CN115605269A

CN115605269A - Improved liquid compositions for cleaning, disinfecting and/or sterilizing

Info

Publication number: CN115605269A
Application number: CN202180033519.8A
Authority: CN
Inventors: S·P·利恩格斯塔达斯; H·J·豪根
Original assignee: Coticolis
Current assignee: Coticolis
Priority date: 2020-03-18
Filing date: 2021-03-18
Publication date: 2023-01-13
Also published as: BR112022018324A2; KR20230006463A; WO2021186000A1; AU2021238760A1; JP2023518701A; CA3170947A1

Abstract

Aspects of the invention relate to improved antimicrobial and/or antiviral compositions comprising an antimicrobial and/or antiviral mixture consisting of H at a final concentration of 3 to 7%v/v ₂ O ₂ And poloxamer at a concentration of 0.1 to 10% w/v. Poloxamers are in a complex hydrogel formulation. The compositions disclosed herein are antimicrobial and/or anti-microbialViral and in particular for cleaning, sterilizing, disinfecting, decontaminating and/or debriding biological surfaces and surfaces of biological materials, for example when provided in hand disinfectants, mouth rinses, nasal rinses and/or for wound care and/or chronic ulcer care as well as for dental prophylaxis and peri-implant health maintenance.

Description

Improved liquid compositions for cleaning, disinfecting and/or sterilizing

Technical Field

Aspects of the present invention relate to a multifunctional cleaning and/or stain repellent composition comprising H ₂ O ₂ And pluronic acid, wherein the composition is in liquid form at room temperature. The compositions described herein inhibit microorganisms and inflammation in a subject, and are particularly useful for skin disinfection, mouth-throat disinfection, nose disinfection, oral prophylaxis and peri-implantitis treatment, implant health maintenance, periodontitis and periodontal health, wound care, or chronic ulcer care.

Background

Biological surfaces, such as skin and mucous membranes and/or surfaces of biological materials, are often in contact with and often colonized by a large number of microorganisms and viruses. Therefore, they often need to be cleaned and/or disinfected with antibacterial and/or antiviral compositions without causing damage to the biological tissue in question and preferably without causing microbial and/or viral resistance.

In particular, the skin of the body (such as, but not limited to, skin on the hands, feet, or face) is often exposed to microorganisms and requires periodic cleaning, sterilization, and/or disinfection to inhibit the settling and/or transfer of pathogens and/or microorganisms and/or viruses.

Hand disinfectant

Hand sanitizer is a liquid or gel that is commonly used to reduce infectious agents on the hands. In most cases in healthcare facilities, alcohol-based type formulations are preferred over washing hands with soap and water. It is generally more effective at killing microorganisms and is generally better tolerated than soap and water. They are typically provided in the form of liquids, gels, wipes and/or foams.

Alcohol-based versions typically contain some combination of isopropanol, ethanol (ethyl alcohol), or n-propanol. Versions containing 60 to 95% alcohol are considered most effective. Hand sanitizers containing at least 60% alcohol or containing "persistent antimicrobials" can kill many different types of bacteria, including antibiotic-resistant bacteria and TB bacteria, but are less effective against viruses.

In general, alcohol-based hand sanitizers inhibit a wide variety of microorganisms, but not spores. Some versions contain compounds, such as glycerin, to prevent skin dryness. The non-alcohol based version may contain benzalkonium chloride, chlorhexidine gluconate, or triclosan. Since they are flammable, care should be taken to use.

Alcohol-based hand sanitizers have been in common use in europe at least since the 80's of the 20 th century. Alcohol-based versions are among the World Health Organization's basic drug List of Essential medicins, the safest and most effective drugs required by the Health system. The wholesale cost of developing countries is about $ 1.40 to $ 3.70 per bottle.

One well documented disadvantage of commercially available hand sanitizer solutions is that the alcohol in the hand sanitizer solution may not have the 10 to 15 second exposure time required to denature proteins and lyse cells. Furthermore, it is usually applied in too low an amount (0.3 ml) or too low a concentration. In environments with high fat or high protein waste (e.g., food processing), the use of alcohol hand rub alone may not be sufficient to ensure proper hand hygiene.

To address this problem, new alcohol gel disinfectants are sold as alcohol rub disinfectants, which kill most bacteria and fungi and block some viruses. Alcohol rub disinfectants containing at least 70% alcohol (primarily ethanol) kill 99.9% of the bacteria on the hands 30 seconds after application and within one minute from 99.99% to 99.999%. Nevertheless, they are significantly less effective against viruses.

The 90% alcohol rub-off is more effective against viruses than most other forms of hand sanitizer. Isopropanol also kills 99.99% or more of all non-spore forming bacteria in less than 30 seconds, whether in the laboratory or on human skin. 90% of alcohol wipes are highly flammable and potentially abusable, but are essential for killing viruses in particular, including enveloped viruses such as influenza, common cold, coronavirus and HIV, but are significantly ineffective against rabies virus.

Hydrogen peroxide

Hydrogen peroxide (H) ₂ O ₂ ) Is a very pale blue liquid, colorless in dilute solution, and slightly viscous than water. It is a weak acid. It has strong oxidizing properties and is therefore a powerful bleaching agent, primarily for paper but also as a disinfectant and oxidizer. Hydrogen peroxide in the form of carbamide peroxide is widely used for tooth whitening (bleaching), whether in professional-application products or in self-application products.

Hydrogen peroxide is unstable and slowly decomposes in the presence of light. Due to its instability, hydrogen peroxide is usually stored in a weakly acidic solution in a dark bottle together with a stabilizer (usually an organophosphate, sodium pyrophosphate, sodium phytate or sodium citrate).

Hydrogen peroxide can be used for sterilization of various surfaces, including surgical tools, and can be used as a Vapor (VHP) for sterilization in rooms. H ₂ O ₂ Exhibit broad spectrum efficacy against viruses and microorganisms including, but not limited to, bacteria, yeast, and bacterial spores. Generally, the activity against gram-positive bacteria is higher than that against gram-negative bacteria; however, the presence of catalase or other peroxidase in these organisms may increase tolerance at lower concentrations. Sporicidal activity sometimes requires higher concentrations of H ₂ O ₂ (10 to 30% v/v) and longer contact time.

Hydrogen peroxide is considered an environmentally safe alternative to chlorine-based bleaches because it degrades to form oxygen and water, and is generally recognized by the U.S. Food and Drug Administration (FDA) as a safe antimicrobial.

Historically, hydrogen peroxide was used to sterilize wounds. Today, it is believed to inhibit healing and lead to scar formation because it destroys newly formed skin cells at high concentrations. This is believed to be caused by the drying effect of the peroxide.

One study found that only very low concentrations (0.03% v/v solution, which is a typical 3%v/v peroxide dilution of 100 fold) can induce healing, and only without repeated administration. 0.5% v/v solution was found to hinder healing. However, recent new studies have shown that peroxides are an important and intrinsic part of the cell signaling and defense system, producing signals that activate local defense cells in response to infection and injury. In line with this, it is also now known that cells use peroxide directly to kill microbes and viruses in their immediate vicinity. With these knowledge, peroxide has gained renewed interest as a biologically active disinfecting substance.

Pluronic acid

Pluronic

Or the poloxamer is a triblock copolymer of poly (ethylene oxide) -poly (propylene oxide) -poly (ethylene oxide) (PEO-PPO-PEO). The synthetic polymers of this group are thermally reversible in aqueous solution. The sol-gel transition is controlled by the composition, molecular weight and concentration of the respective constituent block polymers. The hydrophilic ethylene oxide and hydrophobic propylene oxide give pluronic an amphiphilic structure-meaning that it has a polar water-soluble group attached to a non-polar water-insoluble hydrocarbon chain. The amphiphilic block copolymer molecules self-assemble into micelles (molecular stacking chains) in an aqueous solution. Micelle formation is temperature dependent and affects the degradation characteristics of the biomaterial: below a certain characteristic temperature (called the critical micelle temperature), both the ethylene oxide and propylene oxide blocks are hydrated and the PPO blocks become soluble.

Pluronic may be present as a liquid, paste or solid. Due to their amphiphilic nature (presence of hydrophobic and hydrophilic components), pluronics possess surfactant properties, which allow them to interact with hydrophobic surfaces and biological membranes. The amphiphilicity also results in the ability of the individual block copolymers (referred to as monomers) to associate and form micelles in aqueous solution. When the concentration of the block copolymer is below the Critical Micelle Concentration (CMC), the monomers remain in solution as molecules in water. However, as the block copolymer concentration increases above CMC, the unimers will self-assemble and form micelles, which may assume a spherical, rod-like or lamellar geometry. Their shape depends on the length and concentration of the block copolymers (i.e., EO and PO), and on the temperature. Micelles typically have a hydrophobic core (in this case a PO chain) and a hydrophilic shell (i.e. an EO chain).

Pluronic F-127, also known as Poloxamer (Poloxamer) 407, is commonly used for tissue engineering because of the commercial availability of a consistent product that will undergo a sol-gel transition around physiological temperature and pH. A disadvantage of Pluronic F-127 is its rapid rate of degradation in vivo. To overcome this problem, pluronic F-127 is often cross-linked with another alpha-hydroxy or amino acid to alter the chemical structure of its depsipeptide unit.

Pluronic acid forms a thermosensitive hydrogel, which is typically stabilized by the addition of high molecular weight acids (e.g., hyaluronic acid).

Studies have demonstrated the positive effects of the pluronic acid formulation in reducing inflammation, protecting tissues from damage, and retarding microbial adhesion. In addition, it is EMA and FDA approved, completely biocompatible, and safe for clinical use, with no known deleterious effects on human cells.

Nevertheless, it is difficult to apply as a cleanser because it automatically forms a stable gel (see fig. 1) between temperatures exceeding 18 ℃ or even 12 to 20 ℃, depending on its concentration, which makes it unsuitable for use in small channels and/or on rough surfaces or at body temperature, and for administration with a syringe.

