Multifunctional cleaning and / or wiping composition

Abstract

To provide an antimicrobial and / or anti-inflammatory composition for cleaning and / or wiping biological and / or biomaterial surfaces, for example, insitu implants and / or surfaces in the oral cavity.SOLUTION: The present invention relates to a novel multifunctional wiping and / or anti-fouling composition comprising a composite hydrogel formulation comprising H2O2 at final concentrations of 0. 1-5% v / v and pluronic acid at a concentration of 10-40% w / v, wherein the composition is in liquid form at ambient temperature. The compositions disclosed herein are antimicrobial and / or anti-inflammatory, and are particularly useful in peri-implantitis treatment and implant health maintenance, in periodontitis and periodontal health, and in wound care and chronic ulcer care.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a novel multifunctional wiping and / or anti-fouling composition comprising a composite hydrogel formulation comprising HO at a final concentration of 0.1-5% v / v and pluronic acid at a concentration of 10-40% w / v, the composition being in liquid form at room temperature, e.g., at a temperature of up to 30° C. The compositions disclosed herein are antibacterial and / or anti-inflammatory and are particularly useful in peri-implantitis treatment and implant health maintenance, in periodontitis and periodontal health, and in wound care and chronic ulcer care.

[0002] The present invention further relates to the use of the compositions according to the invention for cleaning and / or wiping biological and / or biomaterial surfaces, such as in particular in situ implants and / or surfaces in the oral cavity. The compositions according to the invention can be used together with implant cleaning and / or wiping tools, such as brushes, burrs or curettes.

[0003] In one embodiment, the composition according to the invention is provided in a kit, wherein the at least two components, H2O2 and pluronic acid, are optionally kept separate and are mixed immediately upon combined and / or simultaneous application. [Background technology]

[0004] In situ biological and / or biomaterial surfaces are in constant contact with and frequently colonized by numerous microorganisms, making them prone to soiling, i.e., the accumulation of biofilms and necrotic tissue, and therefore require regular cleaning and wiping with antibacterial and anti-inflammatory compositions without harming the surrounding biological tissue of the patient and without causing pathogen resistance.

[0005] Biofilm Biofilms are structured microbial communities firmly attached to surfaces and entrapped in a self-produced three-dimensional (3D) extracellular matrix. Biofilms can form on or within biotic or non-biotic surfaces and can exist in natural and industrial environments.

[0006] Biofilms can form on or inside implantable medical tubes and devices, as well as on or inside the human body, such as mucosal surfaces or other bodily orifices, or open wounds, potentially causing infection in patients. The inflammatory response to this leads to the accumulation of necrotic tissue, which in turn leads to a subsequent inflammatory response in the body. Biofilms, in particular, can develop in the oral cavity, often leading to caries or oral diseases such as periodontitis, gingivitis, or peri-implantitis. The extracellular matrix of such biofilms contains polymeric substances such as exopolysaccharides (EPS). The matrix produced by microorganisms can provide an essential scaffold for biofilm assembly. Furthermore, biofilms are extremely difficult to treat or remove from surfaces because they can promote the adhesion and aggregation of pathogens while simultaneously hindering their spread.

[0007] The extracellular matrix contributes to the difficulty of eliminating pathogenic biofilms in the oral cavity and human body, and on biomaterials such as implants and medical devices, by antibodies, antibiotics, and immune cells, which are largely unable to penetrate the dense extracellular matrix and kill embedded microorganisms.

[0008] Biofilms on biological surfaces and implants are removed by chemical and / or mechanical cleaning and / or wiping.

[0009] Wipe Debridement is the medical removal of a patient's dead, damaged, and / or infected tissue to improve the healing ability of remaining healthy tissue. Debridement can be surgical, mechanical, chemical, autolytic (self-digestion), and by maggot therapy, in which certain species of live maggots selectively feed only on necrotic tissue.

[0010] However, mechanical cleaning and / or wiping of surfaces is not sufficient as it fails to provide a secondary chemical and / or biological cleaning / decontamination effect, e.g. leaving the surface open, allowing pathogens to immediately repopulate, or leaving traces of previous pathogen populations in inaccessible areas, e.g. on rough surfaces.

[0011] Thus, there are currently several antibacterial and / or anti-inflammatory agents used in antifouling treatments.

[0012] hydrogen peroxide Hydrogen peroxide (H2O2) is a very pale blue liquid that appears colorless in dilute solution and is slightly more viscous than water. Hydrogen peroxide is a weak acid. Due to its strong oxidizing properties, it is a powerful bleaching agent used primarily in paper bleaching, but is also used as a disinfectant and oxidizing agent. Hydrogen peroxide in the form of carbamide peroxide is widely used for tooth whitening (bleaching) in both professional and self-administered products.

[0013] Hydrogen peroxide is unstable and decomposes slowly in the presence of light. Due to its instability, hydrogen peroxide is usually stored in a dark bottle in a weakly acidic solution with a stabilizer.

[0014] Hydrogen peroxide is used to sterilize various surfaces, including surgical instruments, and may be deployed as a vapor (VHP) for room sterilization. H2O2 exhibits broad-spectrum efficacy against pathogens, including but not limited to viruses, bacteria, yeast, and bacterial spores. Generally, greater activity is seen against gram-positive than gram-negative bacteria, although resistance may develop at lower concentrations due to the presence of catalase or other peroxidases in these organisms. Higher concentrations of H2O2 (10-30% v / v) and longer contact times are required for sporicidal activity.

[0015] Hydrogen peroxide decomposes to form oxygen and water, making it an environmentally safe alternative to chlorine bleach, and is generally recognized as safe as an antimicrobial agent by the U.S. Food and Drug Administration (FDA).

[0016] Historically, hydrogen peroxide was used to disinfect wounds. It is now believed that high concentrations destroy newly formed skin cells, inhibiting healing and inducing scarring. One study found that only very low concentrations (a 0.03% v / v solution, a 100-fold dilution of the typical 3% v / v peroxide) were able to induce healing, but only if not applied repeatedly. A 0.5% v / v solution was found to inhibit healing.

[0017] Pluronic acid Pluronics® or poloxamers are triblock copolymers of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO). This group of synthetic polymers is thermoreversible in aqueous solution. The sol-gel transition depends on the composition, molecular weight, and concentration of each constituent block polymer. Hydrophilic The hydrophobic ethylene oxide and hydrophobic propylene oxide give Pluronics an amphiphilic structure, i.e., a polar water-soluble group attached to a non-polar, water-insoluble hydrocarbon chain. The amphiphilic block copolymer molecules self-assemble into micelles (chains of packed molecules) in aqueous solution. Micelle formation is temperature-dependent and affects the degradation properties of the biomaterial: below a characteristic temperature known as the critical micelle temperature, the ethylene oxide and propylene oxide blocks are both hydrated and the PPO block becomes soluble.

[0018] Pluronics can be found as liquids, pastes, or solids. Their amphiphilic nature (they have both hydrophobic and hydrophilic components) allows them to have surfactant properties that allow them to interact with hydrophobic surfaces and biological membranes. This amphiphilic nature also allows the individual block copolymers, known as unimers, to combine in aqueous solution to form micelles. When the concentration of the block copolymer is below the critical micelle concentration (CMC), the unimers remain in molecular solution in water. However, as the concentration of the block copolymer increases above the CMC, the unimers self-assemble to form micelles, which can adopt spherical, rod-like, or lamellar shapes. Their shape is determined by the length and concentration of the block copolymers (i.e., EO and PO) and the temperature. Micelles typically have a hydrophobic core, in this case, PO chains, and a hydrophilic shell, EO chains.

[0019] [ka]

[0020] Pluronic F-127, also known as poloxamer 407, is often used in tissue engineering because a consistent product that undergoes a sol-gel transition at near-physiological temperature and pH is commercially available. A drawback of Pluronic F-127 is its rapid rate of degradation in vivo. To overcome this problem, Pluronic F-127 is frequently crosslinked with another α-hydroxy or amino acid to modify the chemical structure of its depsipeptide units.

