Natural-origin bioadhesive, biodegradable, protective microfilm barrier composition and method of use

Abstract

The disclosure relates to a bio-adhesive composition that in use forms a barrier on a substrate to prevent antagonists contacting the substrate. The composition may comprise at least 1.0 wt.% of a cellulose derivative, at least 0.1 wt.% of a gum-based compound, and an aqueous-based solvent. The composition may have a viscosity at a point-of-use of at least 10,000 cP.

Description

NATURAL-ORIGIN BIOADHESIVE, BIODEGRADABLE, PROTECTIVE MICROFILM BARRIER COMPOSITION AND METHOD OF USETECHNICAL FIELD

[0001] The present disclosure relates to the field of bio-adhesive microfilm barrier compositions.BACKGROUND ART

[0002] It is to be appreciated that any discussion of documents, devices, acts or knowledge in this specification is included to explain the context of the present disclosure. Further, the discussion throughout th is specification comes about due to the realisation ofthe inventor and / or the identification of certain related art problems by the inventor. Moreover, any discussion of material such as documents, devices, acts or knowledge in this specification is included to explain the context of the disclosure in terms of the inventor’s knowledge and experience and, accordingly, any such discussion should not be taken as an admission that any of the material forms part of the prior art base or the common general knowledge in the relevant art in Australia, or elsewhere, on or before the priority date of the disclosure and claims herein.

[0003] Skin is the outer covering of the human or animal body that serves as a protective barrier between the internal organs and the environment. In humans, it is the largest organ, and it has a complex structure that allows it to perform a variety of functions.

[0004] The skin of humans comprises three layers: the epidermis, the dermis, and the hypodermis (also called subcutaneous tissue). The epidermis is the outermost layer responsible for protecting the body from external damage. It contains several types of cells, including keratinocytes, melanocytes, and Langerhans cells, which play different roles in skin function.

[0005] The dermis is the middle layer of the skin, containing blood vessels, nerves, and connective tissue. It is responsible for providing the skin with its elasticity and strength. The hypodermis is the deepest layer of the skin, and it consists of adipose tissue that provides insulation and cushioning for the body.

[0006] The skin also contains several appendages, such as hair follicles, sweat glands, and sebaceous glands, which play important roles in regulating body temperature and protecting the skin from external factors.

[0007] Overall, the skin is a complex and vital organ that performs a variety of important functions to protect the body and maintain homeostasis.

[0008] The term bio-adhesion describes the adhesion of natural or synthetic materials to biological tissues. Dermophilic bio-adhesive compositions such as cross-linked polymers that form hydrogels have been used in the past for the delivery of drugs such as antibiotics and steroids, over a prolonged period. There is increasing interest in dermophilic bio-adhesive compositions that can similarly adhere to epidermis.

[0009] A face skin primer is a cosmetic product that is applied to the skin before the application of makeup. It is primarily used to create a smooth and even surface for makeup application, helping to minimize the appearance of pores, fine lines, and imperfections. Face primers typically have a lightweight and silky texture that glides easily over the skin, allowing makeup to adhere better and last longer.

[0010] Commonly used types of face skin primers include the following:

[0011] Silicone-based Primers: These primers contain silicone derivatives such as dimethicone, which create a smooth and velvety finish on the skin. Silicone-based primers help to fill in pores and fine lines, resulting in a more flawless complexion.

[0012] Water-based Primers: These primers have a lighter consistency and are suitable for individuals with oily skin or combination skin (having dry areas and oily areas). Water-based primers provide hydration without adding excess oil to the skin.

[0013] Colour-Correcting Primers: These primers are tinted in different shades to counteract specific skin tone concerns. For example, a green-toned primer can neutralize redness, while a purple- toned primer can brighten dull skin.

[0014] Illuminating Primers: These primers contain light-reflecting particles or subtle shimmer to create a radiant glow. Illuminating primers are suitable for individuals who want to achieve a luminous complexion.

[0015] Mattifying Primers: These primers are designed for people with oily skin. They help to control shine and reduce oil production, providing a matte finish.

[0016] Many skincare products and dermal fillers use low molecularweight hyaluronic acid (LMW- HA), which is a naturally occurring substance found in our bodies, particularly in the skin, connective tissues, and eyes. It has gained significant popularity in the field of cosmetic dermatology due to its hydrating and anti-aging properties. When used in skincare products or dermal fillers, hyaluronic acid can provide various benefits for the face and skin.

[0017] A properly functioning dermal system provides protection against various bio-antagonists. Where used herein, the term ‘bio-antagonist’ includes agents that may be toxic or non-toxic and may be living or non-living, organic or inorganic. Bio-antagonists include a wide range of macro, micro and nano particles (e.g., pollutants and dirt) and pathogens (e.g., viruses, bacteria and fungi). Other bioantagonists include industrial and occupational health risks such as soot, cement, lime, asbestos fertilisers and other compositions and compounds that a subject is likely to contact in a workplace.

[0018] When the protection of the dermal system is breached, the bio-antagonist can trigger a range of tissue reactions in the form of infection and / or inflammation.

[0019] A bio-antagonist can trigger local or systemic reactions and depend on many factors, including the nature, affinity, pathogenicity and virality of the bio-antagonist. The reaction may range from mild to moderate or severe in humans or animals.

[0020] The term bio-adhesion describes the adhesion of natural or synthetic materials to biological tissues. Dermophilic bio-adhesive compositions, such as cross-linked polymers that form hydrogels, have been used to deliver drugs, such as antibiotics and steroids, over a prolonged period. There is increasing interest in dermophilic bio-adhesive compositions that can similarly adhere to the epidermis.

[0021] 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.SUMMARY

[0022] An embodiment provides a bio-adhesive composition that in use forms a barrier on a substrate to prevent antagonists contacting the substrate, the composition comprising: at least 1 .0 wt.% of a cellulose derivative; at least 0.1 wt.% of a gum-based compound; and an aqueous-based solvent; wherein the composition has a viscosity at a point-of-use of at least 10,000 cP.

[0023] The cellulose derivative may be present in an amount ranging from 1.0 to 20 wt.%. The cellulose derivative may be present in an amount ranging from 1 .0 to 2.0 wt%. The cellulose derivative may be present in an amount ranging from 2.0 to 4.0 wt%. The cellulose derivative may be present in an amount ranging from 4.0 to 20 wt.%. The cellulose derivative may be selected from the group consisting of hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, and combinations thereof.

[0024] The gum may be present in an amount ranging from 0.05 to 3.0 wt%. The gum may be present in an amount ranging from 0.1 to 1 .0 wt%. The gum may be selected from the group consisting of guar gum, xanthan gum, sclerotium gum, agar agar, and combinations thereof.

[0025] The composition may have a viscosity at point-of-use of at least 15,000 cP, 20,000 cP, or30,000 cP. The composition may have a viscosity at point-of-use of at ranging from 20,000 cP to 70,000 cP.

[0026] The bio-adhesive composition may further comprise a plasticizer. The plasticizer may be present in an amount up to 8.0 wt%. The plasticizer may be selected from the group consisting of glycerol, propylene glycol, polyethylene glycol, and combinations thereof.

[0027] The bio-adhesive composition may have a water content of at least 80wt.%. The bioadhesive composition may have a water content up to 40wt.%.

[0028] The bio-adhesive composition may further comprise an alcohol. The alcohol may be present in an amount ranging from 35 to 85 wt.%.

[0029] The bio-adhesive composition may further comprise ascorbic and / or citric acid and salts thereof.

[0030] The bio-adhesive composition may further comprise one or more additives. The one or more additives may include an emulsifier, skin conditioner, a dye, fragrant, flavourant and / or antimicrobial agent. The one or more additives may include menthol, xylitol, glyceryl caprylate, glyceryl undecylenate and / or benzalkonium chloride.

[0031] The bio-adhesive composition may have a dry-out time of at most 90 seconds.

[0032] The substrate may be a living integument.

[0033] An embodiment provides a method of forming a barrier on a living integument, comprising: applying the bio-adhesive composition as set forth above to the living integument; and allowing the bio-adhesive composition to dry to reduce its water content to form the barrier.

[0034] The living integument may be a hand. The living integument may be a face.

[0035] An embodiment may provide a composition for temporarily adhering to the skin, consequently protecting the skin from contacting bio-antagonists and / or or preventing egress of skin cells.

[0036] An embodiment may alleviate at least one disadvantage associated with the related art.

[0037] An embodiment may overcome or alleviate at least one of the above noted drawbacks of related art systems or at least provide a useful alternative to related art systems.

[0038] In its broadest form, an embodiment provides a bio-adhesive composition comprising one or more natural-origin substances, wherein the bio-adhesive forms a barrier between bio-antagonists and living integument. The microfilm barrier may be physical or physico-chemical, such as, by providing a bactericidal, fungicidal or virucidal effect on pathogenic microorganisms.

[0039] In a first aspect of embodiments described herein, there is provided a bio-adhesive composition comprising:- at least one cellulose derivative,- a carrier solution, and- optionally, one or more excipients, wherein when applied to living integument, the bio-adhesive composition forms a barrier between bioantagonists and the living integument.

[0040] In an embodiment, the barrier is a microfilm having a mesh-like structure for retarding egress of skin cells from living skin and ingress of antagonistic agents.

[0041] The composition may comprise one or more actives such as an antiviral agent, an antibacterial agent (such as an anti-gram positive or anti-gram negative bacterial agent), an antifungal or other pharmaceutically active agent.

[0042] In a second aspect of embodiments described herein there is provided a bio-adhesive metamorphic microfilm composition comprising:- at least one cellulose derivative,- a carrier solution, and optionally one or more excipients, wherein when applied to a living integument, the bio-adhesive metamorphic microfilm forms a barrier between bio-antagonists and the living integument.

[0043] In an embodiment of the bio-adhesive composition, the composition may act as a barrier ‘glove’ or microfilm glove for the hands of a subject to protect them from bio-antagonists. The barrier ‘glove’ may also retard or prevents skin cells from the integument being released into the environment. This may be advantageous in environments such as clean rooms used in industries that require a controlled environment for product manufacture. These include, for example, the electronics, pharmaceutical and medical equipment industries, where airborne particles such as skin cells may contaminate the products being made.

[0044] In a third aspect of embodiments described herein, there is provided a bio-adhesive composition comprising:- 0.4 to 5.0 wt%, preferably 0.50 to 3.00 wt% of one or more cellulose derivatives,- 80.0 to 99.0 wt% of a carrier, and- 0.9 to 5.0 wt% of one or more excipients, wherein when applied to living integument, the bio-adhesive forms a barrier between bio-antagonists and the living integument.

[0045] In a fourth aspect of embodiments described herein, there is provided a bio-adhesive composition comprising:- 0.40 to 3.00 wt% of a cellulose derivative chosen from hydroxypropyl cellulose, hydroxypropyl methylcellulose or hydroxyethyl cellulose,- 0.15 to 3.50 wt% of thickeners,- 80.0 to 99.0 wt% of an aqueous carrier solution,- 0.00 to 3.50 wt% of alcohol, and- 0.01 to 3.0 wt% of other excipients, wherein when applied to living integument, the bio-adhesive forms a barrier between bio-antagonists and the living integument.

[0046] The term “microfilm” when used with reference to the present disclosure, typically means a type of film that is comprised of a mesh-like structure on a micro-scale such as a micro-mesh or a nano-mesh structure.

[0047] Where used herein, the term “metamorphic” refers to a characteristic of the microfilm whereby it has the ability to change its properties from hydrogel to microfilm in response to external stimuli, such as changes in temperature, pressure, humidity or pH.

[0048] Where used herein the term “metamorphic microfilm” refers to a characteristic of the microfilm whereby it has the ability to change its properties in response to external stimuli, such as changes in temperature, pressure or pH. One of the key changes that occur during the changes in external stimuli is a reduction in a number of pores (openings) of cells that are positioned closest to the surface of the microfilm that is facing external environment, and that the pores throughout the microfilm are reduced or have collapsed.

[0049] The cellulose derivatives may be derived from plant matter or synthesised. The cellulose derivative may be chosen from the group comprising methyl cellulose (MC), carboxymethyl cellulose (CMC), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), hydroxy propyl methyl cellulose (HPMC) and other cellulose esters. The cellulose derivative may be hydroxyethyl cellulose or hydroxypropyl cellulose.

[0050] The carrier solution may include one or more biologically compatible liquids such as water, and alcohol. Suitable alcohols may include isopropyl alcohol, propyl glycol, polyethylene glycol, glycerol and mixtures thereof.

[0051] The optional excipients may include thickeners and / or gelling agent such as guar gum, xanthan gum, sclerotium gum, or agar; preservatives such as benzalkonium chloride, glyceryl caprylate (and) glyceryl undecylenate; buffers sequestering agents; emulsifiers, colourants; perfumes and dyes.

[0052] Typically, any dye used in the composition does not stain the skin and may include dyes that are commonly used in cosmetics. These include for example, FD&C (food, drug & cosmetic) dyes, D&C (drug & cosmetic) dyes, lakes, iron oxides and mica.

[0053] In a fifth aspect of embodiments described herein there is provided a method of forming a barrier between bio-antagonists and living integument, the method comprising applying to said integument, a composition comprising;- at least one cellulose derivative,- a carrier solution, and optionally, one or more excipients and / or pharmaceutical actives, wherein the bio-adhesive forms a barrier between bio-antagonists and the living integument.

[0054] The composition of one or more embodiments of the present disclosure may be applied to the integument in any convenient dosage form including, but not limited to, gels, creams, ointments, films, emulsions, aerosols and sprays. The composition may be delivered to epidermis where it may form a coating, onto the epidermal surface. Examples of suitable applicators include squeeze tubes, pumps, sprays and aerosol dispensers.

[0055] Using the aforementioned applicators, the composition may be applied to living integument. For example, the composition may be used as a protective barrier in the nature of a temporary ‘glove’ or “Glove-ln-A-Spray” to protect the hands of a subject from bio-antagonists.

[0056] In a sixth aspect of embodiments described herein there is provided a method of use of a bioadhesive composition, the method comprising the step of combining (in any order), the at least one cellulose derivative, the carrier solution, and the one or more optional excipients and / or pharmaceutical actives.

[0057] In a seventh aspect of embodiments described herein there is provide a method of using a bioadhesive composition, the method comprising the steps of: forming a carrier solution, combining a cellulose derivative with the solution,- combining one or more excipients with the solution and / or pharmaceutical active.

[0058] In an eighth aspect of embodiments described herein, the composition of the first, third or fourth aspect or the foam of the second aspect is used to form a barrier between bio-antagonists and the living integument.

[0059] In a ninth aspect of embodiments described herein, there is an article comprising the barrier formed according to the fifth aspect.

[0060] In essence, one or more embodiments stem from the realisation that a particular composition of one or more ingredients in a thickened solution can provide suitable adhesion to one or more biological surfaces, such as epidermal surfaces, to deliver a prophylactic effect against one or more bio-antagonists.

[0061] Advantages provided by one or more embodiments may comprise the following:• the bio-adhesive composition does not disturb the chemical composition of the epidermis.• the bio-adhesive solution enhances the ability of the epidermis to resist adherence or penetration of pathogens, and• the bio-adhesive composition is readily administered.

[0062] Further scope of applicability of embodiments of the present disclosure will become apparent from the detailed description given hereinafter. However, it should be understood that the detailed description and specific examples, while indicating preferred embodiments, are given by way of illustration only since various changes and modifications within the spirit and scope of the disclosure herein will become apparent to those skilled in the art from this detailed description.DETAILED DESCRIPTION

[0063] The bio-adhesive compositions described herein may address several challenges related to protecting a substrate, such as a living integument, against antagonists. Existing barrier methods may not provide adequate protection against a wide range of potential antagonists while maintaining comfort and ease of use for the wearer. Additionally, traditional gloves or protective coverings may interfere with dexterity and tactile sensation, limiting their practicality in many applications.

[0064] One or more embodiments of the disclosed composition may form a film, such as a thin and flexible microfilm barrier, when applied. This microfilm may adhere closely to the contours of thesubstrate, such as skin, while allowing for natural movement and sensation. In some cases, the barrier may protect against microbial pathogens, allergens, irritants, and other bio-antagonists that could potentially harm or penetrate the skin. The barrier may also help prevent the shedding of skin cells into sensitive environments where contamination must be strictly controlled.

[0065] Unlike conventional barrier methods, one or more embodiments of the bio-adhesive compositions described herein may be applied as a liquid or gel that rapidly dries to form an imperceptible protective layer. This application method may allow for precise coverage of desired areas without the bulk or restrictions of pre-formed gloves or coverings. The resulting barrier may be breathable and comfortable for extended wear in various environmental conditions.

[0066] Furthermore, one or more embodiments of the compositions may be formulated to include additional active ingredients that provide supplementary benefits beyond the physical barrier function. These may include antimicrobial agents, moisturizers, or other compounds to support skin health and enhance protection. The versatility of the formulation may allow for customization to suit different applications and user needs.

[0067] Embodiments will now be described in more detail with reference to the following detailed description.

[0068] One or more embodiments provides a bio-adhesive composition that in use forms a barrier on a substrate to prevent antagonists contacting the substrate, the composition comprising: at least 1 .0 wt.% of a cellulose derivative; at least 0.1 wt.% of a gum-based compound; and an aqueous-based solvent; wherein the composition has a viscosity at a point-of-use of at least 10,000 cP.

[0069] The substrate may be an integument, such as a living integument. The substrate may include biological material, such as fruit, vegetables, and so on. The substrate may be an integument, such as a living integument. The substrate may include living biological material, such as fruits, vegetables, plants, seeds, flowers, and fungi. Furthermore, the substrate may be a non-living biological material and may comprise animal-derived biological materials, such as eggshells, meat, seafood, dairy products, and animal hides. Additionally, the substrate may include processed or prepared food items, such as baked goods, confections, and ready-to-eat meals. The substrate may further extend to non-living and non-biological medical and pharmaceutical materials, including wound dressings, surgical drapes, implants, prosthetic devices, and medical textiles. Moreover, the substrate may encompass non-biological materials, including food packaging surfaces, food preparation equipment, laboratory and medical instruments, consumer goods, textiles, fabrics, leather, synthetic polymers, and various industrial surfaces.

[0070] One or more embodiments provide a bio-adhesive composition comprising; at least one cellulose derivative, a carrier, typically in the form of an aqueous solution and optionally including an alcohol, and optionally, one or more excipients and / or a pharmaceutical actives, wherein when applied to living integument the bio-adhesive forms a barrier between bio-antagonists and the living integument.

[0071] The bio-adhesive may be a metamorphic microfilm as described above, that forms a barrier between bio-antagonists and the living integument.

[0072] In an embodiment, the bio-adhesive composition may be applied to the epidermis of a subject’s hands as a barrier or film ‘glove’ to protect them from bio-antagonists. The bio-adhesive may be a metamorphic microfilm having a mesh-like structure for retarding or preventing egress of skin cells from living skin and ingress of antagonistic agents. The bio-adhesive composition may be applied to the dermis of a subject’s face to act as a ‘primer’ for cosmetics.

[0073] An embodiment provides a bio-adhesive composition that in use forms a barrier on a substrate to prevent antagonists contacting the substrate, the composition comprising: at least 1 .0 wt.% of a cellulose derivative; at least 0.1 wt.% of a gum-based compound; and an aqueous-based solvent; wherein the composition has a viscosity at a point-of-use of at least 10,000 cP. The barrier may be a film that is formed in situ on the substrate. For example, the composition may be applied to the substrate as a liquid or gel which subsequently dries or dehydrates to form a film on the substrate.