Thus, there is clearly a need for additional cleaning and/or disinfecting and/or debriding compositions that can be used to disinfect, sterilize or clean soiled biological and/or biomaterial surfaces (e.g., mucous membranes of the oral or nasal cavity of a subject) or exposed external skin (e.g., hands and feet) of a subject, prevent contamination and/or re-contamination.

Disclosure of Invention

Aspects of the present invention relate to an antimicrobial and/or antiviral composition for cleaning and/or sterilizing, e.g. cleaning and/or sterilizing in situ, a biological surface and/or a surface of a biological material, comprising at least two components:

(a) H at a final concentration of 0.1 to 7%v/v ₂ O ₂ B, and

(b) A complex hydrogel formulation of pluronic acid at a concentration of 0.1 to 10% w/v.

The complex hydrogel formulation is typically a poloxamer. Thus, the composition of the invention comprises an antimicrobial and/or antiviral mixture consisting of:

(a) Final concentration of 3.0 to 7.0% v/v H ₂ O ₂ And are and

(b) A final concentration of 1.0% to 10.0% w/v poloxamer.

Typically, the antimicrobial and/or antiviral composition as disclosed herein comprises a complex hydrogel formulation of component (b) which is a poloxamer, e.g. pluronic acid at a concentration of 0.1-5%w/v, e.g. a concentration of up to 5%w/v, e.g. a concentration of 1.0% -5.0% w/v, e.g. 0.1, 0.5, 1.0 or 1.5% w/v. In one aspect, the composition according to the invention comprises poloxamer at a concentration of 5.0% w/v. The poloxamer can be a mixture of poloxamers. Component (b) may be selected from the group consisting of pluronic acid,

F-127 and poloxamer 407. In a presently preferred aspect, the poloxamer is poloxamer 407.

In some alternatives, the antimicrobial and/or antiviral composition further comprises H of component (a) ₂ O ₂ Having a final concentration of 0.1-7%v/v, e.g., 0.5-3.0%. In one aspect, H of component (a) ₂ O ₂ With a final concentration of 3%v/v.

In one aspect, component (a) and component (b) are provided in a 1:1 ratio.

In some alternatives, the antimicrobial and/or antiviral composition may further comprise water and/or saline, oil, protectant, flavoring, and/or fragrance.

In one aspect, the antimicrobial and/or antiviral composition comprises at least two components:

(a)H ₂ O ₂ and (b) a composite hydrogel formulation comprising a poloxamer (e.g., pluronic acid), which are maintained separate from each other until they are simultaneously mixed and applied to a biological surface and/or a surface of a biological material in situ.

According to this aspect, the antimicrobial and/or antiviral composition comprises a separate component (a) which is a composition comprising H in a concentration of at least 10-50% v/v ₂ O ₂ The composition of (1).

The composition according to some alternatives may further comprise an additional antimicrobial substance. The composition according to some alternatives may further comprise a biologically active substance, typically selected from the group consisting of peptides, drugs, biologically active ions, small molecules, radioactive molecules and radiopaque molecules, or any combination thereof.

Compositions according to some alternatives typically have a shelf life of at least 1 year at Room Temperature (RT).

The composition according to some alternatives may be used for in situ sterilization or disinfection or cleaning of biological surfaces and/or surfaces of biological materials.

Generally, one or more of the compositions described herein can be used to clean, sterilize, or otherwise remove microorganisms, including but not limited to bacteria or viruses, such as the riboviral domain (Riboviria), coronaviridae (Coronaviridae), orthocoronaviridae (orthocoronaviridae), on the skin and/or mucosa of a subject, preferably a human.

In a presently preferred aspect, one or more of the compositions described herein are used to clean or sterilize the skin and/or mucous membranes of coronaviruses, such as SARS-CoV-2.

Accordingly, aspects of the present invention relate to the use of one or more of the antimicrobial and/or antiviral compositions described herein as a hand wash, mouthwash and/or for nasal and/or sinus cleaning to remove, sterilize or inhibit coronaviruses, e.g., SARS-CoV-2, from the skin or mucosa of a subject, preferably a human.

Aspects of the present invention also relate to the use of one or more of the compositions described herein for cleaning and/or disinfecting a biological surface and/or a biomaterial surface, such as in particular cleaning and/or disinfecting an implant and/or an oral surface in situ and/or any surface covered by skin or mucosa.

In some alternatives, one or more of the compositions described herein are incorporated into a kit, wherein at least two components H are added ₂ O ₂ And the pluronic acid are optionally kept separate so that the user can mix the two components just prior to administration.

Thus, the present invention also relates to a method of disinfecting, sterilising, disinfecting and/or decontaminating a biological surface and/or a biomaterial surface comprising applying a composition according to the present invention to the biological surface and/or biomaterial surface, and to a method of cleaning microorganisms of the skin and/or mucosa of a subject comprising applying a composition according to the present invention to the skin and/or mucosa of the subject. Microorganisms include bacteria or viruses or both, such as, but not limited to, the ribovirus domain, the coronaviridae, the Orthomyxoviridae (Orthomyxoviridae), the Caliciviridae (Caliciviridae), or the Reoviridae (Reoviridae), or any combination thereof. Microorganisms include the orthocoronaviridae subfamily, such as, but not limited to, coronavirus, rotavirus (Rotavirus), norovirus (Norovirus) or Influenza a, b, c, or d virus (Influenza virus), or any combination thereof.

Definitions and abbreviations

Aspects of the present invention provide compositions and methods for cleaning and/or disinfecting biological surfaces and/or biological materials, such as implant surfaces.

In the present context, biological surface means any surface covering an anatomical structure and/or tissue, for example skin, including palm and plantar skin, oral and nasal mucosa, gastrointestinal mucosa, larynx, trachea and bronchial mucosa, vaginal mucosa, penile mucosa, hair, nails, fascia, membrane, synovium, enamel or cementum. The term also includes wound surfaces, such as in, on and/or around the following, but not limited to: ulcers, acute wounds, traumatic wounds, surgical wounds, puncture wounds, abrasive wounds, infectious wounds (including herpetic ulcers), papillomas, chancroid and acne, erosive wounds, burns, blisters, scabs, leg ulcers, diabetic ulcers and/or chronic ulcers.

In the present context, the term "biomaterial or implant surface" generally refers to the surface of a medical and/or dental implant.

In the present context, the term "medical implant" includes within its scope any device intended to be implanted and/or attached in the body of a vertebrate, in particular a mammal, e.g. a human, to maintain and restore body function, in particular a prosthesis of any kind of metallic and polymer-based implant in the vascular system or musculoskeletal system or joints and bones, including for relieving pain in these structures. Non-limiting examples of medical implants are leg, arm and hand prostheses, facial prostheses, ocular prostheses, ileostomy devices, intrauterine devices, pacemakers, electrodes, artificial blood vessel structures, stents, cochlear implants, hip prostheses, knee prostheses, elbow prostheses, finger prostheses, cochlear prostheses, or set screws.

In the present context, the term "dental implant" includes within its scope any device intended to be implanted in the oral cavity of a vertebrate, in particular a mammal, such as a human, for example in dental and jaw bone restoration procedures. The dental implant herein is selected from the group consisting of: implants in the oral cavity, rods, bridges, abutments, crowns, caps, dental fillings and prosthetic parts. Dental implants may also be referred to as dental prosthetic devices. Typically, a dental implant is composed of one or more implant components. For example, dental implants typically include a dental fixture, such as an abutment and/or a dental restoration, such as a crown, bridge or denture, coupled to a secondary implant component. However, any device intended for implantation, such as a dental fixture, may be referred to individually as an implant, even if other components are to be connected thereto.

In a second embodiment, the term biomaterial surface includes the surface of any medical device or tool, disposable or non-disposable, designed to temporarily contact living tissue, such as, but not limited to, surgical instruments, electrodes, scalpels, probes and meters, catheters, syringes, scissors, needle holders, contact lenses, wound dressings, bandages, transdermal fixation devices, and/or diagnostic tools, such as ultrasound devices, X-ray machines, and/or imaging devices, for example, various endoscopes, surgical cameras, impression materials, or intraoral scanners.

In this context, the term peroxide is used with hydrogen peroxide and/or (H) ₂ O ₂ ) May be used interchangeably.

A microorganism or microbe is a microscopic organism, which may exist in the form of a single cell or in the form of a cell population. Microorganisms include all unicellular organisms and are therefore very diverse. All archaea and bacteria are microorganisms (prokaryotes). Some protists are related to animals and some to green plants. Many multicellular organisms are microscopic, i.e., micro-animals, some fungi, and some algae.

An antimicrobial agent is an agent that kills or prevents or inhibits the growth of microorganisms. Antimicrobial drugs can be grouped according to the microorganism in which they primarily function. For example, antibiotics are used to treat or inhibit bacteria, and antifungal agents are used to treat or inhibit fungi. They may also be classified according to their function. Agents that kill microorganisms are microbicidal, while those that merely inhibit their growth are referred to as biostatic agents, both of which are encompassed by the term "antimicrobial agents". The use of antimicrobial drugs to treat or inhibit infection is referred to as antimicrobial chemotherapy, while the use of antimicrobial drugs to prevent infection is referred to as antimicrobial prophylaxis.

Viruses are small infectious agents that replicate only in living cells of an organism. Viruses can infect all types of life forms, from animals and plants to microorganisms, including bacteria and archaea.

Antiviral drugs are a class of drugs that are specifically used to treat or inhibit viral infections, but not bacterial infections. Most antiviral agents are used for specific viral infections, while broad spectrum antiviral agents are effective against a wide variety of viruses. Unlike most antibiotics, most antiviral drugs do not destroy their target pathogens; instead, they inhibit their replication and/or development.

Antiviral drugs are a class of antimicrobial agents, a larger group, and also include antibiotics (also known as antibacterials), antifungal and antiparasitic drugs, or monoclonal antibody-based antiviral drugs. Most antiviral agents are considered to be relatively harmless to the host and may therefore be used to treat or inhibit infection. They should be distinguished from virucidal agents, which are not drugs, but which inactivate or destroy viral particles in vivo or in vitro. Some plants (e.g., eucalyptus or australian tea tree) produce natural antiviral agents.