[0021] Pluronic acids form thermosensitive hydrogels, which are typically stabilized by the addition of a high molecular weight acid such as hyaluronic acid.

[0022] Studies have demonstrated the positive effects of pluronic acid formulations in reducing inflammation, protecting tissues from damage, and preventing the adhesion of pathogenic bacteria. Furthermore, pluronic acid formulations have been approved by the EMA and FDA, are fully biocompatible, and can be used clinically safely with no known adverse effects on human cells.

[0023] However, pluronic acid formulations are difficult to apply as cleaning and wiping agents because they automatically form stable gels above 18°C, or even between 12 and 20°C depending on their concentration (see Figure 1), making them unsuitable for use in narrow passages and / or on rough surfaces, and unsuitable for syringe application.

[0024] As a result, there remains a need for means for cleaning and / or wiping soiled biological and / or biomaterial surfaces in situ, or for preventing soiling of said biological and / or biomaterial surfaces in situ, for example by cleaning and / or sterilizing said surfaces in the oral cavity. The present invention presents for the first time such means for effectively cleaning and / or wiping difficult to access areas and / or even rough hard surfaces, such as the oral cavity. Summary of the Invention [Means for solving the problem]

[0025] The present invention provides a novel antimicrobial and / or anti-inflammatory composition for cleaning and / or wiping biological and / or biomaterial surfaces in situ, comprising at least two components: a. H2O2 to a final concentration of 0.1–5% v / v, and b. Composite hydrogel formulations containing pluronic acid at concentrations of 10-40% w / v wherein the composition is liquid at room temperature, for example at a temperature of up to 30°C, for example at a temperature of 20-30°C, for example at 25°C.

[0026] The compositions disclosed herein are characterized in that they contain components a. and b. in a ratio such that the composition is in a liquid state at room temperature, rather than in a gel state.

[0027] In one embodiment of the antibacterial and / or anti-inflammatory composition according to the present invention, the composite hydrogel formulation of component b. comprises pluronic acid in a concentration of 10-40% w / v, for example at least 10% w / v, such as 10, 15, 20, 25, 30, 35 or 40% w / v.

[0028] In another embodiment of the antibacterial and / or anti-inflammatory composition according to the present invention, the composite hydrogel formulation of component b. comprises pluronic acid in a concentration of up to 40% w / v, such as up to 15, 20, 25, 30 or 35% w / v.

[0029] The antibacterial and / or anti-inflammatory composition according to the present invention may be a composition in which the component a, H2O2, has a final concentration of 0.1 to 5% v / v, for example 0.5 to 3.0% v / v.

[0030] The antibacterial and / or anti-inflammatory composition according to the present invention may further comprise water and / or saline.

[0031] The two components of the antimicrobial and / or anti-inflammatory composition according to the present invention may be in one solution, or at least the two components may be kept separate from each other until they are mixed together and applied in situ to a biological surface and / or biomaterial surface.

[0032] In the antibacterial and / or anti-inflammatory composition according to the invention, where the components are kept separate from each other before application, the separate component a. may be a composition comprising H2O2 at a concentration of at least 10-50% v / v.

[0033] The composition according to the present invention may further comprise microparticles having a mean particle size (D50) of 20 to 200 μm, typically at a concentration of about 0.5 to 1000 g / L, for example about 0.5 to 300 g / L.

[0034] The particulates may be organic or inorganic.

[0035] The inorganic fine particles contained in the composition according to the present invention can be selected from metal compounds.

[0036] In another embodiment, the microparticles are polymeric particles, mineral particles and / or metal particles.

[0037] In one embodiment, the microparticles contained in the composition according to the invention are biodegradable and are selected from the group consisting of bare zinc, iron, silicon, magnesium, manganese, silver and palladium.

[0038] In one embodiment, the composition according to the invention further comprises microparticles which release one of the following ions: Ca2+, F-, Sr2+, Mg2+, or microparticles comprising a calcium salt compound powder, a calcium oxide compound powder, a calcium ion source and / or a calcium phosphate compound powder.

[0039] In yet another embodiment, the composition according to the present invention comprises a source of fluoride ions.

[0040] The composition according to the invention may further comprise at least one mesh-forming and / or scaffold-forming component that improves the physical strength and / or chemical longevity of the composition after application.

[0041] Alternatively or additionally, compositions according to the present invention may include a biologically active agent.

[0042] Additionally, the compositions according to the present invention may also contain additional antibacterial and / or cleaning ingredients.

[0043] In one embodiment, the composition according to the invention has a shelf life of at least 1 year at RT.

[0044] The present invention also relates to a kit comprising the composition according to the present invention, which comprises at least two containers, a syringe and a vial, each containing the separate components a. and b., a connector device, an applicator tip and instructions, and optionally a mixing device and a wiping 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 comprise instructions, a mixing device, an applicator tip and a wiping implement such as a brush.

[0045] The antibacterial and / or anti-inflammatory compositions according to the present invention are intended for use in the in situ wiping and / or cleaning of biological and / or biomaterial surfaces, for example in the in situ removal of biofouling, biofilm and / or necrotic tissue from such biological and / or biomaterial surfaces.

[0046] The antibacterial and / or anti-inflammatory compositions according to the present invention are typically employed for use in the treatment and / or prevention of peri-implantitis, gingivitis and / or mucositis, peri-implant mucositis and / or periodontitis.

[0047] Consequently, the present invention relates to a method for treating and / or preventing peri-implantitis, gingivitis and / or mucositis, peri-implant mucositis and / or periodontitis, which method comprises cleaning and / or wiping biological and / or biomaterial surfaces in situ by applying a composition according to the present invention to said soiled, biofilmed and / or necrotic surfaces.

[0048] Definitions and Abbreviations As used herein, the term "microparticles" is intended to describe particles having a mean particle size (D50) of about 1 to 1000 μm. Typically, microparticles having a mean particle size (D50) of 20 to 200 μm are used in the present invention.

[0049] The present invention provides a means for cleaning and / or wiping medical and / or dental implants. In the present context, the term "implant" typically refers to a medical and / or dental implant.

[0050] 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, particularly a mammal such as a human, for example, in a dental restoration procedure. Dental implants are herein selected from the group consisting of implants, bars, bridges, abutments, crowns, caps, and intraoral prosthetic components. Dental implants may also be referred to as dental prosthetic devices. Generally, dental implants are composed of one or more implant components. For example, a dental implant usually includes a dental fixture and / or a dental restoration such as a crown, bridge, or denture connected to a secondary implant component such as an abutment. However, any device such as a dental fixture intended for implantation may be referred to solely as an implant, even if other components are connected to it.

[0051] In the present context, the term "orthopedic implant" includes within its scope any device intended to be implanted in the body of a vertebrate, particularly a mammal such as a human, for the purpose of preserving and restoring function of the musculoskeletal system, particularly the joints and bones, including the relief of pain in those structures. Non-limiting examples of orthopedic implants are artificial hip joints, artificial knee joints, artificial elbow joints, artificial finger joints, artificial cochleae, and fixation screws.

[0052] In the present context, the term "vascular stent" refers to a tubular implant configured for insertion into the blood vessels of vertebrates, particularly mammals such as humans, to prevent or counter localized flow constriction, i.e., to counter a significant reduction in vessel diameter.

[0053] Hard tissues are, for example, bone, cementum, dentin, enamel, teeth, tooth roots, cartilage, and ligaments. Soft tissues are, for example, tissues that connect, support, or surround other structures and organs of the body, but are not hard tissues such as bone. Soft tissues include tendons, ligaments, fascia, skin, fibrous tissue, fat and synovial membranes, muscles, nerves, and blood vessels.

[0054] The term "debridement" in the present context means cleaning a tissue surface, such as a surgically exposed hard and / or soft tissue surface, e.g., to remove biofilms, stones, pathogens, unwanted tissue, cells and cellular debris, scar tissue and / or necrotic tissue. Debridement is performed, for example, to control and / or treat local infections, inflammation, foreign body reactions, pathological conditions and / or regenerative processes (e.g., periodontitis, peri-implantitis).