[0074] As used herein, the term "integument" may refer to a natural outer covering or envelope of an organism. In humans and animals, the integument typically includes the skin and its associated structures such as hair, scales, or feathers. The integument may serve various functions including protection against external factors, regulation of body temperature, and sensory perception. In the context of this disclosure, "integument" may particularly refer to the skin or other external tissue surfaces to which the bio-adhesive composition can be applied to form a protective barrier.

[0075] As used herein, the term "antagonist" may refer to any substance, agent, or factor that opposes, interferes with, or counteracts the normal functioning of a biological system or organism. This may include physical, chemical, or biological entities that can potentially cause harm, irritation, or disruption to living tissues or organisms. The term "bio-antagonist" may specifically refer to biological agents such as pathogens, allergens, or other microorganisms that can adversely affect living systems. Antagonists may encompass a wide range of entities including, but not limited to, bacteria, viruses, fungi, parasites, toxins, pollutants, allergens, dust, particulate matter, industrial contaminants, environmental debris, microplastics, pollen, smoke particles, soot, ash, chemical residues, and other harmful substances that may come into contact with or penetrate the integument. In an embodiment, the bio-adhesive composition may create a barrier, such as a film, that prevents the passage of pathogens across the barrier.

[0076] Cellulose Derivative

[0077] The cellulose derivatives may be derived from plant matter or synthesised. The cellulose derivative may be chosen from the group comprising of methyl cellulose, carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose and other cellulose esters. The cellulose derivative may be hydroxyethyl cellulose, hydroxypropyl methyl cellulose and / or hydroxypropyl cellulose.

[0078] The cellulose derivative contributes to the adhesive properties of the composition and ensures the controlled release of the active ingredient. Without wishing to be bound by theory it isbelieved that the cellulose derivative may form Van der Waals forces with the skin surface, allowing the bio-adhesive to adhere to the skin. Additionally, the bioadhesive may also act as a thickening agent in the formulation, improving its viscosity and stability.

[0079] The cellulose derivative may be present in an amount ranging from 1 .0 to 2.0 wt% of the total composition. In an embodiment, the cellulose derivative may be present in an amount ranging from 1 .1 to 1.9 wt%. The cellulose derivative may be present in an amount ranging from 1.2 to 1.8 wt%. In an embodiment, the cellulose derivative may be present in an amount ranging from 1 .3 to 1 .7 wt%. The cellulose derivative may be present in an amount ranging from 1 .4 to 1 .7 wt%. The cellulose derivative may be present in an amount ranging from 1 .5 to 1 .7 wt%. The cellulose derivative may be present in an amount ranging from 1 .55 to 1 .65 wt%. In an embodiment, the cellulose derivative may be present in an amount of at least 1 .1 wt%. The cellulose derivative may be present in an amount of at least 1.2 wt%. The cellulose derivative may be present in an amount of at least 1.3 wt%. The cellulose derivative may be present in an amount of at least 1 .4 wt%. The cellulose derivative may be present in an amount of at least 1 .5 wt%. In an embodiment, the cellulose derivative may be present in an amount of up to 2.0 wt%. The cellulose derivative may be present in an amount of up to 1 .9 wt%. The cellulose derivative may be present in an amount of up to 1 .8 wt%. The cellulose derivative may be present in an amount of up to 1 .7 wt%.

[0080] The cellulose derivative may be present in an amount ranging from 2.0 to 4.0 wt% of the total composition. In an embodiment, the cellulose derivative may be present in an amount ranging from 2.0 to 3.8 wt%. In an embodiment, the cellulose derivative may be present in an amount ranging from 2.0 to 3.6 wt%. In an embodiment, the cellulose derivative may be present in an amount ranging from 2.0 to 3.4 wt%. In an embodiment, the cellulose derivative may be present in an amount ranging from 2.0 to 3.2 wt%. In an embodiment, the cellulose derivative may be present in an amount ranging from 2.0 to 3.0 wt%. In an embodiment, the cellulose derivative may be present in an amount ranging from 2.0 to 2.9 wt%. In an embodiment, the cellulose derivative may be present in an amount ranging from 2.0 to 2.8 wt%. In an embodiment, the cellulose derivative may be present in an amount ranging from 2.0 to 2.7 wt%. In an embodiment, the cellulose derivative may be present in an amount ranging from 2.1 to 3.0 wt%. In an embodiment, the cellulose derivative may be present in an amount ranging from 2.2 to 3.0 wt%. In an embodiment, the cellulose derivative may be present in an amount ranging from 2.3 to 3.0 wt%. In an embodiment, the cellulose derivative may be present in an amount ranging from 2.3 to 2.7 wt%. In an embodiment, the cellulose derivative may be present in an amount ranging from 2.4 to 2.6 wt%. The cellulose derivative may be present in an amount of about 2.5 wt%.

[0081] The cellulose derivative may be present in an amount of at least 4.0 wt% of the total composition. In an embodiment, the cellulose derivative may be present in an amount of at least 5.0 wt%. The cellulose derivative may be present in an amount of at least 6.0 wt%. In an embodiment, the cellulose derivative may be present in an amount of at least 7.0 wt%. The cellulose derivative may be present in an amount of at least 8.0 wt%. In an embodiment, the cellulose derivative may be present in an amount of at least 10.0 wt%. The cellulose derivative may be present in an amount of up to 20 wt%. The cellulose derivative may be present in an amount of up to 19 wt%. The cellulose derivativemay be present in an amount of up to 18 wt%. The cellulose derivative may be present in an amount of up to 17 wt%. The cellulose derivative may be present in an amount of up to 16 wt%. The cellulose derivative may be present in an amount of up to 15 wt%. The cellulose derivative may be present in an amount ranging from 5 to 15 wt% of the total composition. In an embodiment, the cellulose derivative may be present in an amount ranging from 6 to 14 wt%. The cellulose derivative may be present in an amount ranging from 7 to 13 wt%. In an embodiment, the cellulose derivative may be present in an amount ranging from 8 to 12 wt%. The cellulose derivative may be present in an amount ranging from 9 to 11 wt%. The cellulose derivative may be present in an amount of about 10 wt%.

[0082] Carrier Solution

[0083] The bio-adhesive composition may comprise any convenient solvent such as one or more of alcohol, water and glycerol. The solvent may comprise at least 99.00 wt%, such as 94.55 to 99.99 wt% of the composition.

[0084] The carrier solution may include the following components:

[0085] Glycerol

[0086] Glycerol, also known as glycerin, is a colourless, odorless, viscous liquid that is widely used in various industries, including cosmetics, food, and pharmaceuticals.

[0087] In topical preparations, glycerol is commonly used as a humectant, helping to retain moisture in the skin by attracting water from the environment and the deeper layers of the skin. It is also used as a solvent, a lubricant, and a vehicle for active ingredients.

[0088] Glycerol is found in many skincare products, such as moisturisers, lotions, and creams. It is particularly useful for people with dry, dehydrated, or sensitive skin because it helps to soothe and hydrate the skin, reducing the appearance of fine lines and wrinkles. It is also known to have antimicrobial properties, which makes it beneficial in preventing or treating acne.

[0089] Alcohol

[0090] The carrier solution may include a low-carbon alcohol such as ethanol and / or isopropyl alcohol, also known as isopropanol, is a colourless, flammable liquid with a strong odour. Ethanol and isopropyl alcohol are disinfectants that are used in a variety of applications.

[0091] As a solvent, low-carbon alcohols are used to dissolve and dilute a wide range of substances, including oils, resins, and gums. It is often used in the manufacture of pharmaceuticals, cosmetics, and personal care products. Isopropyl alcohol is also used as a solvent in the production of a variety of consumer products, such as cleaning agents, paints, and inks.

[0092] As a disinfectant, ethanol and / or isopropyl alcohol are effective at killing a wide range of microorganisms, including bacteria, viruses, and fungi. It is often used to disinfect surfaces in hospitals, laboratories, and other healthcare settings. Isopropyl alcohol is also used to disinfect medical equipment and instruments.

[0093] The alcohol content in the composition may vary depending on the specific formulation and intended use. In some embodiments, the alcohol may be present in an amount ranging from 0.1 to 80 wt% of the total composition. In some embodiments, the alcohol may be present in an amount ranging from 35 to 80 wt% alcohol. In some embodiments, the alcohol may be present in an amount ranging from 40 to 80 wt% alcohol. In some embodiments, the alcohol may be present in an amount ranging from 45 to 80 wt% alcohol. In some embodiments, the alcohol may be present in an amount ranging from 50 to 80 wt% alcohol. In some embodiments, the alcohol may be present in an amount ranging from 55 to 80 wt% alcohol. In some embodiments, the alcohol may be present in an amount ranging from 60 to 80 wt% alcohol. In some embodiments, the alcohol may be present in an amount ranging from 65 to 80 wt% alcohol. In some embodiments, the alcohol may be present in an amount ranging from 70 to 80 wt% alcohol. In some embodiments, the alcohol may be present in an amount ranging from 75 to 80 wt% alcohol. In some embodiments, the alcohol may be present in an amount ranging from 50 to 75 wt% alcohol. In some embodiments, the alcohol may be present in an amount ranging from 50 to 70 wt% alcohol. In some embodiments, the alcohol may be present in an amount ranging from 50 to 65 wt% alcohol. In some embodiments, the alcohol may be present in an amount ranging from 50 to 60 wt% alcohol. In some embodiments, the alcohol may be present in an amount ranging from 50 to 55 wt% alcohol.

[0094] In other embodiments where lower alcohol content is desired, the composition may contain 0.5 to 35 wt% alcohol. For certain applications, the alcohol content may range from 1 to 20 wt%. In some cases, the composition may contain 5 to 15 wt% alcohol. The specific alcohol concentration may be adjusted based on factors such as the desired drying time, antimicrobial efficacy, and overall formulation stability.

[0095] Water

[0096] A solvent may include purified water, that is, water that has been treated to remove impurities, such as minerals, chemicals, and microorganisms. This can be achieved through various purification methods, such as distillation, reverse osmosis, or deionisation.

[0097] As a solvent, purified water is a highly effective medium for dissolving a wide range of substances, including salts, acids, bases, and polar organic compounds. It is often used in industrial processes, laboratory experiments, and pharmaceutical preparations as a solvent due to its high purity and low levels of impurities.

[0098] In addition, purified water is used as a solvent in many consumer products, such as cosmetics, cleaning agents, and personal care products. Its use in these products helps ensure that they are safe for use on the skin or around the home.

[0099] The water content of the formulation may vary depending on the specific application and desired properties of the bio-adhesive composition. In some embodiments, the water content may range from 5 to 99 wt.% of the total composition. For formulations with higher viscosity, the water content may be in the range of 80 to 95 wt.%. In some embodiments, the water content may be at least 80 wt.% at least 81 wt.% at least 82 wt.%, at least 83 wt.%, at least 84 wt. %at least 85 wt.%, atleast 86 wt.% at least 87 wt.% at least 88 wt.%, at least 89 wt.%, at least 90 wt.%, at least 91 wt.%, or at least 92 wt.% of the total composition. In an embodiment, a water content of the formulation ranges from 80 to 95 wt.%, such as 85 to 95 wt.%. The water content may range from 5 to 80 wt.%. In some embodiments, the water content may range from 30 to 70 wt.%, 40 to 60 wt.%, or 45 to 55 wt.% of the total composition. For example, when alcohol is included in the composition, a water content of the formulation may be up to 40 wt.%. A water content of the formulation may range from 5 to 40 wt.%. such as about 20 to 36 wt.%. A water content of the formulation may be up to 35 wt.%. A water content of the formulation may be up to 30 wt.%. A water content of the formulation may be up to 25 wt.%. A water content of the formulation may be up to 20 wt.%. A water content of the formulation may be up to 15 wt.%. A water content of the formulation may be up to 10 wt.%. A water content of the formulation may be at least 5 wt.%. A water content of the formulation may be at least 10 wt.%. A water content of the formulation may be at least 15 wt.%. A water content of the formulation may be at least 20 wt.%. A water content of the formulation may be at least 25 wt.%. A water content of the formulation may be at least 30 wt.%. A water content of the formulation may be at least 35 wt.%.

[0100] In certain applications, the water content may be adjusted to balance other components in the formulation. For instance, in formulations containing higher amounts of alcohol, the water content may be reduced to 8 to 40 wt%.

[0101] The specific water content may be selected based on factors such as the desired consistency, drying time, and interaction with other ingredients in the bio-adhesive composition. The optimal water content may also depend on the intended use and application method of the formulation.

[0102] Excipients

[0103] The composition may include one or more excipients and may include thickening agents such as guar gum; preservatives such as benzalkonium chloride; antioxidants such as sodium metabisulphite or propyl gallate; antibacterial and antifungals such as potassium sorbate; antimicrobials such as methyl hydroxybenzoate (methylparaben); buffers; gelling agents; sequestering agents; emulsifiers, colourants; perfumes and dyes.

[0104] Thickening Agent

[0105] The composition may comprise any convenient thickening agent to obtain the optimal viscosity for the composition and may cause the composition to thicken or gel or coagulate. These include food-grade or pharmaceutical-grade thickening agents including, for example, glycerin, carrageenan, sugar, guar gum, methylcellulose, hydroxyethyl cellulose, sclerotium gum, agar agar and / or xanthan gum. The thickeners may be used individually or in combination.

[0106] The thickener (e.g. gum-based compound) may comprise 0.1 to 3.00 wt% of the composition. In an embodiment, the composition includes at least 0.1 wt.% of a gum-based compound. In an embodiment, the composition includes at least 0.15 wt.% of a gum-based compound. In an embodiment, the composition includes at least 0.2 wt.% of a gum-based compound. In an embodiment, the composition includes at least 0.25 wt.% of a gum-based compound. In an embodiment, the composition includes at least 0.3 wt.% of a gum-based compound. In anembodiment, the composition includes at least 0.35 wt.% of a gum-based compound. In an embodiment, the composition includes at least 0.4 wt.% of a gum-based compound. In an embodiment, the composition includes at least 0.45 wt.% of a gum-based compound. In an embodiment, the composition includes at least 0.5 wt.% of a gum-based compound.

[0107] In an embodiment, the composition includes an amount of gum-based compound ranging from 0.1 wt.% to 1 .5 wt.%. In an embodiment, the composition includes an amount of gum-based compound ranging from 0.1 wt.% to 1 .4 wt.%. In an embodiment, the composition includes an amount of gum-based compound ranging from 0.1 wt.% to 1.3 wt.%. In an embodiment, the composition includes an amount of gum-based compound ranging from 0.1 wt.% to 1.2 wt.%. In an embodiment, the composition includes an amount of gum-based compound ranging from 0.1 wt.% to 1.1 wt.%. In an embodiment, the composition includes an amount of gum-based compound ranging from 0.2 wt.% to 1 .5 wt.%. In an embodiment, the composition includes an amount of gum-based compound ranging from 0.3 wt.% to 1 .5 wt.%. In an embodiment, the composition includes an amount of gum-based compound ranging from 0.4 wt.% to 1 .5 wt.%. In an embodiment, the composition includes an amount of gum-based compound ranging from 0.5 wt.% to 1.5 wt.%. In an embodiment, the composition includes an amount of gum-based compound ranging from 0.6 wt.% to 1.5 wt.%. In an embodiment, the composition includes an amount of gum-based compound ranging from 0.7 wt.% to 1 .5 wt.%.

[0108] In an embodiment, the composition includes an amount of gum-based compound ranging from 0.1 wt.% to 0.40 wt.%. In an embodiment, the composition includes an amount of gum-based compound ranging from 0.1 wt.% to 0.30 wt.%. In an embodiment, the composition includes an amount of gum-based compound ranging from 0.1 wt.% to 0.20 wt.%. In an embodiment, the composition includes an amount of gum-based compound ranging from 0.5 wt.% to 1.0 wt.%. In an embodiment, the composition includes an amount of gum-based compound ranging from 0.6 wt.% to 0.9 wt.%. In an embodiment, the composition includes an amount of gum-based compound ranging from 0.7 wt.% to 0.8 wt.%. In an embodiment, the composition includes an amount of gum-based compound ranging from 0.7 wt.% to 1 .1 wt.%. In an embodiment, the composition includes an amount of gum-based compound ranging from 0.8 wt.% to 1 .1 wt.%. In an embodiment, the composition includes an amount of gum-based compound ranging from 0.8 wt.% to 1 .0 wt.%.

[0109] In an embodiment, the thickening agent includes guar gum. Guar gum is a natural polysaccharide derived from the seeds of the guar plant (Cyamopsis tetragonolobus). It is commonly used as a thickener, stabilizer, and emulsifier in a variety of industries, including food, pharmaceuticals, and cosmetics. Guar gum is optionally used in one or more embodiments because of its excellent adhesive properties and its ability to form strong bonds with epidermal surfaces, which allows for the sustained release of targeted molecules or other ingredients.

[0110] Additionally, guar gum is biocompatible and biodegradable, which makes it a safe and effective choice for use in these applications.

[0111] Dye

[0112] The composition may include any convenient biologically compatible dye. Typically, the dye does not stain the skin, and may include dyes that are commonly used in cosmetics. These include for example, FD&C (food, drug & cosmetic) dyes, D&C (drug & cosmetic) dyes, lakes, iron oxides and mica.

[0113] FD&C dyes are synthetic colorants that have been approved by the United States Food and Drug Administration (FDA) for use in food, drugs, and cosmetics. They are water-soluble, nonstaining, and come in various colours. Examples include FD&C Blue No. 1 , FD&C Red No. 40, and FD&C Yellow No. 5. These dyes are often used in cosmetic gels and creams to provide bright and consistent colours.

[0114] D&C dyes are similar to FD&C dyes but are only approved for use in drugs and cosmetics, not food. They are also water-soluble and non-staining. Examples include D&C Blue No. 4, D&C Red No. 33 and D&C Green No. 5. These dyes are used in cosmetic gels and creams for their vibrant colours and non-staining properties.

[0115] Lakes are water-insoluble pigments made by combining FD&C or D&C dyes with a substrate, usually aluminium hydroxide. They are non-staining and provide a wide range of colours. Lakes are commonly used in cosmetic gels and creams to create stable, long-lasting colours that do not bleed or migrate.

[0116] Iron oxides are inorganic pigments that come in various shades such as red, yellow, and black. They are generally considered safe for use on the skin and are non-staining. Iron oxides are used in cosmetic gels and creams to provide stable, long-lasting colours, although they may not be as vibrant as synthetic dyes.

[0117] Mica is a natural mineral often used in cosmetics for its shimmering and light-reflecting properties. Mica can be coated with various dyes and pigments to create a wide range of colours. It is non-staining and is commonly found in cosmetic gels and creams to provide a subtle, shimmering effect.

[0118] In an embodiment the dye is D&C Green No. 5, also known as Acid Green 25, which is a synthetic organic dye with the chemical formula C37H34N2Na2OgS3. It is a green powder that is soluble in water, and it is used primarily in the cosmetics and personal care industries.

[0119] D&C Green No. 5 is used as a colour additive in a variety of cosmetics and personal care products, including soaps, shampoos, conditioners, lotions, creams, makeup, and nail polish. Its primary function is to provide an attractive green hue to the products.