As used in this context, the term "antimicrobial agent" refers to compositions that are effective against microorganisms and viruses. In its broadest sense, one or more of the compositions described herein is an antimicrobial agent, such as an antibacterial or antiviral agent, an antiseptic or virucidal agent.

As used herein, the term "about" or "approximately" means within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, e.g., the limits of the measurement system.

Drawings

FIG. 1: gel boundary of an aqueous saline (physiological conditions) solution of copolymer F-127. The filled circles are data points of the mixture obtained by the tube inversion method. Unfilled squares are data points from the rheological analysis. The graph clearly shows that the pluronic concentration in saline was less than 15% w/v while maintaining fluid, independent of temperature. The fluid pluronic solution forms individual micelles, but the concentration is not high enough for the pluronic micelles to assemble into a cubic gel. Thus, a low pluronic concentration that allows micelle formation but remains liquid and acts as a detergent may be beneficial for tissue friendly cleaning of biological surfaces, but the addition of other reactants that may aid in decontamination is expected to completely disrupt micelle formation.

FIG. 2: a schematic depicting the synergy of mixing pluronic with peroxide. During interaction with pluronic, peroxides generate Reactive Oxygen Species (ROS), degrade nucleic acids and membranes of microorganisms and viruses, and kill bacteria (including anaerobes) and viruses. Peroxides also drive pluronic micelle dissolution, which is offset by the strong tendency of pluronic to form micellar structures. The dynamic equilibrium between dissolved pluronic and micellar pluronic allows for the active entrapment of dirt, organics, and contaminants into the micellar structure. The liquid hydrophilic nature of pluronic hydrogels also promotes the ready entry of ROS into wrinkles and crevices, unimpeded by bubbling. In addition, pluronic hydrogels moisturize the skin and oxygen released by the peroxide helps the wound healing. ROS also have the ability to clean and reactivate (make the surface hydrophilic) titanium, which is one of the most widely used metals in medical and dental implants. The action of ROS alone is too transient to have a significant impact on these processes and does not remove contaminants or provide moisture. Pluronic alone, used to stabilize micelles, is much less effective in contaminant entrapment and does not kill microorganisms or degrade viral nucleic acids. Mixed together at the correct concentration, pluronic micelles form more dynamically, wetting and oxygenation are optimized, and peroxide action is prolonged and increased and maintained on the surface where it is needed.

FIG. 3: growth medium for titanium surfaces (BHII, negative control), H contaminated with streptococcus epidermidis (s. Epidermidis) bacteria ₂ O ₂ 5%v/v + f-127 1% w/v (test 2), H ₂ O ₂ 5%v/v + f-127 7% w/v (test 4), chlorhexidine 0.2% w/v + f-127 7% w/v (test 5) or ethanol 75% v/v + f-127 1% w/v clean. The negative control did not remove bacteria nor destroy bacteria. The peroxide + pluronic acid mixture killed all bacteria, dissolved the biofilm and almost completely removed debris (tests 2 and 4). Test 4 was slightly more effective than test 2, but was not statistically significant. Chlorhexidine (test 5) and ethanol (test 6) do kill most of the bacteria, but do not remove any debris from the surface, thereby severely fouling the surface. In situ sweepingThe surface visualized after cleaning in an electron microscope was drawn. The scale bar is 20 microns.

FIG. 4: the titanium surface contaminated with S.epidermidis bacteria is treated with A) saline (negative control), B) chlorhexidine 0.2% ₂ O ₂ 3%v/v + f-127 pluronic acid 5%w/v clean. After cleaning, the surface was stained with a fluorescent dye, with live cells in green and dead cells in red. The negative control (saline) did not remove any bacteria, nor did it destroy the bacteria. Chlorhexidine kills all bacteria but allows them to contaminate surfaces. The hydrogen peroxide + pluronic acid mixture killed all bacteria, dissolved the biofilm and almost completely removed debris. After cleaning and staining the surface was observed in a confocal microscope.

FIG. 5: s. epidermidis bacteria contain luciferase genes that cause them to fluoresce, regenerating on sterilized titanium surfaces. The results show that D) water containing detergent (SDS, 0.1%), E) water containing 5% pluronic acid and F) brine have minimal disinfection as regeneration of the biofilm occurred within 3-4 hours after cleaning. On the other hand, 0.2% chlorhexidine killed all bacteria and no regeneration was observed, although dead biofilm adhered to and remained on the surface (see fig. 3 and 4). 5%v/v hydrogen peroxide alone (A) cleans the surface well as seen with a delay of about 13 hours before self-healing by biofilm. However, 3%v/v of hydrogen peroxide combined with water containing 5% pluronic acid cleaned surfaces significantly better, delaying regeneration for more than 15 hours.

FIG. 6: the left and right thumbs were sterilized four times, once a day, for five consecutive days using a) a mixture of langanic acid (5%w/v) and hydrogen peroxide (3%v/v) or B) antipa PharmaTM containing ethanol and propan-2-ol. After the disinfection period, both fingers were stained with iron oxide to visualize cracks and fissures. Cracks and fissures can be readily seen as Antibac Pharma ^TM Brown streaky stain on treated thumb, while pluronic-peroxide formulation did not harm the skin of the left finger.

FIG. 7: fingers were marked with permanent ink lines of laboratory markers and subsequently washed with various disinfecting/decontaminating solutionsTo visualize their ability to remove contaminants from the skin. Finger a) was washed with water only. Finger B) was cleaned with warm water and soap. Finger C) was washed with 0.2% chlorhexidine and finger D) was washed with Pyripet ^TM (0.1% cetylpyridinium chloride) rinse. Finger E) with Antibac Pharma ^TM (alcohol-based disinfectant) clean, finger F) clean with bleach (4% sodium hypochlorite). Fingers G) and H) were rinsed with hydrogen peroxide (1% in water and 5%v/v, respectively). Finger I) was washed in aqueous Pluronic acid (5%w/v). Finger J) was sterilized with a mixture of pluronic acid (5%w/v) and hydrogen peroxide (1%v/v). The results show that bleach and hydrogen peroxide are effective in removing ink stains, but the most effective cleaning is achieved by the combination of pluronic acid and hydrogen peroxide.

Detailed Description

There is a long-felt need in the community for compositions described herein that effectively clean, disinfect and/or sterilize biological surfaces and/or biomaterial surfaces (e.g., including but not limited to skin or mucous membranes, such as surfaces in the mouth-throat or nasal cavities). Any one or more of the compositions described herein can be used to quickly and effectively treat or inhibit bacteria or viruses, or both, leaving substantially no contaminating material residues.

The compositions described herein are tissue-friendly nonionic surfactants that are water soluble and easily rinsed off. These compositions comprise non-toxic formulations of the active ingredients well studied in clinical use, particularly for injection, oral and/or dermal administration. The composition described herein for the first time proved to be non-sensitizing and non-irritating in clinical trials. The compositions described herein are compatible with most other therapeutic agents that can be used to combat biological contamination and inflammation.

The compositions described herein have a liquid state at room temperature, allowing trouble-free mixing and application. The composition has a readily flowable liquid consistency and surfactant effect which, when applied to narrow crevices, defects and/or folds in the skin and/or mucous membranes, allows the composition to reach difficult places.

Without being bound by a particular theory or mechanism of action, the compositions described herein are expected to mimic the natural release of Reactive Oxygen Species (ROS) in peroxides produced by human cells. The charge from the active oxygen destroys the microbial membranes, and the oxygen itself is also toxic to anaerobic bacteria. The human cells themselves are protected from ROS by enzymes in their cell membranes, and local tissues may benefit from an increase in oxygen. Without this protection, microorganisms cannot develop resistance because of fundamental differences in their cell membrane design. Thus, the composition can effectively solubilize biofilms, debris and mineral deposits, as well as extracellular organisms at the site of administration.

The use of the compositions presented herein also removes carbon contamination from the surface of the titanium-containing implant and reactivates the titanium dioxide layer of the implant by the release of active oxygen from the liquid hydrogel. This process reestablishes the original charge and hydrophilicity of the implant, restoring its optimal biological surface properties. This is a factor in further survival or even successful reintegration of the treated implant. The composition of the present invention provides an advanced micelle-forming gel formulation that works synergistically with naturally occurring oxygen to break down and remove biofouling, eliminate microorganisms, keep tissues and implants moist, and reactivate the titanium implant surface.

The hydrogel component of the composition and the active oxygen act synergistically to avoid foaming due to oxygen release and to hold the activated oxygen in place on the surface to prolong biological and chemical action. The use of any one or more of the compositions described herein provides moisture and allows charged oxygen to act without the risk of drying out of the skin, tissue and/or implant surfaces, during which time the reactive oxygen species eradicate the microorganisms that are subsequently suspended and entrapped inside the micelle-forming hydrogel. The organic contaminants are then denatured by the action of the strong detergent, decomposed by the active oxygen and dissolved and trapped in the hydrogel. Both hydrogel and oxygen can reduce inflammation and support tissue health. The released reactive oxygen species in turn strengthen the cellular defense network. Under synergistic action, both the gel and the reactive oxygen species remove contaminants, act as antimicrobial and virucidal agents, and reactivate the titanium implant surface. The interaction between pluronic micelle formation and peroxide enhances micelle formation and significantly improves cleaning.

The compositions described herein provide a new formulation of a biocompatible hydrogel-peroxide combination having potent antimicrobial, virucidal and nonionic detergent properties and improved micelle kinetics for solubilizing and entrapping debris and microorganisms, thereby effectively cleaning, disinfecting, sterilizing and/or debriding a biological surface and/or a biomaterial surface in situ. It is easily rinsed off with a towel, paper towel, or with water, but it can also be allowed to air dry and completely decompose into water, oxygen, and carbon dioxide.

