Adaptively responsive materials for medical applications

Abstract

Provided herein is a medical article comprising: a substrate; a polymer coating disposed on the substrate, the coating including a liquid crystal acrylate and a responsive component; and a biocompatible liquid, the biocompatible liquid being contained within the polymeric coating.

Description

[0001] Cross - reference to related applications

[0002] This application claims the benefit of Indian Provisional Patent Application Serial No. 202211063235, filed on November 05, 2022, the entire content of which is incorporated herein by reference.

[0003] Background of the invention

[0004] Field of the Invention

[0005] Materials suitable for medical applications are disclosed herein, and in particular, porous polymer materials capable of absorbing and releasing various substances in a controlled manner.

[0006] Description of the Related Art

[0007] Disinfection is very important in the medical field, including intravenous access and wound care. In terms of intravenous access, disinfection and ensuring the presence of a catheter lock solution are very important because infections and clots in the occluding device can quickly be life - threatening. Nowadays, separate manual steps are used for cleaning the connector, disinfecting the lumen, and introducing the lock solution. Each step requires diligence and care to be done well. This is challenging in a hospital environment and even more so in alternative care settings.

[0008] The presence of bacteremia originating from an I.V. (intravenous) catheter is characterized by catheter - related bloodstream infection (CRBSI), sometimes also referred to as catheter - related sepsis. Bacterial contamination of intravascular catheter infusion connectors (such as needle - free connectors (NFC) and locks) can lead to CRBSI. Before bloodstream infection occurs, the entrance end of the intravascular catheter is often already contaminated with bacteria. This type of contamination occurs during the handling of intravascular line connectors during infusion, drug injection, or blood sample collection connections.

[0009] To reduce the introduction of microorganisms into the lumen via a needleless connector, the Infusion Therapy Standards of Practice (INS) (8th Edition, 2021) recommends either active disinfection using 70% isopropyl alcohol or ethanol-based chlorhexidine swabsticks, or passive disinfection using a disinfection cap. Both active disinfection using ethanol-based chlorhexidine gluconate swabsticks and passive disinfection using a disinfection cap are associated with a lower incidence of catheter-related bloodstream infections (CABSI), while 70% isopropyl alcohol (IPA) swabs were found to be the least effective according to a meta-analysis of quasi-experimental studies. Additionally, the INS reported that ethanol-impregnated sponge devices were unable to effectively decontaminate the internal lumen of stopcocks. Further, the INS recommends changing the needleless connector every 96 hours or according to the manufacturer's specifications. According to the INS, changing to more frequent intervals provides no benefit and may increase the risk of CABSI.

[0010] For wound care, medical tapes have a variety of medical applications, e.g., including as part of an over-the-counter bandage for minor wounds and cuts, medical tapes for securing gauze or securing medical devices to the body, wound dressings, and securing devices for stabilizing intravenous catheters. Depending on the requirements of the application, the tape may need to be waterproof and / or have sufficient strength and resistance to pull-off due to movement / torque. However, generally, the tape needs to be removed first for the procedure, and then another tape is applied after inspection, addition of medication, or other medical intervention.

[0011] Medical Adhesive-Related Skin Injuries (MARSIs) encompass any type of skin injury related to the use of medical adhesive products such as tapes, wound dressings, drug patches, and wound closure materials. These injuries occur when the attachment of the skin to the adhesive within the epidermal cells is stronger, resulting in mechanical trauma, dermatitis, or other injuries. Currently, for patients vulnerable to infection, there are limited opportunities to reduce such problems and these injuries. Current tapes are not reusable, and even if a patient may need to secure his / her wound or catheter for several days, there may be a need for multiple accesses per day. This has also driven the need for multi-use adhesives.

[0012] Accordingly, there is a need in the art for new materials that can be used to provide disinfection and increased comfort for patients. SUMMARY OF THE INVENTION

[0013] The present disclosure provides a medical article that includes: a substrate; a polymeric coating disposed on the substrate, the coating including a liquid crystal acrylate and a responsive component; and a biocompatible liquid contained within the polymeric coating.

[0014] The present disclosure also provides a method of manufacturing a medical article having a polymeric coating disposed on its surface, the method including the steps of: mixing a liquid crystal acrylate, a responsive component, a carboxylic acid, a porogen, and a photoinitiator in a first solvent to provide a liquid monomer mixture; applying the liquid monomer mixture to a substrate; removing the solvent to provide a substrate having the monomer mixture thereon; polymerizing the monomer mixture to provide a substrate having a polymeric coating thereon; immersing the substrate having the polymeric coating thereon into a second solvent to remove the porogen, thereby providing a substrate having a porous polymeric coating; immersing the substrate having the porous polymeric coating into an alkaline solution; and, immersing the porous polymeric coating into a biocompatible liquid, thereby providing a substrate having a porous polymeric coating loaded with the biocompatible liquid.

[0015] The present disclosure also provides a method of using a medical article that includes a substrate, a polymeric coating disposed on the substrate and having at least one liquid crystal acrylate and a responsive component, the polymeric coating including a plurality of pores and a biocompatible liquid, the polymeric coating configured to exhibit a first orientation and a second orientation, in the first orientation the biocompatible liquid being contained within the pores and in the second orientation the biocompatible liquid being expelled from the pores, the method including exposing the medical article to ultraviolet light, thereby causing the polymeric material to exhibit the second orientation and expelling the biocompatible liquid from the polymeric coating.

[0016] Additional non-limiting embodiments are set forth in the numbered clauses below:

[0017] Clause 1. A medical article that includes: a substrate; a polymeric coating disposed on the substrate, the coating including at least one liquid crystal acrylate and a responsive component; and a biocompatible liquid contained within the polymeric coating.

[0018] Clause 2. The medical article according to Clause 1, wherein the polymeric coating is anisotropic.

[0019] Clause 3. The medical article according to Clause 1 or Clause 2, wherein the liquid crystal acrylate includes a liquid crystal diacrylate and a liquid crystal monoacrylate.

[0020] Clause 4. The medical article according to any one of Clauses 1-3, wherein the liquid crystal diacrylate has the following structure:

[0021]

[0022] Clause 5. The medical article according to any one of Clauses 1-4, wherein the liquid crystal diacrylate has the following structure:

[0023]

[0024] Clause 6. The medical article according to any one of Clauses 1-5, wherein the liquid crystal monoacrylate has the following structure:

[0025]

[0026] Clause 7. The medical article according to any one of Clauses 1-6, wherein the liquid crystal monoacrylate has the following structure:

[0027]

[0028] Clause 8. The medical article according to any one of Clauses 1-7, wherein the responsive component is a photo-responsive component including a photo-responsive diacrylate.

[0029] Clause 9. The medical article according to any one of Clauses 1-8, wherein the photo-responsive component includes an azobenzene moiety.

[0030] Clause 10. The medical article according to any one of Clauses 1-9, wherein the photo-responsive diacrylate has the following structure:

[0031]

[0032] Clause 11. The medical article according to any one of Clauses 1-10, wherein the polymer coating further includes a carboxylic acid.

[0033] Clause 12. The medical article according to any one of Clauses 1-11, wherein the carboxylic acid is benzoic acid.

[0034] Clause 13. The medical article according to any one of Clauses 1-12, wherein the polymer coating further includes a photoinitiator.

[0035] Clause 14. The medical article according to any one of Clauses 1-13, wherein the photoinitiator contains phosphorus (phosphorous).

[0036] Clause 15. The medical article according to any one of Clauses 1-14, wherein the photoinitiator has the following structure:

[0037]

[0038] Clause 16. The medical article according to any one of Clauses 1 - 15, wherein the polymer coating comprises a plurality of pores configured to accommodate a liquid therein.

[0039] Clause 17. The medical article according to any one of Clauses 1 - 16, wherein a biocompatible liquid is accommodated within the pores of the polymer coating.

[0040] Clause 18. The medical article according to any one of Clauses 1 - 17, wherein the biocompatible liquid comprises one or more of the following: polyethylene glycol, water, saline, dimethyl sulfoxide (DMSO), ethanol, isopropanol, and chlorhexidine gluconate.

[0041] Clause 19. The medical article according to any one of Clauses 1 - 18, wherein the polymer coating is configured to exhibit a first orientation and a second orientation, in the first orientation the biocompatible liquid is accommodated within the pores, and in the second orientation the biocompatible liquid is discharged from the pores.

[0042] Clause 20. The medical article according to any one of Clauses 1 - 19, wherein the polymer coating is configured to exhibit a first orientation when exposed to visible light and a second orientation when exposed to ultraviolet light.

[0043] Clause 21. The medical article according to any one of Clauses 1 - 20, wherein the substrate comprises a catheter, a catheter hub, a luer connector, and / or a needleless connector (NFC), and wherein the polymer coating is disposed on an inner surface of the medical article.

[0044] Clause 22. The medical article according to any one of Clauses 1 - 21, wherein the substrate is optionally flexible, and the medical article comprises an adhesive layer disposed on the polymer coating such that the polymer coating is disposed between the adhesive and the flexible substrate.

[0045] Clause 23. The medical article according to any one of Clauses 1 - 22, wherein the adhesive layer comprises a plurality of pores.