[0120] Plasticisers

[0121] Plasticisers may be incorporated into the bio-adhesive composition to enhance its flexibility, extensibility, and overall performance. These additives can modify the physical properties of the composition, potentially improving its ability to form a continuous, adherent film on the substrate.

[0122] In some embodiments, the plasticiser may be present in an amount up to 15 wt.% of the total composition. The plasticiser may be present in an amount ranging from 0.1 to 15 wt.%. Theplasticiser may be present in an amount ranging from 0.1 to 14 wt.%. The plasticiser may be present in an amount ranging from 0.1 to 13 wt.%. The plasticiser may be present in an amount ranging from 0.1 to 11 wt.%. The plasticiser may be present in an amount ranging from 0.1 to 10 wt.%. The plasticiser may be present in an amount ranging from 0.1 to 10 wt.%. The plasticiser may be present in an amount ranging from 0.1 to 9 wt.%. The plasticiser may be present in an amount ranging from 0.1 to 8 wt.%. The plasticiser may be present in an amount ranging from 0.1 to 7 wt.%. The plasticiser may be present in an amount ranging from 1 to 13 wt.%. The plasticiser may be present in an amount ranging from 2 to 13 wt.%. In an embodiment, the plasticiser may be present in an amount ranging from 3 to 13 wt.%. In an embodiment, the plasticiser may be present in an amount ranging from 4 to13 wt.%. In an embodiment, the plasticiser may be present in an amount ranging from 4 to 13 wt.%. The plasticiser may be present in an amount of at least 3 wt.%. The plasticiser may be present in an amount of at least 4 wt.%. The plasticiser may be present in an amount of up to 20 wt.%. The plasticiser may be present in an amount of up to 15 wt.%. The plasticiser may be present in an amount of up to14 wt.%. The plasticiser may be present in an amount of up to 13 wt.%. The plasticiser may be present in an amount of up to 12 wt.%. The plasticiser may be present in an amount of up to 11 wt.%. The plasticiser may be present in an amount of up to 10 wt.%. The plasticiser may be present in an amount of up to 9 wt.%. The plasticiser may be present in an amount of up to 8 wt.%. The plasticiser may be present in an amount of up to 7.5 wt.%. The plasticiser may be present in an amount of up to 7 wt.%. The plasticiser may be present in an amount of up to 6.5 wt.%. The plasticiser may be present in an amount of up to 6 wt.%. The specific concentration may be adjusted based on the desired properties of the final product.

[0123] The plasticiser may include glycerol, propylene glycol, polyethylene glycol (PEG), sorbitol, triethyl citrate and / or dibutyl sebacate. The choice and concentration of plasticiser may be influenced by factors such as the specific cellulose derivative used, the desired mechanical properties of the dried film, and the intended application of the bio-adhesive composition. In some cases, a combination of plasticisers may be employed to achieve the optimal balance of properties.

[0124] Preservatives

[0125] The composition may includes one or more preservatives. Suitable preservatives will be well known to those skilled in the art.

[0126] The composition may include up to 0.25 wt% potassium sorbate powder. In an embodiment, the composition may include between 0.00025 and 0.25 wt% potassium sorbate powder.

[0127] In an embodiment, the composition includes between 0.00025 and 0.25 wt% methyl hydroxybenzoate.

[0128] In yet another embodiment, the composition includes between 0.00001 and 0.010 wt % benzalkonium chloride.

[0129] In an embodiment, the composition may include citric acid and / or sodium citrate and salts thereof as a preservative. The citric acid and / or sodium citrate may also function as a pH buffer.

[0130] In an embodiment, the composition includes ascorbic acid (Vitamin C) and / or sodium ascorbate. Ascorbic acid and / or sodium ascorbate may be included to act as a brightening agent. Ascorbic acid and / or sodium ascorbate may be included to act a pH buffer. Use of ascorbic acid and / or sodium ascorbate may result in the composition having a pH ~5.5. Ascorbic acid and / or sodium ascorbate may increase an efficacy of the preservatives.

[0131] Glyceryl caprylate

[0132] Glyceryl caprylate is a natural emollient derived from glycerin and plant fatty acids, usually appearing as a white waxy solid.

[0133] Glyceryl caprylate may be present in the composition in a concentration of 0.075 wt% to 3.00 wt%.

[0134] Glyceryl undecylenate

[0135] Glyceryl undecylenate is typically used as an emulsifier.

[0136] Glyceryl undecylenate may be present in the composition in a concentration of 0.075 wt% to 3.00 wt%.

[0137] Humectant

[0138] Hyaluronic acid (LMW-HA)

[0139] Hyaluronic acid is a naturally occurring substance found in our bodies, particularly in the skin, connective tissues, and eyes. LMW-HA refers to hyaluronic acid molecules that have been fragmented into smaller sizes, typically by enzymatic or chemical processes. LMW-HA has gained attention in the skincare industry due to its unique properties and potential benefits for the skin. In particular, it has gained significant popularity in the field of cosmetic dermatology due to its hydrating and anti-aging properties. When used in skincare products or dermal fillers, hyaluronic acid can provide various benefits for the face and skin, including the following:

[0140] 1 . Hydration: Hyaluronic acid has an exceptional ability to retain moisture. It can hold up to 1 ,000 times its weight in water, making it an excellent hydrating agent. When applied topically, it helps to keep the skin well moisturized, improving its texture, elasticity, and overall appearance.

[0141] 2. Wrinkle reduction: As we age, the natural production of hyaluronic acid in our bodies decreases, leading to the formation of wrinkles and fine lines. By using skincare products or undergoing dermal filler treatments containing hyaluronic acid, you can replenish the lost moisture and plump up the skin, reducing the appearance of wrinkles.

[0142] 3. Volume restoration: Dermal fillers containing hyaluronic acid are commonly used to restore volume to areas of the face that have lost fullness due to aging or other factors. These fillers can be injected into areas such as the cheeks, lips, and under-eye hollows to create a more youthful and rejuvenated appearance.

[0143] 4. Skin firmness and elasticity: Hyaluronic acid stimulates the production of collagen and elastin, which are essential proteins for maintaining the skin's firmness and elasticity.

[0144] 5. By promoting collagen synthesis, hyaluronic acid can improve the overall structure and resilience of the skin.

[0145] 6. Enhanced skin texture: Regular use of hyaluronic acid can help improve the texture of the skin by making it smoother, softer, and more supple. It can also minimize the appearance of pores and promote a more even skin tone.

[0146] 0ther physico-chemical properties of LMW-HA include the following:1 . Penetration: LMW-HA has a smaller molecular size compared to regular hyaluronic acid, allowing it to penetrate the skin more easily. This improved penetration enables it to reach deeper layers of the skin, where it can provide hydration and other benefits.2. Enhanced bioavailability: LMW-HA has been shown to have better bioavailability, meaning it can be more readily absorbed by the skin and exert its effects.3. Increased hydration: Like regular hyaluronic acid, LMW-HA is an excellent humectant and can attract and retain moisture in the skin. Its smaller size may allow it to penetrate more effectively, resulting in enhanced hydration and improved water retention.4. Skin rejuvenation: LMW-HA has been suggested to stimulate the production of collagen and elastin, similar to regular hyaluronic acid. This can help improve the skin's elasticity, firmness, and overall texture, leading to a more youthful appearance.5. Anti-inflammatory effects: LMW-HA has demonstrated potential anti-inflammatory properties, which can be beneficial for soothing and calming the skin. It may help reduce redness, irritation, and sensitivity.

[0147] User Experience

[0148] Menthol

[0149] Menthol is an organic compound made synthetically or obtained from the oils of corn mint, peppermint, or other mints. It is often used for its local anaesthetic and counterirritant qualities to relieve minor throat irritation. Menthol also acts as a weak K-opioid receptor agonist.

[0150] The composition may include crystalline menthol.

[0151] The menthol may be present in the composition in a concentration of 0.00004 to 0.040 wt%.

[0152] Xylitol

[0153] Xylitol is a colourless crystalline solid comprising a particular stereoisomer of the structural formula HO(CH2)(CHOH)s(CH2)OH. Typically, it is classified as a polyalcohol or sugar alcohol, more specifically, an alditol. It is a well-known food additive and sugar substitute in drugs, dietary supplements, confections and other consumable items. It is also added to nasal irrigation solutions and has been found to improve the symptoms of chronic rhinosinusitis. It is allocated European Union code number E967.

[0154] The composition may include crystalline xylitol.

[0155] The xylitol may be present in the composition of the present invention in a concentration of 0.00054 to 0.54000 wt%.

[0156] Dry-out time

[0157] As used herein, the term "dry-out time" refers to the time required for the bio-adhesive composition to transition from its initial liquid or gel state upon application to the substrate to a solidlike state (e.g. a film or barrier) on a surface of the substrate. Typically, the transition from the liquid or gel state to the solid-like state is accompanied by a change in the storage modulus and loss modulus. The solid-like state may still be hydrated (e.g. have >30wt.% water). Accordingly, the term “dry” and variants such as “dried” and “drying” are used in reference to the initial liquid or gel state and means that the formulation has a decreased or reduced water content compared to the initial liquid or gel state, and should be interpreted broadly as a relative reduction in water content compared to its initial application state, rather than an absolute absence of moisture. In some embodiments, the solidlike state of the composition has a water content of at most 25 wt.%. The dry-out time may vary depending on factors such as the composition's formulation, environmental conditions, and the thickness of the applied layer.

[0158] In an embodiment, the dry our time is at most 90 seconds. In an embodiment, the dry our time is at most 80 seconds. In an embodiment, the dry our time is at most 70 seconds. In an embodiment, the dry our time is at most 60 seconds. In an embodiment, the dry our time is at most 50 seconds. In an embodiment, the dry our time is at most 40 seconds. In an embodiment, the dry our time is at most 30 seconds. In an embodiment, the dry ourtime ranged from 30 seconds to 90 seconds.

[0159] Viscosity

[0160] The viscosity of the bio-adhesive composition effects its performance and application characteristics. For example, viscosity may influence the composition's ability to form a uniform barrier, its spreadability on the substrate, and its resistance to flow or dripping after application. The viscosity of the bio-adhesive composition may be higher than that typically observed in nasal spray formulations. Nasal sprays generally have low viscosities, often in the range of up to 500 cP, to allow for easy atomization and spray formation. In contrast, the bio-adhesive composition may have a viscosity at point-of-use of at least 10,000 cP, which is significantly higher than typical nasal spray formulations. This higher viscosity may be beneficial for forming a more stable and persistent barrier on the substrate, reducing the risk of dripping or running after application, and allowing for a more controlled and localized application. The difference in viscosity between the bio-adhesive composition and nasal sprays is primarily due to their distinct intended functions and application methods. While nasal sprays aim for easy dispersion and coverage of the nasal mucosa, the bio-adhesive composition is designed to form a coating on a substrate (e.g. hands) at the point-of-use of the composition. A composition with a viscosity that is too low will simply pour or drip off the substate preventing the formation of a barrier.

[0161] As used herein, the term "point-of-use" refers to the time that the composition is applied to the substate. The point-of-use viscosity represents the rheological properties of the composition at the moment it contacts or is applied to the substrate. Generally, the viscosity at the point-of-contact is similar to the rheological properties of the composition during storage and manufacture, but it may differ e.g. due to shear forces. For example, the composition may be shear-thinning to assist with pumping or application into the substate.

[0162] The composition typically has a viscosity at point-of-use of at least 10,000 cP. In an embodiment, the composition has a viscosity at point-of-use of at least 15,000 cP. In an embodiment, the composition has a viscosity at point-of-use of at least 20,000 cP. In an embodiment, the composition has a viscosity at point-of-use of at least 25,000 cP. In an embodiment, the composition has a viscosity at point-of-use of at least 30,000 cP. In an embodiment, the composition has a viscosity at point-of-use ranging from 20,000 cP to 70,000 cP. In an embodiment, the composition has a viscosity at point-of-use of at most 70,000 cP.

[0163] Example Formulations

[0164] The disclosure may include one or more formulations. The formulations may be used in a wide range of application. However, some formulations may be better suited for specific applications. For example, formulations that are intended for use as a barrier may be different to formulations used to act as a skin primer such as for cosmetics. Different formulations are outlined in Table 1 .1 , Table 1 .2 and Table 1 .3. Formulation A.1 may be better suited to form a barrier on hands, whereas formulation A.2 may be better suited to form a barrier on the face such as a primer for cosmetics.

[0165] Table 1.1

[0166] Table 1.2

[0167] Table 1.3

[0168] In Table 1 .3, the water range remains as the principal “make-up” to guarantee the formula can still sum to 100 % after all other ingredients are set anywhere within their limits. For citric acid, sodium citrate, ascorbic acid, and sodium ascorbate, the dry or hydrated versions can be used interchangeably. The buffer content for formulation can be adjusted to reach pH 5.2 - 5.8 (preferably pH 5.5). The Hydroxyethyl cellulose may have a high to very high molecular weight, for example to achieve final viscosity -55,000 cps ± 10,000 cps at given concentrations.

[0169] In table 1 .3, formulations A.3 and B.3 may be used as aqueous-based compositions to for a barrier on the substrate, formulations C.3 and D.3 may be used as alcohol-based compositions to for a barrier on the substrate, while formulation E.3 may be used as a ‘primer’ to be used in cosmetic applications such as on skin on a face.

[0170] In an embodiment, the formulation may include:

[0171] In an embodiment, the formulation may include:00172] In an embodiment, the formulation may include:00173] Compared to spray-on hydrogels which require low-viscosity with high plasticity to prevent drying, embodiment of the current disclosure have a higher viscosity and lower plasticity to facilitate drying.

[0174] The composition may be at least partly absorbed or adsorbed onto the integument. Absorption occurs when a substance penetrates and diffuses into the bulk of another substance, typically a liquid or a solid. In this process, the absorbed substance is incorporated into the absorbing material at the molecular or atomic level. The absorbed substance becomes evenly distributed throughout the absorbing material, often resulting in changes in the physical or chemical properties of the material.

[0175] Adsorption refers to the attachment or adhesion of molecules or particles onto the surface of a solid or liquid. In this process, the adsorbate (substance being adsorbed) adheres to the adsorbent (the surface) due to attractive forces such as van der Waals forces or electrostatic interactions. Unlike absorption, the adsorbate remains on the surface rather than penetrating the bulk material. The adsorbate may form a monolayer or multiple layers on the adsorbent, depending on the conditions. Activated carbon adsorbing pollutants from air or water is an example of adsorption.

[0176] To summarise, absorption involves the penetration and distribution of a substance into the bulk of another substance, while adsorption involves the attachment of molecules or particles onto the surface of a solid or liquid.

[0177] Embodiments also relate to a method of forming barrier on a living integument. The method may comprise applying an embodiment of the bio-adhesive composition to the living integument and allowing the bio-adhesive composition to dry to reduce its water content to form the barrier. Aspreviously discussed, the barrier may still be hydrated and merely be direr compared to the composition at the time of application onto the integument, but the act of drying causes the bioadhesive composition to adhere or at least attach to the integument. Typically, the bio-adhesive composition has dried enough for a viscosity of the composition to form a thick gel that forms a barrier. The thick gel may then further dry or dehydrate to further reduce the water content.

[0178] The living integument may be a hand. The living integument may be a face.FIGURES

