equal to 50:50). Other ranges are also possible.

[0161] In some embodiments, the water-soluble polymer (e.g., a first water-soluble polymer, a second water-soluble polymer, a third water-soluble polymer) has a specific molecular weight. In some embodiments, the molecular weight of the water-soluble polymer (e.g., independently, a first water-soluble polymer, a second water-soluble polymer, or a third water-soluble polymer) may be greater than or equal to 40 kDa, greater than or equal to 50 kDa, greater than or equal to 75 kDa, greater than or equal to 100 kDa, greater than or equal to 125 kDa, greater than or equal to 150 kDa, greater than or equal to 175 kDa, greater than or equal to 200 kDa, greater than or equal to 250 kDa, greater than or equal to 300 kDa, greater than or equal to 350 kDa, greater than or equal to 400 kDa, greater than or equal to 450 kDa, greater than or equal to 500 kDa, greater than or equal to 600 kDa, greater than or equal to 700 kDa, greater than or equal to 800 kDa, greater than or equal to 900 kDa, greater than or equal to 1000 kDa, greater than or equal to 1500 kDa, greater than or equal to 2000 kDa, or greater than or equal to 2000 kDa. kDa, greater than or equal to 3000 kDa, or greater than or equal to 4000 kDa.In some embodiments, the molecular weight of the water-soluble polymer (e.g., independently, a first water-soluble polymer, a second water-soluble polymer, or a third water-soluble polymer) may be less than or equal to 5000 kDa, less than or equal to 4000 kDa, less than or equal to 3000 kDa, less than or equal to 2000 kDa, less than or equal to 1500 kDa, less than or equal to 1000 kDa, less than or equal to 900 kDa, less than or equal to 800 kDa, less than or equal to 700 kDa, less than or equal to 600 kDa, less than or equal to 500 kDa, less than or equal to 450 kDa, less than or equal to 400 kDa, less than or equal to 350 kDa, less than or equal to 300 kDa, less than or equal to 250 kDa, less than or equal to 200 kDa, less than or equal to 175 kDa, less than or equal to 150 kDa, less than or equal to 125 kDa, less than or equal to 100 kDa, less than or equal to 75 kDa, or less than or equal to 175 kDa. kDa, or less than or equal to 50 kDa. Combinations of the above ranges are also possible (e.g., molecular weight greater than or equal to 40 kDa and less than or equal to 5000 kDa). Other ranges are also possible.

[0162] In some embodiments, the body portion may include a first material, a second material, a third material, a fourth material, etc. The first material, the second material, the third material, the fourth material, etc., may be composed of the same or different materials. For example, in some embodiments, a second body portion containing a second material (e.g., poly(vinyl alcohol)) may be located within a cavity of a first body portion containing a first material (e.g., poly(vinyl alcohol)). However, in some cases, the first component and the second component may contain different materials. In some embodiments, the first material, the second material, the third material, the fourth material, etc., may include a water-soluble polymer. In some embodiments, the water-soluble polymer may be a first water-soluble polymer, a second water-soluble polymer, a third water-soluble polymer, a fourth water-soluble polymer, etc. Combinations of the above ranges are also possible (e.g., a first material containing a fourth water-soluble polymer or a second material containing a first water-soluble polymer).

[0163] As described above and herein, in some embodiments, the body portion includes a component that comprises a second material physically integrated with a first material of the body portion. In some embodiments, the second material comprises a water-soluble polymer that is the same as or different from the first water-soluble polymer (e.g., a third water-soluble polymer).In some embodiments, the second material comprises or is selected from the following: poly(vinyl alcohol), poly(acrylic acid), polyethylene glycol, poly(vinylpyrrolidone), poly(sulfonated betaine methacrylate), poly(sulfonated betaine acrylate), poly(carboxylated betaine methacrylate), poly(carboxylated betaine acrylate), povidone-polyacrylamide, poly(N-(2-hydroxypropyl)methacrylamide), polyazoline, polyphosphate, polyphosphonitrile, polyvinyl acetate, polypropylene glycol, poly(N-isopropylacrylamide), poly(2-hydroxymethyl methacrylate), and combinations thereof. In some embodiments, the second material is poly(acrylic acid); in a set of preferred embodiments, the second material is poly(vinyl alcohol). The second material may have a different chemical composition than the first water-soluble polymer.

[0164] In some embodiments, the second material comprises a water-soluble polymer located within at least a portion (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%) of a plurality of pores (e.g., the pores of the first material). In some embodiments, the second material (e.g., a third water-soluble polymer) is located within less than or equal to 100%, less than or equal to 90%, less than or equal to 80%, less than or equal to 70%, less than or equal to 60%, less than or equal to 50%, less than or equal to 40%, less than or equal to 30%, less than or equal to 20%, or less than or equal to 10% (e.g., at least 10% and less than or equal to 100% of the plurality of pores) of the first material. Combinations of the above ranges are also possible.

[0165] In some embodiments, the component comprises a second material comprising a porous, non-water-soluble polymer. In some embodiments, the second material comprises or is selected from cellulose, cellulose-based materials, nylon, polyethylene terephthalate (e.g., Dacron), poly(1,4-butylene terephthalate), and polyurethane. In some embodiments, the component is composed of woven textiles such as Dacron® (polyethylene terephthalate, also known as polyester), electrospun PVA, cotton, wool, polypropylene (randomized, syndiotactic, isotactic), polyethylene (LLDPE, LDPE, HDPE), cellulose, modified cellulose, hydroxyapatite, and combinations thereof.

[0166] Any water-insoluble polymer can be processed into any porous structure using any technique known to those skilled in the art. Exemplary embodiments include, for example, porous foam cavities, fibers, webs, and mesh structures.For example, in some embodiments, the second polymer material can be processed into yarns and fabrics to produce complex three-dimensional shapes (e.g., tubular geometries with tapered angles, etc.). In some embodiments, the second material can be a woven structure in which two sets of polymer yarns interweave at right angles; in other embodiments, the second material can be a knitted structure in which the loops of the polymer yarns are entangled with each other; and in some cases, according to other embodiments, the second material can be braided in which three or more polymer yarns cross each other in a diagonal pattern.

[0167] The second material (e.g., a third water-soluble polymer) can be present in the device in any suitable amount. For example, in some embodiments, the second material is present in the apparatus in an amount greater than or equal to 0.05 w / w%, greater than or equal to 0.1 w / w%, greater than or equal to 0.2 w / w%, greater than or equal to 0.5 w / w%, greater than or equal to 1.0 w / w%, greater than or equal to 2.0 w / w%, greater than or equal to 3.0 w / w%, greater than or equal to 4.0 w / w%, greater than or equal to 5.0 w / w%, greater than or equal to 10 w / w%, greater than or equal to 20 w / w%, greater than or equal to 30 w / w%, greater than or equal to 40 w / w%, greater than or equal to 50 w / w%, greater than or equal to 60 w / w%, greater than or equal to 70 w / w%, greater than or equal to 80 w / w%, or greater than or equal to 90 w / w% under equilibrium water content conditions. In some embodiments, the second material is present in the device in amounts less than or equal to 95 w / w%, less than or equal to 90 w / w%, less than or equal to 80 w / w%, less than or equal to 70 w / w%, less than or equal to 60 w / w%, less than or equal to 50 w / w%, less than or equal to 40 w / w%, less than or equal to 30 w / w%, less than or equal to 20 w / w%, less than or equal to 10 w / w%, less than or equal to 5.0 w / w%, less than or equal to 4.0 w / w%, less than or equal to 3.0 w / w%, less than or equal to 2.0 w / w%, less than or equal to 1.0 w / w%, less than 0.5 w / w%, less than 0.2 w / w%, or less than 0.1 w / w%. Combinations of the above ranges are also possible (e.g., greater than or equal to 0.05 w / w% and less than or equal to 95 w / w%). Other ranges are also possible.

[0168] In some embodiments, the component is a pre-formed device, such as a pre-formed medical device. In some embodiments, the component is a catheter cuff.

[0169] In some embodiments, the component may comprise a gas-impermeable material, such as a material impermeable to air. For example, in some cases, the material may be impermeable to the following gases: oxygen, nitrogen, carbon dioxide, air, or any combination thereof.

[0170] In some embodiments, the components may comprise a first material, a second material, a third material, a fourth material, etc. The first material, the second material, the third material, the fourth material, etc., may be made of the same or different materials. For example, in some embodiments, a first component comprising a second material and a second component comprising a third material may be combined with a body portion comprising a first material. However, in some cases, the first component and the second component may comprise the same material (e.g., the second material). In some embodiments, the first material, the second material, the third material, the fourth material, etc., may comprise a water-soluble polymer. In some embodiments, the water-soluble polymer may be a first water-soluble polymer, a second water-soluble polymer, a third water-soluble polymer, a fourth water-soluble polymer, etc. Combinations of the above ranges are also possible (e.g., a first material comprising a fourth water-soluble polymer or a second material comprising a first water-soluble polymer).

[0171] Some aspects of this disclosure generally relate to methods of integrating one or more components with a body portion. In some embodiments, the body portion comprising a polymer is softened and positioned to contact one or more components under applied pressure. Without being bound by any particular theory, it is generally considered that softening the body portion softens the polymer, which, under applied pressure, facilitates the diffusion of polymer chains at the bonding junction, thereby forming an integrated article.

[0172] In some embodiments, the body portion containing the polymer is softened during the extrusion of the article. Extrusion methods for preparing the articles of the present invention are described in International Patent Application Publications WO2018 / 237166 and WO2017 / 112878, each of which is incorporated herein by reference in its entirety. Detailed descriptions of the extrusion methods are also described elsewhere herein. However, in summary, in some embodiments, the method of forming the integrated article comprises a polymer mixture containing at least one water-soluble polymer and a solvent. According to some embodiments, the concentration of the polymer mixture is at least 10% w / w. For example, in some cases, the concentration of the polymer mixture is at least 10% w / w, at least 15% w / w, at least 20% w / w, at least 25% w / w, at least 30% w / w, at least 35% w / w, at least 40% w / w, at least 45% w / w, or at least 50% w / w.

[0173] In some embodiments, the solvent may be a homogeneous solvent, such as water, or a heterogeneous mixture, such as a water / DMSO mixture. In a set of preferred embodiments, the solvent is water. In some embodiments, the solvent is a co-solvent (e.g., containing two solvents). Those skilled in the art will understand that a co-solvent system must contain solvents that are miscible with each other or at least partially miscible with each other.For example, in some embodiments, the co-solvent system comprises a first solvent (e.g., water) and a second solvent (e.g., DMSO). The relative ratio of the first solvent to the second solvent is about 0:1, 0.1:0.9, 0.2:0.8, 0.3:0.7, 0.4:0.6, 0.5:0.5, 0.6:0.4, 0.7:0.3, 0.8:0.2, 0.9:0.1, or 1:0.

[0174] In some embodiments, the method includes heating the polymer mixture to a temperature above the melting point of the polymer mixture and extruding the polymer mixture as a bulk portion. In some embodiments, the method includes heating the polymer mixture to a temperature at least 10 degrees, at least 15 degrees, at least 20 degrees, at least 30 degrees, at least 40 degrees, at least 50 degrees, at least 60 degrees, at least 70 degrees, at least 80 degrees, at least 90 degrees, or at least 100 degrees above the melting point of the polymer mixture.

[0175] After extrusion, a component comprising a second material different from the first material (e.g., a conduit sheath) can be positioned to contact the softened body portion under externally applied force to promote interdiffusion of polymer chains at the bonding junctions, thereby forming an integrated article.

[0176] In some embodiments, the solvent (or co-solvent) is removed from the extruded body portion at a temperature above or below the solvent's freezing point. In some preferred embodiments, the solvent is removed from the extruded body portion at a temperature above the solvent's freezing point. In some cases, solvent removal can create multiple pores in the extruded body portion. This is especially true when the co-solvent contains at least one non-solvent for the water-soluble polymer. Without wishing to be bound by any particular theory, it is known in the art that solvent removal from a polymer mixture comprising both solvent and non-solvent (e.g., a water / DMF solution containing PVA) drives phase separation into a non-solvent-rich phase and a solvent / polymer-rich phase. In some embodiments, the evaporation rate can control the porous structure. For example, in some embodiments, slow solvent extraction favors coalescence of the non-solvent phase within the solvent / polymer-rich phase, resulting in larger pores. On the other hand, rapid solvent extraction inhibits the aggregation of the non-solvent phase, resulting in smaller pores.

[0177] In some embodiments, heat (e.g., from a furnace or oven) is used to evaporate the solvent. However, other methods of solvent evaporation are also contemplated. For example, in some embodiments, the extruded body portion is exposed to one or more solvent baths containing a non-solvent for the polymer. In other embodiments, the solvent can be removed by placing the extruded body portion in a stream of inert gas (e.g., argon, nitrogen, etc.). Combinations are also possible. For example, the extruded body portion can be heated, exposed to a solvent bath, and / or exposed to a stream of inert gas.

[0178] Solvent bonding technology is considered superior to other bonding methods (e.g., plastic welding, adhesive bonding, etc.) because bonding can occur below the glass transition temperature of the polymer, although this is not necessary. The materials described herein can be heated using any methods and / or techniques known to those skilled in the art. For example, in some embodiments, heating of the material for bonding formation can be accomplished using a split die bonder, an RF welding machine, or a hot air press. The temperature and processing time required to reflow the body portion to form the bond can vary depending on the hydration level of the body portion (e.g., poly(vinyl alcohol)) and the thickness of the materials being bonded. For example, based on these factors, the processing temperature can be in the range of greater than or equal to 60°C and less than or equal to 95°C, and the processing time can be in the range of greater than or equal to 15 seconds and less than or equal to 5 minutes. In some embodiments, the processing temperature may be greater than or equal to 60°C, greater than or equal to 65°C, greater than or equal to 70°C, greater than or equal to 75°C, greater than or equal to 80°C, greater than or equal to 85°C, greater than or equal to 90°C, or greater than or equal to 95°C. In some embodiments, the processing temperature may be less than or equal to 95°C, less than or equal to 90°C, less than or equal to 85°C, less than or equal to 80°C, less than or equal to 75°C, less than or equal to 70°C, less than or equal to 65°C, or less than or equal to 60°C.

[0179] In some embodiments, the processing time may be greater than or equal to 15 seconds, greater than or equal to 30 seconds, greater than or equal to 45 seconds, greater than or equal to 60 seconds, greater than or equal to 2 minutes, greater than or equal to 3 minutes, greater than or equal to 4 minutes, or greater than or equal to 5 minutes. In some cases, the processing time may be less than or equal to 5 minutes, less than or equal to 4 minutes, less than or equal to 3 minutes, less than or equal to 2 minutes, less than or equal to 60 seconds, less than or equal to 45 seconds, less than or equal to 30 seconds, or less than or equal to 15 seconds.

[0180] For example, in some embodiments, the bonding method includes exposing the body portion to a solvent to soften the polymer and heating the body portion to further soften the material. In some embodiments, the body portion is heated to a temperature less than or equal to 100°C, less than 90°C, less than or equal to 80°C, less than or equal to 70°C, less than or equal to 60°C, or less than or equal to 50°C. In a set of preferred embodiments, the method includes heating the body portion to a temperature less than or equal to 100°C.

[0181] The body portion may be dehydrated, partially hydrated, or fully hydrated during the bonding process.In some embodiments, the water content of the body portion during binding is greater than or equal to 5% w / w, greater than or equal to 10% w / w, greater than or equal to 20% w / w, greater than or equal to 30% w / w, greater than or equal to 40% w / w, or greater than or equal to 50% w / w. In some embodiments, the water content of the body portion during binding is less than or equal to 50% w / w, less than or equal to 40% w / w, less than or equal to 30% w / w, less than or equal to 20% w / w, less than or equal to 10% w / w, or less than or equal to 5% w / w.

[0182] In some embodiments, any solvent known to those skilled in the art can be used to hydrate the body portion. Some preferred embodiments include the use of aqueous solvents, such as aqueous buffers. Some exemplary embodiments include, but are not limited to, phosphate-buffered saline, MEPS, TRIS, citrate-sodium citrate buffer, citrate-sodium phosphate buffer, sodium acetate-acetate buffer, imidazole buffer, and carbonate buffer. In some cases, the main body and / or components may be hydrated for a set period of time (e.g., overnight) to achieve an equilibrium water content (e.g., steady-state conditions – no longer absorbing or releasing water). Without wishing to be bound by any particular theory, it is generally known in the art that varying the concentration of the buffer solution can be used to control the equilibrium water content of the material, and that higher salt concentrations result in higher hydration rates.

[0183] In some cases, the hydration period may be greater than or equal to 1 hour, greater than or equal to 5 hours, greater than or equal to 10 hours, greater than or equal to 15 hours, greater than or equal to 20 hours, or greater than or equal to 24 hours; in other cases, the hydration period may be less than or equal to 24 hours, less than or equal to 20 hours, less than or equal to 15 hours, less than or equal to 10 hours, less than or equal to 5 hours, or less than or equal to 1 hour.

[0184] Those skilled in the art will understand that bonding can lead to undesirable flow / flashing of the materials bonded together. Therefore, in some cases, tools designed to prevent undesirable flow / flashing of materials may be used. Examples of tools include, but are not limited to, split-type mold bonding machines / RF welding machines with specific geometries, and / or heat-shrinkable materials of fluorinated ethylene propylene (FEP) (and / or PEEK and / or nylon and / or polyolefin) shaped to appropriate sizes and shapes for hot air treatment. The latter is particularly useful because the compression of the material promotes strong contact patches and chain entanglement of the materials to be bonded.

[0185] In some embodiments, the method includes cooling the integrated article.The article can be cooled using any technique known to those skilled in the art. In some embodiments, the method includes cooling the article at ambient temperature without any external control. However, in some cases, the method includes cooling the article in a controlled manner, for example, by using an indirect heat exchanger. As a supplement or alternative, the integrated article can be placed in an oven, where cooling is achieved by systematically reducing the temperature at discrete intervals.

