WO2025012855A1

WO2025012855A1 - Polymeric hydrogels with dual cooling and heating functionalities

Info

Publication number: WO2025012855A1
Application number: PCT/IB2024/056766
Authority: WO
Inventors: Somaye Akbari; Zeinab GHORBANI AMODIZAJ; Mohammad Hassan KANANI-JAZI; Mahya SEMNANIREZA; Mehdi AKBARI
Original assignee: Individual
Current assignee: Individual
Priority date: 2023-07-11
Filing date: 2024-07-11
Publication date: 2025-01-16
Anticipated expiration: 2026-01-11
Also published as: WO2025012855A4

Abstract

The present disclosure relates to polymeric hydrogels with dual cooling and heating functionalities and methods for their preparation. The hydrogels exhibit antibacterial and antifungal properties and are fabricated using a combination of amine-terminated dendritic polymers, boric acid, borax, and a water-soluble polymer. This results in a versatile hydrogel with enhanced dimensional stability, suitable for applications such as pads, transdermal patches, ice-cold gel, and deodorant rolls.

Description

Polymeric Hydrogels with Dual Cooling and Heating Functionalities

Cross-Reference to Related Disclosure

[0001 ] This disclosure claims the benefit ofpriority from the granted IR patent application 140250140003002652, filed on July 11 , 2023, entitled “Polymeric Hydrogels with Dual Cooling and Heating Functionalities” which is incorporated herein by reference in their entirety.

Technical Field

[0002] This disclosure generally relates to the field of advanced polymeric materials, specifically polymeric hydrogels with dual cooling and heating functionalities, and methods for their preparation. More particularly, the disclosure relates to polymeric hydrogels that not only possess dual cooling and heating functionalities but also exhibit antibacterial and antifungal properties. The disclosure also includes a method for fabricating these cross-linked polymeric hydrogels, which involves the interaction of amine-terminated dendritic groups, boric acid, borax, and a water- soluble polymer.

Background Art

[0003] Hydrogels are three-dimensional cross-linked polymer networks capable of absorbing water or biofluids. These compounds can absorb large quantities of water without dissolving. Hydrogels generally have a stimulating effect on tissue and are superior to other materials in terms of permeability. With increasing water content, these compounds exhibit improved antithrombotic activity.

[0004] Depending on the type of cross-linking, hydrogels can be categorized into physical and chemical hydrogels.

[0005] A physical hydrogel is formed when the macromolecules of a water-soluble polymer are linked together by physical interactions such as electrostatic attraction, hydrogen bonding, hydrophobic effects, van der Waals forces, or the formation of crystalline domains and chain entanglements. Examples of physical hydrogels include gelatin gel, calcium alginate gel, and polyvinyl alcohol. The formation of physical hydrogels is usually a reversible process. The hydrogel can be dissolved by changing environmental conditions such as pH, ionic strength, temperature, and type of solvent.

[0006] In contrast, a chemical hydrogel is formed when the macromolecules of a water- soluble polymer are irreversibly linked together by covalent bonds. The most common methods for fabricating chemical hydrogels are: (1 ) polymerization of a hydrophilic monomer in the presence of a cross-linking agent; and (2) cross-linking of pre-formed macromolecules to create water-soluble polymers. One issue with the first approach is that it typically involves unsaturated monomers (e.g., in free radical polymerization), which are generally harmful or even toxic.

[0007] Some water-soluble polymers can be easily cross-linked by reacting with low- molecular-weight cross-linkers. An example is the use of glutaraldehyde to crosslink hydroxyl groups and amine-containing polymers such as polyvinyl alcohol, cellulose ether, chitosan, guar gum, and gelatin. However, due to the toxicity of glutaraldehyde compounds, their use is not recommended, especially for medical products.

[0008] While hydrogels generally have beneficial properties, they tend to shrink over time by releasing trapped water. This results in poor formulation stability in terms of strength and dimensional stability. Furthermore, hydrogels may serve as a favorable medium for the growth of bacteria and fungi, leading to potential skin infections.

[0009] The aforementioned methods have several drawbacks, including timeconsuming processes, hydrogel shrinkage, and dimensional instability. Therefore, there is a need for a reusable, convenient, and dimensionally stable formulation and method for producing hydrogels.

Summary of Invention

[0010] This summary is intended to provide an overview of the subject matter of the present disclosure, and is not intended to identify essential elements or key elements of the subject matter, nor is it intended to be used to determine the scope of the claimed implementations. The proper scope of the present disclosure may be ascertained from the claims set forth below in view of the detailed description below and the drawings. [0011 ] In one general aspect, the present disclosure describes a method for fabricating a polymeric hydrogel with dual cooling and heating functionalities. The method may include steps of preparing a polymer solution by dissolving a water-soluble polymer in water with continuous stirring; preparing a cross-linking solution by dissolving at least one cross-linker in water; forming a reaction mixture by adding the crosslinking solution dropwise to the polymer solution; preparing a co-cross-linking solution by dissolving at least one dendritic polymer having amine-terminated groups in water; and obtaining the polymeric hydrogel by mixing the co-cross- linking solution with the reaction mixture.