[0046] Clause 24. The medical article according to any one of Clauses 1 - 23, wherein the adhesive layer comprises one or more of the following: 2 - ethylhexyl acrylate, acrylic acid, isobutyl methacrylate, poly(ethylene glycol) methyl ether methacrylate, and poly(ethylene glycol) diacrylate.

[0047] Clause 25. The medical article according to any one of Clauses 1-24, wherein the substrate comprises one or more of the following: polyester, polyurethane, olefin, polyamide, and acrylic polymer, ethylene-vinyl acetate, polyether, and its derivatives.

[0048] Clause 26. A method of manufacturing a medical article having a polymer coating disposed on its surface, the method comprising: mixing at least one liquid crystal acrylate, a responsive component, a carboxylic acid, a pore former, and a photoinitiator in a first solvent to provide a liquid monomer mixture; applying the liquid monomer mixture to a substrate; removing the solvent to provide a substrate having the monomer mixture thereon; polymerizing the monomer mixture to provide a substrate having a polymer coating thereon; dipping the substrate having the polymer coating thereon into a second solvent to remove the pore former, thereby providing a substrate having a porous polymer coating; dipping the substrate having the porous polymer coating into an alkaline solution; and dipping the porous polymer coating into a biocompatible liquid, thereby providing a substrate having a porous polymer coating loaded with the biocompatible liquid.

[0049] Clause 27. The method according to Clause 26, wherein the liquid monomer mixture is applied to the substrate by a cell method or a spin coating method.

[0050] Clause 28. The method according to Clause 26 or Clause 27, wherein the first solvent is tetrahydrofuran (THF).

[0051] Clause 29. The method according to any one of Clauses 26-28, wherein the second solvent is cyclohexane and / or ethanol.

[0052] Clause 30. The method according to any one of Clauses 26-29, wherein the alkaline solution comprises potassium hydroxide (KOH).

[0053] Clause 31. The method according to any one of Clauses 26-30, wherein the liquid crystal acrylate comprises liquid crystal diacrylate and liquid crystal monoacrylate.

[0054] Clause 32. The method according to any one of Clauses 26-31, wherein the liquid crystal diacrylate has the following structure:

[0055]

[0056] Clause 33. The method according to any one of Clauses 26-32, wherein the liquid crystal diacrylate has the following structure:

[0057]

[0058] Clause 34. The method according to any one of Clauses 26-33, wherein the liquid crystal monoacrylate has the following structure:

[0059]

[0060] Clause 35. The method according to any one of Clauses 26-34, wherein the liquid crystal monoacrylate has the following structure:

[0061]

[0062] Clause 36. The method according to any one of Clauses 26-35, wherein the responsive component is a photo-responsive diacrylate.

[0063] Clause 37. The method according to any one of Clauses 26-36, wherein the photo-responsive component includes an azobenzene moiety.

[0064] Clause 38. The method according to any one of Clauses 26-37, wherein the photo-responsive diacrylate has the following structure:

[0065]

[0066] Clause 39. The method according to any one of Clauses 26-38, wherein the carboxylic acid is benzoic acid.

[0067] Clause 40. The method according to any one of Clauses 26-39, wherein the photoinitiator contains phosphorus.

[0068] Clause 41. The method according to any one of Clauses 26-40, wherein the photoinitiator has the following structure:

[0069]

[0070] Clause 42. The method according to any one of Clauses 26-41, wherein the biocompatible liquid includes one or more of the following: polyethylene glycol, water, saline, dimethyl sulfoxide (DMSO), ethanol, isopropanol, and chlorhexidine gluconate.

[0071] Clause 43. A method of using a medical article according to any one of Clauses 1-25, the method comprising exposing the medical article to ultraviolet light such that the polymeric material exhibits a second orientation and expels the biocompatible liquid from the polymeric coating. Description of the Drawings

[0072] Figure 1 Shows exemplary applications of materials according to non-limiting embodiments disclosed herein;

[0073] Figures 2A to 2BSchematic diagram showing an exemplary application of a material according to a non - restrictive embodiment disclosed herein;

[0074] Figures 3A to 3B is the chemical structure of a diacrylate useful in materials according to a non - restrictive embodiment disclosed herein;

[0075] Figures 4A to 4B is the chemical structure of a methacrylate useful in materials according to a non - restrictive embodiment disclosed herein;

[0076] Figure 5 is the chemical structure of a photo - responsive diacrylate useful in materials according to a non - restrictive embodiment disclosed herein;

[0077] Figure 6 is the chemical structure of a carboxylic acid useful in materials according to a non - restrictive embodiment disclosed herein;

[0078] Figures 7A to 7B is the chemical structure of a pore - forming agent useful in materials according to a non - restrictive embodiment disclosed herein;

[0079] Figure 8 is the chemical structure of a photo - initiator useful in materials according to a non - restrictive embodiment disclosed herein;

[0080] Figure 9 shows the chemical structure of the composition (composition liquid crystal mixture) of a liquid crystal mixture of a material according to a non - restrictive embodiment disclosed herein;

[0081] Figure 10 shows the chemical structure of the composition of a liquid crystal mixture of a material according to a non - restrictive embodiment disclosed herein; and

[0082] Figure 11 shows the chemical structure of the composition of a liquid crystal mixture material of a material according to a non - restrictive embodiment disclosed herein. Detailed Description

[0083] For the purposes of the following detailed description, it should be understood that, unless explicitly stated to the contrary, the present invention may assume various alternative variations and step sequences. In addition, except for any operating examples or where otherwise indicated, all numbers representing quantities of ingredients, such as used in the specification and claims, are to be understood as being modified in all instances by the term "about". Accordingly, unless otherwise indicated, the numerical parameters set forth in the following specification and attached claims are approximations that may vary depending upon the properties sought to be obtained by the present invention.

[0084] While the numerical ranges and parameters setting forth the broad scope of the invention are approximations, the numerical values set forth in the specific embodiments are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements.

[0085] In addition, it should be understood that any numerical range recited herein is intended to include all sub-ranges subsumed therein. For example, the range "1 to 10" is intended to include all sub-ranges between the recited minimum value of 1 and the recited maximum value of 10 (and including the recited minimum value of 1 and the recited maximum value of 10), that is, having a minimum value equal to or greater than 1 and a maximum value equal to or less than 10.

[0086] The present invention provides a polymeric material for use with a medical article that allows secretion and uptake of a biocompatible liquid that can be used in a variety of medical applications. The polymeric material of the present invention, which exhibits switching properties (e.g., changing state or orientation, as will be described below), has the advantage that it is suitable for use with biocompatible liquids. Without being bound by theory, it is believed that the polymeric materials described herein exhibit polarity suitable for use with such biocompatible liquids.

[0087] As used herein, the term "polymer" refers to oligomers and homopolymers (e.g., prepared from a single monomer species), copolymers (e.g., prepared from at least two different monomer species), terpolymers (e.g., prepared from at least three different monomer species), and graft polymers. The term "polymer" as used herein encompasses liquid crystal polymers. Hereinafter, the terms "polymeric material" and "liquid crystal polymer network (LCN)" may be used interchangeably.

[0088] In non-limiting embodiments, the polymeric materials described herein include one or more acrylates, such as alkyl or hydroxyalkyl esters of (meth)acrylic acid. Non-limiting examples of suitable acrylates include: alkyl esters of (meth)acrylic acid, such as methyl (meth)acrylate, ethyl (meth)acrylate, butyl (meth)acrylate, isobutyl (meth)acrylate, 2-ethylhexyl (meth)acrylate, lauryl (meth)acrylate, octyl (meth)acrylate, glycidyl (meth)acrylate, isononyl (meth)acrylate, isodecyl (meth)acrylate, vinyl (meth)acrylate, ethyl acetoacetoxy (meth)acrylate, propyl acetoacetoxy (meth)acrylate, and combinations thereof. Non-limiting examples of (meth)acrylic acid hydroxyalkyl esters include hydroxyethyl (meth)acrylate, hydroxypropyl (meth)acrylate, hydroxybutyl (meth)acrylate, and combinations thereof. Hereinafter, "acrylate" and "liquid crystal acrylate" may be used interchangeably. In non-limiting embodiments, useful acrylates (such as, diacrylates) may crosslink during the formation of the polymer composition. In non-limiting embodiments, one or more acrylates included in the polymeric materials described herein are attached to a mesogenic moiety, optionally aligning the polymeric material.

[0089] In non-limiting embodiments, the polymeric material includes one or more diacrylates and one or more monoacrylates. Non-limiting embodiments of suitable diacrylates and monoacrylates are as Figures 3A to 4B shown, where n = 1 to 99, optionally 3 to 11, including all values and subranges therebetween.

[0090] In non-limiting embodiments, the polymeric materials described herein include responsive components. As used herein, "responsive component" refers to a component that can exhibit multiple orientations depending on the type of stimulus (light, temperature, electrical stimulus) to which it is exposed. In non-limiting embodiments, the responsive component is a photo-responsive component, where the component switches orientation depending on the type of light to which it is exposed. For example, when exposed to visible light, the component may have a first orientation, while when exposed to ultraviolet (UV) light, the component may have a second orientation. In non-limiting embodiments, the responsive component includes an azobenzene moiety or a derivative thereof. In non-limiting embodiments, the photo-responsive component is a diacrylate. Non-limiting embodiments of suitable diacrylates are as Figure 5As shown, where n = 1 to 99, including all values and sub-ranges therebetween. In non-limiting embodiments, the responsive component is responsive to electrical stimuli, where the component changes orientation based on the type / amount of electrical stimulus to which it is exposed (e.g., frequency, voltage, and / or current). In non-limiting embodiments, the responsive component is temperature-responsive and changes orientation based on the amount of heat / temperature stimulus to which it is exposed (e.g., elevated temperature, room temperature, and / or below room temperature).

