DESC:FIELD OF THE INVENTION
The present disclosure relates to a substrate treated with anti-infective compositions and methods of coating a range of substrates with the said anti-infective compositions. In particular, the present invention comprises a composition with one or more germicidal/ virucidal agents to act on viruses or bacteria and destroy it before entering the host. Further the present invention also relates to a process for preparing the said anti-infective compositions and the various types of face masks using the substrate layer coated with the said compositions.
BACKGROUND OF THE INVENTION
Inhalation of air contaminated with harmful viruses and / or other microorganisms is a common route of infection for humans leading to various respiratory tract infections. Respiratory tract infections (RTIs) are infectious diseases involving the respiratory tract. Tuberculosis, coronavirus, novel coronavirus and the like, a myriad of known or unknown pathogens cause diseases transmitted through the respiratory tract. The diseases transmitted through respiratory tract are characterized in that the pathogen can be transmitted through sputum, droplets and even through the air exhaled by the patients. The surrounding healthy population may also become infected after inhaling the pathogens or viruses exhaled by the patient.
The most effective method for controlling the spread of infectious diseases is to control the source of infection, cut off the transmission route and protect the susceptible population. Face masks are universally used in the medical profession and elsewhere to reduce the risk of transferring infectious bacteria, virus and the like.
A surgical mask is a loose-fitting, disposable device that creates a physical barrier between the mouth and nose of the wearer and prevent potential contaminants in the or from the immediate environment. If worn properly, a surgical mask is meant to help block large-particle droplets, splashes, sprays, splatter that may contain germs (viruses and bacteria), keeping it from reaching your mouth and nose.
Surgical masks are cost effective and easy to use, but lesser efficient to protect from germs and other contaminants. On the other hand, N95 respiratory masks are more efficient but costly and difficult to use for general public. In situations such as Covid 19 pandemic, use of masks is expected to play a significant role to reduce spread of the infection and contamination, provided the masks are efficient and used by maximum people.
It is well known in the related technology field to incorporate an anti-bacterial agent into a material or fabric intended for use in medical applications to guard against the transfer of contagious and potentially lethal pathogens. The incorporation of such agents has been accomplished by coating the outer surface of the material, by interply coating of multi-ply fabric or material, or by chemically incorporating the coating agent into the material at the time of production.
CN205794904U discloses a multifunctional anti-infective mask, comprising: a mask body, the mask body comprising a bacteriostatic layer, an isolating filter layer and a skin-friendly layer in order from the outside to the inside. Bacteriostatic layer is made of cotton cloth or bamboo fiber material nonwoven fabric. Bamboo and hemp fibers exhibit good antibacterial properties. The isolation filter layer of the mask body is made of a melt-blown polypropylene fiber material. The melt-blown polypropylene fiber material has strong filtering performance, and can effectively prevent harmful gases from outside, bacteria and the like from entering the mouth and nose of the human body through the mask.
US7845351B2 provides a face mask which includes a body portion that has an outer layer that has been treated with a germicidal agent comprising, polyhexamethylene biguanide, citric acid and N-alkyl polyglycosidein in an effective amount.
US6120784A relates to a method of imparting anti-pathogenic properties to a substrate material comprising: (a) preparing a coating composition containing an anti-pathogenic agent consisting essentially of PVP-I and N-9.
JP2002065879A provides a mask for covering a mouth and a nose, comprising a filter carrying a biguanite antibacterial agent.
WO2011016462A1 discloses a face mask which does not allow a virus or the like to remain in the outer surface of the mask main body and can exhibit high antibacterial and antiviral actions and which has improved air permeability, collecting properties, and productivity. The mask main body includes a first fiber sheet and a second fiber sheet. The first fiber sheet is composed of hydrophobic fibers. The second fiber sheet further includes a first fiber layer and a second fiber layer. The first fiber layer is configured as a fiber layer made of polyolefin fibers containing an inorganic antibacterial agent.
IN202011045474 relates to a multilayer reusable activated carbon face mask for preventing viral infection. Wherein, the multilayer face mask comprises at least one layer of activated carbon layer which is very effective to protect users from germs and specially covid-19 virus and also reduce the odor.
IN202041018811 discloses a process for the fabrication of woven fabric with herbal extract, wherein said treated fabric is capable of being used as one or more of the layers in breathable face masks. Said process involves steaming the woven fabric at 100°C for 30 minutes, followed by immersing the steamed fabric into an herbal extract solution, while being simultaneously subjected to heat. The treated fabric is then pressed and dried.
IN3254/MUM/2013 the present invention relates to nanofiber based antimicrobial face mask for protection against viruses and a process of preparing face mask thereof. The face mask is prepared by using composite filter media having an antimicrobial nanoparticle filled nanofiber layer deposited on the surface of nonwoven substrate.
Many of the foregoing applications represent products or compounds which if used in the manner contemplated herein and fully disclosed hereinafter would prove irritating to the skin, difficult to adhere firmly on the cloth or difficult to commercially produce. Such treatments may be useful to control the disease by inducing or maintaining remission, or by reducing recurrence. However, there still exists a need in the art for additional therapies which are effective and do not have side effects. Therefore, there is a need to develop masks which are efficacious, economical, easy to use and dispose and can effectively contain the spread of the infection causing bacteria, viruses or pathogens.
OBJECTS OF THE INVENTION
The main object of the present invention is to provide a substrate treated with anti-infective composition comprising one or more germicidal or virucidal agents to act on viruses or bacteria and destroy them before entering the host.

