Formulation and hydrogels formed therefrom

Abstract

An embodiment provides a composition that forms a film on mucosal lining to prevent contact of particles, pollutants and / or pathogens with the mucosal lining. The composition includes an aqueous-based solution, a cellulose-based compound, and a polysaccharide-based thickener. In some embodiments, the composition includes one or more electrolytes including salts of sodium, potassium, calcium and magnesium.

Description

[0001] Formulation and hydrogels formed therefrom

[0002] Technical field

[0003] The present disclosure relates to formulations and hydrogels formed therefrom for providing a protection barrier such as on mucosal lining in the nasal cavity.

[0004] Background

[0005] Nasal mucosa (nasal mucous membranes) line the nasal cavity, which serves different functions. Nasal mucosa consists mainly of pseudostratified columnar epithelium with goblet cells. This mucosa plays role in warming, humidifying, and filtering the air breathed through the nose. The epithelial cells in the nasal mucosa help maintain a stable temperature by keeping the surface moist, and the mucosa functions as a barrier to one or more external particles, pollutants, and harmful pathogens and resists dehydration.

[0006] A properly functioning nasal mucosa provides protection against external particles, pollutants, and harmful pathogens but also maintains a tolerance to non-harmful microbes and benign environmental substances. When this protection is breached, harmful pathogens or particles can trigger a range of tissue reactions in the form of infection and / or inflammation. The reactions can be local or systemic and depend on many factors, including the pathogen's nature, affinity, pathogenicity and virality or external particles’ chemical and physical properties.

[0007] Most materials are not mucoadhesive as they do not readily adhere to mucosa. However, mucophilic and mucoadhesive compositions, such as some cross-linked polymers that form hydrogels, have been used. There is increasing interest in mucophilic and mucoadhesive compositions that can similarly adhere to mucosa.

[0008] Summary

[0009] An embodiment provides a composition that forms a film on mucosal lining to prevent contact of particles, pollutants and / or pathogens with the mucosal lining, the composition comprising: an aqueous-based solution; hydroxyethyl cellulose; and a polysaccharide-based thickener including xanthan gum and / or guar gum; and one or more electrolytes including salts of sodium, potassium, calcium and magnesium. An embodiment provides a composition that forms a film on mucosal lining to prevent contact of particles, pollutants and / or pathogens with the mucosal lining, the composition comprising: an aqueous-based solution; a cellulose-based compound; and a polysaccharide-based thickener.

[0010] The composition may contain up to 98 wt.% of the aqueous-based solution, up to 1 wt.% cellulose-based compound and up to 0.5 wt.% polysaccharide-based thickener. In an embodiment, the composition contains 90-98 wt.% of the aqueous-based solution, 0.1-1.0 wt.% cellulose-based compound, and 0.1-0.5 wt.% polysaccharide-based thickener. The cellulose-based compound may include hydroxyethyl cellulose. The polysaccharide-based thickener may include xanthan gum and / or guar gum. The aqueous-based solution may include a polyol having one or more terminal hydroxyls. The polyol may include a triol such as glycerine. A wt.% ratio of [water]:[polyol] may range from

[0090] :[5] to [99.9]:[0.1 ].

[0011] The composition may further comprise one or more electrolytes. The one or more electrolytes may include one or more of salts of sodium, potassium, calcium and magnesium. The salts may include sodium chloride, potassium chloride, calcium gluconate and / or magnesium chloride. The sodium salt may have a concentration up to 0.9 wt.%. The potassium salt may have a concentration up to 0.2 wt.%. The calcium salt may have a concentration up to 0.3 wt.%. The magnesium salt may have a concentration up to 0.2 wt.%.

[0012] The composition may further comprise a flavourant including xylitol and / or L-menthol. The composition may further comprise a buffer such configured to buffer a pH of the aqueousbased solution. The buffer may include citric acid and / or trisodium citrate. The buffer may have a concentration up to 0.05 wt.%. The composition may further comprise one or more preservatives. The preservatives may include methyl 4-hydroxybenzoate, potassium sorbate, benzalkonium chloride. Each of the one or more preservatives may have a concentration ranging from 0.001 -0.5wt.%. The mucosal lining may include mucosal tissue. A pH of the composition may range from 5.2 to 5.8.

[0013] An embodiment provides a method of forming a composition that forms a film on mucosal lining to prevent contact of particles, pollutants and / or pathogens with the mucosal lining, the composition comprising: dissolving a cellulose-based compound in a polyol having one or more terminal hydroxyls to form dissolved cellulose-based compound; dissolving a polysaccharide-based thickener in a polyol having one or more terminal hydroxyls to form dissolved polysaccharide-based thickener; and diluting the dissolved cellulose-based compound and dissolved polysaccharide-based thickener with an aqueous-based solution to form the composition.

[0014] An embodiment provides a method of forming a composition that forms a film on mucosal lining to prevent contact of particles, pollutants and / or pathogens with the mucosal lining, the composition comprising: dissolving a cellulose-based compound in a polyol having one or more terminal hydroxyls to form dissolved cellulose-based compound; dissolving a polysaccharide-based thickener including xanthan gum and / or guar gum in a polyol having one or more terminal hydroxyls to form dissolved polysaccharide-based thickener; and diluting the dissolved cellulose-based compound and dissolved polysaccharide-based thickener with an aqueous-based solution having one or more electrolytes including salts of sodium, potassium, calcium and magnesium to form the composition.

[0015] The polyol having one or more terminal hydroxyls may include glycerine. The aqueous-based solution may be heated above room temperature when the dissolved cellulose-based compound and dissolved polysaccharide-based thickener are added to the aqueous-based solution. The aqueous-based solution may be heated up to 75°C. Diluting the dissolved cellulose-based compound and dissolved polysaccharide-based thickener with the aqueousbased solution may include stirring to mix the dissolved cellulose-based compound and dissolved polysaccharide-based thickener in the aqueous-based solution.

[0016] The cellulose-based compound may include hydroxyethyl cellulose. The polysaccharide- based thickener may include xanthan gum and / or guar gum. After the cellulose-based compound and polysaccharide-based thickener have been diluted to form the composition, the composition may contain up to 98 wt.% of the aqueous-based solution, up to 1wt.% cellulose-based compound and up to 0.5wt.% polysaccharide-based thickener. The composition may contain 90-98 wt.% of the aqueous-based solution, 0.1-1 .Owt.% cellulose- based compound, and 0.1-0.5wt.% polysaccharide-based thickener.

[0017] The method may further comprise dissolving one or more electrolytes in the aqueous-based solution prior to diluting the dissolved cellulose-based compound and dissolved polysaccharide-based thickener with the aqueous-based solution. The one or more electrolytes may include one or more of salts of sodium, potassium, calcium and magnesium. The salts may include sodium chloride, potassium chloride, calcium gluconate and / or magnesium chloride.

[0018] Once the composition is formed, the sodium salt may have a concentration up to 0.9 wt.%. Once the composition is formed, the potassium salt may have a concentration up to 0.2 wt.%. Once the composition is formed, the calcium salt may have a concentration up to 0.3 wt.%. Once the composition is formed, the magnesium salt may have a concentration up to 0.2 wt.%.

[0019] The method may further comprise dissolving a flavourant including xylitol and / or L-menthol in the aqueous-based solution prior to diluting the dissolved cellulose-based compound and dissolved polysaccharide-based thickener with the aqueous-based solution. The method may further comprise dissolving a buffer in the aqueous-based solution prior to diluting the dissolved cellulose-based compound and dissolved polysaccharide-based thickener with the aqueous-based solution. The buffer may be configured to buffer a pH of the aqueous-based solution. The buffer may include citric acid and / or trisodium citrate. Once the composition is formed, the buffer may have a concentration up to 0.05 wt.%.

[0020] The method may further comprise dissolving one or more preservatives in the aqueousbased solution prior to diluting the dissolved cellulose-based compound and dissolved polysaccharide-based thickener with the aqueous-based solution. The preservatives may include methyl 4-hydroxybenzoate, potassium sorbate, benzalkonium chloride. Once the composition is formed, each of the one or more preservatives may have a concentration ranging from 0.001 -0.5wt.%. The aqueous-based solution may be at a temperature of 65°C. The method may further comprise adjusting a pH of the aqueous-based solution to range from 5.2 to 5.8.

[0021] An embodiment provides a method of forming a composition that forms a film on mucosal lining to prevent contact of particles, pollutants and / or pathogens with the mucosal lining, the composition comprising: dissolving a cellulose-based compound in a polyol having one or more terminal hydroxyls to form dissolved cellulose-based compound; dissolving a polysaccharide-based thickener in a polyol having one or more terminal hydroxyls to form dissolved polysaccharide-based thickener; diluting the dissolved cellulose-based compound and dissolved polysaccharide-based thickener with an aqueous-based solution to form the composition; and adjusting a pH of the composition to between 5.2 and 5.8, such as between 5.4 and 5.6.

[0022] An embodiment provides a method of forming a film or hydrogel on mucosal lining to prevent contact of particles, pollutants and / or pathogens with the mucosal lining, the method comprising: providing the composition as set forth above; and applying the composition to the mucosal lining.

[0023] Applying the composition to a mucosal tissue may include spraying the composition to form a mist or spray that deposits onto the mucosal lining upon contact thereby forming a film of the composition on the mucosal lining. The mucosal lining may be nasal mucosa.

[0024] An embodiment provides a hydrogel that in use is applied of mucosal lining to prevent contact of particles, pollutants and / or pathogens with the mucosal lining, the hydrogel comprising: up to 98 wt.% of an aqueous phase prior to any dehydration of the hydrogel; up to 1 wt.% of a cellulose-based compound; and up to 0.5 wt.% of a polysaccharide-based thickener.