[0091] In non-limiting embodiments, the polymeric materials described herein include acids such as carboxylic acids and their derivatives. Suitable carboxylic acids include, but are not limited to, aromatic carboxylic acids, dicarboxylic acids, tricarboxylic acids, and combinations thereof. In non-limiting embodiments, the carboxylic acid is benzoic acid or a derivative thereof. Non-limiting embodiments of suitable carboxylic acids are as Figure 6 shown, where n = 1 to 99, including all values and sub-ranges therebetween.

[0092] In non-limiting embodiments, the polymeric materials are formed from a monomer mixture (such as a liquid monomer mixture), as will be described below. To facilitate polymerization, in non-limiting embodiments, the liquid monomer mixture includes a photoinitiator. In non-limiting embodiments, at least a residual amount of the photoinitiator remains in the final polymeric material. Suitable photoinitiators (e.g., photoinitiators activated by light having a wavelength in the range of 300 nm to 440 nm) are known to those skilled in the art and can include Irgacure 819, which is commercially available from BASF (Ludwigshafen, Germany). Non-limiting embodiments of suitable photoinitiators are as Figure 8 shown.

[0093] In non-limiting embodiments, the polymeric materials described herein are porous materials. In non-limiting embodiments, the pores of the polymeric materials allow for the accommodation and retention of a biocompatible liquid within the polymeric materials and are exposed to one or another type of light (as briefly described above). Porous polymeric materials can be prepared by adding a pore former to the various monomer / polymer components described above, followed by removal of the pore former (e.g., by exposure to a solvent). Inorganic salts, sugars, polyvinyl acetate (PVA), polyethylene glycol (PEG), sucrose crystals, gelatin spheres, paraffin spheres, or any other non-reactive liquid crystal molecules that undergo phase separation during the polymerization of a liquid crystal mixture are examples of suitable pore formers. Non-limiting embodiments of suitable pore formers are as Figures 7A to 7B shown.

[0094] As described above, the polymeric materials described herein can be used as a vehicle for storing / delivering biocompatible liquids, such as therapeutic compositions, for example by accommodating and / or retaining within the pores of the polymeric material. Those skilled in the art will understand that any suitable biocompatible liquid can be included, depending on the application. In non-limiting embodiments, the biocompatible liquid includes preservatives, antibacterial agents, fungicides, antifungal agents, and / or antiviral agents. In non-limiting embodiments, the biocompatible liquid includes one or more drugs, such as but not limited to analgesic compositions, anti-inflammatory compositions, and the like. In non-limiting embodiments, the biocompatible liquid is one or more of polyethylene glycol (PEG), water, saline, dimethyl sulfoxide (DMSO), ethanol, isopropyl alcohol, povidone iodine, and chlorhexidine gluconate (CHG).

[0095] Those skilled in the art will understand that the various components described above can be included in various amounts (for each component) and various ratios (for each component relative to another component or relative to the total amount of the liquid monomer mixture or the final polymer material). As described below, in non-limiting embodiments, the total solids content of the liquid monomer mixture (acrylate, reactive component, acid, pore former, and / or photoinitiator in a solvent) can range from about 10 wt% to about 70 wt%, optionally from about 20 wt% to about 50 wt%, including all values and sub-ranges therebetween. In non-limiting embodiments, the monomer mixture used to form the polymer materials described herein can include about 1 wt% to about 10 wt%, optionally about 3 wt% to about 7 wt%, optionally about 6 wt%, optionally about 5.6 wt%, optionally about 3 wt%, optionally about 3.4 wt% (including all values and sub-ranges therebetween) of one or more liquid crystal diacrylates; about 1 wt% to about 10 wt%, optionally about 2 wt% to about 5 wt%, optionally about 3 wt%, optionally about 2.8 wt%, optionally about 2 wt%, optionally about 1.7 wt% (including all values and sub-ranges therebetween) of one or more liquid crystal monoacrylates; about 2 wt% to about 10 wt%, optionally about 4 wt% to about 8.5 wt%, optionally about 8 wt%, optionally about 8.3 wt%, optionally about 5 wt% (including all numerical values and sub-ranges therebetween) of one or more responsive components; about 15 wt% to about 45 wt%, optionally about 20 wt% to about 40 wt%, optionally about 35 wt%, optionally about 33 wt%, optionally about 33.3 wt%, optionally about 20 wt% (including all numerical values and sub-ranges therebetween) of one or more acids or acid derivatives; about 1 wt% to about 5 wt%, optionally about 1 wt%, optionally about 2 wt% to about 3 wt%, optionally about 2 wt% (including all numerical values and sub-ranges therebetween) of one or more photoinitiators; and / or, about 30 wt% to about 80 wt%, optionally about 40 wt% to about 70 wt%, optionally about 50 wt%, optionally about 49 wt%, optionally about 70 wt%, optionally about 69 wt% (including all values and sub-ranges therebetween) of one or more pore formers.

[0096] In non-limiting embodiments, the polymeric materials described herein exhibit anisotropy. In terms of the function of the above polymeric materials, without being bound by theory, when included together with various other components described herein, the above responsive materials provide a liquid crystal polymer network (LCN) as the polymeric material, which can exhibit anisotropic deformation due to its unique anisotropic properties in response to external stimuli (e.g., light, temperature, and electric field) (see, e.g., White et al., Programmable and Adaptive Mechanics with Liquid Crystal Polymer Networks and Elastomers. Nat. Mater. 2015, 14, 1087 - 1098, the content of which is incorporated herein by reference in its entirety). Original studies on the linear thermal expansion of LCNs showed that LCNs with uniaxial planar alignment tend to expand perpendicular to the molecular director and contract parallel to the director. For the photoinduced deformation of LCNs, typically, the principle is based on the so-called photochemical effect. The photochemical effect is based on the light-initiated trans-to-cis isomerization of added azobenzene molecules. The azobenzene moiety can be provided by reactive groups similar to those of liquid crystal monomers, such that it can be covalently embedded in the network after polymerization. The cis-trans isomerization of azobenzene and the co-alignment of the mesogenic units of LCNs disrupt the molecular order of LCNs, resulting in anisotropic macroscopic deformation. In addition to using photoinitiators, applying a high-frequency electric field can also cause macroscopic anisotropic deformation of LCNs. In such non-limiting embodiments, polar groups with large dipole moments that can respond to an alternating electric field can be used.

[0097] Based on these principles, in a porous LCNs system filled with liquid, when an external stimulus is applied, the LCNs can exhibit macroscopic anisotropic deformation and thus squeeze and release a biocompatible liquid. In a light-driven system, the principle is based on the photo-isomerization of copolymerized azobenzene moieties. More specifically, a liquid-infused liquid crystal polymer coating with homeotropic alignment is fabricated on a substrate. The coating is copolymerized with photo-responsive azobenzene molecules. Under ultraviolet light irradiation, the azobenzene moiety changes from the rod-like trans state to the bent cis state, thereby generating a contractile force along the molecular alignment of the coating. Then, this force is applied to the liquid crystal polymer network, resulting in a decrease in the molecular order of the polymer network. Thus, the disordered polymer network can squeeze, expel, and release the stored liquid. When irradiated with visible light, the azobenzene can relax back to the stable trans state, thereby generating a suction force. Combining with the elasticity of the polymer network, the liquid released at the surface can be reabsorbed.

[0098] In a non-limiting embodiment, under ultraviolet light irradiation within the absorption band of the azobenzene trans isomer (e.g., at a wavelength of 365 nm), the biocompatible liquid can be extruded, expelled, and released onto the surface of the coating. When irradiated with visible light within the absorption band of the azobenzene cis isomer (e.g., at a wavelength of 455 nm), the liquid released at the surface can be reabsorbed by the coating. Thus, the coating can be refilled. The release and uptake of the biocompatible liquid are completely reversible. And this reversible process can be repeated multiple times without significant liquid loss due to evaporation.

[0099] When the coating / device for liquid infusion is exposed to air for a relatively long time (e.g., several hours), the stored liquid will escape from the polymer network due to evaporation. In this case, the dry coating can still be refilled by absorbing some additional liquid sprayed onto the surface of the coating. The absorption can be based on the following three principles: (1) liquid diffusion based on chemical potential; (2) capillary forces induced by pores within the polymer network; (3) possible additional capillary forces induced by the isomerization of the azobenzene moiety from the cis state to the trans state upon exposure to blue light.

[0100] In the case of electro-induced liquid secretion and uptake, liquid secretion is based on liquid diffusion, electrothermal effects, and the deformation of the liquid crystal polymer network under the influence of a radio frequency (RF) alternating electric field. When the RF electric field is turned off, liquid uptake occurs, which is induced by the combined action of capillary forces and polymer elasticity.