[0179] Further disclosure, objects, advantages and aspects of preferred and other embodiments of the present application may be better understood by those skilled in the relevant art by reference to the following description of embodiments taken in conjunction with the accompanying drawings, which are given by way of illustration only, and thus are not limitative of the disclosure herein, and in which:• Fig. 1 is a plot depicting the average Log10TCID50mL-1 recovery of Human Coronavirus OC43 following incubation for 0, 0.5, 3 and 6 hours with a HTS Transwell® pore size of 3 pm or 5 pm. The dotted line indicates the limit of detection (LOD).• Fig. 2 is a plot depicting the average molecular quantification of Human Coronavirus OC43 following incubation for 0, 0.5, 3 and 6 hours with a HTS Transwell® pore size of 3 pm or 5 pm. The dotted line indicates the limit of detection (LOD).• Fig. 3 is a plot depicting the average LogioTCID50mL-1recovery of Human Influenza A H1 N1 following incubation for 0, 0.5, 3 and 6 hours with a HTS Transwell® pore size of 3 pm or 5 pm. The dotted line indicates the limit of detection (LOD).• Fig. 4 is a plot depicting the average molecular quantification of Human Influenza A H1 N1 following incubation for 0, 0.5, 3 and 6 hours with a HTS Transwell® pore size of 3 pm or 5 pm. The dotted line indicates the limit of detection (LOD).• Fig. 5 is a plot depicting the average LogioTCID50mL-1recovery of Human Rhinovirus 1A following incubation for 0, 0.5, 3 and 6 hours with a HTS Transwell® pore size of 5 pm. The dotted line indicates the limit of detection (LOD).• Fig. 6 depicts the standard curve for a 10-fold serial dilution series of Human Coronavirus OC43.• Fig. 7 depicts the standard curve fora 10-fold serial dilution series of Human Influenza A H1 N1 .• Fig. 8 is a plot depicting the average Log recovery of Human Coronavirus OC43 following transfer of virus through 5 pm HTS Transwell® membrane after 0.5 hours with three concentrations of each test product (100%, 75% and 0.01 %). The lower dotted line indicates the limit of detection (LOD). The upper dotted line indicates 4 Log reduction compared to no product control. Error bars indicate standard deviation.• Fig. 9 is a plot depicting the average total genomic RNA quantification of Human Coronavirus OC43 following transfer of virus through 5 pm HTS Transwell® membrane after 0.5 hours withthree concentrations of each test product (100%, 75% and 0.01 %). The lower dotted line indicates the limit of detection (LOD). The upper dotted line indicates 4 Log reduction compared to no product control. Error bars indicate standard deviation.• Fig. 10 is a plot of average Log recovery of Human Coronavirus OC43 following transfer of virus through 5 pm HTS Transwell® membrane after 3 hours with three concentrations of each test product (100%, 75% and 0.01 %). The lower dotted line indicates the limit of detection (LOD). The upper dotted line indicates 4 Log reduction compared to no product control. Error bars indicate standard deviation.• Fig.11 is a plot of average total genomic RNA quantification of Human Coronavirus OC43 following transfer of virus through 5 pm HTS Transwell® membrane after 3 hours with three concentrations of each test product (100%, 75% and 0.01 %). The lower dotted line indicates the limit of detection (LOD). The upper dotted line indicates 4 Log reduction compared to no product control. Error bars indicate standard deviation.• Fig. 12 is a plot of the average Log recovery of Human Coronavirus OC43 following transfer of virus through 5 pm HTS Transwell® membrane after 6 hours with three concentrations of each test product (100%, 75% and 0.01 %). The lower dotted line indicates the limit of detection (LOD). The upper dotted line indicates 4 Log reduction compared to no product control. Error bars indicate standard deviation.• Fig.13 is a plot of average total genomic RNA quantification of Human Coronavirus OC43 following transfer of virus through 5 pm HTS Transwell® membrane after 6 hours with three concentrations of each test product (100%, 75% and 0.01 %). The lower dotted line indicates the limit of detection (LOD). The upper dotted line indicates 4 Log reduction compared to no product control. Error bars indicate standard deviation.• Fig. 14 is a plot of average Log recovery of Human Influenza A H1 N1 following transfer of virus through 5 pm HTS Transwell® membrane after 0.5 hours with three concentrations of each test product (100%, 75% and 0.01 %). The lower broken line indicates the limit of detection (LOD). The upper broken line indicates 4 Log reduction compared to no product control. Error bars indicate standard deviation.• Fig. 15 is a plot of average total genomic RNA quantification of Human Influenza A H1 N1 following transfer of virus through 5 pm HTS Transwell® membrane after 0.5 hours with three concentrations of each test product (100%, 75% and 0.01 %). The lower broken line indicates the limit of detection (LOD). The upper broken line indicates 4 Log reduction compared to no product control. Error bars indicate standard deviation.• Fig. 16 is a plot of average Log recovery of Human Influenza A H1 N1 following transfer of virus through 5 pm HTS Transwell® membrane after 3 hours with three concentrations of each test product (100%, 75% and 0.01 %). The lower broken line indicates the limit of detection (LOD).The upper broken line indicates 4 Log reduction compared to no product control. Error bars indicate standard deviation.• Fig. 17 is a plot of average total genomic RNA quantification of Human Influenza A H1 N1 following transfer of virus through 5 pm HTS Transwell® membrane after 3 hours with three concentrations of each test product (100%, 75% and 0.01 %). The lower broken line indicates the limit of detection (LOD). The upper broken line indicates 4 Log reduction compared to no product control. Error bars indicate standard deviation.• Fig. 18 is a plot of average Log recovery of Human Influenza A H1 N1 following transfer of virus through 5 pm HTS Transwell® membrane after 6 hours with three concentrations of each test product (100%, 75% and 0.01 %). The lower broken line indicates the limit of detection (LOD). The upper broken line indicates 4 Log reduction compared to no product control. Error bars indicate standard deviation.• Fig. 19 is a plot of average total genomic RNA quantification of Human Influenza A H1 N1 following transfer of virus through 5 pm HTS Transwell® membrane after 6 hours with three concentrations of each test product (100%, 75% and 0.01 %). The lower broken line indicates the limit of detection (LOD). The upper broken line indicates 4 Log reduction compared to no product control. Error bars indicate standard deviation.• Fig. 20 is a plot of average Log recovery of Human Rhinovirus 1 A following transfer of virus through 5 pm HTS Transwell® membrane after 0.5 hours with three concentrations of each test product (100%, 75% and 0.01 %). The lower broken line indicates the limit of detection (LOD). The upper broken line indicates 4 Log reduction compared to no product control. Error bars indicate standard deviation.• Fig. 21 is a plot of average total genomic RNA quantification of Human Rhinovirus 1 A following transfer of virus through 5 pm HTS Transwell® membrane after 0.5 hours with three concentrations of each test product (100%, 75% and 0.01 %). The lower broken line indicates the limit of detection (LOD). The upper broken line indicates 4 Log reduction compared to no product control. Error bars indicate standard deviation.• Fig. 22 is a plot of average Log recovery of Human Rhinovirus 1 A following transfer of virus through 5 pm HTS T ranswell® membrane after 3 hours with three concentrations of each test product (100%, 75% and 0.01 %). The lower broken line indicates the limit of detection (LOD). The upper broken line indicates 4 Log reduction compared to no product control. Error bars indicate standard deviation.• Fig. 23 is a plot of the average total genomic RNA quantification of Human Rhinovirus 1A following the transfer of virus through 5 pm HTS Transwell® membrane after 3 hours with three concentrations of each test product (100%, 75% and 0.01 %). The lower broken line indicates the limit of detection (LOD). The upper broken line indicates 4 Log reduction compared to no product control. Error bars indicate standard deviation.• Fig. 24 is a plot of the average Log recovery of Human Rhinovirus 1 A following the transfer of the virus through 5 pm HTS Transwell® membrane after 6 hours with three concentrations of each test product (100%, 75% and 0.01 %). The lower broken line indicates the limit of detection (LOD). The upper broken line indicates 4 Log reduction compared to no product control. Error bars indicate standard deviation.• Fig. 25 is a plot of average total genomic RNA quantification of Human Rhinovirus 1 A following transfer of virus through 5 pm HTS Transwell® membrane after 6 hours with three concentrations of each test product (100%, 75% and 0.01 %). The lower broken line indicates the limit of detection (LOD). The upper broken line indicates 4 Log reduction compared to no product control. Error bars indicate standard deviation.• Fig. 26 is a standard curve for a 10-fold serial dilution series of Human Coronavirus OC43.• Fig. 27 is a standard curve for a 10-fold serial dilution series of Human Influenza A H1 N1 .• Fig. 28 is as standard curve for a 10-fold serial dilution series of Human Rhinovirus 1 A.• Fig. 29 depicts cross-sectional morphologies of the Round 1 freeze-dried gels: LQMN_C_02023 (Fig. 29A), LQMN_C_02048 (Fig. 29B), LQMN_B_02051 (Fig. 29C), LQMN_C_02052 (Fig. 29D) and LQMN_C_02065 (Fig. 29E).• Fig. 30 depicts cross-sectional morphologies of the Round 2 freeze-dried gel samples: LQMN_B_03015 (Fig. 30A), LQMN_B_03047 (Fig. 30B), LQMN_B_03053 (Fig. 30C), and LQMN_B_03066 (Fig. 30D).• Fig. 31 depicts surface morphologies of the Round 1 air-dried gel samples in low magnifications: LQMN_C_02023 (Fig. 31 A), LQMN_C_02048 (Fig. 31 B), LQMN_B_02051 (Fig. 31 C), LQMN_C_02052 (Fig. 31 D) and LQMN_C_02065 (Fig. 31 E).• Fig. 32 depicts hierarchical surface morphologies of the Round 1 air-dried gel samples in high magnifications: LQMN_C_02023 (Figs 32A-C), LQMN_C_02048 (Figs 32D-F), LQMN_B_02051 (Figs 32G-I), LQMN_C_02052 (Figs 32J-L), and LQMN_C_02065 (Figs 32M-O).• Fig. 33 depicts surface morphologies of air-dried gel samples: LQMN_B_03015 (Fig. 33A), LQMN_B_03047 (Fig. 33B), LQMN_B_03053 (Fig. 33C), and LQMN_B_03066 (Fig. 33D).• Fig. 34 are SEM images depicting air-dried microfilms with different thicknesses. The scale bar represents 20 pm.• Fig. 35 is a schematic representation of formation of a microfilm once an embodiment of a composition is applied to skin.EXAMPLES

[0180] Embodiments will be further described with reference to the following non-limiting examples.

[0181] Formulations

[0182] Exemplary formulations of one or more embodiment the composition of the present disclosure include Table 1 .1 and Table 1 .2.

[0183] Embodiments of the composition may be applied to the integument in any convenient dosage form. The composition may be delivered to an external layer such as, epidermis where it may form a coating, be absorbed, or be adsorbed onto the epidermal surface. In an embodiment, the composition is suitable for topical application.

[0184] The composition may be at least partly absorbed onto the integument. Absorption occurs when a substance penetrates and diffuses into the bulk of another substance, typically a liquid or a solid. In this process, the absorbed substance is incorporated into the absorbing material at the molecular or atomic level. The absorbed substance becomes evenly distributed throughout the absorbing material, often resulting in changes in the physical or chemical properties of the material.

[0185] The bio-adhesive composition may be made by combining the components in any convenient order. For instance, Example B above may be manufactured by:• combining a portion of a cellulose derivative with a portion of the alcohol and / or purified water to form a solution;• combining a portion of thickener with the solution;• combining the remainder of the alcohol with the solution.• combining the remainder of the purified water with the solution;• combining any excipients with the solution; and• combining any pharmacological actives with the solution.

[0186] The target integument may be, for example, epidermal tissue at any location on the body to form a temporary coating.

[0187] The ingredients of the composition may be temporarily chemically or physically linked into the bio-adhesive composition. Without wishing to be bound by theory it is postulated that one or more embodiments of the composition either acts as a barrier to hinder bio-antagonists, or holds the bioantagonist, thus preventing the bio-antagonist from entering the matrix of integument, such as epidermal cells.

[0188] If the bio-antagonist is a pathogen that is in contact with (or held by) the barrier, this will facilitate interaction with components of bio-adhesive composition. This is advantageous if the bioadhesive includes an anti-pathogenic agent because it increases the likelihood of inhibition of activity and replication of the pathogen and, optimally, eventual death of the pathogen.

[0189] Example of Virucidal Efficacy and Example of Barrier Efficacy

[0190] The present disclosure will be illustrated with reference to the following examples• LQMN_B_03015 (HEC, 4 Electrolytes, No Alcohol)• LQMN_B_03047 (HEC, No Electrolytes, No Alcohol)• LQMN_B_03053 (HEC, NaCI, No Alcohol)• LQMN_B_03066 (HEC, Guar Gum, NaCI, No Alcohol).

[0191] Table 2:

[0192] The present disclosure will be illustrated with reference to the following examples in which the virucidal efficacy is tested using a modified viral suspension test method according to European Standard BS EN 14476:2013+A2:2019.

[0193] This European Standard specifies a test method and the minimum requirements for virucidal activity of chemical disinfectant and antiseptic products that form a homogeneous physically stable preparation when diluted with hard water or in the case of ready-to-use products, that is, products that are not diluted when applied, with water. Products can only be tested at a concentration of 80 % (97 %, with a modified method for special cases) as some dilution is always produced by adding the test organisms and interfering substance.

[0194] Furthermore, the European Standard applies to products that are used in the medical area in the fields of hygienic handrub, hygienic handwash, instrument disinfection by immersion, surface disinfection by wiping, spraying, flooding or other means and textile disinfection. This European Standard applies to areas and situations where disinfection is medically indicated. Such indications occur in patient care, for example: - in hospitals, in community medical facilities, and in dental institutions; - in clinics of schools, of kindergartens, and of nursing homes; and may occur in the workplace and in the home. It may also include services such as laundries and kitchens supplying products directly for the patients. The method described is intended to determine the activity of commercial formulations or active substances under the conditions in which they are used.

[0195] The four examples above were tested to assess the cytotoxicity of the formulations as a spray and the effect of different pore sizes on recovery of three respiratory viruses.

[0196] Study tier: Tier 3b: Customised test method for R&D purposes

[0197] Materials and Methods

[0198] Test microorganisms - Cell types:• MRC-5 (ATCC® CCL-171 ™) - Passage number: PD 40.1• MDCK (NBL-2) (ATCC® CCL-34™) - Passage number: 24• H1-HeLa (ATCC® CRL-1958™) - Passage number: 17

[0199] Viruses• Human Coronavirus OC43 (ATCC® VR-1558™) - Amplification number: 1• Human Influenza type A H1 N1 (ATCC® VR-1520™) - Amplification number: 1• Human Rhinovirus 1A (ATCC® VR-1559™) - Amplification number: 2

[0200] The details of the test items used in this study are outlined in Table 2.Test item Item size LOT numberCorning HTS Transwell® 96-well insert 3 pm pore size 32221003Corning HTS Transwell® 96-well insertmPore s'ze22521037

[0201] Equipment and media - Equipment• Biosafety cabinet class II - BioMat, ThermoFisher Scientific, UK• CO2 incubator - Thermo Scientific, UK Rotor-gene Q thermal cycler - Qiagen, UK• GoTaq® 1-step RT-qPCR Master Mix - Promega, UK• Heat block• Microscope - Motic AE2000, UK• QIAamp Viral RNA Mini kit - Qiagen, UK• Tissue culture plates - SLS, UK• HTS Transwell®96-well insert - Corning, UK• UKAS calibrated pipettes - Sartorius, Scientific Laboratory Supplies (SLS), UK• UKAS calibrated multichannel pipettes - Gilson®, SLS, UK

[0202] Media• Eagle’s Modified Essential Medium (EMEM) - ATCC, UK• Foetal bovine serum (FBS) - ThermoFisher Scientific, UK• Leibowitz’s L-15 Medium - Gibco™, UK• Penicillin-streptomycin - ThermoFisher Scientific, UK• TPCK T rypsin - ThermoFisher Scientific, UK

[0203] Method

[0204] Phase 1 : Cytotoxicity screen of four products

[0205] To assess potential cytotoxic effects of the four products which could potentially interfere with viral recovery assays, each neat product was initially diluted to 3% (to mimic maximum amount of product cells would be exposed to following viral recovery assay) before further ten-fold serial dilutions and plating onto 96-well plates containing MRC-5, MDCK or H1-HeLa cells, at a set seeding density for each cell line. Plates were then incubated under appropriate conditions for each cell for 24 hours. Following incubation cells were visually inspected for any cytotoxic effects.

[0206] Phase 2: Pilot: Screening of the effect of different pore sizes on recovery of three viruses

[0207] Viral quantification

[0208] For assessment of viral recovery through HTS Transwell® membranes with pore sizes of either 3 pm or 5 pm, viral stocks of Human Coronavirus OC43, Human Influenza A H1 N1 and Human Rhinovirus 1 A were used. Firstly 100 pL of appropriate media was added to each well of the receiving plate, before 125 pL of viral stock was added to each well of the Transwell® plate. Virus passing through the HTS Transwell® membrane and into the media in the receiving plate was then recovered at 0.5, 3 and 6 hours. Virus added directly to media was recorded as 0 hours and used to assess initial viral titre. 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 A H1 N1) or H1-HeLa cells (Human Rhinovirus 1A). MRC-5 cells were then incubated at 35 °C; 5%CO2for 6 days, MDCK cells at 35 °C; 5% CO2 for 5 days and H1-HeLa cells at 33 °C; No CO2 for 6 days. Following incubation, cells were visually inspected for cytopathic effects of viral infection.

[0209] Molecular quantification

[0210] For both Human coronavirus OC43 and Human Influenza A H1 N1 , 70 pL samples were individually taken for each HTS Transwell® pore size (3 pm and 5 pm) and time point (0, 0.5, 3 and 6 hours) in triplicate. For Human Rhinovirus 1 A only the 5 pm pore size was assessed. 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. The Cq values obtained were compared to the relevant standard curve generated from 10-fold dilution series of Human Coronavirus OC43, Human Influenza A H1 N1 or Human Rhinovirus 1 A to obtain the final total genomic concentration (Log10TCID50mL-1)..

[0211] Statistical analysis

[0212] Average total genomic concentrations (LogioTCID50mL-1) are presented as mean ± standard deviation (SD) from the 3 independent replicates per sample. A two-tailed students t-test was used to assess statistical differences between the detected LogioTCID50mL-1data from each pore size and time point. Data were considered statistically significant when p < 0.05.

[0213] Results

[0214] Phase 1 - Cytotoxicity screen of four products

[0215] Cytotoxicity of four products on MRC-5 Cells to support Human Coronavirus OC43 testing

[0216] All four samples tested showed no cytotoxic response. The negative and positive controls passed system suitability criteria.

[0217] Table 3: A summary of qualitative morphological grading of cytotoxic effects of four products on MRC-5 cells, according to visual microscopy scoring criteria, following 24 hours treatment. Controls ran at a single concentration.Negative control - EMEM (Neat) 0*Positive control - Triton X-100 (0.1 %) 4*LQMN_B_03047 0 0 0 0LQMN_B_03053 0 0 0 0LQMN_B_03066 0 0 0 0LQMN_B_03015 0 0 0 0

[0218] Cytotoxicity of four products on MDCK Cells to support Human influenza A (HI ND testing

[0219] All four samples tested showed no cytotoxic response. The negative and positive controls passed system suitability criteria.

[0220] Table 4: A summary of qualitative morphological grading of cytotoxic effects of four products on MDCK cells, according to visual microscopy scoring criteria, following 24 hours treatment. Controls ran at a single concentration.Negative control - EMEM (Neat) 0*Positive control - Triton X-100 (0.1 %) 4*LQMN_B_03047 0 0 0 0LQMN_B_03053 0 0 0 0LQMN_B_03066 0 0 0 0LQMN_B_03015 0 0 0 0

[0221] Cytotoxicity of Four Products on H1-HeLa Cells to support Human Rhinovirus 1 A testing

[0222] Table 5: A summary of qualitative morphological grading of cytotoxic effects of four products on H1 -HeLa cells, according to visual microscopy scoring criteria, following 24 hours treatment. Controls ran at a single concentration.Negative control - EMEM (Neat) 0*Positive control - Triton X-100 (0.1 %) 4*LQMN_B_03047 0 0 0 0LQMN_B_03053 0 0 0 0LQMN_B_03066 0 0 0 0LQMN_B_03015 0 0 0 0

[0223] Phase 2: Pilot: Screening of the effect of 3 urn and 5 urn HTS Transwell® pore size on recovery of Human Coronavirus OC43 and Human Influenza A H1 N1

[0224] Human Coronavirus OC43

[0225] Viral quantification

[0226] Average viral recoveries of above 7.00 Log10TCID50mL-1 were observed from both the 3 pm and 5 pm HTS Transwell® pore sizes at all timepoints. The results are recorded in Fig. 1 .

[0227] Molecular quantification

[0228] An average total genomic RNA quantification of above 7.00 LogioTCID50mL-1was observed across all timepoints for both the 3 pm & 5 pm HTS Transwell® pore size. The results are recorded in Fig. 2.

[0229] Human Influenza A H1 N1

[0230] Viral quantification

[0231] Average viral recoveries observed from the 5 pm HTS Transwell® pore size were above 7.00 LogioTCID50mL-1. Average viral recoveries observed from the 3 pm HTS Transwell® pore size were below 7.00 LogioTCID50mL-1, with the exception of the 0 hour timepoint which had an observed average recovery of 7.00 LogioTCID50mL-1. The results are depicted in Fig. 3.

[0232] Molecular quantification

[0233] An average total genomic RNA quantification of above 7.00 LogioTCID50mL-1was observed across all timepoints for the 3 pm HTS Transwell® pore size. Average detection remained above 7.00 LogioTCID50mL-1for the 5 pm HTS Transwell® pore size, this sample recovery reduced to 6.57 ± 0.95 LogioTCID50mL-1after 6 hours incubation. The results are depicted in Fig. 4.

[0234] Phase 2: Pilot: Screening of the effect of 5 urn HTS Transwell® pore size on recovery of Human Rhinovirus 1A

[0235] Viral quantification

[0236] All average viral recoveries observed from the 5 pm HTS T ranswell® pore size were above 7.00 LogioTCID50mL-1. The results are depicted in Fig.5.

[0237] Discussion

[0238] The COVID-19 pandemic has given rise to in vitro diagnostic tests, focusing on airway infections, preventions and treatments. To accurately assess the efficacy of these treatments, method customisation and optimisation to test against SARS-CoV-2 surrogates such as Human Coronavirus OC43 is utilised.

[0239] Corning HTS Transwell® plates with a pore size of 3 pm or 5 pm were tested against Human Coronavirus OC43 & Human Influenza A H1 N1 to ascertain viral recoveries & potential losses arising from passage through the HTS Transwell® membrane. For Human Rhinovirus 1A only the 5 pm pore size was assessed. Cytotoxicity testing was also performed to identify any potential cytotoxic effects of the test products.

[0240] High levels of Human Coronavirus OC43 and Human Influenza A H1 N1 recovery were demonstrated at both 3 pm or 5 pm pore size but higher overall recoveries were observed with the 5 pm pore sizes.

[0241] All timepoints for Human Coronavirus OC43, Human Influenza A H1 N1 and Human Rhinovirus 1A using the 5 pm plates showed recoveries of > 7.00 LogioTCID50mL for both the molecular and TCID50 testing.