[0025] An embodiment provides a hydrogel that in use is applied of mucosal lining to prevent contact of particles, pollutants and / or pathogens with the mucosal lining, the hydrogel comprising: up to 98 wt.% of an aqueous phase prior to any dehydration of the hydrogel; up to 1 wt.% of hydroxyethyl cellulose; up to 0.5 wt.% of a polysaccharide-based thickener including xanthan gum and / or guar gum; and one or more electrolytes including salts of sodium, potassium, calcium and magnesium.

[0026] The hydrogel may comprise prior to any dehydration of the hydrogel 90-98 wt.% of the aqueous-based solution, 0.1-1.0wt.% cellulose-based compound, and 0.1-0.5wt.% polysaccharide-based thickener. The cellulose-based compound may include hydroxyethyl cellulose. The polysaccharide-based thickener may include xanthan gum and / or guar gum. The aqueous phase may include a polyol having one or more terminal hydroxyls. The polyol may include a triol such as glycerine. A wt.% ratio of [water]:[polyol] ranges from

[0090] :[5] to

[0097] :[0.1] priorto any dehydration of the hydrogel.

[0027] The hydrogel may further comprise one or more electrolytes. The one or more electrolytes may include one or more of salts of sodium, potassium, calcium and magnesium. The salts may include sodium chloride, potassium chloride, calcium gluconate and / or magnesium chloride. Priorto any dehydration of the hydrogel, the sodium salt may have a concentration up to 0.9 wt.%. Priorto any dehydration of the hydrogel, the potassium salt may have a concentration up to 0.2 wt.%. Prior to any dehydration of the hydrogel, the calcium salt may have a concentration up to 0.3 wt.%. Prior to any dehydration of the hydrogel, the magnesium salt may have a concentration up to 0.2 wt.%.

[0028] The hydrogel may further comprise a flavourant including xylitol and / or L-menthol. The hydrogel may further comprise a buffer such configured to buffer a pH of the aqueous phase. The buffer may include citric acid and / or trisodium citrate. Priorto any dehydration of the hydrogel, the buffer may have a concentration up to 0.05 wt.%.

[0029] The hydrogel may further comprise comprising one or more preservatives. The preservatives may include methyl 4-hydroxybenzoate, potassium sorbate, benzalkonium chloride. Priorto any dehydration of the hydrogel, each of the one or more preservatives may have a concentration ranging from 0.001 wt.% to 0.5wt.%. Prior to formation of the hydrogel, a pH of an aqueous phase of the hydrogel may range from 5.2 to 5.8.

[0030] Brief Description of the Drawings

[0031] Embodiments will now be described, by way of example only, with reference to the accompanying non-limiting drawings, in which:

[0032] Figure 1 is a schematic representation of nasal mucosa and interaction with an embodiment of a hydrogel.

[0033] Figure 2 shows scanning electron microscopy (SEM) images of cross-sectional morphologies of freeze-dried samples of an embodiment of a composition with various concentrations. Figure 3 shows SEM images of surface morphologies of freeze-dried samples of an embodiment of a composition with various concentrations.

[0034] Figure 4 shows SEM images of surface morphologies of an air-dried sample of an embodiment of a composition at different magnifications.

[0035] Figure 5 show a table of different samples and their associated composition used for morphology analysis using SEM.

[0036] Detailed Description

[0037] Embodiments relate to a composition that forms a film on mucosal lining to prevent contact of particles, pollutants and / or pathogens with the mucosal lining. The composition can be used to form a hydrogel. In this way, the film formed by the composition may be the hydrogel. Put anyway, the composition may form a hydrogel barrier that prevents contact of particles, pollutants and / or pathogens with the underlying mucosal lining. The formulation may be used on any type of mucosal lining and may also include epithelial tissue. In an embodiment, the mucosal lining includes mucosal tissue. For example, the composition may be delivered to the nasal cavity, for example by spraying or by applying a gel to the nasal cavity, to form a film / hydrogel barrier on the nasal mucosa. In this way, the composition may also be referred to as a mucophilic solution or mucophilic composition.

[0038] The composition may be in any convenient dosage form including gels, creams, ointments, suppositories, films, emulsions, aerosols and sprays. The composition may be delivered to a mucosa where it may form a coating, be absorbed, or be adsorbed onto the mucosal surface. The composition may form a non-porous coating that resists contact of the mucosa with pathogens.

[0039] As used herein, the term “particle” and derivatives such as “particles” means a microorganism, any foreign substance or material that originates outside the body and enters the respiratory system through breathing, which can cause irritation or inflammatory reactions in the mucosal tissue, which lines the respiratory tract. Common examples include: Dust: Fine particles of solid matter that can be composed of soil, pollen, mould spores, fibres, and skin cells. When inhaled, dust can trigger allergies or respiratory issues.

[0040] Pollen: Microscopic grains released by plants for reproduction. Pollen can cause allergic reactions, commonly known as hay fever, when inhaled.

[0041] Smoke Particles: Small particles generated by combustion processes, such as from fires, cigarettes, or industrial emissions. These can irritate the respiratory system and lead to conditions like bronchitis or worsen asthma.

[0042] Airborne Chemicals: Gases and fine particles from chemical sources, like industrial pollutants, vehicle exhaust, or volatile organic compounds (VOCs) from household products, can irritate the mucosal lining or trigger allergic reactions. These particles interact with the mucosal tissues of the respiratory system, potentially leading to symptoms like sneezing, coughing, nasal congestion, and in severe cases, respiratory distress. The body's immune response to these particles can result in inflammation, which is a part of the body's mechanism to remove or neutralise the irritants.

[0043] As used herein, the term “pollutant” means an external particle that can be inhaled and refers to any foreign substance or material that originates outside the body and enters the respiratory system through breathing. These particles can cause irritation or inflammatory reactions in the mucosal tissue which lines the respiratory tract. Common examples include:

[0044] Pollutants that can be inhaled and cause irritation, inflammatory reactions, and illness in nasal and respiratory system tissues, which are typically airborne substances that negatively impact health when they enter the respiratory tract. These pollutants can be classified into several main types:

[0045] Particulate Matter (PM): These are tiny particles or droplets in the air, such as dust, dirt, soot, and smoke. Particulate matter can be further classified by size (e.g., PM10 and PM2.5, which refer to particles with diameters that are 10 micrometres and 2.5 micrometres and smaller, respectively). Smaller particles are particularly harmful as they can penetrate deeper into the lungs and enter the bloodstream, causing cardiovascular, respiratory, and other systemic effects.

[0046] Volatile Organic Compounds (VOCs): Organic chemicals with high vapor pressure at ordinary room temperature. Common sources include industrial emissions, vehicle exhaust, and chemical solutions. In the presence of sunlight, VOCs can react with NOx to form ozone.

[0047] Heavy Metals: Metals like lead, mercury, cadmium, and arsenic can be present in the air in particulate form. These metals can be inhaled and pose significant health risks, including respiratory, neurological, and systemic diseases.

[0048] When these pollutants are inhaled, they can irritate the airways and mucosal lining of the respiratory system, leading to inflammation and various symptoms, including coughing, wheezing, shortness of breath, and exacerbation of asthma or chronic obstructive pulmonary disease (COPD). Chronic exposure can lead to more severe health issues, including increased risk of cardiovascular diseases and lung cancer.

[0049] As used herein, the term “pathogen” means a microorganism that can be inhaled and cause irritation, inflammatory reactions, and illness in nasal and respiratory system tissues. Pathogens are infectious agents that enter the body through the respiratory route. These pathogens are typically microorganisms, including viruses, bacteria, and fungi, which can thrive and multiply within the respiratory tract, leading to various diseases. The following are some common types of inhaled pathogens:

[0050] Viruses: These are the smallest and simplest infectious agents, requiring a host to replicate. Common respiratory viruses include:

[0051] Influenza (flu): Causes seasonal flu outbreaks and can lead to severe respiratory illness.

[0052] Rhinoviruses: The primary cause of the common cold.

[0053] Coronaviruses: Including strains that cause severe diseases like SARS, MERS, and COVID-19.

[0054] Respiratory Syncytial Virus (RSV): A major cause of respiratory illness in infants and elderly individuals.

[0055] Bacteria: These can cause a range of respiratory infections, from mild to lifethreatening, including:

[0056] Streptococcus pneumoniae: Causes pneumonia, bronchitis, and ear infections. Mycobacterium tuberculosis: Causes tuberculosis, a severe lung infection. Bordetella pertussis: Causes whooping cough, a highly contagious respiratory disease.

[0057] Fungi: Certain fungi can be inhaled as spores, leading to infections, especially in individuals with weakened immune systems. Common examples include:

[0058] Histoplasma capsulatum: Causes histoplasmosis, often affecting the lungs.

[0059] Aspergillus species: These can lead to aspergillosis, which affects the respiratory system and sometimes becomes invasive or disseminated in immunocompromised individuals.

[0060] When inhaled, these pathogens can settle in the nasal passages, sinuses, or deeper respiratory tract, including the lungs. The body's immune response to these pathogens can cause inflammation, leading to symptoms such as sneezing, coughing, sore throat, and difficulty breathing. In severe cases, these infections can lead to significant illness requiring medical attention, and some may become chronic or life-threatening, particularly in vulnerable populations.

[0061] In an embodiment, the composition may be used to form a film that is a non-porous solid coating that keeps pathogens away from reaching or contacting tissue membranes. The composition may be thickened to a gel or sol-gel. A sol-gel results when micro-particles or molecules in a colloidal solution (the sol) agglomerate or link up to form an integrated network (the gel).