[0101] The present disclosure also provides a medical article having a polymer material described herein coated on at least one surface. Any medical article can be coated with the polymer material, but in a particular embodiment, the present disclosure contemplates medical articles that can benefit from the ability of the above materials to retain, release, and / or reabsorb biocompatible liquids. In a non-limiting embodiment, the medical article is a medical article attached to a patient's skin. In a non-limiting embodiment, the medical article is a medical tape, a bandage, and / or a wound dressing. In a non-limiting embodiment, the medical article (such as a tape, a bandage, and / or a wound dressing) includes a substrate, an optional flexible substrate, a polymer material as described herein, and an adhesive. Suitable substrates for wound dressings / tapes are known to those skilled in the art and can include one or more of polyester, polyurethane, olefin, polyamide, acrylic polymer, ethylene-vinyl acetate, silicone, foam, fluoropolymer, paper, non-woven polymer material, polyether, and its derivatives, can be transparent, translucent, or opaque, and can be formed into any suitable shape. In a non-limiting embodiment, the polymer material is disposed between the substrate and the adhesive. Suitable adhesives for medical applications are known to those skilled in the art and can include one or more of 2-ethylhexyl acrylate, acrylic acid, isobutyl methacrylate, poly(ethylene glycol) methyl ether methacrylate, and poly(ethylene glycol) diacrylate, cyanoacrylate, silicone, polyisobutylene.

[0102] In a non-limiting embodiment, the adhesive is porous such that the biocompatible liquid contained and / or retained within the polymer material can flow through the adhesive to contact, for example, the skin of the wearer. In a non-limiting embodiment, the surface area of any adhesive layer is less than the surface area of the polymer material layer. Without being bound by theory, the biocompatible liquid helps to remove the substrate containing the adhesive from the skin, reducing irritation and / or pain that would otherwise be caused. Potential advantages of using such a loaded polymer material include, but are not limited to, adjustable surface adhesion (e.g., strong adhesion before liquid release and easy peeling after liquid release without damaging the substrate, wound, or skin), the possibility of assisting in wound treatment (e.g., based on the release of a therapeutic composition carried by the liquid), and / or reusability (e.g., based on refilling the secreted liquid). In a non-limiting embodiment, the biocompatible liquid includes a preservative, an antibacterial agent, a bactericide, an antifungal agent, and / or an antiviral agent. In a non-limiting embodiment, the biocompatible liquid includes one or more analgesic and / or anti-inflammatory components. The released liquid can penetrate into the interface between the adhesive layer and the skin surface, reducing friction. Under a specific force, such a polymer plaster can be peeled off (as Figure 2BAs shown). When the stored biocompatible liquid is depleted, the polymer patch can be refilled with the same or a different liquid type. Thus, the polymer patch can be reused multiple times and can be used for the examination and treatment of various medical applications, such as dressings, fixation devices, bandages, and other temporary fixation devices for medical applications.

[0103] In non-limiting embodiments, the medical article is a device for intravenous access, such as a cannula, catheter, adapter, connector (e.g., Luer connector, needleless connector (NFC)), and / or any instrument that can be introduced into the vasculature or come into contact with blood. In non-limiting embodiments, the inner surface, lumen, and / or any part in contact with blood of the device can be coated with a polymer material as described herein. It is a solution for creating an adaptive responsive material for locking / self-cleaning applications, capable of controlling the secretion and absorption of disinfectants / self-cleaning liquids (such as but not limited to CHG, DMSO, IPA, ethanol, etc.). In non-limiting embodiments, the medical article can be formed from polyethylene terephthalate (PET), polycarbonate (PC), polyurethane, polytetrafluoroethylene (PTFE), polystyrene, silicone, and combinations thereof, and the medical article can be a surface grafting agent to improve the adherence of the polymer materials described herein.

[0104] The present disclosure also provides a method of manufacturing a medical article, the medical article being coated on at least one of its surfaces with a polymeric material described herein. The method can include the step of dissolving one or more acrylates (e.g., liquid crystal acrylates) described herein, together with a responsive component described herein, an acid described herein, a pore former described herein, and a photoinitiator described herein, in a solvent. Suitable solvents for preparing the acrylate liquid monomer mixture are known to those skilled in the art and can include tetrahydrofuran (THF), dichloromethane (DCM), 2-methyltetrahydrofuran, diethyl ether, 1,2-dimethoxyethane (DME), and 1,4-dioxane. The liquid monomer mixture can then be applied to a substrate using any suitable method. In non-limiting embodiments, the sample cell method or spin coating method can be used. Thereafter, the solvent can be removed (e.g., the liquid monomer mixture can be dried), and the substrate having the monomer mixture thereon can be subjected to polymerization conditions, such as by exposing the mixture to ultraviolet light. Thereafter, the polymeric material can be impregnated or washed with a solvent to remove the pore former, leaving a porous polymeric material. By impregnating or washing the porous polymeric material with a basic solution, residual hydrogen bonds can be broken and polymeric salts can be formed. Suitable basic solutions are known to those skilled in the art and can include potassium hydroxide (KOH), sodium hydroxide (NaOH), and ammonium hydroxide (NH4OH). A biocompatible liquid (or a combination thereof) can then be loaded into the porous polymeric material by impregnating the material into the biocompatible liquid.

[0105] The present disclosure also provides a method of using a medical article, the medical article being coated on at least one of its surfaces with a polymeric material described herein. As described above, the medical article can be any suitable medical article, including but not limited to cannulas, catheters, fittings, connectors (e.g., Luer connectors, needleless connectors (NFC)), and / or any device capable of being introduced into the vasculature or contacting blood. The method can include the steps of providing a medical article coated on at least one of its surfaces with a polymeric material as described herein, and exposing the medical article to visible light and / or ultraviolet light such that the polymeric material exhibits a first orientation and a second orientation, in the first orientation a biocompatible liquid as described herein is received within the pores, and in the second orientation the biocompatible liquid is expelled from the pores. As described herein, in non-limiting embodiments, the polymeric coating is configured to exhibit the first orientation when exposed to visible light and the second orientation when exposed to ultraviolet light.

[0106] Example 1

[0107] The sample cell is composed of two glass slides: one is coated with 3-(trimethoxysilyl)propyl methacrylate to enhance surface adhesion, and the other is coated with a polyimide layer to provide vertical alignment. The coating thickness is controlled by defined spacers. The size range of the spacers is 5 to 50 μm. The liquid crystal monomer mixture is filled into the empty sample cell by capillary force in the isotropic phase. After maintaining the constant temperature for 20 minutes, the mixture is cooled to its smectic phase, at which time the mixture polymerizes under ultraviolet irradiation. A cut-off filter that allows light with a wavelength > 400 nm to pass through is used and placed between the sample cell and the ultraviolet light source. After photopolymerization, the glass slides can be removed using a blade. The coating is supported by the glass slides.

[0108] To remove the pore-forming agent, the coating is immersed in a solvent bath for 24 hours. The solvents used include, but are not limited to, cyclohexane and ethanol. The residual solvent is removed by evaporation at room temperature.

[0109] To break the hydrogen bonds and form polymer salts, the coating is immersed in an alkaline bath. The alkaline solutions used include, but are not limited to, KOH solutions. The concentration of the KOH solution is in the range of 0.05 to 0.5 M, and the immersion time is in the range of 30 s to 60 min.

[0110] After the base treatment, the coating is transferred to a liquid reservoir containing a disinfectant / self-cleaning liquid (including, but not limited to, DMSO, ethanol, isopropanol, or a mixture). Let the coating refill for 24 hours.

[0111] Example 2

[0112] The glass plate is coated with 3-(trimethoxysilyl)propyl methacrylate to enhance surface adhesion. The liquid crystal monomer mixture is dissolved in THF. The concentration of the solid in the solution ranges from 20 wt% to 50 wt%. The solution is coated onto the glass plate using a spin coater. The spin coating parameters are: (1) the rotation speed is in the range of 300 rpm to 1000 rpm, depending on the solid concentration; (2) the acceleration is in the range of 100 rpm / s to 500 rpm / s. After spin coating, the coating is transferred to a heating stage maintained at 90 °C for 5 minutes to evaporate THF. Then, the monomer coating is slowly cooled to its smectic phase. Depending on the composition of the monomer mixture, the temperature of the smectic phase varies from sample to sample. At the temperature of the smectic phase, the sample undergoes photopolymerization under ultraviolet irradiation. A cut-off filter that allows light with a wavelength > 400 nm to pass through is used and placed between the sample cell and the ultraviolet light source.

[0113] To remove the pore former, the coating was immersed in a solvent bath for 24 hours. The solvents used include but are not limited to cyclohexane and ethanol. The residual solvent was removed by evaporation at room temperature.

[0114] To break the hydrogen bonds and form polymer salts, the coating was immersed in an alkaline bath. The alkaline solutions used include but are not limited to KOH solution. The concentration of the KOH solution ranges from 0.05 to 0.5 M. The immersion time ranges from 30 seconds to 60 minutes.

[0115] After the basic treatment, the coating was transferred to a liquid reservoir containing a disinfectant / self-cleaning liquid (including but not limited to DMSO, ethanol, isopropanol or mixtures). The coating was allowed to refill for 24 hours.