The compositions disclosed herein provide novel and improved methods of cleaning, disinfecting, sterilizing and/or disinfecting skin, mucous membranes and/or implant surfaces. In particular alternatives, for example, any one or more of the compositions described herein are incorporated into mouthwashes and/or nasal rinses, and these formulations may be used to prevent, treat, inhibit or ameliorate oral and/or nasal diseases (e.g., caries, periodontitis, gingivitis, mucositis, peri-implantitis, sinusitis and/or rhinitis). In a further alternative, the oral irrigation solution and/or the nasal irrigation solution may be used in a method of inhibiting bacterial or viral infection (e.g. SARS-CoV-2) in the oral or nasal mucosa of a subject, e.g. a human.

The desired formulations described herein are based on hydrogen peroxide (H) ₂ O ₂ ) And pluronic acid at a concentration such that the resulting composition is in the form of an aqueous liquid at physiological temperatures. H of the composition ₂ O ₂ The components may be in the form of concentrates (at a concentration of at least 10-50% v/v) in separate vials for mixing immediately prior to use, or provided as an emulsion or directly dissolved as a hydrogel composed at least in part of pluronic acid and water and/or physiological saline, with typical final concentrations of 0.5 to 7%. The pluronic component itself may be any one or combination of pluronic acids, such as form F-127. The concentration of pluronic acid is generally 0.1-10% w/v, e.g., 0.1 to 7%w/v, e.g., 0.1 to 2.5% w/v. That is, the concentration of pluronic acid in any one or more of the compositions described herein may beIs at least or equal to 0.1%, 0.5%, 1.0%, 1.5%, 2.0%, 2.5%, 3.0%, 3.5%, 4.0%, 4.5%, 5.0%, 5.5%, 6.0%, 6.5%, 7.0%, 7.5%, 8.0%, 8.5%, 9.0%, or 10% w/v or a percentage w/v within a range defined by any two of the above-mentioned percentages.

Pluronic acid is used in the compositions disclosed herein as both a solubilizer and a cleanser, as well as a humectant. In the presence of peroxide, the hydrogel formulation establishes a dynamic micelle forming solution. This dynamic state helps to effectively dissolve and entrap particles, microorganisms and contaminants during the cleaning process (see e.g., fig. 2).

The present invention is based on the synergistic effect between pluronic acid and peroxide. Pluronic acid has the ability to form micelles. This ability generally increases with increasing temperature and transitions to the gel state under physiological conditions (e.g., >20 degrees celsius). The addition of peroxide allows the pluronic acid to remain liquid even at physiological temperatures.

The present inventors have for the first time disclosed that micelles are more dynamic and less stable when mixed with hydrogen peroxide, and are in "dynamic" equilibrium with peroxide radical activity even at high temperatures. In practice, this means that in the presence of peroxide, the micellar structure is solubilized and constantly reformed when the gel is applied to human tissues, skin and/or mucous membranes. This action keeps the hydrogel fluid at high temperatures as well and significantly increases the detergent, denaturing and entrapment effects of pluronic acid.

In combination with the action of hydrogen peroxide to release free radicals on viral particles, microorganisms and necrotic tissue, micelles turn to dissolve and entrap organic contaminants, which are then removed when the gel dries, wipes off or washes away.

Desirably, the addition of hydrogen peroxide to the pluronic acid in the compositions described herein increases the temperature at which gelation occurs, e.g., pluronic gels containing low concentrations of peroxide are liquid at room temperature and therefore can be administered through a syringe needle or from a dispensing bottle without clogging the nozzle. This is not possible with pluronic acid alone because it has begun to form a stable "micelle-filled" gel at room temperature, even at low concentrations, in a narrow compartment and/or at the "vapor front" at the dispenser nozzle, thus making it difficult to squeeze a pump applicator through the narrow tip of a syringe or dispensing bottle. Therefore, pluronic gels for wound care are sold in the form of boxed or tube gels. The increased effect of the combination of peroxide and pluronic acid was unexpected and unexpected.

Liquid formulations of pluronic hydrogels in combination with peroxides also help during application. It enables the cleaning and/or disinfecting composition to reach folds, wrinkles, crevices, cracks, narrow spaces and/or undercuts that are not reached by pluronic gel alone because of its gel-forming properties that make it viscous at physiological temperatures. It is therefore more effective in cleaning rough (implant) surfaces, narrow spaces, such as folds, crevices and wrinkles on the skin and mucous membranes and between teeth.

Composition comprising a metal oxide and a metal oxide

Aspects of the present invention relate to novel antimicrobial and/or antiviral compositions that can be used to clean, disinfect, sterilize, disinfect, and/or decontaminate biological surfaces and/or biomaterial surfaces in situ. In some alternatives, the above composition comprises two components:

a. h at a final concentration of 0.1 to 7%v/v ₂ O ₂ And are and

b. a complex hydrogel formulation of pluronic acid at a concentration of 0.1 to 10% w/v.

In some of the above-mentioned compositions, H ₂ O ₂ Is at least or equal to 0.1%, 0.5%, 1.0%, 1.5%, 2.0%, 2.5%, 3.0%, 3.5%, 4.0%, 4.5%, 5.0%, 5.5%, 6.0%, 6.5%, or 7.0%w/v or a percentage w/v within a range defined by any two of the above mentioned percentages. In some of the above-mentioned compositions, the final concentration of pluronic acid is at least or equal to 0.1%, 0.5%, 1.0%, 1.5%, 2.0%, 2.5%, 3.0%, 3.5%, 4.0%, 4.5%, 5.0%, (ii) a,5.5%, 6.0%, 6.5%, 7.0%, 7.5%, 8.0%, 8.5%, 9.0% or 10% w/v or a percentage w/v within a range defined by any two of the above mentioned percentages.

Preferably, the compositions are formulated such that they remain liquid at physiological temperature, for example at a temperature of at most 40 ℃, for example at a temperature of 20-40 ℃, for example at 37 ℃, for example 20, 22, 24, 26, 28, 30, 32, 34, 36, 38 or 40 ℃ or a temperature within a range defined by any two of the above mentioned temperatures.

Some of the compositions disclosed herein are characterized in that they contain a low concentration of pluronic acid, which renders the compositions in a liquid rather than a gel state at elevated temperatures, a desirable characteristic for their use in situ cleaning, disinfecting, sterilizing, disinfecting and/or decontaminating biological surfaces and/or biomaterial surfaces. In particular, liquid hydrogels are desirable when the compositions are incorporated into hand sanitizers, mouth rinses, and/or solutions for nasal and/or sinus cleaning, particularly for washing viruses off the skin and mucous membranes.

The compositions disclosed herein comprise at least two components (a) and (b) in a ratio such that the composition is in a liquid state at physiological temperatures rather than in a more viscous or gel-like state. A typical concentration ratio between component (a) and component (b) is about 1:1 (H) ₂ O ₂ Concentration: pluronic acid concentration). Generally, the higher the concentration of pluronic acid, the higher the H required ₂ O ₂ The concentration is such that the composition remains liquid at a temperature of 25-40 ℃. However, too high a concentration of peroxide can destroy the amphiphilic properties of pluronic acid and disrupt micelle formation, rendering it useless as a detergent and/or desaturator.

In an alternative embodiment of the antimicrobial and/or antiviral composition according to the invention, the complex hydrogel formulation of component (b) comprises pluronic acid at a concentration of 0.1-10% w/v, e.g. at a concentration of 10% w/v, e.g. an amount within a range defined by 0.1, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9 or 9.5% w/v or any two of the above mentioned concentrations.

In another alternative of the antimicrobial and/or antiviral composition according to the invention, the complex hydrogel formulation of component (b) comprises pluronic acid in a concentration of at most 10% w/v, e.g. an amount of at most 0.1, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9 or 9.5% w/v or within a range defined by any two of the above-mentioned concentrations.

The antimicrobial and/or antiviral composition according to the invention may be wherein component (a) is H ₂ O ₂ Compositions having a final concentration of 0.1 to 7%v/v, e.g., 0.5 to 3%v/v, e.g., 0.1 to 5%v/v. In one embodiment, H of component (a) ₂ O ₂ Having a final concentration of no more than 7%v/v, such as 0.1 to 7%v/v, such as 1, 2, 3, 4, 5, 6, or 7%v/v.

The antimicrobial and/or antiviral composition according to the present invention may further comprise water and/or physiological saline.

The two components of the antimicrobial and/or antiviral composition according to the invention may be in one solution, or at least two components may be kept separate from each other, such that they can be mixed simultaneously and applied to the biological surface and/or the surface of the biological material in situ.

In the antimicrobial and/or antiviral composition according to the invention, wherein the components are kept separate from each other prior to administration, the separate component (a) may be a H comprising a concentration of at least 10-50% v/v, e.g. at most 10, 20, 30, 40 or 50% >/v ₂ O ₂ The composition of (1). In an alternative embodiment, the composition of the invention comprises H in a concentration of 30% v/v ₂ O ₂ 。

Emulsifiers and/or viscosity regulators

In some alternatives, the antimicrobial and/or antiviral composition according to the invention further comprises one or more emulsifiers and/or viscosity modifiers. The emulsifier and/or viscosity modifier may be selected from the group consisting of: glycerin, glycol, polyethylene glycol (PEG), polyoxyethylene polyoxypropylene block copolymer (pluronic polyol), glycol alginate (PGA), CMC (carboxymethyl cellulose), glycerin, aloe vera gel, alginate, hyaluronic Acid (HA), and chitosan, or any combination thereof.

The antimicrobial and/or antiviral composition according to the present invention may further comprise one or more detergents selected from the group consisting of SDS (sodium dodecyl sulfate), sodium stannate, sodium pyrophosphate, 8-hydroxyquinoline (oxine), and SLS (sodium lauryl sulfate), or any combination thereof.

The antimicrobial and/or antiviral composition according to the present invention may further comprise one or more fragrances or flavoring oils such as, but not limited to, perfumes and oils of spearmint, peppermint, wintergreen, sassafras, clove, sage, eucalyptus, marjoram, cinnamon, and methyl salicylate or menthol or any combination thereof.