[0012] The above general aspect may have one or more of the following features. According to one implementation, the water-soluble polymer may include at least one of polyvinyl alcohol (PVA), polyacrylic acid (PAA), polyvinylpyrrolidone (PVP), carbomer, and polyacrylamide (PAAM). In some other implementations, preparing a polymer solution may include dissolving the water-soluble polymer with at least one of PVA, PAA, PVP, carbomer, and PAAM in water. The concentration of the polymer solution may include between 5 wt.% and 20 wt.% of the weight of the polymeric hydrogel. In some exemplary implementations, preparing a polymer solution may include dissolving a mixture of the water-soluble polymer and a water- soluble additive polymer in water. The water-soluble polymer may be either PVA or carbomer, while the water-soluble additive polymer may include at least one of PVP, starch, or combinations thereof. The concentration of the additive polymer may include between 2 wt.% and 10 wt.% of the weight of the water-soluble polymer.

[0013] In some implementations, preparing the cross-linking solution may include dissolving at least one of boric acid or borax in water. In addition, in some examples, preparing the cross-linking solution may include dissolving a mixture of boric acid and borax in water, with a boric acid to borax ratio of between about 1 and 1 .5. In an exemplary implementation, the concentration of the boric acid, and borax may include between 0.01 wt.% and 10 wt.% of the weight of the water- soluble polymer.

[0014] In some implementations, preparing the co-cross-linking solution may include the steps of dissolving dendritic polymer having amine-terminated groups in water to obtain a dendritic polymer solution; adding a plurality of guest compounds to the dendritic polymer solution; and continuously stirring to obtain the co-cross-linking solution. In some cases, the dendritic polymer having amine-terminated groups may include at least one of dendrimer polymers, hyperbranched polymers, and dendriGems. In another implementation, preparing the co-cross-linking solution may include dissolving dendrimer polymer having amine-terminated groups in water. The dendrimer polymer having amine-terminated groups may include at least one of polyamidoamine, polypropylene imine, and polyethylene imine. The dendritic polymer has a concentration between 2 wt.% and 15 wt.% of the weight of the water-soluble polymer. The guest compounds have a concentration between 1 wt.% and 20 wt.% of the weight of the water-soluble polymer. An exemplary guest compound may include at least one of softening agent, dermal absorption drugs, and transdermal drugs.

[0015] In another general aspect, the present disclosure describes a polymeric hydrogel with dual cooling and heating functionalities for use in manufacturing a pad, ice-cold gel, transdermal pad, patch, and deodorant roll. The polymeric hydrogel includes a water-soluble polymer and a cross-linker based on dendritic polymer having amine-terminated groups, boric acid, and borax.

[0016] The above general aspect may have one or more of the following features: for example, the polymeric hydrogel with dual cooling and heating functionalities may include, a water-soluble polymer; a cross-linker based on a mixture of boric acid, and borax; a co-cross-linker based on dendritic polymer having amine-terminated groups; and a plurality of guest compounds uniformly dispersed in the polymeric hydrogel.

[0017] In some implementations, the water-soluble polymer may include at least one of PVA, PAA, PVP, carbomer, and PAAM. In another implementation, the dendritic polymer having amine-terminated groups may include at least one of dendrimer polymers, hyperbranched polymers, and dendriGems. The guest compounds may include at least one of softening agents, dermal absorption drugs, and transdermal drugs. The guest compounds have a concentration between 1 wt.% and 20 wt.% of the weight of the water-soluble polymer. [0018] In another general aspect, the present disclosure describes an exemplary cooling/heating pad including a layer of a polymeric hydrogel coated on a substrate.

[0019] The above general aspect may have one or more of the following features: for example, the polymeric hydrogel formulation may include a water-soluble polymer; a cross-linker based on a mixture of boric acid, and borax; a co-cross-linker based on dendritic polymer having amine-terminated groups; and a plurality of guest compounds with a concentration between about 1 % and about 20% of the weight of the water-soluble polymer dispersed in a polymeric hydrogel.

[0020] The term "polymeric hydrogel" in this disclosure refers to both the method of fabrication and the formulation of the hydrogel. Terms such as pad, ice-cold gel, transdermal pad, patch, and deodorant roll refer to physical products that may incorporate the polymeric hydrogel described herein. These products can take various forms, including but not limited to sheets, pads, films, or other hydrogel supports.

[0021 ] Other exemplary systems, methods, features, and advantages of the implementations will be or will become, apparent to one of ordinary skill in the art upon examination of the following figures and detailed description. It is intended that all such additional systems, methods, features, and advantages be included within this description and this summary, be within the scope of the implementations and be protected by the claims herein.

Technical Problem

[0022] The technical problem addressed by the present disclosure involves the limitations of existing polymeric hydrogels used in cooling and heating applications. Conventional hydrogels often suffer from insufficient mechanical strength, poor dimensional stability and limited functionality, which limits their effectiveness and versatility. For example, many hydrogels tend to shrink or lose their shape over time, affecting their performance and durability. In addition, these hydrogels typically provide either cooling or warming effects, but not both, so separate products must be used for different therapeutic needs. This lack of multifunctionality leads to additional inconvenience and cost for users. Furthermore, conventional hydrogels may not have inherent antibacterial or antifungal properties, making them less suitable for medical and personal care applications where hygiene is important. These shortcomings must be addressed to improve the reusability, reliability, and overall efficacy of polymeric hydrogels in various applications.

Solution to Problem

[0023] The solution of the present disclosure is to develop a method and formulate a new type of polymeric hydrogel that overcomes the limitations of conventional hydrogels. The present disclosure describes a method for fabricating polymeric hydrogels that exhibit dual cooling and heating functionalities, while also possessing antibacterial and antifungal properties. These hydrogels further demonstrate host-guest interaction capabilities. This is achieved by incorporating amine-terminated dendritic groups, boric acid, borax, and a water-soluble polymer into the hydrogel formulation.