[0242] For the 3 pm plates, recoveries of > 7.00 Log10TCID50mL-1 were observed by molecular testing at all timepoints for Human Coronavirus OC43 and Human Influenza A H1 N1 , but not by TCID50 testing for Human Influenza A H1 N1 . Recoveries of > 7.00 LogioTCID50mL-1were only observed at the 0 hour timepoint whilst the 0.5, 3 & 6 hour timepoints all demonstrated recoveries of < 7.00 LogioTCID50mL-1(6.45, 6.50 & 6.05 LogioTCID50mL-1respectively).

[0243] Despite recoveries of > 7.00 LogioTCID50mL-1being observed across all the molecular data, it is deemed that the 5 pm pore size plates be used in future testing as TCID50 testing will be the main output during later phases. The 5 pm pore size plates achieved recoveries high enough to ascertain potential 4 log reductions, as well as being used in previous studies, so their performance is well characterised. Due to their being a global shortage of HTS Transwell® plates worldwide, it is also recommended that the testing proceed forward with more readily available 5 pm pore size plates.

[0244] Cytotoxicity testing of all four test products showed no cytotoxic response at any of the potential contact concentrations. It is therefore deemed that cellular cytotoxicity is unlikely to interfere with future testing.

[0245] TCID50 Raw Data for the results discussed above10.50Control - 0 hour 10.50 9.948.838.170.5 hours 9.00 8.899.509.173 hours 8.83 9.289.839.336 hours 10.00 9.7810.00

[0246] Table 6: Average Log10TCID50mL-1 recovery results for Coronavirus OC43 following application to 3 pm HTS Transwell® membranes and incubation at the required contact times. verage Log recover ( Log 1 oTC I DsomL-1)10.50Control - 0 hour 10.50 10.5010.508.830.5 hours 8.50 9.069.839.673 hours 9.50 9.178.338.676 hours 7.83 8.338.50

[0247] Table 7:. Average Log10TCID50mL-1 recovery results for Coronavirus OC43 following application to 5 pm HTS Transwell® membranes and incubation at the required contact times. verage Log recover ( Log 1 oTC I DsomL-1)7.00Control - 0 hour 7.00 7.007.006.170.5 hours 6.67 6.446.506.673 hours 6.33 6.506.506.336 hours 5.50 6.066.33

[0248] Table 8: Average LogwTCIDSOmL-1recovery results for Influenza type A H1 N1 following application to 3 pm HTS Transwell® membranes and incubation at the required contact times.Control - 0 hour 8.17 8.337.677.000.5 hours 7.83 7.337.178.503 hours 7.33 7.617.006.506 hours 7.17 6.897.00

[0249] Table 9: Average LogioTCID50mL-1recovery results for Influenza type A H1 N1 following application to 5 pm HTS Transwell® membranes and incubation at the required contact times.Average Log recover (LogioTCIDsomL1)8.17Control - 0 hour 7.50 7.787.678.000.5 hours 7.67 7.948.178.173 hours 8.50 8.177.838.006 hours 7.50 7.677.50

[0250] Table 10:. Average LogioTCID50mL-1recovery results for Rhinovirus 1A following application to 5 pm HTS Transwell® membranes and incubation at the required contact times.

[0251] Standard curves for RT-qPCR quantification

[0252] Human Coronavirus OC43

[0253] Fig. 6 depicts the standard curve for a 10-fold serial dilution series of Human Coronavirus OC43.

[0254] Human Influenza A H1 N1

[0255] Fig. 7 depicts the standard curve for a 10-fold serial dilution series of Human Influenza A H1 N1.

[0256] Control criteria for cytotoxicity testing

[0257] Table 11 Cytotoxicity assay controls & system suitability criteria. * Refer to criteria outlined in Table G. Sy 3stem suitability Expected system .3„ „3. _criteriasuitability outcomeTriton X-100 at 0.1 % > Grade 3* or < 70% Demonstrate(w / v) Viability cytotoxic response 2 x 104cells seeded 2 Grade 2* or > 70% No cytotoxicper well Viability response observed

[0258] A summary of the scoring criteria used for visual microscopy endpoint are outlined below in Table 12.

[0259] Table 12: Qualitative morphological grading of cytotoxicity of test items._ Discrete intracytoplasmic granules, no cell lysis, no reductionof cell growth.Not more than 20% of the cells are round, loosely attached1 and without intracytoplasmic granules, or show changes inmorphology; occasional lysed cells are. present; only slight growth inhibition observable.Not more than 50% of the cells are round, devoid2 Mild of.intracytoplasmic granules, no extensive cell lysis; not more than 50% growth inhibition observable.Not more than 70% of the cell layers contain rounded cells or3 Moderate are lysed, cell layers not completely destroyed, but more that50% growth inhibition observable.4 Severe Nearly complete or complete destruction of the cell layers.

[0260] Examples of the Physical Barrier Functions

[0261] The aim of this example is to assess the physical barrier functions of four spray formulations tested as barrier complexes against three respiratory viruses.

[0262] Study tier: Tier 3b - Customised test method for R&D purposes

[0263] Materials and Methods

[0264] Test microorganisms - Cell types:• MRC-5 (ATCC® CCL-171 ™) - Passage number: PD 32.6• MDCK (NBL-2) (ATCC® CCL-34™) - Passage number: 24• H1-HeLa (ATCC® CRL-1958™) - Passage number: 23

[0265] Viruses:Human Coronavirus OC43 (ATCC® VR-1558™) - Amplification number: 1• Human Influenza A H1 N1 (ATCC® VR-1520™) - Amplification number: 1• Human Rhinovirus 1A (ATCC® VR-1559™) - Amplification number: 2

[0266] Test items

[0267] The details of the test items used in this study are outlined in Table 13.LQMN_B_03015 Liquid Not ProvidedLQMN_B_03047 Liquid Not ProvidedLQMN_B_03053 Liquid Not ProvidedLQMN_B_03066 Liquid Not Provided

[0268] Equipment and media

[0269] Equipment• Biosafety cabinet class II - BioMat, ThermoFisher Scientific, UK• CO2 incubator - ThermoFisher Scientific, UK• GoTaq® 1-step RT-qPCR Master Mix - Promega, UK• HTS Transwell® 96-well plates - Corning, UK• Microscope - Motic AE2000, UK• QIAamp Viral RNA Mini kit - Qiagen, UK• Rotor-gene Q thermal cycler - Qiagen, UK• Tissue culture plates - ThermoFisher Scientific, UK• UKAS calibrated pipettes - Sartorius, Scientific Laboratory Supplies (SLS), UK• UKAS calibrated multichannel pipettes - Gilson®, SLS, UK

[0270] Media• Eagle’s Modified Essential Medium (EMEM) - Pan Biotech, UK• Foetal bovine serum (FBS) - ThermoFisher Scientific, UK• Leibowitz’s L-15 Medium - Gibco™, UK• Penicillin-streptomycin - ThermoFisher Scientific, UK• TPCK T rypsin - ThermoFisher Scientific, UK

[0271] Method

[0272] Assessment of the physical barrier functions ofthe four spray formulations tested as barrier complexes against Human Coronavirus OC43, Human Influenza A H1 N1 and Human Rhinovirus 1 A

[0273] 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 andallowed 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 125 pL 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 1 A). 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 CO2 for 6 days. Following incubation, cells were visually inspected for cytopathic effects of viral infection.

[0274] Molecular quantification

[0275] 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. The Cq values obtained 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 (LogioTCID50mL-1).

[0276] Statistical analysis

[0277] Average total viral concentrations (LogioTCID50mL-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 LogioTCID50mL-1data from each product concentration compared to the no product control at each time point. Data were considered statistically significant if p < 0.05.

[0278] Results

[0279] Assessment of the physical barrier functions of four spray formulations tested as barrier complexes against Human Coronavirus OC43, Human Influenza A H1 N1 and Human Rhinovirus 1 A

[0280] Human Coronavirus OC43 - 0.5 hours

[0281] Viral recovery

[0282] At 0.5 hours the average total viral recovery for Human Coronavirus OC43 from the no product control was 11.83 ± 0.38 LogioTCID50mL-1(Table 2, Figure 1). At 100% test item concentration, LQMN_B_03015, LQMN_B_03053 and LQMN_B_03066 had average recoveries of 7.08 ± 1 .38, 5.50 ± 0.25 and 4.58 ± 0.80 respectively. This resulted in Log reductions of 4.75 ± 1 .75, 6.33 ± 0.58 and 7.25 ± 1 .00 for LQMN_B_03015, LQMN_B_03053 and LQMN_B_03066 respectively. At 75% test item concentration, LQMN_B_03015, LQMN_B_03053 and LQMN_B_03066 had averagerecoveries of 7.17 ± 1 .84, 3.25 ± 0.43 and 4.92 ± 1 .63 respectively. This resulted in Log reductions of 4.67 ± 1 .53, 8.58 ± 0.29 and 6.92 ± 1 .53 for LQMN_B_03015, LQMN_B_03053 and LQMN_B_03066 respectively when compared to the no product control.

[0283] Table 14:. Average Log recovery and reduction results for Human Coronavirus OC43 following transfer of virus through 5 pm HTS Transwell® membrane after 0.5 hours at three concentrations of each test product (100%, 75% and 0.01 %), when compared to the no product control. N / A = Not applicable. NR = No reduction. SD = Standard deviation. *p < 0.05. Viral titre determined by TCID50 and Spearman-Karber method. Average Log Average reduction ± SD ReductionNo product N / A 11.83 ± 0.38 N / A N / A100% 7.08 ± 1.38* 4.75 ± 1.75 > 99.99LQMN_B_03015 75% 7.17 ± 1.84* 4.67 ± 1 .53 > 99.990.01 % 11.17 ± 1.38 0.67 ± 1.66 78.46100% 9.08 ± 5.06 2.75 ± 5.41 99.82LQMN_B_03047 75% 12.08 ± 0.38 NR NR0.01 % 10.92 ± 0.80 0.92 ± 1.15 87.89100% 5.50 ± 0.25* 6.33 ± 0.58 > 99.99LQMN_B_03053 75% 3.25 ± 0.43* 8.58 ± 0.29 > 99.990.01 % 9.42 ± 1.94 2.42 ± 2.27 99.62100% 4.58 ± 0.80* 7.25 ± 1.00 > 99.99LQMN_B_03066 75% 4.92 ± 1.63* 6.92 ± 1 .53 > 99.990.01 % 11.00 ± 0.66 0.83 ± 0.63 85.32

[0284] The results are depicted in Fig. 8.

[0285] Molecular quantification

[0286] At 0.5 hours an average total genomic quantification for Human Coronavirus OC43 of 8.85 ± 0.26 LogioTCID50mL-1was detected from the no product control (Table 3, Figure 2). At 100% test item concentration, LQMN_B_03015, LQMN_B_03053 and LQMN_B_03066 had average quantifications of 2.11 ± 0.15, 1 .68 ± 0.06 and 2.62 ± 0.37 respectively. This resulted in Log reductions of 6.74 ± 0.15, 7.17 ± 0.06 and 6.23 ± 0.37 for LQMN_B_03015, LQMN_B_03053 and LQMN_B_03066 respectively. At 75% test item concentration, LQMN_B_03053 had an average quantification of 2.29 ± 0.08, resulting in a Log reduction of 6.56 ± 0.08 when compared to the no product control.

[0287] Table 15: Average total genomic RNA quantification and reduction results for Human Coronavirus OC43 following transfer of virus through 5 pm HTS Transwell® membrane after 0.5 hours with three concentrations of each test product (100%, 75% and 0.01 %), when compared to the no product control. N / A = Not applicable. NR = No reduction. SD = Standard deviation.Average Log Average Log AverageTest item Concentration detection ± SD reduction ± SD ReductionNo product N / A 8.85 ± 0.26 N / A N / A100% 2.11 ± 0.15 6.74 ± 0.15 > 99.99LQMN_B_03015 75% 6.35 ± 0.44 2.50 ± 0.44 99.690.01 % 8.19 ± 0.31 0.66 ± 0.31 78.13100% 7.56 ± 0.05 1.29 ± 0.05 94.87LQMN_B_03047 75% 8.05 ± 0.06 0.80 ± 0.06 84.180.01 % 9.1 1 ± 0.05 NR NR100% 1.68 ± 0.06 7.17 ± 0.06 > 99.99LQMN_B_03053 75% 2.29 ± 0.08 6.56 ± 0.08 > 99.990.01 % 8.75 ± 0.01 0.10 ± 0.01 20.73100% 2.62 ± 0.37 6.23 ± 0.37 > 99.99LQMN_B_03066 75% 5.01 ± 0.03 3.84 ± 0.03 99.990.01 % 8.87 ± 0.02 NR NR

[0288] The results are depicted in Fig. 9.

[0289] Human Coronavirus OC43 - 3 hours

[0290] Viral recovery

[0291] At 3 hours the average total viral recovery for Human Coronavirus OC43 from the no product control was 10.83 ± 0.38 LogioTCID50mL-1(Table 4, Figure 3). At 100% test item concentration, LQMN_B_03015, LQMN_B_03047, LQMN_B_03053 and LQMN_B_03066 had average recoveries of 4.33 ± 0.29, 3.08 ± 1.51 , 3.58 ± 1 .42 and 5.17 ± 0.52 respectively. This resulted in Log reductions of 6.50 ± 0.43, 7.75 ± 1 .64, 7.25 ± 1 .25 and 5.67 ± 0.29 for LQMN_B_03015, LQMN_B_03047, LQMN_B_03053 and LQMN_B_03066 respectively. At 75% test item concentration, LQMN_B_03015, LQMN_B_03047, LQMN_B_03053 and LQMN_B_03066 had average recoveries of 4.08 ± 0.52, 4.58 ± 2.67, 4.25 ± 1.15 and 4.17 ± 0.80 respectively. This resulted in Log reductions of 6.75 ± 0.50, 6.25 ± 2.61 , 6.58 ± 0.80 and 6.67 ± 0.76 for LQMN_B_03015, LQMN_B_03047, LQMN_B_03053 and LQMN_B_03066 respectively when compared to the no product control.

[0292] Table 16: Average Log recovery and reduction results for Human Coronavirus OC43 following transfer of virus through 5 pm HTS Transwell® membrane after 3 hours at three concentrations of each test product (100%, 75% and 0.01 %), when compared to the no product control. N / A = Not applicable. NR = No reduction. SD = Standard deviation. *p < 0.05. Viral titre determined by TCID50 and Spearman-Karber method.Average Log Average Log AverageTest item Concentration recovery ± SD reduction ± SD ReductionNo product N / A 10.83 ±0.38 N / A N / A100% 4.33 ±0.29* 6.50 ±0.43 >99.99LQMN_B_03015 75% 4.08 ± 0.52* 6.75 ±0.50 >99.990.01% 11.75 ±0.43 NR NR100% 3.08 ±1.51* 7.75 ±1.64 >99.99LQMN_B_03047 75% 4.58 ± 2.67* 6.25 ±2.61 >99.990.01% 10.33 ±0.38 0.50 ±0.50 68.38100% 3.58 ±1.42* 7.25 ±1.25 >99.99LQMN_B_03053 75% 4.25 ±1.15* 6.58 ±0.80 >99.990.01% 10.33 ± 1.42 0.50 ± 1.30 68.38100% 5.17 ±0.52* 5.67 ±0.29 >99.99LQMN_B_03066 75% 4.17 ±0.80* 6.67 ±0.76 >99.990.01% 10.50 ± 1.15 0.33 ± 1.26 53.58

[0293] The results are depicted in Fig.10.

[0294] Molecular quantification

[0295] At 3 hours an average total genomic quantification for Human Coronavirus OC43 of 8.49 ± 0.54 LogioTCID50mL-1was detected from the no product control (Table 5, Figure 4). At 100% test item concentration, LQMN_B_03015, LQMN_B_03053 and LQMN_B_03066 had average quantifications of 2.18 ± 0.59, 1.52 ± 0.38 and 2.49 ± 0.42 respectively. This resulted in Log reductions of 6.32 ± 0.63, 6.98 ± 0.01 and 6.01 ± 0.32 for LQMN_B_03015, LQMN_B_03053 and LQMN_B_03066 respectively. At 75% test item concentration, LQMN_B_03066 had an average quantification of 2.05 ± 0.25, resulting in a Log reduction of 6.44 ± 0.54 when compared to the no product control.

[0296] Table 17: Average total genomic RNA quantification and reduction results for Human Coronavirus OC43 following transfer of virus through 5 pm HTS T ranswell® membrane after 3 hours with three concentrations of each test product (100%, 75% and 0.01%), when compared to the no product control. N / A = Not applicable. NR = No reduction. SD = Standard deviation.Average Log Average Log AverageTest item Concentration detection ± SD reduction ± SD reduction (%)No product N / A 8.49 ± 0.54 N / A N / A100% 2.18 ±0.59 6.32 ±0.63 >99.99LQMN_B_03015 75% 6.40 ± 0.03 2.10 ±0.18 99.200.01% 7.45 ±0.63 1.05 ±0.20 91.06100% 6.76 ±0.18 1.73 ±0.65 98.16LQMN_B_03047 75% 7.70 ± 0.20 0.79 ± 0.38 83.860.01% 8.16 ±0.65 0.33 ±0.06 53.52100% 1.52 ± 0.38 6.98 ± 0.01 > 99.99LQMN_B_03053 75% 5.31 ± 0.06 3.19 ± 0.42 99.940.01 % 8.88 ± 0.01 NR NR100% 2.49 ± 0.42 6.01 ± 0.32 > 99.99LQMN_B_03066 75% 2.05 ± 0.25 6.44 ± 0.54 > 99.990.01 % 8.69 ± 0.32 NR NR

[0297] The results are depicted in Fig .11 .

[0298] Human Coronavirus OC43 - 6 hours

[0299] Viral recovery

[0300] At 6 hours the average total viral recovery for Human Coronavirus OC43 from the no product control was 11.17 ± 0.52 LogioTCID50mL-1(Table 6, Figure 5). At 100% test item concentration, LQMN_B_03015, LQMN_B_03047, LQMN_B_03053 and LQMN_B_03066 had average recoveries of 4.42 ± 2.50, 3.92 ± 0.72, 4.58 ± 0.95 and 4.08 ± 0.63 respectively. This resulted in Log reductions of 6.75 ± 2.70, 7.25 ± 1 .15, 6.58 ± 0.63 and 7.08 ± 0.38 for LQMN_B_03015, LQMN_B_03047, LQMN_B_03053 and LQMN_B_03066 respectively. At 75% test item concentration, LQMN_B_03015, LQMN_B_03047, LQMN_B_03053 and LQMN_B_03066 had average recoveries of 4.58 ± 1.28, 4.50 ± 0.50, 5.42 ± 1.04 and 3.83 ± 0.14 respectively. This resulted in Log reductions of 6.58 ± 1 .38, 6.67 ± 0.80, 5.75 ± 1.52 and 7.33 ± 0.63 for LQMN_B_03015, LQMN_B_03047, LQMN_B_03053 and LQMN_B_03066 respectively when compared to the no product control.