[0055] As used herein, a "biofilm" comprises an extracellular matrix and one or more microorganisms, such as, but not limited to, bacteria, fungi, algae, and protozoa, attached to a surface. For example, but not limited to, such surfaces can include teeth, mucous membranes, apatite, bone, and non-living (e.g., implants, dentures, pipes, etc.) surfaces.

[0056] In the present context, the term "peroxide" is used interchangeably with hydrogen peroxide (H2O2).

[0057] Microorganisms or pathogens are microscopic organisms that may exist in their single-cell form or in colonies of cells. Microorganisms are extremely diverse as they include all single-celled organisms. Archaea and bacteria are all microorganisms (prokaryotes). Some protists are related to animals and some to green plants. Many multicellular organisms are microscopic, i.e., tiny animals, some fungi and some algae.

[0058] Antibacterial agents are drugs that kill or stop the growth of microorganisms. Antibacterial agents can be grouped according to the microorganisms they primarily act on. For example, antibiotics are used against bacteria, and antifungals are used against fungi. They are also classified according to their function. Drugs that kill pathogenic bacteria are bactericidal, while those that only inhibit growth are called bacteriostatic; both are included in the term "antibacterial agent." The use of antibacterial agents to treat infection is known as antibacterial chemotherapy, while the use of antibacterial agents to prevent infection is known as antibacterial prophylaxis.

[0059] Viruses are small infectious agents that replicate only within the living cells of an organism. They can infect all types of life forms, from animals and plants to microorganisms, including bacteria and archaea.

[0060] Antivirals are a class of drugs used specifically to treat viral, rather than bacterial, infections. Most antivirals are used for specific viral infections, while broad-spectrum antivirals are effective against a wide range of viruses. Unlike most antibiotics, antivirals do not destroy the targeted pathogen; instead, they inhibit its growth.

[0061] Antivirals are a class of antibacterial agents, a larger group that also includes antibiotics (also called antibacterials), antifungals, and antiparasitics, or antivirals based on monoclonal antibodies. Many antivirals are used to treat infections because they are considered relatively harmless to the host. Antivirals should be distinguished from viricides, which are not drugs but inactivate or destroy virus particles either inside or outside the body. Natural antivirals are produced by several plants, such as eucalyptus and Australian tea tree.

[0062] As used in this context, the term "antimicrobial" means that the composition is effective against pathogens and viruses. In its broadest sense, the compositions of the present invention are antimicrobial, i.e., antibacterial, antiviral, bactericidal and / or viricidal.

[0063] As used herein, the term "about" or "approximately" means within an acceptable error range for a particular value, as determined by one of ordinary skill in the art, which is determined in part by how the value is measured or determined, i.e., the limitations of the measurement system. [Brief explanation of the drawings]

[0064] [Figure 1A] 1A: Sol-gel transition temperature of Pluronic f-127 in H2O2 at a concentration of 3.5% v / v (bottom graph) compared to the sol-gel transition temperature of Pluronic f-127 in pure water (top graph). [Figure 1B] 1B: Sol-gel transition of Pluronic f-127 (30% w / v) in hydrogen peroxide at different concentrations (v / v) with respect to %H2O2. DETAILED DESCRIPTION OF THE INVENTION

[0065] The compositions described herein can be applied to biological and / or biomaterial surfaces, e.g., These include, but are not limited to, a long-sought means to effectively clean and / or wipe oral surfaces in situ, treating them quickly and effectively without damaging the surface structures being cleaned and leaving essentially no contaminant residue, while at the same time exhibiting antibacterial and / or anti-inflammatory effects.

[0066] The composition described herein is a water-soluble, easily rinsed-off, tissue-friendly, non-ionic surfactant. It contains a non-toxic formulation of active ingredients that have been thoroughly studied in clinical use, making it particularly suitable for injection, oral, and dermal application. The composition described herein for the first time has been proven non-sensitizing and non-irritating in clinical trials. The composition of the present invention is compatible with other treatments for biofouling and inflammation.

[0067] The compositions described herein have a liquid state that facilitates easy mixing and application at room temperature. At temperatures below 30°C, such as room temperature, the compositions exhibit an easily flowing liquid consistency with a surfactant effect that allows the composition to reach difficult locations when applied to narrow defects. Once applied, the micelles begin to bind at the patient's natural body temperature and quickly form a stable gel at body temperature, allowing for prolonged and intimate contact with the implant surface and tissue at the application site.

[0068] The compositions described herein are further formulated to contain bioabsorbable microparticles that aid in the mechanical cleaning of micro-rough implant surfaces, facilitating the cleaning of surfaces with intact, original structure. The gel-particle suspension is used with a cleaning implement, such as a brush (e.g., TiBrush®), or other cleaning device.

[0069] The composition of the present invention mimics the natural release of reactive oxygen species (ROS) from peroxides produced by human cells. The charges from ROS disrupt the membranes of pathogenic bacteria, and oxygen itself is toxic to anaerobic bacteria. Human cells themselves are protected from ROS by enzymes in their cell membranes, and local tissues may benefit from increased oxygen. Pathogenic bacteria lack such protection and, due to fundamentally different cell membrane design, are unable to develop resistance. Thus, the composition can effectively dissolve biofilms, debris, and mineral deposits, as well as extracellular organic matter at the application site.

[0070] Additionally, the acidity of the peroxide helps the cells dissolve mineral deposits, decomposing and removing extracellular organic matter and calcified material from the contaminated implant.

[0071] Cells use peroxide as a second messenger system to activate cellular defenses against pathogens. The compositions disclosed herein mimic this signal, stimulating and strengthening the local cellular defense network.

[0072] Using the compositions presented herein, the active oxygen released from the hydrogel removes carbon contaminants from the titanium-containing implant surface and reactivates the titanium dioxide layer of the implant. This process reestablishes the implant's original charge and hydrophilicity, restoring optimal biological surface properties, which are key factors for the further survival or successful reintegration of the treated implant. This effect is visualized in the experimental section by improved cell spreading and superhydrophilicity.

[0073] The composition is an advanced micelle-forming gel formulation that works synergistically with naturally occurring oxygen to break down and remove biofouling, eliminate pathogens, moisturize tissues and implants, and revitalize titanium implant surfaces.

[0074] The hydrogel component and active oxygen of the composition act synergistically to avoid foaming and direct oxygen to the surface. The composition provides moisture, allowing charged oxygen to act without the risk of drying out the tissue and / or implant, while the reactive oxygen eliminates pathogens, which become suspended and trapped in the gel formed at body temperature. Organic contaminants are then denatured by the powerful surfactant effect, decomposed by the reactive oxygen, dissolved, and trapped in the gel. Both the gel and oxygen reduce inflammation and support tissue health. The gel formed at body temperature prolongs the local effect of the reactive oxygen, which in turn strengthens the cellular defense network. Synergistically, the gel and the reactive oxygen remove contaminants and reactivate the implant surface. The inverse thermodynamics of the gel, combined with the destructive effect of the reactive oxygen, create an equilibrium between the micelle-sol and gel states, significantly increasing the cleaning effect.

[0075] The compositions described herein are novel formulations of biocompatible hydrogels with strong nonionic surfactant properties that have improved sol-gel kinetics for solubilizing and capturing debris and pathogens for effective in situ cleaning and / or wiping of biological and / or biomaterial surfaces. The compositions are easily washed off with water and completely decompose into water, oxygen, and carbon oxides.

[0076] The compositions disclosed herein provide new and improved means for treating and eliminating biofilms, preventing biofilm formation, degrading biofilm extracellular matrix, and inhibiting the viability and growth of bacteria within biofilms. In particular, the subject matter disclosed herein provides compositions for the prevention and / or treatment of oral diseases (e.g., caries, periodontitis, gingivitis, mucositis, and / or peri-implantitis).