Advantageous Effects of Invention

[0024] The polymeric hydrogels disclosed in this disclosure exhibit significant advantageous effects. Firstly, the dual cooling and heating functionalities of these hydrogels make them versatile for various applications, such as medical pads, transdermal drug delivery systems, and personal care products. This dual functionality enhances user comfort and provides therapeutic benefits by covering both cooling and heating needs in a single material. In addition, the hydrogels exhibit excellent dimensional stability, significantly reducing shrinkage and maintaining structural integrity over time. Furthermore, these hydrogel pads are reusable, which enhances their practicality. This stability is crucial for ensuring consistent performance and reliability in various applications.

[0025] Moreover, the polymeric hydrogels disclosed possess antibacterial and antifungal properties, which are highly beneficial for medical and personal care applications. These properties help prevent infections and promote better hygiene, making the hydrogels suitable for use in wound care and skin contact products. The disclosed fabrication method is both biocompatible and efficient, utilizing nontoxic cross-linking agents such as boric acid and borax, as well as dendritic polymers with amine-terminated groups. This approach not only enhances the safety and biocompatibility of the hydrogels but also simplifies the production process, making it scalable for industrial applications.

Brief Description of Drawings

[0026] The drawing figures depict one or more implementations in accord with the present teachings, by way of example only, not by way of limitation. In the figures, like reference numerals refer to the same or similar elements.

[0027] FIG. 1A illustrates a flowchart of an exemplary method for fabricating a polymeric hydrogel , consistent with one or more exemplary embodiments of the present disclosure.

[0028] FIG. 1 B illustrates a flowchart of an exemplorary method for preparing a co- cross-linking solution containing amine-terminated dendritic polymer, consistent with one or more exemplary embodiments of the present disclosure.

[0029] FIG. 2 illustrates a general overview of an exemplary cooling/heating pad including the hydrogel layer, substrate, and plastic cover, consistent with one or more exemplary embodiments of the present disclosure.

[0030] FIG. 3 presents a Fourier Transform Infrared Spectroscopy (FTIR) spectra comparing the second-generation PAMAM dendrimer, the PVA/PAMAM -boric acid-borax hydrogel, and the PVA/boric acid hydrogel, highlighting key vibrational peaks and their significance, consistent with one or more exemplary embodiments of the present disclosure.

Description of Embodiments

[0031 ] In the following detailed description, numerous specific details are set forth by way of examples in order to provide a thorough understanding of the relevant teachings. However, it should be apparent that the present teachings may be practiced without such details. In other instances, well-known methods, procedures, components, and/or circuitry have been described at a relatively high level, without detail, in order to avoid unnecessarily obscuring aspects of the present teachings.

[0032] The following detailed description is presented to enable a person skilled in the art to make and use the methods and devices disclosed in exemplary embodiments of the present disclosure. For purposes of explanation, specific nomenclature is set forth to provide a thorough understanding of the present disclosure. However, it will be apparent to one skilled in the art that these specific details are not required to practice the disclosed exemplary embodiments. Descriptions of specific exemplary embodiments are provided only as representative examples. Various modifications to the exemplary implementations will be readily apparent to one skilled in the art, and the general principles defined herein may be applied to other implementations and applications without departing from the scope of the present disclosure. The present disclosure is not intended to be limited to the implementations shown but is to be accorded the widest possible scope consistent with the principles and features disclosed herein.

[0033] FIG. 1A illustrates a flowchart of an implementation of a method for fabricating polymeric hydrogel based amine-terminated dendritic groups. The method 100 may include a step 110 of preparing a polymer solution by dissolving a water- soluble polymer in water and continuously stirring; a step 120 of preparing a crosslinking solution by dissolving at least one cross-linker in water, wherein the crosslinker includes boric acid and borax; a step 130 of forming a reaction mixture by adding the cross-linking solution dropwise to the polymer solution; a step 140 of preparing a co-cross-linking solution by dissolving at least one dendritic polymer having amine-terminated groups in water; and a step 150 of obtaining the polymeric hydrogel by mixing the co-cross-linking solution with the reaction mixture.

[0034] Referring to FIG. 1A, according to one or more implementations, the step 110 of preparing the polymer solution may include dissolving a water-soluble polymer in water with continuous stirring. Furthermore, in one implementation, dissolving a water-soluble polymer in water may include dissolving at least one of PVA, PAA, PVP, carbomer, and PAAM in water.

[0035] Referring next to step 120, in some implementations, the preparation of the cross-linking solution may include dissolving the cross-linker including boric acid or borax in the water. In one implementation, preparation of the cross-linking solution may include dissolving a mixture of the boric acid and borax, with a boric acid to borax ratio of between about 1 and 1 .5. [0036] With respect to step 130, in some implementations, forming the reaction mixture may include adding the cross-linking solution dropwise to the polymer solution while being stirred by a stirrer such as a mechanical stirrer, a sonicator, or other similar homogenizers. In one implementation, reacting the water-soluble polymer with a first cross-linking solution may include forming chemical bonds between borate ions from borax with the hydroxyl groups (OH) present on the water-soluble polymer like PVA. This interaction leads to the formation of reversible ester bonds between borate ions and PVA.

[0037] Referring next to step 140, in some implementations, preparing of co-cross- linking solution containing a dendritic polymer having amine-terminated and a plurality of guest compounds by chemically or physically reacting the amine- terminated dendritic polymer with guest compounds. In one implementation, functional groups of dendritic groups, such as the amine-terminated dendritic groups of a polyamidoamine (PAMAM) dendritic polymer, can act as reactive sites capable of attracting and binding to guest molecules of interest. The hollow spaces between the branches of the dendritic polymer, including the extended branches of a PAMAM dendritic polymer, can serve as cages or spaces where guest molecules of interest may be enclosed or encapsulated.