[0186] Some aspects of this disclosure generally relate to methods of shaping articles (e.g., conduits) comprising a body portion. In some embodiments, the body portion comprises a hydrophilic porous material containing a lumen (e.g., a tubular structure). In some embodiments, the shaping of the article is achieved by first molding the hydrophilic porous material into a desired shape and then heating the hydrophilic porous material to lock in the desired structure. In some embodiments, the hydrophilic porous material is heated before molding into the desired structure. Without being bound by any particular theory, it is generally believed that heating hydrophilic porous materials (e.g., poly(vinyl alcohol)) increases the chain mobility of polymer chains within the hydrophilic porous material, thereby allowing the material to be flexible or moldable at certain elevated temperatures, which then solidifies and maintains the desired shape upon cooling.

[0187] In some embodiments, the hydrophilic porous material is heated to a temperature above its glass transition temperature but below its melting temperature. For example, in some embodiments, the hydrophilic porous material is heated to a temperature greater than or equal to 70°C, greater than or equal to 90°C, greater than or equal to 100°C, greater than or equal to 125°C, greater than or equal to 150°C, greater than or equal to 175°C, greater than or equal to 200°C, or greater than or equal to 225°C. In some embodiments, the hydrophilic porous material is heated to a temperature less than or equal to 225°C, less than or equal to 200°C, less than or equal to 175°C, less than or equal to 150°C, less than or equal to 125°C, less than or equal to 100°C, less than or equal to 90°C, or less than or equal to 70°C.

[0188] In some embodiments, shaping the hydrophilic porous material includes bending it into a desired shape (e.g., a twist, a curve, a circle, etc.). In some cases, bending the hydrophilic porous material includes pressing the hydrophilic porous material into a mold having a desired shape. As a supplement or alternative, bending the hydrophilic porous material includes inserting the material into a cavity of the hydrophilic porous material and bending the material into a desired shape (e.g., a “V” geometry). Bending the hydrophilic porous material can also be achieved by physically deforming the hydrophilic porous material (e.g., bending the distal end to a desired angle relative to the proximal end).

[0189] In some embodiments, the article may be formed using thermoforming, for example, by placing a wire (nickelinol, steel, etc.) within the lumen and thermally heating the article to mold it into a desired shape. Alternatively or complementary, the article may be placed within a metal housing (e.g., a tube, mold cavity, etc.) and thermally heated to mold the article into a desired shape. By limiting the dimensions of the initial component to the desired shape, the shape can be bent, straightened, compressed, or stretched. Edges may be rounded to allow for easy fluid flow, reduce abrasion, and decrease surface area, which contributes to catheter placement, catheter life, and patient comfort.

[0190] In some embodiments, the forming method includes forming a dual-lumen article (e.g., a dual-lumen catheter) from a first body portion containing a first lumen and a second body portion containing a second lumen. In some embodiments, forming a dual-lumen article may be achieved by swelling the first body portion to make it flexible and / or bendable and placing the second body portion within the first lumen of the first body portion.

[0191] Exemplary solvents configured to swell the first body portion include, but are not limited to, water, dimethyl sulfoxide, and any combination thereof. For example, in some embodiments, the solvent contains water at or above 100% w / w, including or equal to 0% w / w, 10% w / w, 20% w / w, 30% w / w, 40% w / w, 50% w / w, 60% w / w, 70% w / w, 80% w / w, 90% w / w, or more. In some embodiments, the solvent comprises water at or below 100% w / w, 90% w / w, 80% w / w, 70% w / w, 60% w / w, 50% w / w, 40% w / w, 30% w / w, 20% w / w, 10% w / w, or 0% w / w. Combinations of the above ranges are also possible (e.g., greater than or equal to 10% w / w and less than or equal to 90% w / w).

[0192] In some embodiments, the solvent comprises DMSO at or above 0% w / w, 10% w / w, 20% w / w, 30% w / w, 40% w / w, 50% w / w, 60% w / w, 70% w / w, 80% w / w, 90% w / w, or 100% w / w.In some embodiments, the solvent comprises DMSO at less than or equal to 100% w / w, less than or equal to 90% w / w, less than or equal to 80% w / w, less than or equal to 70% w / w, less than or equal to 60% w / w, less than or equal to 50% w / w, less than or equal to 40% w / w, less than or equal to 30% w / w, less than or equal to 20% w / w, less than or equal to 10% w / w, or less than or equal to 0% w / w. Combinations of the above ranges are also possible (e.g., greater than or equal to 10% w / w and less than or equal to 90% w / w).

[0193] In one set of preferred embodiments, the solvent is a homogeneous solution of DMSO. In another set of preferred embodiments, the solvent is a homogeneous solution of water.

[0194] In some embodiments, the solvent causes the first body portion to swell (e.g., the solvent is absorbed within the non-crosslinked water-soluble polymer network of the body portion). Those skilled in the art will understand that the swelling ratio (e.g., the increase in the weight fraction of material due to solvent absorption) can be used to quantify the degree of swelling, for example, of a hydrogel. According to some embodiments, the swelling ratio of the first body portion placed in the solvent may be greater than or equal to 10%, greater than or equal to 25%, greater than or equal to 50%, greater than or equal to 100%, greater than or equal to 250%, greater than or equal to 500%, greater than or equal to 1000%, greater than or equal to 2000%, or greater than or equal to 3000%. In other cases, the swelling ratio of the body portion placed in the solvent may be less than or equal to 3000%, less than or equal to 2000%, less than or equal to 1000%, less than or equal to 500%, less than or equal to 250%, less than or equal to 100%, less than or equal to 50%, less than or equal to 25%, or less than or equal to 10%.

[0195] In some embodiments, the second body portion is heated and / or mechanically deformed until the outer diameter of the second body portion is smaller than the first inner diameter of the first cavity (e.g., in a swollen state), thereby allowing the second body portion to be placed within the first body portion. As described elsewhere herein, heating is generally considered to increase the mobility of the polymer chains containing the second body portion, thereby allowing manipulation (e.g., stretching and / or compression, etc.) of the second body portion. Any technique known to those skilled in the art can be used to reduce the outer diameter of the second body portion. For example, in some embodiments, the second body portion may be heated and stretched; alternatively, a smaller diameter material may be placed into the cavity of a hydrophilic porous material, and the second body may be radially compressed to the desired outer diameter.

[0196] In some embodiments, the outer diameter of the second body portion may vary along an axial dimension (e.g., a central axis). For example, in some embodiments, the second body includes a proximal end of a first outer dimension and a distal end of a second outer dimension different from the first outer dimension.Configurations in which the second outer dimension is smaller than the first outer dimension taper towards the distal end of the second body; conversely, configurations in which the first outer dimension is smaller than the second outer dimension taper towards the proximal end of the second body. Other configurations are also possible. For example, the outer diameter of the second body portion can increase and decrease periodically (e.g., sinusoidally) to produce a corrugated geometry. Other geometries and configurations are also possible.

[0197] In some embodiments, assembling a dual-cavity article includes inserting the second body portion into the cavity of the first body portion and drying the dual-cavity article. It is not desirable to be bound by any particular theory, but it is generally believed that drying the article removes the absorbed solvent from the first body portion, causing the first body portion to shrink, thereby trapping the second body portion within the first body portion. In some embodiments, as described on pages 30 / 54 of the specification (CN 121195019 A), the dual-cavity article is dried until the equilibrium water content is less than or equal to 5% w / w, less than or equal to 4% w / w, less than or equal to 3% w / w, less than or equal to 2% w / w, less than or equal to 1% w / w, less than or equal to 0.5% w / w, less than or equal to 0.25% w / w, less than or equal to 0.1% w / w, or less than or equal to 0.05% w / w.

[0198] In some embodiments, the dual-cavity article includes one or more surface features (e.g., barbs, protrusions, hooks, etc.) at the interface between the first body portion and the second body portion, configured to mechanically reinforce the interface between the first body portion and the second body portion. In some embodiments, the first body portion includes one or more surface features; while in other cases, the second body portion may include one or more surface features. In some cases, the first body portion includes one or more surface features configured to engage one or more surface features on the second body portion (e.g., similar to a lock and a key). In some embodiments, drying the article causes one or more surface features to engage opposing surfaces, thereby mechanically reinforcing the interface between the first body portion and the second body portion.

[0199] Some aspects of this disclosure generally relate to methods of inserting any of the articles described herein into an object in which this is desired. The articles described herein are at least partially composed of a body portion comprising a first material comprising a hydrophilic water-soluble polymer. In some embodiments, the article is an intravenous catheter. Without wishing to be bound by any particular theory, it is considered that processing parameters increase chain entanglement between hydrophilic water-soluble polymers and non-covalent bonding (e.g., hydrogen bonding) between adjacent polymer chains, resulting in a physically cross-linked polymer network. Physically cross-linked hydrogels, such as chemically cross-linked hydrogels, can absorb large amounts of water within their cross-linked network.Therefore, in some embodiments, the article can be inserted into an object (e.g., a vein) in a dehydrated state, a partially (dehydrated) hydrated state, or a fully hydrated state (e.g., a swollen state).

[0200] In some embodiments, the article is in a dehydrated state when the water content of the article is less than or equal to 5% w / w. According to some embodiments, the article is (at least partially) hydrated when the water content of the article is greater than or equal to 5% w / w and less than or equal to 50% w / w. For example, in some embodiments, the article is (at least partially) hydrated when the water content is greater than or equal to 5% w / w, greater than or equal to 10% w / w, greater than or equal to 20% w / w, greater than or equal to 30% w / w, greater than or equal to 40% w / w, or greater than or equal to 50% w / w. In some embodiments, the article is hydrated when the water content is less than or equal to 50% w / w, less than or equal to 40% w / w, less than or equal to 30% w / w, less than or equal to 20% w / w, less than or equal to 10% w / w, or less than or equal to 5% w / w.

[0201] In some embodiments, the article (e.g., an intravenous catheter) comprises a polymer material comprising a first water-soluble polymer having a plurality of pores, a lumen, and a distal end comprising a tip geometry adapted for intravenous insertion into a subject. Some non-limiting embodiments of possible tip geometries include beveled tip cores, beveled tip cannulas, lancet tip cores, posterior beveled cores, posterior beveled cannulas, cannula tip cores, Franseen tip cannulas, or tapered tip cores. In some embodiments, the tip comprises a symmetrical geometry; however, in some embodiments, the tip comprises an asymmetrical geometry.

[0202] In some embodiments, at least a portion of the article is in a dehydrated state and has a Young's modulus greater than or equal to 500 MPa, greater than or equal to 750 MPa, greater than or equal to 1 GPa, greater than or equal to 2 GPa, greater than or equal to 4 GPa, or greater than or equal to 5 GPa. In some embodiments, at least a portion of the article is in a dehydrated state and has a Young's modulus less than or equal to 10 GPa, less than or equal to 5 GPa, less than or equal to 4 GPa, less than or equal to 2 GPa, less than or equal to 1 GPa, or less than or equal to 750 MPa. Combinations of the above ranges are also possible (e.g., greater than or equal to 500 MPa and less than or equal to 10 GPa). Other ranges are also possible. In some embodiments, the article, having at least a portion having a Young's modulus greater than or equal to 500 MPa, is inserted into a subject (e.g., into a vein) without the aid of a needle or other venous puncture device.For example, a portion of the article (e.g., the tip of the article) may have a needle-like design and sufficient Young's modulus, allowing the article to penetrate the skin, subcutaneous tissue, and / or vein wall of the object (e.g., facilitating needleless insertion of a vascular catheter).

[0203] In some embodiments, after the article is inserted into the object, at least a portion of the article may undergo rapid hydration (e.g., by the flow of fluid within the article (e.g., within the lumen of the article), by exposure to a biological fluid, such as blood, of the object). Advantageously, such an article allows for needleless insertion of a catheter into the object, such that the article remains in the patient's body (e.g., and is used as a catheter).

[0204] In some embodiments, the intravenous catheter is inserted in a dehydrated state. In some embodiments, the intravenous catheter has a first water content during insertion and a second water content after insertion. For example, the catheter may have a water content of less than or equal to 5% w / w during insertion and a water content of greater than or equal to 5% w / w and less than or equal to 50% w / w after insertion. It is not desirable to be bound by any particular theory; it is generally believed that after insertion into a vein of the recipient, the catheter will absorb blood components (e.g., serum, plasma, etc.) within its physical crosslinking network and subsequently swell within the vein (e.g., the water content will increase) to its final size.

[0205] In some embodiments, the intravenous catheter may swell to its final size within greater than or equal to 5 seconds or less than or equal to 60 minutes (e.g., under EWC). For example, in some embodiments, the intravenous catheter may swell to its final size within greater than or equal to 5 seconds, greater than or equal to 10 seconds, greater than or equal to 30 seconds, greater than or equal to 1 minute, greater than or equal to 5 minutes, greater than or equal to 10 minutes, greater than or equal to 20 minutes, greater than or equal to 30 minutes, greater than or equal to 40 minutes, greater than or equal to 50 minutes, or greater than or equal to 60 minutes. In some embodiments, the intravenous catheter can swell to its final size within 60 minutes or less, 50 minutes or less, 40 minutes or less, 30 minutes or less, 20 minutes or less, 10 minutes or less, 5 minutes or less, 1 minute or less, 30 seconds or less, 10 seconds or less, or 8 seconds. Combinations of the above ranges are also possible (e.g., greater than or equal to 5 seconds and less than or equal to 60 minutes, greater than or equal to 1 minute and less than or equal to 5 minutes, greater than or equal to 5 minutes and less than or equal to 30 minutes). Other ranges are also possible. Advantageously, the mechanical properties of the article can be adjusted to give it a specific swelling time (e.g., the time to swell to its final size under EWC), for example, using the methods described herein.

[0206] In some embodiments, the intravenous catheter is inserted in a hydrated or partially hydrated state. Therefore, in some cases, the water content of the catheter may be greater than or equal to 5% w / w and less than or equal to 50% w / w before insertion. Where the catheter is not fully hydrated before insertion (e.g., less than 50%), the catheter will continue to draw fluid from the venous system until an equilibrium swelling ratio (e.g., 50%) is reached. In some embodiments, the water content of the catheter may be greater than or equal to 5% w / w, greater than or equal to 10% w / w, greater than or equal to 20% w / w, greater than or equal to 30% w / w, greater than or equal to 40% w / w, or greater than or equal to 50% w / w before insertion into the object. In some embodiments, the water content of the catheter may be less than or equal to 50% w / w, less than or equal to 40% w / w, less than or equal to 30% w / w, less than or equal to 20% w / w, less than or equal to 10% w / w, or less than or equal to 5% w / w before insertion into the object. Combinations of the above ranges are also possible (e.g., greater than or equal to 5% w / w and less than or equal to 50% w / w).

[0207] In some embodiments, the inner diameter of the lumen decreases after insertion into the patient. Based on the teachings of this specification, those skilled in the art will understand that the articles described herein (e.g., intravenous catheters) can be used, for example, to administer (e.g., drugs, crystalloids, colloids, etc.) and / or to aspirate (e.g., blood) fluids from a subject in need. Importantly, insertion of the device / article of the invention into a subject's venous system does not cause substantial hemolysis and is therefore generally considered safe.

[0208] Extrusion methods for preparing the articles of the invention are described in International Patent Application Publications WO2018 / 237166 and WO2017 / 112878, which are incorporated herein by reference in their entirety. In some embodiments, the use of methods including extrusion makes it possible to produce devices with a high aspect ratio. One embodiment of the method for preparing the material involves 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, as per the solvent removal specification (pages 32 / 54, 41 CN 121195019 A), thereby generating a physically cross-linked matrix, and continuing to remove the solvent until the physically cross-linked matrix is ​​a micron-porous or nanoporous solid material. Physical cross-linking can occur during cooling of the mixture and / or in a solvent removal environment. Additional polymers can be incorporated into the pores of the material.

[0209] Figures 9A to 9C illustrate embodiments of an apparatus for preparing porous solid materials.The illustrated apparatus 100 includes: a syringe pump 102 for receiving at least one syringe 104; an optional heating jacket (not shown) for heating the syringe; a die 106; a heating element 108 and a power cable 109 therefor, which provides heating to the die 106 as needed (details not shown in FIG. 9A); a dispensing spool 110 for a mandrel 112; an uptake spool 114 for the mandrel and a motor (not shown); and a bath 116 for extruding material 117, wherein the bath has temperature control for cooling or heating, shown as a heat exchanger 118, which includes heat exchange tubes 120 located in the bath 116. The die 106 receives the mandrel 110 therethrough. A feed line 122 from the syringe to the die 106 supplies feed to the apparatus 100. The system for this embodiment may also include a weighing station, a jacketed container for heating and mixing the solution for loading into the syringe, and a solvent removal environment for further drying of the tube removed from the bath 116. The system may also have a heating station for annealing the tube or other extruded product by heating when desired. A core tube made of PTFE, as well as wire, air, gas, non-solvent liquid, or other materials, may be used for the core.

[0210] For example, in use, the polymer is heated in a suitable solvent in a jacketed container and placed into the syringe 104. One or more polymers may be present and radiopaque agents or other additives may be added. One or more syringes having the same or different mixtures may be used. The syringe containing the polymer is heated to a predetermined temperature, for example, not exceeding 80°C to 95°C, and degassed before extrusion. The syringe 104 is mounted on a syringe pump 102 with a wrap heater to maintain the temperature during extrusion. A core 112 loops through a die 106 (e.g., a heated external die), which feeds material into an extrusion bath 116 and is subsequently connected to a motor-driven take-up reel 114. The bath temperature is controlled using a heat exchanger 118 (e.g., a cooler); the extruded material can be extruded at temperatures ranging from -30°C to 75°C; other temperatures may be used, and 0°C is a commonly available set temperature for extrusion. Those skilled in the art will immediately understand that all ranges and values ​​between clearly defined limits are considered, and that any of the following may be used as upper or lower limits: -30°C, -25°C, -20°C, -15°C, -10°C, -5°C, 0°C, 5°C, 10°C, 15°C, 20°C, 25°C, 30°C, 35°C, 40°C, 45°C, 50°C, 55°C, 60°C, 65°C, 70°C, 75°C.The motor speed of the reel 114, which can be controlled (e.g., a puller), is used to adjust the outer diameter specification dimensions around the core 112. For example, in embodiments where a conduit is prepared, adjusting the die size, material feed rate, core diameter, and pull speed plays a role in adjusting the final tube specification. In this embodiment, the polymer feed rate can be adjusted, for example, by controlling the syringe pump 102. Connector 122 connects one or more syringes to the die head 106. Many pumps and other tools for controlled-feed polymer solutions are known. This apparatus and method can be adapted to a stretching process, but alternative feeding processes can be used.

