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WO2021186000A1 - Composition liquide améliorée pour le nettoyage, l'assainissement et/ou la désinfection - Google Patents

Composition liquide améliorée pour le nettoyage, l'assainissement et/ou la désinfection Download PDF

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Publication number
WO2021186000A1
WO2021186000A1 PCT/EP2021/057024 EP2021057024W WO2021186000A1 WO 2021186000 A1 WO2021186000 A1 WO 2021186000A1 EP 2021057024 W EP2021057024 W EP 2021057024W WO 2021186000 A1 WO2021186000 A1 WO 2021186000A1
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WIPO (PCT)
Prior art keywords
composition according
pluronic
antimicrobial
composition
sanitizing
Prior art date
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PCT/EP2021/057024
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English (en)
Inventor
Ståle Petter LYNGSTADAAS
Håvard J. HAUGEN
Original Assignee
Corticalis As
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from EP20164065.3A external-priority patent/EP3881901A1/fr
Application filed by Corticalis As filed Critical Corticalis As
Priority to JP2022554494A priority Critical patent/JP2023518701A/ja
Priority to KR1020227035200A priority patent/KR20230006463A/ko
Priority to BR112022018324A priority patent/BR112022018324A2/pt
Priority to CA3170947A priority patent/CA3170947A1/fr
Priority to CN202180033519.8A priority patent/CN115605269A/zh
Priority to AU2021238760A priority patent/AU2021238760A1/en
Publication of WO2021186000A1 publication Critical patent/WO2021186000A1/fr
Priority to US17/939,570 priority patent/US20230020320A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/22—Peroxides; Oxygen; Ozone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/90—Block copolymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/005—Antimicrobial preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/10—Washing or bathing preparations