[0038] Details regarding step 140 are illustrated in FIG. 1 B. In detail, FIG. 1 B illustrates a flowchart of an implementation of a method for preparation of the co-cross-linking solution, consistent with one or more implementations of the present disclosure.

[0039] Referring to FIG. 1 B, according to one or more implementations, the method of preparation of co-cross-linking 140 may include a step 141 of preparing the dendritic polymer solution by dissolving at least one dendritic polymer having amine-terminated groups in water; a step 142 of adding a plurality of guest compounds to the dendritic polymer solution; and a step 143 of continuously stirring to obtain the co-cross-linking solution.

[0040] Referring to step 141 , in some implementations, preparing the dendritic polymer solution may include dissolving at least one dendritic polymer having amine- terminated groups including at least one of dendrimer polymers, hyperbranched polymers, or dendriGems in water. [0041 ] Dendritic polymers are artificial macromolecules characterized by tree-like topological structures, highly branched arrangements with great regularity, empty spaces between the branches, compact shapes, and numerous reactive end groups. As used herein, an exemplary highly branched structure refers to a macromolecule with extensive branching originating from a core region. Examples of highly branched dendritic macromolecules include, but are not limited to, dendrimers, hyperbranched polymers, dendrigraft polymers, core-shell dendrimers, and dendriGem.

[0042] An exemplary dendrimer includes a core, hyperbranched arms extending from the core with repeated units, and surface functional groups. These surface functional groups are located on the outermost layer of the dendrimer in a multivalent fashion and significantly influence the dendrimer's physical and chemical properties. Due to the abundance of hollow spaces between interior branches, the dendritic structure can host a wide variety of nonpolar or charged guest molecules in its hollow spaces or pockets through hydrophobic or hydrogen- bond interactions. Additionally, the abundance of surface functional groups allows the dendritic structure to host a variety of nonpolar or charged guest molecules on its surface through electrostatic interactions.

[0043] A gem ini surfactant may include two monomeric surfactant molecules that may be covalently linked by a spacer. Two polar head groups of the aforementioned monomeric surfactant molecules may be cationic, anionic, or nonionic. For example, double quaternary ammonium salts are among cationic gemini surfactants. These polar head groups may determine the classification and properties of surfactants. Gemini surfactant could be attached to the surface of dendrimers or it could be utilized for the core in the dendrimer synthesis to make dendriGem. In both cases, the functionality and activity of dendriGem could be more than dendrimer.

[0044] An exemplary, preparing the dendritic polymer solution may include dissolving dendrimer polymer having amine-terminated groups in water. The dendrimer polymer having amine-terminated groups may include at least one of polyamidoamine, polypropylene imine, and polyethylene imine. The dendritic polymer has a concentration between 2 wt.% and 15 wt.% of the weight of the water-soluble polymer. [0045] Referring next to step 142, in some implementations, the guest compounds may include a plurality of softening agents, dermal absorption drugs, and transdermal drugs. In one implementation, the softening agents may include glycerol or propylene glycol. In another implementation, dermal absorption drug may include at least one of the nicotine drugs, Asenapine, Clobetasol propionate, Hydrocortisone, Ketoconazole, Triamcinolone NN, Ibuprofen, Nitroglycerin, or Diclofenac. In some other implementations, transdermal drugs may include a plurality of Hyaluronic acid, Lidocaine, Methyl salicylate, essential oils, vitamins, calamine, and honey. An exemplary essential oils may include at least one of lavender, thyme, eucalyptus, sage, yarrow, mint, aloe vera, cucumber, tea tree, olive, peppermint, coconut, menthol, or their derivatives. The guest compounds have a concentration between 1 wt.% and 20 wt.% of the weight of the water- soluble polymer.

[0046] Referring back to FIG. 1 A, according to one or more implementations, the step 150 of forming the polymeric hydrogel may include mixing the co-cross-linking solution with the reaction mixture. In one implementation, reacting the co-cross- linking solution with the reaction mixture may include forming chemical bonds among amine-terminated dendritic groups, boric acid, borax, and a water-soluble polymer. An exemplary reaction of the co-cross-linking solution with the reaction mixture may include forming physical bonds between amine-terminated dendritic groups and hydroxyl groups or carboxylic groups of the water-soluble polymer. Amine-terminated dendritic polymer acts as a chelating agent. Abundant amine groups in dendritic polymers (NH2) can donate electron pairs and form coordinate covalent bonds with Lewis acids like boric acid (B(OH)s). This interaction between dendritic polymers and boric acid/borax can create stable complexes with ring structures. Dendritic complexes with borate ions might also interact with unreacted hydroxyl groups on water-soluble polymer chains, introducing new crosslinking points and potentially affecting the final hydrogel structure. The synergistic effect between amine-terminated dendritic polymers and cross-linkers within the structure of polymeric hydrogels may result in highly effective cross-linked hydrogels with enhanced dimensional stability and more capability to adsorb water. This dimensional stability as well as more water adsorption may make developing patches or pads with cooling or heating functionalities. [0047] In some implementations, a polymeric hydrogel may be used in manufacturing a cooling/heating pad, ice-cold gel, transdermal pad, and deodorant roll. In one implementation, the polymeric hydrogel may include a water-soluble polymer; a cross-linker based on the mixture of boric acid and borax, with the boric acid to borax ratio of between about 1 and 1.5; a co-cross-linker based on amine- terminated dendritic polymer; and a plurality of guest compounds uniformly dispersed in the polymeric hydrogel. The water-soluble polymer may include at least one of PVA, PAA, PVP, carbomer, and PAAM. An exemplary dendritic polymer having amine-terminated groups may include at least one of dendrimer polymers, hyperbranched polymers, and dendriGems. The guest compounds may include at least one of softening agents, dermal absorption drugs, and transdermal drugs. The guest compounds have a concentration between 1 wt.% and 20 wt.% of the weight of the water-soluble polymer. The softening agents may include glycerol, or propylene glycol. In another implementation, dermal absorption drug may include at least one of the nicotine drugs, Asenapine, Clobetasol propionate, Hydrocortisone, Ketoconazole, Triamcinolone NN, Ibuprofen, Nitroglycerin, or Diclofenac. In some other implementations, transdermal drugs may include a plurality of Hyaluronic acid, Lidocaine, Methyl salicylate, essential oils, vitamins, calamine, and honey. An exemplary essential oils may include at least one of lavender, thyme, eucalyptus, sage, yarrow, mint, aloe vera, cucumber, tea tree, olive, peppermint, coconut, menthol, or their derivatives. The guest compounds have a concentration between 1 wt.% and 20 wt.% of the weight of the water- soluble polymer.