Another object of the present invention is to provide a substrate treated with anti-infective composition comprising:
a) One or more germicidal or virucidal agents
b) Adhesive polymer imparting low viscosity
c) Solvent(s)
d) Optionally other excipients

Still another object of the present invention is to provide anti-infective composition coated on paper, coated papers, synthetic papers, paper/film laminates, non-woven material, non-woven laminates.
Another object of the present invention is to provide a substrate coated with anti-infective composition usable in different types of face masks and other medical cloth layer to reduce spread of infections.

DETAILED DESCRIPTION OF THE INVENTION
In order to make the matter of the invention clear and concise, the following definitions are provided for specific terms used in the description.

As used herein, the term "coated substrate" refers to any substrate which ultimately, in finished form, contains the anti-infective component, whether the component is coated on the surface of the substrate, is imbedded in the substrate during substrate production, is coated as a single composition or in a dual or multilayered design, or is included in the finished substrate in another manner, as described hereinafter.

The term "multilayer”, as used hereinafter, refers to consisting of a number of a number of woven layers stacked on top of each other and held together with connection yarns in the third dimension (Z-direction).

The term "pathogen" and “infective” in its various forms is used herein to mean and include such terms as viral, bacterial and SARS-COV-2 (severe acute respiratory syndrome coronavirus). Therefore, reference to an "anti-pathogen" or “anti-infective” includes reference to anti-viral, anti-bacterial and/or anti-SARS-COV-2 compositions and their anti-viral, anti-bacterial and/or anti-SARS-COV-2 activity.

The present invention relates to providing a substrate coated with anti-infective compositions comprising one or more germicidal or virucidal agents to act on viruses or bacteria and destroy them before entering the host. Upon contact of the formulation with a pathogen in presence of moisture, the anti-infective agent(s) are released to break the lipid envelope of the viruses or act on the cell wall of the bacteria and thus inactivate it.

The substrate referred throughout the disclosure may be selected from paper, coated papers, synthetic papers, paper/film laminates, non-woven material like spun bonded fabrics, two-phase fabrics and spun laced fabrics, non-woven laminates having non-woven substrate laminated to a film such as polyethylene, polypropylene or polyurethane or combination of non-woven fabric with a microporous film laminated thereon.

Paper – The paper substrates include medium weight papers which do not easily tear or shred, but which also not too heavy. The paper should be able to withstand the winding tension of the coating machine. It is intended that the paper once coated act as barrier for pathogens in dry state and become activated, releasing the anti-infective compounds of invention, to eliminate the pathogens when wet. Suitable examples of paper substrates include those made from wood pulp and processed with cellulosic fibers. Additionally, coated papers and synthetic papers may also be suitable for use.