Definitions

  • compositions described herein inhibit microbes and inflammation in a subject and are particularly useful for dermal sanitizing, oral-laryngeal sanitizing, nasal sanitizing, in oral prophylaxis and periimplantitis treatment, implant health maintenance, in periodontitis and periodontal health, in wound care or chronic ulcer care.
  • Biological surfaces like skin and mucosa and/or biomaterial surfaces are in constant contact with and frequently colonized by a plethora of microorganisms and virus. They therefore frequently require cleaning and/or sanitizing with compositions that are antibacterial and/or antiviral without causing harm to the biological tissue in question and preferably without causing microbial and/or viral resistance.
  • the skin of the body such as but not limited to on the hands, the feet, or the face is often exposed to microorganisms and needs to be cleaned, sterilized and/or sanitized regularly to inhibit settlement and/or transfer of pathogens and/or microbes and/or viruses.
  • a hand sanitizer is a liquid or gel, typically used to decrease infectious agents on the hands.
  • Formulations of the alcohol-based type are preferable to hand washing with soap and water in most situations in the healthcare setting. It is generally more effective at killing microorganisms and often better tolerated than soap and water. They are typically available as liquids, gels, wipes and/or foams.
  • Alcohol-based versions typically contain some combination of isopropyl alcohol, ethanol (ethyl alcohol), or n-propanol. Versions that contain 60 to 95% alcohol are considered most effective. Hand sanitizers containing at least 60% alcohol or containing a "persistent antiseptic" kill many different kinds of bacteria, including antibiotic resistant bacteria and TB bacteria, but are less effective against virus.
  • alcohol-based hand sanitizers inhibit a variety of microorganisms but not spores. Some versions contain compounds such as glycerol to prevent drying of the skin. Non- alcohol-based versions may contain benzalkonium chloride, chlorhexidine gluconate or triclosan. Care should be taken as they are flammable.
  • Alcohol-based hand sanitizers have been commonly used in Europe since at least the 1980s.
  • the alcohol-based version is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system.
  • the wholesale cost in the developing world is about US$1.40-3.70 per bottle.
  • Alcohol rub sanitizers which kill most bacteria, and fungi, and stop some viruses.
  • Alcohol rub sanitizers containing at least 70% alcohol (mainly ethyl alcohol) kill 99.9% of the bacteria on hands 30 seconds after application and 99.99% to 99.999% in one minute. Still, they are notably less effective against virus.
  • 90% alcohol rubs are more effective against viruses than most other forms of hand washing. Isopropyl alcohol will also kill 99.99 % or more of all non-spore forming bacteria in less than 30 seconds, both in the laboratory and on human skin. 90% alcohol rubs are highly flammable and have a potential for abuse, but are necessary to use to kill especially viruses, including enveloped viruses such as the flu virus, the common cold virus, coronaviruses, and HIV, though is notably ineffective against the rabies virus.
  • Hydrogen peroxide is a very pale blue liquid which appears colourless in a dilute solution, slightly more viscous than water. It is a weak acid. It has strong oxidizing properties and is therefore a powerful bleaching agent that is mostly used for bleaching paper but has also found use as a disinfectant and as an oxidizer. Hydrogen peroxide in the form of carbamide peroxide is widely used for tooth whitening (bleaching), both in professionally- and in self-administered products.
  • Hydrogen peroxide is unstable and slowly decomposes in the presence of light. Because of its instability, hydrogen peroxide is typically stored with a stabilizer, typically organophosphates, sodium pyrophosphate, sodium phytate or sodium citrate, in a weakly acidic solution in a dark coloured bottle. Hydrogen peroxide may be used for the sterilization of various surfaces, including surgical tools and may be deployed as a vapour (VHP) for room sterilization. H2O2 demonstrates broad-spectrum efficacy against virus and microbes including, but not limited to, bacteria, yeasts, and bacterial spores.
  • Hydrogen peroxide is seen as an environmentally safe alternative to chlorine-based bleaches, as it degrades to form oxygen and water and is generally recognized as safe as an antimicrobial agent by the U.S. Food and Drug Administration (FDA).
  • FDA Food and Drug Administration
  • Pluronics® or poloxamers are tri-block copolymers of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO).
  • PEO-PPO-PEO poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)
  • This group of synthetic polymers is thermo- reversible in aqueous solutions. The sol-gel transition is governed by the composition, molecular weight and concentration of each constituent block polymer.
  • the hydrophilic ethylene oxide and the hydrophobic propylene oxide give pluronics an amphiphilic structure - meaning it has a polar, water-soluble group attached to a nonpolar water-insoluble hydrocarbon chain.
  • Amphiphilic block copolymer molecules self-assemble into micelles (a packed chain of molecules) in aqueous solution. Micelle formation is temperature dependent and affects the degradation properties of the biomaterial: below a certain characteristic temperature, known as the critical micelle temperature, both the ethylene and
  • Pluronics can be found either as liquids, pastes or solids. Due to their amphiphilic characteristics (presence of hydrophobic and hydrophilic components), pluronics possess surfactant properties which allow them to interact with hydrophobic surfaces and biological membranes. Being amphiphilic also results in the ability of the individual block copolymers, known as unimers, to combine and form micelles in aqueous solutions. When the concentration of the block copolymers is below that of the critical micelle concentration (CMC), the unimers remain as molecular solutions in water. However, as the block copolymer concentration is increased above the CMC, the unimers will self-assemble and form micelles, which can take on spherical, rod-shaped or lamellar geometries. Their shapes depend on the length and concentration of the block copolymers (i.e. EO and PO), and the temperature. Micelles usually have a hydrophobic core, in this case the PO chains, and a hydrophilic shell, the EO chains.
  • Pluronic F-127 also known as Poloxamer 407
  • Pluronic F-127 is often used in tissue engineering because of the commercial availability of a consistent product that will undergo a sol-gel transition near physiological temperature and pH.
  • a disadvantage of Pluronic F-127 is its fast degradation rate in vivo. To overcome this problem, Pluronic F-127 is frequently crosslinked with another a-hydroxy or amino acid in order to alter the chemical structure of its depsipeptide unit.
  • thermo-sensitive hydrogels which are typically stabilized by addition of high-molecular-weight acids, such as hyaluronic acid.
  • the need for additional cleaning and/or sterilizing and/or debriding compositions which can be used to disinfect, sterilize or clean, prevent fouling and/or refouling of a fouled biological surface and/or a biomaterial surface, such as the mucosa of the oral or nasal cavity of a subject, or the exposed outer skin of a subject, such as hands and feet, is manifest.
  • aspects of the present invention relate to an antimicrobial and/or anti-viral composition for cleaning and/or sterilizing a biological surface and/or a biomaterial surface e.g. in situ, comprising at least two components:
  • composition of the present invention comprises an antimicrobial and/or anti viral mixture consisting of:
  • an antimicrobial and/or anti-viral composition as disclosed herein comprises a composite hydrogel formulation of component (b), which is a poloxamer, such as pluronic acid at a concentration of 0.1-5%w/v, such as at a concentration of at the most 5%w/v, such as at a concentration of between 1 0%-5.0% w/v, such as 0.1 , 0.5, 1.0 or 1 5%w/v.
  • component (b) can be selected from the group consisting of pluronic acid, Pluronic® F-127 and Poloxamer 407. In a presently preferred aspect, the poloxamer is Poloxamer 407.
  • An antimicrobial and/or anti-viral composition in some alternatives further comprises a H2O2 of component (a), which has a final concentration of 0.1-7%v/v, such as a final concentration of 0, 5-3,0 %v/v.
  • the H202 of component (a) has a final concentration of 3% v/v.
  • component (a) and component (b) are provided in a 1:1 ratio.
  • An antimicrobial and/or anti-viral composition in some alternatives can further comprise water and/or physiological saline, oils, preservatives flavors and/or fragrances.
  • an antimicrobial and/or anti-viral composition comprises the at least two components:
  • an antimicrobial and/or anti-viral composition comprises a separate component (a), which is a composition that comprises H2O2 at a concentration of at least 10- 50%v/v.
  • composition according to some alternatives can further comprise an additional antimicrobial substance.
  • a composition according to some alternatives can further comprise a bioactive substance, typically selected from the group consisting of peptides, drugs, bioactive ions, small molecules, radioactive molecules, and radio-opaque molecules or any combination thereof.
  • a composition according to some alternatives typically has a shelf-life of at least 1 years at room temperature (RT).
  • a composition according to some alternatives is useful for sterilizing or sanitizing or cleaning a biological surface and/or a biomaterial surface in situ.
  • compositions described herein can be used to clean, sterilize, or otherwise rid the skin and/or mucosa of a subject, preferably a human, from microbes, including but not limited to bacteria or virus, such as Riboviria, Coronaviridae, or Orthocoronavirinae.
  • compositions described herein are used to clean or sterilize skin and/or mucosa from a Coronavirus, such as SARS-CoV-2.
  • aspects of the present invention relate to the application of one or more of the antimicrobial and/or anti-viral compositions described herein as a hand wash, oral wash and/or for nasal and/or sinus cleansing, so as to remove, sterilize, or inhibit a Coronavirus, such as SARS-CoV-2 from the skin or mucosa of a subject, preferably a human.
  • a Coronavirus such as SARS-CoV-2
  • compositions described herein for cleaning and/or sanitizing a biological surface and/or a biomaterial surface, such as in particular an implant in situ and/or a surface in the oral cavity and/or any surface covered by skin or mucosa.
  • compositions described herein are incorporated in a kit, wherein the at least two components, H2O2 and pluronic acid, are optionally kept separate such that a user may mix the two components just prior to application.
  • the invention consequently also relates to a method of sanitizing, sterilizing, disinfecting and/or decontaminating a biological surface and/or a biomaterial surface comprising applying the composition according to the present invention to a biological surface and/or a biomaterial surface, as well as a method of cleaning skin and/or mucosa of a subject from microbes comprising applying the composition according to the present invention to the skin and/or mucosa of a subject.
  • the microbes comprise bacteria or virus or both, such as, but not limited to Riboviria, Coronaviridae, Orthomyxoviridae, Caliciviridae or Reoviridae or any combination thereof.
  • the microbes comprise Orthocoronavirinae, such as, but not limitted to Coronavirus, Rotavirus, Norovirus or Influenza virus type A, B, C or D or any combination thereof.
  • compositions and methods to clean and/or sanitize a biological surface and/or a biomaterial, such as an implant surface is provided.
  • a biological surface refers to any surface covering an anatomical structure and/or tissue, such as skin including palmar and plantar skin, oral and nasal mucosa, gastrointestinal mucosa, laryngeal, tracheal and bronchial mucosa, vaginal mucosa, penile mucosa, hair, nails, fasciae, membranes, synovial membranes, dental enamel or dental cementum.
  • the term also encompasses a wound surface, such as in, on and/or surrounding, but not limited to, an ulcer, acute wound, wound from trauma, surgical wound, puncture wound, abrasive wound, infected wound including herpes ulcer, papilloma, chancre and acne, erosive wound, burn, blister, scab, leg ulcer, diabetic ulcer and/or chronic ulcer.
  • a wound surface such as in, on and/or surrounding, but not limited to, an ulcer, acute wound, wound from trauma, surgical wound, puncture wound, abrasive wound, infected wound including herpes ulcer, papilloma, chancre and acne, erosive wound, burn, blister, scab, leg ulcer, diabetic ulcer and/or chronic ulcer.
  • biomaterial or implant surface typically refers to a surface of a medical and/or dental implant.
  • the term “medical implant” includes within its scope any device intended to be implanted into and/or attached to the body of a vertebrate animal, in particular a mammal such as a human, for preservation and restoration of the function of the body, particularly a prosthesis of any kind, metallic and polymer-based implants in the vascular system or in the musculoskeletal system or in joints and bones, including for alleviation of pain in these structures.
  • Non-limiting examples of medical implants are leg, arm and hand prosthesis, facial prosthesis, eye prosthesis, ileostomy devices, intrauterine devices, pacemakers, electrodes, artificial vascular structures, stents, cochlear implants, hip-joint prostheses, knee prostheses, elbow prostheses, finger prostheses, cochlear prostheses, or fixation screws.
  • the term “dental implant” includes within its scope any device intended to be implanted into the oral cavity of a vertebrate animal, in particular a mammal such as a human, for example in tooth and jaw restoration procedures.