[0048] FIG. 2 illustrates a general overview of an implementation of a cooling/heating pad. The cooling/heating pad 200 may include a substrate 210; a layer of a polymeric hydrogel formulation 220; and a plastic substrate 230.

[0049] In one implementation, the polymeric hydrogel formulation may include a water- soluble polymer, a cross-linker based on a mixture of boric acid and borax; a co- cross-linker based on dendritic polymer having amine-terminated groups; and a plurality of guest compounds with a concentration between about 1 % and about 20% of the weight of the water-soluble polymer dispersed in a polymeric hydrogel.

[0050] In another implementation, forming the layer of the polymeric hydrogel formulation on the substrate may include utilizing one or a combination of the following techniques: wire wound rod coating, knife-over-roll (KOR) coating, reverse-roll coating, extrusion slot die coating, slot die coating, film applicator, curtain coating, or any combination thereof.

[0051 ] In some other implementations, forming the layer of the polymeric hydrogel formulation on the substrate may include forming the layer of the polymeric hydrogel formulation on the substrate with a uniform thickness between about 60 pm and about 140 pm. The layer of the polymeric hydrogel may have a uniform thickness between about 120 nm and about 130 nm on the substrate. The substrate may be a backing layer and may include one of polyethylene terephthalate (PET), polyolefins, high-density polyethylene (HDPE), low-density polyethylene (LDPE), polypropylene (PP), polyurethanes (PU), polyether amides (PEA), ethylene vinyl acetate (EVA), or combinations thereof.

Examples

Example 1 : Fabrication of a PVA/PAMAM-boric acid-borax hydrogel

[0052] In this example, a polymeric hydrogel having dual cooling and heating functionalities was obtained using PVA, a mixture of boric acid and borax, and second-generation polyamidoamine by a process similar to the example method 100 as presented in FIG. 1. In order to form the polymeric hydrogel, a polymeric solution was prepared by dissolving 5 g of PVA in 25 mL of deionized water. Next, the cross-linking solution was prepared by dissolving a mixture of boric acid (0.075 g) and borax (0.075 g) in 5 ml of deionized water. This cross-linking solution was then added dropwise to the polymer solution to form the reaction mixture. A co- cross-linker solution was prepared by dissolving 0.5 g of second-generation polyamidoamine, 0.45 g of glycerol, and 0.075 g of essential oil in 20 mL of deionized water. The PVA/PAMAM-boric acid-borax polymeric hydrogel was formed by mixing the co-cross-linking solution with the reaction mixture and no further step is required.

Example 2: Fabrication of a PVA/boric acid hydrogel

[0053] In this example, a polymeric hydrogel was obtained using polyvinyl alcohol (PVA) and boric acid. To form the polymeric hydrogel, a polymeric solution was prepared by dissolving 5 g of PVA in 30 mL of deionized water. Next, a crosslinking solution was prepared by dissolving 0.15 g of boric acid in 10 mL of deionized water. Additionally, a solution was prepared by dissolving 0.45 g of glycerol and 0.075 g of essential oil in 10 mL of deionized water. The PVA/borax polymeric hydrogel was formed by mixing the cross-linking solution, the solution containing glycerol and essential oil, and the PVA solution. The hydrogel shown in Example 2 was prepared to compare the effect of the formulation disclosed in the present disclosure, focusing on the simultaneous presence of dendritic compounds and borax as cross-linking agents.

Example 3: Fabrication of a PVA/dendriGem-boric acid-borax hydrogel

[0054] In this example, a polymeric hydrogel with dual cooling and heating functionalities was prepared using PVA, a mixture of boric acid and borax, and dendriGem, following a process similar to the example method 100 depicted in FIG. 1. To form the polymeric hydrogel, 5 g of PVA were dissolved in 25 mL of deionized water to prepare a polymer solution. A cross-linking solution was then prepared by dissolving 0.075 g of boric acid and 0.075 g of borax in 5 mL of deionized water. This cross-linking solution was added dropwise to the polymer solution to create the reaction mixture. Additionally, a co-cross-linker solution was prepared by dissolving 0.5 g of dendriGem, 0.45 g of glycerol, and 0.075 g of essential oil in 20 mL of deionized water. The PVA/dendriGem-boric acid-borax polymeric hydrogel was formed by combining the co-cross-linker solution with the reaction mixture, with no further steps required.