[0116] Example 3

[0117] The sample cell consists of two glass slides: one is a flexible polymer film coated with 3-(trimethoxysilyl)propyl methacrylate to enhance surface adhesion; and the other is a glass slide coated with a polyimide layer to provide vertical alignment. In this case, the substrate for supporting the coating is the flexible polymer film, including but not limited to polyethylene terephthalate (PET). The PET can be coated with a thin layer of indium tin oxide to change the surface chemistry. The coating thickness is controlled by a defined spacer. The size of the spacer ranges from 5 to 50 μm. The chemicals used to form the polymer coating are the same as those used in 1. The liquid crystal monomer mixture was filled into the empty sample cell by capillary force in the isotropic phase. After 20 minutes of constant temperature, the mixture was cooled to its smectic phase, at which time the mixture polymerized under ultraviolet irradiation. A cut-off filter that allows light with a wavelength > 400 nm to pass through was used and placed between the sample cell and the ultraviolet light source. After photopolymerization, the glass slide can be removed using a blade. The coating is supported by the flexible polymer film.

[0118] To remove the pore former, the coating was immersed in a solvent bath for 24 hours. The solvents used include but are not limited to cyclohexane and ethanol. The residual solvent was removed by evaporation at room temperature.

[0119] To break the hydrogen bonds and form polymer salts, the coating was immersed in an alkaline bath. The alkaline solutions used include but are not limited to KOH solution. The concentration of the KOH solution ranges from 0.05 to 0.5 M. The immersion time ranges from 30 seconds to 60 minutes.

[0120] After the basic treatment, transfer the coating to a liquid reservoir containing a disinfectant / self-cleaning liquid (including but not limited to DMSO, ethanol, isopropanol). Let the coating refill for 24 hours.

[0121] Then, the refilled coating can trigger liquid secretion and uptake when illuminated. To prevent the liquid from evaporating from the top surface of the coating, a sealing layer can be used. The sealing layer can be an adhesive layer that can impart the required adhesion force to the coating when the coating comes into contact with the measurement substrate or the skin. To allow the liquid to be released at the surface of the coating, the adhesive layer can contain a certain number of pores; that is, the surface area of the adhesive layer is smaller than the surface area of the polymer coating.

[0122] Example 4

[0123] A PET flexible film coated with a thin layer of indium tin oxide is treated with a thin layer of 3-(trimethoxysilyl)propyl methacrylate using a coating technique including but not limited to spin coating, dip coating, and chemical vapor deposition. Dissolve the liquid crystal monomer mixture in THF. The concentration of the solid in the solution ranges from 20 wt% to 50 wt%. Use a spin coater to coat the solution onto the PET film. The spin coating parameters are: (1) the rotation speed is in the range of 300 rpm to 1000 rpm, depending on the solid concentration; (2) the acceleration is in the range of 100 rpm / s to 500 rpm / s. After spin coating, transfer the coating to a heating stage at 90 °C for 5 minutes to evaporate THF. Then, slowly cool the monomer coating to its smectic phase. Depending on the composition of the monomer mixture, the temperature of the smectic phase varies from sample to sample. At the temperature of the smectic phase, the sample undergoes photopolymerization under ultraviolet irradiation. Use a cut-off filter that allows light with a wavelength > 400 nm to pass through and place it between the sample cell and the ultraviolet light source.

[0124] To remove the pore-forming agent, immerse the coating in a solvent bath for 24 hours. The solvents used include but not limited to cyclohexane and ethanol. Evaporate the remaining solvent at room temperature.

[0125] To break the hydrogen bonds and form polymer salts, immerse the coating in an alkaline bath. The alkaline solutions used include but not limited to KOH solutions. The concentration of the KOH solution is in the range of 0.05 to 0.5 M. The immersion time is in the range of 30 seconds to 60 minutes.

[0126] After the basic treatment, transfer the coating to a liquid reservoir containing a disinfectant / self-cleaning liquid (including but not limited to DMSO, ethanol, isopropanol). Let the coating refill for 24 hours.

[0127] Then, the re-filled coating can trigger liquid secretion and uptake upon illumination. To prevent the liquid from evaporating from the top surface of the coating, a sealing layer can be used. The sealing layer can be an adhesive layer, which can impart the required adhesion to the coating when the coating is in contact with the measurement substrate or the skin. To allow the liquid to be released at the surface of the coating, the adhesive layer should contain a certain amount of pores, i.e., the surface area of the adhesive layer is smaller than the surface area of the coating.

[0128] Example 5

[0129] The polymer coatings produced in Example 3 and Example 4 can be used for medical articles. A schematic diagram is as Figure 1 shown. The catheter needleless connector (NFC) or the lumen or any other medical device can be coated with the liquid crystal polymer. The catheter connector or the lumen coating component materials (such as polyethylene terephthalate (PET), polycarbonate (PC), polyurethane (PU), PTFE, polystyrene, silicone, etc.) can be surface grafted to enhance the adhesion of the LCN coating (list two to three graft types).

[0130] It should be noted that the schematic form of the adaptive responsive materials for the lock / self-cleaning applications with controlled secretion and uptake for medical device applications is not limited to the illustrated embodiments, and any medical device or non-medical device ( Figure 1 , the top plate) that is difficult to clean with standard procedures and requires disinfection or self-cleaning can be of any length and size according to the use. Under ultraviolet irradiation ( Figure 1 , the middle plate), the coating releases the liquid to the surface through the pores on the lumen or catheter surface. Under ultraviolet irradiation, the coating can eject the liquid through the pores of the LCN coating onto the lumen surface or catheter surface. In response to external stimuli (such as light, electric field or temperature), the LCN coating can release and absorb the secreted liquid multiple times, form droplets and establish a liquid layer at the interfacial surface area (Figure 01). Thus, the catheter / lumen surface will be self-cleaned or disinfected ( Figure 1 , the bottom plate). In addition, the polymer substrate can be coated on any medical device, including but not limited to dressings, fixation devices, bandages, etc., which may require multiple on / off operations, so that various medical applications can be examined and treated. Such polymer substrates or coatings can also be applied to various medical devices for purposes such as temporary attachment, drug delivery, self-cleaning, etc.

[0131] Example 6

[0132] The sample cell is composed of two glass slides: one is coated with 3-(trimethoxysilyl)propyl methacrylate to enhance surface adhesion, and the other is coated with a polyimide layer to provide vertical alignment. The coating thickness is controlled by defined spacers. The size of the spacers ranges from 5 to 50 μm. The liquid crystal monomer mixture is filled into the empty sample cell by capillary force in the isotropic phase. After maintaining a constant temperature for 20 minutes, the mixture is cooled to its smectic phase, at which time the mixture polymerizes under ultraviolet irradiation. A cut-off filter that allows light with a wavelength > 400 nm to pass through is used and placed between the sample cell and the ultraviolet light source. After photopolymerization, the glass slides can be removed using a blade. The coating is supported by the glass slides.

[0133] To remove the pore-forming agent, the coating is immersed in a solvent bath for 24 hours. The solvents used include but are not limited to cyclohexane and ethanol. The residual solvent is removed by evaporation at room temperature.

[0134] To break the hydrogen bonds and form polymer salts, the coating is immersed in an alkaline bath. The alkaline solutions used include but are not limited to KOH solutions. The concentration of the KOH solution ranges from 0.05 to 0.5 M. The immersion time ranges from 30 seconds to 60 minutes.

[0135] After the basic treatment, the coating is transferred to a liquid reservoir containing a biocompatible liquid (including but not limited to polyethylene glycol, glycerol, DMSO, water, ethanol, isopropanol or mixtures). The blend is used to reduce the viscosity of the polymer glycol and also reduce the evaporation of the liquid. Let the coating refill for 24 hours.

[0136] Example 7

[0137] The glass plate is coated with 3-(trimethoxysilyl)propyl methacrylate to enhance surface adhesion. The liquid crystal monomer mixture is dissolved in THF. The concentration of the solid in the solution ranges from 20 wt% to 50 wt%. The solution is coated onto the glass plate using a spin coater. The spin coating parameters are: (1) the rotation speed ranges from 300 rpm to 1000 rpm, depending on the solid concentration; (2) the acceleration ranges from 100 rpm / s to 500 rpm / s. After spin coating, the coating is transferred to a heat source (e.g., a heating stage / heating plate) and maintained at a temperature of 90 °C for 5 minutes to evaporate THF. Then, the monomer coating is slowly cooled to its smectic phase. Depending on the composition of the monomer mixture, the temperature of the smectic phase varies from sample to sample. At the temperature of the smectic phase, the sample undergoes photopolymerization under ultraviolet irradiation. A cut-off filter that allows light with a wavelength > 400 nm to pass through is used and placed between the sample cell and the ultraviolet light source.

[0138] To remove the pore former, the coating was immersed in a solvent bath for 24 hours. The solvents used include, but are not limited to, cyclohexane and ethanol. The residual solvent was removed by evaporation at room temperature.

[0139] To break the hydrogen bonds and form polymer salts, the coating was immersed in an alkaline bath. The alkaline solutions used include, but are not limited to, KOH solutions. The concentration of the KOH solution ranges from 0.05 to 0.5 M. The immersion time ranges from 30 seconds to 60 minutes.