  • Dental implants are herein selected from the group consisting of: Implants, bars, bridges, abutments, crowns, caps, dental fillings and prosthetic parts in the oral cavity. Dental implants may also be denoted as dental prosthetic devices.
  • a dental implant is composed of one or several implant parts.
  • a dental implant usually comprises a dental fixture coupled to secondary implant parts, such as an abutment and/or a dental restoration such as a crown, bridge or denture.
  • any device, such as a dental fixture, intended for implantation may alone be referred to as an implant even if other parts are to be connected thereto.
  • biomaterial surface includes the surface of any medical device or tool, disposable or not, designed to come in temporary contact with living tissue, such as, but not limited to, surgical instruments, electrodes, scalpels, probes and gauges, catheters, syringes, scissors, needle holders, contact lenses, wound dressings, band aids, transdermal fixing devices, and/or diagnostic tools like ultrasound devices, x-ray machines and/or imaging equipment, e.g. various scopes, surgical cameras, impression materials or intraoral scanners.
  • any medical device or tool disposable or not, designed to come in temporary contact with living tissue, such as, but not limited to, surgical instruments, electrodes, scalpels, probes and gauges, catheters, syringes, scissors, needle holders, contact lenses, wound dressings, band aids, transdermal fixing devices, and/or diagnostic tools like ultrasound devices, x-ray machines and/or imaging equipment, e.g. various scopes, surgical cameras, impression materials or intraoral scanners.
  • peroxide is used interchangeably with Hydrogen peroxide and/or (H2O2).
  • a microorganism, or microbe is a microscopic organism, which may exist in its single-celled form or in a colony of cells. Microorganisms include all unicellular organisms and so are extremely diverse. All of the Archaea and Bacteria are microorganisms (Prokaryotes). Some protists are related to animals and some to green plants. Many of the multicellular organisms are microscopic, namely micro-animals, some fungi and some algae.
  • An antimicrobial is an agent that kills microorganisms or stops or inhibits their growth.
  • Antimicrobial medicines can be grouped according to the microorganisms they act primarily against. For example, antibiotics are used to treat or inhibit bacteria, and antifungals are used to treat or inhibit fungi. They can also be classified according to their function. Agents that kill microbes are microbicidal, while those that merely inhibit their growth are called biostatic both are included in the term” antimicrobial”.
  • the use of antimicrobial medicines to treat or inhibit infection is known as antimicrobial chemotherapy, while the use of antimicrobial medicines to prevent infection is known as antimicrobial prophylaxis.
  • a virus is a small infectious agent that replicates only inside the 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 medication used specifically for treating or inhibiting viral infections rather than bacterial ones. Most antivirals are used for specific viral infections, while a broad-spectrum antiviral is effective against a wide range of viruses. Unlike most antibiotics, most antiviral drugs do not destroy their target pathogen; instead they inhibit their replication and/or development.
  • Antiviral drugs are one class of antimicrobials, a larger group which also includes antibiotic (also termed antibacterial), antifungal and antiparasitic drugs, or antiviral drugs based on monoclonal antibodies. Most antivirals are considered relatively harmless to the host, and therefore can be used to treat or inhibit infections. They should be distinguished from viricides, which are not medication but deactivate or destroy virus particles, either inside or outside the body. Natural antivirals are produced by some plants such as eucalyptus or Australian tea trees.
  • antimicrobial refers to a composition that is effective against microbes and virus.
  • one or more of the compositions described herein are antimicrobial, e.g., antibacterial or antiviral, a bactericide or a viricide.
  • 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 limitations of the measurement system.
  • Figure 1 Gel boundaries for aqueous saline (physiological conditions) solutions of copolymer F-127.
  • the filled circles are data points obtained by the tube inversion method for the mixture.
  • the unfilled squares are data points from rheometric analyses.
  • the chart clearly indicates that pluronic concentrations below 15% w/v in saline remains fluid independent of temperature. Fluid pluronic solutions form independent micelles, but the concentration is not high enough for the pluronic micelles to assemble into a cubic gel. Thus, low pluronic concentrations that allow for micelle formation but stay liquid and act as detergent may be good for tissue-friendly cleaning of biological surfaces, but addition of other reactants that can contribute to the decontamination is expected to completely disrupt the micelle formation.
  • FIG. 2 Schematic drawing depicting the synergistic effects from mixing pluronic with peroxide.
  • the peroxide generates active oxygen (ROS) degrade microbial and viral nucleic acids and membranes, and kills bacteria, including anaerobes, and viruses.
  • ROS active oxygen
  • the peroxide also drives pluronic micelle dissolution that is countered by the strong tendency of pluronic to form micelle structures.
  • the dynamic equilibrium between solubilized and micelle pluronic allow for an active entrapment of dirt, organics and contaminants into the micelle structure.
  • the liquid hydrophilic nature of the pluronic hydrogel also promotes easy access for the ROS to wrinkles and crevices, unhindered by foaming.
  • the pluronic hydrogel moisture the skin and the oxygen released from the peroxide helps the wound to heal.
  • the ROS also has the ability to clean and reactivate (make the surface hydrophilic) titanium, one of the most widely used metal in medical and dental implants.
  • the effect of ROS alone is too brief to have a significant impact on these processes and would not remove the contaminants or provide moisture.
  • Pluronic alone for stable micelles that is far less effective in contaminant entrapment and do not kill microbes or degrade viral nucleic acids.
  • Mixed together in the right concentration pluronic micelle formation is more dynamic, moistening and oxygenation is optimized, and the peroxide action is prolonged and increased and kept at the surface where it is needed.
  • FIG. 3 Titanium surfaces contaminated with S. Epidermidis bacteria was cleaned with growth medium (BHI, Negative control), H202 5% v/v + f-127 1% w/v (Test 2), H202 5% v/v + f-1277% w/v (Test 4), Chlorhexidine 0,2% w/v + f-1277% w/v (Test 5) or Ethanol 75% v/v + f-127 1% w/v.
  • the negative control did not remove the bacteria, nor was the bacteria destroyed.
  • the peroxide + pluronic acid mix killed all bacteria, dissolved the biofilm and removed the debris almost completely (Tests 2 & 4). Test 4 was slightly, but not statistically significant, more effective than Test 2.
  • Chlorhexidine (Test 5) and Ethanol (Test 6) did kill most of the bacteria but did not remove any debris from the surface, leaving the surfaces heavily contaminated. Surfaces visualized after cleaning in a scanning electron microscope. Scale bar is 20 micrometres.
  • FIG. 5 Regrowth of S. Epidermidis bacteria, harbouring the luciferase gene making them fluorescent, on sanitized titanium surfaces.
  • Hydrogen peroxide, 5% v/v, alone (A) cleaned the surface well as seen by a delay of about 13 hours before the biofilm restored itself. However, hydrogen peroxide 3% v/v combined with 5% pluronic acid in water cleaned the surface significantly better, delaying regrowth with more than 15 hours.
  • Figure 6 Left and right thumbs were sanitized four times daily for five consecutive days with a mix of A) pluronic acid (5% w/v) and hydrogen peroxide (3% v/v) or B) Antibac PharmaTM containing ethanol and propan-2-ol respectively. After the sanitizing period both fingers were stained with iron oxide to visualize fissures and cracks. Fissures and cracks are easily visible as brown striated stains on the Antibac PharmaTM treated thumb, whereas the pluronic-peroxide formulation caused no harm to the skin of the left finger.
  • Fingers were marked with a line of permanent ink from a laboratory marker that was subsequently washed off with various sanitizing/decontaminating solutions to visualize their ability to remove contaminants from the skin.
  • Finger A was washed only with water.
  • Finger B was cleaned with warm water and soap.
  • Finger C) was cleaned with 0,2% chlorhexidine and finger D) was rinsed with PyrispetTM (0,1% cetyl-pyridinium chloride).
  • Finger E) was cleaned with Antibac PharmaTM (Alcohol based sanitizer), finger F) was cleaned with bleach (4% Sodium hypochlorite).
  • Fingers G) and H) were rinsed with hydrogen peroxide (1% and 5% v/v in water respectively).
  • Finger I was washed in a solution of pluronic acid in water (5% w/v).
  • Finger J was sanitized with a mix of pluronic acid (5% w/v) and hydrogen peroxide (1% v/v). The results show that bleach and hydrogen peroxide is effective in removing the ink stain, but that the most efficient cleaning is obtained by the combination of pluronic acid and hydrogen peroxide.
  • compositions which effectively clean, disinfect and/or sanitize a biological surface and/or a biomaterial surface e.g., including but not limited to skin or mucosa, such as a surface in the oro- laryngeal or nasal cavity. Any one or more of the compositions described herein are useful for the rapid and effective treatment or inhibition of bacteria or virus or both essentially without leaving contaminating material residues.
  • compositions are water soluble and easy to rinse off, tissue-friendly non-ionic surfactant. These compositions comprise a non-toxic formulation of well-studied active ingredients in clinical use, which is particularly suitable for injectable, oral and/or cutaneous applications.
  • the herein for the first time described composition is proven to be non-sensitizing and non-irritating in clinical tests.
  • the compositions described herein are compatible with most other therapeutic agents useful against biofouling and inflammation.
  • compositions described herein have a liquid state at room temperature that allows trouble-free mixing and application.
  • the compositions have an easy flowing liquid consistency with a surfactant effect that allows the compositions to reach difficult places when applied into narrow crevices, defects and/or folds on skin and/or mucosa.
  • compositions described herein mimic the natural release of reactive oxygen species (ROS) from peroxide produced by human cells.
  • ROS reactive oxygen species
  • the charge from the reactive oxygen destroys microbial membranes and the oxygen itself is also toxic to anaerobic bacteria.
  • the human cells themselves are protected against ROS by enzymes in their cell membrane and the local tissue can benefit from the increase in oxygen. Microbes have no such protection, nor can they develop resistance because of fundamental differences in their cell-membrane design.
  • the composition can effectively dissolve biofilm, debris and mineral deposits, as well as, dissolve extracellular organics at the application site.
  • the use of the herein presented compositions also remove carbon contamination from a titanium containing implant surface and reactivate the titanium dioxide layer of the implant. This process re-establishes the original charge and hydrophilicity of the implant, restoring its optimal biological surface properties. This is a factor for further survival, or even successful reintegration, of said treated implant.
  • the present compositions provide an advanced micelle forming gel formulation that works in synergy with natural occurring oxygen to break down and remove biofouling, eliminate microbes, keep tissue and implant moist and reactivate titanium implant surfaces.
  • the hydrogel component of the compositions and the active oxygen work in synergy to avoid foaming from oxygen release and to keep activated oxygen in place at the surface for a prolonged biological and chemical effect.
  • the use of any one or more of the compositions set forth herein provides moisture and allows the charged oxygen to work without risk of drying out skin, tissue and/or implant surfaces, during which the active oxygen eradicates microbes that are then suspended and entrapped inside the micelle-forming hydrogel.
  • Organic contaminants are in turn denatured by the strong detergent effect, broken down by the active oxygen and dissolved and entrapped in the hydrogel. Both hydrogel and oxygen reduce inflammation and support tissue health. The active oxygen released in turn strengthens the cellular defence network.
  • the gel and the active oxygen both removes contaminants, acts as an antimicrobial and viricidal agent and reactivates a titanium implant surface.
  • the interaction between the pluronic micelle formation and peroxide potentiates micelle formation and increases the cleaning effect significantly.
  • compositions provide a novel formula of a biocompatible hydrogel- peroxide combination with strong, antimicrobial, viricidal and non-ionic detergent properties with improved micelle dynamics for solubilization and entrapment of debris and microbes for effectively cleaning, sanitizing, sterilizing and/or debriding a biological surface and/or a biomaterial surface in situ. It is easily rinsed off with a towel, wipe or by water, but it can also be left to air-dry and will completely decompose to water, oxygen and carbon dioxide.
  • compositions provide a novel and improved approach to cleaning, sanitizing, sterilizing and/or disinfecting skin, mucosa and/or implant surfaces.