Example 4: Fabrication of a PVA/PVP/PAMAM-boric acid-borax hydrogel

[0055] In this example, a polymeric hydrogel having dual cooling and heating functionalities was prepared by using a mixture of PVA, PVP, starch, a mixture of boric acid and borax, and second-generation polyamidoamine, utilizing a method similar to exemplary method 100 presented in FIG. 1A. A polymeric solution was prepared by dissolving 5 g of PVA, 0.1 g of PVP, and 0.1 g of starch in 25 mL of deionized water. The polymeric solution was stirred at a temperature of approximately 60° C, for about three (3) hours. In the next step, a cross-linking solution was prepared by dissolving a mixture of 0.075 g of boric acid and 0.075 g of borax in 5 mL of deionized water. A reaction mixture was formed by adding the cross-linking solution dropwise to the polymer solution. A co-cross-linking solution was prepared by dissolving 0.5 g of second-generation polyamidoamine and 0.45 g of glycerol in 15 mL of deionized water. Additionally, 0.075 g of essential oil was dissolved in 5 mL of ethanol and then added to the co-cross-linking solution. The PVA/PVP/PAMAM-boric acid-borax polymeric hydrogel was formed by mixing the co-cross-linking solution with the reaction mixture.

Example 5: Characterization Tests

[0056] In this example, the results of some characterization tests performed on the PVA/PAMAM-boric acid-borax hydrogel, and PVA/boric acid hydrogel (prepared as described in detail in connection with Examples 1 , and 2) are presented.

[0057] Referring to FIG. 3, a Fourier transform infrared (FTIR) spectra of the second- generation PAMAM dendrimer 301 , the PVA/PAMAM-boric acid-borax hydrogel 302, and the PVA/boric acid hydrogel 303 is shown. In FIG. 3, the FTIR spectra of the second-generation PAMAM dendrimer 301 indicate the presence of characteristic vibrational peaks of amide and amine at 1648 cm^-1 and 1550 cm^-1, respectively. The peak at 1170 cm’¹ is related to C-N stretching adsorption. The peaks appearing in the range of 2800-3000 cm’¹ indicate the presence of stretching C-H bonds in the compound, and the bending peaks of these bonds appear in the region of 1200 to 1400 cm’¹. For the PVA/boric acid hydrogel 302, the peaks at 2913 cm’¹ and 2940 cm’¹ can be attributed to the symmetric and asymmetric C-H stretching vibrations, respectively. The peak at 1737 cm’¹ corresponds to the stretching vibrations of the C=O bond confirming the new carboxylic group bonding between the hydroxyl group and borate. A broad band peak at 3318 cm’¹ is attributed to O-H stretching vibration from the hydroxyl groups either complexed with boric acid and forming intermolecular hydrogen bonding. For PVA/PAMAM- boric acid-borax hydrogel 303, the adsorption peaks at 967 cm’¹ and 848 cm’¹ were assigned to the out-of-plane bending vibration of BH₂ and B-0 stretching from the residual B(OH)4^_, respectively. This confirms the cross-linking between PVA, PAMAM, and borax, as well as the presence of a borax network and a small amount of B(OH)4^_ within the hydrogels. The presence of the stretching vibration of the amide group (1648 cm’¹) and bending vibration of N-H (1560 cm’¹) confirms the presence of PAMAM in the structure of the PVA/PAMAM-boric acid-borax hydrogel 303. A small shift in the peak of amine groups from 1550 cm’¹ to a higher frequency of 1560 cm’¹ after cross-linking indicates the involvement of amine groups in forming a physical bond between amine groups and hydroxyl groups of PVA during the preparation process.

[0058] The adhesion between polymeric hydrogel samples and forearm skin was evaluated according to the ASTM D903 peel strength testing standard. This test employed a customized 180° peeling method using an Instron (USA) 5566 tensile testing machine, configured with a 10 N load cell and a rate of 300 mm/min. This test aimed to assess the adhesion of hydrogel and non-slippage characteristics when applied directly to the skin. For this purpose, strips of polymeric hydrogel samples, 1 cm in width and at least 6 cm in length were carefully cut. These strips were separated from the skin by a peeling action, with the separation occurring progressively in a direction parallel to the length of the sample. Adhesion energy was calculated from the stress-strain curve, which is typically characterized by peaks and troughs. Specifically, the area under the force-elongation curve represents the mechanical energy (J) required to separate the hydrogel from the skin. This energy was divided by the peeled area (m²) to obtain the adhesion energy (J/m²). The adhesion energy between the polymeric hydrogel samples and forearm skin was 1 .01 J/m² for the PVA/boric acid hydrogel and 0.61 J/m² for the PVA/PAMAM-boric acid-borax hydrogel. The PVA/boric acid hydrogel exhibited twice the adhesion energy compared to the PVA/PAMAM-boric acid-borax hydrogel. This excessive adhesion of the dendrimer-free hydrogel on the skin was unfavorable, as pieces of the hydrogel remained on the skin after the test.