[0062] The composition may be formed from phytochemicals. Without wishing to be bound by theory, it is believed that the composition (which may also be referred to as a mucophilic solution) when applied to an area of living tissue, such as mucosa, forms a coating or film that hinders the passage of external particles, pollutants and harmful pathogens into the mucosa or holds the same. Again, without wishing to be bound by theory, it is postulated that during the time the pathogen is held, they are prevented from entering the matrix of mucosal cells and causing infection. Furthermore, if it is held or hindered, the pathogen will have more time to interact with the phytochemicals introduced with the mucophilic solution. This increases the likelihood of inhibition of activity and replication / transcription of the pathogen and, optimally, eventual death of the pathogen.

[0063] As used herein, the term ‘prophylaxis’ is intended to mean the preservation of health, prevention of the spread of disease and prevention of one or more external particles, pollutants, and harmful pathogens coming in contact with living human or other animal living tissue.

[0064] In an embodiment, the composition (or mucophilic solution) comprises: an aqueous-based solution; a cellulose-based compound; a polysaccharide-based thickener.

[0065] The cellulose-based compound may include cellulose modified with hydroxyalkyl grounds. For example, the cellulose-based compound may include hydroxyethyl cellulose, hydroxypropyl methyl cellulose and / or hydroxypropylmethyl cellulose. The cellulose-based compound may include methyl cellulose and / or carboxymethyl cellulose. The cellulose-based compound may include a mixture of two or more cellulose-based compounds. In an embodiment, the cellulose-based compound is hydroxyethyl cellulose. It should be appreciated that the cellulose-based compound may be provided in different grades having different average molecular weight(s) and / or polydispersity. In an embodiment, an average molecular weight cellulose-based compound is >500kDa. In an embodiment, an average molecular weight cellulose-based compound is approximately 1MDa.

[0066] A concentration of the cellulose-based compound may be up to 1 wt.%. A concentration of the cellulose-based compound may be up to 0.9 wt.%. A concentration of the cellulose- based compound may be up to 0.8 wt.%. A concentration of the cellulose-based compound may be up to 0.7 wt.%. A concentration of the cellulose-based compound may be up to 0.6 wt.%. A concentration of the cellulose-based compound may be at least 0.1 wt.%. A concentration of the cellulose-based compound may be at least 0.2 wt.%. A concentration of the cellulose-based compound may be at least 0.3 wt.%. A concentration of the cellulose- based compound may be at least 0.4 wt.%. A concentration of the cellulose-based compound may be at least 0.5 wt.%. In an embodiment, concentration of the cellulose-based compound ranges from 0.01 to 1.0 wt.%. In an embodiment, concentration of the cellulose- based compound ranges from 0.1 to 1 .0 wt.%. In an embodiment, concentration of the cellulose-based compound ranges from 0.2 to 0.9 wt.%. In an embodiment, concentration of the cellulose-based compound ranges from 0.3 to 0.9 wt.%. In an embodiment, concentration of the cellulose-based compound ranges from 0.4 to 0.9 wt.%. In an embodiment, concentration of the cellulose-based compound ranges from 0.5 to 0.9 wt.%. In an embodiment, concentration of the cellulose-based compound ranges from 0.5 to 0.8 wt.%. In an embodiment, concentration of the cellulose-based compound ranges from 0.5 to 0.7 wt.%. The cellulose-based compound is typically dissolved in the aqueous-based solution. However, depending on the form of the cellulose-based compound, it may be suspended and / or dissolved in the aqueous-based solution.

[0067] The polysaccharide-based thickener may help the composition to thicken, gel or coagulate. The polysaccharide-based thickener may include food-grade or pharmaceutical-grade thickeners including, for example, glycerin, carrageenan, sugar, natural gums, guar gum, methylcellulose, hydroxyethyl cellulose, Aloe barbadensis (aloe vera), xanthan gum, starches, pectins and agar-agar or proteins such as gelatin. In an embodiment, polysaccharide-based thickener may include xanthan gum and / or guar gum. In an embodiment, polysaccharide-based thickener includes xanthan gum. In an embodiment, polysaccharide-based thickener includes guar gum. In an embodiment, a concentration of the polysaccharide-based thickener may range from 0.01 to 0.5 wt.%. In an embodiment, a concentration of the polysaccharide-based thickener may range from 0.1 to 0.5 wt.%. The polysaccharide-based thickener is typically dissolved in the aqueous-based solution. However, depending on the form of the polysaccharide-based thickener, it may be suspended and / or dissolved in the aqueous-based solution.

[0068] The aqueous-based solution may be water-based. For example, the aqueous-based solution may include distilled water. The aqueous-based solution may include co-solutions such as polyols and / or alcohols that help to dissolve and / or stabilise the cellulose-based compound and / or polysaccharide-based thickener. The polyol may have one or more terminal hydroxyls. The polyol may be a triol. In an embodiment, the polyol includes glycerol (also known as glycerine or glycerin). In an embodiment, a wt.% ratio of the [water]:[polyol] ranges from

[0090] :

[0010] to [99.9]:[0.1], In an embodiment, a wt.% ratio of the [water]:[polyol] ranges from

[0095] :[5] to [99.9]:[0.1], In an embodiment, a wt.% ratio of the [water]:[polyol] ranges from

[0090] :[5] to

[0099] :

[0001] . The aqueous-based solution may include ethanol as a co-solution.

[0069] The composition may include up to 99.9wt.% of the aqueous-based solution. The composition may include up to 99.5wt.% of the aqueous-based solution. The composition may include up to 99 wt.% of the aqueous-based solution. The composition may include up to 98 wt.% of the aqueous-based solution. The composition may include at least 80 wt.% of the aqueous-based solution. The composition may include at least 85 wt.% of the aqueousbased solution. The composition may include at least 90 wt.% of the aqueous-based solution. The composition may include at least 95 wt.% of the aqueous-based solution. In an embodiment, may contain 90-97 wt.% of the aqueous-based solution.

[0070] In an embodiment, the composition is a sol-gel comprising 0.10 wt.% to 1 .00 wt.% of the cellulose-based compound, 0.001 wt.% to 0.500 wt.% of the polysaccharide-based thickener, and 92 wt.% to 98 wt% of an aqueous-based solutions comprising water:glycerol:ethanol in a ratio of 96:3:1. In an embodiment, the composition contains up to 97 wt.% of the aqueousbased solution, up to 1 wt.% cellulose-based compound and up to 0.5 wt.% polysaccharide- based thickener. In an embodiment, the composition contains 90-97 wt.% of the aqueousbased solution, 0.1-1.0 wt.% cellulose-based compound, and 0.1-0.5 wt.% polysaccharide- based thickener.

[0071] A pH of the composition may be >5.0. A pH of the composition may be <7.0. A pH of the composition may be <6.0. A pH of the composition may be selected based on an isoelectric point of one or both of the cellulose-based compound and the polysaccharide-based thickener. In an embodiment, a pH of the composition may range from 5.2 to 5.8. The composition may further comprise a buffer such configured to buffer a pH of the aqueousbased solution. The buffer may include citric acid and / or trisodium citrate. The buffer may have a concentration up to 0.05 wt.%.

[0072] The incorporation of a buffer in the formulation may help in optimising in preserving the composition. While the buffer was not initially expected to affect the barrier efficacy, it assisted in maintaining the appropriate pH range that enables optimal preservative function. The inventors found that the applicant’s previous formulation as outlined in WO2022217319A1 , had unexpectedly failed efficacy testing despite using preservative concentrations within typical pharmaceutical ranges. This failure was attributed to the limited dispersion, transfer, and efficacy of preservatives in the viscous hydrogel system. By adding a buffer to adjust and maintain the pH between 5.2 and 5.8, particularly to provide a favourable environment for potassium sorbate, the preservative efficacy was significantly improved. This pH optimisation, in combination with adjustments to preservative concentrations, allowed the formulation to pass preservative efficacy tests. The buffer's role in maintaining this specific pH range may help to contributes to the overall stability, safety, and effectiveness of the composition.

[0073] The composition may further comprise one or more electrolytes. The electrolytes may be selected to match or at least closely match the electrolyte profile of the mucosal lining such as nasal mucosa. This may help to minimise any physiological response induced upon application of the composition to form the film on the mucosal lining. The one or more electrolytes may include one or more of salts of sodium, potassium, calcium and magnesium.

[0074] The inclusion of electrolytes, particularly the combination of salts of sodium, potassium, calcium, and magnesium, in the composition provided in some embodiments unexpected advantages in barrier function and efficacy. Initially, it was not anticipated that this combination of salts would significantly enhance the composition's protective properties, as natural nasal mucus containing similar salt concentrations does not exhibit substantial antiviral activity. However, testing revealed a surprising progression in efficacy from formulations with no salt, to those with saline only, to those having the four-salt combination. This improvement was particularly noteworthy given that sodium chloride at saline concentration (0.9%) is known to have only a moderate antiviral effect in vitro. Furthermore, the specific interaction between these salts and the cellulose / gum structure of the gel was not predictable based on existing literature. Salts can affect the hydrogen and ionic bonds between cellulose chains, altering the crystalline and porous structures of the gel in complex ways. The combination and concentrations of the one or more electrolyte salts used in this composition resulted in a synergistic effect, enhancing both the physical barrier properties and the overall efficacy of the formulation in ways that were not expected based on the applicant’s prior formulation (see WO2022217319A1) or the properties of the individual components.