  • any one or more of the compositions described herein are incorporated into a mouth wash and/or nasal rinse and these formulations can be used to prevent, treat, inhibit, or ameliorate, an oral and / or nasal disease (e.g., dental caries, periodontitis, gingivitis, mucositis, peri-implantitis, sinusitis and/or rhinitis).
  • said mouth rinses and/or nasal rinses can be used in methods to inhibit bacterial or viral infections, such as SARS-CoV-2 in the oral or nasal mucosa of a subject, such as a human.
  • the desired formulations set forth herein are based on the combination of hydrogen peroxide (H2O2) and pluronic acid in such a concentration that the resulting composition is in a watery liquid form at physiological temperatures.
  • H2O2 component of the composition can either be in the form of a concentrate (at a concentration of at least 10-50%v/v.) in a separate vial for mixing immediately before use, or provided as an emulsion or dissolved directly into a hydrogel, said hydrogel at least partly consisting of pluronic acid and water and/or physiological saline, with a typical final concentration of 0.5 - 7%.
  • the pluronic component itself can be any one or a combination of the pluronic acids, e.g. the F-127 variety.
  • the concentration of pluronic acid is typically 0.1-10% w/v, such as 0.1-7% w/v, such as 0.1 -2.5% w/v. That is, the concentration of pluronic acid in any one or more of the compositions described herein can be 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 that is within a range defined by any two of the aforementioned percentages.
  • Pluronic-acid works both as solubilizer and detergent in the composition disclosed herein, as well as a moisturizer.
  • the hydrogel formulation establishes a dynamic micelle forming solution. This dynamic state facilitates efficient solubilization and entrapment of particles, microbes and pollutants during the cleaning procedure (see e.g. Figure 2).
  • the present innovation is based on a synergetic effect between pluronic acid and peroxide.
  • Pluronic acid has an ability to form micelles. This ability usually increases with increasing temperature and is shifted toward a gel state at physiological conditions (such as at >20 degrees Celsius).
  • the peroxide addition allows the pluronic acid to stay in the liquid state even at physiological temperature.
  • the micelles are more dynamic and less stable and in a “dynamic” equilibrium with the peroxide radical activity even under high temperature.
  • the micelle transitions dissolve and entrap organic contamination that are then removed when the gel dries off, is wiped off, or washed off.
  • the addition of hydrogen peroxide to the pluronic acid in the compositions described herein increases the temperature at when gelation occurs e.g., that the pluronic gel, containing low concentrations of peroxide, is liquid at room temperate and thus can be applied through a syringe needle or from a dispenser bottle without clogging the nozzle.
  • pluronic acid alone because it starts forming a stable “packed micelle” gel already at room temperature, even at low concentrations when in narrow compartments and/or at the “vapor front” at the nozzle of the dispenser,, thus is very hard to squeeze through a narrow tip of a syringe, or a pump applicator from a dispenser bottle pluronic gel for wound care is therefore sold as gel in a box or a tube.
  • the increased effect from the combination of peroxide and pluronic acid was unexpected and surprising.
  • the liquid formulation of the pluronic hydrogel in combination with peroxide also assists during application. It enables the cleaning and/or sanitizing composition to reach folds, wrinkles, crevices, fissures, narrow spaces and/or undercuts that a pluronic gel alone cannot reach because of its gel forming nature making it viscous at physiological temperatures. Thus, it is more efficient in cleaning rough (implant) surfaces, narrow spaces such as folds, fissures and wrinkles on skin and mucosa and between teeth.
  • compositions which can be used for cleaning, sanitizing, sterilizing, disinfecting and/or decontaminating a biological surface and/or a biomaterial surface in situ.
  • the aforementioned compositions comprise two components: a. H2O2 at a final concentration of between 0.1 - 7 %v/v, and b. a composite hydrogel formulation of pluronic acid at a concentration of 0.1 - 10%w/v.
  • the final concentration of H2O2 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 that is within a range defined by any two of the aforementioned percentages.
  • 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%, 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 that is within a range defined by any two of the aforementioned percentages.
  • said compositions are formulated so that they remain a liquid at physiological temperatures, such as at a temperature of at the most 40°C, such as at a temperature between 20-40 , such as at 37°C e.g., 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, or 40°C or at a temperature that is within a range defined by any two of the aforementioned temperatures.
  • compositions are characterized in that they comprise a low concentration of pluronic acid, which allows the composition to be in a liquid state in high temperature instead of in a gel-state, which a desirable feature for it to be usable for cleaning, sanitizing, sterilizing, disinfecting and/or decontaminating a biological surface and/or a biomaterial surface in situ.
  • the liquid state of the hydrogel is desired when the composition is incorporated into a hand sanitizer, hand wash, oral wash and/or for nasal and/or sinus cleansing solution, in particular for washing virus off of skin and mucosa.
  • compositions comprise the at least two components (a) and (b) in such a ratio that the composition is in a liquid state at physiological temperatures instead of in a more viscous or gel-like state.
  • Typical ratios of concentrations between component (a) and component (b) are approximately 1 :1 (concentration of H2O2: concentration of pluronic acid).
  • concentration of H2O2 concentration of pluronic acid
  • the higher the concentration of the pluronic acid the higher the concentration of the H2O2 is needed to keep the composition in a liquid state at temperatures of between 25-40°C.
  • too high concentrations of peroxide will destroy the pluronic acid amphiphilic properties and disrupt micelle formation, rendering it useless as a detergent and/or a desaturating agent.
  • the composite hydrogel formulation of component (b) comprises pluronic acid at a concentration of 0.1-10%w/v, such as at a concentration of 10% w/v, such as of 0.1 , 0.5, 1 ,
  • the composite hydrogel formulation of component (b) comprises pluronic acid at a concentration of at the most 10% w/v, such as at the most 0.1 , 0.5, 1 , 1.5, 2, 2.5, 3,
  • An antimicrobial and/or anti-viral composition according to the present invention can be a composition wherein the H2O2 of component (a) has a final concentration of 0.1-7%v/v, such as 0.5-3%v/v, such as 0.1-5%v/v. In one embodiment, the H2O2 of component (a) has a final concentration of no more than 7 %v/v, such as 0.1-7%v/v, such as 1, 2, 3, 4, 5, 6 or 7 %v/v.
  • An antimicrobial and/or anti-viral composition according to the present invention can further comprise water and/or physiological saline.
  • the two components of the antimicrobial and/or anti-viral composition according to the present invention can be in one solution or the at least two components can be kept separate from each other such that they can be simultaneously mixed and applied to a biological surface and/or a biomaterial surface in situ.
  • the separate component (a) can be a composition that comprises H2O2 at a concentration of at least 10- 50%v/v, such as at the most 10, 20, 30, 40 or 50% v/v.
  • a composition of the present invention comprises H2O2 at a concentration of 30%v/v.
  • Emulsifier(s) and/or viscosity modifier(s) are examples of Emulsifier(s) and/or viscosity modifier(s)
  • the antimicrobial and/or anti-viral composition according to the present invention further comprises one or more emulsifier(s) and/or viscosity modifier(s).
  • Said emulsifier and/or viscosity modifier may be selected from the group consisting of glycerine, glycols, polyethylene glycols (PEG), polyoxyethylene polyoxypropylene block copolymer (pluronic polyols), polyglycol alginate (PGA), CMC (carboxyl methyl cellulose), glycerol, Aloe Vera gel, alginate, hyaluronic acid (HA) and chitosan or any combination thereof.
  • the antimicrobial and/or anti-viral composition according to the present invention may also comprise one or more detergent(s) selected from the group consisting of SDS (sodium dodecyl sulphate), sodium stannate, sodium pyrophosphate, oxine and SLS (sodium lauryl sulphate) or any combination thereof.
  • SDS sodium dodecyl sulphate
  • sodium stannate sodium stannate
  • sodium pyrophosphate sodium pyrophosphate
  • oxine oxine
  • SLS sodium lauryl sulphate
  • the antimicrobial and/or anti-viral composition according to the invention may further comprise one or more fragrance or flavouring oil(s), 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.
  • fragrance or flavouring oil(s) 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 anti-viral composition according to the invention may further comprise one or more weak acidic buffers.
  • the antimicrobial and/or anti-viral composition according to the invention may further comprise one or more stabilizers such as, but not limited to organophosphates, carboxylate salts, sodium pyrophosphate, sodium phytate, colloidal stannate or sodium citrate or any combination thereof.
  • stabilizers such as, but not limited to organophosphates, carboxylate salts, sodium pyrophosphate, sodium phytate, colloidal stannate or sodium citrate or any combination thereof.
  • compositions according to the present invention can comprise a bioactive substance, typically selected from the group consisting of EMD, peptides, drugs, bio active ions, small molecules, radioactive molecules, antimicrobial molecules and radio-opaque molecules or any combination thereof.
  • a bioactive substance typically selected from the group consisting of EMD, peptides, drugs, bio active ions, small molecules, radioactive molecules, antimicrobial molecules and radio-opaque molecules or any combination thereof.
  • compositions according to the present invention can also comprise an additional antimicrobial substance and/or cleaning component.
  • an additional antimicrobial substance provided in one or more of the compositions according to the present invention can be selected from the non-exclusive list consisting of amoxicillin, doxycycline, cephalexin, ciprofloxacin, clindamycin, metronidazole, azithromycin, sulfamethoxazole and trimethoprim or any combination thereof.
  • a further antimicrobial substance provided in one or more of the compositions according to the present invention is an alcohol, tetracycline, doxycycline, macrolides, penicillin (stabilized), chlorhexidine, chloramines or mixtures thereof.
  • compositions according to the present invention comprises an additional anti-viral substance.
  • compositions according to the present invention comprises an additional anti-inflammatory, antiphlogistic, coagulating, anesthetic and/or pain-killing agent or substance.
  • one or more of the compositions according to the present invention comprises one or more of prophylactic and/or anti-tooth-decay agents, such as, but not limited to, hydrogen fluoride, sodium fluoride, or stannous fluoride or any combination thereof.
  • prophylactic and/or anti-tooth-decay agents such as, but not limited to, hydrogen fluoride, sodium fluoride, or stannous fluoride or any combination thereof.
  • a composition according to the present invention in one aspect has a shelf-life of at least 1 years at room temperature (RT).
  • kits comprising a composition described herein, wherein said kit comprises at least two containers comprising said separated components (a) and (b), respectively, a syringe and a vial, a connector device, an applicator tip and an instruction leaflet and, optionally a mixing device and a cleaning tool, such as but not limited to a brush.
  • Said kit can provide the two components (a) and (b) in a two-chamber syringe, in which case the kit further can comprise an instruction leaflet, a mixing device, an applicator tip and a cleaning tool, such as but not limited to a brush and/or a wipe.
  • An antimicrobial and/or anti-viral composition according to the present invention can be mixed before application and eventual storage or stored separately and mixed directly or shortly before and/or at the time of application.
  • the application therefore, in another aspect is directed to a kit comprising a first container comprising component (a), a second container comprising component (b), and optionally at least one more (third or forth etc.) container comprising a component (c), (d), (e) etc.), which can e.g. comprise paper and/or cotton wipes, such as but not limited to wet-wipes, microparticles and/or a mesh-forming substance and/or a bioactive substance and/or a cleaning component and/or a further antimicrobial and/or anti-viral substance.
  • kit may also comprise instructions for the preparation of the composition of the invention.
  • the kit may also comprise one or more device(s) for the application of the composition to a subject.
  • a device may e.g. be a dispenser bottle, a blister pack, a double blister pack, a syringe and/or an implant cleaning and/or sanitizing tool for cleaning and/or sanitizing an implant, such as in the oral cavity.
  • kits of the invention may also comprise one or more of the compositions described herein in one or more container(s) and an implant cleaning and/or sanitizing tool for cleaning and/or decontamination of an implant in the oral cavity.
  • a kit comprising a composition according to the present invention typically provides the two components (a) and (b) in a two-chamber device that allows for easy mixing of the components prior to and/or or during application.