The antimicrobial and/or antiviral composition according to the invention may further comprise one or more weakly acidic buffers.

The antimicrobial and/or antiviral composition according to the present invention may further comprise one or more stabilizers such as, but not limited to, organophosphates, carboxylates, sodium pyrophosphate, sodium phytate, colloidal stannate or sodium citrate or any combination thereof.

Biologically active substance

Alternatively or additionally, one or more of the compositions according to the invention may comprise a biologically active substance, typically selected from the group consisting of: EMD, peptides, drugs, bioactive ions, small molecules, radioactive molecules, antimicrobial molecules, and radiopaque molecules, or any combination thereof.

Cleaning composition and antimicrobial material

Furthermore, one or more of the compositions according to the invention may also comprise additional antimicrobial substances and/or cleaning components.

In this context, the additional antimicrobial substance provided in one or more of the compositions according to the invention may be selected from the non-exclusive list consisting of: amoxicillin, doxycycline, cephalexin, ciprofloxacin, clindamycin, metronidazole, azithromycin, sulfamethoxazole, and trimethoprim, or any combination thereof.

In one aspect, the additional antimicrobial substance provided in one or more of the compositions according to the invention is an alcohol, tetracycline, doxycycline, macrolide, penicillin (stabilized), chlorhexidine, chloramine, or mixtures thereof.

In one aspect, one or more of the compositions according to the invention comprise an additional antiviral substance.

In one aspect, one or more of the compositions according to the invention comprise an additional anti-inflammatory agent or substance, blood clotting agent or substance, anesthetic agent or substance, and/or analgesic agent or substance.

In one aspect, one or more of the compositions according to the present invention comprise one or more prophylactic and/or anti-caries agents, such as, but not limited to, hydrogen fluoride, sodium fluoride, or stannous fluoride, or any combination thereof.

Shelf life of at least 1 year at Room Temperature (RT)

The composition according to the invention has in one aspect a shelf life of at least 1 year at Room Temperature (RT).

Reagent kit

Aspects of the invention also relate to kits comprising the compositions described herein, wherein the kit comprises at least two containers, syringes and vials, connector devices, applicator tips and instruction booklets, respectively, containing the separate components (a) and (b), and optionally a mixing device and a cleaning implement, such as, but not limited to, a brush. The kit may provide the two components (a) and (b) in a two-chamber syringe, in which case the kit may further include an instruction booklet, a mixing device, an applicator tip, and a cleaning implement such as, but not limited to, a brush and/or a wipe.

The antimicrobial and/or antiviral composition according to the invention may be mixed prior to administration and final storage, or stored separately and mixed directly or shortly before and/or at the time of administration. Thus, in a further aspect, the present application relates to a kit comprising a first container comprising component (a), a second container comprising component (b) and optionally at least one more (third or fourth etc.) container comprising components (c), (d), (e) etc., which may for example comprise paper and/or cotton wipes such as but not limited to wet wipes, particulates and/or a web forming substance and/or a biologically active substance and/or a cleaning component and/or another antimicrobial and/or antiviral substance.

Optionally, such kits may further comprise instructions for preparing the compositions of the invention. The kit may also include one or more devices for administering the composition to a subject. Such a device may for example be a dispensable bottle, a blister pack, a double blister pack, a syringe and/or an implant cleaning and/or disinfecting tool for cleaning and/or disinfecting an implant, for example an implant in the oral cavity.

The kits of the present invention may further comprise one or more compositions described herein in one or more containers and an implant cleaning and/or disinfecting means for cleaning and/or decontaminating implants in the oral cavity.

In a preferred aspect herein, a kit comprising a composition according to the invention typically provides the two components (a) and (b) in a two-compartment device which allows for easy mixing of the components before and/or during administration. Typically, such devices may be two-compartment syringes, two-compartment pump action dispense bottles, double blister (blister in blister) packs, or wet wipe blisters containing individual blisters containing peroxide to be destroyed prior to application.

The kit may also comprise a container, such as a blister pack and/or a face tissue, such as a sterile wipe for applying the composition according to the invention.

Use of

The compositions disclosed herein are intended for use in cleaning, disinfecting, sterilizing and/or disinfecting biological surfaces and/or biomaterial surfaces in situ.

In one aspect of the invention, the antimicrobial and/or antiviral composition according to the invention is used for in situ sterilization, disinfection and/or disinfection of biological surfaces and/or surfaces of biological materials.

Thus, the antimicrobial and/or antiviral composition according to the present invention is generally used for cleaning, sterilizing, disinfecting and/or sanitizing the skin and/or mucous membranes to remove microorganisms.

In particular, the microorganisms to be killed or removed by the composition according to the invention are selected from the group consisting of bacteria and viruses, for example from the non-exclusive group consisting of the riboviral domains, in particular the coronaviridae (e.g. Sars-Cov-2) or orthocoronaviridae subfamily.

The antimicrobial and/or antiviral composition according to the invention is particularly suitable for killing and/or removing coronaviruses, for example from the skin and/or mucous membranes, including the hands, the face or the oral or nasal cavity.

Thus, in a preferred aspect herein, the present invention also relates to the use of the antimicrobial and/or antiviral composition according to the present invention as a hand wash, a mouth wash, a tooth wash, for nasal and/or sinus cleaning and/or for washing away viruses on the skin and mucous membranes.

Thus, in a preferred aspect herein, the present invention also relates to the use of the antimicrobial and/or antiviral composition according to the present invention as a hand sanitizer, a mouth rinse, a sinus rinse, a nasal rinse and/or a disinfecting wipe.

The compositions disclosed herein may also be used for application in peri-implant defects, and the formulations may be tailored to suit various clinical procedures, such as, but not limited to, treatment and prevention of oral infections, to maintain oral and/or nasal health, and subsequent post-operative application to the skin, mucosa, and/or oral-laryngeal and/or nasal cavities.

The compositions disclosed herein may also be used in other oral procedures, such as during surgical cleaning of periodontal defects, in preparation prior to regenerative procedures, periodontal maintenance therapy, periodontitis prevention (by a dental hygienist), and endodontic treatment, both in root canal procedures and apical surgery.

In addition, the compositions disclosed herein may also be used to clean and/or debride the exterior of the oral cavity, such as, but not limited to, in orthopedic remedial procedures, disinfection of transdermal devices, skin wound care for cleaning acute wounds, and/or cleaning chronic ulcers and burns.

The antimicrobial and/or antiviral composition according to the invention may be used for the treatment and/or prevention of peri-implantitis, gingivitis and/or mucositis, peri-implant mucositis and/or periodontitis in general or for disinfecting the oral cavity against infectious diseases or before oral surgical procedures.

Peri-implantitis is a typical complication associated with oral dental repair by use of implants, such as peri-implant disease, which is well known to those skilled in the art as an inflammatory response to oral microbes with concomitant loss of the implant's bone support. The etiology of the disease depends on the state of the tissue surrounding the implant, implant design, roughness, poor alignment of implant components, external morphology and excessive mechanical loading.

The antimicrobial and/or antiviral compositions described herein provide several methods for effective and rapid cleaning of implants and/or for disinfecting or decontaminating tissue surfaces in the oral cavity without substantially damaging the delicate structures or the implant surfaces and/or the tissue surfaces themselves, and without substantially leaving contaminating material residues on the treated surfaces.

Thus, the present invention relates in one aspect to the use of an antimicrobial and/or antiviral composition as defined herein and/or a kit for the preparation of a composition of the invention as defined herein as a medical device or medicament.

Thus, the present invention relates to the use of an antimicrobial and/or antiviral composition according to the present invention for cleaning and/or disinfecting and/or decontaminating implants in the oral cavity (e.g. in situ implants), tissue surfaces in the oral cavity (e.g. the outer surfaces of tissues in the oral cavity), surgically exposed surfaces in the oral cavity, wounds in the oral cavity (e.g. wounds resulting from peri-implantitis or surgical wounds), periodontal and/or periodontal wounds, and/or oral hard tissue defects.

Implant body

The present invention also relates to the use of an antimicrobial and/or antiviral composition as defined herein and/or a kit for the preparation of a composition of the invention as defined herein for: for the preparation of a pharmaceutical and/or cosmetic composition for cleaning and/or decontaminating implants in the oral cavity (e.g., in situ implants), hard surfaces in the oral cavity (e.g., the outer surface of hard tissue in the oral cavity, surgically exposed hard surfaces in the oral cavity), wounds in the oral cavity (e.g., wounds caused by peri-implantitis or surgical wounds), periodontal and/or periodontal wounds, and/or oral hard tissue defects.

The present invention also relates to an antimicrobial and/or antiviral composition as defined herein or a kit for preparing a composition of the invention as defined herein for cleaning, disinfecting, sterilizing, disinfecting and/or debriding an implant in the oral cavity (e.g. an in situ implant), a hard surface in the oral cavity (e.g. the outer surface of hard tissue in the oral cavity, a surgically exposed hard surface in the oral cavity), a wound in the oral cavity (e.g. a wound caused by peri-implantitis or a surgical wound), a periodontal and/or periodontal wound and/or an oral hard tissue defect.

Orolaryngeal and nasal medical applications

In dentistry and otorhinolaryngology, nasal and oral irrigants are used before and after surgery to reduce the microbial load during surgery or to treat infections. Infections of the oral, laryngeal and nasal mucosa lead to the formation of mucus which can fill the sinuses and cause congestion of the nasal cavity and sinuses and microbial accumulation on the tongue, tonsils, teeth and gums. The present invention also relates to the use of an antimicrobial and/or antiviral composition as defined herein as a mouthwash, nasal rinse and/or sinus rinse for disinfecting and cleaning the oral, laryngeal and/or nasal anatomy and/or surfaces.