[0075] The salts may include sodium chloride, potassium chloride, calcium gluconate and / or magnesium chloride. The sodium salt may have a concentration up to 0.9 wt.%. The potassium salt may have a concentration up to 0.2 wt.%. The calcium salt may have a concentration up to 0.3 wt.%. The magnesium salt may have a concentration up to 0.2 wt.%. The concentration of one or more salts may be selected depending on whether an isotonic, hypertonic or hypotonic saline solution is required. For example, hypertonic solutions are primarily used for their osmotic effect, which helps reduce swelling in the nasal passages by drawing out excess water from the mucosal tissues. This can be particularly beneficial for relieving nasal congestion in conditions like sinusitis or after sinus surgery. On the other hand, hypotonic solutions may be used where even gentler solutions are necessary, though their effectiveness and specific uses can vary.

[0076] The composition may further comprise a flavourant including xylitol and / or L-menthol. The flavourant may help to make the composition more acceptable to be received by a user. For example, L-menthol may help to provide a pleasant taste to assist with a user applying the composition to e.g. nasal mucosa. The flavourant may be provided in crystalline form. The flavourant may be dissolved or suspended in the aqueuous-based solution. The flavourant may have a concentration of 0.001 wt.% to 1 .0 wt%. The flavourant may have a concentration of 0.001 wt.% to 0.90 wt%. The flavourant may have a concentration of 0.001 wt.% to 0.80 wt%. The flavourant may have a concentration of 0.001 wt.% to 0.70 wt%. The flavourant may have a concentration of 0.001 wt.% to 0.60 wt%. The flavourant may have a concentration of 0.001 wt.% to 0.50 wt%. The flavourant may have a concentration of 0.01 wt.% to 0.50 wt%. The flavourant may have a concentration of 0.01 wt.% to 0.40 wt%. The flavourant may have a concentration of 0.01 wt.% to 0.30 wt%. The flavourant may have a concentration up to 0.50 wt%. The flavourant may have a concentration up to 0.40 wt%. The flavourant may have a concentration up to 0.30 wt%.

[0077] The composition may include one or more preservatives. The preservatives include methyl 4- hydroxybenzoate, potassium sorbate, benzalkonium chloride. Each of the one or more preservatives may have a concentration ranging from 0.001 -0.5wt.%. A concentration of potassium sorbate powder in the composition may range from 0.125wt.% to 0.30 wt.%. A concentration of methyl 4-hydroxybenzoate in the composition may range from 0.05 wt.% to 0.40 wt.%. A concentration of benzalkonium chloride aq. 50% in the composition may range from 0.005 wt.% to 0.050 wt.%.

[0078] The composition may include a pharmaceutically acceptable excipient. The composition may further comprise one or more compounds chosen from antiviral, antibacterial (including anti- gram positive and anti-gram negative bacteria), antifungal compounds, or other pharmaceutically active compounds.

[0079] In an embodiment, the composition is hydroxyethyl cellulose-based sol-gel that includes: 0.10wt.% to 1.00 wt.%, such as 0.50 wt.% to 0.60 wt.% of hydroxyethyl cellulose; up to 0.50 wt.%, such as 0.10 wt.% to 0.20 wt.% of guar gum and / or up to 0.50 wt.%, such as 0.10 wt.% to 0.16 wt.% of xanthan gum.

[0080] The sol of the sol-gel may include an aqueous-based solution that includes water:glycerol:ethanol mixture ranging from 90:2:0 to 95:4:2 based on an overall wt.% of the composition.

[0081] An embodiment of the composition may include:

[0082] Component Concentration (wt.% of composition) HEC 0.10 to 1 .00, such as 0.50 to 0.70

[0083] Xanthan gum 0.10 to 0.50, such as 0.20 to 0.25 Glycerine 0.10 to 5.00, such as 1 .00 to 2.00

[0084] Benzalkonium chloride (50% aq.) 0.005 to 0.05, such as 0.05 to 0.10 Methyl 4-hydroxybenzoate 0.05 to 0.40, such as 0.20 to 0.25 Potassium sorbate 0.10 to 0.30, such as 0.1 to 0.2

[0085] Water 90.0 to 97.0, such as 92.0 to 94.0

[0086] Sodium chloride 0.10 - 3.00, such as 0.90

[0087] Potassium chloride 0 - 0.20

[0088] Calcium gluconate monohydrate 0 - 0.30

[0089] Magnesium chloride hexahydrate 0 - 0.20 Citric Acid (Anhydrous) 0 - 0.05 Trisodium citrate dihydrate 0 - 0.20

[0090] An embodiment of the composition may include:

[0091] Composition A Composition B Component

[0092] Content (wt.%) Content (wt.%)

[0093] Water 90.0-97.0 90.0- 97.0

[0094] Glycerine 0.10-5.00 0.10- 5.00

[0095] Ethanol 0.00-2.00 0.00-2.00

[0096] Hydroxyethyl cellulose 0.10- 1.00 0.10- 1.00

[0097] Xanthan Gum 0.00 0.10- 0.50

[0098] Guar Gum 0.10-0.50 0.00

[0099] Xylitol 0.00- 1.00 0.00- 1.00

[0100] L-Menthol 0.00- 0.10 0.00- 0.10

[0101] Methyl 4-hydroxybenzoate 0.05 - 0.40 0.05 - 0.40

[0102] Potassium sorbate 0.10-0.30 0.10- 0.30

[0103] Benzalkonium chloride aq.50% 0.005 - 0.05 0.005 - 0.05

[0104] Sodium chloride 0.90 0.90

[0105] Potassium chloride 0.00 - 0.20 0.05 - 0.20

[0106] Calcium gluconate monohydrate 0.00 - 0.30 0.01 - 0.30

[0107] Magnesium chloride 0.00- 0.20 0- 0.20 hexahydrate

[0108] Citric Acid (anhydrous) 0.00 - 0.05 0.001 - 0.05

[0109] Trisodium citrate dihydrate 0.00- 0.20 0.01 - 0.20

[0110] An embodiment of the composition may include:

[0111] Composition C Composition D Component

[0112] Content (wt.%) Content (wt.%)

[0113] Water 94.56 94.40

[0114] Glycerine 2.677 2.677

[0115] Hydroxyethyl cellulose 0.560 0.560

[0116] Xanthan Gum or Guar Gum 0.160 0.160

[0117] Xylitol 0.432 0.432

[0118] L-Menthol 0.010 0.010

[0119] Methyl 4-hydroxybenzoate 0.100 0.200

[0120] Potassium sorbate 0.200 0.200

[0121] Benzalkonium chloride aq. 50% 0.016 0.040

[0122] Sodium chloride 0.900 0.900

[0123] Potassium chloride 0.127 0.127

[0124] Calcium gluconate monohydrate 0.179 0.179

[0125] Magnesium chloride hexahydrate 0.081 0.081

[0126] Citric Acid (anhydrous) - 0.005

[0127] Trisodium citrate dihydrate - 0.020

[0128] Embodiments also relate to formation of a film, such as a hydrogel film, to prevent contact of particles, pollutants and / or pathogens with the epidermis including mucosal lining. A method of forming the film may include: providing an embodiment of the composition; and applying the composition to a mucosal tissue.

[0129] Applying the composition to a mucosal tissue may include spraying the composition to form a mist or spray that deposits onto the mucosal tissue upon contact thereby a film of the composition on the mucosal tissue. Alternatively, the composition may be applied as a gel or similar solution to the mucosal tissue to form the film of the composition thereon. The mucosal tissue may be nasal mucosa. The composition may have a viscosity that that is sufficiently low to allow cilia to move in their normal manner to help clear foreign matter from the nasal passages.

[0130] Upon application to the mucosal tissue, the film, which is typically in hydrogel form, begins to dry or dehydrate. This dehydration is generally initiated at an upper surface of the film that is exposed to airflow in the nasal cavity, as shown in Figure 1 . Dehydration causes the water domains of the hydrogel is shrink, causing a reduction in the size of any pores located towards the upper surface of the hydrogel. This is also accompanied by a reduction in thickness of the film / hydrogel. To assist with forming the film, the formulation may be mucoadhesive. For example, the formulation may include boronated-functionalised components such as boronated-functionalised cellulose-derivatives to assist with adhesion. It should be appreciated that depending on a water content of the mucous onto which the hydrogel / film is applied, the hydrogel / film may experience localised hydration. Accordingly, a water content of the hydrogel / film may vary upon application to the mucosal tissue.

[0131] The disclosure also extends to a hydrogel formed from an embodiment of the composition. Any reference to concentrations of the components of the hydrogel are referenced to the concentration at hydrogel formation and prior to any dehydration (or further hydration) of the hydrogel. In an embodiment, a hydrogel that in use is applied of dermis to prevent contact of particles, pollutants and / or pathogens with the epidermis including mucosal lining, comprises: up to 98 wt.% of an aqueous phase prior to any dehydration of the hydrogel; up to 1 wt.% of a cellulose-based compound; and up to 0.5 wt.% of a polysaccharide-based thickener.

[0132] The hydrogel may have concentrations of components as outlined above for the composition. The aqueous phase of the hydrogel is formed from the aqueous-based solution of the composition. It should be appreciated that the aqueous phase of the hydrogel may change overtime with respect to the aqueous-based solution of the composition, for example from diffusion of solutes and solvents in and out of the aqueous phase of the hydrogel. Accordingly, any reference to a makeup of the aqueous phase is made with reference to a freshly formed hydrogel and not one that has been subject to equilibration with a surrounding environment unless context makes it clear otherwise. The hydrogel may have a viscosity or elastic properties that that lows allow cilia to move in their normal manner to help clear foreign matter from the nasal passages.