  • a two-chamber device can be a two-chamber syringe, a two-chamber pump-action dispenser bottle a double blister (blister in blister) pack, or a wet-wipe blister containing a separate blister, containing peroxide, to be broken by force prior to application.
  • the kit can further comprise a container, such as a blister-pack and/or tissues, such as sanitizing wipes for applying the composition according to the present invention.
  • a container such as a blister-pack and/or tissues, such as sanitizing wipes for applying the composition according to the present invention.
  • composition is intended for use in cleaning, sanitizing, disinfecting and/or sterilizing a biological surface and/or a biomaterial surface in situ.
  • the antimicrobial and/or anti-viral composition according the present invention is for use in sterilizing, disinfecting and/or sanitizing a biological surface and/or a biomaterial surface in situ.
  • an antimicrobial and/or anti-viral composition according to the present invention is typically used for cleaning, sterilizing, disinfecting and/or sanitizing skin and/or mucosa from microbes.
  • the microbes to be killed or removed by the composition according to the present invention are selected from the group consisting of bacteria and virus, such as selected from the non-exclusive group consisting of Riboviria, in particular Coronaviridae (e.g., Sars-Cov-2), or Orthocoronavirinae.
  • An antimicrobial and/or anti-viral composition according to the present invention is in particular well-suited for killing and/or removing Coronaviruses, such as from skin and/or mucosa, including from hands, face, or oral or nasal cavities.
  • the present invention thus in a presently preferred aspect also relates to the application of an antimicrobial and/or anti-viral composition according to the present invention as a hand wash, oral wash, tooth wash, for nasal and/or sinus cleansing, and/or for washing virus off skin and mucosa.
  • the present invention thus in a presently preferred aspect also relates to the application of an antimicrobial and/or anti-viral composition according to the present invention as a hand sanitizer, mouth wash, sinus rinse, nasal rinse and/or sanitizing wipes.
  • composition is also useful for application in peri-implant defects, and the formulation may be tailored to fit with various clinical procedures, such as but not limited to treating and preventing oral infections , for maintaining oral and/or nasal health and post operative follow-up administrations to skin, mucosa and/or oro-laryngeal and/or nasal cavities.
  • composition can also be used for other oral procedures, such as during surgical cleaning of periodontal defects, for preparation before regenerative procedures, in periodontal maintenance treatment, in periodontitis prophylaxis (by dental hygienists), as well as in endodontics, both in root-canal procedures and in apical surgery.
  • the presently disclosed composition can further be used for cleaning and/or debriding outside the oral cavity, such as, but not limited to in orthopaedic revision surgery, sanitizing of transdermal devices, in dermal wound care for cleaning of acute wounds and/or in cleaning of chronic ulcers and burns.
  • An antimicrobial and/or anti-viral composition according to the present invention can typically be employed for use in the treatment and/or prevention of peri-implantitis, gingivitis and/or mucositis, peri-implant mucositis and/or periodontitis or for the sanitizing of the oral cavity against contagious disease or prior to oral surgery procedures.
  • Periimplantitis is a typical complication related to orodental rehabilitation through the use of implants, e.g., a peri-implant disease, which is well-known to the person skilled in the art as an inflammatory reaction to oral microbes in which there is an accompanied loss of the bony support of the implant.
  • the aetiology of the disease is conditioned by the status of the tissue surrounding the implant, implant design, degree of roughness, the poor alignment of implant components, external morphology and excessive mechanical load.
  • the presently described antimicrobial and/or anti-viral composition offers several approaches for an effective and rapid cleaning of an implant and/or for sanitizing or decontaminate a tissue surface in the oral cavity essentially without damaging of the delicate structure or of the implant surface and/or the tissue surface itself, and essentially without leaving contaminating material residues on the treated surface.
  • the invention therefore in one aspect is directed to the antimicrobial and/or anti-viral composition as defined herein and/or the kit for preparing the composition of the invention as defined herein, for use as a medical device or a medicament.
  • the present invention relates to the use of an antimicrobial and/or anti-viral composition according to the present invention for cleaning and/or sanitizing and/or decontaminate an implant in the oral cavity, such as an implant in situ, a tissue surface in the oral cavity, such as an outer surface of a tissue in the oral cavity, a surgically exposed surface in the oral cavity, a wound in the oral cavity, such as a wound resulting from periimplantitis or a surgical wound, a periodontal defect and/or periodontal wound, and/or an oral hard tissue defect.
  • an implant in the oral cavity such as an implant in situ
  • a tissue surface in the oral cavity such as an outer surface of a tissue in the oral cavity, a surgically exposed surface in the oral cavity
  • a wound in the oral cavity such as a wound resulting from periimplantitis or a surgical wound, a periodontal defect and/or periodontal wound, and/or an oral hard tissue defect.
  • the invention also relates to the use of the antimicrobial and/or anti-viral composition as defined herein and/or the kit for preparing the composition of the invention as defined herein, for the preparation of a medicament and/or a pharmaceutical and/or cosmetic composition, for cleaning and/or decontaminating an implant in the oral cavity, such as an implant in situ, a hard surface in the oral cavity, such as an outer surface of a hard tissue in the oral cavity, a surgically exposed hard surface in the oral cavity, a wound in the oral cavity, such as a wound resulting from periimplantitis or a surgical wound, a periodontal defect and/or periodontal wound, and/or an oral hard tissue defect.
  • an implant in the oral cavity such as an implant in situ
  • a hard surface in the oral cavity such as an outer surface of a hard tissue in the oral cavity, a surgically exposed hard surface in the oral cavity
  • a wound in the oral cavity such as a wound resulting from periimplantitis or a surgical wound, a periodon
  • the invention is also directed to the antimicrobial and/or anti-viral composition as defined herein or the kit for preparing the composition of the invention as defined herein for use cleaning, sanitizing, disinfecting, sterilizing and/or debriding an implant in the oral cavity, such as an implant in situ, a hard surface in the oral cavity, such as an outer surface of a hard tissue in the oral cavity, a surgically exposed hard surface in the oral cavity, a wound in the oral cavity, such as a wound resulting from periimplantitis or a surgical wound, a periodontal defect and/or periodontal wound, and/or an oral hard tissue defect.
  • an implant in the oral cavity such as an implant in situ
  • a hard surface in the oral cavity such as an outer surface of a hard tissue in the oral cavity, a surgically exposed hard surface in the oral cavity
  • a wound in the oral cavity such as a wound resulting from periimplantitis or a surgical wound, a periodontal defect and/or periodontal wound, and
  • nasal and mouth rinses are used pre- and post-surgery to lower the microbial burden during a procedure, or to treat infections.
  • the infection of oro- larynx and nasal mucosa leads to formation of mucus that can fill up sinuses and cause nasal and sinus congestion and microbe accumulation on tongue, tonsils, teeth and gums.
  • the invention is also directed to the antimicrobial and/or anti-viral composition as defined herein for use as mouth wash, nasal rinse and/or sinus rinse for the disinfection and cleaning of oral, laryngeal and/or nasal anatomical structures and/or surfaces.
  • An antimicrobial and/or anti-viral composition according to the present invention is in general intended for use in cleaning, disinfecting, sanitizing and/or decontaminating a biological surface and/or a biomaterial surface in situ, e.g. for use in removal of virus, microbes, including but not limited to bacteria, yeasts, and bacterial spores, and dirt from such a biological surface and/or a biomaterial surface in situ.
  • Biofilms that can be prevented, eliminated and/or treated by the composition of the present disclosure include, but are not limited to, biofilms present within the oral cavity, e.g., on the surface of teeth, on the surface of mucosal/soft-tissues such as gingivae/periodontium and inside a tooth canal (e.g. the endodontic canal).
  • biofilms that can be prevented, eliminated and/or treated by the composition of the present disclosure include biofilms on the urinary tract, lung, gastrointestinal tract, on and/or within chronic wounds, and present on the surface (e.g., implants) and within medical devices and medical lines, e.g., catheters, medical instruments or medical tubing.
  • composition of the present disclosure can be used to reduce the growth and/or inhibit the viability of one or more microorganisms, e.g., bacteria in a biofilm.
  • microorganisms e.g., bacteria in a biofilm.
  • the bacteria, which can be inhibited can include Streptococcus mutctns (S.
  • the bacteria are S. mutans, which is present within biofilms found in the oral cavity, e.g., on the surface of teeth.
  • microorganisms most commonly associated with implant failure are spirochetes and mobile forms of Gram-negative anaerobes. Diagnosis can be based on changes of colour in the gum, bleeding and probing depth of peri-implant pockets, suppuration, x-ray and gradual loss of bone height around the tooth.
  • the antibiotic therapy proven to be most efficacious in the antibiogram has so far been the association of amoxycillin and clavulanic acid.
  • microbial infections in the oral cavity can of course also include fungal and/or viral infections.
  • An antimicrobial and/or anti-viral composition according to the present invention is effective for killing bacteria, fungus and/or virus.
  • a composition according to the present invention is for use in cleaning skin and/or mucosa from virus such as, but not limited to, Riboviria, such as Coronaviridae, such as Orthocoronavirinae and Orthomyxoviridae such as Influenza A, B, C and D virus, Arbovirus and Isavirus, and such as Rotavirus, Norovirus, Adenovirus, Papillomavirus, Herpes virus, Hepatitis virus, Small Pox virus, Parvovirus, Ebola virus, Measles virus or Rabies virus.
  • Riboviria such as Coronaviridae, such as Orthocoronavirinae and Orthomyxoviridae such as Influenza A, B, C and D virus, Arbovirus and Isavirus, and such as Rotavirus, Norovirus, Adenovirus, Papillomavirus, Herpes virus, Hepatitis virus, Small Pox virus, Parvovirus, Ebola virus, Mea
  • composition according to the present invention is for use in cleaning skin and/or mucosa from Coronavirus or Influenza virus.
  • composition described herein is antimicrobial, without causing microbial resistance, as well as anti-viral.
  • the present invention relates to a method for cleaning, sanitizing, treating and /or preventing contagious diseases, infections, gingivitis and/or mucositis, peri-implant mucositis, peri-implantitis, periodontitis, tooth decay, and/or sinusitis and rhinitis, comprising cleaning of a biological surface and/or a biomaterial surface in situ by applying a composition according to the present invention to said fouled, filmed and/or contaminated structure, tissue or surface.
  • Example 1 The following Examples have been included to provide guidance to one of ordinary skill in the art for practicing representative embodiments of the presently disclosed subject matter. Considering the present invention and the general level of skill in the art, those of skill can appreciate that the following Examples are intended to be exemplary only and that numerous changes, modifications, and alterations can be employed without departing from the scope of the presently disclosed subject matter.
  • Example 1 The following Examples have been included to provide guidance to one of ordinary skill in the art for practicing representative embodiments of the presently disclosed subject matter. Considering the present invention and the general level of skill in the art, those of skill can appreciate that the following Examples are intended to be exemplary only and that numerous changes, modifications, and alterations can be employed without departing from the scope of the presently disclosed subject matter. Example 1
  • Pluronic® F-127 added to an aqueous solution can change its thickness depending on the concentration and temperature.
  • F-127 is a non-ionic, surfactant polyol with a molecular weight of 12500 Daltons.
  • aqueous poloxamer solution The technique used for making aqueous poloxamer solution is simple. Weighed amount of the f-127 is slowly added to a known weight of cold water (less than 10 °C) with careful stirring. The stirring rate should be controlled so as to maintain a slight vortex in the liquid. Too rapid a stirring rate will cause aeration and the formation of foam.
  • Table 1 Compositions of suspensions containing 5% pluronic Acid F-127 (Zigma Aldrich) in water and a range of Hydrogen Peroxide (Sigma Aldrich). After dissolving the f-127 in cold water, the right amount of hydrogen peroxide was added, mixing was done by inverting tubes carefully to avoid foaming, and the solutions were left on the bench at room temperature for 10 minutes. When all the polymer has been added, stirring can be continued (while keeping the solution cool) until a clear solution is formed or the container can be placed in a refrigerator and left undisturbed for several hours, at which time solution is complete. The H2O2 was mixed in by slight stirring for a few seconds when the experiment started.