[0211] In some embodiments, a composition (e.g., a prepolymer composition) can be provided prior to forming the polymer material (e.g., for extrusion). In some embodiments, the composition comprises an aqueous solution. The aqueous solution may contain a penetrant at a concentration greater than or equal to 0.01 M and less than or equal to 8 M. The aqueous solution may contain a radiopaque agent in an amount greater than or equal to 0 w / w% and less than or equal to 50 w / w% (e.g., less than or equal to 40 w / w%). The composition may also contain a water-soluble polymer having a molecular weight greater than or equal to 40 kDa and less than or equal to 5000 kDa and present in solution in an amount greater than or equal to 10 w / w% and less than or equal to 50 w / w%.

[0212] In some embodiments, the composition forms a swellable polymer material upon extrusion.

[0213] In some embodiments, the penetrant is present in solution at a concentration greater than or equal to 0.01 M, greater than or equal to 0.1 M, greater than or equal to 0.5 M, greater than or equal to 1 M, greater than or equal to 2 M, greater than or equal to 3 M, greater than or equal to 4 M, greater than or equal to 5 M, or greater than or equal to 6 M. In some embodiments, the penetrant is present in solution at a concentration less than or equal to 8 M, less than or equal to 6 M, less than or equal to 4 M, less than or equal to 2 M, less than or equal to 1 M, less than or equal to 0.5 M, or less than or equal to 0.1 M. Combinations of the above ranges are also possible (e.g., greater than or equal to 0.01 M and less than or equal to 8 M). The penetrant is described in more detail herein.

[0214] In some embodiments, the anti-radiation agent is present in solution in amounts greater than or equal to 0 w / w%, greater than or equal to 5 w / w%, greater than or equal to 10 w / w%, greater than or equal to 15 w / w%, greater than or equal to 20 w / w%, greater than or equal to 25 w / w%, greater than or equal to 30 w / w%, greater than or equal to 35 w / w%, greater than or equal to 40 w / w%, or greater than or equal to 45 w / w%.In some embodiments, the radiopaque agent is present in solution in amounts less than or equal to 50 w / w%, less than or equal to 45 w / w%, less than or equal to 40 w / w%, less than or equal to 35 w / w%, less than or equal to 30 w / w%, less than or equal to 25 w / w%, less than or equal to 20 w / w%, less than or equal to 15 w / w%, less than or equal to 10 w / w%, or less than or equal to 5 w / w%. Combinations of the above ranges are also possible (e.g., greater than or equal to 0 w / w% and less than or equal to 50 w / w%). Other ranges are also possible. The radiopaque agent is described in more detail below.

[0215] In some embodiments, the water-soluble polymer is present in solution in amounts greater than or equal to 10 w / w%, greater than or equal to 13 w / w%, greater than or equal to 15 w / w%, greater than or equal to 20 w / w%, greater than or equal to 25 w / w%, greater than or equal to 30 w / w%, greater than or equal to 35 w / w%, greater than or equal to 40 w / w%, or greater than or equal to 45 w / w%. In some embodiments, the water-soluble polymer is present in solution in amounts less than or equal to 50 w / w%, less than or equal to 45 w / w%, less than or equal to 40 w / w%, less than or equal to 35 w / w%, less than or equal to 30 w / w%, less than or equal to 25 w / w%, less than or equal to 20 w / w%, less than or equal to 15 w / w%, or less than or equal to 13 w / w%. Combinations of the above ranges are also possible (e.g., greater than or equal to 10 w / w% and less than or equal to 50 w / w%). In some embodiments, the water-soluble polymer is present in the solution in an amount greater than or equal to 13 w / w%.

[0216] In some embodiments, the method for forming the polymer material and / or device described herein includes providing a mixture comprising a first water-soluble polymer and a penetrant (e.g., a salt) as described above. In some embodiments, the mixture is extruded. In some embodiments, the extruded mixture is extruded onto a core material to form a polymer material disposed 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 a penetrant is introduced into the polymer material. In some embodiments, the polymer material is heated (e.g., after the solution is introduced into the penetrant). In some embodiments, the solution flows against the flow of the polymer material. In some embodiments, the polymer material may be dried.

[0217] In a set of exemplary embodiments, the method for forming the polymer material and / or device described herein includes physically integrating a body portion with one or more components.In some embodiments, the method includes providing a mixture comprising a first water-soluble polymer and a penetrant (e.g., a salt), wherein the first water-soluble polymer is present in the mixture in an amount greater than or equal to 10 w / w% (e.g., greater than or equal to 13 w / w%, or greater than or equal to 13 w / w% and less than or equal to 50 w / w%) relative to the total weight of the mixture; performing the following steps: extruding the mixture onto a core material at atmospheric pressure at a temperature greater than or equal to 65 °C (e.g., greater than or equal to 65 °C and less than or equal to 100 °C) to form a polymer material disposed on a core material (e.g., a solid rod or gas); exposing the polymer material to a non-solvent of the polymer material at a temperature less than or equal to 28 °C (e.g., less than or equal to 28 °C and greater than or equal to -20 °C) for greater than or equal to 15 minutes (e.g., greater than or equal to 1 hour and less than or equal to 240 hours); placing the polymer material in contact with a component comprising a second material different from the first water-soluble polymer and / or a penetrant (e.g., a salt) to form an integrated article; and then integrating the product into the product. (See page 43 of specification 34 / 54) CN 121195019 A The polymer material is heated to a temperature greater than or equal to 25°C (e.g., greater than or equal to 30°C, or greater than or equal to 30°C and less than or equal to 65°C) for, for example, for a duration greater than or equal to 1 hour (e.g., greater than or equal to 1 hour and less than or equal to 48 hours, or greater than or equal to 3 hours and less than or equal to 48 hours) to dry the polymer material.

[0218] In some embodiments, the non-solvent comprises an alcohol. In some embodiments, the non-solvent is ethanol, methanol, propanol, butanol, pentanol, hexanol, heptanol, octanol, decanol, dodecyl alcohol, dimethyl sulfoxide, ethyl acetate, acetate ester, propionate ester, ether, dimethylformamide, dimethylacetamide, acetone, acetonitrile, ethylene glycol, propylene glycol, glycerol, air, vacuum, or combinations 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).

[0219] In some embodiments, the extrusion step of the mixture is performed at atmospheric pressure at a temperature greater than or equal to 65°C, greater than or equal to 70°C, greater than or equal to 75°C, greater than or equal to 80°C, greater than or equal to 85°C, greater than or equal to 90°C, greater than or equal to 95°C, greater than or equal to 100°C, or greater than or equal to 105°C. In some embodiments, the extrusion step of the mixture is performed at atmospheric pressure at a temperature less than or equal to 110°C, less than or equal to 105°C, less than or equal to 100°C, less than or equal to 95°C, less than or equal to 90°C, less than or equal to 85°C, less than or equal to 80°C, less than or equal to 75°C, or less than or equal to 70°C. Combinations of the above ranges are also possible (e.g., greater than or equal to 65°C and less than or equal to 110°C). Other ranges are also possible.Based on the teachings of this specification, those skilled in the art will understand that additional pressures (e.g., greater than atmospheric pressure, less than atmospheric pressure) and / or temperatures are also possible.

[0220] In some embodiments, the step of exposing the polymer material to a non-solvent of the polymer material is performed at a temperature less than or equal to 28°C, less than or equal to 25°C, less than or equal to 20°C, less than or equal to 15°C, less than or equal to 10°C, less than or equal to 5°C, less than or equal to 0°C, less than or equal to -5°C, less than or equal to -10°C, or less than or equal to -15°C. In some embodiments, the step of exposing the polymer material to a non-solvent of the polymer material is performed at a temperature greater than or equal to -20°C, greater than or equal to -15°C, greater than or equal to -10°C, greater than or equal to -5°C, greater than or equal to 0°C, greater than or equal to 5°C, greater than or equal to 10°C, greater than or equal to 15°C, greater than or equal to 20°C, or greater than or equal to 25°C. Combinations of the above ranges are also possible (e.g., less than or equal to 28°C and greater than or equal to -20°C). Other ranges are also possible.

[0221] In some embodiments, the step of exposing the polymer material to a non-solvent of the polymer material (e.g., at a temperature less than or equal to 28°C and greater than or equal to -20°C) is performed for more than or equal to 1 hour, more than or equal to 2 hours, more than or equal to 4 hours, more than or equal to 6 hours, more than or equal to 8 hours, more than or equal to 10 hours, more than or equal to 15 hours, more than or equal to 20 hours, more than or equal to 30 hours, more than or equal to 40 hours, more than or equal to 50 hours, more than or equal to 60 hours, more than or equal to 80 hours, more than or equal to 100 hours, more than or equal to 120 hours, more than or equal to 140 hours, more than or equal to 160 hours, more than or equal to 180 hours, more than or equal to 200 hours, or more than or equal to 220 hours. In some embodiments, the step of exposing the polymer material to a non-solvent of the polymer material is performed for less than or equal to 240 hours, less than or equal to 220 hours, less than or equal to 200 hours, less than or equal to 180 hours, less than or equal to 160 hours, less than or equal to 140 hours, less than or equal to 120 hours, less than or equal to 100 hours, less than or equal to 80 hours, less than or equal to 60 hours, less than or equal to 50 hours, less than or equal to 40 hours, less than or equal to 30 hours, less than or equal to 20 hours, less than or equal to 15 hours, less than or equal to 10 hours, less than or equal to 8 hours, less than or equal to 6 hours, less than or equal to 4 hours, or less than or equal to 2 hours. Combinations of the above ranges are also possible (e.g., greater than or equal to 1 hour and less than or equal to 240 hours). Other ranges are also possible.

[0222] In some embodiments, the step of introducing a component comprising a second material different from the first water-soluble polymer and an optional penetrant (e.g., a salt) into the polymer material includes heating the polymer material and the component to a temperature greater than or equal to 25°C, greater than or equal to 30°C, greater than or equal to 35°C, greater than or equal to 40°C, greater than or equal to 45°C, greater than or equal to 50°C, greater than or equal to 55°C, or greater than or equal to 60°C. In some embodiments, the polymer material and the component are heated to a temperature less than or equal to 65°C, less than or equal to 60°C, less than or equal to 55°C, less than or equal to 50°C, less than or equal to 45°C, less than or equal to 40°C, less than or equal to 35°C, or less than or equal to 30°C. Combinations of the above ranges are also possible (e.g., greater than or equal to 25°C and less than or equal to 65°C). Other ranges are also possible.

[0223] In some cases, as described in International Patent Application Publication No. WO2020 / 132065, it may be desirable to incorporate one or more biomolecules into the integrated article. Therefore, in some embodiments, a solution comprising one or more compounds, a target agent (therapeutic agent, biological agent, etc.), and optionally a permeabilizer may be allowed to flow adjacent to (e.g., directly adjacent to) the integrated article for a specific amount of time. In some embodiments, the solution is allowed to flow adjacent to the integrated article for greater than or equal to 3 hours, greater than or equal to 5 hours, greater than or equal to 6 hours, greater than or equal to 8 hours, greater than or equal to 10 hours, greater than or equal to 12 hours, greater than or equal to 16 hours, greater than or equal to 20 hours, greater than or equal to 24 hours, greater than or equal to 28 hours, greater than or equal to 32 hours, greater than or equal to 36 hours, greater than or equal to 40 hours, or greater than or equal to 44 hours. In some embodiments, the solution is allowed to flow adjacent to the integrated article for less than or equal to 48 hours, less than or equal to 44 hours, less than or equal to 40 hours, less than or equal to 36 hours, less than or equal to 32 hours, less than or equal to 28 hours, less than or equal to 24 hours, less than or equal to 20 hours, less than or equal to 16 hours, less than or equal to 12 hours, less than or equal to 10 hours, less than or equal to 8 hours, less than or equal to 6 hours, or less than or equal to 5 hours. Combinations of the above ranges are also possible (e.g., greater than or equal to 3 hours and less than or equal to 48 hours). Other ranges are also possible. Combinations of the above temperatures and times are also possible.

[0224] In some embodiments, the method includes annealing the integrated article to a temperature greater than or equal to 80°C (e.g., greater than or equal to 80°C and less than or equal to 250°C) for greater than or equal to 60 minutes (e.g., greater than or equal to 60 minutes and less than or equal to 480 minutes).In some embodiments, the integrated article is annealed at a temperature greater than or equal to 80°C, greater than or equal to 90°C, greater than or equal to 100°C, greater than or equal to 120°C, greater than or equal to 140°C, greater than or equal to 160°C, greater than or equal to 180°C, greater than or equal to 200°C, greater than or equal to 220°C, or greater than or equal to 240°C. In some embodiments, the integrated article is annealed at a temperature less than or equal to 250°C, less than or equal to 240°C, less than or equal to 220°C, less than or equal to 200°C, less than or equal to 180°C, less than or equal to 160°C, less than or equal to 140°C, less than or equal to 120°C, less than or equal to 100°C, or less than or equal to 90°C. Combinations of the above ranges are also possible (e.g., greater than or equal to 80°C and less than or equal to 250°C). Other ranges are also possible.

[0225] In some embodiments, the integrated article (e.g., body parts and components) is annealed for 30 minutes or more, 60 minutes or more, 80 minutes or more, 100 minutes or more, 120 minutes or more, 160 minutes or more, 200 minutes or more, 240 minutes or more, 280 minutes or more, 320 minutes or more, 360 minutes or more, 400 minutes or more, or 440 minutes or more. In some embodiments, the integrated article is annealed for 480 minutes or more, 440 minutes or more, 400 minutes or more, 360 minutes or more, 320 minutes or more, 280 minutes or more, 240 minutes or more, 200 minutes or more, 160 minutes or more, 120 minutes or more, 100 minutes or more, or 80 minutes or more. Combinations of the above ranges are also possible (e.g., greater than or equal to 60 minutes and less than or equal to 480 minutes). Other ranges are also possible. Combinations of the above temperature and time are also possible.

[0226] 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 a polymer material (e.g., a body portion) has been formed on the core material. In some cases, the core material may be physically removed and / or dissolved.Specification 36 / 54 pages 45 CN 121195019 A

[0227] In one exemplary embodiment, the method includes using a mixture comprising at least one water-soluble polymer, salt, and water (e.g., a solution as described above and herein), wherein at least one water-soluble polymer is present in the mixture in an amount greater than or equal to 10 w / w% relative to the total weight of the mixture, performing the following steps: heating the mixture to a temperature greater than or equal to 65°C, cooling the mixture after heating to a temperature at least 20°C lower than the melting point of the mixture, and mechanically shaping the mixture. In some embodiments, after cooling the mixture, the mixture may be extruded onto a core material at a temperature greater than or equal to 65°C to form a polymer material disposed on the core material. The method may involve exposing the polymer material to a non-solvent of the polymer material at a temperature less than or equal to 28°C for greater than or equal to 4 hours, and removing at least a portion of the core material from the polymer material.

[0228] In some embodiments, the step of cooling the mixture includes cooling it to a temperature at least 20°C, at least 25°C, at least 30°C, at least 35°C, at least 40°C, at least 45°C, at least 50°C, at least 60°C, at least 70°C, at least 80°C, or at least 90°C below the melting point of the mixture. In some embodiments, the step of cooling the mixture includes cooling it to a temperature less than or equal to 100°C, less than or equal to 90°C, less than or equal to 80°C, less than or equal to 70°C, less than or equal to 60°C, less than or equal to 50°C, less than or equal to 45°C, less than or equal to 40°C, less than or equal to 35°C, less than or equal to 30°C, or less than or equal to 25°C below the melting point of the mixture. Combinations of the above ranges are also possible (e.g., at least 20°C below and less than or equal to 100°C). Other ranges are also possible. The mixture may be cooled for any suitable amount of time.

[0229] In some embodiments, the mixture may be mechanically shaped. In some embodiments, the composition (e.g., the mixture prior to extrusion) may be mechanically shaped by kneading, rolling, cutting, or combinations thereof.

[0230] In some embodiments, the mixture is mixed at a temperature greater than or equal to 80°C, greater than or equal to 90°C, greater than or equal to 100°C, greater than or equal to 120°C, greater than or equal to 140°C, greater than or equal to 160°C, greater than or equal to 180°C, greater than or equal to 200°C, greater than or equal to 220°C, or greater than or equal to 240°C. In some embodiments, the mixture is mixed at a temperature less than or equal to 250°C, less than or equal to 240°C, less than or equal to 220°C, less than or equal to 200°C, less than or equal to 180°C, less than or equal to 160°C, less than or equal to 140°C, less than or equal to 120°C, less than or equal to 100°C, or less than or equal to 90°C.Combinations of the above ranges are also possible (e.g., greater than or equal to 80°C and less than or equal to 250°C). Other ranges are also possible.

[0231] In some embodiments, the method includes adsorbing a target compound (e.g., a drug) into a polymer material, as described above and herein.

[0232] In some embodiments, the polymer material and / or device described herein may be exposed to and / or contain a humectant. In some embodiments, at least a portion of the humectant is disposed on the surface of the polymer material and / or device (e.g., a body portion) (e.g., an aluminal and / or non-aluminal surface). For example, in some embodiments, a portion of the humectant 70 is disposed on the surface of device 10. In some embodiments, greater than or equal to 30%, greater than or equal to 40%, greater than or equal to 50%, greater than or equal to 60%, greater than or equal to 70%, greater than or equal to 80%, greater than or equal to 90%, or all of the humectant is disposed on the surface of the polymer material and / or device (e.g., a body portion). In some embodiments, less than or equal to 100%, less than or equal to 90%, less than or equal to 80%, less than or equal to 70%, less than or equal to 60%, less than or equal to 50%, and less than or equal to 40% of the humectant are disposed on the surface of the polymer material and / or device (e.g., the body portion). Combinations of these ranges are also possible (e.g., 40% to 100%).