[0301] Table 18: Average Log recovery and reduction results for Human Coronavirus OC43 following transfer of virus through 5 pm HTS Transwell® membrane after 6 hours at three concentrations of each test product (100%, 75% and 0.01 %), when compared to the no product control. N / A = Not applicable. NR = No reduction. SD = Standard deviation. *p < 0.05. Viral titre determined by TCID50 and Spearman-Karber method.Average Log Average reduction ± SD ReductionNo product N / A 11.17 ±0.52 N / A N / A100% 4.42 ±2.50* 6.75 ±2.70 >99.99LQMN_B_03015 75% 4.58 ± 1.28* 6.58 ± 1.38 >99.990.01% 11.58 ±0.38 NR NR100% 3.92 ±0.72* 7.25 ±1.15 >99.99LQMN_B_03047 75% 4.50 ± 0.50* 6.67 ±0.80 >99.990.01% 10.50 ±0.25 0.67 ±0.76 78.46100% 4.58 ±0.95* 6.58 ±0.63 >99.99LQMN_B_03053 75% 5.42 ± 1.04* 5.75 ± 1.52 >99.990.01% 11.08 ±0.52 0.08 ±0.29 17.46100% 4.08 ±0.63* 7.08 ±0.38 >99.99LQMN_B_03066 75% 3.83 ±0.14* 7.33 ±0.63 >99.990.01% 11.00 ±0.66 0.17 ±0.58 31.87

[0302] The results are depicted in Fig.12.

[0303] Molecular quantification (6 hours)

[0304] At 6 hours an average total genomic quantification for Human Coronavirus OC43 of 8.57 ± 0.06 LogioTCID50mL-1was detected from the no product control (Table 7, Figure 6). At 100% test item concentration, LQMN_B_03015, LQMN_B_03053 and LQMN_B_03066 had average quantifications of 1.75 ± 0.24, 2.46 ± 0.43 and 2.69 ± 0.26 respectively. This resulted in Log reductions of 6.82 ± 0.24, 6.12 ± 0.43 and 5.88 ± 0.26 for LQMN_B_03015, LQMN_B_03053 and LQMN_B_03066 respectively. At 75% test item concentration, LQMN_B_03053 and LQMN_B_03066 had average quantifications of 2.85 ± 0.14 and 3.54 ± 0.11 , resulting in Log reductions of 5.72 ± 0.14 and 5.04 ± 0.11 when compared to the no product control.

[0305] Table 19: Average total genomic RNA quantification and reduction results for Human Coronavirus OC43 following transfer of virus through 5 pm HTS Transwell® membrane after 6 hours with three concentrations of each test product (100%, 75% and 0.01%), when compared to the no product control. N / A = Not applicable. NR = No reduction. SD = Standard deviation. Average Log Averagereduction ± SD eduction (%)No product N / A 8.57 ± 0.06 N / A N / A100% 1.75 ±0.24 6.82 ±0.24 >99.99LQMN_B_03015 75% 5.86 ± 0.39 2.71 ± 0.39 99.810.01% 9.02 ±0.09 NR NR100% 7.19 ±0.53 1.38 ±0.53 95.87LQMN_B_03047 75% 7.81 ± 0.07 0.76 ± 0.07 82.580.01% 7.67 ±0.78 0.90 ±0.78 87.397100% 2.46 ± 0.43 6.12 ± 0.43 > 99.99LQMN_B_03053 75% 2.85 ± 0.14 5.72 ± 0.14 > 99.990.01 % 8.68 ± 0.06 NR NR100% 2.69 ± 0.26 5.88 ± 0.26 > 99.99LQMN_B_03066 75% 3.54 ± 0.11 5.04 ± 0.11 > 99.990.01 % 8.73 ± 0.08 NR NR

[0306] The results are depicted in Fig.13.

[0307] Human Influenza A H1 N1 - 0.5 hours

[0308] Viral recovery

[0309] At 0.5 hours the average total viral recovery for Human Influenza A H1 N1 from the no product control was 7.50 ± 0.25 LogioTCID50mL-1(Table 8, Figure 7). At 100% test item concentration, LQMN_B_03015, LQMN_B_03047, LQMN_B_03053 and LQMN_B_03066 had average recoveries of 1 .75 ± 0.25, 2.25 ± 0.66, 2.00 ± 0.25 and 1 .58 ± 0.14 respectively. This resulted in Log reductions of 5.75 ± 0.50, 5.25 ± 0.50, 5.50 ± 0.25 and 5.92 ± 0.14 for LQMN_B_03015, LQMN_B_03047, LQMN_B_03053 and LQMN_B_03066 respectively. At 75% test item concentration, LQMN_B_03015, LQMN_B_03053 and LQMN_B_03066 had average recoveries of 2.58 ± 0.29, 2.75 ± 0.66 and 3.25 ± 0.66 respectively. This resulted in Log reductions of 4.92 ± 0.38, 4.75 ± 0.75 and 4.25 ± 0.66 for LQMN_B_03015, LQMN_B_03053 and LQMN_B_03066 respectively when compared to the no product control.

[0310] Table 20: Average Log recovery and reduction results for Human Influenza A H1 N1 following transfer of virus through 5 pm HTS Transwell® membrane after 0.5 hours at three concentrations of each test product (100%, 75% and 0.01 %), when compared to the no product control. N / A = Not applicable. NR = No reduction. SD = Standard deviation. *p < 0.05. Viral titre determined by TCID50 and Spearman-Karber method.Average Log Averagereduction ± SD eduction (%)No product N / A 7.50 ±0.25 N / A N / A100% 1.75 ±0.25* 5.75 ±0.50 >99.99LQMN_B_03015 75% 2.58 ±0.29* 4.92 ± 0.38 >99.990.01% 7.25 ±0.25 0.25 ±0.43 43.77100% 2.25 ±0.66 5.25 ±0.50 >99.99LQMN_B_03047 75% 5.50 ±0.25* 2.00 ± 0.25 99.000.01% 7.50 ±0.50 NR NR100% 2.00 ±0.25* 5.50 ±0.25 >99.99LQMN_B_03053 75% 2.75 ±0.66* 4.75 ± 0.75 >99.990.01% 6.58 ±0.14* 0.92 ±0.38 87.89100% 1.58 ±0.14* 5.92 ±0.14 >99.99LQMN_B_03066 75% 3.25 ±0.66* 4.25 ± 0.66 >99.990.01% 6.92 ±0.76 0.58 ±0.72 73.90

[0311] The results are depicted in Fig.14.

[0312] Molecular quantification

[0313] At 0.5 hours an average total genomic quantification for Human Influenza A H1N1 of8.88± 0.22 LogioTCID50mL-1was detected from the no product control (Table 9, Figure 8). At 100% test item concentration, LQMN_B_03015, LQMN_B_03053 and LQMN_B_03066 had average quantifications of 3.93 ± 0.09, 4.24 ± 0.15 and 3.76 ± 0.09 respectively. This resulted in Log reductions of 4.95 ± 0.09, 4.64 ± 0.15 and 5.12 ± 0.09 for LQMN_B_03015, LQMN_B_03053 and LQMN_B_03066 respectively when compared to the no product control.

[0314] Table 21: Average total genomic RNA quantification and reduction results for Human Influenza A H1N1 following transfer of virus through 5 pm HTS Transwell® membrane after 0.5 hours with three concentrations of each test product (100%, 75% and 0.01%), when compared to the no product control. N / A = Not applicable. NR = No reduction. SD = Standard deviation. Average Log Averagereduction ± SD eduction (%)No product N / A 8.88 ± 0.22 N / A N / A100% 3.93 ±0.09 4.95 ±0.09 >99.99LQMN_B_03015 75% 6.64 ±0.17 2.24 ±0.17 99.420.01% 8.61 ±0.08 0.26 ±0.08 45.65100% 6.63 ±0.32 2.25 ±0.32 99.44LQMN_B_03047 75% 7.83 ±0.11 1.05 ±0.11 91.140.01% 8.56 ±0.08 0.32 ±0.08 52.48100% 4.24 ±0.15 4.64 ±0.15 >99.99LQMN B 03053 75% 5.36 ± 0.05 3.52 ± 0.05 99.970.01 % 8.00 ± 0.20 0.88 ± 0.20 86.94100% 3.76 ± 0.09 5.12 ± 0.09 > 99.99LQMN_B_03066 75% 5.66 ± 0.17 3.22 ± 0.17 99.940.01 % 8.18 ± 0.04 0.70 ± 0.04 80.13

[0315] The results are depicted in Fig. 15.

[0316] Human Influenza A H1 N1 - 3 hours

[0317] Viral recovery

[0318] At 3 hours the average total viral recovery for Human Influenza A H1 N1 from the no product control was 7.50 ± 0.25 LogioTCID50mL-1(Table 10, Figure 9). At 100% test item concentration, LQMN_B_03015, LQMN_B_03047, LQMN_B_03053 and LQMN_B_03066 had average recoveries of 1 .50 ± 0.00, 1 .83 ± 0.29, 1 .83 ± 0.29 and 1 .67 ± 0.14 respectively. This resulted in Log reductions of 6.00 ± 0.25, 5.67 ± 0.14, 5.67 ± 0.38 and 5.83 ± 0.29 for LQMN_B_03015, LQMN_B_03047, LQMN_B_03053 and LQMN_B_03066 respectively. At 75% test item concentration, LQMN_B_03015, LQMN_B_03047, LQMN_B_03053 and LQMN_B_03066 had average recoveries of 2.58 ± 1 .46, 1 .75 ± 0.25, 1 .58 ± 0.14 and 1 .83 ± 0.29 respectively. This resulted in Log reductions of 4.92 ± 1 .66, 5.75 ± 0.43, 5.92 ± 0.29 and 5.67 ± 0.14 for LQMN_B_03015, LQMN_B_03047, LQMN_B_03053 and LQMN_B_03066 respectively when compared to the no product control.

[0319] Table 22: Average Log recovery and reduction results for Human Influenza A H1 N1 following transfer of virus through 5 pm HTS Transwell® membrane after 3 hours at three concentrations of each test product (100%, 75% and 0.01 %), when compared to the no product control. N / A = Not applicable. NR = No reduction. SD = Standard deviation. *p < 0.05. Viral titre determined by TCID50 and Spearman-Karber method.Average Log Averagereduction ± SD eduction (%)No product N / A 7.50 ± 0.25 N / A N / A100% 1.50 ±0.00* 6.00 ±0.25 >99.99LQMN_B_03015 75% 2.58 ± 1.46* 4.92 ± 1.66 >99.990.01% 7.08 ±0.29 0.42 ±0.38 61.69100% 1.83 ±0.29* 5.67 ±0.14 >99.99LQMN_B_03047 75% 1.75 ±0.25* 5.75 ±0.43 >99.990.01% 7.92 ±0.58 NR NR100% 1.83 ±0.29* 5.67 ±0.38 >99.99LQMN_B_03053 75% 1.58 ±0.14* 5.92 ±0.29 >99.990.01% 8.17 ±0.38 NR NR100% 1.67 ±0.14* 5.83 ±0.29 >99.99LQMN_B_03066 75% 1.83 ±0.29* 5.67 ±0.14 >99.990.01% 7.08 ±0.52 0.42 ±0.38 61.69

[0320] The results are depicted in Fig.16.

[0321] Molecular quantification

[0322] At 3 hours an average total genomic quantification for Human Influenza A H1 N1 of 8.55 ± 0.12 LogioTCID50mL-1was detected from the no product control (Table 11, Figure 10). At 100% test item concentration, LQMN_B_03015, LQMN_B_03053 and LQMN_B_03066 had average quantifications of 3.90 ± 0.25, 4.02 ± 0.12 and 3.63 ± 0.88 respectively. This resulted in Log reductions of 4.64 ± 0.03, 4.53 ± 0.06 and 4.92 ± 0.23 for LQMN_B_03015, LQMN_B_03053 and LQMN_B_03066 respectively. At 75% test item concentration, LQMN_B_03053 had an average quantification of 4.09 ± 0.15, resulting in a Log reduction of 4.45 ± 0.88 when compared to the no product control.

[0323] Table 23:. Average total genomic RNA quantification and reduction results for Human Influenza A H1N1 following transfer of virus through 5 pm HTS Transwell® membrane after 3 hours with three concentrations of each test product (100%, 75% and 0.01%), when compared to the no product control. N / A = Not applicable. NR = No reduction. SD = Standard deviation.Average Log Average Log AverageTest item Concentration detection ± SD reduction ± SD reduction (%)No product N / A 8.55 ±0.12 N / A N / A100% 3.90 ±0.25 4.64 ±0.03 >99.99LQMN_B_03015 75% 5.56 ± 0.09 2.99 ± 0.07 99.900.01% 8.51 ±0.03 0.03 ±0.02 7.58100% 4.91 ±0.07 3.64 ±0.05 99.98LQMN_B_03047 75% 8.00 ± 0.02 0.55 ±0.12 71.510.01% 8.75 ±0.05 NR NR100% 4.02 ± 0.12 4.53 ± 0.06 > 99.99LQMN_B_03053 75% 4.09 ± 0.15 4.45 ± 0.88 > 99.990.01 % 8.20 ± 0.06 0.35 ± 0.09 55.42 100% 3.63 ± 0.88 4.92 ± 0.23 > 99.99LQMN_B_03066 75% 4.78 ± 0.09 3.77 ± 0.12 99.980.01 % 8.59 ± 0.23 NR NR

[0324] The results are depicted in Fig. 17.

[0325] Human Influenza A H1 N1 - 6 hours

[0326] Viral recovery

[0327] At 6 hours the average total viral recovery for Human Influenza A H1 N1 from the no product control was 6.50 ± 0.43 LogioTCID50mL-1(Table 12, Figure 11). At 100% test item concentration, LQMN_B_03015, LQMN_B_03047, LQMN_B_03053 and LQMN_B_03066 had average recoveries of 1 .83 ± 0.14, 1 .75 ± 0.25, 1 .83 ± 0.14 and 1 .58 ± 0.14 respectively. This resulted in Log reductions of 4.67 ± 0.52, 4.75 ± 0.50, 4.67 ± 0.52 and 4.92 ± 0.52 for LQMN_B_03015, LQMN_B_03047, LQMN_B_03053 and LQMN_B_03066 respectively. At 75% test item concentration, LQMN_B_03047, LQMN_B_03053 and LQMN_B_03066 had average recoveries of 2.50 ± 0.25, 1 .75 ± 0.43 and 1.92 ± 0.14 respectively. This resulted in Log reductions of 4.00 ± 0.25, 4.75 ± 0.75 and 4.58 ± 0.58 for LQMN_B_03047, LQMN_B_03053 and LQMN_B_03066 respectively when compared to the no product control.

[0328] Table 24: Average Log recovery and reduction results for Human Influenza A H1 N1 following transfer of virus through 5 pm HTS Transwell® membrane after 6 hours at three concentrations of each test product (100%, 75% and 0.01 %), when compared to the no product control. N / A = Not applicable. NR = No reduction. SD = Standard deviation. *p < 0.05. Viral titre determined by TCID50 and Spearman-Karber method.Average Log Averagereduction ± SD eduction (%)No product N / A 6.50 ± 0.43 N / A N / A100% 1.83 ±0.14* 4.67 ±0.52 >99.99LQMN_B_03015 75% 2.92 ± 0.80* 3.58 ±0.76 99.970.01% 6.25 ±0.00 0.25 ±0.43 43.77100% 1.75 ±0.25* 4.75 ±0.50 >99.99LQMN_B_03047 75% 2.50 ± 0.25* 4.00 ±0.25 99.990.01% 6.83 ±0.58 NR NR100% 1.83 ±0.14* 4.67 ±0.52 >99.99LQMN_B_03053 75% 1.75 ±0.43* 4.75 ±0.75 >99.990.01% 7.25 ±0.25 NR NR100% 1.58 ±0.14* 4.92 ±0.52 >99.99LQMN_B_03066 75% 1.92 ±0.14* 4.58 ±0.58 >99.990.01% 6.08 ±0.14 0.42 ±0.52 61.69

[0329] The results are depicted in Fig.18.

[0330] Molecular quantification

[0331] At 6 hours an average total genomic quantification for Human Influenza A H1 N1 of 8.50 ± 0.18 LogioTCID50mL-1was detected from the no product control (Table 13, Figure 12). At 100% test item concentration, LQMN_B_03015 and LQMN_B_03053 had average quantifications of 4.32 ± 0.12 and 3.90 ± 0.16 respectively. This resulted in Log reductions of 4.17 ± 0.12 and 4.60 ± 0.16 for LQMN_B_03015 and LQMN_B_03053 respectively. At 75% test item concentration, LQMN_B_03053 had an average quantification of 3.90 ± 0.18, resulting in a Log reduction of 4.59 ± 0.18 when compared to the no product control.

[0332] Table 25: Average total genomic RNA quantification and reduction results for Human Influenza A H1N1 following transfer of virus through 5 pm HTS Transwell® membrane after 6 hours with three concentrations of each test product (100%, 75% and 0.01%), when compared to the no product control. N / A = Not applicable. NR = No reduction. SD = Standard deviation.Average Log Average Log AverageTest item Concentration detection ± SD reduction ± SD reduction (%)No product N / A 8.50 ±0.18 N / A N / A100% 4.32 ±0.12 4.17 ±0.12 >99.99LQMN_B_03015 75% 5.00 ± 0.30 3.49 ± 0.30 99.970.01% 8.36 ±0.06 0.13 ±0.06 26.43100% 6.75 ±0.07 1.75 ±0.07 98.23LQMN_B_03047 75% 7.91 ±0.16 0.59 ±0.16 74.120.01% 8.68 ±0.24 NR NR100% 3.90 ±0.16 4.60 ±0.16 >99.99LQMN_B_03053 75% 3.90 ± 0.18 4.59 ± 0.18 > 99.990.01 % 7.84 ± 0.18 0.65 ± 0.18 77.85100% 4.51 ± 0.07 3.99 ± 0.07 99.90LQMN_B_03066 75% 6.52 ± 0.07 1.97 ± 0.07 98.940.01 % 8.07 ± 0.05 0.43 ± 0.05 62.73

[0333] The results are depicted in Fig. 19.

[0334] Human Rhinovirus 1 A - 0.5 hours

[0335] Viral recovery

[0336] At 0.5 hours the average total viral recovery for Human Rhinovirus 1 A from the no product control was 7.33 ± 0.14 LogioTCID50mL-1(Table 14, Figure 13). At 100% test item concentration, LQMN_B_03015, LQMN_B_03047, LQMN_B_03053 and LQMN_B_03066 had average recoveries of 2.50 ± 0.00, 3.50 ± 1.52, 2.50 ± 0.00 and 2.50 ± 0.00 respectively. This resulted in Log reductions of 4.83 ± 0.14, 3.83 ± 1.38, 4.83 ± 0.14 and 4.83 ± 0.14 for LQMN_B_03015, LQMN_B_03047, LQMN_B_03053 and LQMN_B_03066 respectively when compared to the no product control.

[0337] Table 26:. Average Log recovery and reduction results for Human Rhinovirus 1 A following transfer of virus through 5 pm HTS Transwell® membrane after 0.5 hours at three concentrations of each test product (100%, 75% and 0.01 %), when compared to the no product control. N / A = Not applicable. NR = No reduction. SD = Standard deviation. *p < 0.05. Viral titre determined by TCID50 and Spearman-Karber method. Average Log Averagereduction ± SD eduction (%)No product N / A 7.33 ± 0.14 N / A N / A100% 2.50 ± 0.00* 4.83 ± 0.14 > 99.99LQMN_B_03015 75% 4.92 ± 0.52* 2.42 ± 0.38 99.620.01 % 7.25 ± 0.25 0.08 ± 0.38 17.46100% 3.50 ± 1.52* 3.83 ± 1.38 99.99LQMN_B_03047 75% 6.17 ± 0.80 1.17 ± 0.76 93.190.01 % 7.17 ± 0.14 0.17 ± 0.14 31 .87100% 2.50 ± 0.00* 4.83 ± 0.14 > 99.99LQMN_B_03053 75% 5.25 ± 0.25* 2.08 ± 0.14 99.180.01 % 7.50 ± 0.43 NR NR100% 2.50 ± 0.00* 4.83 ± 0.14 > 99.99LQMN_B_03066 75% 5.42 ± 0.52* 1.92 ± 0.58 98.790.01 % 7.42 ± 0.52 NR NR

[0338] The results are depicted in Fig. 20.