[0133] The disclosure also formation of the composition. Accordingly, an embodiment provides a method of forming a composition that forms a film on mucosal lining to prevent contact of particles, pollutants and / or pathogens with the mucosal lining, the composition comprising: dissolving a cellulose-based compound in a polyol having one or more terminal hydroxyls to form dissolved cellulose-based compound; dissolving a polysaccharide-based thickener in a polyol having one or more terminal hydroxyls to form dissolved polysaccharide-based thickener; and diluting the dissolved cellulose-based compound and dissolved polysaccharide-based thickener with an aqueous-based solution to form the composition.

[0134] As described above, the polyol may have one or more terminal hydroxyls includes glycerine. The aqueous-based solution may be heated above room temperature when the dissolved cellulose-based compound and dissolved polysaccharide-based thickener are diluted by the aqueous-based solution. The aqueous-based solution may be heated up to 75°C. The aqueous-based solution may be heated up to 70°C. The aqueous-based solution may be heated up to 65°C. The aqueous-based solution may be heated up to 60°C. The aqueousbased solution may be heated up to 55°C. The aqueous-based solution may be heated up to 50°C. The aqueous-based solution may be heated up to 45°C. The aqueous-based solution may be heated up to 40°C. The aqueous-based solution may be heated up to 35°C. The aqueous-based solution may be heated up to 30°C. The aqueous-based solution may be heated above room temperature. The aqueous-based solution may be heated to at least 30°C. The aqueous-based solution may be heated to at least 35°C. The aqueous-based solution may be heated to at least 40°C. The aqueous-based solution may be heated to at least 45°C. The aqueous-based solution may be heated to at least 50°C. The aqueousbased solution may be heated to at least 55°C. The aqueous-based solution may be heated to at least 60°C. The aqueous-based solution may be heated to at least 65°C. The aqueous based solution may be at a temperature of 65°C.

[0135] The step of diluting the dissolved cellulose-based compound and dissolved polysaccharide- based thickener with the aqueous-based solution may including stirring to mix the dissolved cellulose-based compound and dissolved polysaccharide-based thickener in the aqueousbased solution.

[0136] The cellulose-based compound, the polysaccharide-based thickener and their concentrations relative to each other and the aqueous-based solution may be that as described for the composition.

[0137] The cellulose-based compound and the polysaccharide-based thickener may be dissolved in the same polyol. For example, the cellulose-based compound and the polysaccharide-based thickener may be formed in the same volume of polyol to form a mixture of dissolved cellulose-based compound and polysaccharide-based thickener. The dissolved cellulose- based compound may be diluted in the aqueous-based solution prior to addition of the dissolved polysaccharide-based thickener to the aqueous-based solution. The dissolved cellulose-based compound may be diluted in the aqueous-based solution after addition of the dissolved polysaccharide-based thickener to the aqueous-based solution. Forming the dissolved cellulose-based compound and dissolved polysaccharide-based thickener in polylol(s) may help to ensure complete dissolution of the cellulose-based compound and polysaccharide-based thickener to minimise or eliminate formation of aggregates and the like.

[0138] The cellulose-based compound and / or polysaccharide-based thickener may be dissolved in the same or different polyol at room temperature. The cellulose-based compound and / or polysaccharide-based thickener may be dissolved in the same or different polyol at a temperature ranging from 20°C to 25°C. The cellulose-based compound and / or polysaccharide-based thickener may be dissolved in the same or different polyol at a temperature ranging from 20°C to 22°C. The cellulose-based compound and / or polysaccharide-based thickener may be dissolved in the same or different polyol above room temperature.

[0139] The method may include dissolving one or more electrolytes in the aqueous-based solution. Dissolution of the one or more electrolytes may occur prior to diluting the dissolved cellulose- based compound and dissolved polysaccharide-based thickener with the aqueous-based solution. Alternatively, dissolution of the one or more electrolytes may occur after diluting the dissolved cellulose-based compound and dissolved polysaccharide-based thickener with the aqueous-based solution. The one or more electrolytes and their concentrations may be that as described for the composition.

[0140] The method may include dissolving a flavourant in the aqueous-based solution. Dissolution of the flavourant in the aqueous-based solution may occur prior to diluting the dissolved cellulose-based compound and dissolved polysaccharide-based thickener with the aqueousbased solution. Alternatively, dissolution of the flavourant in the aqueous-based solution may occur after diluting the dissolved cellulose-based compound and dissolved polysaccharide- based thickener with the aqueous-based solution. The flavourant may include xylitol and / or L-menthol. A concentration of the flavourant may be that as described for the composition.

[0141] The method may include dissolving a buffer in the aqueous-based solution. The buffer may include two or more buffers. The buffer is configured to buffer a pH of the aqueous-based solution. The buffer may be dissolved in the aqueous-based solution prior to diluting the dissolved cellulose-based compound and dissolved polysaccharide-based thickener with the aqueous-based solution. Alternatively, the buffer may be dissolved in the aqueous-based solution after diluting the dissolved cellulose-based compound and dissolved polysaccharide- based thickener with the aqueous-based solution. The buffer(s) and their concentrations may be that as described for the composition.

[0142] The method may include dissolving one or more preservatives in the aqueous-based solution. The one or more preservatives may be dissolved in the aqueous-based solution prior to diluting the dissolved cellulose-based compound and dissolved polysaccharide- based thickener with the aqueous-based solution. Alternatively, the one or more preservatives may be dissolved in the aqueous-based solution after diluting the dissolved cellulose-based compound and dissolved polysaccharide-based thickener with the aqueousbased solution. The one or more preservatives and their concentrations may be that as described for the composition.

[0143] The method may include adjusting a pH of the aqueous-based solution to range from 5.2 to 5.8. The pH of the aqueous-based solution may be adjusted by addition of the buffers. The pH of the aqueous-based solution may be adjusted by adding and acid or base. The pH of the aqueous-based solution may be adjusted after formation of the composition. The pH of the aqueous-based solution may be adjusted prior to diluting the dissolved cellulose-based compound and dissolved polysaccharide-based thickener with the aqueous-based solution.

[0144] Embodiments of the present disclosure stem from the realisation that a particular composition of one or more phytochemicals in a thickened solution can provide suitable adhesion to nasal mucosal surfaces to deliver a prophylactic and / or barrier blocking effect against one or more one or more external particles, pollutants and / or harmful pathogen / s. Furthermore, without wishing to be bound by theory, it is thought that the combination of the thickened solution and excipients provides a physical barrier. In particular, the composition may be readily delivered as a nasal solution to resist infection or inflammatory reaction by one or more external particles, pollutants and / or harmful pathogen / s.

[0145] One or more embodiments may have one or more of the following advantages: the composition / hydrogel does not disturb, the chemical composition of mucosa or the function of cilia; the composition / hydrogel resists adherence and / or penetration of one or more external particles, pollutants and / or harmful pathogen / s the composition / hydrogel is readily administered; and / or the composition / hydrogel can be conveniently delivered nasally.

[0146] In the claims that follow and in the preceding description of the disclosure, except where the context requires otherwise due to express language or necessary implication, the word “comprise” or variations such as “comprises” or “comprising” is used in an inclusive sense, i.e. to specify the presence of the stated features but not to preclude the presence or addition of further features in various embodiments.

[0147] It is to be understood that, if any prior art publication is referred to herein, such reference does not constitute an admission that the publication forms a part of the common general knowledge in the art, in Australia or any other country.

[0148] Modifications and variations as would be apparent to a skilled addressee are deemed to be within the scope of the present disclosure. All art-known functional equivalents of any such materials and methods are intended to be included in this disclosure. The terms and expressions which have been employed are used as terms of description and not of limitation, and there is no intention that in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognised that various modifications are possible within the scope of the disclosure claimed. Thus, it should be understood that although the present disclosure has been specifically disclosed by examples, preferred embodiments and optional features, modification and variation of the concepts herein disclosed may be resorted to by those skilled in the art, and that such modifications and variations are considered to be within the scope of this disclosure as defined by the appended claims.

[0149] Thought the above embodiments and Examples below for a composition, hydrogel and method of forming the composition have been described with reference to mucosal lining, one or more embodiments may be applicable to epidermal tissue. Accordingly, an embodiment may provide a composition, hydrogel, or formation of a composition that is used to form a barrier lining to prevent contact of particles, pollutants and / or pathogens with the epidermal tissue.

[0150] Examples

[0151] Non-limiting examples will now be described. Example 1 - Formation of composition - Sample 1

[0152] Step 1 :

[0153] Purified water (94.982g) was heated up to 65°C and left heating at this temperature and stirring (580rpm).

[0154] Step 2:

[0155] Sodium chloride (0.900g), methyl hydroxybenzoate (0.100g), xylitol (0.432g), potassium sorbate (0.200g), benzalkonium chloride 50% (0.016g) were added slowly to the solution at Step 1 and the resulting mixture was left heating and stirring until homogeneous (particularly until full dissolution of methyl paraben crystals). After the mixture became homogeneous, L- menthol (0.010g) was added (to avoid loss by evaporation). The mixture was left stirring while being heated at 65°C.

[0156] Heating the water helps to increase the rate of dissolution, especially for components that have poor solubility. Adding volatile components last, such as L-menthol, helps to minimize loss due to evaporation.

[0157] Step 3:

[0158] Guar gum (0.190g) was dissolved in glycerol (1 .000g), the solution was added to the solution at Step 2 and the resulting mixture was left stirring while being heated at 65°C.

[0159] Step 4:

[0160] Hydroxyethyl cellulose (0.670g) was dissolved in glycerol (1 .500g), and the solution was added to the solution at Step 3 and the resulting mixture was left stirring while being heated at 65°C. The resulting mixture was left stirring vigorously for further 30 minutes, then the mixture was allowed to cool down to room temperature.