[0059] In this example, antibacterial activity tests of the polymeric hydrogels were performed using the AATCC Test Method 100-2004. To obtain a 1 x10⁵ bacterial suspension, a small amount of the microorganism colony was added to the test tube containing the culture medium tryptic soy broth using a sterile syringe. This was done in such a way that the optical adsorption peak of the suspension, which corresponds to McFarland 0.5 (1 x10⁸ CFU/mL), was 0.08-0.1 at a wavelength of 600 nm. Then the samples were diluted 10³ times and a suspension corresponding to 1x10⁵ CFU/mL was prepared. The polymeric hydrogel samples were cut into circles with a diameter of 48 ± 0.1 mm and sterilized in an autoclave (temperature 121 °C and pressure 15 Ib/inch2) for 20 minutes. Then, 1 mL of the 1 X10⁵ CFU/mL microbial suspension was prepared in the liquid culture medium with the samples in 100 mL Media-Lab Bottle containers. The containers were placed in the incubator at a temperature of approximately 37 °C for 24 hours. In this example, the antibacterial activities of polymeric hydrogel samples against Staphylococcus aureus as a gram-positive bacterium and Escherichia coli as a gram -negative bacterium were investigated. After 24 hours, 100 mL of physiological serum (normal saline) was added to the containers and shaken vigorously. The reason for choosing the physiological serum is to create a balanced osmotic pressure. 1 mL of each container containing 100 mL of physiological serum, the microbial suspension mixed with different samples in serial dilutions 10°, 10¹, and 10², was transferred separately to a plate (petri dish, sterile plastic containers for the preparation of solid culture media). Then 15 ml of tryptic soy agar (45 °C) was added to each sample and shaken simultaneously to mix the microbial suspension well in the molten agar. The plates were stored at laboratory temperature (25 °C) until solidified. Finally, the plates were placed upside down in the incubator at a temperature of 37 °C for 24 hours. At the end of incubation, the plates were removed from the incubator and examined for the number of colonies formed. The colony count results were measured using the Image J-1 ,49V software. According to the results, the number of colonies for the PVA/boric acid hydrogel was 1 .5x10⁸ for both Gram-positive and Gram-negative bacteria. In contrast, the number of colonies for the PVA/PAMAM-boric acid-borax hydrogel was 2.8x10³ for Grampositive bacteria and 0.9x10³ for Gram-negative bacteria. The antibacterial results of the samples demonstrate that the presence of PAMAM dendrimer in the hydrogel has an excellent antibacterial performance against both Gram -positive and Gram-negative bacteria.

[0060] The fungal resistance test for the polymeric hydrogels was performed according to the ASTM G21 standard. Test samples were placed on an agar medium that lacked carbon (no energy source available) but contained essential mineral salts needed for fungal growth. This carbon-free environment forces the fungi to grow on the test samples rather than on the surrounding agar surface. After placed sample on the mineral salt medium, the test samples were inoculated with a thick spore suspension containing three different fungal species. The inoculated fungal species included Fusarium graminearum, Penicillium funiculosum, and Aspergillus brasiliensis. The small volume of the spore preparation is applied directly to the test samples. The petri dish plates are then closed and incubated at 28 °C with 90% relative humidity for up to 28 days. Every seven days, the samples are checked to monitor progress. After 28 days, the samples are given a semi- quantitative yield score based on fungal growth. The evaluation was carried out according to the following criteria by rating the state of fungal growth as set forth in

TABLE 1

- Excellent (Exc): Fungal growth state is from 0 to 1 ;

- Good: Fungal growth state is from 2 to 3; and

- Poor (NG): Fungal growth state is from 4 to 5.

TABLE 1

Fungal resistance test for hydrogel samples

Samples

PVA/boric acid hydrogel PVA/PAMAM-boric acid-borax hydrogel

Days 7 14 21 28 7 14 21 28

Penicillium funiculosum 0 2 2 2 0 1 1 1

Fusarium graminearum 0 1 1 1 1 1 1 1

Aspergillus brasiliensis 1 2 2 2 1 1 1 1

[0061 ] TABLE 2 shows the results of the temperature tests for the polymeric hydrogel. To assess the cooling effect, the polymeric hydrogels were placed in the refrigerator for 24 hours. Before the test began, the wrist was cleaned and the initial temperature was measured. The polymeric hydrogel was then placed on the wrist. During the eight hours, the temperature in the wrist area was measured at various intervals. The test was repeated five times and the average results are shown in TABLE 2. The PVA/PAMAM-boric acid-borax hydrogel and PVA/dendriGem-boric acid-borax hydrogel have a cooling effect on the skin for about 11 -11 .5 hours. In contrast, the PVA/boric acid hydrogel only cools the skin for 7 hours. When the samples are removed from the refrigerator, the PVA/boric acid hydrogel spreads and exposes a larger surface area to the air. This increased surface area leads to faster drying and lower efficiency. TABLE 2

The cooling temperature test for polymeric hydrogel

. . , PVA/PAMAM- PVA/dendriGem-

PVA/bonc acid , . , , , . , ,

. . . boric acid-borax boric acid-borax h^ydrogel hydrogel hydrogel

Measured room temperature (°C) 27.6 ± 3.0 27.6 ± 3.0 27.6 ± 3.0

Measured body temperature (°C) 33.1 ± 1.0 33.1 ± 1.0 33.1 ± 1.0

Pad temperature before tes (°C)t 25.2 ± 0.5 25.2 ± 0.5 25.2 ± 0.5

The lowest body temperature achieved _{25 0 ± 0 5 25 0 ± 0 5 25 0 ± 0 5} with the pad (°C)

The time it took for the temperature of the pad on the skin to reach body 0.5-1 1-1.5 1-1.5 temperature (h) the optimal cooling duration (h) 7 11.5 11

Spreadability test after 48 h (%) 39.1 21.2 20.5

Industrial Applicability

[0062] The disclosed polymeric hydrogel composition finds broad applicability across various industries due to its unique combination of dual-temperature responsiveness and enhanced stability. In the biomedical field, the hydrogel can be utilized for targeted drug delivery systems, wound dressings, and tissue engineering scaffolds, benefiting from its ability to respond to physiological temperatures and maintain structural integrity under varying thermal conditions. The cosmetic industry can leverage the hydrogel's properties in formulations of skincare and personal care products, where controlled release of active ingredients and stability are paramount.