[0233] In some embodiments, at least a portion of the humectant is inside the polymer material and / or device (e.g., the body portion). In some embodiments, at least a portion of the humectant is inside the polymer material and / or device (e.g., the body portion). For example, in some embodiments, a portion of the humectant 70 is inside the device 10 (e.g., absorbed into the body of the device). In some embodiments, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or all of the humectant is inside the polymer material and / or device (e.g., the body portion). In some embodiments, less than 100%, 90%, 80%, 70%, 60%, 50%, or 40% of the humectant is inside the polymer material and / or device (e.g., the body portion). Combinations of these ranges are also possible (e.g., 30% to 100%).

[0234] In some embodiments, the humectant is a nonionic surfactant (i.e., a surfactant having an uncharged hydrophilic head and a hydrophobic tail) or an amphoteric surfactant (i.e., a surfactant having a net uncharged hydrophilic head and a hydrophobic tail).In some embodiments, the humectant is a nonionic surfactant selected from the following: sugar alcohols, poloxamer, triacetin, alpha-hydroxy acids, polyethylene glycol, polypropylene glycol, ethylene glycol, propylene glycol, hexanediol, butylene glycol, glycerin, sorbitol, mannitol, xylitol, maltitol, erythritol, threitol, arabitol, ribitol, galactitol, fucitol, iditol, inositol, volemitol, maltitol, lactitol, maltotriol, maltotetratitol, polyglycitol, and combinations thereof. In some embodiments, the humectant comprises an oil such as vitamin E. In some embodiments, the humectant comprises a salt such as sodium chloride, potassium chloride, and / or choline phosphate.

[0235] In some embodiments, the polymeric materials and / or devices described herein are exposed to and / or contain greater than or equal to 0.1 w / w% humectant, greater than or equal to 0.5 w / w% humectant, greater than or equal to 1 w / w% humectant, greater than or equal to 5 w / w% humectant, greater than or equal to 10 w / w% humectant, or greater than or equal to 20 w / w% humectant. In some embodiments, the polymeric materials and / or devices described herein are exposed to and / or contain less than or equal to 30 w / w% humectant, less than or equal to 25 w / w% humectant, less than or equal to 20 w / w% humectant, less than or equal to 15 w / w% humectant, less than or equal to 10 w / w% humectant, less than or equal to 5 w / w% humectant, or less than or equal to 1 w / w% humectant. Combinations of these ranges are also possible (e.g., 0.1 w / w% to 30 w / w% humectant or 1 w / w% to 10 w / w% humectant). The porous solid (e.g., made by the apparatus of Figures 1D to 1F) can be annealed. Furthermore, the porous solid, with or without pre-annealing, can be treated to further incorporate a bulk-integrated polymer. In Figure 3A, material 210 containing a porous solid matrix 212 is desolvated, exposed to a mixture containing a polymer in a resolvation solvent, and resolvated in the mixture to form material 212 with a bulk-integrated polymer 214. A cross-section of matrix 212 (Figure 3B) shows an outermost region 216 (where the pores of matrix 212 are filled); an intermediate region 218 (where the polymer density in the pores is lower, with less filling and / or fewer occupied pores); and an inner region 220 (where the polymer has not yet permeated). The matrix can be solvated and / or desolvated before exposure to the mixture, provided that it is desolvated upon exposure to the mixture, allowing water-soluble polymers to migrate into the matrix.

[0236] In some embodiments, the method of wetting the device and / or polymer material includes placing the extruded segment in a solution containing a humectant (e.g., glycerin or poloxamer). In some embodiments, the solution contains a humectant greater than or equal to 1 w / w%, greater than or equal to 5 w / w%, greater than or equal to 10 w / w%, greater than or equal to 15 w / w%, greater than or equal to 20 w / w%, or greater than or equal to 25 w / w%. In some embodiments, the solution contains a humectant less than or equal to 35 w / w%, less than or equal to 30 w / w%, less than or equal to 25 w / w%, less than or equal to 20 w / w%, less than or equal to 15 w / w%, less than or equal to 10 w / w%, or less than or equal to 5 w / w. Combinations of these ranges are also possible (e.g., 1 to 35 w / w%). In some embodiments, the solution contains a surfactant. In some embodiments, the solution contains PBS.

[0237] In some embodiments, the extruded segment is placed in the solution for a period of time. In some embodiments, the time period is greater than or equal to 1 hour, greater than or equal to 2 hours, or greater than or equal to 3 hours. In some embodiments, as described on pages 38 / 54 of CN 121195019 A, the time period is less than or equal to 4 hours, less than or equal to 3 hours, or less than or equal to 2 hours. Combinations of these ranges are also possible (e.g., 3 hours or 1 to 4 hours).

[0238] In some embodiments, the solution is maintained at a certain temperature while the extruded section is exposed to the solution. In some embodiments, the temperature is greater than or equal to 20°C, greater than or equal to 30°C, greater than or equal to 37°C, greater than or equal to 40°C, greater than or equal to 50°C, or greater than or equal to 60°C. In some embodiments, the temperature is less than or equal to 70°C, less than or equal to 60°C, less than or equal to 55°C, less than or equal to 50°C, less than or equal to 40°C, less than or equal to 37°C, or less than or equal to 30°C. Combinations of these ranges are also possible (e.g., 20 to 70°C, 37 to 55°C, or 45°C).

[0239] In some embodiments, the extruded segment may be dried (e.g., in a convection oven) after being removed from the solution. In some embodiments, the extruded segment is dried at a certain temperature. In some embodiments, the temperature is greater than or equal to 20°C, greater than or equal to 30°C, or greater than or equal to 40°C. In some embodiments, the temperature is less than or equal to 50°C, less than or equal to 40°C, or less than or equal to 30°C. Combinations of these ranges are also possible (e.g., 30°C or 20 to 50°C). In some embodiments, the extruded segment is dried for a period of time.In some embodiments, the time period may be greater than or equal to 1 hour, greater than or equal to 2 hours, or greater than or equal to 3 hours. In some embodiments, the time period may be less than or equal to 4 hours, less than or equal to 3 hours, or less than or equal to 2 hours. Combinations of these ranges are also possible (e.g., 3 hours, or 1 to 4 hours).

[0240] In some embodiments, the bioactive agent may be incorporated into the article.

[0241] In some embodiments, the methods described herein do not involve a freeze-thaw process and / or a freezing process and / or a thawing process. Furthermore, the method can also be used to prepare solid porous materials that are virtually non-swellable or non-swellable (e.g., 0% to 100% w / w swelling at EWC), even in the absence of a covalent crosslinking agent. Those skilled in the art will immediately recognize that all ranges and values ​​between clearly defined limits are to be expected, wherein, for example, any of the following may be used as upper or lower limits: 0% w / w, 5% w / w, 10% w / w, 15% w / w, 20% w / w, 25% w / w, 30% w / w, 40% w / w, 50% w / w, 60% w / w, 70% w / w, 80% w / w, 90% w / w, 95% w / w, 100% w / w, wherein swelling is measured as: swelling% = 100 × (total weight at EWC - dry weight) / dry weight, where dry weight is the weight of the material without water.

[0242] In some embodiments, the extruded sample has a horizontal chain orientation and arrangement along the sample length (in the extrusion direction). The polymer chain orientation is produced by the extrusion process. Not wanting to be bound by theory, in some embodiments, it is believed that the horizontal chain orientation and alignment along the sample length contributes to an increase in inner and / or outer diameter by a percentage greater than the percentage increase in length when the sample swells.

[0243] In some embodiments, a combination of one or more of the following is available: extrusion of a hydrophilic polymer in a solvent; cold extrusion; and extrusion into a bath to rapidly remove the solvent from the extrudate. Furthermore, in some embodiments, additional solvent removal and / or annealing processes provide further practicality for preparing the desired porous solid.

[0244] In some embodiments, the requirement for nanoporous materials includes a high polymer concentration of more than about 10% w / w in a polymer-solvent mixture with a high level of crosslinking.A skilled technician will immediately recognize that all ranges and values ​​between the clearly defined limits are predictable, where, for example, any of the following can be used as an upper or lower limit: 10% w / w, 12% w / w, 15% w / w, 16% w / w, 17% w / w, 18% w / w, 19% w / w, 20% w / w, 25% w / w, 30% w / w, 35% w / w, 40% w / w, 45% w / w, 50% w / w, 55% w / w, 60% w / w, 70% w / w, 80% w / w, 90% w / w, 95% w / w, or 99% w / w of polymer by weight of the total polymer-solvent mixture. In some embodiments, the polymer is substantially solvated, meaning it is a true solution, or at least half of the polymer is dissolved and the remainder is at least suspended. In some embodiments, solvation of the polymer facilitates the alignment of polymer chains during extrusion and crosslinking between polymers. Without being bound by any particular theory, a high concentration of the starting polymer-solvent mixture may contribute to this. According to some embodiments, it is believed that the possible chain alignment of the material as it passes through the die promotes more intrapolymer crosslinking relative to interpolymer crosslinking. In some embodiments, it is believed that extrudates or otherwise formed mixtures entering a desolvation environment (whether gaseous or liquid) further collapse the pore structure before the dense, concentrated polymer is fully crosslinked, thereby improving link proximity and promoting additional crosslinking density. In some embodiments, it is helpful to deposit the extruded or otherwise formed material directly into a solvent-removed environment. In some embodiments, further solvent removal may continue to cause the material to collapse until a desired endpoint in terms of structure and / or properties is reached. In some embodiments, an annealing process may further promote strength.

[0245] On the other hand, freezing methods rely on increasing reinforcement by forcing the ultra-concentrated microregions to also achieve link proximity and improve crosslinking density, while retaining large porosity due to the presence of ice crystals in the overall gel structure. Desolvation produces forced, highly concentrated microregions, but these do not generate macropores. In contrast, gels pre-formed before dehydration or freezing form macropores due to the nature of the method. Furthermore, the inventors’ work shows that such nanoporous solids have greater strength than macroporous materials.

[0246] Hydrogels can also be prepared by using a lower polymer concentration in the polymer-solvent mixture, typically less than 10% w / w of polymer in the polymer-solvent mixture.Those skilled in the art will immediately recognize that all ranges and values ​​between clearly defined limits are to be expected, where, for example, any of the following can be used as an upper or lower limit: 2% w / w, 5% w / w, 7% w / w, 8% w / w, 9% w / w, or 10% w / w of polymer by weight of the total polymer-solvent mixture. Alternatively or additionally, the polymer-solvent mixture is not extruded into a solvent removal environment.

[0247] Micron-porous materials can be prepared under process conditions intermediate between nanoporous solids and hydrogels. One embodiment is to prepare the material using conditions comparable to those for preparing nanoporous materials, but stopping solvent removal before reaching the nanoporous solid structure.

[0248] Extruding hydrophilic polymers in a solvent helps in the preparation of high-strength materials. The use of solvents in extrusion starting materials is at least uncommon. Typically, extrusion uses a solid material that has been heated to a flowable temperature and then extruded and subsequently cooled by various methods. For example, thermoplastic extrusion of pure PVA is considered feasible. However, such extrusion lacks the polymer structure required for the preparation of porous solids and instead exhibits properties more similar to conventional thermoplastics. According to operational theory, pure PVA extrusion will lack the quality of hydrogen bonding that occurs in an aqueous ionic solvent state. The temperatures suitable for preparing PVA that can flow in extrusion will produce a poorly cohesive material at the die, making it difficult to form a continuous shape. It is difficult to prepare extruded PVA to form high aspect ratio shapes, such as tubes, and it is difficult to use them in the extrusion process. PVA and other hydrophilic polymers have high viscosity and are difficult to dissolve. It has been observed that a narrow temperature working band is particularly usable, for example, 85°C to 95°C. Below about 85°C, PVA cannot really melt and therefore cannot be completely amorphous for extrusion. Above about 95°C, the loss of boiling and evaporation makes the process inefficient. These temperature ranges can be compensated for by increasing the pressure to above atmospheric pressure, but the use and expansion of pressurized systems are challenging. These processes are carried out effectively at temperatures below the boiling point of the polymer-solvent material.

[0249] The cohesive strength of the flowing polymer-solvent mixture is weak when it leaves the die. Using a core to support the mixture at the mold is possible for maintaining shape at the mold. This contrasts with typical core extrusion used in coating processes (e.g., coated wires for mobile phone chargers). Typical methods that avoid the use of solvents or significant solvent concentrations have relatively high cohesive strength, allowing them to easily retain tubes after leaving the mold and are independent of active bonding, such as hydrogen bonding in hydrophilic polymers that form a coherent shape as they are removed from the mold. Specification 40 / 54 pages 49 CN 121195019 A

[0250] It is possible to place the molded polymer-solvent mixture into a solvent removal environment.Most extrusions do not use bath temperatures equal to or below room temperature. Furthermore, the use of solvent-removing baths is atypical relative to conventional processes; baths or other solvent-removing environments help to fully solidify the extruded material, allowing it to remain stable at the core and concentric, whereas otherwise the melt would become teardrop-shaped. It would also be destroyed at the end of extrusion when attempting to collect it, as it is still molten. Conventional baths containing water cause PVA or similar hydrophilic polymer materials to lose their shape due to swelling, dissolution, or both. Molding processes involving the preparation of polymer-solvent mixtures (which are formed in a mold and subsequently placed in a solvent-removing environment) do not have the advantage of the chain alignment observed in extrusion. However, properly controlled temperature and solvent removal can produce materials with high strength and controlled pore structures.

[0251] Porous solids are highly smooth and can be used in a hydrated state and can be readily combined with other materials. In the case of conduits, for example, extensions, Luer locks, suture wings, etc., are available. In some embodiments, it is permissible for the copolymer to be extruded in a range of 0.1% to 10% w / w or no more than 10% w / w of the second polymer as the first polymer, and no more than 5% w / w is also permissible. Those skilled in the art will readily recognize that all ranges and values ​​between the clearly defined limits are contemplated, wherein, for example, any of the following may be used as upper or lower limits: 0.1% w / w, 0.2% w / w, 0.4% w / w, 0.5% w / w, 0.8% w / w, 1% w / w, 2% w / w, 3% w / w, 4% w / w, 5% w / w, 6% w / w, 8% w / w, 10% w / w.

[0252] In some embodiments, salt may be used to control the strength of the material. Not limited to any particular theory, the salt may be part of the physical crosslinking, effectively acting as a low molecular weight crosslinking agent between polymer chains.

[0253] Some embodiments of the polymer blend include at least one first hydrophilic polymer and at least one second hydrophilic polymer in a solvent, which are extruded as described herein. Some examples include combinations of one or more of the following: PVA, PAA, PEG, PVP, polyalkylene glycol, hydrophilic polymers, and combinations thereof. Some examples of concentrations include at least one second hydrophilic polymer present in amounts ranging from 1 part to 10,000 parts of the first hydrophilic polymer. Those skilled in the art will readily recognize that all ranges and values ​​between the clearly defined limits are to be expected, wherein, for example, any of the following may be used as upper or lower limits: 1, 2, 10, 100, 1000, 1500, 2000, 2500, 3000, 4000, 5000, 6000, 7000, 8000, 9000, 10000 parts.Examples of polymer concentrations in polymer-solvent mixtures include a first polymer present at a first concentration and one or more additional polymers present at a second concentration, wherein the first polymer concentration and the additional polymer concentration are independently selected from 0.1% w / w to 99% w / w, for example, 0.1% w / w, 0.2% w / w, 0.3% w / w, 0.4% w / w, 0.5% w / w, 0.6% w / w, 1% w / w, 2% w / w, 3% w / w, 4% w / w, 5% w / w, 6% w / w, 7% w / w, 8% w / w, 9% w / w, 10% w / w, 11% w / w, 12% w / w, 13% w / w, 14% w / w, 15% w / w, 16% w / w, 17% w / w, 18% w / w, 19% w / w, 20% w / w, 25%. w / w, 30% w / w, 33% w / w, 35% w / w, 40% w / w, 45% w / w, 50% w / w, 55% w / w, 60% w / w, 65% w / w, 70% w / w, 75% w / w, 80% w / w, 85% w / w, 90% w / w, 95% w / w. In addition, non-hydrophilic polymers and / or non-hydrophilic blocks in block polymers may be present, wherein the concentration of such polymers and / or such blocks is typically less than about 10% w / w, for example, 0.1% w / w, 0.2% w / w, 1% w / w, 2% w / w, 3% w / w, 4% w / w, 5% w / w, 6% w / w, 7% w / w, 8% w / w, 9% w / w, 10% w / w.

[0254] Some embodiments include a porous matrix conditioned with a water-soluble polymer, which loses no more than 20% to 90% w / w of the water-soluble polymer under comparable conditions; those skilled in the art will readily recognize that all ranges and values ​​between well-defined limits are to be expected, e.g., 20% w / w, 25% w / w, 30% w / w, 33% w / w, 40% w / w, 50% w / w, 60% w / w, 70% w / w, 80% w / w, 90% w / w.

[0255] In some embodiments, the bulk-incorporated material may be presented as a monolayer at the surface. The term monolayer means a layer of single-molecule thickness. A monolayer does not depend on the cohesion between molecules of the monolayer to remain stably present on the surface. At least one water-soluble polymer forms the monolayer. In contrast, even the thickness of a thin, self-crosslinked polymer coating corresponds to the thickness of a network formed by a crosslinked polymer. For example, a cross-linked PVA coating can be formed on the surface, but such a coating depends on the interconnection between PVA molecules and necessarily forms a cross-linked network.Therefore, some embodiments include a water-soluble polymer that exists on the surface of a porous solid but is not covalently bonded to the surface and that the polymer is not part of the network.