[0077] The present invention itself is based on the combination of hydrogen peroxide (HO) and pluronic acid at concentrations such that the composition is in liquid form at room temperature, i.e., temperatures below 30°C, but converts to a gel state in situ at the application site upon temperature increase to body temperature. The HO component of the composition can be provided in the form of a concentrate (at least 10-50% v / v concentration) in a separate vial for mixing immediately before use, typically in embodiments applied with a Luer-Lock mixing connector, or directly dissolved in a hydrogel consisting of pluronic acid and water (or saline), typically at a final concentration of 0.5-5%. The pluronic acid component itself can be any of the pluronic acid varieties, e.g., F-127. The concentration of pluronic acid is typically 0.1-10% w / v, e.g., 0.1-2.5% w / v.

[0078] Pluronic acid acts as both a solubilizer and a surfactant in the compositions disclosed herein, as well as a moisturizer and dynamic viscosity modifier. When the hydrogel formulation is heated to body temperature, the micelles of pluronic acid self-assemble into a packed structure, forming a viscous gel. This allows the gel to remain at the application site and exert its activity where needed. The activity of this hydrogel is further enhanced by the addition of charged oxygen, which dissolves the packed micellar structure, thereby establishing a dynamic equilibrium between the sol and gel states. This dynamic state promotes efficient solubilization and capture of particles, pathogens, and contaminants during the wiping procedure.

[0079] The innovation of the present invention is based on the synergistic effect between pluronic acid and peroxide. Pluronic acid has an inverse thermodynamic ability to form "packed" micellar structures in which multiple micelles combine to form a hydrogel. This ability increases with increasing temperature, resulting in a transition to a gel state under physiological conditions (e.g., >20°C). This sol-gel transition forms a stable gel that functions for long periods of time as a wound dressing, for example on living skin, mucous membranes, or wounds, capable of absorbing moisture and / or organic pollutants to some extent.

[0080] However, when mixed with hydrogen peroxide, the sol-gel transition is more dynamic and less stable, and the present invention discloses for the first time that the transition between the sol state (single solubilized micelles) and the gel state (packed micellar structure) is in "dynamic" equilibrium with the radical activity of peroxide, even under physiological conditions (=high temperature). This effectively means that in the presence of peroxide, the packed micellar structure dissolves and is constantly reformed (not only by lowering or raising the temperature), even when the gel is applied to human tissues / skin / mucosa. This effect significantly increases the surfactant and scavenging effects of pluronic acid.

[0081] Combined with the effect of hydrogen peroxide releasing free oxygen radicals on virus particles, pathogens, and necrotic tissue, the sol-gel transition dissolves and traps organic contaminants, which are then removed by washing off the gel.

[0082] Another advantage of the compositions of the present invention is that adding hydrogen peroxide to pluronic acid increases the temperature at which the packed micellar structure forms; that is, pluronic gels containing low concentrations of peroxide are liquid at room temperature and can be applied through a syringe needle or from a dispenser bottle without clogging the nozzle. This is not possible with pluronic acid alone, because pluronic acid begins to form a stable "packed micellar" gel at room temperature, making it very difficult to squeeze through the thin tip of a syringe or from a dispenser bottle through a pump applicator. For this reason, pluronic gels for wound care are sold as gels in boxes or tubes.

[0083] The increased efficacy of the combination of a weak peroxide and pluronic acid was unexpected and surprising.

[0084] The reduced viscosity of Pluronic hydrogels in combination with peroxide also aids in application. The nature of the gel state at physiological temperatures allows cleaning and / or wiping compositions to reach tight spaces and undercuts that Pluronic gel alone cannot reach. Therefore, it is more effective at cleaning rough (implant) surfaces, tight spaces such as between bone and implants / teeth, and skin creases.

[0085] composition The present invention provides a novel antimicrobial and / or anti-inflammatory composition for cleaning and / or wiping biological and / or biomaterial surfaces in situ, comprising at least two components: a. H2O2 at a final concentration of 0.1-5 v / v, and b. Composite hydrogel formulations containing pluronic acid at concentrations of 10-40% w / v and which is liquid at room temperature, for example at a temperature of up to 30°C, for example at a temperature of 20-30°C, for example at 25°C.

[0086] The compositions disclosed herein are characterized by containing components a and b in a ratio such that the composition is in a liquid state, not a gel state, at room temperature. A typical concentration ratio between components a and b is approximately 1:10 (HO concentration: pluronic acid concentration). Generally, the higher the pluronic acid concentration, the higher the HO concentration required to maintain the composition in a liquid (sol) state at temperatures between 20 and 30°C. Exemplary concentration ratios may be, for example, >2.0% v / v HO:15% w / v pluronic acid, >2.5% v / v HO:20% w / v pluronic acid, >3 v / v HO:25% w / v pluronic acid, >3.5% v / v HO:30% w / v pluronic acid, or >5% v / v HO:40% w / v pluronic acid.

[0087] In one embodiment of the antibacterial and / or anti-inflammatory composition according to the present invention, the composite hydrogel formulation of component b. comprises pluronic acid in a concentration of 10-40% w / v, for example at least 10% w / v, such as 10, 15, 20, 25, 30, 35 or 40% w / v.

[0088] In another embodiment of the antibacterial and / or anti-inflammatory composition according to the present invention, the composite hydrogel formulation of component b. comprises pluronic acid in a concentration of up to 40% w / v, such as up to 15, 20, 25, 30 or 35% w / v.

[0089] The antibacterial and / or anti-inflammatory composition according to the present invention may be a composition in which the final concentration of HO in component a is 0.1-5% v / v, for example, 0.5-3% v / v, for example, 0.1-5% v / v. In one embodiment, the final concentration of HO in component a is 5% v / v or less, for example, 0.1-5% v / v, for example, 1, 2, 3, 4, or 5% v / v.

[0090] The antibacterial and / or anti-inflammatory composition according to the present invention may further comprise water and / or saline.

[0091] The two components of the antimicrobial and / or anti-inflammatory composition according to the present invention may be in one solution, or at least the two components are kept separate from each other until they are mixed together and applied in situ to a biological and / or biomaterial surface.

[0092] In antibacterial and / or anti-inflammatory compositions according to the invention, in which the components are kept separate from one another prior to application, the separate component a. may be a composition comprising HO in a concentration of at least 10-50% v / v, for example up to 10, 20, 30, 40 or 50% v / v. In one embodiment, the composition of the invention comprises HO in a concentration of 30% v / v.

[0093] emulsifiers and / or viscosity modifiers In one embodiment, the antibacterial and / or anti-inflammatory composition according to the invention further comprises one or more emulsifiers and / or viscosity modifiers, which may be selected from the group consisting of glycerin, glycol, polyethylene glycol (PEG), polyoxyethylene polyoxypropylene block copolymers (pluronic polyols), polyglycol alginate (PGA), CMC (carboxymethyl cellulose), glycerol, aloe vera gel, alginic acid, hyaluronic acid (HA) and chitosan.

[0094] The antibacterial and / or anti-inflammatory composition according to the present invention may also comprise one or more surfactants selected from the group consisting of SDS (sodium dodecyl sulfate), sodium stannate, sodium pyrophosphate, oxine and SLS (sodium lauryl sulfate).

[0095] The antibacterial and / or anti-inflammatory compositions according to the present invention may further comprise one or more fragrance oils such as, but not limited to, oils of spearmint, peppermint, wintergreen, sassafras, clove, sage, eucalyptus, marjoram, cinnamon, and methyl salicylate and menthol.

[0096] The antibacterial and / or anti-inflammatory compositions according to the present invention may further comprise one or more weakly acidic buffering agents.

[0097] fine particles The composition according to the present invention further comprises fine particles having an average particle size (D50) of 20 to 200 μm. The fine particles are typically present at a concentration of about 0.5 to 1000 g / L, for example, about 0.5 to 300 g / L.

[0098] The composition according to the present invention comprises Ca 2+ , F - , Sr 2+ and Mg 2+The particle may include particles that emit one or more ions selected from the group consisting of:

[0099] In one aspect, a composition according to the present invention comprises microparticles of a calcium salt compound powder selected from the group consisting of calcium sulfate, calcium carbonate, calcium aluminate, calcium lactate, calcium nitrate, calcium citrate, calcium acetate, calcium stearate, calcium fumarate, calcium malate, calcium chloride, calcium bromide, calcium fluoride, calcium iodide, calcium saccharin, calcium oxalate, calcium gluconate, calcium propionate, calcium caseinate, calcium glycerophosphate, and combinations thereof.