[0161] At Step 2 and Step 3, guar gum (a polysaccharide-based thickener) and hydroxyethyl cellulose (a cellulose-based compound) is dissolved in glycerol without increasing its viscosity, which in turn allows for easier dissolution in the aqueous mixture at Step 4. It was found that poorly mixed thickeners tend to form large gelled particles that are wet on outside while being dry on the inside and unable to further dissolve. To help minimise this, a high shear mixer may be utilised as it physically breaks down large particles, creating a more even and smooth mix in the final product. A summary of the composition formed in Example 1

[0162] Component Content (wt%)

[0163] Water 94.982

[0164] Glycerol 2.500

[0165] Sodium chloride 0.900

[0166] Hydroxyethyl cellulose 0.670

[0167] Xylitol 0.432

[0168] Potassium sorbate 0.200

[0169] Methyl 4-hydroxybenzoate 0.100

[0170] Guar Gum 0.190

[0171] Benzalkonium chloride aq. 50% 0.016

[0172] L-Menthol 0.010

[0173] Example 2 - Formation of composition - Sample 2

[0174] The method used to form the formation for Example 2 is similar to that described for Example 1.

[0175] Step 1 :

[0176] Purified water (94.407g) was heated up to 65°C and left heating at this temperature and stirring (580rpm) for the next step.

[0177] Step 2:

[0178] Sodium chloride (0.900g), potassium chloride (0.127g), magnesium chloride hexahydrate (0.081g) and calcium gluconate monohydrate (0.179g), methyl hydroxybenzoate (0.200g), xylitol (0.432g), potassium sorbate (0.200g), benzalkonium chloride 50% (0.040g), citric acid monohydrate (0.0062g) and sodium citrate dihydrate (0.0207g) were added slowly to the Phase 1 mixture and the resulting mixture was left heating and stirring until homogeneous (Particularly until full dissolution of methyl paraben crystals). After the mixture became homogeneous, L-menthol (0.010g) was added last to avoid loss by evaporation. The mixture was left stirring while being heated at 65°C.

[0179] Step 3:

[0180] Xanthan gum (0.160g) was dissolved in glycerol (1 .077g), the solution was added to the solution prepared at Step 2 and the resulting mixture was left stirring while being heated at 65°C.

[0181] Step 4:

[0182] Hydroxyethyl cellulose (0.560g) was dissolved in glycerol (1 .600g), the solution was added to the solution prepared at Step 3 and the resulting mixture was left stirring while being heated at 65°C.The resulting mixture was left stirring vigorously for further 30 minutes and the pH of the mixture was measured. If necessary, the pH was adjusted to pH 5.5 with addition of citric acid monohydrate solution 10% w / w or sodium citrate dihydrate solution 10% w / w followed by additional 15 minutes of stirring. Then the mixture was allowed to cool down to room temperature. The citric acid solution was used to adjust the pH when a pH of the final mixture was higher than 5.5. The sodium citrate solution was used to adjust the pH when a pH of the final mixture was lower than 5.5.

[0183] A summary of the composition formed in Example 2

[0184] Component Content (wt%)

[0185] Water 94.407

[0186] Glycerol 2.677

[0187] Sodium chloride 0.900

[0188] Hydroxyethyl cellulose 0.560

[0189] Xylitol 0.432

[0190] Potassium sorbate 0.200

[0191] Methyl 4- hydroxy benzoate 0.200

[0192] Calcium gluconate monohydrate 0.179

[0193] Xanthan Gum 0.160

[0194] Potassium chloride 0.127

[0195] Magnesium chloride hexahydrate 0.081

[0196] Benzalkonium chloride aq. 50% 0.040

[0197] Sodium citrate dihydrate 0.020

[0198] L-Menthol 0.010

[0199] Citric acid monohydrate 0.006

[0200] Example 3 - Scanning Electron Microscopy (SEM) analysis of hydrogels

[0201] 3.1 Experimental

[0202] Samples used to assess differences in morphology as determined by SEM analysis were prepared from a composition outlined in Figure 5. The composition for this study was prepared similarly to the method outlined in Example 1 and Example 2.

[0203] For microscope observations, 500 pl of each mucophilic solution was transferred into a 48- well plate using a 1 ml pipette. The pipette tip was shortened for taking Sample E. Sample E was too viscous for pipetting and could only be transferred into the wells using a spatula. The well plate containing the gels was placed into a freezer at -80 °C for 8 hrs. Subsequently, the samples were freeze-dried at -50°C for 24 hrs using a freeze-dryer. In addition, a separate sample of Sample A was air-dried at 34°C and ambient pressure in an oven for 3 hours, and this air-dried sample was designated as Sample A-A.

[0204] Following freeze-drying, the samples were attached to aluminium stubs using double-sided conductive carbon tape and coated with a layer of platinum. Surface and cross-sectional images were acquired from the samples using a Zeiss Gemini SEM (Carl Zeiss Microscopy, Germany) with a 30 pm aperture and 5 kV accelerating voltage. The samples were fractured under liquid nitrogen for the cross-section observation.

[0205] 3.2 - Results

[0206] When applied to the nasal cavity, the composition (i.e. mucophilic solution) will be subjected to air in the nasal cavity with a flow rate of about 4 to 6 L / min at 32°C to 34°C, which can easily dehydrate the sprayed hydrogel film (i.e. coating) formed upon application or deposition of the composition in the nasal cavity. Air dehydration impacts the hydrogel’s properties substantially due to evaporation or dehydration.

[0207] The Samples A-E were prepared at a range of concentrations to evaluate their structural properties in hydrated and dehydrated states using scanning electron microscope (SEM) imaging. The hydrogel formed from Sample A-A usually showed a solid and compact structure with no evident pores on the micron scale. However, it should be appreciated that the hydrogel formed from Sample A-A would likely have pores on the nano-scale although this was not explored using SEM.

[0208] The morphological studies show different structures in bulk and at the surface of the samples. Figure 2 illustrates the cross-section morphologies of the freeze-dried samples obtained by SEM. The dried Sample A (Figure 2(a)), Sample B (Figure 2(b)), Sample C (Figure 2(c)), Sample D (Figure 2(d)), and Sample E (Figure 2(e)) show the typical porous structure of a freeze-dried hydrogel with a continuous porous gel skeleton. The dried samples demonstrate a heterogeneous macrostructure with irregular pore shapes. However, this macrostructure / morphology may be a result of factors such as the formulation, preparation method, freeze-drying process (temperature & pressure used), or the sample’s water content.

[0209] At all the concentrations tested, the samples displayed macropores larger than 100 pm, which were mostly disconnected. Microporous structures can also be observed on the walls of the macropores as marked with arrows in Figure 2(a) and 2(e), for Sample A and Sample D, respectively. The micropores in Sample E (Figure 2(e)i) are smaller than the pores in Sample A (Figure 2(a)i), which could be caused by the greater gel concentration. The pore sizes can decrease by increasing the mass concentration in the hydrogels. Although the microporous structures varied, they were mostly disconnected in both Sample E and Sample A. No microporous structures were observed in Sample B and Sample D.

[0210] The surface morphologies of the freeze-dried gels are shown in Figure 3(a)-(d). The decrease of the water content reduced the pore size, resulting in a decrease in surface roughness to some extent. For instance, the pore size on the surface of Sample A Figure 3(a)) is more than 100 pm, whereas the pore size is as small as 50 pm and 10 pm on the surface of Sample B (Figure 3 (b)) and Sample E (Figure 3 (d)) respectively. This observation indicates that the surface of the gels is porous for all tested water contents of the gel. On the contrary, the air-dried Sample A-A shows a non-porous surface at all tested magnifications in Figure 4(a)-(d). Without being bound by theory, it is thought that surface tension and similar factors experienced in air drying prevent the formation of pores on the micron scale.

[0211] For all samples there is an absence of pores large enough for passage of pathogens such as respiratory viruses. This indicates that air-drying of mucophilic solutions according results in a compact and continuous surface, which is consistent with previous findings for other airdried hydrogels.

[0212] 3.3 Conclusion

[0213] In this study, we observed that Samples A-E show a typical hydrogel porous structure after freeze-drying with pore sizes ranging from 5 to 150 pm. The observed pores constitute the liquid portion of the gel in the hydrated state. The pore size of the gels formed from Sample A-E were found to be directly proportional to water content as the porosity and pore size in Sample A was larger than compared with Sample E. In addition, the surface morphology of gels formed from Sample A-E showed porosity, which indicated the surface contained water. Decreased surface pore size was apparent as the water content decreased.

[0214] In contrast, Sample A-A which was air dried was non-porous structure. This demonstrates that Sample A, and also presumably Samples B-E, forms a solid and non-porous coating on the inside of the nasal cavity after application and air-drying that occurs due to the nasal breathing airflow and the local temperature of the cavity. As a result, the solid coating can act as a barrier and keep viruses, including human coronavirus 229E, away from the mucosal wall of the nasal cavity.

[0215] We note, however, that the pore structure of gels subject to freeze-drying can vary. As mentioned earlier, the pore size in the freeze-dried gels may vary due to several different factors such as cooling rate or pressure of the freeze-drying process. Hence, the inventors acknowledge that the pore sizes of the gels formed from Samples A-E are not absolute and may vary if the pre-freezing and freeze-drying process methodology are changed. However, the groups are comparable since all samples were prepared by the same protocol.