[0256] Those skilled in the art who read this disclosure will be able to adapt its principles based on what is known about extrusion or other molding techniques to obtain alternative methods and apparatus for achieving the same end product as described herein. An expanded embodiment of the process may be suitable for use with, for example, a multi-zone screw extruder that provides a solvent mixture via a suitable injector or hopper and has zones controlled to provide cold extrusion. Features of, for example, a syringe pump may be replaced by a properly metered and controlled liquid or solid polymer feed system.

[0257] As described elsewhere herein, this disclosure provides guidance for combining a body portion with one or more components. In some embodiments, a body portion containing a polymer is softened using heat and placed in contact with one or more components under applied pressure. Alternatively or supplemented, the components are softened and placed in contact with the body portion under applied pressure. In other embodiments, a solvent comprising a water-soluble polymer is used to soften the body portion (or component) and place it into contact with the component (or body portion) under applied pressure. It is not desirable to be bound by any particular theory, but generally it is considered that softening the body portion (or component) softens the polymer, which, in the presence of applied pressure, facilitates the interdiffusion of polymer chains at the bonding joint, thereby forming an integrated article of article.

[0258] In some embodiments, bonding can be performed using a desolvated (e.g., dehydrated or dried state, EWC less than or equal to 5% w / w), partially hydrated, or fully hydrated state (EWC about 50% w / w) body portion and / or component. In a preferred set of embodiments, bonding is performed in a desolvated state.

[0259] It is not desirable to be bound by any particular theory, but generally it is considered that heating the bonding joint between the body portion and / or component while in a desolvated state produces a polymer melt (e.g., a polymer above the glass transition temperature but below the melting temperature) at the bonding joint. Applying pressure at the bonding joint allows polymer chains from the body portion to flow freely into the component, and polymer chains from the component to flow freely into the body portion. Upon cooling, the polymer chains of the body portion become physically entangled and integrated into the component body, and the polymer chains of the component become physically entangled and integrated into the body portion. For example, in some cases, the polymer chains of the component may become entangled within the porous body structure of the body portion.

[0260] The bulk incorporation modifies not only the surface of the body portion and / or component, but also the portion below the surface (e.g., at least 1 to 5000 μm or within that range); those skilled in the art will readily recognize that all ranges and values ​​between well-defined limits are contemplated, for example

[0261] As an alternative or supplement, a solvent comprising a water-soluble polymer can be used to soften the bonding joint, said solvent being configured to swell or rehydrate the porous body portion and / or component. For example, the body portion (e.g., a porous hydrophilic material) can be exposed to a mixture comprising a solvating polymer (poly(vinyl alcohol)) to introduce it into the pores during desolvation of the porous matrix. The solvent has an affinity for the matrix and is introduced as the matrix absorbs the solvent. The solvent in the mixture of polymers having bulk incorporation can be selected to have an affinity for the matrix such that it is absorbed into the desolvated matrix, but need not be the same as the solvent in the matrix. Generally, the hydrophilic solvent in the mixture will be absorbed into a hydrophilic porous matrix that is at least partially desolvated and contains the hydrophilic solvent, and those skilled in the art can adjust various solvents as needed to create suitable conditions when the intended purpose of incorporation is desired.

[0262] A hydrophilic solvent is a solvent that is freely miscible with water at 20°C or present in the mixture at a concentration in which it is freely miscible with water. Specification 42 / 54 pages 51 CN 121195019 A

[0263] Desolvation means that the matrix is ​​free of solvent, for example, completely dry, or with respect to the solvent contained therein having an EWC below that of the matrix. If the solvent in the matrix is ​​not water, the EWC of the material can be calculated based on a measurement of the solvent, i.e., where appropriate, the term EWC can be used for non-aqueous solvents. For example, a hydrophilic matrix can be solvated in an aqueous solution of an alcohol and will have an EWC for that solvent. Some implementations include desolvation amounts of porous solids from 1 to 100, and those skilled in the art will immediately recognize that all ranges and values ​​between the clearly defined limits are to be expected: 1% w / w, 5% w / w, 10% w / w, 15% w / w, 20% w / w, 33% w / w, 40% w / w, 50% w / w, 60% w / w, 70% w / w, 80% w / w, 90% w / w, 95% w / w, 99% w / w, 100% w / w, which refers to the total weight of the solvent that can be removed.

[0264] Without being bound by any particular theory, it is considered that porous materials can be desolvated (dehydrated, in the case where water is the solvent in the porous material) and exposed to polymers in a solution that resolvates the porous material, such that the polymers are introduced into the pores. The polymer then forms a physical bond with the matrix material defining the pores, and for practical purposes, is permanently incorporated into the bulk of the material by at least partially filling the pores and by physically bonding with the matrix.As an alternative or supplement, the polymer has a hydrodynamic radius that causes the polymer to exhibit a diameter exceeding the opening diameter of the pore, allowing the polymer to be permanently incorporated into the pores of the material, especially when the material will be used in water or physiological solutions. Generally, if the bulk-incorporated polymer is solvated in a polymer that wets the pores of the porous solid, the polymer can be introduced into the pores of the matrix upon matrix resolvation. When the hydrophilic porous matrix is ​​below the EWC of the matrix, a mixture containing the polymer for bulk incorporation is introduced because the solvent of the polymer matches the matrix material, for example, wetting the pores of the material. For example, a hydrophilic solvent will typically wet the pores of a hydrophilic matrix.

[0265] A material containing a porous matrix of polymers linked by non-covalent bonds is a preferred embodiment because such materials can be prepared 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 a physically cross-linked water-soluble polymer defining the pores. At the equilibrium water content (EWC) of the matrix, the solid concentration of these water-soluble polymers can be at least 33% w / w of the matrix, but other concentrations may also be used.

[0266] Thus, one embodiment of the method of incorporating polymers into a porous material includes providing a material comprising a porous hydrophilic matrix comprising one or more water-soluble polymers (also referred to herein as matrix polymers) physically cross-linked with each other to form the matrix. The material having the matrix is ​​exposed to a solvent comprising one or more polymers solvated in the solvent (also referred to as bulk-incorporated polymers, preferably, wherein the polymers are water-soluble, and wherein the solvent is also referred to as conditioning mixtures or bulk-incorporated mixtures), wherein the matrix is ​​below the EWC and hydrophilic relative to the solvent before exposure to the solvent. The material is desolvated before exposure to the solvent having the bulk-incorporated polymers.

[0267] In some embodiments, the bulk-incorporation process produces an outer region in which pores are filled, an intermediate region in which most or most of the pores are filled, and an inner region in which little or no polymer penetration is observed. The bulk incorporation not only modifies the pores at the surface but also modifies the pores below the surface (e.g., at least 1 μm to 5000 μm or within that range); those skilled in the art will immediately recognize that all ranges and values ​​between well-defined limits are to be expected, for example. The percentage of pores with polymer can be determined as described above, and permeability grading can be performed by percentage cutoff values, for example, 100% pores in the first region, 50% pores in the second region, and 0% pores in the third region.

[0268] The bulk incorporation process is preferably carried out with a porous matrix made of a water-soluble polymer and can be carried out without hydrophobic structural domains in the polymer (e.g., a matrix made solely of PVA). The polymer can be physically crosslinked to form the matrix.Therefore, some embodiments include materials comprising a matrix that is free of hydrophobic domains or made of a water-soluble polymer free of hydrophobic domains, as described on pages 43 / 54 of the specification, CN 121195019 A, or free of any non-water-soluble polymers. However, some hydrophobic domains may be permitted when a hydrophilic matrix is ​​prepared using a water-soluble polymer with physical crosslinking without destroying the matrix thus formed. Some embodiments of the invention include polymers forming porous matrices with a hydrophobic content of 0% w / w, 1% w / w, 2% w / w, 3% w / w, 4% w / w, 5% w / w, 7% w / w, 8% w / w, 9% w / w, 10% w / w, 11% w / w, 12% w / w, or 15% w / w.

[0269] A porous matrix consisting essentially of a water-soluble polymer refers to a polymer crosslinked to form the matrix with a content of up to 3% w / w. RO agents (e.g., salts) are not polymers crosslinked to form the matrix. A porous matrix consisting essentially of physically cross-linked polymers refers to a matrix that contains no reagents that form covalent bonds between the polymers, or contains a small amount of such reagents such that no more than about 6% of the polymers (in terms of the number of polymers) are cross-linked with each other using such reagents, for example, wherein the stoichiometric ratio of the number of polymers to the bifunctional cross-linking agent is at least 100:3. Similarly, a matrix that is essentially free of covalent bonds is prepared using cross-linked polymers in which no more than about 6% of the polymers (by number) are non-covalently cross-linked. The number of covalent bonds in the matrix can be similarly limited to a stoichiometric ratio of 100:3 to 100:100, for example, any one of 100:3, 100:5, 100:10, 100:15, 100:20, 100:25, 100:30, 100:40, 100:50, 100:60, 100:70, 100:80, 100:90, or 100:100. For example, hydrogels prepared by free radical polymerization typically have 100% polymers linked together by covalent bonds, and the polymer:covalent stoichiometric ratio of the hydrogel is 100:100.

[0270] As described elsewhere, porous solids can be prepared to have a controlled pore size range and can be prepared to provide a matrix without pores larger than a certain diameter. The diameter can be measured under suitable conditions, such as in distilled water at EWC. Therefore, some embodiments include polymers embedded in a porous matrix without pores larger than 1 to 5000 μm; those skilled in the art will readily recognize that all ranges and values ​​between well-defined limits are to be expected, for example

[0271] the porous solid may be present in other materials as described elsewhere herein, such as radiopaque (RO) agents as a complement to but not part of the matrix.RO agents typically contribute little to the crosslinking that provides matrix strength. Similarly, other materials may be present in the matrix rather than as part of it, such as wires and reinforcing materials. It is understood that a matrix prepared by physical crosslinking is a type of matrix that can be prepared from materials with defined pores of a diameter, and contrasts with hydrogels having polymer strands that are typically separated from each other and connected in a network structure (e.g., formed by free radical polymerization or by reacting monomers / polymers in solution). Such a network is generally not expected to be able to stably incorporate polymers into its pores using polymer absorption processes without covalent bonding. Porous materials are described in detail herein, and these may be freely selected for use with bulk-incorporated polymers as guided by the disclosure herein. Porous materials having the bulk properties described herein may be selected.

[0272] The bulk-incorporated polymer may be a polymer for porous solids as described elsewhere herein. Some examples are water-soluble polymers. Water-soluble polymers may be, for example, polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), polyacrylic acid (PAA), polyacrylamide, hydroxypropyl methacrylamide, polyazoline, polyphosphates, polyphosphazenes, poly(vinyl acetate), polypropylene glycol, poly(N-isopropylacrylamide) (PNIPAM), polysaccharides, sulfonated hydrophilic polymers (e.g., sulfonated polyphenylene ether, Nafion®, sulfobetaine methacrylate), and their iodine-added variants (e.g., PVA-I, PVP-I), or variants with additional side groups, copolymers thereof, and combinations thereof. The solvent may contain one or more polymers, meaning polymers with different chemical compositions, such as PVA and PEG. The term "polymer" refers to one or more polymers.

[0273] The solubility of the water-soluble polymer used in the porous matrix or for bulk incorporation may be selected, for example, at 20°C, at least 1 g / 100 ml, 2 g / 100 ml, 5 g / 100 ml, or 10 g / 100 ml in water. The polymer may be selected as linear or branched.Some embodiments include polymers or hydrophilic polymers with molecular weights, for example, from 40 k to 5000 k Daltons; those skilled in the art will readily recognize that all ranges and values ​​between well-defined limits are contemplated, wherein, for example, any of the following may be used as upper or lower limits: 40 k, 50 k, 100 k, 125 k, 150 k, 250 k, 400 k, 500 k, 600 k, 750 k, 800 k, 900 k, 1 million, 1.5 million, 2 million, 2.5 million, 3 million molecular weights. The molecular weight of the polymer may be selected based on the available pore size in the porous solid. Nanoporous or microporous materials are preferred.

[0274] The polymer incorporated into the bulk may be selected to be the same as, the same as at least one of the polymers constituting the porous matrix, or different from the polymers forming the porous matrix.

[0275] The concentration of the polymer incorporated into the solvent in the bulk can be any concentration in which the polymer enters the solution, as mentioned in reference to the solvent at the start of the method. Note that polymers or other non-solventized materials not in the solution are destined not to enter the pores. In some embodiments, the concentration is from 1% w / w to 50% w / w; those skilled in the art will readily recognize that all ranges and values ​​between the well-defined limits are to be expected, e.g., 1% w / w, 2% w / w, 3% w / w, 4% w / w, 5% w / w, 10% w / w, 15% w / w, 20% w / w, 25% w / w, 30% w / w, 33% w / w, 35% w / w, 40% w / w, 50% w / w.

[0276] Where appropriate, the solvent may be selected to solvate the polymer and provide a solvent to be absorbed by the porous solid. Generally, hydrophilic solvents are preferred for hydrophilic matrices. The solvent may be water, organic or aqueous, or free of them, e.g., free of organic solvents. In some embodiments, the water concentration is from 0 w / w% to 99 w / w%, for example, 0 w / w%, 5 w / w%, 10 w / w%, 15 w / w%, 20 w / w%, 25 w / w%, 30 w / w%, 40 w / w%, 50 w / w%, 60 w / w%, 70 w / w%, 80 w / w%, 90 w / w%, 95 w / w%, or 99 w / w%.

[0277] The temperature of the mixture is adjusted not to exceed the melting temperature of the porous solid matrix. The temperature range can be, for example, from 10°C to 100°C, such as 10°C, 20°C, 30°C, 37°C, 40°C, 50°C, 60°C, 70°C, 80°C, or 90°C.

[0278] The exposure time is preferably a period of time required for the porous solid to reach EWC in the mixture. In some embodiments, the duration can include 2, 4, 6, 8, 10, 12, 16, 20, 24, and 48 hours.Stirring and temperature can be controlled to affect exposure time, for example, to accelerate the attainment of EWC or to control the viscosity of the mixture. Salt and / or penetrant content can be adjusted to contribute to, for example, solubility, viscosity, and / or EWC.

[0279] Some embodiments provide guidance on the salt concentration used to adjust the mixture. Some examples of salt concentrations are 0.1% w / w to 2% w / w. Generally, monovalent cations with smaller atomic radii penetrate deeper into porous solids, while larger cations penetrate less. Some examples of salts are salts containing monovalent, divalent, or other cations, such as salts of sodium, potassium, lithium, copper, quaternary ammonium (where R is hydrogen, alkyl, or aryl), magnesium, calcium, copper, iron, or zinc. Generally, the physiological pH of the buffer solution can be used for the mixture. The pH can be adjusted to increase or decrease penetration into the matrix, and the solvent may include or omit the buffer salt. Some examples of pH are 4 to 10, such as 4, 5, 6, 7, 8, 9, or 10.

[0280] The viscosity of the mixture, when referring to water-soluble polymers and solvents, is affected by: pH (higher pH, higher viscosity), polymer concentration and / or molecular weight, and polymer branching, where an increase in any of these generally results in higher viscosity. Generally, higher viscosity reduces the penetration of the bulk incorporated polymer into the porous solid. One embodiment is a porous material comprising a water-soluble polymer embedded in the pores of a porous matrix. The matrix may comprise physically cross-linked water-soluble polymers that are cross-linked to form the matrix and define the pores. The matrix may have characteristics as disclosed herein, such as polymer content, polymer weight percentage, strength, Young's modulus, coverage, pore size, etc.

[0281] The surface coverage of the water-soluble polymer in the porous matrix can be complete. Wherein, complete coverage under SEM conditions, where the pores on the underlying surface are not visible, indicates coverage under EWC. The coverage may be less than 100%, for example, 50% to 100%; those skilled in the art will immediately recognize that all ranges and values ​​between the well-defined limits are to be expected, for example, 50%, 60%, 70%, 80%, 90%, 95%, 98%, 99%, 99.9% or 100%.

[0282] The inclusion of the bulk can reduce the physical properties of the porous solid. Thus, some embodiments include porous solids, such as those disclosed herein, which, compared to the same material not treated with a water-soluble polymer, have a Young's modulus and / or tensile strength that are 1% to 20% lower due to treatment with a water-soluble polymer; those skilled in the art will immediately recognize that all ranges and values ​​between the well-defined limits are to be expected, for example, 1%, 2%, 3%, 4%, 5%, 7%, 9%, 10%, 12%, 15% or 20%.The test for stability incorporating water-soluble polymers involves immersing the test device in a physiologically representative fluid (PBS) within a circulatory peristaltic loop at body temperature, with the device placed directly in the pump head at a flow rate of 10 to 12 mL / s at 150 rpm for 24 hours, resulting in approximately 500,000 mechanical sample compressions with a volumetric throughput of 0.1225 cm³*s⁻¹*cm⁻². While the test revealed losses up to 25%, other test standards can be used, such as losses from 0% w / w to 50% w / w, for example, 1% w / w, 5% w / w, 10% w / w, 15% w / w, 20% w / w, 25% w / w, 30% w / w, 40% w / w, and 50% w / w. Other tests may be performed, for example, under static exposure to excess PBS for 1 to 52 weeks, such as 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 10 weeks, 20 weeks, 30 weeks, 40 weeks, 50 weeks, or 52 weeks, with a loss of 0% w / w to 5% w / w, such as 1% w / w, 2% w / w, 3% w / w, 4% w / w, or 5% w / w.

[0283] This disclosure relates in some aspects to porous materials (e.g., porous hydrophilic materials, body portions, etc.). Methods for producing biocompatible porous solids, such as micron-porous or nanoporous solid materials with low protein adsorption properties and providing a basis for non-biofouling devices, are provided herein. Surface properties and other properties with reduced protein adsorption can be provided by modifying the starting polymer concentration, molecular weight, solvent removal, molding process, and hardening / annealing process. Some embodiments include producing a variety of continuous shapes by extruding polymer mixtures. The mixtures may be further hardened and annealed. These processes can be used to produce tough and highly smooth materials. Some embodiments include extruding the polymer mixture into a shape having one or more cavities with different diameters and wall thicknesses.