[0100] In another embodiment, the composition according to the present invention comprises particulates comprising a calcium oxide compound powder selected from the group consisting of calcium oxide, calcium peroxide, calcium hydroxide, and combinations thereof.

[0101] In another aspect, the composition according to the present invention comprises microparticles providing a calcium ion source selected from the group consisting of calcium chloride, calcium sulfate, calcium aluminosilicate, calcium carbonate, calcium chloride, calcium ascorbate and calcium oxide, and the phosphate ion source is sodium phosphate diphosphate.

[0102] In yet another aspect, the composition according to the present invention comprises microparticles comprising a calcium phosphate compound powder selected from the group consisting of octacalcium phosphate, heptacalcium phosphate, pentacalcium phosphate, tetracalcium phosphate, tricalcium phosphate, dicalcium phosphate, monocalcium phosphate, calcium pyrophosphate, calcium metaphosphate, calcium phosphinate, amorphous calcium phosphate, calcium hydroxide phosphate, and combinations thereof.

[0103] In yet another embodiment, the composition according to the present invention comprises additional microparticles of a compound selected from the group consisting of silica, silicate glass, quartz, zinc oxide, barium sulfate, barium silicate, strontium silicate, barium borosilicate, strontium borosilicate, borosilicate, lithium silicate, amorphous silica, bismuth compounds, ammoniated or deammoniated calcium phosphate, alumina, zirconia, tin oxide, titania, apatite, silica glass fillers, calcium silicate-based fillers, hydroxyapatite, barium sulfate, bismuth subcarbonate, iron, silicon, magnesium, zinc, silver, manganese, palladium, radium, or mixtures thereof.

[0104] In yet another aspect, a composition according to the present invention comprises particulates that are polymer particles, mineral particles, metal particles, barium boroaluminosilicate glass, fluoroaluminosilicate glass, silica, silicate glass, quartz, barium silicate glass, strontium silicate glass, barium borosilicate glass, borosilicate glass, barium aluminofluorosilicate glass, lithium silicate, amorphous silica, barium magnesium aluminosilicate glass, barium aluminosilicate glass, strontium aluminum borosilicate glass; strontium aluminofluorosilicate glass, amorphous silica, zirconium silicate glass, or mixtures thereof.

[0105] Additionally, the composition according to the present invention may further comprise a fluoride ion source, wherein the fluoride ion source is selected from the group consisting of Na2SiF6, CaF2, SrF2, NaF, NaPO3F, NaKF6PO3, K2SiF6, F6, NaP, NaSbF6, KSbF6, F6KP and and mixtures thereof.

[0106] When the composition according to the invention is intended for use in cleaning and / or wiping dental implants having a metal surface, the microparticles are preferably biocompatible and solid (hard) and may also be biodegradable.

[0107] The solid particulates can be selected from the group of materials consisting of TiO2, zirconium oxide, diamond dust (carbon), polymers, polylactic acid (beans), minerals, ceramics, aluminum trioxide, calcium carbonate, calcium phosphate, apatite crystals, bone ceramic particles (hydroxyapatite / calcium phosphate), titanium, zirconium, aluminum oxide, carborundum, pumice and silica.

[0108] The choice of material for the solid particulates is preferably made depending on which material, e.g., metal implant or hard tissue surface, is to be cleaned / wiped with the composition of the present invention, to match the roughness of the material and allow for efficient cleaning / wiping of the material while still not damaging the material.

[0109] One advantage of selecting the particular size of the microparticles is that the diameter of the cavities typically formed by surface treatment of dental implants is 80 to 180 pm. Thus, the presence of solid microparticles in the compositions of the present invention makes the compositions particularly suitable for in situ cleaning and / or wiping of implants in the oral cavity, as the microparticles are of a size that allows them to penetrate the cavities to clean them, yet are large enough not to cause an inflammatory response and / or to be encapsulated by the body in fibrous capsules.

[0110] The particulates may be organic or inorganic.

[0111] The organic microparticles included in the compositions according to the present invention are selected from the non-limiting group consisting of crystals of amino acids, biopolymers, chitosan, alginic acid, pluronic acid, collagen, hyaluronic acid, PEG and organic acids (including but not limited to insoluble salts thereof such as tartar).

[0112] The inorganic fine particles contained in the composition according to the present invention are selected from metal compounds, for example, from the group consisting of iron, titanium, silicon, magnesium, zinc, zirconium, silver, manganese, palladium, radium, calcium and barium.

[0113] In one embodiment, the microparticles contained in the composition according to the invention are biodegradable and are selected from the group consisting of bare zinc, iron, silicon, magnesium, manganese, silver and palladium.

[0114] Antibacterial and / or anti-inflammatory compositions according to the present invention that include microparticles are typically formulated as a suspension of solid particles in a liquid.

[0115] Mesh-forming and scaffold-forming components The composition according to the invention may further comprise at least one mesh-forming and / or scaffold-forming component, typically selected from the group consisting of silk fibers, carbon fibers, silicates, borosilicates, collagen and spider web threads, to improve the physical strength and / or chemical longevity of the composition after application.

[0116] biologically active substances Alternatively or additionally, compositions according to the present invention may comprise a bioactive agent, typically selected from the group consisting of EMDs, peptides, drugs, bioactive ions, small molecules, radioactive molecules, antimicrobial molecules and radiopaque molecules.

[0117] Cleansing ingredients and antibacterial substances Additionally, the compositions according to the present invention may also contain additional antibacterial and / or cleaning ingredients.

[0118] In the present context, the further antibacterial substance comprised in the composition according to the invention is selected from the non-exclusive list consisting of amoxicillin, doxycycline, cephalexin, ciprofloxacin, clindamycin, metronidazole, azithromycin, sulfamethoxazole and trimethoprim.

[0119] In one embodiment, the further antibacterial agent comprised in the composition according to the invention is tetracycline, doxycycline, macrolides, penicillin (stabilized), chlorhexidine, chloramine and mixtures thereof.

[0120] In one embodiment, the composition according to the invention comprises a further anti-inflammatory substance.

[0121] At least 1 year shelf life at room temperature (RT) In one embodiment, the composition according to the invention has a shelf life of at least 1 year at RT.

[0122] kit The present invention also relates to a kit comprising the composition according to the present invention, which comprises at least two containers, a syringe and a vial, each containing the separate components a. and b., a connector device, an applicator tip and instructions, and optionally a mixing device and a wiping 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 comprise instructions, a mixing device, an applicator tip and a wiping implement such as, but not limited to, a brush.

[0123] The antibacterial and / or anti-inflammatory compositions according to the invention are mixed before application and final storage, or stored separately and mixed immediately or shortly before and / or at the time of application.Thus, in another 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 further (such as a third or fourth) container comprising components c), (d), e), etc.), which may for example comprise microparticles and / or mesh-forming materials and / or biologically active materials and / or wiping components and / or further antibacterial and / or anti-inflammatory materials.

[0124] Optionally, such kit can also include instructions for preparing the composition of the present invention.The kit can also include one or more devices for applying the composition to a subject.Such device can be, for example, a syringe or an implant cleaning and / or wiping tool for cleaning and / or wiping implants, such as in the oral cavity.

[0125] Preferably, the implant cleaning and / or debriding tool comprises an elongate base member formed by at least two wires twisted together, and a plurality of bristles secured between and extending away from said twisted wires, thereby positioned in a cleaning section at a first end of said base member; said bristles being made of titanium and / or a titanium alloy. The kits of the invention may also comprise a composition of the invention in one or more containers, and an implant cleaning and / or wiping implement for cleaning and / or wiping an implant in the oral cavity.

[0126] An example of such an implant cleaning / wiping tool for cleaning dental implants and / or wiping hard tissue surfaces is disclosed in US Pat. No. 6,345,406, and another example is shown in WO2009 / 083281.