[0216] Example 4 - Assessment of the physical barrier functions of hydrogels

[0217] 4.1 - Method

[0218] 4.1.1 - Assessment of physical barrier

[0219] To provide quantitative data on the ability of four formulations to create a barrier and prevent Human Coronavirus OC43, Human Influenza A H1 N1 and Human Rhinovirus 1A infection, viral recovery was assessed after transit through 5 pm pore size HTS Transwell® membranes. Fifty microlitres of each product, at concentrations of 100%, 75% and 0.01% was added to wells and allowed to dry for 60 minutes, resulting in a barrier thickness of ~2.5 - 3 mm. Once dry, 100 pL of appropriate media was added to each well of the receiving plate. An aliquot of 125pL of viral stock suspension was then applied to each well of the HTS Transwell® plate, containing the pre-dried product barriers. Virus passing through the product barrier and HTS Transwell® membrane into the media in the receiving plate was recovered at 0.5, 3 and 6 hours. Virus added to wells of the HTS Transwell® plate containing no product were used to assess unimpeded viral transfer through the membrane. Fifty microlitres of virus-containing media was removed and subjected to 10-fold serial dilutions before plating onto MRC-5 cells (Human Coronavirus OC43), MDCK cells (Human Influenza type A H1 N1) and H1-HeLa cells (Human Rhinovirus 1A). MRC-5 cells were then incubated at 35 °C; 5% CO2 for 6 days, MDCK cells at 35 °C; 5% CO2 for 5 days and H1-HeLa cells at 33 °C; No CO2for 6 days. Following incubation, cells were visually inspected for cytopathic effects of viral infection.

[0220] Sample 1 and Sample 2 used in this test correspond, respectively, to gels formed using the composition as outlined in Example 1 and Example 2.

[0221] 4.1.2 Molecular quantification

[0222] For each virus, 70 pL samples were individually taken for each product concentration (100%, 75% and 0.01%) and time point (0, 0.5, 3 and 6 hours) in triplicate. Ribonucleic acid (RNA) was extracted from each sample using the QIAamp Viral RNA mini kit (Qiagen) according to manufacturer’s instructions. To quantify viral presence, samples were subjected to RT-qPCR using the GoTaq® 1-step RT-qPCR Master Mix (Promega) and species-specific primers. Obtained Cq values were compared to the relevant standard curve generated from 10-fold dilution series of either Human Coronavirus OC43, Human Influenza type A H1 N1 or Human Rhinovirus 1A to obtain final total viral concentrations (Log10TCID50mL-1).

[0223] 4.1.3 Statistical analysis

[0224] Average total viral concentrations (Log10TCID50mL-1) are presented as mean ± standard deviation (SD) from the 3 independent replicates per sample. A two-tailed unpaired Student’s t-Test was used to assess statistical differences between the detected Log10TCID50mL-1 data from each product concentration compared to the no product control at each time point. Data were considered statistically significant if p < 0.05.

[0225] 4.2 Results

[0226] 4.2.1 - Human Coronavirus OC43

[0227] The results for recovery of Human Coronavirus OC43 through different hydrogel formulation of an embodiment of the current disclosure is outlined in Table 2.

[0228] Control samples recorded the following average total viral recovery for Human Coronavirus OC43:

[0229] 0.5 hours: 11 .83 ± 0.38 LogioTCIDsomL1

[0230] 3.0 hours: 10.83 ± 0.38 LogioTCIDsomL1

[0231] 6.0 hours: 11 .17 ± 0.52 LogioTCIDsomL1 Table 2. Average Log recovery and reduction results for Human Coronavirus OC43 following transfer of virus through 5 gm HTS Transwell® membrane after 0.5, 3 or 6 hours at three concentrations of each test product (100%, 75% and 0.01%), when compared to the no product control.

[0232] N / A = Not applicable. NR = No reduction. SD = Standard deviation. *p < 0.05. Viral titre determined by TCID50 and Spearman-Karber method.

[0233] 4.2.2 - Human Rhinovirus 1A

[0234] The results for recovery of Human Influenza A H1 N1 through different hydrogel formulation of an embodiment of the current disclosure is outlined in Table 3.

[0235] Control samples recorded the following average total viral recovery for Human Coronavirus OC43:

[0236] 0.5 hours: 7.50 ± 0.25 LogioTCIDsomL-13.0 hours: 7.50 ± 0.25 LogioTCIDsomL-1

[0237] 6.0 hours: 6.50 ± 0.43 LogioTCIDsomL-1 Table 3. Average Log recovery and reduction results for Human Rhinovirus 1A following transfer of virus through 5 gm HTS Transwell® membrane after 0.5, 3 or 6 hours at three concentrations of each test product (100%, 75% and 0.01%), when compared to the no product control.

[0238] N / A = Not applicable. NR = No reduction. SD = Standard deviation. *p < 0.05. Viral titre determined by TCID50 and Spearman-Karber method.

[0239] 4.2.3 - Human Rhinovirus 1A The results for recovery of Human Influenza A H1 N1 through different hydrogel formulation of an embodiment of the current disclosure is outlined in Table 4.

[0240] Control samples recorded the following average total viral recovery for Human Coronavirus

[0241] OC43: 0.5 hours: 7.33 ± 0.14 LogioTCIDsomL-1

[0242] 3.0 hours: 8.08 ± 0.14 LogioTCIDsomL1

[0243] 6.0 hours: 8.33 ± 0.38 LogioTCIDsomL1 Table 4. Average Log recovery and reduction results for Human Rhinovirus 1A following transfer of virus through 5 gm HTS Transwell® membrane after 0.5, 3 or 6 hours at three concentrations of each test product (100%, 75% and 0.01%), when compared to the no product control.

[0244] N / A = Not applicable. NR = No reduction. SD = Standard deviation. *p < 0.05. Viral titre determined by TCID50 and Spearman-Karber method.

[0245] 4.3 - Summary

[0246] Respiratory viral infections (RVIs) can be associated with a wide range of clinical manifestations ranging from self-limited upper respiratory tract infections to more serious conditions requiring hospitalisation. Such infections constitute the most frequent reason for medical consultations in the world and they have a considerable impact on quality of life and productivity. Therefore, the prevention and treatment of RVIs remain major clinical goals.

[0247] All positive controls showed viral recoveries above the assay limit of detection for both viral recovery and genomic quantification and all negative controls showed no indications of viral CPE. Therefore, all assays are deemed to be valid. All Log reductions were calculated in comparison to the no product control.

[0248] 4.3.1 - Human Coronavirus OC43

[0249] Sample 1

[0250] Application of Sample 1 to the 5 pm HTS Transwell® membrane at 100% and 75% concentrations resulted in > 4 Log reductions in viral recovery for Human Coronavirus OC43 at all three time points. Molecular quantification demonstrated > 4 Log reductions for Human Coronavirus OC43 at 100% concentration at all three time points. At 75% concentration, > 4 Log reductions were demonstrated at 3 and 6 hours.

[0251] Sample 2

[0252] Application of Sample 2 to the 5 pm HTS Transwell® membrane at 100% and 75% concentrations resulted in > 4 Log reductions in viral recovery for Human Coronavirus OC43 at all three time points. Molecular quantification demonstrated > 4 Log reductions for Human Coronavirus OC43 at 100% concentration at all three time points.

[0253] 4.3.2 - Human Influenza A H1N1

[0254] Sample 1

[0255] Application of Sample 1 to the 5 pm HTS Transwell® membrane at 100% and 75% concentrations resulted in > 4 Log reductions in viral recovery for Human Influenza A H1 N1 at all three time points. Molecular quantification demonstrated > 4 Log reductions for Human Influenza A H1 N1 at 100% concentration at 0.5 and 3 hours only.

[0256] Sample 2

[0257] Application of Sample 2 to the 5 pm HTS Transwell® membrane at 100% concentration resulted in > 4 Log reductions in viral recovery for Human Influenza A H1 N1 at all three time points. At 75% concentration, > 4 Log reductions were observed at 0.5 and 3 hours only. Molecular quantification demonstrated > 4 Log reductions for Human Influenza A H1 N1 at 100% concentration at all three time points.

[0258] 4.3.3 - Human Rhinovirus 1A

[0259] Sample 1

[0260] Application of Sample 1 to the 5 pm HTS Transwell® membrane at 100% concentration resulted in > 4 Log reductions in viral recovery for Human Rhinovirus 1 A at all three time points. Molecular quantification demonstrated > 4 Log reductions for Human Rhinovirus 1A at 100% concentration at all three time points.

[0261] Sample 2

[0262] Application of Sample 2 to the 5 pm HTS Transwell® membrane at 100% concentration resulted in > 4 Log reductions in viral recovery for Human Rhinovirus 1 A at all three time points. At 75% concentration, > 4 Log reductions were observed at 3 and 6 hours only. Molecular quantification demonstrated > 4 Log reductions for Human Rhinovirus 1A at 100% concentration at all three time points. At 75% concentration, > 4 Log reductions were observed at 6 hours only.

[0263] 4.4 - Discussion

[0264] For this study, Sample 1 and Sample 2 were tested as barrier complexes against three respiratory viruses (Human Coronavirus OC43, Human Influenza A H1 N1 and Human Rhinovirus 1A). Both viral recovery via TCIDso and viral quantification via molecular detection demonstrated > 4 Log reductions for test items Sample 1 and Sample 2 against all three viruses.

[0265] Comparing results for TCID50 versus molecular detection showed greater viral concentration could be quantified via molecular detection, leading to occasional discrepancies when comparing results. However, it must be noted that viral quantification using molecular detection does not discriminate between infectious and non-infectious virus whereas viral recovery as measured by TCIDso is a measurement of infectious virus only. Comparison of the overall data set shows a high degree of similarity and consistency between the two methodologies.

[0266] In conclusion, the results shown above for both viral recovery and molecular detection show that Sample 1 and Sample 2 demonstrated good effectiveness as barrier complexes against each of the viruses used when applied to the 5 pm HTS Transwell® membrane at 100% and 75% concentrations.