[0140] After the basic treatment, the coating was transferred to a liquid reservoir containing a biocompatible liquid (including, but not limited to, polyethylene glycol, DMSO, water, ethanol, isopropanol, or a mixture). The blend was used to reduce the viscosity of the polymer glycol and also to reduce the evaporation of the liquid. The coating was allowed to refill for 24 hours.

[0141] Example 8

[0142] The sample cell consists of two glass slides: one is a flexible polymer film coated with 3-(trimethoxysilyl)propyl methacrylate to enhance surface adhesion; and the other is a glass slide coated with a polyimide layer to provide vertical alignment. In this case, the substrate for supporting the coating is a flexible polymer film, including, but not limited to, polyethylene terephthalate (PET). The PET can be coated with a thin layer of indium tin oxide to change the surface chemistry. The coating thickness is controlled by a defined spacer. The size of the spacer ranges from 5 to 50 μm. The chemicals used to form the polymer coating are the same as those used in 1. The liquid crystal monomer mixture was filled into the empty sample cell by capillary force in the isotropic phase. After 20 minutes of constant temperature, the mixture was cooled to its smectic phase, at which temperature the mixture polymerized under ultraviolet irradiation. A cut-off filter that allows light with a wavelength > 400 nm to pass through was used and placed between the sample cell and the ultraviolet light source. After photopolymerization, the glass slide can be removed using a blade. The coating is supported by the flexible polymer film.

[0143] To remove the pore former, the coating was immersed in a solvent bath for 24 hours. The solvents used include, but are not limited to, cyclohexane and ethanol. The residual solvent was removed by evaporation at room temperature.

[0144] To break the hydrogen bonds and form polymer salts, the coating was immersed in an alkaline bath. The alkaline solutions used include, but are not limited to, KOH solutions. The concentration of the KOH solution ranges from 0.05 to 0.5 M. The immersion time ranges from 30 seconds to 60 minutes.

[0145] After the basic treatment, the coating is transferred to a liquid reservoir containing a biocompatible liquid (including but not limited to polyethylene glycol, DMSO, water, ethanol, isopropanol). The blend is used to reduce the viscosity of the polymer glycol and also reduce the evaporation of the liquid. Let the coating refill for 24 hours.

[0146] Then, the refilled coating can trigger liquid secretion and uptake upon illumination. To prevent the liquid from evaporating from the top surface of the coating, a sealing layer can be used. The sealing layer can be an adhesive layer that can impart the required adhesion to the coating when the coating comes into contact with the measurement substrate or the skin. To allow the liquid to be released at the surface of the coating, the adhesive layer should contain a certain amount of pores, i.e., the surface area of the adhesive layer is smaller than the surface area of the coating.

[0147] Example 9

[0148] A PET flexible film coated with a thin layer of indium tin oxide is treated with a thin layer of 3-(trimethoxysilyl)propyl methacrylate to enhance surface adhesion using a coating technique including but not limited to spin coating, dip coating, and chemical vapor deposition. The liquid crystal monomer mixture is dissolved in THF. The concentration of solids in the solution ranges from 20 wt% to 50 wt%. The solution is coated onto the PET film using a spin coater. The spin coating parameters are: (1) the rotation speed is in the range of 300 rpm to 1000 rpm, depending on the solid concentration; (2) the acceleration is in the range of 100 rpm / s to 500 rpm / s. After spin coating, the coating is transferred to a heating stage at 90 °C for 5 minutes to evaporate THF. Then, the monomer coating is slowly cooled to its smectic phase. Depending on the composition of the monomer mixture, the temperature of the smectic phase varies from sample to sample. At the temperature of the smectic phase, the sample undergoes photopolymerization under ultraviolet irradiation. A cut-off filter that allows light with a wavelength > 400 nm to pass through is used and placed between the sample cell and the ultraviolet light source.

[0149] To remove the pore former, the coating is immersed in a solvent bath for 24 hours. The solvents used include but not limited to cyclohexane and ethanol. The residual solvent is removed by evaporation at room temperature.

[0150] To break the hydrogen bonds and form polymer salts, the coating is immersed in an alkaline bath. The alkaline solutions used include but not limited to KOH solutions. The concentration of the KOH solution is in the range of 0.05 to 0.5 M. The immersion time is in the range of 30 seconds to 60 minutes.

[0151] After the basic treatment, the coating is transferred to a liquid reservoir containing a biocompatible liquid (including but not limited to polyethylene glycol, DMSO, water, ethanol, isopropanol). The blend is used to reduce the viscosity of the polymer glycol and also to reduce the evaporation of the liquid. Let the coating refill for 24 hours.

[0152] Then, the refilled coating can trigger liquid secretion and uptake when illuminated. To prevent the liquid from evaporating from the top surface of the coating, a sealing layer can be used. The sealing layer can be an adhesive layer that can impart the required adhesion to the coating when the coating contacts the measurement substrate or the skin. To allow the liquid to be released at the surface of the coating, the adhesive layer should contain a certain amount of pores, that is, the surface area of the adhesive layer is smaller than the surface area of the coating.

[0153] Example 10

[0154] The coatings prepared in Example 8 and Example 9 can be combined with a substrate and an adhesive in a medical device. Materials for making the adhesive include but are not limited to 2-ethylhexyl acrylate, acrylic acid, isobutyl methacrylate, poly(ethylene glycol) methyl ether methacrylate, or poly(ethylene glycol) diacrylate. The polymer adhesive is synthesized by photopolymerization. More specifically, a low percentage of a photoinitiator is added to the above monomer mixture, and the mixture is polymerized under ultraviolet irradiation for 30 minutes in a nitrogen atmosphere. After photopolymerization, the polymer is impregnated into a solvent to remove the residues of unreacted monomers and photoinitiators. The final polymer adhesive can be safely used on the skin of humans or animals.

[0155] The design of the adhesion tunable polymer material is as Figure 2A and Figure 2B shown. The liquid crystal polymer coating is supported by a flexible PET film. On top of the coating, a pressure-sensitive adhesive layer is coated. The top adhesive can be coated by spin-coating or spraying a mixture of a synthetic adhesive and a solvent. The adhesive layer also acts as a protective layer and a sealing layer. The adhesive layer contains pores with sizes in the range of 5 μm to 2 mm. The thickness of the adhesive layer is in the range of 500 nm to 5 μm. It should be noted that the planar shape of the adhesion tunable liquid secretion polymer material for medical device applications is not limited to the illustrated examples and can adopt any acceptable shape (such as circular, square, rectangular, trapezoidal, etc.) according to the purpose, with no limit on length and size.

[0156] When there is no ultraviolet illumination ( Figure 2A ), at a certain force and a certain tilt angle, the film cannot be peeled off from the measurement substrate. Under ultraviolet illumination ( Figure 2B) The coating releases the liquid to the surface through the pores of the adhesive layer. This results in a decrease in surface adhesion. Therefore, under a certain force and a certain tilt angle, the coating can be easily peeled off.

[0157] Example 11

[0158] The liquid crystal monomer mixture consists of 69 wt% of molecule 1, 3.4 wt% of molecule 2, 1.7 wt% of molecule 3, 5.0 wt% of molecule 4, 20 wt% of molecule 5, and 1 wt% of molecule 6. The chemical structures of molecules 1 to 6 are as Figure 9 shown. The monomers are mixed in THF to form a homogeneous mixture. After the evaporation of THF, the monomer mixture is filled into an empty sample cell at 80 °C, and the sample is kept at 80 °C for 30 minutes. The sample cell is composed of a PET substrate and a glass plate. Then, a layer of 3-(trimethoxysilyl)propyl methacrylate is coated on the PET substrate pre-coated with a thin ITO layer to improve adhesion; and the glass plate is coated with a polyimide layer (SE-5661, Nissan Chemical) to provide vertical alignment. Then the sample is cooled to 30 °C and exposed to ultraviolet light for 1 hour for photopolymerization. The polymerized coating is immersed in a cyclohexane bath for 24 hours to remove the pore-forming agent. Then, the coating without the pore-forming agent is transferred to a KOH solution with a concentration of 0.05 M and immersed for 1 minute. Next, the coating is refilled with DMSO or a blend of DMSO and PEG with a volume ratio in the range of 10 / 90 to 100 / 0.

[0159] Example 12

[0160] A different liquid crystal monomer mixture consists of 49 wt% of molecule 1, 5.6 wt% of molecule 2, 2.8 wt% of molecule 3, 8.3 wt% of molecule 4, 33.3 wt% of molecule 5, and 2 wt% of molecule 6. The chemical structures of molecules 1 to 6 are as Figure 10 shown. The monomers are mixed with THF to form a homogeneous mixture with a concentration of 50 wt. After the evaporation of THF, the monomer mixture is spin-coated onto the ITO-PET film. The ITO-PET plate is coated with an adhesion-improving layer of 3-(trimethoxysilyl)propyl methacrylate. It is performed at a spin-coating speed of 500 rpm with an acceleration of 200 rpm / s. After spin-coating, the monomer coating is heated to 90 °C and the sample is kept for 10 minutes to evaporate the solvent. Then, the sample is cooled to 52 °C and exposed to ultraviolet light for 1 hour for photopolymerization. The polymerized coating is immersed in a cyclohexane bath for 24 hours to remove the pore-forming agent. Then, the coating without the pore-forming agent is transferred to a KOH solution with a concentration of 0.1 M and immersed for 5 minutes. Next, the coating is refilled with a blend of PEG and water with a volume ratio of 10 / 90 to 100 / 0.