[0339] Molecular quantification

[0340] At 0.5 hours an average total genomic quantification for Human Rhinovirus 1 A of 8.06 ± 0.17 LogioTCID50mL-1was detected from the no product control (Table 15, Figure 14). At 100% testitem concentration, LQMN_B_03015 and LQMN_B_03066 had average quantifications of 3.41 ± 0.09 and 3.25 ± 0.15 respectively. This resulted in Log reductions of 4.66 ± 0.09 and 4.81 ± 0.15 for LQMN_B_03015 and LQMN_B_03066 respectively when compared to the no product control.

[0341] Table 27: Average total genomic RNA quantification and reduction results for Human Rhinovirus 1 A following transfer of virus through 5 pm HTS Transwell® membrane after 0.5 hours with three concentrations of each test product (100%, 75% and 0.01 %), when compared to the no product control. N / A = Not applicable. NR = No reduction. SD = Standard deviation. Average Log Averagereduction ± SD eduction (%)No product N / A 8.06 ± 0.17 N / A N / A100% 3.41 ± 0.09 4.66 ± 0.09 > 99.99LQMN_B_03015 75% 7.45 ± 0.04 0.61 ± 0.04 75.460.01 % 8.06 ± 0.29 0.01 ± 0.29 1.17100% 7.02 ± 0.16 1.04 ± 0.16 90.90LQMN_B_03047 75% 8.49 ± 0.05 NR NR0.01 % 7.48 ± 0.16 0.58 ± 0.16 73.79100% 7.44 ± 0.09 0.62 ± 0.09 76.03LQMN_B_03053 75% 7.64 ± 0.06 0.42 ± 0.06 62.130.01 % 8.77 ± 0.15 NR NR100% 3.25 ± 0.15 4.81 ± 0.15 > 99.99LQMN_B_03066 75% 6.98 ± 0.32 1.08 ± 0.32 91 .660.01 % 8.15 ± 0.22 NR NR

[0342] The results are depicted in Fig. 21 .

[0343] Human Rhinovirus 1 A - 3 hours

[0344] Viral recovery

[0345] At 3 hours the average total viral recovery for Human Rhinovirus 1A from the no product control was 8.08 ± 0.14 LogioTCID50mL-1(Table 16, Figure 15). At 100% test item concentration, LQMN_B_03015, LQMN_B_03053 and LQMN_B_03066 had average recoveries of 2.58 ± 0.14, 2.67 ± 0.14 and 2.67 ± 0.14 respectively. This resulted in Log reductions of 5.50 ± 0.25, 5.42 ± 0.29 and 5.42 ± 0.14 for LQMN_B_03015, LQMN_B_03053 and LQMN_B_03066 respectively. At 75% test item concentration, LQMN_B_03015 and LQMN_B_03053 had average recoveries of 3.00 ± 0.50 and 2.83 ± 0.38 respectively. This resulted in Log reductions of 5.08 ± 0.63 and 5.25 ± 0.50 for LQMN_B_03015 and LQMN_B_03053 respectively when compared to the no product control.

[0346] Table 28: Average Log recovery and reduction results for Human Rhinovirus 1 A following transfer of virus through 5 pm HTS Transwell® membrane after 3 hours at three concentrations of each test product (100%, 75% and 0.01 %), when compared to the no product control. N / A = Not applicable. NR = No reduction. SD = Standard deviation. *p < 0.05. Viral titre determined by TCID50 and Spearman-Karber method.Average Log Averagereduction ± SD eduction (%)No product N / A 8.08 ±0.14 N / A N / A100% 2.58 ±0.14* 5.50 ±0.25 >99.99LQMN_B_03015 75% 3.00 ± 0.50* 5.08 ±0.63 >99.990.01% 7.50 ±0.43 0.58 ±0.52 73.90100% 4.42 ±0.38* 3.67 ±0.52 99.98LQMN_B_03047 75% 8.00 ± 0.25 0.08 ±0.14 17.460.01% 7.50 ±0.43 0.58 ±0.38 73.90100% 2.67 ±0.14* 5.42 ±0.29 >99.99LQMN_B_03053 75% 2.83 ± 0.38* 5.25 ±0.50 >99.990.01% 7.17 ±0.14* 0.92 ±0.29 87.89100% 2.67 ±0.14* 5.42 ±0.14 >99.99LQMN_B_03066 75% 5.25 ± 0.25* 2.83 ±0.14 99.850.01% 7.17 ±0.38* 0.92 ±0.38 87.89

[0347] The results are depicted in Fig.22.

[0348] Molecular quantification

[0349] At3 hours an average total genomic quantification forHuman Rhinovirus 1Aof8.12 ±0.10 LogioTCID50mL-1was detected from the no product control (Table 17, Figure 16). At 100% test item concentration, LQMN_B_03015 and LQMN_B_03066 had average quantifications of 3.12 ± 0.11 and 2.77 ± 0.64 respectively. This resulted in Log reductions of 5.00 ± 0.11 and 5.35 ± 0.64 for LQMN_B_03015 and LQMN_B_03066 respectively when compared to the no product control.

[0350] Table 29: Average total genomic RNA quantification and reduction results for Human Rhinovirus 1 A following transfer of virus through 5 pm HTS Transwell® membrane after 3 hours with three concentrations of each test product (100%, 75% and 0.01%), when compared to the no product control. N / A = Not applicable. NR = No reduction. SD = Standard deviation. Average Log Averagereduction ± SD eduction (%)No product N / A 8.12 ±0.10 N / A N / A100% 3.12 ±0.11 5.00 ±0.11 >99.99LQMN_B_03015 75% 4.78 ± 0.23 3.34 ± 0.23 99.950.01% 7.88 ±0.29 0.24 ±0.29 42.24100% 4.17 ±0.31 3.95 ±0.31 99.99LQMN_B_03047 75% 7.23 ± 0.41 0.89 ± 0.41 87.030.01% 8.88 ±0.08 NR NR100% 7.02 ±0.14 1.10 ±0.14 92.13LQMN_B_03053 75% 7.37 ± 0.26 0.75 ± 0.26 82.120.01% 7.42 ±0.22 0.70 ±0.22 79.90Average Log Averagereduction ± SD eduction (%)100% 2.77 ± 0.64 5.35 ± 0.64 > 99.99LQMN_B_03066 75% 5.58 ± 0.12 2.54 ± 0.12 99.710.01 % 9.24 ± 0.06 NR NR

[0351] The results are depicted in Fig. 23.

[0352] Human Rhinovirus 1 A - 6 hours

[0353] Viral recovery

[0354] At 6 hours the average total viral recovery for Human Rhinovirus 1A from the no product control was 8.33 ± 0.38 LogioTCID50mL-1(Table 18, Figure 17). At 100% test item concentration, LQMN_B_03015 and LQMN_B_03066 had average recoveries of 2.92 ± 0.72 and 2.75 ± 0.25 respectively. This resulted in Log reductions of 5.42 ± 1.04 and 5.58 ± 0.38 for LQMN_B_03015 and LQMN_B_03066 respectively. At 75% test item concentration, LQMN_B_03015 and LQMN_B_03053 had average recoveries of 2.92 ± 0.52 and 3.67 ± 1 .01 respectively. This resulted in Log reductions of 5.42 ± 0.80 and 4.67 ± 1.01 for LQMN_B_03015 and LQMN_B_03053 respectively when compared to the no product control.

[0355] Table 30:. Average Log recovery and reduction results for Human Rhinovirus 1 A following transfer of virus through 5 pm HTS Transwell® membrane after 6 hours at three concentrations of each test product (100%, 75% and 0.01 %), when compared to the no product control. N / A = Not applicable. NR = No reduction. SD = Standard deviation. *p < 0.05. Viral titre determined by TCID50 and Spearman-Karber method. Average Log Averagereduction ± SD eduction (%)No product N / A 8.33 ± 0.38 N / A N / A100% 2.92 ± 0.72* 5.42 ± 1.04 > 99.99LQMN_B_03015 75% 2.92 ± 0.52* 5.42 ± 0.80 > 99.990.01 % 7.25 ± 0.25* 1.08 ± 0.29 91.75100% 6.83 ± 0.52* 1.50 ± 0.87 96.84LQMN_B_03047 75% 7.75 ± 0.43 0.58 ± 0.80 73.900.01 % 7.33 ± 0.38* 1.00 ± 0.25 90.00100% 4.58 ± 0.76* 3.75 ± 0.66 99.98LQMN_B_03053 75% 3.67 ± 1.01* 4.67 ± 1 .01 > 99.990.01 % 7.58 ± 0.29 0.75 ± 0.66 82.22100% 2.75 ± 0.25* 5.58 ± 0.38 > 99.99LQMN_B_03066 75% 6.67 ± 1.01 1.67 ± 1.01 97.850.01 % 7.25 ± 0.50* 1.08 ± 0.88 91.75

[0356] The results are depicted in Fig. 24.

[0357] Molecular quantification

[0358] At 6 hours an average total genomic quantification for Human Rhinovirus 1A of 8.53 ± 0.11 LogioTCID50mL-1was detected from the no product control (Table 19, Figure 18). At 100% test item concentration, LQMN_B_03015 and LQMN_B_03066 had average quantifications of 3.80 ± 0.64 and 4.25 ± 0.23 respectively. This resulted in Log reductions of 4.73 ± 0.64 and 4.28 ± 0.23 for LQMN_B_03015 and LQMN_B_03066 respectively. At 75% test item concentration, LQMN_B_03015 had an average quantification of 4.43 ± 0.54, resulting in a Log reduction of 4.10 ± 0.54 when compared to the no product control.

[0359] Table 31 : Average total genomic RNA quantification and reduction results for Human Rhinovirus 1 A following transfer of virus through 5 pm HTS Transwell® membrane after 6 hours with three concentrations of each test product (100%, 75% and 0.01 %), when compared to the no product control. N / A = Not applicable. NR = No reduction. SD = Standard deviation.Average Log Average Log AverageTest item Concentration detection ± SD reduction ± SD reduction (%)No product N / A 8.53 ± 0.11 N / A N / A100% 3.80 ± 0.64 4.73 ± 0.64 > 99.99LQMN_B_03015 75% 4.43 ± 0.54 4.10 ± 0.54 > 99.990.01 % 8.01 ± 0.14 0.52 ± 0.14 70.12100% 6.88 ± 0.29 1.65 ± 0.29 97.77LQMN_B_03047 75% 7.30 ± 0.18 1.23 ± 0.18 94.080.01 % 8.82 ± 0.00 NR NR100% 7.60 ± 0.25 0.93 ± 0.25 88.36LQMN_B_03053 75% 7.86 ± 0.23 0.67 ± 0.23 78.480.01 % 8.47 ± 0.23 0.06 ± 0.23 12.92100% 4.25 ± 0.23 4.28 ± 0.23 > 99.99LQMN_B_03066 75% 8.59 ± 0.11 NR NR0.01 % 8.06 ± 0.41 0.47 ± 0.41 66.48

[0360] The results are depicted in Fig. 25

[0361] Summary

[0362] 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.

[0363] 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.

[0364] Human Coronavirus OC43

[0365] LQMN B 03015

[0366] Application of LQMN_B_03015 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.

[0367] Molecular quantification demonstrated > 4 Log reductions for Human Coronavirus OC43 at 100% concentration at all three time points.

[0368] LQMN B 03047

[0369] Application of LQMN_B_03047 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 3 and 6 hours only.

[0370] Molecular quantification did not demonstrate any > 4 Log reductions for Human Coronavirus OC43 at any concentration at any of the three time points.

[0371] LQMN B 03053

[0372] Application of LQMN_B_03053 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.

[0373] 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 0.5 and 6 hours.

[0374] LQMN B 03066

[0375] Application of LQMN_B_03066 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.

[0376] 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.

[0377] Human Influenza A H1 N1

[0378] LQMN B 03015

[0379] Application of LQMN_B_03015 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.

[0380] Molecular quantification demonstrated > 4 Log reductions for Human Influenza A H1 N1 at 100% concentration at all three time points.

[0381] LQMN B 03047

[0382] Application of LQMN_B_03047 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 3 and 6 hours only.

[0383] Molecular quantification did not demonstrate any > 4 Log reductions for Human Influenza A H1 N1 at any concentration at any of the three time points.

[0384] LQMN B 03053

[0385] Application of LQMN_B_03053 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.

[0386] Molecular quantification demonstrated > 4 Log reductions for Human Influenza A H1 N1 at 100% concentration at all three time points. At 75% concentration, > 4 Log reductions were demonstrated at 3 and 6 hours only.

[0387] LQMN B 03066

[0388] Application of LQMN_B_03066 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.

[0389] Molecular quantification demonstrated > 4 Log reductions for Human Influenza A H1 N1 at 100% concentration at 0.5 and 3 hours only.

[0390] Human Rhinovirus 1A

[0391] LQMN B 03015

[0392] Application of LQMN_B_03015 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.

[0393] 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.

[0394] LQMN B 03047

[0395] Application of LQMN_B_03047 to the 5 pm HTS Transwell® membrane at any concentration did not result in any > 4 Log reductions for Human Rhinovirus 1A at any concentration at any of the three time points.

[0396] Molecular quantification did not demonstrate any > 4 Log reductions for Human Rhinovirus 1 A at any concentration at any of the three time points.

[0397] LQMN B 03053

[0398] Application of LQMN_B_03053 to the 5 pm HTS Transwell® membrane at 100% concentration resulted in > 4 Log reductions in viral recovery for Human Rhinovirus 1A at 0.5 and 3 hours only. At 75% concentration, > 4 Log reductions were observed at 3 and 6 hours only.

[0399] Molecular quantification did not demonstrate any > 4 Log reductions for Human Rhinovirus 1 A at any concentration at any of the three time points.

[0400] LQMN B 03066

[0401] Application of LQMN_B_03066 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.

[0402] Molecular quantification demonstrated > 4 Log reductions for Human Rhinovirus 1A at 100% concentration at all three time points.

[0403] Discussion

[0404] For this study, four test items (LQMN_B_03015, LQMN_B_03047, LQMN_B_03053 and LQMN_B_03066) were tested as barrier complexes against three respiratory viruses (Human Coronavirus OC43, Human Influenza A H1 N1 and Human Rhinovirus 1A).

[0405] Both viral recovery via TCID50 and viral quantification via molecular detection demonstrated > 4 Log reductions fortest items LQMN_B_03015 and LQMN_B_03066 against all three viruses.

[0406] Test item LQMN_B_03053 demonstrated > 4 Log reductions against all three viruses when measured via TCID50, but only against Human Coronavirus OC43 and Human Influenza A H1 N1 when measured via molecular detection.

[0407] Test item LQMN_B_03047 demonstrated > 4 Log reductions against Human Coronavirus OC43 and Human Influenza A H1 N1 when measured via TCID50. No > 4 log reductions were observed via molecular detection.

[0408] 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 TCID50 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.

[0409] In conclusion, the results shown above for both viral recovery and molecular detection show that test items LQMN_B_03015, LQMN_B_03053 and LQMN_B_03066 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. However, both viral recovery and molecular detection results suggest that LQMN_B_03047 is not as effective in forming a barrier complex against the test viruses.

[0410] Future work could include the evaluation of different barrier thickness to closer reflect the real word use of test items as nasal sprays, and also to assess of the use of viable-only PCR to quantify infectious virus only and further increase consistency between results obtained by TCID50 recovery and molecular detection.

[0411] Viral recovery raw data

[0412] Table 32: Viral recovery results for Human Coronavirus OC43 at 0.5 hours following application of test items to the 5 pm HTS Transwell® membrane.No product N / A 12.25 11.75 11.50100% 5.50 7.75 8.00LQMN_B_03015 75% 9.25 5.75 6.500.01 % 9.75 12.50 11 .25100% 3.25 12.25 11 .75LQMN_B_03047 75% 12.00 12.50 11.750.01 % 10.00 11.50 11.25100% 5.25 5.75 5.50LQMN_B_03053 75% 3.50 3.50 2.750.01 % 7.25 1 1.00 10.00100% 4.00 5.50 4.25LQMN_B_03066 75% 5.00 6.50 3.250.01 % 1 1.50 10.25 11.25

[0413] Table 33: Viral recovery results for Human Coronavirus OC43 at 3 hours following application of test items to the 5 pm HTS Transwell® membrane.No product N / A 10.75 11 .25 10.50100% 4.00 4.50 4.50LQMN_B_03015 75% 3.50 4.50 4.250.01 % 11.50 12.25 1 1.50100% 1 .50 3.25 4.50LQMN_B_03047 75% 1 .50 6.25 6.000.01 % 10.75 10.25 10.00100% 4.75 4.00 2.00LQMN_B_03053 75% 4.50 5.25 3.000.01 % 8.75 1 1.50 10.75100% 4.75 5.75 5.00LQMN_B_03066 75% 3.25 4.75 4.500.01 % 9.25 10.75 11.50

[0414] Table 34: Viral recovery results for Human Coronavirus OC43 at 6 hours following application of test items to the 5 pm HTS Transwell® membrane.No product N / A 10.75 11 .00 11 .75100% 7.00 2.00 4.25LQMN_B_03015 75% 3.50 6.00 4.250.01 % 12.00 1 1.25 1 1.50100% 4.75 3.50 3.50LQMN_B_03047 75% 5.00 4.00 4.500.01 % 10.75 10.50 10.25100% 3.50 5.00 5.25LQMN_B_03053 75% 5.75 6.25 4.250.01 % 10.50 1 1.25 1 1.50100% 4.00 3.50 4.75LQMN_B_03066 75% 4.00 3.75 3.750.01 % 10.25 1 1.50 1 1.25

[0415] Table 35: Viral recovery results for Human Influenza A H1 N1 at 0.5 hours following application of test items to the 5 pm HTS Transwell® membrane.No product N / A 7.50 7.25 7.75100% 1.75 2.00 1 .50LQMN_B_03015 75% 2.25 2.75 2.750.01 % 7.50 7.25 7.00100% 1.75 2.00 3.00LQMN_B_03047 75% 5.25 5.50 5.750.01 % 8.00 7.00 7.50100% 1.75 2.00 2.25LQMN_B_03053 75% 3.50 2.50 2.250.01 % 6.50 6.75 6.50100% 1.50 1.50 1 .75LQMN_B_03066 75% 4.00 2.75 3.000.01 % 7.75 6.25 6.75

[0416] Table 36: Viral recovery results for Human Influenza A H1 N1 at 3 hours following application of test items to the 5 pm HTS Transwell® membrane.No product N / A 7.75 7.50 7.25100% 1.50 1.50 1 .50LQMN_B_03015 75% 2.00 1.50 4.250.01 % 7.25 6.75 7.25100% 2.00 2.00 1 .50LQMN_B_03047 75% 1.50 2.00 1.750.01 % 8.25 7.25 8.25100% 2.00 1.50 2.00LQMN_B_03053 75% 1 .50 1 .75 1 .500.01 % 8.50 8.25 7.75100% 1.75 1.50 1 .75LQMN_B_03066 75% 2.00 2.00 1.500.01 % 7.25 7.50 6.50