[0267] It is noted that the efficacy for both Sample 1 and Sample 2 was superior to the applicant’s prior formulation as outlined in WO2022217319.

Claims

Claims1 . A composition that forms a film on mucosal lining to prevent contact of particles, pollutants and / or pathogens with the mucosal lining, the composition comprising: an aqueous-based solution; hydroxyethyl cellulose; a polysaccharide-based thickener including xanthan gum and / or guar gum; and one or more electrolytes including salts of sodium, potassium, calcium and magnesium.

2. A composition of claim 1 , containing up to 98 wt.% of the aqueous-based solution, up to 1 wt.% cellulose-based compound and up to 0.5 wt.% polysaccharide-based thickener.

3. A composition of claim 2, containing 90-98 wt.% of the aqueous-based solution, 0.1- 1 .0 wt.% cellulose-based compound, and 0.1 -0.5 wt.% polysaccharide-based thickener.

4. A composition of any one of claims 1 to 3, wherein the aqueous-based solution includes a polyol having one or more terminal hydroxyls.

5. A composition of claim 4, wherein the polyol includes a triol such as glycerine.

6. A composition of claim 4 or 5, wherein a wt.% ratio of [water]:[polyol] ranges from [90]:[5] to [99.9]:[0.1 ].

7. A composition of any one of claims 1 to 6, wherein the salts include sodium chloride, potassium chloride, calcium gluconate and / or magnesium chloride.

8. A composition of any one of claims 1 to 7, wherein the sodium salt has a concentration up to 0.9 wt.%, the potassium salt has a concentration up to 0.2 wt.%, the calcium salt has a concentration up to 0.3 wt.%, and the magnesium salt has a concentration up to 0.2 wt.%.

9. A composition of any one of claims 1 to 8, further comprising a flavourant includingxylitol and / or L-menthol.

10. A composition of any one of claims 1 to 9, further comprising a buffer such configured to buffer a pH of the aqueous-based solution.

11. A composition of claim 10, wherein the buffer includes citric acid and / or trisodium citrate.

12. A composition of claim 10 or 11 , wherein the buffer has a concentration up to 0.05 wt.%.

13. A composition of any one of claims 1 to 12, further comprising one or more preservatives.

14. A composition of claim 13, wherein the preservatives include methyl 4- hydroxybenzoate, potassium sorbate, benzalkonium chloride.

15. A composition of claim 13 or 14, wherein each of the one or more preservatives has a concentration ranging from 0.001 -0.5wt.%.

16. A composition of any one of claims 1 to 15, wherein the mucosal lining includes mucosal tissue.

17. A composition of any one of claims 1 to 16, wherein a pH of the composition ranges from 5.2 to 5.8.

18. A method of forming a composition that forms a film on mucosal lining to prevent contact of particles, pollutants and / or pathogens with the mucosal lining, the composition comprising: dissolving a cellulose-based compound in a polyol having one or more terminal hydroxyls to form dissolved cellulose-based compound; dissolving a polysaccharide-based thickener including xanthan gum and / or guar gum in a polyol having one or more terminal hydroxyls to form dissolved polysaccharide-based thickener; and diluting the dissolved cellulose-based compound and dissolved polysaccharide-based thickener with an aqueous-based solution having one or moreelectrolytes including salts of sodium, potassium, calcium and magnesium to form the composition.

19. A method of claim 18, wherein the polyol having one or more terminal hydroxyls includes glycerine.

20. A method of claim 18 or 19, wherein the aqueous-based solution is heated above room temperature when the dissolved cellulose-based compound and dissolved polysaccharide-based thickener are added to the aqueous-based solution.

21. A method of claim 20, wherein the aqueous-based solution is heated up to 75°C and diluting the dissolved cellulose-based compound and dissolved polysaccharide-based thickener with the aqueous-based solution includes stirring to mix the dissolved cellulose-based compound and dissolved polysaccharide-based thickener in the aqueous-based solution.

22. A method of any one of claims 18 to 21 , wherein after the cellulose-based compound and polysaccharide-based thickener have been diluted to form the composition, the composition contains up to 98 wt.% of the aqueous-based solution, up to 1wt.% cellulose-based compound and up to 0.5wt.% polysaccharide-based thickener.

23. A method of claim 22, wherein the composition contains 90-98 wt.% of the aqueousbased solution, 0.1-1 .Owt.% cellulose-based compound, and 0.1-0.5wt.% polysaccharide-based thickener.

24. A method of any one of claims 18 to 23, further comprising dissolving the one or more electrolytes in the aqueous-based solution prior to diluting the dissolved cellulose- based compound and dissolved polysaccharide-based thickener with the aqueousbased solution.

25. A method of any one of claims 18 to 24, wherein the salts include sodium chloride, potassium chloride, calcium gluconate and / or magnesium chloride.

26. A method of any one of claims 18 to 25, wherein, once the composition is formed, the sodium salt has a concentration up to 0.9 wt.%, the potassium salt has a concentration up to 0.2 wt.%, the calcium salt has a concentration up to 0.3 wt.%, andthe magnesium salt has a concentration up to 0.2 wt.%.

27. A method of any one of claims 18 to 26, further comprising dissolving a flavourant including xylitol and / or L-menthol in the aqueous-based solution prior to diluting the dissolved cellulose-based compound and dissolved polysaccharide-based thickener with the aqueous-based solution.

28. A method of any one of claims 18 to 27, further comprising dissolving a buffer in the aqueous-based solution prior to diluting the dissolved cellulose-based compound and dissolved polysaccharide-based thickener with the aqueous-based solution, the buffer configured to buffer a pH of the aqueous-based solution.

29. A method of claim 28, wherein the buffer includes citric acid and / or trisodium citrate.

30. A method of claim 28 or 29, wherein, once the composition is formed, the buffer has a concentration up to 0.05 wt.%.

31. A method of any one of claims 18 to 30, further comprising dissolving one or more preservatives in the aqueous-based solution prior to diluting the dissolved cellulose- based compound and dissolved polysaccharide-based thickener with the aqueousbased solution.

32. A method of claim 31 , wherein the preservatives include methyl 4-hydroxybenzoate, potassium sorbate, benzalkonium chloride.

33. A method of claim 31 or 32, wherein, once the composition is formed, each of the one or more preservatives has a concentration ranging from 0.001 -0.5wt.%.

34. A method of any one of claims 18 to 33, wherein the aqueous-based solution is at a temperature of 65°C.

35. A method of any one of claims 18 to 34, further comprising adjusting a pH of the aqueous-based solution to range from 5.2 to 5.8.

36. A method of forming a film or hydrogel on mucosal lining to prevent contact of particles, pollutants and / or pathogens with the mucosal lining, the method comprising:providing the composition of any one of claims 1 to 17; and applying the composition to the mucosal lining.

37. A method of claim 36, wherein applying the composition to a mucosal lining includes spraying the composition to form a mist or spray that deposits onto the mucosal lining upon contact thereby forming a film of the composition on the mucosal lining.

38. A method of claim 36 or 37, wherein the mucosal tissue is nasal mucosa.

39. A hydrogel that in use is applied of mucosal lining to prevent contact of particles, pollutants and / or pathogens with the mucosal lining, the hydrogel comprising: up to 98 wt.% of an aqueous phase prior to any dehydration of the hydrogel; up to 1 wt.% of hydroxyethyl cellulose; up to 0.5 wt.% of a polysaccharide-based thickener including xanthan gum and / or guar gum; and one or more electrolytes including salts of sodium, potassium, calcium and magnesium.

40. A hydrogel of claim 39, comprising prior to any dehydration of the hydrogel 90-98 wt.% of the aqueous-based solution, 0.1-1 .Owt.% cellulose-based compound, and 0.1-0.5wt.% polysaccharide-based thickener.

41. A hydrogel of claim 39 or 40, wherein the aqueous phase includes a polyol having one or more terminal hydroxyls.

42. A hydrogel of claim 41 , wherein the polyol includes a triol such as glycerine.

43. A hydrogel of claim 41 or 42, wherein a wt.% ratio of [water]:[polyol] ranges from [90]:[5] to [97]:[0.1] prior to any dehydration of the hydrogel.

44. A hydrogel of any one of claims 39 to 43, wherein the salts include sodium chloride, potassium chloride, calcium gluconate and / or magnesium chloride.

45. A hydrogel of any one of claims 39 to 44, wherein, prior to any dehydration of the hydrogel, the sodium salt has a concentration up to 0.9 wt.%, the potassium salt has a concentration up to 0.2 wt.%, the calcium salt has a concentration up to 0.3 wt.%,and the magnesium salt has a concentration up to 0.2 wt.%.

46. A hydrogel of any one of claims 39 to 45, further comprising a flavourant including xylitol and / or L-menthol.

47. A hydrogel of any one of claims 39 to 46, further comprising a buffer such configured to buffer a pH of the aqueous phase.

48. A hydrogel of claim 47, wherein the buffer includes citric acid and / or trisodium citrate.

49. A hydrogel of claim 47 or 48, wherein, prior to any dehydration of the hydrogel, the buffer has a concentration up to 0.05 wt.%.

50. A hydrogel of any one of claims 39 to 49, further comprising one or more preservatives.

51. A hydrogel of claim 50, wherein the preservatives include methyl 4-hydroxybenzoate, potassium sorbate, benzalkonium chloride.

52. A hydrogel of claim 50 or 51 , wherein, prior to any dehydration of the hydrogel, each of the one or more preservatives has a concentration ranging from 0.001 wt.% to 0.5wt.%.

53. A hydrogel of any of claims 39 to 52, wherein, prior to formation of the hydrogel, a pH of an aqueous phase of the hydrogel ranges from 5.2 to 5.8.

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