Micro-organisms

The antimicrobial and/or antiviral composition according to the present invention is generally intended for use in situ cleaning, disinfecting and/or decontaminating a biological surface and/or a biomaterial surface, for example for in situ removal of viruses, microorganisms including but not limited to bacteria, yeasts and bacterial spores and dirt from such a biological surface and/or biomaterial surface.

Biofilms that may be prevented, eliminated and/or treated by the compositions of the present invention include, but are not limited to, biofilms present in the oral cavity, such as biofilms on tooth surfaces, on mucosal/soft tissue surfaces (e.g., gingival/periodontal ligament), and within dental tubes (e.g., endodontic tubes).

In certain embodiments, biofilms that may be prevented, eliminated, and/or treated by the compositions of the present invention include biofilms on and/or within the urinary tract, lungs, gastrointestinal tract, chronic wounds, and/or chronic wounds, and biofilms present on surfaces (e.g., implants) and within medical devices and lines (e.g., catheters, medical devices, or medical tubes).

The compositions of the present invention may be used to reduce the growth of and/or inhibit the viability of one or more microorganisms (e.g., bacteria in a biofilm). <xnotran> , (Streptococcus mutctns, S.mutctns), (Streptococcus sobrinus), (Streptococcus sctnguis, sctnguinis), (Streptococcus gordonii), streptococcus omlis, (Streptococcus mitis), (Actinomyces odontolyticus), (Actinomyces viscosus), (Aggregcttibctcter ctctinomycetemcomitctns), ictctobctcillus spp., (Porphyromoncts gingivctlis), (Prevotellct intermedia), (Bacteroides forsythus), (Treponema denticola), (Fusobacterium nucleatum), (Campylobacter rectus), (Eikenella corrodens), (Veillonella spp.), (Micromonas micros), (Porphyromonas cangingivalis), (Haemophilus actinomycetemcomitans), (Actinomyces spp.), (Bacillus spp.), (Mycobacterium spp.), (Fusobacterium spp.), (Streptococcus spp.), (Staphylococcus aureus), (Streptococcus pyogenes), (Streptococcus agalectiae), (Proteus mirabilis), (Elebsiella pneumoniae), (Acinetobacter spp.), </xnotran> Certain species of the genus Enterococcus (Enterococcus spp.), certain species of the genus Prevotella (Prevotella spp.), certain species of the genus Porphyromonas (Porphyromonas spp.), certain species of the genus Clostridium (Clostridium spp.), stenotrophomonas maltophilia (Stenotrophora), porphyromonas gingivalis (P. Gingivalis), candida albicans (Candida albicans), escherichia coli (Escherichia coli) and/or Pseudomonas aeruginosa (Pseudomonas aeruginosa). In certain embodiments, the bacterium is streptococcus mutans, which is present in a biofilm found in the oral cavity, e.g., on the surface of the teeth.

The most relevant microorganisms for implant failure are spirochetes and mobile forms of gram-negative anaerobes. The diagnosis may be based on changes in gingival color, bleeding and probing depth of the peri-implant pocket, suppuration, x-ray and gradual loss of bone height around the tooth. To date, the antibiotic therapy that has proven most effective in the antibiogram is a combination of amoxicillin and clavulanic acid. In addition to bacterial infections, microbial infections in the oral cavity may of course also include fungal and/or viral infections.

The antimicrobial and/or antiviral composition according to the present invention is effective in killing bacteria, fungi and/or viruses.

Generally, the compositions according to the invention are used for cleansing the skin and/or mucous membranes of viruses such as, but not limited to, the ribovirus domain, for example of the family coronaviridae, for example of the subfamily orthocoronaviridae and orthomyxoviridae, for example of the influenza a, b, c and d viruses, arboviruses (arboviruses) and isavus viruses (isavus), and also, for example, rotaviruses, norovirus, adenovirus (Adenovirus), papilloma viruses (Papillomavirus), herpes viruses (Herpes viruses), hepatitis viruses (hepatis viruses), smallpox viruses (Small Pox viruses), parvoviruses (paraviruses), ebola viruses (Ebola viruses), measles viruses (Measles viruses) or Rabies viruses (Rabies viruses).

In a preferred aspect herein, the composition according to the invention is used for cleansing the skin and/or mucous membranes of coronaviruses or influenza viruses.

More importantly, the compositions described herein are antimicrobial, do not cause microbial resistance, and are antiviral.

Accordingly, the present invention relates to a method for cleaning, disinfecting, treating and/or preventing infectious diseases, infections, gingivitis and/or mucositis, peri-implant inflammation, periodontitis, caries and/or sinusitis and rhinitis, comprising cleaning a biological surface and/or a biomaterial surface in situ by applying a composition according to the present invention to said scaled, filmed and/or contaminated structure, tissue or surface.

Examples

The following examples are included to provide guidance to those skilled in the art for practicing representative embodiments of the subject matter disclosed herein. In view of the present disclosure and the general level of skill in the art, those skilled in the art will appreciate that the following embodiments are intended to be exemplary only, and that numerous changes, modifications, and alterations may be employed without departing from the scope of the subject matter disclosed herein.

Example 1

Analysis of Planick micelle formation in the Presence of peroxide

Added to aqueous solutions

F-127 may vary in thickness depending on concentration and temperature. F-127 is a nonionic surfactant polyol having a molecular weight of 12500 daltons.

As can be seen in FIG. 1, the gel boundary of the aqueous saline (physiological conditions) solution of copolymer F-127. The filled circles are data points of the mixture obtained by the tube inversion method. Unfilled squares are data points from the rheological analysis. The graph clearly shows that pluronic concentrations in saline less than 15% w/v remain fluid regardless of temperature. The fluid pluronic solution forms individual micelles, but not at a high enough concentration to allow the pluronic micelles to assemble into a cubic gel. Thus, a low pluronic concentration that allows micelle formation but remains liquid and acts as a detergent may be advantageous for tissue-friendly cleaning of biological surfaces, but the addition of other powerful reactants that may aid in decontamination would be expected to completely interrupt micelle formation, thereby eliminating the detergent and denaturation required.

Adding peroxide to pluronic f-127 gel

To test whether micelle formation (as seen by the ability to foam and dissolve oil) can still be obtained when low concentrations of pluronic f-127 are mixed with various antimicrobial agents in water (see example 3), hydrogen peroxide was tested over a wide range of peroxide concentrations (table 1).

The technique for preparing the aqueous poloxamer solution is simple. Weighed f-127 was slowly added to a known weight of cold water (below 10 ℃) with careful stirring. The stirring speed should be controlled to maintain a slight vortex in the liquid. Too fast a stirring speed may result in aeration and foam formation.

Sample (I)	Plannic F-127 (gr)	H ₂ O(ml)	50％H ₂ O ₂ (ml)
				0	2.5	50.00	0.00(0.0％)
1	2.5	49.90	0.10(0.1％)
				2	2.5	49.50	0.50(0.5％)
3	2.5	49.00	1.00(1.0％)
				4	2.5	48.50	1.50(1.5％)
5	2.5	47.00	3.00(3.0％)
				6	2.5	44.00	6.00(6.0％)
7	2.5	38.00	12.00(12.0％)

Table 1: composition of a suspension containing 5% pluronic acid F-127 (Sigma Aldrich) in water and a series of hydrogen peroxide (Sigma Aldrich). After dissolving f-127 in cold water, add the appropriate amount of hydrogen peroxide, mix by carefully inverting the tube to avoid foaming, and leave the solution at room temperatureOn the bench for 10 minutes. When all the polymer is added, stirring may be continued (while keeping the solution cool) until a clear solution is formed, or the container may be placed in a refrigerator and left to stand for several hours, at which point the solution is complete. At the beginning of the experiment, H was added by gentle stirring for a few seconds ₂ O ₂ And (4) mixing.

Table 2: after incubation, all solutions were still liquid (no gel formation as expected) and vortexed, and the ability to form foam (as a simple measure of surfactant effect) was scored on a scale of 0 (no foam) to 3 (large amount of foam). As expected, sample 0 scored the highest, and the addition of hydrogen peroxide reduced foaming at both low and high concentrations. Surprisingly, there is no linear relationship in the reduction of foaming. In fact, samples 2 to 4 scored as high as the control, indicating that micelle formation and surfactant effects were retained in these samples. The solution of the test sample can then absorb how many oil droplets from the tip of the needle before becoming cloudy (mineral oil stained with oil red (Sigma Aldrich)). Turbidity is an indication of macroscopic emulsions, at which stage the oil droplets become so large that they disperse light. Positive control sample 0 absorbed 7 oil droplets before becoming cloudy. The negative control sample 7 became cloudy in the first drop. However, no expected linearity between these extremes was observed. Surprisingly, samples 2 (0.5% peroxide) and 3 (1.0% peroxide) actually absorbed almost twice the number of droplets as the positive control before turbidity was observed. This indicates that pluronic f-127 micelle formation at low concentrations (= liquid solutions) is actually more efficient and more dynamic in the presence of low concentrations of hydrogen peroxide in the range of 0.5 to 1.5 volume% (in 5%w/v f-127 solutions).

Example 2

Testing of the biocompatibility of pluronic acid in combination with peroxide

And (3) testing procedures:

biocompatibility testing part 5 of the biological evaluation of medical devices according to ISO 10993-5: in vitro cytotoxicity assays were performed.

Colorimetric assays (e.g., MTT, WST-1 or LDH) have not been used because peroxide suspensions degrade the indicator colors used in these assays and therefore cannot be used. Alternatively, use [ 2 ] ³ H]Radiolabelling with thymidine incorporation was used to analyze the cytotoxicity of pluronic-peroxide solutions on Normal Human Dermal Fibroblasts (NHDF) (Lonza walker ville, inc.