[0417] Table 37: Viral recovery results for Human Influenza A H1 N1 at 6 hours following application of test items to the 5 pm HTS Transwell® membrane.No product N / A 6.25 6.25 7.00100% 1 .75 2.00 1.75LQMN_B_03015 75% 2.00 3.50 3.250.01 % 6.25 6.25 6.25100% 2.00 1.50 1.75LQMN_B_03047 75% 2.50 2.25 2.750.01 % 6.50 7.50 6.50100% 1 .75 2.00 1.75LQMN_B_03053 75% 2.25 1.50 1 .500.01 % 7.25 7.00 7.50100% 1 .50 1.75 1.50LQMN_B_03066 75% 2.00 2.00 1 .750.01 % 6.25 6.00 6.00

[0418] Table 38: Viral recovery results for Human Rhinovirus 1 A at 0.5 hours following application of test items to the 5 pm HTS Transwell® membrane.No product N / A 7.25 7.50 7.25100% 2.50 2.50 2.50LQMN_B_03015 75% 4.75 5.50 4.500.01 % 7.50 7.00 7.25100% 2.50 5.25 2.75LQMN_B_03047 75% 6.75 6.50 5.250.01 % 7.00 7.25 7.25100% 2.50 2.50 2.50LQMN_B_03053 75% 5.00 5.50 5.250.01 % 7.25 8.00 7.25100% 2.50 2.50 2.50LQMN_B_03066 75% 6.00 5.25 5.000.01 % 7.25 7.00 8.00

[0419] Table 39: Viral recovery results for Human Rhinovirus 1A at 3 hours following application of test items to the 5 pm HTS Transwell® membrane.No product N / A 8.25 8.00 8.00100% 2.50 2.50 2.75LQMN_B_03015 75% 2.50 3.50 3.000.01 % 7.25 7.25 8.00100% 4.00 4.75 4.50LQMN_B_03047 75% 8.25 8.00 7.750.01 % 7.75 7.75 7.00100% 2.50 2.75 2.75LQMN_B_03053 75% 2.50 2.75 3.250.01 % 7.00 7.25 7.25100% 2.75 2.50 2.75LQMN_B_03066 75% 5.50 5.25 5.000.01 % 7.25 6.75 7.50

[0420] Table 40: Viral recovery results for Human Rhinovirus 1 A at 6 hours following application of test items to the 5 pm HTS Transwell® membrane.No product N / A 8.00 8.25 8.75100% 3.75 2.50 2.50LQMN_B_03015 75% 3.50 2.50 2.750.01 % 7.25 7.00 7.50100% 7.00 7.25 6.25LQMN_B_03047 75% 8.00 8.00 7.250.01 % 7.25 7.00 7.75100% 3.75 5.25 4.75LQMN_B_03053 75% 2.75 4.75 3.500.01 % 7.75 7.75 7.25100% 2.50 3.00 2.75LQMN_B_03066 75% 7.25 5.50 7.250.01 % 7.75 7.25 6.75

[0421] Standard curves for RT-qPCR quantification

[0422] Human Coronavirus OC43

[0423] Fig. 26 is a standard curve for a 10-fold serial dilution series of Human Coronavirus OC43.

[0424] Human Influenza A H1 N1

[0425] Fig. 27 is a standard curve for a 10-fold serial dilution series of Human InfluenzaA H1 N1 .

[0426] Human Rhinovirus 1A

[0427] Fig. 28 is as standard curve for a 10-fold serial dilution series of Human Rhinovirus 1A.

[0428] Microfilm structure

[0429] The composition of Formula D referred to above (LQMN B 03066) was modified as set out in Table 41 to study the effect of different compositions on morphological properties.

[0430] Test solutions were prepared in different concentrations according to an internal protocol. The solutions were characterised in two rounds to study the effect of compositions on morphological properties. The first round of the study included LQMN_C_02023, LQMN_C_02048, LQMN_B_02051 , LQMN_C_02052 and LQMN_C_02065, while in the second round LQMN_B_03015, LQMN_B_03047, LQMN_B_03053, LQMN_B_03066 were studied. Table 41 shows the compositions of those solutions.

[0431] Table 41 : The compositions of the solutions studied in Round 1 and 2.

[0432] Microscope Observations

[0433] For microscope observations, 500 pl of each of samples 1 to 9 were transferred into a 48-well plate by using a 1000 pL pipette. Then, the samples were immediately transferred to a -80 °C freezer for 8 h. After that, the samples, in the form of gels, were freeze-dried at -50 °C for 48 h using a freeze- dryer machine to provide freeze-dried gel samples. Another batch of samples were dried at 35 °C and ambient pressure in an oven for 3 hours to provide air-dried gels.

[0434] The samples were subsequently attached to aluminium stubs using double-sided conductive carbon tape and coated with a layer of platinum. Images were acquired from the surface and crosssection of 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 crosssection observation.

[0435] Result and discussion

[0436] Morphology of the freeze-dried samples

[0437] The structures of freeze-dried samples 1 to 5 (LQMN_C_02023,LQMN_C_02048LQMN_C_02048, LQMN_B_02051 , LQMN_C_02052 and LQMN_C_02065), are shown in Fig. 29. LQMN_C_02023 (Figure 29A) and LQMN_C_02048 (Figure 29B) possess interconnected structures with similar pore sizes (< less 100 pm), while LQMN_B_02051 (Figure 29C), LQMN_C_02052 (Figure 29D) and LQMN_C_02065 (Figure 29E) show disconnected porousstructures with large pore sizes. This difference in morphologies is due to the presence of electrolytes in the samples in accordance with Table 41. For instance, the interconnected pores in LQMN_C_02023 (Figure 29A) became disconnected structures after adding electrolytes in LQMN_C_02052 (Figure 29D). Similar differences can be observed by comparing LQMN_C_02048 (Figure 29B) and LQMN_C_02065 (Figure 29E). Hence, evidence suggests the addition of electrolytes to the gel compositions isolates the pores and increases their sizes to a few hundred micrometres.

[0438] The structures of freeze-dried LQMN_B_03015, LQMN_B_03047, LQMN_B_03053, and LQMN_B_03066 are shown in Fig. 30. LQMN_B_03047 (Figure 30B) is the only gel showing the interconnected porous structure, whereas LQMN_B_03015 (Fig. 30A), LQMN_B_03053 (Figure 30C), and LQMN_B_03066 (Fig. 30D) possess disconnected porous structures. According to Table 41 , three of these tested samples contain NaCI or other electrolytes in their formulation, while LQMN_B_03047 does not. This shows a similar effect of electrolytes on the disconnected porosity of the gels presented in Figure 1. LQMN_B_03053 and LQMN_B_03066 containing NaCI, a strong electrolyte, display isolated pores in the sample’s structures. NaCI particles were marked in the SEM images of the relevant samples. Another observation is related to the reduced pore sizes in LQMN_B_03053 (Fig. 30C), and LQMN_B_03066 (Fig. 30D).

[0439] Evidence suggests that limitation of multiple electrolytes to NaCI only does cause a decrease in pore size. This indicates that the variation in the amount of electrolyte can proportionally alter the pore size in HEC-based gels, regardless of whether it contains xanthan or guar gum.

[0440] The composition of hydrogels can play a significant role in determining their properties, including the structure of the porosity formed during the freeze-drying process. The nature of the solvents used, concentration of thickeners, use of additives with potential effects on the gelling matrix etc. are all parameters affecting the properties and structure of the hydrogels. NaCI and electrolytemix change the interconnected structures to disconnected porosity in samples. The disconnected porosity in free-dried electrolyte hydrogels has been reported in past studies including PVA hydrogels treated with (NH^SC^ and KI electrolytes (Wei, J. & Wang, Q. Small Methods 3, 1900558 (2019), electrolyte hydrogel based on methacrylated chondroitin sulfate and polyacrylic acid (Shang, Y., Wei, J., Wu, C. & Wang, Q., ACS Appl. Mater. Interfaces 10, 42959-42966 (2018)), and polyacrylamide hydrogel cross-linked by methacrylated graphene oxide (Jin, X. et al., Nano Res. 12, 1 199-1206 (2019);. Chan, C. Y. et al., J. Mater. Chem. A 9, 2043-2069 (2021)).

[0441] Morphology of air-dried samples

[0442] Fig. 31 illustrates the surface morphologies (with low magnifications) of the air-dried LQMN_C_02023, LQMN_C_02048, LQMN_B_02051 , LQMN_C_02052 and LQMN_C_02065. All samples possess pores or cracks on the surface; however, LQMN_B_02051 (Fig. 31 C) and LQMN_C_02065 (Fig. 31 E) show large holes on their surfaces. High-magnified hierarchical images of the air-dried samples are represented in Fig. 32 for observation of the continuous solid surfaces. LQMN_C_02023 (Fig. 32C) and LQMN_C_02048 (Fig. 32F) i.e. solutions without electrolytes are theonly samples showing non-porous surfaces in the highest magnifications. On the opposite, LQMN_C_02065 (Fig. 320) shows a porous surface with a pore size range 50-600 nm.

[0443] The surface morphologies (with low magnifications) of the air-dried LQMN_B_03015, LQMN_B_03047, LQMN_B_03053, LQMN_B_03066 are shown in Figure 33. Adding NaCI to the formulation makes the surface of the fully air-dried gels more brittle as seen for LQMN_B_03047 (Fig. 33B), LQMN_B_03053 (Fig. 33C), and LQMN_B_03066 (Fig. 33D). Furthermore, the surface of LQMN_B_03015 (Fig. 33A) includes many cracks, which can be related to the presence of electrolytes. Electrolytes can influence the water evaporation rate and the air-drying properties of the hydrogels.

[0444] On one hand, dissolving the hydrating salt in the hydrogel to form hydrated ions can effectively reduce the vapour pressure of the water and thus slow the evaporation rate (Lu, K., Jiang, T., Hu, H. & Wu, M., Front. Chem. 8, 546728 (2020)) thus it is expected to provide a more uniform and smoother dried surface. On the other hand, the incorporation of electrolytes and salts can increase the brittleness of the hydrogels, which results in cracks and fractures on the dried surface (Kundu, S. K., Yoshida, M. & Shibayama, M., J. Phys. Chem. B 114, 1541-1547 (2010)) - as per the current study.

[0445] It is worth noting the effects of electrolytes on the water evaporation rate and air-drying properties of hydrogels can be complex and depend on the specific electrolyte, concentration, and gel composition used.

[0446] Figure 34 displays the SEM images of embodiments of air-dried films (Formulae A-D) with different thicknesses. According to the figure, the thickness of the film ranges between 4 to 15 pm as measured by Imaged (version 1.8.0). The variation in thickness is related to the cast volume of the gels in the petri dish during the sample preparation. Furthermore, the film is folded in the figure (the bottom image), indicating the flexibility of the film in the dry state. This property allows for a barrier having a solid and dense barrier while providing dexterity and sensory function, such as when applied over dermis.

[0447] Formation process of microfilm on skin

[0448] SEM images revealed that one or more embodiments of the microfilm has a porous microstructure in its hydrated state, which transforms into a thin and dense film upon dehydration. Without being bound by theory, Figure 35 illustrates what is thought to be the process of microfilm formation in three phases. In Phase 1 , a hydrated hydrogel film forms on the skin immediately after application. Phase 2 depicts the dehydration process, where water molecules transition from a liquid to a gaseous state due to environmental conditions such as room temperature, skin temperature, barometric pressure, and relative humidity. As dehydration continues, the film shrinks. In Phase 3, once dehydration is complete, a shrunken microfilm forms on the skin. This microfilm is dense and thin with a great breathability because of nanoscale openings.

[0449] Limitations

[0450] There are many published papers relating to the study of pore structures using freeze- drying. 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, it is noted that the pore sizes of the gel samples are not absolute values and may vary with changes to the pre-freezing and freeze-drying process methodology. However, the tested groups illustrated here are comparable since all samples were prepared and analysed by the same protocol. Cryo-SEM is recommended to reduce (or prevent) sideeffects of the freezing process on the morphology of hydrogels. When cryo-SEM is used, pore structure is mainly affected by the composition and preparation of gels.

[0451] Conclusions

[0452] Compositional parameters can significantly influence the pore structure of one or more embodiments of the dried compositions. The electrolyte mixes and presence of sodium chloride (NaCI) resulted in disconnected pores in the morphology of free-dried gel samples. It is hypothesised a solution with isolated pores, such as LQMN_C_02052, LQMN_C_02065, LQMN_B_03053, and LQMN_B_03066, can provide a better physical barrier preventing the passage of small particles such as allergens or viruses.

[0453] From air-dried observation, while most of the surfaces are cracked, the samples containing NaCI show more cracks on the fully dried surfaces than other gels. While the performance of the gels with electrolytes when completely dried may be limited, they may be more suited to use in locations such as the nasal cavity where it is unlikely to reach complete dehydration. Specific solvents / additives, with lower vapour pressure than water may be added to those formulations for potential retention of the flexibility of the solid matrix.

[0454] While this disclosure has been described in connection with specific embodiments thereof, it will be understood that it is capable of further modification(s). This application is intended to cover any variations uses or adaptations of the disclosure following in general, the principles of the disclosure and including such departures from the present disclosure as come within known or customary practice within the art to which the disclosure pertains and as may be applied to the essential features hereinbefore set forth.

[0455] As the present disclosure may be embodied in several forms without departing from the spirit ofthe essential characteristics ofthe disclosure, itshould be understood that the above described embodiments are not to limit the present disclosure unless otherwise specified, but rather should be construed broadly within the spirit and scope ofthe disclosure as defined in the appended claims. The described embodiments are to be considered in all respects as illustrative only and not restrictive.

[0456] Various modifications and equivalent arrangements are intended to be included within the spirit and scope of the disclosure and appended claims. Therefore, the specific embodiments are to be understood to be illustrative of the many ways in which the principles of the present disclosure may be practiced. In the following claims, means-plus-function clauses are intended to cover structures as performing the defined function and not only structural equivalents, but also equivalent structures.

[0457] When a Markush group or other grouping is used herein, all individual members of the group and all combinations and sub-combinations possible of the group members are intended to be individually included in the disclosure. Every combination of components described or exemplified herein can be used to practice the disclosure, unless otherwise stated.

[0458] Whenever a range is given in the specification, for example, a temperature range, a time range, or a composition or concentration range, all intermediate ranges and subranges, as well as all individual values included in the ranges given are intended to be included in the disclosure. It will be understood that any subranges or individual values in a range or subrange that are included in the description herein can be excluded from the claims herein.

[0459] As used herein, "comprising" is synonymous with "including", "containing" or "characterized by" and is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. As used herein, "consisting of excludes any element, step, or ingredient not specified in the claim element. As used herein, "consisting essentially of’ does not exclude materials or steps that do not materially affect the basic and novel characteristics of the claim. The broad term "comprising" is intended to encompass the narrower "consisting essentially of and the even narrower "consisting of." Thus, in any recitation herein of a phrase "comprising one or more claim element" (e.g., "comprising A), the phrase is intended to encompass the narrower, for example, "consisting essentially of A" and "consisting of A" Thus, the broader word "comprising" is intended to provide specific support in each use herein for either "consisting essentially of or "consisting of." The disclosure illustratively described herein suitably may be practiced in the absence of any element or elements, limitation or limitations which is not specifically disclosed herein.

[0460] One of ordinary skill in the art will appreciate that materials and methods, other than those specifically exemplified can be employed in the practice of the disclosure without resort to undue experimentation. 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 recognized 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, 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.

[0461] Each references cited herein is incorporated by reference herein in their entirety. Such references may provide sources of materials; alternative materials, details of methods, as well as additional uses of the disclosure.

Claims

Claims:1 . A bio-adhesive composition that in use forms a barrier on a substrate to prevent antagonists contacting the substrate, the composition comprising: at least 1 .0 wt.% of a cellulose derivative; at least 0.1 wt.% of a gum-based compound; and an aqueous-based solvent; wherein the composition has a viscosity at a point-of-use of at least 10,000 cP.

2. The bio-adhesive composition of claim 1 , wherein the cellulose derivative is present in an amount ranging from 1 .0 to 20 wt.%3. The bio-adhesive composition of claim 2, wherein the cellulose derivative is present in an amount ranging from 1 .0 to 2.0 wt%.

4. The bio-adhesive composition of claim 2, wherein the cellulose derivative is present in an amount ranging from 2.0 to 4.0 wt%.

5. The bio-adhesive composition of claim 2, wherein the cellulose derivative is present in an amount ranging from 4.0 to 20 wt.%6. The bio-adhesive composition of any one of claims 1 to 5, wherein the cellulose derivative is selected from the group consisting of hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, and combinations thereof.

7. The bio-adhesive composition of any one of claims 1 to 6, wherein the gum is present in an amount ranging from 0.05 to 3.0 wt%.

8. The bio-adhesive composition of claim 7, wherein the gum is present in an amount ranging from 0.1 to 1 .0 wt%.

9. The bio-adhesive composition of any one of claims 1 to 8, wherein the gum is selected from the group consisting of guar gum, xanthan gum, sclerotium gum, agar agar, and combinations thereof.

10. The bio-adhesive composition of any one of claims 1 to 9, wherein the composition has a viscosity at point-of-use of at least 15,000 cP, 20,000 cP, or 30,000 cP.1 1 . The bio-adhesive composition of claim 10, wherein the composition has a viscosity at point- of-use of at ranging from 20,000 cP to 70,000 cP.

12. The bio-adhesive composition of any one of claims 1 to 1 1 , further comprising a plasticizer.

13. The bio-adhesive composition of claim 12, wherein the plasticizer is present in an amount up to 8.0 wt%.

14. The bio-adhesive composition of claim 12 or 13, wherein the plasticizer is selected from the group consisting of glycerol, propylene glycol, polyethylene glycol, and combinations thereof.

15. The bio-adhesive composition of any one of claims 1 to 14, having a water content of at least 80wt.%.

16. The bio-adhesive composition of any one of claims 1 to 14, having a water content up to 40wt.%.

17. The bio-adhesive composition of any one of claims 1 to 16, further comprising an alcohol.

18. The bio-adhesive composition of claim 17, wherein the alcohol is present in an amount ranging from 35 to 85 wt.%.

19. The bio-adhesive composition of any one of claims 1 to 18, further comprising ascorbic and / or citric acid and salts thereof.

20. The bio-adhesive composition of any one of claims 1 to 19, further comprising one or more additives.21 . The bio-adhesive composition of claim 20, wherein the one or more additives includes an emulsifier, skin conditioner, a dye, fragrant, flavourant and / or antimicrobial agent.

22. The bio-adhesive composition of claim 20, wherein the one or more additives includes menthol, xylitol, glyceryl caprylate, glyceryl undecylenate and / or benzalkonium chloride.

23. The bio-adhesive composition of any one of claims 1 to 22, having a dry-out time of at most 90 seconds.

24. The bio-adhesive composition of any one of claims 1 to 23, wherein the substrate is a living integument.

25. A method of forming a barrier on a living integument, comprising:applying the bio-adhesive composition of any one of claims 1 to 24 to the living integument; and allowing the bio-adhesive composition to dry to reduce its water content to form the barrier.

26. The method of claim 25, wherein the living integument is a hand.

27. The method of claim 25, wherein the living integument is a face.

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