Paper/Film laminates – Paper/film laminate substrates in which the paper substrate is generally laminated to a polymeric film are also suitable paper substrates. They find particular application to the uses specified above with respect to paper substrates, but are further suitable in other applications where durability and low porosity are important considerations. The film component of a paper/film laminate is usually a material such as polyethylene, polypropylene or polyurethane, which enhances the hold-out of the substrate preventing the coating from penetrating through the composite.

Woven cloths - Cotton cloth or cotton mixed with polyester cloth after coating can be used in different types of masks including N-95 masks, surgical masks, simple cloth masks, reusable plastic cover masks with replaceable filter. Woven cloth has low microbial filtration efficiency than the non-woven cloths, however the coating with anti-infective formulation increase efficiency of the woven cloth used in face masks to reduce the spreadability of the infection. Moreover, the coating with low viscosity formulation does not have significant impact on breathability through coated woven cloth. The present investigation also reveal that the coated layer can be utilized along with the non-woven layers in surgical face masks and N-95 face masks to enhance the efficiency of these masks beyond filtration ability without significantly influencing the breathability.

Woven and Non-Woven Laminates- Non-woven substrates include spun bonded fabrics and melt blown fabrics. While non-woven substrates offer many advantages, they also represent special coating considerations. Often, non-woven substrates have been treated to enhance water and even alcohol repellency. Thus, many of these fabrics are attractive as operating room fabrics. These fabrics, however, are more likely than other substrates to experience coating absorption and penetration. To protect against these potential problems, which may occur with traditional web coating techniques, spray or dip coating methods have been found herein to provide suitable alternatives. When using these methods, the subject formulation is modified generally to achieve a thinner formula with lower solids content. The coating of non-woven fabric has significant influence on the breathability through it. In those applications where the coating is provided in a multilayered design, such as face masks, the various coating layers may be provided on the same or on varying substrate materials. Further, in those instances where woven substrates are coated with the coating formulation, the woven and nonwoven substrates may be placed into a single finished product construction.
The foregoing substrates are exemplary only. Any other substrates known to the skilled person and accepts the anti-infective composition in a manner to act against the pathogen, is suitable for adaptation or application.
The anti-infective compositions of the present invention can be applied on multiple substrates directly by spraying the composition or by preparing a coating layer that is usable in different types of face masks which effectively protects against the transmission of the viral and bacterial infection including SARS-COV-2.

The suitable coating techniques used in present invention to prepare coated substrates include spray and dip coating techniques. Spray coating is highly suitable for more porous substrates as it affords greater control over penetration of the coating into the substrate. With spray coating the coating formulation is essentially atomized into a fine mist so that it can be applied to the porous substrate without excess penetration. In order to atomize the coating formulation, it should be of low viscosity. Proper atomization of the coating is important to the even and uniform application of the coating, as are the amount and pressure of air flow. 3D printing principles used to automize the spray coating. Dip coating is another viable alternative coating method. Dip coating is probably the simplest form of coating in terms of equipment; however, uniformity of coating requires that great care be taken to control the rate of withdrawal of the substrate from the coating, solvent evaporation, drainage, etc. In this technique, the substrate is passed from a lead-in roll to an immersion roll placed in or over a coating pan. The immersion roll is positioned high or low depending on the desire to coat only one or both sides of the paper. This method, like spray coating, requires low solids content of the coating formulation and is significantly affected by the porosity of the substrate, as well as by environmental and mechanical parameters.
For spray and dip coating, the standard formulation is typically diluted to generally 5-20% solids, preferably 10% solids, as compared to a 25%-35% solids range usable with roll coating methods and technique.
The coated substrates obtained from present disclosure may either be sealed during the manufacturing of N-95 mask or layered in a surgical mask or sewed on a simple cloth mask or fitted on a reusable plastic cover mask. In the last type the mask shaped cover is made of plastic obtained through molding method or through 3D printing. The filter of the plastic mask can be replaced regularly and molded cover can be sanitized with soap or sanitizer.
The virucidal agents used in the present invention may be selected from anionic surfactant like alpha olefin sulfonate, sodium lauryl sulfate, etc or acids like citric acid, any mineral acid or cyclodextrins like modified cyclodextrins, derivative of cyclodextrins.
The germicidal agents disclosed in the present invention may be selected from quaternary ammonium compounds such as benzalkonium chloride, cetrinnide, cetylpyridinium chloride and other quarternized polymers; biguanides such as polyhexamethylene biguanide, chlorhexidine, alexidine and salts thereof; quaternary ammonium silicone, polyquarternary amine and combinations thereof.
The composition of the present invention acts in a synergistic manner when the one or more germicidal or virucidal agents are used. Presence of surfactant and acid in the composition provides a basic and acidic environment respectively, thus helping in neutralizing the nucleic acids of most viruses. Cyclodextrins used in the composition sequester the cholesterol from the viruses thus causing structural disruption of the viral envelope.