Hydrocolloid gels due to testing: (

Gel, medline Industries, madlain, illinois) and pluronic-peroxide Gel (20% pluronic f-127 aqueous solution containing 3% hydrogen peroxide) were not diluted into cell culture media. NHDF cells also cannot grow directly on gels because they lack surface properties. To overcome this problem, NHDF cells were inserted in cell culture(s) (II)

Millipore corp., belerica, maryland, usa) inserted into wells containing test gel diluted against cell culture medium 1:1. NHDF cells were cultured at 37C and 5% CO ₂ (ii) cell culture in Dulbecco's PBS in 24-well plates

Insulin (CC-4021J), rhFGF-B (CC-4065J) and FBS (CC-4161J) were incubated for 24 hours in Lonza Walkerville, U.S.A.). After 24 hours of growth in the presence of test substance or control (no gel and gelatin gel), 0.5. Mu.L will be ³ H-thymidine (Perkinelmer, boston, USA) is added to the wells containing cells. After 12 hours exposure to thymidine, cells were washed 3 times in cold PBS and lysed with 250 μ Ι _ of 1M NaOH. 200 μ L of the lysed cell solution was then transferred to 3ml of Insta-gel-2-Pluss liquid scintillation fluidIn (1). Then in a liquid scintillation analyzer (

1500Perkin Elmer) were counted.

Results and conclusions: no difference in counts was observed between the sample exposed to the pluronic-peroxide solution and the control, indicating that NHDF cells grew at a normal rate in the presence of these test gels. The pluronic acid gel containing hydrogen peroxide is safe and biocompatible. The silverasorb gel showed a significant reduction in the number of counts, indicating a slow cell growth in the presence of the gel, as also repeatedly reported in the scientific literature, indicating that this gel is slightly toxic to NHDF cells.

Example 3

Chemical cleaning efficacy of peroxide-containing liquid pluronic f-127 solutions

The following cleaning solutions were tested:

experimental setup:

stock cultures of Streptococcus Epidermidis (Streptococcus Epidermidis) were established in BHI broth and grown to log phase.

The streptococcus epidermidis cultures were introduced into chemically pure (c.p.) titanium cell culture plates and allowed to form a multilayer biofilm on the surface over a period of 2 days. After biofilm establishment, the disks were rinsed several times in sterile, cold PBS until only adherent cells were present on the surface.

The disc with the biofilm thereon was then immersed in the test gel or control for 5 minutes ± 5 seconds to ensure that the entire disc was covered with the test gel at all times. The discs were then rinsed in cold PBS on a shaker for 10 minutes, rinsed clean and viewed in a bench-top scanning electron microscope to see how much bacteria remained on the test surface.

Results and conclusions:

this experiment shows that with H ₂ O ₂ Increased and pluronic f-127 concentration, improved cleaning efficacy. However, the difference between test 1 and test 4 was surprisingly small and not statistically significant, as all four tests performed very well and almost no bacteria remained on the surface. As expected, the negative control was completely covered with bacteria and had no effect of PBS washing. The positive chlorhexidine and ethanol controls were unexpectedly ineffective. Almost all biofilm remains on the surfaces of both groups. Subsequent analysis of the regeneration of bacteria from these surfaces indicated that all of the bacteria in both tests were dead, but that most of the biofilm remained attached to the surface, forming a fouling layer, which provided a powerful bridgehead for new biofilm formation if new fouling occurred.

The surprising finding in this study appears to be a synergistic effect between hydrogen peroxide and pluronic f-127, not only killing bacteria, but also breaking down and dissolving the entire biofilm, leaving an almost completely decontaminated surface (fig. 3). The concentrations of peroxide and pluronic can be reduced to 3% hydrogen peroxide in 1% pluronic acid without losing much of the effect compared to stronger solutions. This also suggests that the synergy between hydrogen peroxide and pluronic acid can be fine-tuned and may have an optimal concentration relationship, allowing rapid and dynamic micellar (detergent and denaturing) action while maintaining the effectiveness of active oxygen release to kill microorganisms and solubilize organic molecules. The concentrations of both peroxide and pluronic for this optimal formulation appear to be lower than would be expected based on the effects of the individual components when the components are mixed together.

As shown in FIG. 3, growth medium for titanium surface (BHI, negative control), H contaminated with S.epidermidis bacteria ₂

O

₂ 5%v/v + f-127 1% w/v (test 2), H ₂ O ₂ 5%v/v + f-127 7% w/v (test 4), chlorhexidine 0.2%V + f-127 7% w/v (test 5) or ethanol 75% v/v + f-127 1% w/v clean. The negative control did not remove bacteria nor destroy bacteria. The peroxide + pluronic acid mixture killed all bacteria, dissolved the biofilm and almost completely removed debris (tests 2 and 4). Test 4 was slightly more effective than test 2, but was not statistically significant. Chlorhexidine (test 5) and ethanol (test 6) did kill most of the bacteria, but did not remove any debris from the surface, thereby severely contaminating the surface. The cleaned surface was observed in a scanning electron microscope. The scale bar is 20 microns.

Example 4

Staining of viable and dead bacteria on a decontaminated surface

The titanium surface, contaminated with S.epidermidis bacteria and grown as a biofilm in BHI broth, was removed from the growth medium and immersed in the disinfectant solution for 5 minutes on a slow shaker. 0.2% with A) saline (negative control), B) chlorhexidine w/v or C) H ₂ O ₂ 3%v/v + f-127 pluronic acid 5%w/v sterilized the discs. After cleaning, the surface was stained with a fluorescent dye, with live microorganisms green and dead microorganisms red. The negative control (saline) did not remove any microorganisms nor the biofilm. Chlorhexidine kills all microorganisms but allows dead cells to contaminate the surface. The hydrogen peroxide + pluronic acid mixture killed all microorganisms, dissolved the biofilm and almost completely decontaminated. After cleaning and staining, the surface was observed in a confocal microscope (fig. 4).

Example 5

Regeneration of streptococcus epidermidis after disinfection of contaminated titanium surfaces

Streptococcus epidermidis bacteria (containing a luciferase gene which causes them to fluoresce) are regenerated on the sterilised titanium surface. The surface was first contaminated with bacteria and incubated in BHI broth until the surface was completely covered with biofilm. The titanium plates were then immersed in the disinfectant solution and placed on a slow shaker for 5 minutes. After sterilization, the discs were rinsed with copious amounts of sterile water, then covered again with BHI medium and incubated at 37 ℃. The discs were placed in a fluorometer every one hour to measure the regeneration of bacteria by the amount of fluorescence compared to untreated calibration control and sterile discs. The results show (see FIG. 5B), that D) water containing detergent (SDS 0.1% w/v water, E) water containing 5% pluronic acid and F) brine had minimal disinfection effect, since regeneration of biofilm occurred 3-4 hours after cleaning. On the other hand, 0.2% chlorhexidine killed all bacteria and no regeneration was observed, although dead biofilm adhered and remained on the surface (see fig. 3 and 4). 5%v/v hydrogen peroxide, alone (A) cleans the surface well as seen by a delay of about 13 hours before self-healing by biofilm. However, 3%v/v hydrogen peroxide combined with water containing 5% pluronic acid cleaned the surface significantly better, delaying regeneration for more than 15 hours (see also fig. 5A).

Example 6

Peroxide-containing pluronic is more skin friendly than alcohol-containing hand sanitizer

Using A) Pluronic acid (5%w/v) and hydrogen peroxide (3%v/v) or B) Antibac Pharma containing ethanol and propan-2-ol ^TM The mixture of (1) was used to wash and disinfect the left and right thumbs four times, once a day for five consecutive days. After completion of the day 5 disinfection procedure, both fingers were stained with a print red (iron oxide) solution to observe cracks and fissures in the skin. After dyeing, the fingers were thoroughly washed with soap in warm water, air dried and photographed in the sun. Cracks and fissures in the thumb skin are easily seen as streaky brown staining. After Antibac Pharma ^TM The treated fingers showed deep cracks and fissures and the skin was rough, dry and hard. However, the pluronic-peroxide formulation did not cause damage to the skin of the left thumb, leaving the skin intact and soft. This indicates that the pluronic-peroxide formulation is more biocompatible and tissue friendly than alcohol-based hand sanitizer (fig. 6).

Example 7

Efficacy of the disinfecting solution in removing organic pollutants

To demonstrate the ability of hand sanitizing and cleaning solutions to remove stains and contaminants from skin, a set of products and solutions were tested for permanent ink stains. Permanent blue ink line for finger (Lyreco) ^TM Laboratory permanent marker). Ink was applied with a pen and allowed to air dry for about 5 minutes. The fingers were then cleaned with various disinfecting solutions for about 6 to 8 seconds, simulating the normal application time of hand disinfecting solutions in daily life. The disinfectant was thoroughly wiped off with a paper towel and the fingers were photographed using iPhone X in the sunlight using automatic exposure control. The intensity of the remaining stain was considered as an anti-visual indicator of the cleaning efficacy of the test solution. Finger a) was washed with water only. Finger B) was washed with warm water and soap. Finger C) was washed with 0.2% chlorhexidine and finger D) was washed with Pyripet ^TM (0.1% cetylpyridinium chloride) rinse. Finger E) with Antibac Pharma ^TM (alcohol-based disinfectants containing ethanol and propan-2-ol) clean, finger F) clean with bleach (4% sodium hypochlorite). Fingers G) and H) were rinsed with hydrogen peroxide (1% in water and 5%v/v, respectively). Finger I) was washed in a solution of pluronic acid f-127 in water (5%w/v). Finger J) was sterilized with a mixture of pluronic acid (5%w/v) and hydrogen peroxide (1%v/v). The results show that bleach and hydrogen peroxide are very effective in removing permanent ink stains. However, surprisingly, the most effective stain removal was obtained by combining pluronic acid and weak hydrogen peroxide (fig. 7).

Example 8

For skin disinfection applications, two-compartment dispensing bottles.

The two-component pluronic-peroxide solution described herein is intended for hand disinfection after possible exposure to viral contamination. Viruses are genetic codes (RNA or DNA) enclosed in protein envelopes that protect and transmit genetic information. Most disinfectants only attack (denature or repair) the protein envelope, rendering the virus no longer very infectious, but do not remove the virus itself or attack the viral genome. Both combinations of peroxide and pluronic are available. Peroxides degrade proteins, RNA and DNA, while pluronic also denatures proteins and dissolves organic matter into its micellar structure, thereby thoroughly destroying and removing viral particles and other contaminants and dirt on the skin.