[0284] One embodiment of a method for preparing nanoporous solid materials includes: heating a mixture containing a polymer and a solvent (the polymer mixture), extruding the mixture into a solvent-removing environment, and removing the solvent from the crosslinked matrix until a nanoporous solid material is formed. According to the method, one or more of these actions can be combined. Furthermore, cooling the mixture as it exits the mold is possible. Without being bound by any particular operational theory, it is shown that crosslinking the polymer during passage through the mold initially forms a porous matrix that is not a true nanoporous solid material because it does not have a pore structure despite having spaces between the polymer strands. When the solvent is removed under suitable conditions, the crosslinked structure becomes a nanoporous solid. Crosslinking begins when the polymer mixture is extruded through the mold and as the mixture cools. Crosslinking can continue while the solvent is being removed.The transformation to form nanoporous materials occurs with solvent removal and is generally considered to be completed or substantially completed at this stage (meaning 90% or more). The resulting material can be further processed by annealing with or without additional solvents or plasticizers. This process, as well as other extrusion or other molding processes and / or materials (including bulk incorporation processes) described herein, may not contain one or more of the following: covalent crosslinking agents, agents that promote covalent crosslinking, radiation that crosslinks polymer chains, freezing, thawing, freeze-thaw cycles, more than one freeze-thaw cycle, ice crystal formation, foaming agents, surfactants, hydrophobic polymers, hydrophobic polymer segments, reinforcing materials, wires, braids, nonporous solids, and fibers.

[0285] Porous materials can be prepared by an extrusion process that includes passing a polymer mixture through a die into a cooling environment. The cooling environment may also be a solvent removal environment. It is a dehydration environment when the solvent is water. The die may have a core through which the polymer mixture can be shaped around the core. Additional solvent removal environments and / or annealing environments may be used.

[0286] The extrusion process for the polymer-solvent mixture can be carried out by cold extrusion. The term cold extrusion refers to a process like that described on pages 46 / 54 of this specification, 55 CN 121195019 A, which involves passing the polymer-solvent mixture through a die and does not require heating the polymer-solvent mixture to above its boiling point during the entire process of preparing and extruding the polymer-solvent mixture. Therefore, in cold extrusion, the die is held below the boiling point of the polymer-solvent mixture. Although many solvents can be used, water is generally a usable solvent, in which case the die is held at 100°C or lower, although lower temperatures may be available as discussed above.

[0287] The term polymer mixture refers to a polymer in solution dissolved or suspended in a solvent. The solvent can be, for example, water, an aqueous solution, an organic solvent, or a combination thereof. Heating the polymer mixture may include heating the mixture to a temperature above the melting point of the polymer. Generally, when a solution reaches its melting point, the solution changes from a turbid state to a clear state. The aqueous solution contains water, for example, 10% to 100% (w / w or v / v) of the liquid is water; those skilled in the art will immediately recognize that all ranges and values ​​between well-defined limits are to be expected, such as 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90%, or at least one of these.

[0288] Extrusion is a method that can be used to shape materials. Other shaping methods may be used, such as molding, casting, or thermoforming of the polymer-solvent mixture. Generally, the polymer-solvent mixture is prepared without boiling and shaped into a certain form, and the shape is exposed to controlled solvent removal conditions using the guidance provided herein to prepare nanoporous or microporous materials. An annealing process may be included.Hydrogels that are not microporous or nanoporous materials can also be prepared.

[0289] Heated polymer mixtures can be molded or otherwise shaped as they cool, or molded / shaped and immediately cooled. Molding is a broad term referring to transforming material from an amorphous molten state into an end-user product or into an intermediate shape for further processing. Molding encompasses casting, layering, coating, injection molding, drawing, and extrusion. Molding can be performed using injection molding settings, where the mold is made of a material with thermally conductive properties, making it easy to heat to enhance the flow of the injected polymer mixture and to cool rapidly in a cooling environment. In other embodiments, the molding process can be accomplished by extruding the polymer mixture through a mold to form a continuous material.

[0290] Cooling the polymer mixture can include, for example, cooling the extruded material, as in the case of passing the polymer material through a mold. One implementation of cooling is a temperature lower than the boiling point of the polymer mixture, or alternatively at least 20°C lower than the polymer mixture's Tm, for example, a liquid bath 20°C, 30°C, 40°C, 50°C, 60°C, 70°C, 80°C, 90°C, 100°C, or 110°C below the boiling point or polymer Tm, or alternatively, a bath or other environment at a temperature between -50°C and 30°C; those skilled in the art will immediately recognize that all ranges and values ​​between clearly defined limits are contemplated, wherein, for example, any of the following may be used as upper or lower limits: -50°C, -45°C, -25°C, -20°C, -10°C, -5°C, -4°C, 0°C, 15°C, 20°C, 25°C, 30°C. Cooling can be carried out in a solvent-free environment. Freezing temperatures can be avoided. The polymer chains are cooled to a point that promotes intermolecular hydrogen bonding and fixes chain motion, free from the constraints of any particular operational theory. This can occur at temperatures up to 30°C, or even higher if time permits. The bath can be aqueous and, by adjusting with salt or other penetrants, can be provided with a certain permeability value to remove solvents from aqueous materials with relatively low permeability values ​​through osmotic pressure and diffusion. The bath can also be other solvents that freeze at lower temperatures than water, thus allowing the use of temperatures below 0°C without freezing the solvent or material. For example, in the case of hydrophilic copolymers used in conjunction with PVA, temperatures above 20°C can be used for crosslinking and chain fixation will occur at much higher temperatures.

[0291] A solvent removal environment refers to an environment that significantly accelerates solvent removal compared to drying under ambient conditions. Such an environment can be unheated, meaning it is not above ambient temperature, for example, not above 20°C. Such an environment can be a vacuum, such as a vacuum chamber, a salt bath, or a bath for removing solvents from a polymer mixture. For example, an aqueous polymer mixture can be introduced into an ethanol bath, replacing water with ethanol. The ethanol can then be removed. A salt bath can be, for example, a high salt concentration bath (1 M to 6 M).The processing time during solvent removal and / or cooling can be independently selected from 1 to 240 hours; those skilled in the art will immediately recognize that all ranges and values ​​between clearly defined limits are to be expected, wherein, for example, any of the following can be used as upper or lower limits as specified on pages 47 / 54 of CN 121195019 A: 1, 2, 5, 10, 24 hours, 1, 2, 5, 7, 10 days. The salt can be a salt that dissociates to produce ions with a single, double, or triple charge.

[0292] One or more solvent removal environments can be used, or an environment can be adjusted for temperature. Thus, a cooling bath can be used, followed by solvent removal in an oven or vacuum oven. A washing step can be performed before or after cooling or solvent removal, for example by immersion in a series of solvents of different concentrations, different salt solutions, different proportions of ethanol or other solvents.

[0293] One embodiment involves extruded material that has already undergone a solvent removal process (including exposure to a salt bath), immersing the material in a series of H2O baths (new or replaced) for a period of time (e.g., 2 to 48 hours, 4 to 24 hours) to remove excess salt from the casting material or end-user device. The material is removed from the washing step and dehydrated to remove excess water. Dehydration can be carried out at temperatures, for example, 20°C to 95°C. Dehydration is generally carried out at 37°C for more than 24 hours.

[0294] One embodiment involves a polymer mixture that has been extruded or otherwise molded, subsequently exposed to a high-salt-concentration bath (1 M to 6 M) for an inversely related period of time; the high salt content shortens the required immersion time; for example, immersing it in a 6 M NaCl solution for 16 to 24 hours. After immersion, the material is rinsed off the salt solution. The material is now tough and can be removed from any molded part that has been present since the initial molding. Alternatively, after salt or other baths, the material is immersed in a water bath and dehydrated to remove excess water. Dehydration can be carried out at temperatures ranging from 20°C to 95°C. Dehydration can be carried out at 37°C for more than 4 hours, more than 24 hours, or 2 to 150 hours; those skilled in the art will immediately recognize that all ranges and values ​​between the clearly defined limits are to be expected, wherein, for example, any of the following can be used as upper or lower limits: 2, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 120, 144, 150 hours. For example, it has been observed that dehydration at 40°C for 6 to 24 hours is usable.

[0295] In another embodiment, NaCl is incorporated into the starting polymer solution at a concentration of 0.1 to 3 M per volume of the final polymer mixture. The polymer is dissolved in the heated solution under stirring, and then brought to a point above its melting point. Dry NaCl is slowly added to the solution under stirring until completely dissolved. The slightly turbid solution is then introduced into the feed for shaping by injection molding, casting, extrusion, and / or drawing.At the end of each process, quenching is performed to rapidly reduce the temperature and form a solid material. In this embodiment, additional salt soaking is not required. After the material has hardened, if necessary, the material is removed from any molding process component and rinsed in water to remove salt and dehydrate.

[0296] The term annealing, as used in the context of semi-crystalline polymers or solid porous materials, refers to heat treatment at an annealing temperature comparable to the melting temperature of the polymer or related material. This temperature is typically lower than the melting temperature on an absolute temperature scale and is within about 0% to 15% of the melting temperature. Plasticizers or other additive materials can affect the melting temperature, usually by lowering it. For example, for pure PVA, the annealing temperature will be within about 10% of the melting point of PVA; in the presence of other materials, the annealing temperature will typically be lower. One operational theory is that annealing is a stress-mitigating process combined with an increase in the size of crystalline regions in the annealed material. Unlike metals, annealing increases the strength of the annealed material. Annealing can be performed in one or more of the following ways: in air or in a gas or in the absence of oxygen or water, such as in nitrogen, in a vacuum of nitrogen, under argon, or using an oxygen scavenger. For example, experiments have been conducted on annealing dehydrated PVA nanoporous materials. Annealing is used to increase the crystallinity in the PVA network, further reducing the pore size of the PVA network and decreasing the adsorption properties of the final gel surface. Annealing can be performed at temperatures, for example, from 100°C to 200°C; in a preferred embodiment, this step is performed by immersing the dehydrated gel in a mineral oil bath. Incorporating the polymer bulk into the porous solid may also include the annealing process already described above for the porous solid. Annealing can be performed after exposing the desolvated porous solid to a mixture containing the polymer to be incorporated. The Tg of the material can be increased or decreased depending on the residual solvent content and / or the presence of a second hydrophilic polymer to be incorporated. As already described, the annealing process conditions can therefore be adjusted to depend on the temperature, time, heating rate, and cooling rate of the substrate.

[0297] Annealing can be performed in a gas or liquid under ambient pressure, elevated pressure, or low pressure (vacuum pressure). The liquid may be a low molecular weight polymer (up to 2000 Da) or other materials (e.g., mineral oil). Some examples of low molecular weight polymers are: silicone oil, glycerin, polyols, and polyethylene glycol with a molecular weight of less than 500 Da. One possible embodiment is annealing in a glycerin bath at, for example, 140°C for 1 to 3 hours; glycerin is used to further reduce the fouling properties of the gel through the interaction and neutralization of free hydroxyl terminal groups in the PVA network. The annealed nanoporous material is cooled, removed from the annealing bath, and rinsed off the bath medium using a series of extended soaking rinses. The product is then dehydrated in preparation for final sterilization.

[0298] Various types of dies can be used, such as longitudinal, angular, transverse, and helical extruders, as well as single-polymer extruders for extruding a single polymer and multilayer extruders for simultaneously extruding multiple polymer layers or other layers. Continuous operation heads and cyclic heads can be used. Various materials can be incorporated into the layers or as layers: for example, reinforcing materials, fibers, wires, braided materials, braided yarns, braided plastic fibers, etc. Similarly, such materials may not be excluded. Furthermore, porous solids can be made to have certain properties, such as Young's modulus, tensile strength, solids content, polymer composition, porous structure, or solvent content, which are known and therefore can be measured independently of a variety of other materials. Thus, some embodiments include the materials disclosed herein, which are described according to the properties of said materials without regard to a variety of other incorporated materials. For example, nanoporous solids have a known specific Young's modulus, even if the material has reinforcing wires that contribute to additional strength.

[0299] The core can be used with the extrusion die. The core can be air, water, liquid, solid, non-solvent, or gas. Those skilled in the art who read this disclosure will recognize that a variety of extrusion methods can be used with these different types of cores. Cores made of polytetrafluoroethylene (PTFE) tubing are available. In some embodiments, the core is wire.

[0300] Multi-lumen tubes have multiple channels running through their profile. These extrudates can be custom-modified to meet device designs. Multi-lumen tubes have variable outer diameters (OD), a variety of custom inner diameters (ID), and a variety of wall thicknesses. Such tubes can be obtained in a variety of shapes: round, oval, triangular, square, semi-circular, and crescent-shaped. These lumens can be used for wires, fluids, gases, wires, and a variety of other requirements. The number of lumens in a multi-lumen tube is limited only by the size of the OD. In some embodiments, the OD can be as large as 0.5 inches, the ID as small as 0.002 inches, and the web and wall thickness can be as thin as 0.002 inches. Tight tolerances can be maintained in inches. A skilled technician will immediately recognize that all ranges and values ​​within the clearly defined limits are to be expected, wherein, for example, any of the following may be used 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. Tolerances may be, for example, 0.0005 to 0.1 inches; a skilled technician will immediately recognize that all ranges and values ​​within the clearly defined limits are to be expected, wherein, for example, any of the following may be used 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.

[0301] Braided reinforced tubing can be fabricated in a variety of structures. For example, it can be braided using round or flat, single-ended or double-ended wires as small as 0.001 inches. A variety of materials can be used to fabricate braided reinforced tubing, including stainless steel, beryllium copper, and silver, as well as monofilament polymers. The braid can be wound at different weft densities on many thermoplastic substrates, such as nylon or polyurethane. The advantages of braided tubing shafts are their high torsional capacity and kink resistance. The characteristics of the tubing can be altered to suit performance requirements by changing several factors during the braiding process. After braiding is complete, a secondary extrusion can be applied to the top of the braided tubing to encapsulate the braid and provide a smooth finish. When braided reinforced tubing is required, walls as thin as 0.007 inches can be achieved.

[0302] The devices, tubings, kits, and methods described herein can be applied to any suitable object. As used herein, the term "object" refers to an individual living organism, such as a human or animal. In some embodiments, the object is a mammal (e.g., a human, a non-human primate, or a non-human mammal), a vertebrate, a laboratory animal, a domesticated animal, an agricultural animal, or a companion animal. Some non-limiting examples of the object include humans, non-human primates, cattle, horses, pigs, sheep, goats, dogs, cats, or rodents (e.g., mice, rats, hamsters), birds, fish, or guinea pigs. Generally, the invention is intended for human use. In some embodiments, the object may exhibit health benefits, for example, after application to the device. Specification 49 / 54 pages 58 CN 121195019 A

[0303] Products having a desired aspect ratio, such as at least 3:1, can be prepared, including end-user products or intermediate products, or materials, which, when referred to herein, include nanoporous materials, microporous materials, and hydrogels. The aspect ratio increases as the length of the device increases and the width decreases. Those skilled in the art will immediately recognize that all ranges and values ​​between clearly defined limits are predictable, with any of the following, for example, serving 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 highly advantageous for certain devices (e.g., many types of catheters). In principle, the tube can be continuously extruded without any limitation on length. Such devices include, for example, tubes, rods, cylinders, and have a cross-section with a square, polygonal, or circular profile. One or more cavities can be provided in any of them. The device can be made of a single material, substantially a single material, or multiple materials, including multiple layers or reinforcing materials, fibers, wires, braided materials, braided wires, braided plastic fibers, as already discussed.

[0304] In particular, the extrusion method specifies the concentric placement of the cavities; concentric is the opposite of eccentric, the latter meaning that the cavity is off-center.In the case of multiple cavities, the cavities can be positioned such that the cavities are symmetrically placed: symmetry is the opposite of eccentric placement of the cavities (due to poorly controlled processes). Some embodiments include the above-described device with an aspect ratio of at least 3:1, having multiple cavities that are not eccentrically placed or a single cavity concentric with the longitudinal axis of the device.

[0305] Porous solids such as nanoporous materials, microporous materials, and strong hydrogels can be used to prepare catheters or medical fibers. These can be made into polymers with bulk incorporation and can have a variety of features described thereto. Some examples of catheters are central venous catheters, hubed catheters, peripherally inserted central catheters, midline catheters, peripheral catheters, tunneled catheters, dialysis access catheters, hemodialysis catheters, vascular access port catheters, peritoneal dialysis catheters, urinary catheters, nerve catheters, peritoneal catheters, intra-aortic balloon pump catheters, diagnostic catheters, interventional catheters, drug delivery catheters, etc.), shunts, wound drainage devices (external, including ventricular, ventriculoperitoneal, and lumbar cisternoperitoneal), and infusion ports. Porous solids can be used to prepare implantable devices, including permanent or temporary fully implantable and percutaneous implantable devices. Porous solid materials can be used to prepare blood-contact devices or devices that contact body fluids, including ex vivo and / or in vivo devices, and including blood-contact implants. Examples of such devices include: drug delivery devices (e.g., insulin pumps), tubing, contraceptive devices, feminine hygiene products, endoscopes, implants (including those with a small diameter <6 mm), pacemakers, implantable cardioverter-defibrillators, cardiac resynchronization devices, cardiovascular device guides, 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, including drug delivery systems. The catheter may comprise a tubular nanoporous material that engages with other devices using fasteners (e.g., Luer fasteners or fittings). Radiopaque agents may be added to the material, fiber, or device. The term radiopaque agent refers to a reagent commonly used in the medical device industry to add radiopaque properties to materials, such as barium sulfate, bismuth, or tungsten. RO agents may be incorporated, for example, at 5% w / w to 50% w / w of the total solids weight, such as 5%, 10%, 20%, 30%, 40%, or 50%.

[0306] Medical fibers made from porous solid materials include, for example, sutures, yarns, medical textiles, braids, meshes, knitted or woven meshes, nonwoven fabrics, and applications of devices based thereon. The fibers are strong yet flexible. These fibers can be used to prepare materials that resist fatigue and abrasion.