Sufficient anti-infective activity is achieved by the composition of present invention when the concentration of solids (non-volatile) is 3-15% and viscosity is from about 7-30cp.
The anti-infective agents used in the composition of the present invention are in an amount of between about 0.001% and 20%.

The anti-infective composition of the present invention also includes adhesive polymer that enhances the viscosity of the composition. Suitable agents include polyvinyl alcohol, modified cellulose materials such as methylcellulose, hydroxypropyl cellulose and hydroxypropyl methylcellulose. Preferably the polymer used in present invention is polyvinyl alcohol. Parateck® coat, a particle engineered polyvinyl alcohol with a unique particle structure that enables rapid dissolution even at low temperature, is more preferably used in the present disclosure.

The composition further includes solvent which may be selected from water and/or organic solvent like ethanol, propanol.

The anti-infective composition of the present invention may optionally contain other excipients selected from lubricant, plasticizer, surfactant and the like that are known to a person skilled in the art.

Further scope of the present invention is to provide the anti-infective composition either as spray or sprinkling solution that can be used on clothes, hard surfaces, etc to reduce the spread of infection or that may be coated on a substrate targeted for use in medical type application such as face mask, surgical gown, hospital bed cover, etc or for maintaining personal hygiene like on saloon dress covers.

While using the disclosed composition on 10–50-time dilution as spray or sprinkling solution about 0.3-0.5ml per 100cm2 is to be applied. If sprayed on non-disposable cotton mask then the preparation should be applied everyday after washing the face mask. The formulation is stable at room temperature for up to 6 months.

Some of the products using coated substrates obtained from the present invention are shown in Fig 1, Fig 2 and Fig 3. The breathability was tested using differential pressure gauge. The air pressure drop through the coated layer was measured and the difference between after coating and before coating was noted.
Fig 1 (a & b)– A N-95 mask having additional coated woven layer where sealing of coated layer in mask is using ultrasonic mechanism. Here for the first-time cotton woven layer is incorporated in non woven layers of N-95 mask
Breathability test - <2.5 cm of H2O
Fig 2 – Surgical mask with additional coated woven layer wherein the coated layer is incorporated in 3-ply mask
Breathability test: <2 cm of H2O
Fig 3 - Multi layer filter for reusable plastic cover mask wherein the coated layer is incorporated in multilayered filters that are precisely manufactured to fit in reusable plastic cover masks.
Breathability test: <2 cm of H2O
Examples of the invention
Example 1 – Composition containing virucidal ingredients without preservative

Ingredients Concentration
Ascorbic acid 0.05-2%
Sodium alpha olefin sulfate 0.01-3%
Polyvinyl alcohol 5-88
(Parteck Coat) 0.2-15%
Water 20%
Ethanol (absolute) 80%

Example 2 – Composition containing Virucidal ingredients with preservative
Ingredients Concentration
Ascorbic acid 0.05-2%
Sodium alpha olefin sulfate 0.01-3%
Polyvinyl alcohol 5-88
(Parteck Coat) 0.2-15%
Hydroxypropyl beta-cyclodextrin 0.2-5%
Benzalkonium chloride 0.001-0.05%
Water 30%
Ethanol (absolute) 70%