[0127] The implant cleaning / wiping tool disclosed in WO2009 / 083281 has bristles with a diameter of 0.2 mm. In one embodiment of the present invention, a composition of the present invention containing solid particulates of a size that allows for efficient cleaning of implants and / or hard surfaces in the oral cavity is particularly suitable for use with this tool. In this embodiment, the particulates optimally have a size of about 150 pm, for example, 100-150 pm, because the body is more likely to take up the particles in fibrous capsules when the particles are 10-100 pm.

[0128] Thus, the present invention in one aspect comprises: a. at least two containers containing components a. and b., respectively; b. Syringes and vials; c. connector device; d. applicator tip, and e. Instructions The present invention relates to a kit comprising the composition of any one of the preceding claims, comprising:

[0129] In another aspect, the present invention provides a method for producing a pharmaceutical composition comprising: f. Mixed Devices, and g. Cleaning tools It further relates to a kit comprising:

[0130] In a preferred embodiment herein, a kit comprising a composition according to the present invention typically provides the two components a. and b. in a two-chamber syringe, and further comprises instructions, a mixing device, an applicator tip, and optionally a wiping implement.

[0131] In one aspect of the invention, the kit further comprises a bone graft material, for example, any commercially available bone graft material (Titanoxyd scaffold, BioOss, Emdogain, biceramics, SmartBone, etc.).

[0132] use The compositions disclosed herein are intended to be used to clean and / or wipe biological and / or biomaterial surfaces in situ.

[0133] The compositions disclosed herein are particularly useful for application to peri-implant defects, but can be formulated to suit a variety of clinical procedures.

[0134] For example, formulations used to treat and / or prevent peri-implantitis typically contain relatively high contents of active oxygen and mechanically scavenging particulates.

[0135] Typical formulations for treating and / or preventing peri-implant mucositis include increased active oxygen and increased sol-gel activity.

[0136] For peri-implant maintenance, peri-implant prophylaxis, and post-operative follow-up Typical formulations of contain high active oxygen concentrations.

[0137] However, the compositions disclosed herein are also used in other oral procedures, such as during surgical debridement of periodontal defects, preparation before regenerative procedures, periodontal maintenance treatments, periodontitis prophylaxis (dental hygiene), and endodontic therapy for both endodontic and periapical surgery.

[0138] Additionally, the compositions disclosed herein can further be used for extraoral cleansing and / or debridement, including but not limited to, orthopedic revision surgery, debridement of transdermal devices, skin wound care for cleansing acute wounds and / or debridement of chronic ulcers and burns.

[0139] The antibacterial and / or anti-inflammatory compositions according to the present invention may typically be employed for use in the treatment and / or prevention of peri-implantitis, gingivitis and / or mucositis, peri-implant mucositis and / or periodontitis.

[0140] Peri-implantitis is a typical complication associated with oral and dental rehabilitation using implants, i.e., peri-implant disease, and is known to those skilled in the art as an inflammatory reaction accompanied by loss of bony support of the implant. The etiology of this disease is conditioned by the condition of the peri-implant tissues, the implant design, the degree of roughness, the malalignment of the implant components, the external morphology, and excessive mechanical loads.

[0141] The antimicrobial and / or anti-inflammatory compositions described herein provide, for the first time, a means to effectively and quickly clean implants and / or wipe hard surfaces in the oral cavity without essentially damaging the anatomical structures or the implants and / or hard surfaces themselves, and without essentially leaving any contaminating residue on the treated surfaces.

[0142] Thus, in one aspect the present invention relates to an antibacterial and / or anti-inflammatory composition as defined herein for use as a medicament and / or a kit for preparing a composition of the invention as defined herein.

[0143] Thus, the present invention relates to the use of an antibacterial and / or anti-inflammatory composition according to the present invention for cleaning and / or debridement of implants in the oral cavity, such as in situ implants, hard surfaces in the oral cavity, such as the outer surfaces of oral hard tissues, surgically exposed hard surfaces in the oral cavity, wounds in the oral cavity, such as wounds resulting from peri-implantitis or surgical wounds, periodontal defects and / or periodontal wounds, and / or oral hard tissue defects, etc.

[0144] The present invention also relates to the use of an antibacterial and / or anti-inflammatory composition as defined herein for the preparation of a medicinal and / or pharmaceutical and / or cosmetic composition for cleaning and / or debridement of implants in the oral cavity such as in situ implants, hard surfaces in the oral cavity such as the external surfaces of oral hard tissues, surgically exposed hard surfaces in the oral cavity, wounds in the oral cavity such as wounds resulting from peri-implantitis or surgical wounds, periodontal defects and / or periodontal wounds, and / or oral hard tissue defects, and / or kits for preparing the compositions of the invention as defined herein.

[0145] The present invention also relates to an antimicrobial and / or anti-inflammatory composition as defined herein or a kit for preparing a composition of the invention as defined herein for use in cleaning and / or debridement of implants in the oral cavity such as in situ implants, hard surfaces in the oral cavity such as the outer surfaces of oral hard tissues, surgically exposed hard surfaces in the oral cavity, oral wounds such as wounds resulting from peri-implantitis or surgical wounds, periodontal defects and / or periodontal wounds, and / or oral hard tissue defects, etc.

[0146] Another preferred embodiment herein relates to the use of the antibacterial and / or anti-inflammatory composition according to the invention in conjunction with an implant cleaning and / or cleaning tool for cleaning implants and / or wiping hard surfaces in the oral cavity, said implant cleaning and / or cleaning tool being characterized in that it comprises an elongate base member, for example formed by at least two wires twisted together, and a plurality of bristles fixed between and extending away from the twisted wires, thereby arranged in a cleaning section at a first end of the base member, said bristles comprising or consisting of titanium and / or a titanium alloy.

[0147] Many medical implants, such as dental implants, orthopedic implants, and vascular stents, are metallic, i.e., made from metal materials. As a result, the present invention relates to the use of the antibacterial and / or anti-inflammatory composition of the present invention, alternatively in combination with an implant cleaning and / or wiping tool, for cleaning and / or wiping implants made from metal materials. Examples of metal materials commonly used to construct metallic medical implants include steel, titanium, zirconium, tantalum, niobium, hafnium, and their alloys. In particular, titanium and titanium alloys have been shown to be suitable for use in constructing medical implants.

[0148] On the other hand, both medical implants and dental implants may be at least partially, and even completely (full ceramic implants), made of porcelain and / or ceramics, such as zirconium oxide and / or hydroxyapatite, or any other ceramic or porcelain material known to those skilled in the art as suitable for implant technology. Accordingly, the present invention also relates to the use of the antibacterial and / or anti-inflammatory composition according to the present invention, alternatively in conjunction with an implant cleaning and / or wiping tool, for cleaning and / or wiping implants made of or containing porcelain and / or ceramics. Consequently, the present invention also relates to the use of the composition of the present invention for the preparation of a medicinal and / or pharmaceutical and / or cosmetic composition for cleaning and / or wiping implants made of or containing porcelain and / or ceramics. The present invention also relates, alternatively, to the composition of the present invention used for cleaning and / or wiping implants made of or containing porcelain and / or ceramics.

[0149] Dental implants are typically used in restorative dental procedures for patients missing one or more teeth. Dental implants include a dental fixture used as a substitute for an artificial tooth root. The dental fixture thus functions as the root of a new tooth. The dental fixture is typically a screw, i.e., it has a screw shape and is typically made of titanium, titanium alloy, zirconium, or zirconium alloy. After the screw is surgically implanted into the jawbone, bone tissue grows around the screw, securing it in the bone with the bone in close contact with the implant surface. After the implant screw is firmly anchored in the jawbone, it can be extended by attaching an abutment to the screw. The abutment, like the screw, may also be made of titanium, titanium alloy, zirconium, or zirconium alloy. The shape and size of the abutment used are adjusted to accurately reach the mucosa after attachment to the screw. A dental restoration, such as a crown, bridge, or denture, can then be attached to the abutment. Alternatively, the implant screw may be shaped and sized to reach the mucosa after implantation, allowing a dental restoration such as a crown, bridge, or denture to be attached directly to the screw without the need for an abutment.