  • Turbidity is a sign of macro-emulsion, a stage where oil droplets become so big that they disperse light.
  • the positive control Sample 0, absorbed 7 oil droplets before getting turbid.
  • the negative control sample 7, turned turbid with the first droplet. The expected linearity between these extremes was however not observed.
  • sample 2 (0.5% Peroxide) and 3 (1.0% peroxide) actually absorbed almost twice as many droplets than the positive control before turbidity was observed.
  • the biocompatibility test was performed according to ISO 10993-5:2009 Biological evaluation of medical devices Part 5: Tests for in vitro cytotoxicity.
  • test samples could not be diluted into the cell culture medium.
  • NHDF cells grow directly onto the gel due their lack of surface properties.
  • the NHDF cells were grown on cell culture inserts (Millicell®,
  • NHDF cells were cultivated in 24 well plates for 24 hours at 37C and 5% C02 with Dulbecco’s PBS cell culture media (FGM®-2 with Insulin (CC-4021 J), rhFGF-B (CC-4065J) and FBS (CC-4161 J), Lonza Walkervill, MD USA). After 24 hours growing in presence of test substances or controls (no gel and gelatin gel) 0.5 pL 3 H-thymidine (PerkinElmer, Boston, USA) was added into the wells containing the cells.
  • test substances or controls no gel and gelatin gel
  • a stock Streptococcus Epidermidis culture was established in BHI broth and allowed to grow to log phase.
  • the S. Epidermidis culture was introduced to cell culture disks of c.p. titanium and allowed to for a multilayer biofilm on the surface over a period of 2 days. After the biofilm had been established, the discs were rinsed several times in sterile, cold PBS until only adherent cells was present on the surfaces.
  • the discs with biofilm on were then submerged in test gel or control for 5 minutes ⁇ 5 sec. making sure that the entire discs were covered by the test gels all the time.
  • the discs were then rinsed for 10 minutes in cold PBS on a shaker, rinsed off and viewed in a table-top scanning electron microscope to see how many bacteria that were left on the test surfaces.
  • Test 4 was slightly, but not statistically significant, more effective than Test 2. Chlorhexidine (Test 5) and Ethanol (Test 6) did kill most of the bacteria but did not remove any debris from the surface, leaving the surfaces heavily contaminated. Surfaces visualized after cleaning in a scanning electron microscope. Scale bar is 20 micrometres.
  • Pluronic with peroxide is more skin-friendly than an alcohol containing hand-sanitizer
  • Finger A) was washed only with water.
  • Finger B) was cleaned with warm water and soap.
  • Finger C) was cleaned with 0.2% chlorhexidine and finger D) was rinsed with PyrispetTM (0.1% cetyl-pyridinium chloride).
  • Finger E) was cleaned with Antibac PharmaTM (Alcohol based sanitizer containing ethanol and propan-2-ol), finger F) was cleaned with bleach (4% Sodium hypochlorite).
  • Finger G) and H) was rinsed with hydrogen peroxide (1% and 5% v/v in water respectively).
  • Finger I) was washed in a solution of pluronic acid f-127 in water (5% w/v).
  • Finger J was sanitized with a mix of pluronic acid (5% w/v) and hydrogen peroxide (1% v/v).
  • the results show that bleach and hydrogen peroxide is very effective in removing the permanent ink stain.
  • the most efficient removal of the stain is obtained by the combination of pluronic acid and weak hydrogen peroxide (Figure 7).
  • the two-component pluronic-Peroxide solution described here is intended for hand sanitizing after possible exposure to virus contamination.
  • Virus are genetic code (RNA or DNA) wrapped in a protein envelope to protect and transmit the genetic information.
  • Most sanitizers only attack (denature or fix) the protein envelope so that the virus is no longer very contagious, but do not remove the virus perse or attack the virus genome.
  • the combination of peroxide and pluronic do both. The peroxide degrades both proteins and RNA and DNA, and the pluronic also denatures proteins and dissolves the organic material into its micelle structure, completely destroying and removing the viral particles from the skin, together with other contaminants and dirt.
  • a 500 ml dispenser bottle is divided in two chambers; one containing 400 milliliters of f-127 pluronic acid at 10% w/v in water, and one chamber containing 100 milliliters of Hydrogen Peroxide 25% v/v in water.
  • a pump with two inlets pumps liquid from both chambers into the dispenser tip for mixing and application.
  • the mixed solution is evenly distributed over the hands as with any other sanitizer, left to work for some seconds and is then rinsed off under running tap water. There is no need to apply any soap as the liquid itself also work as a detergent.
  • the clean hands are dried off with a paper towel or air dried. No extraordinary precautions or actions are necessary to remove the solution.
  • the solution is completely harmless after rinsing and will decompose to water, oxygen and carbon dioxide with no environmental footprint or impact.
  • the two-component pluronic-peroxide solution described here is intended for hand sanitizing after possible exposure to virus contamination.
  • Virus are genetic code (RNA or DNA) wrapped in a protein envelope to protect and transmit the genetic information.
  • Most sanitizers only attack (denature or fix) the protein envelope so that the virus is no longer very contagious, but do not remove the virus per se or attack the virus genome.
  • the combination of peroxide and pluronic do both. The peroxide degrades both proteins and RNA and DNA, and the pluronic also denatures proteins and dissolves the organic material into its micelle structure, completely destroying and removing the viral particles from the skin, together with other contaminants and dirt.
  • a 500 ml dispenser bottle contains a biphasic emulsion in two equal parts.
  • One part of the emulsion contains f-127 pluronic acid in an oily suspension (10% w/v). Etheric oils or perfume can be added for pleasant smell.
  • the other phase contains a water solution with hydrogen peroxide (10% v/v).
  • the bottle is shaken vigorously and a pump with dispenser tip is used to apply the emulsion mix onto hands.
  • the emulsion is evenly distributed over the hands as with any other sanitizer, left to work for some seconds and is then rinsed off under running tap water or simply left to air dry.
  • No extraordinary precautions or actions is necessary to remove the solution.
  • the solution completely harmless after rinsing and will decompose to water, oxygen and carbon dioxide with no environmental footprint.
  • the remaining oils will protect the skin from drying and make it smooth.
  • the two-component pluronic-peroxide solution described here is intended for hand sanitizing after possible exposure to virus contamination.
  • Virus are genetic code (RNA or DNA) wrapped in a protein envelope to protect and transmit the genetic information.
  • Most sanitizers only attack (denature or fix) the protein envelope so that the virus is no longer very contagious, but do not remove the virus per se or attack the virus genome.
  • the combination of peroxide and pluronic do both. The peroxide degrades both proteins and RNA and DNA, and the pluronic also denatures proteins and dissolves the organic material into its micelle structure, completely destroying and removing the viral particles from the skin, together with other contaminants and dirt.
  • a 1 ml blister pack is contained inside another 5 ml blister pack.
  • the inner blister pack contains hydrogen peroxide (25 % v/v)
  • the outer blister pack contains 3 ml f-127 pluronic acid in perfumed water (10 % w/v) and the first blister pack.
  • the inner blister pack is ruptured by applying manual force, then mixed by squeezing the outer pack.
  • After mixing the outer blister pack is opened and the content is evenly distributed over the hands as with any other sanitizer, left to work for some seconds and is then rinsed off under running tap water. There is no need to apply any soap as the liquid itself also work as a detergent.
  • the clean hands are dried off with a paper towel or air dried. No extraordinary precautions or actions is necessary to remove the solution.
  • the solution completely harmless after rinsing and will decompose to water, oxygen and carbon dioxide with no environmental footprint or impact.
  • the two-component pluronic-Peroxide solution described here is intended for hand sanitizing after possible exposure to virus contamination.
  • Virus are genetic code (RNA or DNA) wrapped in a protein envelope to protect and transmit the genetic information.
  • Most sanitizers only attack (denature or fix) the protein envelope so that the virus is no longer very contagious, but do not remove the virus per se or attack the virus genome.
  • the combination of peroxide and pluronic do both. The peroxide degrades both proteins and RNA and DNA, and the pluronic also denatures proteins and dissolves the organic material into its micelle structure, completely destroying and removing the viral particles from the skin, together with other contaminants and dirt.
  • a 1 ml blister pack is contained inside another 5 ml blister pack.
  • the inner blister pack contains hydrogen peroxide (25 % v/v)
  • the outer blister pack contains 3 ml f-127 pluronic acid (10 % w/v) in perfumed water, a folded paper tissue and the first blister pack.
  • the inner blister pack is ruptured by applying manual force, then mixed by squeezing the pack.
  • the outer blister pack is opened and the folded paper tissue, now activated with the peroxide-pluronic mix used to wipe the skin, hands or contaminated surfaces free of dirt, microbes and viral contaminants.
  • the clean hands, skin or surface is left to dry in air. No extraordinary precautions or actions is necessary to remove the solution.
  • the solution completely harmless after rinsing and will decompose to water, oxygen and carbon dioxide with no environmental footprint or harm to the skin.
  • Virus are genetic code (RNA or DNA) wrapped in a protein envelope to protect and transmit the genetic information. Most viral sanitizers only attack (denature or fix) the protein envelope so that the virus is no longer very contagious, but do not remove the virus per se or attack the virus genome. The combination of peroxide and pluronic does both.
  • the peroxide degrades both proteins and RNA and DNA, and the pluronic also denatures proteins and dissolves the organic material into its micelle structure, completely destroying and removing the viral particles from the oral cavity and throat, together with other microbes, contaminants and mucus.
  • a 1000 ml dispenser bottle is divided in two chambers; one containing 800 milliliters of f-127 pluronic acid at 5% w/v in saline with sodium fluoride and taste and smell modifiers, and one chamber containing 200 milliliters of hydrogen peroxide 16% v/v in water.
  • a pump with two inlets is used to pumps liquid from both chambers into the dispenser tip for mixing and application. 10 milliliters of the mixed solution are used to rinse the mouth and throat for about 1 minute, and then spat out in the sink.
  • the solution completely harmless after rinsing and will decompose to water, oxygen and carbon dioxide with no environmental footprint or health impact.
  • the mouthwash can also be used against oral infections periodontitis and peri-implantitis and tooth decay, both prophylactically and for post-surgery infection control and maintenance treatment after periodontal or implant-related procedures. It can also be used to clean toothbrushes and intra-oral devices (dentures, anti-snoring devices, orthodontic appliances etc.) to avoid re-infection from repeated use.
  • Virus are genetic code (RNA or DNA) wrapped in a protein envelope to protect and transmit the genetic information. Most viral sanitizers only attack (denature or fix) the protein envelope so that the virus is no longer very contagious, but do not remove the virus per se or attack the virus genome. The combination of peroxide and pluronic does both.
  • the peroxide degrades both proteins and RNA and DNA, and the pluronic also denatures proteins and dissolves the organic material into its micelle structure, completely destroying and removing the viral particles from the nasal cavity and sinuses, together with other contaminants and mucus.
  • the nasal/sinus rinse can also be used against nasal infections or against acute and chronic sinusitis.
  • the solution can also be used both prophylactically and for post-surgery infection control after otorhinolaryngeal procedures.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Birds (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Emergency Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Inorganic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Cosmetics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Detergent Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Des aspects de la présente invention concernent une composition antimicrobienne et/ou antivirale améliorée comprenant un mélange antimicrobien et/ou antiviral constitué de : H2O2 à une concentration finale comprise entre 3 et 7 % v/v, et un poloxamère à une concentration de 0,1 à 10 % p/v. Le poloxamère se trouve dans une formulation d'hydrogel composite. La composition de l'invention est antimicrobienne et/ou antivirale et est particulièrement utile pour nettoyer, stériliser, désinfecter, assainir, décontaminer et/ou débrider les surfaces biologiques et les surfaces des biomatériaux, par exemple lorsqu'elle est fournie dans un désinfectant pour les mains, un bain de bouche, un rinçage nasal et/ou pour le soin des plaies et/ou des ulcères chroniques et pour la prophylaxie dentaire et le maintien de la santé péri-implantaire.
PCT/EP2021/057024 2020-03-18 2021-03-18 Composition liquide améliorée pour le nettoyage, l'assainissement et/ou la désinfection WO2021186000A1 (fr)