Example 3 - Composition containing virucidal ingredients with preservative
Ingredients Concentration
Ascorbic acid 0.05-2%
Sodium alpha olefin sulfate 0.01-3%
Polyvinyl alcohol 5-88
(Parteck Coat) 0.2-15%
Hydroxypropyl beta-cyclodextrin 0.2-5%
Water 30%
Ethanol (absolute) 70%

General process of preparing the composition-
Polyvinyl alcohol was dissolved in warm water (40-50 deg C) under stirring. To this solution, ascorbic acid, sodium alpha olefin sulfate and/or hydroxypropyl beta-cyclodextrin were added under stirring. To the resulting solution, ethanol was slowly added followed by benzalkonium chloride. The contents were mixed properly and then either coated on a substrate or filled in spray bottle.
SARS-Cov 2 Antiviral Testing
The Cytotoxicity Assay was done on the test composition (20 time diluted - Example 2) using Remdesivir as control. The Assay was done on a 96-well plate format in 3 wells for each sample. 1*10e4 VeroE6 cells were plated per well and incubated at 37C overnight for the monolayer formation. Next-day, cells were incubated with the test substance (TS) at the indicated concentration. The control cells were incubated with 1.4% ethanol only. The cells were infected with SARS- Cov2 at a MOI of 0.01. 24 and 48 hours later, viral RNA was extracted from 100mcl culture supernatant and subjected to qRT-PCR (in duplicates) where It values for N and E gene sequence were determined. Inhibition of virus replication is determined based on the fold change in the Ct value in TS-treated cells compared to the control.

Results for test composition (20 time diluted) –
N gene sequence E gene sequence
24h 71% inhibition 55% inhibition
48h 99% inhibition 99% inhibition

Results compared with Remdesivir positive control
N gene sequence E gene sequence
24h 90% inhibition 89% inhibition
48h 99% inhibition 99% inhibition

,CLAIMS:We claim,
1) A substrate treated with anti-infective composition comprising:
a) One or more germicidal or virucidal agents
b) Adhesive polymer imparting low viscosity
c) Solvent(s)
d) Optionally other excipients
2) The substrate of claim 1, is selected from paper, coated papers, synthetic papers, paper/film laminates, non-woven material like spun bonded fabrics, two-phase fabrics and spun laced fabrics, non-woven laminates having non-woven substrate laminated to a film such as polyethylene, polypropylene or polyurethane or combination of non-woven fabric with a microporous film laminated thereon.
3) The substrate of claim 1, is coated with anti-infective compositions using roll-coating, spray coating, slot coating and dip coating.
4) The anti-infective composition according to claim 1, comprises virucidal agents selected from anionic surfactant like alpha olefin sulfonate, sodium lauryl sulfate, etc or acids like citric acid, ascorbic acid, any mineral acid or cyclodextrins like modified cyclodextrins, derivative of cyclodextrins.
5) The anti-infective composition according to claim 1, comprises germicidal agents selected from quaternary ammonium compounds such as benzalkonium chloride, cetrinnide, cetylpyridinium chloride and other quarternized polymers; biguanides such as polyhexamethylene biguanide, chlorhexidine, alexidine and salts thereof; quaternary ammonium silicone, polyquarternary amine and combinations thereof.
6) The anti-infective composition of the preceding claims, comprises germicidal and/or virucidal agents in an amount of between about 0.001% and 20%.
7) The anti-infective composition of claim 1, wherein the adhesive polymer is selected from polyvinyl alcohol, modified cellulose materials such as methylcellulose, hydroxypropyl cellulose and hydroxypropyl methylcellulose.
8) The anti-infective composition of claim 1, comprises solvents selected from water and/or organic solvent such as ethanol, 2-propanol.
9) The anti-infective composition of claim 1, wherein the optional excipients may be selected from lubricant, plasticizer, surfactant and the like.
10) The anti-infective composition of preceding claims, further can be provided as spray or sprinkling solution to be applied on any surface before use.
11) N-95 masks with additional woven layer made of the anti-infective composition of claim 1 coated substrate.
12) The N-95 masks with additional coated substrate layer of claim 11 for use to prevent the spread of infections such as COVID-19.
13) The multilayer filter preparations, using 3D printing or any precision extrusion method comprising of at least one woven layer coated with the composition of claim 1, for face mask cover.