[0307] In some embodiments, the devices described herein are medical devices, or are configured for use with medical devices, such as catheters, hubs, cuffs, balloons, shunts, wound drainage devices, infusion ports, drug delivery devices, tubes, contraceptive devices, feminine hygiene devices, endoscopes, grafts, pacemakers, implantable cardioverter-defibrillators, cardiac resynchronization devices, cardiovascular device guides, ventricular assist devices, endotracheal tubes, tracheostomy tubes, implantable sensors, ventilator pumps, and ophthalmic devices. In some embodiments, the catheter is selected from central venous catheters, peripheral central catheters, midline catheters, peripheral catheters, tunneled catheters, dialysis access catheters, urinary catheters, nerve catheters, percutaneous transluminal angioplasty catheters, and / or peritoneal catheters. See also the specification, pages 50 / 54, 59 CN 121195019 A. Some suitable uses will be described in more detail below.

[0308] In some embodiments, the devices and compositions described herein are applied to a subject. In some embodiments, the device may be administered orally, rectally, vaginally, nasally, intravenously, subcutaneously, or transurethral. In some cases, the device may be administered into a cavity, epidural space, vein, artery, orifice, external orifice, and / or abscess. A non-limiting example of an orifice includes a wound. A non-limiting example of a wound includes a wound opening created through the skin for venous access (e.g., as an insertion site).

[0309] The term "medically acceptable" generally refers to a highly purified material that is free of contaminants and is non-toxic. When used in the context of biomaterials or medical devices, the term "consistently consisting of" refers to a material or device having no more than 3% w / w of other materials or components that would not render the device unsuitable for its intended medical use. Equilibrium water content (EWC) is a term that refers to the water content of a material when its wet weight becomes constant and before the material degrades. Generally, materials with high solids content are observed to be at equilibrium water content over 24 to 48 hours. For the purpose of measuring EWC, distilled water is used unless otherwise specified.

[0310] The term w / v refers to weight per volume, such as g / L or mg / mL. The terms biomaterial and biomedical material are used interchangeably herein and cover biomedically acceptable materials for use in the biomedical field, such as as implants, catheters, blood contact materials, tissue contact materials, diagnostic assays, medical kits, tissue sample processing, or other medical purposes. Furthermore, while the materials described are suitable for biomedical uses, they are not limited thereto and can be produced as general materials. Physiological saline refers to a phosphate buffer solution having a pH of 7 to 7.4 and a human physiological osmolarity at 37°C.

[0311] The term molecular weight (MW) is measured in g / mol. Unless otherwise stated, the MW of a polymer refers to weight-average MW. When the polymer is part of a porous solid, the term MW refers to the polymer before crosslinking. When specifying the distance between crosslinks, it is the weight-average MW between crosslinks unless otherwise stated. The abbreviations k represent thousands, M represent millions, and G represent billions, so 50k MW means 50,000 MW. Dalton is also a unit of MW, and when used for polymers, it also refers to the weight average.

[0312] Publications, journal articles, patents, and patent applications cited herein are incorporated herein for all purposes, wherein in case of conflict, this specification shall prevail. Features of the embodiments described herein may be mixed and matched as directed by the need to produce an operable method or product.

[0313] As used herein, the term “therapeutic agent” or also referred to as “medicine” means an agent which is administered to a subject to treat a disease, disorder, or other clinically recognized ailment or for preventative purposes, and has a clinically significant effect on the subject’s body to treat and / or prevent the disease, disorder, or ailment.

[0314] As used herein, when a component is referred to as being “adjacent” to another component, it may be directly adjacent to (e.g., in contact with) that component, or there may be one or more intervening components. A component “directly adjacent” to another component means that there are no intervening components.

[0315] “Object” means any animal, such as a mammal (e.g., a human). Some non-limiting examples of an object include humans, non-human primates, cattle, horses, pigs, sheep, goats, dogs, cats, or rodents (e.g., mice, rats, hamsters), birds, fish, or guinea pigs. Generally, the invention is directed to human use. In some embodiments, the object may exhibit health benefits, for example, after the application of a self-righting device.

[0316] As used herein, “fluid” is given in its common sense, i.e., a liquid or gas. A fluid cannot maintain a defined shape and will flow over an observable time period to fill the container in which it is placed. Therefore, a fluid may have any suitable viscosity that allows it to flow. In the presence of two or more fluids, those skilled in the art can independently select each fluid from virtually any fluid (liquid, gas, etc.) on pages 51 / 54 of the specification, 60 CN 121195019 A.

[0317] Examples

[0318] Example 1

[0319] The following examples generally describe the formation of catheter tips according to some embodiments described herein.

[0320] “Soft” material of the tip

[0321] The tip is fused (glued or thermally bonded) to a material of lower hardness to help reduce trauma during insertion.Attach a PVA tip annealed / heat-treated to 120°C (injection-molded or extruded and cut) to a PVA tube annealed / heat-treated to 150°C. Attachment is achieved using PVA adhesive (10% PVA in water), which is dried and annealed to 120-150°C. Attachment is also achieved using radio frequency or localized heating with water as a solvent, allowing the material to flow back to the desired attachment location.

[0322] "Hard" material of the tip

[0323] The tip is fused (glued or heat-bonded) to a material of higher hardness to aid insertion through the skin, subcutaneous layer, and blood vessel walls (arteries or veins). Attach a PVA tip annealed / heat-treated to 170°C (injection-molded or extruded and cut) to a PVA tube annealed / heat-treated to 150°C. Attachment is achieved using PVA adhesive (10% PVA in water), which is dried and annealed to 120-150°C. Attachment is also achieved using radio frequency or localized heating with water as a solvent, allowing the material to flow back to the desired attachment location.

[0324] Example 2

[0325] The following examples generally relate to the formation of catheters with shape memory. Shape formation was observed to occur at temperatures greater than or equal to 70°C, 90°C, 120°C, 150°C, and 170°C (with increasing temperature exposure, generally providing a more rigid and clearer memory for the mandrel shape below). Shape memory is achieved using a stainless steel mandrel bent into a specific desired shape, radius, or curvature. Straight or curved catheter tubes are extruded and partially hydrated in water or salt solutions (sodium chloride or phosphate buffered saline) or alcohol / water solutions (85% ethanol / 15% water), making them sufficiently flexible to be placed on straight, curved, bent, annular, or spiral shapes to induce shape memory upon drying (<90°C) and subsequently annealing (>90°C) to 120°C. Figures 14A to 14C are photographs of exemplary formed catheters. Figure 14A is a photograph of a partially hydrated straight catheter. Figure 14B is a photograph of a partially hydrated straight conduit (in 2.2% sodium chloride) on a molded mandrel. Figure 14C (top) shows the molded mandrel. Figure 14C (bottom) is a photograph of an exemplary conduit that has been dried at 95°C for 90 minutes, annealed at 150°C for 90 minutes, and rehydrated in 1× phosphate-buffered saline at 37°C, with the mandrel removed.

[0326] When attempting to reshape the lumen from a circular to a D-shape, hydrating the conduit and drying it at different temperatures imparts varying degrees of aspect ratio similar to the shape of the underlying mandrel, generally proportional to temperature (see Figures 15A to 15C).

[0327]

[0328]

[0329] Although several embodiments of the invention have been described and illustrated herein, those skilled in the art will readily contemplate a variety of other methods and / or structures for performing the functions described herein and / or obtaining the results described herein and / or one or more advantages, and each of such variations and / or modifications is considered to be within the scope of the invention. More generally, those skilled in the art will readily understand that all parameters, dimensions, materials, and constructions described herein are intended to be exemplary, and actual parameters, dimensions, materials, and / or constructions will depend on one or more specific applications of the teachings of the invention. Those skilled in the art will recognize, or can determine, many equivalents of some specific embodiments of the invention described herein using only conventional experiments. Therefore, it should be understood that the foregoing embodiments are given by way of example only, and that the invention can be practiced in ways other than those specifically described and claimed within the scope of the appended claims and their equivalents. The invention relates to each individual feature, system, device, material, kit, and / or method described herein. Furthermore, any combination of two or more such features, systems, devices, materials, kits, and / or methods is included within the scope of the invention if such features, systems, devices, materials, kits, and / or methods are not inconsistent with each other.

[0330] Unless explicitly stated otherwise, nouns without quantifiers used herein in the specification and claims should be understood to mean "at least one / a."

[0331] The phrase "and / or" as used herein in the specification and claims should be understood to mean "any one or both" of elements that are co-existing in some cases and separate in others. Unless explicitly stated otherwise, other elements may optionally exist in addition to those specifically identified by the "and / or" clause, whether related to or unrelated to those specifically identified elements. Therefore, as a non-limiting example, when used in conjunction with open-ended language such as “comprising”, reference to “A and / or B” may in one embodiment refer to A without B (optionally including elements other than B); in another embodiment, it may refer to B without A (optionally including elements other than A); in yet another embodiment, it may refer to both A and B (optionally including other elements); and so on.

[0332] “Or” as used herein in the specification and claims should be understood to have the same meaning as “and / or” as defined above.For example, when items in the list are separated, “or / or” or “and / or” should be interpreted as inclusive, that is, including multiple elements or at least one of the elements in the list, but also including more than one, as well as optional additional items not listed. Only explicitly indicating the opposite terms, such as “only one” or “exact one”, or when used in the claims, “consisting of” will refer to including multiple elements or exactly one element in the list. In general, the term “or / or” as used herein, when preceded by an exclusive term (e.g., “any,” “one,” “only one,” or “exact one”), should be understood only to indicate an exclusive alternative (i.e., “one or the other but not both”). “Substantially consisting of” when used in the claims should have its ordinary meaning as used in the field of patent law.

[0333] As used herein in the specification and claims, when referring to a list of one or more elements, the phrase “at least one” should be understood to mean at least one element selected from any one or more elements in the list, but not necessarily including each and at least one of each element specifically listed in the list, and does not exclude any combination of elements in the list. This limitation also allows for the optional presence of other elements besides those specifically identified in the element list as referred to by the phrase "at least one," whether related to or unrelated to those specifically identified elements. Thus, as a non-limiting 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") in one embodiment may refer to at least one A, optionally including more than one A, while B is absent (and optionally including elements other than B); in another embodiment, it may refer to at least one B, optionally including more than one B, while A is absent (and optionally including elements other than A); in yet another embodiment, it may refer to at least one A, optionally including more than one A, and at least one B, optionally including more than one B (and optionally including other elements); etc.

[0334] In the claims and the above description, all transitional phrases such as "comprising," "including," "with," "having," "containing," "involving," "holding," etc., should be understood as open-ended, that is, as meaning including but not limited to. As described in Section 2111.03 of the Patent Examination Procedure Manual of the U.S. Patent Office, only the transitional phrases “composed of…” and “consistently composed of…” should be closed or semi-closed transitional phrases, respectively.Specification page 53 / 54 62 CN 121195019 A

[0335] Unless otherwise specified or indicated, any term used herein relating to, for example, one or more devices, structures, forces, fields, flows, directions / trajectories, and / or their subcomponents, and / or combinations thereof, and / or any other tangible or intangible elements not listed above that are suitable for being characterized by such terms, or their shape, orientation, arrangement and / or geometric relationship, shall be understood not to require absolute conformity to the mathematical definition of such terms, but rather to indicate conformity to the mathematical definition of such terms to the extent that the subject matter so characterized can be understood by one of skill in the field most closely related to such subject matter. Examples of such terms relating to shape, orientation, and / or geometric relationships include, but are not limited to, terms describing the following: shape – e.g., circular, square, annular / ring, rectangular / rectangular, triangular / triangular, cylindrical / cylindrical, elliptical / elliptical, (n) polygonal / (n) polygonal, etc.; angular orientation – e.g., vertical, orthogonal, parallel, vertical, horizontal, collinear, etc.; profile and / or trajectory – e.g., planar / planar, coplanar, hemispherical, semi-hemispherical, linear / linear, hyperbolic, parabolic, flat, curved, straight, arc-shaped, sinusoidal, tangent / tangent, etc.; direction – e.g., north, south, east, west, etc.; surface and / or bulk material properties and / or spatial / temporal resolution and / or distribution – Examples of terms include smooth, reflective, transparent, clear, opaque, rigid, impermeable, homogeneous, inert, non-wetting, insoluble, stable, unchanging, constant, homogeneous, etc.; and many other terms that are obvious to those skilled in the art. As an example, a preparation apparatus described herein as “square” does not require that such an apparatus have perfectly planar or linear faces or sides intersecting at exactly 90-degree angles (in fact, such an apparatus may exist only as a mathematical abstraction), but rather, as understood by those skilled in the art or as specifically described, the shape of such an apparatus should be understood to approximate, to the extent that the exemplified preparation techniques are generally achievable and have been achieved, a mathematically defined “square.” As another example, two or more preparation apparatuses described herein as “aligned” will not require that such an apparatus have perfectly aligned faces or sides (in fact, such an apparatus may exist only as a mathematical abstraction), but rather, as understood by those skilled in the art or as specifically described, the arrangement of such apparatuses should be understood to approximate, to the extent that the exemplified preparation techniques are generally achievable and have been achieved, a mathematically defined “alignment.”Instruction manual page 54 / 54, page 63, CN 121195019 A, Figure 1; Instruction manual figure 1 / 14 page, page 64, CN 121195019 A, Figure 2; Instruction manual figure 2 / 14 page, page 65, CN 121195019 A, Figure 3; Figure 4; Instruction manual figure 3 / 14 page, page 66, CN 121195019 A, Figure 5A; Figure 5B; Instruction manual figure 4 / 14 page, page 67, CN 121195019 A, Figure 6A; Figure 6B; Figure 6C; Instruction manual figure 5 / 14 page, page 68, CN 121195019 A, Figure 7; Instruction manual figure 6 / 14 page, page 69, CN 121195019 A, Figures 8A-8B; Instruction manual figure 7 / 14 page, page 70, CN 121195019 A, Figure 9A; Figure 9B; Instruction manual figure 8 / 14 page, page 71, CN 121195019 A, Figure 9C; Figure 10 Instruction manual figures 9 / 14 page 72 CN 121195019 A Figure 11A Figure 11B Instruction manual figures 10 / 14 page 73 CN 121195019 A Figure 12 Instruction manual figures 11 / 14 page 74 CN 121195019 A Figure 13 Figure 14A Figure 14B Instruction manual figures 12 / 14 page 75 CN 121195019 A Figure 14C Figure 15A Figure 15B Instruction manual figures 13 / 14 page 76 CN 121195019 A Figure 15C Instruction manual figures 14 / 14 page 77 CN 121195019 A.

Claims

1. Products, which include: The main body portion, wherein the main body portion comprises a first material containing a water-soluble polymer; and A component physically integrated with the main body, the component comprising a second material different from the first material. One or more of the following are true: i) The Young's modulus of the first material in the dehydrated state is greater than or equal to 500 MPa, and the Young's modulus of the first material in the equilibrium water content state is less than or equal to 300 MPa and greater than or equal to 5 MPa. ii) The first material is configured to expand from a dehydrated state to an equilibrium water content state in an amount greater than or equal to 5 w / w% and less than or equal to 50 w / w% within 60 minutes at 25°C. iii) The first material does not contain covalent crosslinks between the water-soluble polymers forming the first material; and / or iv) The first material contains pores, each pore having a diameter of 1 μm or less.

2. Products, which include: A hydrophilic porous polymer material containing a water-soluble polymer, the hydrophilic porous polymer material comprising a plurality of pores, wherein the hydrophilic porous polymer material does not have covalent crosslinks between the water-soluble polymers; and A component physically integrated with the hydrophilic porous polymer material, the component comprising a second material different from the first material, wherein the component comprises a plurality of fibers, and at least a portion thereof is embedded within the hydrophilic porous polymer material.

3. Products, which include: The main body portion, wherein the main body portion comprises a first material containing a water-soluble polymer, the first material comprising a plurality of pores; and A component physically integrated with the main body portion, such that at least a portion of the component is embedded within the main body portion, the component comprising a second material different from the first material.

4. A method for forming an integrated article, comprising: The following steps are performed using a polymer mixture comprising at least one water-soluble polymer and a solvent, wherein the polymer mixture has at least 10% w / w of the at least one water-soluble polymer: Heating the polymer mixture to a temperature above the melting point of the polymer mixture, Extruded polymer blends are used as the main component; as well as The solvent is removed from the extruded body portion at a temperature above the freezing point of the solvent until the body portion is porous, wherein the body portion is a porous body portion comprising the at least one water-soluble polymer, and the porous body portion is prepared without using a covalent crosslinking agent that forms covalent crosslinks between the polymers extruded to prepare the porous body portion. During the step of extruding the polymer mixture, the component is physically integrated with the body portion to form the integrated article, wherein the component comprises a second material different from the first material.

5. A method for forming an integrated article, comprising: Expose the main body to the solvent; Optionally, the main body portion is heated to a temperature less than or equal to 100°C. The main body portion comprises a first material containing a water-soluble polymer, such that the water-soluble polymer softens in the presence of the solvent. In the presence of the solvent, the main body portion is brought into contact with the component, thereby physically integrating the component with the main body portion to form the integrated article; and Cool the integrated product.

6. A method for forming an integrated article, comprising: Expose the main body to the solvent. The main body portion comprises a first material containing a first water-soluble polymer, and the solvent comprises water and a second water-soluble polymer. In the presence of a solvent, the main body portion is brought into contact with the component, thereby physically integrating the component and the main body portion to form the integrated article; as well as The integrated product is dried at least partially.

7. Articles, which include: The main body portion, wherein the main body portion comprises a first material containing a water-soluble polymer; A solution coating disposed on a portion of the surface of the main body portion, wherein the solution coating comprises water and polyvinyl alcohol, wherein the polyvinyl alcohol is present in the solvent in an amount greater than or equal to 0.1% by weight and less than or equal to 25% by weight; as well as The component is in physical contact with the solution coating, such that the component is adhered to the body portion by the solution coating.

8. The article or method according to any of the preceding claims, wherein the solvent comprises a water-soluble polymer, the concentration of which is lower than the concentration of the water-soluble polymer used to form the first material.