Priority Applications (7)

Application Number Priority Date Filing Date Title
JP2022554494A JP2023518701A (ja) 2020-03-18 2021-03-18 洗浄、消毒、および／または殺菌するための改良型液体組成物
KR1020227035200A KR20230006463A (ko) 2020-03-18 2021-03-18 세정, 소독 및/또는 살균을 위한 개선된 액체 조성물
BR112022018324A BR112022018324A2 (pt) 2020-03-18 2021-03-18 Composição líquida melhorada para limpeza, sanitização e/ou desinfecção
CA3170947A CA3170947A1 (fr) 2020-03-18 2021-03-18 Composition liquide de h2o2 et de poloxamere aux fins de nettoyage, d'assainissement et/ou de desinfection
CN202180033519.8A CN115605269A (zh) 2020-03-18 2021-03-18 用于清洁、消毒和/或杀菌的改良液体组合物
AU2021238760A AU2021238760A1 (en) 2020-03-18 2021-03-18 Improved liquid composition for cleaning, sanitizing and/or disinfecting
US17/939,570 US20230020320A1 (en) 2020-03-18 2022-09-07 Liquid Composition for Cleaning, Sanitizing and/or Disinfecting

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
EP20164065.3 2020-03-18
EP20164065.3A EP3881901A1 (fr) 2020-03-18 2020-03-18 Composition liquide améliorée pour le nettoyage, l'aseptisation et/ou la désinfection
US202016840921A 2020-04-06 2020-04-06
US16/840,921 2020-04-06