[0150] As a result, the present invention provides dental fixtures such as screws, abutments, and The present invention relates to the use of the antibacterial and / or anti-inflammatory composition according to the present invention, alternatively in combination with an implant cleaning and / or wiping tool, for cleaning and / or wiping any part of a dental implant selected from the group consisting of dental restorations such as crowns, bridges, or dentures. Accordingly, the present invention also relates to the use of the composition according to the present invention for the preparation of a medicinal and / or pharmaceutical and / or cosmetic composition for cleaning and / or wiping any part of a dental implant selected from the group consisting of dental fixtures such as screws, abutments, and dental restorations such as crowns, bridges, or dentures. The present invention also relates to the composition according to the present invention used for cleaning and / or wiping any part of a dental implant selected from the group consisting of dental fixtures such as screws, abutments, and dental restorations such as crowns, bridges, or dentures.

[0151] The present invention further relates to the use of the antibacterial and / or anti-inflammatory composition according to the present invention, alternatively in conjunction with an implant cleaning and / or wiping tool, for cleaning and / or wiping orthopedic implants, such as orthopedic implants used for maintaining and restoring the function of the musculoskeletal system, particularly joints and bones, including pain relief in these structures, and / or for cleaning and / or wiping vascular stents, i.e., tubular implants configured for insertion into blood vessels to prevent or counter localized flow stenosis. Consequently, the present invention also relates to the use of the composition of the present invention for the preparation of a medicament for cleaning and / or wiping orthopedic implants, such as orthopedic implants used for maintaining and restoring the function of the musculoskeletal system, particularly joints and bones, including pain relief in these structures, and / or for cleaning and / or wiping vascular stents. The present invention also relates to compositions of the present invention used to clean and / or wipe orthopedic implants, such as orthopedic implants utilized to maintain and restore function of the musculoskeletal system, particularly joints and bones, including pain relief in these structures, and / or to clean and / or wipe vascular stents.

[0152] The surfaces of or near medical implants, such as dental implants, orthopedic implants, and vascular stents, may need to be cleaned after placement. This is particularly important when infection or contamination occurs, causing a progressive degenerative process in the bone adjacent to the implant known as peri-implantitis. In such cases, the surface of the diseased implant must be cleaned of pathogens and contaminants to halt disease progression and ensure reintegration of the implant. Failure to clean the implant surface can ultimately lead to bone and implant loss, making further replacement treatment difficult or even impossible. Furthermore, the surface of a vascular stent may need to be cleaned during implantation to remove clots, and the interior of the vascular stent, i.e., the cavity within the vascular stent, may need to be cleaned endoscopically during a subsequent procedure to prevent restenosis, i.e., occlusion of the blood vessel.

[0153] Therefore, the present invention relates to the use of the antibacterial and / or anti-inflammatory composition according to the present invention, alternatively in conjunction with an implant cleaning and / or wiping tool, for cleaning and / or wiping an implant or its vicinity after placement. Consequently, the present invention also relates to the use of the composition of the present invention for the preparation of a medicament for cleaning and / or wiping an implant or its vicinity after placement. The present invention also relates to the composition of the present invention used for cleaning and / or wiping an implant or its vicinity after placement.

[0154] Additionally, it may be advantageous or necessary to clean a surgically exposed hard tissue surface for a variety of reasons. For example, it may be advantageous or necessary to clean a surgically exposed hard tissue surface prior to a regenerative procedure, i.e., to prepare the hard tissue surface for the regenerative procedure. Cleaning a surgically exposed hard tissue surface to prepare the surface for the regenerative procedure may be performed. Examples of conditions that may be relevant to the procedure for which it may be beneficial or necessary are: peri-implantitis, periodontitis lesions, marginal periodontitis, apical periodontitis, furcation defects, apical granulomas and cysts, bone cysts, bone tumors, osteogranulomas, bone cancer, (infected) tooth extraction sockets, sicca alveolar inflammation ("dry socket"), irrigation of apicoectomy defects, focal osteomyelitis, trauma-induced defects, implant resection or revision, fracture resection or revision, and removal of temporary bone implants (such as orthopedic bone plates, retainers, and screws). Additionally, it may be beneficial or necessary to debride articular surfaces in arthritic joints, and to debride such surfaces before performing cartilage and ligament regeneration procedures.

[0155] The present invention therefore relates to the use of the antibacterial and / or anti-inflammatory composition according to the invention, alternatively in conjunction with an implant cleaning and / or cleaning device, for cleaning and / or wiping surgically exposed hard tissue surfaces before regenerative procedures. Consequently, the present invention also relates to the use of the composition of the present invention for the preparation of a medicinal and / or pharmaceutical and / or cosmetic composition for cleaning and / or wiping surgically exposed hard tissue surfaces before regenerative procedures. The present invention also relates to the composition of the present invention used for cleaning and / or wiping surgically exposed hard tissue surfaces before regenerative procedures.

[0156] The antibacterial and / or anti-inflammatory compositions of the present invention can alternatively be used in conjunction with an implant cleaning and / or wiping tool during surgery to clean the surface of a metallic medical implant after infection and / or bone resorption. For example, the compositions can be used to clean the surface of a metallic dental implant and / or a metallic orthopedic implant. Thus, the compositions can be used to remove, for example, bacterial biofilm, debris, calculus, or fibrous tissue from the surface of a dental implant, such as a titanium screw. Alternatively, the compositions can be used with an additional cleaning agent (i.e., an antibacterial agent) to remove bacterial biofilm from the vicinity of a dental fixture during implantation. The compositions can also be used to clean the surface or vicinity of an abutment. Consequently, the present invention also relates to the use of the compositions of the present invention for the preparation of a medicament for cleaning, for example, removing bacterial biofilm, debris, calculus, or fibrous tissue from the surface of a metallic dental implant, such as a titanium screw or abutment, or a metallic orthopedic implant. The present invention also relates to the compositions of the present invention used to clean, e.g., remove, bacterial biofilm, debris, calculus, or fibrous tissue from the surface of a metallic dental implant or metallic orthopedic implant, such as a titanium screw or abutment.

[0157] Additionally, the antibacterial and / or anti-inflammatory compositions according to the present invention may alternatively be utilized in conjunction with an implant cleaning and / or wiping tool to remove cement remnants, bacterial biofilm, debris, tartar, or fibrous tissue from the surface of an orthopedic implant, or to remove plaque from the surface of a vascular stent. Alternatively, the compositions are utilized to clean the interior of a vascular stent, i.e., the cavity within the vascular stent, in an endoscopic procedure during subsequent treatment due to restenosis, i.e., occlusion of a blood vessel.

[0158] A procedure involving the use of an antibacterial and / or anti-inflammatory composition according to the present invention, alternatively in conjunction with an implant cleaning and / or debridement tool, can include, for example: surgically exposing the hard tissue surface to be treated; removing the inflamed soft tissue; debridement of the surface by applying an antibacterial and / or anti-inflammatory composition according to the present invention, alternatively in conjunction with an implant cleaning and / or debridement tool; applying a (regenerative) treatment if necessary; replacing the soft tissue; suturing for good primary closure and wound stability; and allowing the wound to heal.

[0159] In particular, the antibacterial and / or anti-inflammatory compositions according to the present invention may alternatively be used for implant cleaning. In conjunction with cleaning and / or wiping tools, it is an efficient tool for wiping surgically exposed root surfaces, furcation defects and bone defects prior to regenerative treatments (i.e., by, for example, Straumann® Emdogain, bone graft material, autogenous bone, membranes, etc.), and the antibacterial and / or anti-inflammatory composition according to the invention, alternatively in conjunction with implant cleaning and / or wiping tools, is particularly effective for the removal of granulation tissue, as well as the removal of mineralized biofilm (dental plaque) stones and subgingival calculus.

[0160] The antibacterial and / or anti-inflammatory compositions according to the present invention may alternatively be advantageously utilized in conjunction with implant cleaning and / or wiping implements for cleaning and / or wiping both "hard" metallic medical and / or dental implants having relatively hard surfaces, such as, for example, steel medical implants, and "soft" metallic medical implants having delicate surfaces, such as, for example, titanium, titanium alloy, zirconium or zirconium alloy medical and / or dental implants.