The 500ml distribution bottle is divided into two chambers; one containing 400 ml of 10% w/v aqueous f-127 pluronic acid and one containing 100 ml of 25% v/v aqueous hydrogen peroxide. A pump with two inlets pumps the liquid from the two chambers into the dispenser tip for mixing and administration. As with any other disinfectant, the mixed solution is evenly distributed on the hands, allowed to act for a few seconds, and then rinsed clean under running tap water. No soap needs to be applied, as the liquid itself also acts as a detergent. Clean hands are wiped dry with paper towels or air dried. The solution can be removed without special precautions or actions. The solution is completely harmless after rinsing and will decompose into water, oxygen and carbon dioxide leaving no environmental footprint or influence.

Example 9

For skin disinfection applications, dispensing bottles with lotion.

The 500ml dispense bottle contained two equal portions of the biphasic emulsion. A portion of the emulsion contained f-127 pluronic acid in an oily suspension (10% w/v). Etheric oils or fragrances may be added to obtain a pleasant odour. The other phase contained an aqueous solution containing hydrogen peroxide (10% v/v). Prior to application, the bottle was shaken vigorously and the emulsion mixture was then spread on the hands using a pump with a dispenser tip. Like any other disinfectant, the emulsion is evenly distributed on the hands, allowed to act for a few seconds, and then rinsed clean under running tap water or simply air dried. No soap needs to be applied, as the liquid itself can also be used as a detergent. The solution can be removed without special precautions or actions. The solution is completely harmless after rinsing and will decompose into water, oxygen and carbon dioxide, which has no environmental footprint. The remaining oil will protect the skin from dryness and make it smooth.

Example 10

Application for skin disinfection, blister in blister package

A 1ml blister pack is contained within another 5ml blister pack. The inner blister pack contained hydrogen peroxide (25% v/v), the outer blister pack contained 3ml flavoured water containing f-127 pluronic acid (10% w/v) and the first blister pack. If desired, the inner blister pack is ruptured by the application of manual force and then mixed by squeezing the outer package. After mixing, the outer blister pack was opened and the contents were evenly distributed on the hands, allowed to act for a few seconds just like any other disinfectant was used, and then rinsed clean under running tap water. No soap needs to be applied, as the liquid itself also acts as a detergent. Clean hands are wiped dry with paper towels or air dried. The solution can be removed without special precautions or actions. The solution is completely harmless after rinsing and will decompose into water, oxygen and carbon dioxide without environmental footprint or impact.

Example 11

Application for skin disinfection, wet wipes

A 1ml blister pack is contained within another 5ml blister pack. The inner blister pack contained hydrogen peroxide (25% v/v) and the outer blister pack contained 3ml of flavoured, folded paper towels and first blister pack containing f-127 pluronic acid (10% w/v). If desired, the inner blister pack is ruptured by the application of manual force and then mixed by squeezing the pack. After mixing, the outer blister pack is opened and the paper towel is folded, now activated with a peroxide-pluronic mixture, for wiping the skin, hands or contaminated surfaces to remove dirt, microbial and viral contaminants. No soap needs to be applied, as the liquid itself also acts as a detergent. The clean hands, skin or surface are air dried. The solution can be removed without special precautions or actions. The solution is completely harmless after rinsing, and decomposes into water, oxygen and carbon dioxide, without environmental footprint and damage to the skin.

Example 12

Mouthwash application for oral disinfection, dispensing bottle with emulsion

The two-component pluronic-peroxide solution described herein is intended for use in controlling microorganisms or oral disinfection during a pandemic of infectious virus. Viruses are genetic codes (RNA or DNA) enclosed in protein envelopes that protect and transmit genetic information. Most viral disinfectants only attack (denature or repair) the protein envelope, rendering the virus no longer very infectious, but do not remove the virus itself or attack the viral genome. Both combinations of peroxide and pluronic are available. Peroxides degrade proteins as well as RNA and DNA, while pluronic also denatures proteins and dissolves organic matter into micellar structures, thereby thoroughly destroying and removing viral particles and other microorganisms, contaminants, and mucus in the mouth and throat.

The 1000ml distribution bottle is divided into two chambers; one containing 800 ml of the salt water containing 5%w/v f-127 pluronic acid and sodium fluoride and taste and odor modifiers and one chamber containing 200 ml of water containing 16% v/v hydrogen peroxide. A pump with two inlets is used to pump the liquid from the two chambers into the dispenser tip for mixing and application. The 10 ml mixed solution was used to rinse the mouth and throat for about 1 minute and then expectorated in a sink. No brushing or rinsing with water is required after application, since the liquid itself is not harmful to the human body, but it is not harmful. The solution can be removed without special precautions or actions. The solution is completely harmless after rinsing and decomposes into water, oxygen and carbon dioxide with no environmental footprint or health impact.

Mouthwashes can also be used to prevent oral infections, periodontitis and peri-implantitis and dental caries, both for prophylactic use and for post-operative infection control and maintenance treatment following periodontal or implant-related procedures. It can also be used to clean toothbrushes and intraoral devices (dentures, anti-snoring devices, orthodontic appliances, etc.) to avoid re-infection from repeated use.

Example 13

Nasal/sinus irrigation solution

Disposable bottle with applicator for nasal and sinus irrigation fluid applications

The two-component pluronic-peroxide solutions described herein are intended for nasal/sinus irrigation to prevent congestion from rhinovirus infection, or for virus removal during an infectious influenza or coronavirus pandemic. Viruses are genetic codes (RNA or DNA) enclosed in protein envelopes that protect and transmit genetic information. Most viral disinfectants only attack (denature or repair) the protein envelope, rendering the virus no longer very infectious, but do not remove the virus itself or attack the viral genome. Both combinations of peroxide and pluronic are available. Peroxides degrade proteins as well as RNA and DNA, while pluronic also denatures proteins and dissolves organic matter into micellar structures, thereby thoroughly destroying and removing viral particles and other contaminants and mucus in the nasal cavity and sinuses.

50ml of hydrogen peroxide (5%v/v in saline) was added to a 250ml disposable soft (squeezable) bottle with a nasal applicator top containing 200 ml of 1.25% w/v saline containing f-127 pluronic acid and mixed by vigorous shaking. The head was placed over the sink and the bottle containing the mixture was then placed against one nostril and carefully squeezed until the liquid flowed out of the other nostril and into the sink below. This procedure was repeated until the bottle was empty. Blowing nose after the application is finished. After the application, the liquid does not need to be washed and is harmless to human bodies. The solution can be removed without special precautions or actions. The solution is completely harmless after rinsing and decomposes into water, oxygen and carbon dioxide without environmental footprint or health impact.

Nasal/sinus irrigation solutions may also be used to treat nasal infections or acute and chronic sinusitis. The solution can also be used prophylactically and for post-operative infection control following ear-nose-throat procedures.

Claims

1. A composition comprising an antimicrobial and/or antiviral mixture consisting of:

(a)H ₂ O ₂ final concentration of 3.0 to 7.0% v/v, and

(b) Poloxamer, at a concentration of 0.1 to 10.0% w/v.

2. The composition of claim 1, wherein the concentration of poloxamer is between 1.0 and 5.0% w/v.

3. The composition of claim 2, wherein the concentration of the poloxamer is up to 5.0% w/v.

4. The composition of any of the preceding claims, where component (b) is a composite hydrogel formulation.

5. The composition of any one of the preceding claims, wherein the poloxamer is a mixture of poloxamers.

6. A composition according to any preceding claim, wherein component (b) is selected from the group consisting of pluronic acid, gamma-aminobutyric acid, and combinations thereof,

F-127 and poloxamer 407.

7. A composition according to any preceding claim, wherein H of component (a) is ₂ O ₂ 3.0% v/v.

8. The composition of any of the preceding claims, wherein component (a) and component (b) are provided in a 1:1 ratio.

9. The composition of any one of the preceding claims, further comprising water and/or physiological saline.

10. A composition according to any preceding claim, wherein component:

(a)H ₂ O ₂ and are and

(b) A poloxamer,

are kept separate from each other prior to use.

11. The composition of any one of the preceding claims, further comprising an additional biologically active substance.

12. The composition of claim 11, wherein the biologically active substance is selected from the group consisting of EMD, peptides, drugs, biologically active ions, such as fluoride ions, small molecules, radioactive molecules, antimicrobial molecules, and radiopaque molecules, or any combination thereof.

13. A composition according to any preceding claim, further comprising an additional antimicrobial material.

14. Composition according to any one of the preceding claims, wherein the composition has a shelf life of at least 1 year at room temperature.

15. A method of disinfecting, sterilising, disinfecting and/or decontaminating a biological surface and/or a biomaterial surface comprising applying the composition according to any one of claims 1 to 14 to the biological surface and/or biomaterial surface.

16. A method of cleansing the skin and/or mucous membranes of a subject of microorganisms comprising applying the composition according to any one of claims 1 to 14 to the skin and/or mucous membranes of a subject.

17. The method of any one of claims 15 and 16, wherein the microorganism comprises a bacterium or a virus or both.

18. The method of claim 17, wherein the microorganism comprises a riboviral domain.

19. The method of claim 17, wherein the microorganism comprises a coronaviridae, orthomyxoviridae, caliciviridae, or reoviridae, or any combination thereof.

20. The method of claim 17, wherein the microorganism comprises the orthocoronaviridae subfamily.

21. The method of claim 17, wherein the microorganism comprises a coronavirus, rotavirus, norovirus or influenza a virus, influenza b virus, influenza c virus or influenza d virus, or any combination thereof.

22. The method of claim 17, wherein the microorganism comprises Sars-Cov-2.

23. The method of any one of claims 1 to 14, wherein the composition is incorporated into a hand sanitizer, a mouthwash, a nasal cleansing solution, a sinus cleansing solution, or a skin cleansing solution.