9. The article or method according to any of the preceding claims, wherein the solvent comprises water and polyvinyl alcohol, wherein the polyvinyl alcohol is present in the solvent in an amount greater than or equal to 0.1% by weight and less than or equal to 25% by weight.

10. The article or method according to any of the preceding claims, wherein the hydrolysis level of the solvent is greater than or equal to 80%, such that the solvent contains less than or equal to 20% acetate groups.

11. The article or method according to any of the preceding claims, wherein the solvent comprises water.

12. The article or method according to any of the preceding claims, wherein the solvent comprises water and a water-soluble polymer.

13. The article of manufacture according to any of the preceding claims, wherein the article of manufacture comprises a cavity.

14. The article of manufacture according to any of the preceding claims, wherein the article of manufacture comprises a hemodialysis catheter, a peripherally inserted central venous catheter (PICC), a central venous catheter, a midline catheter, a peripheral catheter, a urinary catheter, a nerve catheter, a peritoneal catheter, and / or an infusion port.

15. The article of manufacture according to any of the preceding claims, wherein the article of manufacture is configured for use with medical articles, such as catheters, balloons, shunts, wound drainage tubes, infusion ports, drug delivery articles, tubes, contraceptive articles, feminine hygiene products, endoscopes, grafts, pacemakers, implantable cardioverter defibrillators, cardiac resynchronization devices, cardiovascular product leads, ventricular assist devices, endotracheal tubes, tracheostomy tubes, implantable sensors, ventilator pumps, and ophthalmic articles.

16. The article or method according to any of the preceding claims, wherein the polymer material is free of a covalent crosslinking agent.

17. The article or method according to any of the preceding claims, wherein the polymer material has a Young's modulus of 5 to 100 MPa at equilibrium water content (EWC).

18. The article or method according to any of the preceding claims, wherein the article comprises a plurality of interconnected holes.

19. The article or method according to any of the preceding claims, wherein the component comprises a plurality of fibers.

20. The article or method according to any of the preceding claims, wherein the component is a catheter cuff.

21. The article or method according to any of the preceding claims, wherein the body portion comprises a second material, the second material comprising a first water-soluble polymer at a concentration lower than that of the first water-soluble polymer in the first material.

22. The article or method according to any of the preceding claims, wherein the water-soluble polymer may entrain an insoluble compound selected from: therapeutic agents, bioactive compounds, woven textiles, metal meshes, color indicators, radiopaque agents, and reaction indicators.

23. The article or method according to any of the preceding claims, wherein the water-soluble polymer incorporates a conductive indicator to assist in the detection of the electrocardiogram p wave.

24. The article or method according to claim 23, wherein the conductive indicator comprises iron powder that is insoluble in physiological fluids entrained in PVA.

25. The article or method according to any of the preceding claims, wherein the water-soluble polymer encapsulation is selected from the following woven textiles: Dacron® (polyethylene terephthalate, also known as polyester), electrospun PVA, cotton, wool, polypropylene (random, syndiotactic, isotactic) and polyethylene (LLDPE, LDPE, HDPE).

26. The article or method according to any of the preceding claims, wherein the intended use of the article or method is selected from combining bandages, tissue growths, scaffolds, shunts, braided tubes and wall scaffolds with an additional PVA substrate.

27. The article or method according to any of the preceding claims, wherein the first water-soluble polymer is combined with a second water-soluble polymer to create a new geometry or to reinforce one or more components physically integrated with the body portion.

28. The article or method of claim 27, wherein bonding comprises hydrating and heating the first water-soluble polymer and the second water-soluble polymer to be bonded into an overlap joint.

29. The article or method according to any of the preceding claims, wherein heating causes the first water-soluble polymer to flow into the second water-soluble polymer.

30. The article or method according to any of the preceding claims, wherein heating causes the second water-soluble polymer to flow into the first water-soluble polymer.

31. The article or method according to any of the preceding claims, wherein the combination further comprises cooling the first water-soluble polymer and the second water-soluble polymer.

32. The article or method according to any of the preceding claims, wherein cooling the polymer forms the integrated article.

33. The article or method according to any of the preceding claims, wherein the water-soluble polymer is hydrated in solution until equilibrium hydration is reached.

34. The article or method according to any of the preceding claims, wherein the equilibrium hydration % is from about 0.1% to 100%.

35. The article or method according to any of the preceding claims, wherein the solution comprises a phosphate buffered saline solution with a concentration of about 0.1 M to 10 M.

36. The article or method according to any of the preceding claims, wherein the bonding is performed using a hot air table of a specific geometry, a split mold bonding machine, or an RF welding machine.

37. The article or method according to any of the preceding claims, wherein the bonding temperature is 60°C to 95°C.

38. The article or method according to any of the preceding claims, wherein the bonding time is from 15 seconds to 5 minutes.

39. The article or method according to any of the preceding claims, wherein the bonding is accomplished using FEP heat shrink formed to a size and shape suitable for hot air treatment.

40. The article or method according to any of the preceding claims, wherein the bonding further comprises pressing the bonding to improve chain entanglement of the materials to be bonded.

41. A method for reshaping a hydrophilic porous material, comprising: The hydrophilic porous material is bent into a desired shape, the hydrophilic porous material comprising a cavity; Heating hydrophilic porous materials in a curved configuration to 90°C or higher in: a) The step of bending a hydrophilic porous material includes pressing the hydrophilic porous material into a mold having a desired shape; and / or b) The step of bending a hydrophilic porous material includes inserting the material into a cavity of the hydrophilic porous material to provide a desired shape; and / or c) The step of bending the hydrophilic porous material includes physically deforming the hydrophilic porous material. And for any of (a) to (c), one or more of the following hold true: i) The hydrophilic porous material has a Young's modulus greater than or equal to 500 MPa in the dehydrated state, and a Young's modulus less than or equal to 300 MPa and greater than or equal to 5 MPa in the equilibrium water content state. ii) The hydrophilic porous material is configured to expand from a dehydrated state to an equilibrium water content state in an amount greater than or equal to 5 w / w% and less than or equal to 50 w / w% within 60 minutes at 25°C. iii) The hydrophilic porous material does not contain covalent crosslinks between the water-soluble polymers forming the hydrophilic porous material; and iv) The hydrophilic porous material comprises pores, each pore having a diameter of 1 μm or less.

42. Articles comprising: An elongated tube, wherein the elongated tube comprises a first material containing a water-soluble polymer; The elongated tube comprises a first part and a second part. In the relaxed state of the elongated tube, the radius of curvature of the first part is different from the radius of curvature of the second part. One or more of the following are true: v) The Young's modulus of the first material in the dehydrated state is greater than or equal to 500 MPa, and the Young's modulus in the equilibrium water content state is less than or equal to 300 MPa and greater than or equal to 5 MPa. vi) The first material is configured to expand from a dehydrated state to an equilibrium water content state in an amount greater than or equal to 5 w / w% and less than or equal to 50 w / w% within 60 minutes at 25°C. vii) The first material does not contain covalent crosslinks between the water-soluble polymers that form the first material; as well as viii) The first material contains pores, each pore having a diameter of 1 μm or less.

43. A double-cavity article, comprising: A first body portion, the first body portion comprising a first material containing a water-soluble polymer, the first body portion comprising a first cavity having a first inner diameter; and The second body portion comprises a second material different from the first material, and includes a second cavity. The outer diameter of the first portion of the second body portion is smaller than the first inner diameter of the first cavity, and the second inner diameter of the second portion of the second body portion is approximately equal to the first inner diameter. The second main body portion is at least partially disposed within the first main body portion. One or more of the following are true: ix) The Young's modulus of the first material in the dehydrated state is greater than or equal to 500 MPa, and the Young's modulus of the first material in the equilibrium water content state is less than or equal to 300 MPa and greater than or equal to 5 MPa. x) The first material is configured to expand from a dehydrated state to an equilibrium water content state in an amount greater than or equal to 5 w / w% and less than or equal to 50 w / w% within 60 minutes at 25°C. xi) The first material does not contain covalent crosslinks between the water-soluble polymers that form the first material; as well as xii) The first material contains pores, each pore having a diameter of 1 μm or less.

44. A method for forming a double-cavity article, comprising: The first body portion comprising a first material comprising a water-soluble polymer is swelled in a solvent, and the first body portion comprises a first cavity having a first inner diameter; The second main body portion is heated and / or mechanically deformed, the second main body portion comprising a second material different from the first material, such that the outer diameter of the second main body portion is smaller than the first inner diameter of the first cavity; The second main body portion is inserted into the cavity of the first main body portion to form a dual-cavity article; as well as The dual-cavity article is dried, causing the first main body portion to shrink.

45. The article or method according to any of the preceding claims further includes one or more surface features (e.g., barbs, protrusions) at the interface between the first body portion and the second body portion, said one or more surface features being configured to mechanically reinforce the interface between the first body portion and the second body portion.

46. ​​The article or method according to any of the preceding claims further includes one or more surface features (e.g., barbs, protrusions) at the interface between the first body portion and the second body portion, said one or more surface features being configured to mechanically reinforce the interface between the first body portion and the second body portion.

47. The article or method according to any of the preceding claims, wherein the article is shaped using thermoforming.

48. The article or method according to any of the preceding claims, wherein thermoforming occurs at a temperature greater than 90°C.

49. The article or method according to any of the preceding claims, wherein thermoforming includes inserting a wire into a cavity of the article, placing the article into a mold, and heating the mold into a designed shape.

50. The article or method according to any of the preceding claims, wherein the article shape is bent, straightened, compressed, or stretched by limiting the size of the initial component to a desired shape.

51. The article or method according to any of the preceding claims, wherein the edges of the article may be rounded to allow easy fluid flow, reduce abrasion, and reduce surface area, which may contribute to placement, catheter life, and patient comfort.

52. The article or method according to any of the preceding claims, wherein the solvent comprises water.

53. The article or method according to any of the preceding claims, wherein the solvent comprises water and a water-soluble polymer.

54. The article or method according to any of the preceding claims, wherein the solvent comprises a water-soluble polymer at a concentration lower than that of the water-soluble polymer used to form the first material.

55. The article or method according to any of the preceding claims, wherein the solvent comprises water and polyvinyl alcohol, wherein the polyvinyl alcohol is present in the solvent in an amount greater than or equal to 0.1% by weight and less than or equal to 25% by weight.

56. The article or method according to any of the preceding claims, wherein the hydrolysis level of the solvent is greater than or equal to 80%, such that the solvent contains less than or equal to 20% acetate groups.

57. The article of manufacture according to any of the preceding claims, wherein the article of manufacture comprises a cavity.

58. The article of manufacture according to any of the preceding claims, wherein the article of manufacture comprises a hemodialysis catheter, a peripherally inserted central venous catheter (PICC), a central venous catheter, a midline catheter, a peripheral catheter, a urinary catheter, a nerve catheter, a peritoneal catheter, and / or an infusion port.

59. The article of manufacture according to any of the preceding claims, wherein the article of manufacture is configured for use with medical articles, such as catheters, balloons, shunts, wound drainage tubes, infusion ports, drug delivery articles, tubes, contraceptive articles, feminine hygiene products, endoscopes, grafts, pacemakers, implantable cardioverter defibrillators, cardiac resynchronization devices, cardiovascular product leads, ventricular assist devices, endotracheal tubes, tracheostomy tubes, implantable sensors, ventilator pumps, and ophthalmic articles.

60. The article or method according to any of the preceding claims, wherein the polymer material is free of a covalent crosslinking agent.

61. The article or method according to any of the preceding claims, wherein the polymer material has a Young's modulus of 5 to 100 MPa at equilibrium water content (EWC).

62. The article or method according to any of the preceding claims, wherein the article comprises a plurality of interconnected holes.

63. The article or method according to any of the preceding claims, wherein the component comprises a plurality of fibers.

64. The article or method according to any of the preceding claims, wherein the component is a catheter cuff.

65. The article or method according to any of the preceding claims, wherein the body portion comprises a second material, the second material comprising a first water-soluble polymer at a concentration lower than that of the first water-soluble polymer in the first material.

66. The article or method according to any of the preceding claims, wherein the water-soluble polymer may entrain an insoluble compound selected from therapeutic agents, bioactive compounds, woven textiles, metal meshes, color indicators, radiopaque agents, and reaction indicators.

67. The article or method according to any of the preceding claims, wherein the water-soluble polymer incorporates a conductive indicator to assist in the detection of the electrocardiogram p wave.

68. The article or method according to claim 23, wherein the conductive indicator comprises iron powder insoluble in physiological fluids entrained in the PVA.

69. The article or method according to any of the preceding claims, wherein the water-soluble polymer encapsulation is selected from the following woven textiles: Dacron® (polyethylene terephthalate, also known as polyester), electrospun PVA, cotton, wool, polypropylene (random, syndiotactic, isotactic) and polyethylene (LLDPE, LDPE, HDPE).

70. The article or method according to any of the preceding claims, wherein the intended use of the article or method is selected from combining bandages, tissue growths, scaffolds, shunts, braided tubes, and wall scaffolds with an additional PVA substrate.

71. The article or method according to any of the preceding claims, wherein the first water-soluble polymer and the second water-soluble polymer are combined to produce a new geometry or to reinforce one or more components physically integrated with the body portion.

72. The article or method of claim 27, wherein bonding comprises hydrating and heating the first and second water-soluble polymers to be bonded into an overlap joint.

73. The article or method according to any of the preceding claims, wherein heating causes the first water-soluble polymer to flow into the second water-soluble polymer.

74. The article or method according to any of the preceding claims, wherein heating causes the second water-soluble polymer to flow into the first water-soluble polymer.

75. The article or method according to any of the preceding claims, wherein the combination further comprises cooling the first water-soluble polymer and the second water-soluble polymer.

76. The article or method according to any of the preceding claims, wherein cooling the polymer forms an integrated article.

77. The article or method according to any of the preceding claims, wherein the water-soluble polymer is hydrated in solution until equilibrium hydration is reached.

78. The article or method according to any of the preceding claims, wherein the equilibrium hydration % is from about 0.1% to 100%.

79. The article or method according to any of the preceding claims, wherein the solution comprises a phosphate-buffered saline solution with a concentration of about 0.1 M to 10 M.

80. The article or method according to any of the preceding claims, wherein the bonding is performed using a hot air station of a specific geometry, a split mold bonding machine, or an RF welding machine.

81. The article or method according to any of the preceding claims, wherein the bonding temperature is 60°C to 95°C.

82. The article or method according to any of the preceding claims, wherein the bonding time is from 15 seconds to 5 minutes.

83. The article or method according to any of the preceding claims, wherein the bonding is accomplished using FEP heat shrink formed to a size and shape suitable for hot air treatment.

84. The article or method according to any of the preceding claims, wherein the bonding further comprises pressing the bonding to improve chain entanglement of the materials to be bonded.

85. An intravenous catheter, comprising: A polymeric material comprising a first water-soluble polymer having multiple pores; cavity; and The distal end includes a tip geometry adapted for intravenous insertion into the object; The polymer material has a water content of less than 5 w / w% and greater than or equal to 0.1 w / w% in the dehydrated state, and the polymer material is configured to expand from the dehydrated state to the equilibrium water content state in an amount of greater than or equal to 5 w / w% and less than or equal to 50 w / w% within 60 minutes at 25°C.

86. A system comprising an intravenous catheter according to any of the preceding claims, and components configured for administering a therapeutic agent and / or fluid to a subject and / or extracting bodily fluids from the subject.

87. Including the following methods: An intravenous catheter is inserted into a vein, the intravenous catheter comprising: A polymeric material comprising a first water-soluble polymer having multiple pores; cavity; and distal end, the distal end comprising a tip geometry adapted for intravenous insertion into the object; in, During the insertion step, the water content of the conduit is less than or equal to 5 w / w%. And the intravenous catheter is expanded to a water content greater than or equal to 5 w / w% and less than or equal to 50 w / w.

88. Including the following methods: An intravenous catheter is inserted into a vein, the intravenous catheter comprising: A polymeric material containing a first water-soluble polymer having multiple pores, wherein the water content of the polymeric material is greater than or equal to 5 w / w% and less than or equal to 50 w / w%. cavity; and The distal end includes a tip geometry adapted for intravenous insertion into the object; One or more of the following are true: i) The polymer material has a Young's modulus greater than or equal to 500 MPa in the dehydrated state and a Young's modulus less than or equal to 300 MPa and greater than or equal to 5 MPa in the equilibrium water content state. ii) The polymer material does not contain covalent crosslinks between the water-soluble polymers that form the polymer material; as well as iii) The polymer material contains pores, each pore having a diameter of 1 μm or less.

89. The catheter or method according to any of the preceding claims, wherein the polymer material is free of a covalent crosslinking agent.

90. The conduit or method according to any of the preceding claims, wherein the article comprises a plurality of interconnected holes.

91. The conduit or method according to any of the preceding claims, wherein the polymer material has a Young's modulus greater than or equal to 500 MPa in a dehydrated state and a Young's modulus less than or equal to 300 MPa and greater than or equal to 5 MPa in an equilibrium water content state.

92. The catheter or method according to any of the preceding claims, wherein the intravenous catheter is configured for insertion into a subject in a dehydrated state.

93. The catheter or method according to any of the preceding claims, wherein the intravenous catheter is configured to be inserted into the object in a state of at least partial hydration.

94. The catheter or method according to any of the preceding claims, further comprising administering fluid to the subject via the intravenous catheter.

95. The catheter or method according to any of the preceding claims, further comprising drawing blood from the subject through the intravenous catheter.

96. The catheter or method according to any of the preceding claims, wherein the intravenous catheter exhibits a hemolysis level of less than or equal to 10%.

97. The catheter or method according to any of the preceding claims, wherein the softening rate of the intravenous catheter is: for a 3-point ratio, the force in the insertion state to the final hydration state is reduced by at least 99%.

98. The catheter or method according to any of the preceding claims, wherein the distal end of the catheter is tip-treated.

99. The catheter or method according to any of the preceding claims, wherein the proximal end of the catheter is designed with a hub.

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