[0161] When a polymeric material is applied to the skin surface of a medical mannequin, the coating adheres firmly to the surface even when a certain force is applied, prior to liquid release. When the coating is exposed to ultraviolet light with a dose of 0.4 J / cm 2 , under an external force of 30° parallel to the surface of the medical mannequin, the coating easily detaches from the medical mannequin. When the polymeric material is applied to a glass substrate, the coating adheres firmly to the glass even when a certain force is applied, prior to liquid release. When the coating is exposed to ultraviolet light with a dose of 0.5 J / cm 2 , under an external force of 180° parallel to the surface of the substrate, the coating easily peels off from the substrate.

[0162] Example 13

[0163] Another trigger factor for inducing liquid secretion and uptake is an electric field. Different from the light-driven system, the electro-driven liquid secretion is based on liquid diffusion, electrothermal effect, and the deformation of a liquid crystal polymer network under the influence of a radio frequency (RF) alternating electric field. When the radio frequency field is turned off, liquid uptake occurs, which is induced by the combined action of capillary force and polymer elasticity. In this case, the chemical properties of the liquid crystal polymer coating must be modified. Figure 11 Examples of liquid crystal compositions are given in []. Molecular 1 is used as a pore former but also for forming a smectic phase structure. Liquid crystal diacrylate 1 and monoacrylate 2 are used to form a liquid crystal polymer network. Molecular 4 is a benzoic acid derivative, which is used to increase the polymer polarity. Photoinitiator 5 is used to generate free radicals and initiate polymerization.

[0164] Example 14

[0165] The liquid crystal polymer coating can be fabricated by one of two alternative methods: the sample cell method or the spin coating method. The explanation of each method is as follows:

[0166] Sample cell method. The sample cell is composed of two glass slides: one is a flexible interdigitated electrode (IDE) substrate coated with indium tin oxide (ITO), and this substrate is coated with 3-(trimethoxysilyl)propyl methacrylate to enhance surface adhesion; the other is a glass slide coated with a polyimide layer to provide vertical alignment. In this case, the substrate for supporting the coating is a flexible IDE polymer film, including but not limited to polyethylene terephthalate (PET). The coating thickness is controlled by a defined spacer. The size range of the spacer is 5 to 50 μm. The liquid crystal monomer mixture is filled into the empty sample cell by capillary force in the isotropic phase. After 20 minutes of constant temperature, the mixture is cooled to its smectic phase, and at this temperature, the mixture undergoes polymerization under ultraviolet irradiation. After photopolymerization, the glass slide can be removed using a blade. The coating is supported by the flexible IDE substrate.

[0167] Spin coating method . The PET flexible film coated with a thin layer of indium tin oxide is treated with a thin layer of 3-(trimethoxysilyl)propyl methacrylate using a coating technique, including but not limited to spin coating, dip coating, and chemical vapor deposition, to enhance surface adhesion. The liquid crystal monomer mixture is dissolved in THF. The concentration of the solid in the solution is in the range of 20 wt% to 50 wt%. The solution is coated onto the PET substrate using a spin coater. The spin coating parameters are: (1) the rotation speed is in the range of 300 rpm to 1000 rpm, depending on the solid concentration; (2) the acceleration is in the range of 100 rpm / s to 500 rpm / s. After spin coating, the coating is transferred to a heating stage at 90 °C for 5 minutes to evaporate THF. Then, the monomer coating is slowly cooled to its smectic phase. Depending on the composition of the monomer mixture, the temperature of the smectic phase varies from sample to sample. At the temperature of the smectic phase, the sample undergoes photopolymerization under ultraviolet irradiation using an ultraviolet LED lamp.

[0168] To remove the pore former, the coating is immersed in a solvent bath for 24 hours. The solvents used include but not limited to cyclohexane and ethanol. The residual solvent is removed by evaporation at room temperature. To break the hydrogen bonds and form polymer salts, the coating is immersed in an alkaline bath. The alkaline solutions used include but not limited to KOH solutions. The concentration of the KOH solution is in the range of 0.05 to 0.5 M. The immersion time is in the range of 30 seconds to 60 minutes. After the basic treatment, the coating is transferred to a liquid reservoir containing a self-cleaning or disinfecting solution (including but not limited to DMSO, ethanol, isopropanol, etc.). The blend is used to reduce the viscosity of the polymer glycol and also reduce the evaporation of the liquid. For the initial coating, the coating filling time is 24 hours. It is expected that optimization will shorten this time.

[0169] Example 15

[0170] The liquid crystal polymer coating is fabricated by one of two alternative methods: the sample cell method or the spin coating method. An explanation of each method is as follows:

[0171] Sample cell method . The sample cell consists of two glass slides: one with interdigitated electrodes (IDE) coated with 3-(trimethoxysilyl)propyl methacrylate to enhance surface adhesion, and the other a plain glass coated with a polyimide layer to provide vertical alignment. The electrodes include, but are not limited to, indium tin oxide (ITO). The coating thickness is controlled by defined spacers. The size of the spacers ranges from 5 to 50 μm. The liquid crystal monomer mixture is filled into the empty sample cell by capillary force in the isotropic phase. After maintaining a constant temperature for 20 minutes, the mixture is cooled to its smectic phase, at which temperature the mixture polymerizes under ultraviolet irradiation. After 1 hour of photopolymerization, the glass slides can be removed using a blade. Finally, the coating is attached to the IDE glass substrate.

[0172] Spin coating method . The IDE glass plate is coated with 3-(trimethoxysilyl)propyl methacrylate to enhance surface adhesion. The electrodes include, but are not limited to, ITO. The liquid crystal monomer mixture is dissolved in THF. The concentration of solids in the solution ranges from 20 wt% to 50 wt%. The solution is coated onto the ITO glass plate using a spin coater. The spin coating parameters are: (1) the rotation speed ranges from 300 rpm to 1000 rpm, depending on the solid concentration; (2) the acceleration ranges from 100 rpm / s to 500 rpm / s. After spin coating, the coating is transferred to a heating stage maintained at 90 °C for 5 minutes to evaporate the THF. Then, the monomer coating is slowly cooled to its smectic phase. Depending on the composition of the monomer mixture, the temperature of the smectic phase varies from sample to sample. At the temperature of the smectic phase, the sample undergoes photopolymerization under ultraviolet irradiation using an ultraviolet LED lamp.

[0173] After 1 hour of photopolymerization, the coating is immersed in a solvent bath for 24 hours to remove the pore former. The solvents used include, but are not limited to, cyclohexane and ethanol. The residual solvent is removed by evaporation at room temperature. To break the hydrogen bonds and form polymer salts, the coating is immersed in an alkaline bath. The alkaline solutions used include, but are not limited to, KOH solutions. The concentration of the KOH solution ranges from 0.05 to 0.5 M. The immersion time ranges from 30 seconds to 60 minutes, depending on the concentration of the benzoic acid derivative. After the basic treatment, the coating is transferred to a liquid reservoir containing a biocompatible liquid (including, but not limited to, polymer glycol, DMSO, water, ethanol, isopropanol, or a mixture). Using the mixture can not only reduce the viscosity of the polymer glycol but also reduce the evaporation of the liquid. Let the coating refill for 24 hours.

[0174] Example 16

[0175] The liquid crystal polymer coating is fabricated by one of two alternative methods: the sample cell method or the spin coating method. An explanation of each method is as follows:

[0176] Sample cell method . The sample cell consists of two glass slides: one is a flexible IDE substrate coated with ITO, which is coated with 3-(trimethoxysilyl)propyl methacrylate to enhance surface adhesion; the other is a glass slide coated with a polyimide layer to provide vertical alignment. In this case, the substrate for supporting the coating is a flexible IDE polymer film, including but not limited to PET. The coating thickness is controlled by defined spacers. The size range of the spacers is 5 to 50 μm. The liquid crystal monomer mixture is filled into the empty sample cell by capillary force in the isotropic phase. After 20 minutes of constant temperature, the mixture is cooled to its smectic phase, at which temperature the mixture polymerizes under ultraviolet irradiation. After photopolymerization, the glass slide can be removed using a blade. The coating is supported by the flexible IDE substrate.

[0177] Spin coating method . A PET flexible film coated with a thin layer of indium tin oxide is treated with a thin layer of 3-(trimethoxysilyl)propyl methacrylate using a coating technique, including but not limited to spin coating, dip coating, and chemical vapor deposition, to enhance surface adhesion. The liquid crystal monomer mixture is dissolved in THF. The concentration of solids in the solution ranges from 20 wt% to 50 wt%. The solution is coated onto the PET substrate using a spin coater. The spin coating parameters are: (1) the rotation speed ranges from 300 rpm to 1000 rpm, depending on the solid concentration; (2) the acceleration ranges from 100 rpm / s to 500 rpm / s. After spin coating, the coating is transferred to a hot plate / heated plate at 90 °C for 5 minutes to evaporate THF. Then, the monomer coating is slowly cooled to its smectic phase. Depending on the composition of the monomer mixture, the temperature of the smectic phase varies from sample to sample. At the temperature of the smectic phase, the sample undergoes photopolymerization under ultraviolet irradiation using an ultraviolet LED lamp.