Related Child Applications (1)

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US17/939,570 Continuation US20230020320A1 (en) 2020-03-18 2022-09-07 Liquid Composition for Cleaning, Sanitizing and/or Disinfecting

Publications (1)

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WO2021186000A1 true WO2021186000A1 (fr) 2021-09-23

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JP (1) JP2023518701A (fr)
KR (1) KR20230006463A (fr)
CN (1) CN115605269A (fr)
AU (1) AU2021238760A1 (fr)
BR (1) BR112022018324A2 (fr)
CA (1) CA3170947A1 (fr)
WO (1) WO2021186000A1 (fr)

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KR102613224B1 (ko) 2023-05-19 2023-12-12 국방과학연구소 생물학 작용제의 제독 방법

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6254857B1 (en) * 2000-05-24 2001-07-03 Colgate-Palmolive Company Effervescent whitening dentifrice having oxygen-derived sensory signal
WO2002026922A1 (fr) * 2000-09-28 2002-04-04 Novartis Ag Compositions et procedes de nettoyage de verres de contact
WO2005030172A1 (fr) * 2003-09-24 2005-04-07 The Regents Of The University And Methods Compositions antimicrobiennes en nanoemulsion et methodes associees
US20060198797A1 (en) * 2005-11-07 2006-09-07 Giniger Martin S Stand-alone or enhancer composition for oral care
WO2007066837A1 (fr) * 2005-12-06 2007-06-14 Lg Household & Health Care Ltd. Systemes de distribution d'un composant de blanchiment des dents faisant appel a la gelification in situ
US20090252775A1 (en) * 2005-01-28 2009-10-08 B. Braun Medical Ag Virucidal disinfectant
US20100179368A1 (en) * 2008-11-07 2010-07-15 Aries Associates, Inc. Novel Chemistries, Solutions, and Dispersal Systems for Decontamination of Chemical and Biological Systems
US20120039821A1 (en) * 2010-08-13 2012-02-16 Robell Research, Inc. Dental Activating Gel
US20160220675A1 (en) * 2013-09-11 2016-08-04 Glenn Abrahmsohn Hypertonic antimicrobial therapeutic compositions
WO2019032061A2 (fr) * 2016-11-23 2019-02-14 Yeditepe Universitesi Composition insectifuge antimicrobienne

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6254857B1 (en) * 2000-05-24 2001-07-03 Colgate-Palmolive Company Effervescent whitening dentifrice having oxygen-derived sensory signal
WO2002026922A1 (fr) * 2000-09-28 2002-04-04 Novartis Ag Compositions et procedes de nettoyage de verres de contact
WO2005030172A1 (fr) * 2003-09-24 2005-04-07 The Regents Of The University And Methods Compositions antimicrobiennes en nanoemulsion et methodes associees
US20090252775A1 (en) * 2005-01-28 2009-10-08 B. Braun Medical Ag Virucidal disinfectant
US20060198797A1 (en) * 2005-11-07 2006-09-07 Giniger Martin S Stand-alone or enhancer composition for oral care
WO2007066837A1 (fr) * 2005-12-06 2007-06-14 Lg Household & Health Care Ltd. Systemes de distribution d'un composant de blanchiment des dents faisant appel a la gelification in situ
US20100179368A1 (en) * 2008-11-07 2010-07-15 Aries Associates, Inc. Novel Chemistries, Solutions, and Dispersal Systems for Decontamination of Chemical and Biological Systems
US20120039821A1 (en) * 2010-08-13 2012-02-16 Robell Research, Inc. Dental Activating Gel
US20160220675A1 (en) * 2013-09-11 2016-08-04 Glenn Abrahmsohn Hypertonic antimicrobial therapeutic compositions
WO2019032061A2 (fr) * 2016-11-23 2019-02-14 Yeditepe Universitesi Composition insectifuge antimicrobienne

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CA3170947A1 (fr) 2021-09-23
JP2023518701A (ja) 2023-05-08
KR20230006463A (ko) 2023-01-10
BR112022018324A2 (pt) 2022-11-22
AU2021238760A1 (en) 2022-10-06
CN115605269A (zh) 2023-01-13

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