[0063] Additionally, the present disclosure relates to a versatile polymeric hydrogel designed to provide relief from migraine pain, reduce fever, diminish inflammation, and alleviate itching caused by insect bites through non-medicinal means by creating a cooling effect. More specifically, this disclosure can be employed in facial masks by incorporating optional guest compounds into the hydrogel formulation, such as aloe vera, vitamins, calamine, and essential oils. Additionally, when the hydrogel of the present disclosure is heated, it can be used for the localized treatment of muscle cramps.

Claims

[Claim 1 ] A method for fabricating a polymeric hydrogel, comprising: a) preparing a polymer solution by dissolving a water-soluble polymer in water with continuous stirring; wherein the water-soluble polymer comprises at least one of polyvinyl alcohol, polyacrylic acid, polyvinylpyrrolidone, carbomer, starch, and polyacrylamide; b) preparing a cross-linking solution by dissolving at least one cross-linker in water, wherein the cross-linker comprises boric acid and borax; c) forming a reaction mixture by adding the cross-linking solution dropwise to the polymer solution; d) preparing a co-cross-linking solution, wherein the preparing a co-cross- linking solution comprises steps of:

- dissolving at least one dendritic polymer having amine-terminated groups in water to obtain a dendritic polymer solution;

- adding a plurality of guest compounds to the dendritic polymer solution; and

- continuously stirring to obtain the co-cross-linking solution, e) forming the polymeric hydrogel by mixing the co-cross-linking solution with the reaction mixture.

[Claim 2] The method according to claim 1 , wherein the concentration of the water- soluble polymer comprises between 5 wt.% and 20 wt.% of the weight of the polymeric hydrogel.

[Claim 3] The method according to claim 1 , wherein the water-soluble polymer comprises at least one of polyvinyl alcohol, carbomer, polyvinylpyrrolidone, and starch.

[Claim 4] The method according to claim 1 , wherein the dendritic polymer having amine-terminated groups comprises at least one of dendrimer polymers, hyperbranched polymers, and dendriGems.

[Claim 5] The method according to claim 4, wherein the dendrimer polymers having amine-terminated dendritic groups comprises at least one of polyamidoamine, polypropylene imine, and polyethylene imine.

[Claim 6] The method according to claim 1 , wherein the concentration of the dendritic polymer comprises between 2 wt.% and 15 wt.% of the weight of the water- soluble polymer.

[Claim 7] The method according to claim 1 , wherein the concentration of boric acid and borax comprises between 0.01 wt.% and 10 wt.% of the weight of the water-soluble polymer.

[Claim 8] The method according to claim 1 , wherein the plurality of guest compounds comprises at least one of softening agents, dermal absorption drugs, and transdermal drugs.

[Claim 9] The method according to claim 8, wherein the dermal absorption drug comprises at least one of nicotine, Asenapine, Clobetasol propionate, Hydrocortisone, Ketoconazole, triamcinolone NN, Ibuprofen, Nitroglycerin, or Diclofenac.

[Claim 10] The method according to claim 8, wherein the transdermal drugs comprise at least one of Hyaluronic acid, Lidocaine, Methyl salicylate, essential oils, vitamins, calamine, or honey.

[Claim 11 ] The method according to claim 10, wherein the essential oils comprise at least one of lavender, thyme, eucalyptus, sage, yarrow, mint, aloe vera, cucumber, tea tree, olive, peppermint, coconut, menthol, and their derivatives.

[Claim 12] A polymeric hydrogel for use in manufacturing a cooling/heating pad, ice cold gel, transdermal pad, and deodorant roll, comprising:

- a water-soluble polymer; wherein the water-soluble polymer comprises at least one of polyvinyl alcohol, carbomer, polyvinylpyrrolidone, and starch;

- a cross-linker, wherein the cross-linker comprises a mixture of boric acid and borax, with a boric acid to borax ratio of between about 1 and 1 .5;

- a co-cross-linker, wherein the co-cross-linker comprises at least one of dendrimer polymers, hyperbranched polymers, and dendriGems; wherein the concentration of the dendritic polymer comprises between 2 wt.% and 15 wt.% of the weight of the water-soluble polymer; and

- a plurality of guest compounds, uniformly dispersed in the polymeric hydrogel, wherein the concentration of the guest compounds comprises between 1 wt.% and 20 wt.% of the weight of the water-soluble polymer.

[Claim 13] The method according to claim 12, wherein the concentration of boric acid and borax comprises between 0.01 wt.% and 10 wt.% of the weight of the water-soluble polymer.

[Claim 14] The method according to claim 12, wherein the dendrimer polymers comprises at least one of polyamidoamine, polypropylene imine, and polyethylene imine.

[Claim 15] The method according to claim 12, wherein the plurality of guest compounds comprises at least one of softening agents, dermal absorption drugs, and transdermal drugs.

[Claim 16] The method according to claim 15, wherein the dermal absorption drug comprises at least one of the nicotine drugs, Asenapine, Clobetasol propionate, Hydrocortisone, Ketoconazole, Triamcinolone NN, Ibuprofen, Nitroglycerin, or Diclofenac.

[Claim 17] The method according to claim 15, wherein the transdermal drugs comprise at least one of Hyaluronic acid, Lidocaine, Methyl salicylate, essential oils, vitamins, calamine, and honey, i