[0178] To remove the pore former, the coating was immersed in a solvent bath for 24 hours. The solvents used include, but are not limited to, cyclohexane and ethanol. The residual solvent was removed by evaporation at room temperature. To break the hydrogen bonds and form polymer salts, the coating was immersed in an alkaline bath. The alkaline solutions used include, but are not limited to, KOH solutions. The concentration of the KOH solution ranges from 0.05 to 0.5 M. The immersion time ranges from 30 seconds to 60 minutes. After the basic treatment, the coating was transferred to a liquid reservoir containing a biocompatible liquid (including, but not limited to, polyethylene glycol, DMSO, water, ethanol, isopropanol). Using the mixture can not only reduce the viscosity of the polymer glycol, but also reduce the evaporation of the liquid. The coating was refilled for 24 hours. A variety of solvents can be used, including DMSO, ethanol, isopropanol, including mixtures with larger molecules. The demonstration sample was made by blending polyethylene glycol with other smaller molecules, providing opportunities for the selection of drugs and other active agents for secretion and uptake.

[0179] Although the present disclosure has been described in detail for purposes of illustration based on the presently considered to be the most practical and preferred embodiments or aspects, it is to be understood that such detail is solely for that purpose and that the present disclosure is not limited to the disclosed embodiments or aspects, but rather, the present disclosure is intended to cover modifications and equivalent arrangements within the spirit and scope of the appended claims. For example, it is to be understood that the present disclosure contemplates that, to the extent possible, one or more features of any embodiment may be combined with one or more features of any other embodiment.

Claims

1. A medical article, the medical article comprising: A substrate; A polymer coating disposed on the substrate, the coating comprising at least one liquid crystal acrylate and a responsive component; And A biocompatible liquid contained within the polymer coating.

2. The medical article according to claim 1, wherein, The polymer coating is anisotropic.

3. The medical article according to claim 1, wherein, The liquid crystal acrylate comprises a liquid crystal diacrylate and a liquid crystal monoacrylate.

4. The medical article according to claim 3, wherein, The liquid crystal diacrylate has the following structure:

5. The medical article according to claim 3, wherein, The liquid crystal diacrylate has the following structure:

6. The medical article according to claim 3, wherein, The liquid crystal monoacrylate has the following structure:

7. The medical article according to claim 3, wherein, The liquid crystal monoacrylate has the following structure:

8. The medical article according to claim 3, wherein, The responsive component is a photo-responsive component comprising a photo-responsive diacrylate.

9. The medical article according to claim 8, wherein, The photo-responsive component comprises an azobenzene moiety.

10. The medical article according to claim 8, wherein, The photo-responsive diacrylate has the following structure:

11. The medical article according to claim 1, wherein, The polymer coating further comprises a carboxylic acid.

12. The medical article according to claim 11, wherein, The carboxylic acid is benzoic acid.

13. The medical article according to claim 1, wherein, The polymer coating further comprises a photoinitiator.

14. The medical article according to claim 13, wherein, The photoinitiator contains phosphorus.

15. The medical article according to claim 13, wherein, The photoinitiator has the following structure:

16. The medical article according to claim 1, wherein, The polymer coating includes a plurality of pores configured to contain a liquid therein.

17. The medical article according to claim 16, wherein, The biocompatible liquid is contained within the pores of the polymer coating.

18. The medical article according to claim 17, wherein, The biocompatible liquid comprises one or more of the following: polyethylene glycol, water, saline, dimethyl sulfoxide (DMSO), ethanol, isopropanol, and chlorhexidine gluconate.

19. The medical article according to claim 17, wherein, The polymer coating is configured to exhibit a first orientation and a second orientation, in the first orientation the biocompatible liquid is contained within the pores, and in the second orientation the biocompatible liquid is discharged from the pores.

20. The medical article according to claim 19, wherein, The polymer coating is configured to exhibit the first orientation when exposed to visible light and the second orientation when exposed to ultraviolet light.

21. The medical article according to claim 1, wherein, The substrate comprises a catheter, a catheter adapter, a luer connector, and / or a needleless connector (NFC), and wherein the polymer coating is disposed on the inner surface of the medical article.

22. The medical article according to claim 1, wherein, The substrate is optionally flexible, and the medical article includes an adhesive layer disposed on the polymer coating such that the polymer coating is disposed between the adhesive and the flexible substrate.

23. The medical article according to claim 22, wherein, The adhesive layer includes a plurality of pores.

24. The medical article according to claim 22, wherein, The adhesive layer comprises one or more of the following: 2-ethylhexyl acrylate, acrylic acid, isobutyl methacrylate, poly(ethylene glycol) methyl ether methacrylate, and poly(ethylene glycol) diacrylate.

25. The medical article according to claim 22, wherein, The substrate comprises one or more of the following: polyester, polyurethane, olefin, polyamide, acrylic polymer, ethylene-vinyl acetate, polyether, and derivatives thereof.

26. A method of manufacturing a medical article having a polymer coating disposed on its surface, the method comprising: Mixing at least one liquid crystal acrylate, a responsive component, a carboxylic acid, a pore former, and a photoinitiator in a first solvent to provide a liquid monomer mixture; Applying the liquid monomer mixture to a substrate; Removing the solvent to provide a substrate having the monomer mixture thereon; Polymerizing the monomer mixture to provide a substrate having a polymer coating thereon; Immerse the substrate having the polymer coating into a second solvent to remove the pore former, thereby providing a substrate having a porous polymer coating; Immerse the substrate having the porous polymer coating into an alkaline solution; And Immerse the porous polymer coating into a biocompatible liquid, thereby providing a substrate having a porous polymer coating loaded with the biocompatible liquid.

27. The method according to claim 26, wherein, Apply the liquid monomer mixture to the substrate by the sample cell method or the spin coating method.

28. The method according to claim 26, wherein, The first solvent is tetrahydrofuran (THF).

29. The method according to claim 26, wherein The second solvent is cyclohexane and / or ethanol.

30. The method according to claim 26, wherein, The alkaline solution includes potassium hydroxide (KOH).

31. The method according to claim 26, wherein The liquid crystal acrylate includes liquid crystal diacrylate and liquid crystal monoacrylate.

32. The method according to claim 31, wherein, The liquid crystal diacrylate has the following structure:

33. The method according to claim 31, wherein, The liquid crystal diacrylate has the following structure:

34. The method according to claim 31, wherein The liquid crystal monoacrylate has the following structure:

35. The method according to claim 31, wherein, The liquid crystal monoacrylate has the following structure:

36. The method according to claim 31, wherein, The responsive component is a photo-responsive diacrylate.

37. The method according to claim 36, wherein, The photo-responsive component includes an azobenzene moiety.

38. The method according to claim 36, wherein, The photo-responsive diacrylate has the following structure:

39. The method according to claim 31, wherein The carboxylic acid is benzoic acid.

40. The method according to claim 31, wherein, The photoinitiator contains phosphorus.

41. The method according to claim 31, wherein, The photoinitiator type has the following structure:

42. The method according to claim 31, wherein, The biocompatible liquid includes one or more of the following: polyethylene glycol, water, saline, dimethyl sulfoxide (DMSO), ethanol, isopropanol, and chlorhexidine gluconate.

43. A method of using a medical article, the medical article comprising: A substrate; a polymer coating disposed on the substrate and including at least one liquid crystal acrylate and a responsive component, the polymer coating including a plurality of pores and a biocompatible liquid, the polymer coating configured to exhibit a first orientation and a second orientation, in the first orientation the biocompatible liquid is contained within the pores, and in the second orientation the biocompatible liquid is discharged from the pores, the method including exposing the medical article to ultraviolet light, thereby causing the polymer material to exhibit the second orientation and discharge the biocompatible liquid from the polymer coating.

44. The method according to claim 43, wherein, The biocompatible liquid includes one or more of the following: polyethylene glycol, water, saline, dimethyl sulfoxide (DMSO), ethanol, isopropanol, and chlorhexidine gluconate.

45. The method according to claim 43, wherein, The medical article includes a catheter, a catheter adapter, a luer connector, and / or a needleless connector (NFC), and wherein the polymer coating is disposed on an inner surface of the medical article.

46. The method according to claim 43, wherein, The substrate is flexible, and the medical article includes an adhesive layer disposed on the polymer coating such that the polymer coating is disposed between the adhesive and the flexible substrate.

47. The method according to claim 46, wherein, The adhesive layer includes a plurality of pores.

48. The method according to claim 46, wherein, The adhesive layer includes one or more of the following: 2-ethylhexyl acrylate, acrylic acid, isobutyl methacrylate, poly(ethylene glycol) methyl ether methacrylate, and poly(ethylene glycol) diacrylate.

49. The method according to claim 46, wherein The substrate includes one or more of the following: polyester, polyurethane, olefin, polyamide, acrylic polymer, ethylene-vinyl acetate, polyether, and their derivatives.

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