[0161] Furthermore, the antibacterial and / or anti-inflammatory compositions according to the invention do not leave behind contaminants, i.e. material residues, that are incompatible with the reintegration of the implanted structure, and therefore the risk of inflammation is minimal.

[0162] In particular, the antibacterial and / or anti-inflammatory composition according to the present invention can be used in conjunction with an implant cleaning and / or debridement tool to perform a relatively quick debridement procedure on surfaces that are otherwise difficult to clean and / or difficult to reach using manual instruments. A quick procedure ensures a better treatment outcome. As mentioned above, it is well known that the incidence and frequency of adverse effects, such as postoperative effects, are directly related to, and often proportional to, the time spent debridement of surgically exposed hard tissue surfaces. Therefore, a quick debridement procedure ensures a better overall treatment outcome.

[0163] The use of the antibacterial and / or anti-inflammatory composition according to the invention, alternatively in conjunction with an implant cleaning and / or debridement tool, is particularly advantageous when the treatment plan for the defect includes the placement of a titanium implant or any other device made from titanium, since only titanium, but not other metal ions or polymers, can induce undesirable and / or adverse clinical and / or biological effects that may contaminate the treated area and interfere with the outcome of planned and / or future implant procedures.

[0164] oral hygiene In oral hygiene and dentistry, cleaning refers to the removal of plaque and tartar accumulated on teeth, which is routinely performed by technicians for medical, hygienic and purely cosmetic reasons.Therefore, in one embodiment, the antibacterial and / or anti-inflammatory composition according to the present invention is used to remove plaque and tartar accumulated on patients' natural teeth or dental implants, again alternatively in conjunction with an implant cleaning and / or cleaning tool.The antibacterial and / or anti-inflammatory composition according to the present invention contains oxygen radicals, and is therefore particularly suitable for use in bleaching natural teeth and / or artificial teeth.

[0165] microorganisms The antibacterial and / or anti-inflammatory compositions according to the invention are generally intended for use in wiping and / or cleaning biological and / or biomaterial surfaces in situ, for example for use in the in situ removal of biofouling, biofilm and / or necrotic tissue from such biological and / or biomaterial surfaces.

[0166] Biophiles that can be prevented, eliminated and / or treated by the compositions of the present disclosure Biofilms include, but are not limited to, biofilms present within the oral cavity, for example, on tooth surfaces, mucosal / soft tissue surfaces such as gingiva / periodontal tissue, and within dental canals (eg, endodontic canals).

[0167] In certain embodiments, biofilms prevented, eliminated, and / or treated by the compositions of the present disclosure include biofilms present in the urinary tract, lungs, gastrointestinal tract, on and / or within chronic wounds, and on surfaces (e.g., implants), and within medical devices and medical lines, such as catheters, medical instruments, and medical tubing.

[0168] The compositions of the present disclosure are used to reduce the growth and / or inhibit the viability of one or more microorganisms, such as bacteria within a biofilm. For example, but not limited to, bacteria include Streptococcus mutans (S. mutans), Streptococcus sobrinus, Streptococcus sanguis (S. sctnguinis), Streptococcus gordonii, Streptococcus oralis, Streptococcus mitis, Actinomyces odontolyticus, Actinomyces viscosus, Aggregatibacter actinomycetemcomitans, and the like. Lactobacillus spp., Porphyromonas gingivalis, Prevotella intermedia, Bacteroides forsythus, Treponema denticola, Fusobacterium nucleatum, Campylobacter rectus, Eikenella corodins, corrodens, Veillonella spp., Micromonas micros, Porphyromonas cangingivalis, Haemophilus actinomycetemcomitans, Actinomyces spp., Bacillus spp., Mycobacterium spp., Fusobacterium spp., Streptococcus spp., Staphylococcus aureus, Group A hemolytic streptococci, Group B hemolytic streptococci (Streptococcus agalectiae), Proteus mirabilis mirabilis, Elebsiella pneumoniae, Acinetobacter spp., Enterococcus spp., Prevotella spp., Porphyromonas spp., Clostridium spp., Stenotrophomonas maltophilia, P. cangingivalis, Candida albicans, Escherichia coli, and / or Pseudomonas aeruginosa. In certain embodiments, the bacterium is S. mutans, which is present in the oral cavity, for example, in biofilms found on the surfaces of teeth.

[0169] The microorganisms most commonly associated with implant defects are spirochetes and migratory forms of gram-negative anaerobes. Diagnosis may be based on changes in gingival color, bleeding and probing of the peri-implant pocket, suppuration, x-rays, and gradual loss of bone height around the teeth. The antibiotic therapy that has proven most effective so far is the combination of amoxicillin and clavulanic acid. Naturally, pathogenic infections in the oral cavity can include fungal and / or viral infections in addition to bacterial infections.

[0170] The antibacterial and / or anti-inflammatory compositions according to the present invention are effective in killing bacteria, fungi and / or viruses.

[0171] Additionally, the compositions described herein are antibacterial and anti-inflammatory without causing microbial resistance.

[0172] Consequently, the present invention relates to a method for treating and / or preventing peri-implantitis, gingivitis and / or mucositis, peri-implant mucositis and / or periodontitis, which method comprises cleaning and / or wiping biological and / or biomaterial surfaces in situ by applying a composition according to the present invention to said soiled, filmed and / or necrotic surfaces. [Example]

[0173] The following examples are included to provide guidance to those skilled in the art for practicing representative embodiments of the subject matter disclosed herein. Given the present invention and the general level of skill in the art, those skilled in the art will appreciate that the following examples are intended to be illustrative only, and that numerous changes, modifications, and variations are available without departing from the scope of the subject matter disclosed herein. [Example]

[0174] Decomposition of methylene blue when mixed with 3% v / v H2O2 and release of fluoride at various concentrations Methylene blue (MB) has the molecular formula: C 16 H 18 Methylene blue (MB) is a heterocyclic aromatic chemical compound with NSCl (AldrichSigmaAldrich, Oslo, Norway). MB has many applications in various different fields, such as biology and chemistry. MB is an example of an organic material, and as such, it is commonly used as an agent to simulate bacteria and to investigate the decomposition characteristics of H2O2, as seen in multiple publications. Therefore, MB degradation is used as a model for the in vivo degradation of organic materials, such as bacteria or dead, damaged, and / or infected tissue. At room temperature, it appears as a solid, odorless, dark green powder, and when dissolved in water, it produces a blue solution. Upon decomposition in solution, MB becomes colorless. Methylene blue was analyzed by UV-vis spectrophotometry (Lambda25, Perkin Elmer, USA), where it absorbs light at 690 cm. This instrument was used to quantify MB degradation.

[0175] The objective was to determine whether methylene blue could be degraded by 5% HO (PERDROGEN® 30% HO (v / v), Sigma Aldrich AS, Oslo, Norway) alone, without ACP, in a composite hydrogel formulation containing pluronic acid (Sigma Aldrich AS, Oslo, Norway) at a concentration of 5% w / v. Increasing concentrations of amorphous calcium phosphate ACP (by mixing two precursor components; component A contained 40 MB in a mixture of monobasic and dibasic ammonium phosphate at pH 5.5) were then added to the solution, up to a maximum concentration of 8 g / L.

[0176] Measurements were taken every 3 minutes for 1 hour. The pH of the suspension containing MB was also recorded. The suspension was stirred before each measurement to prevent sedimentation of ACP particles.

[0177] When 15% v / v HO (PERDROGEN® 30% HO (v / v), Sigma Aldrich AS, Oslo, Norway) alone was mixed with MB, almost no degradation was found. Surprisingly, the presence of 0.25 g / L ACP in the suspension allowed for MB degradation. Increasing the concentration of ACP particles in the suspension increased MB degradation. Increasing the concentration of ACP particles slightly decreased the pH from 3.7 without ACP to 2.8 with 1 M ACP.

[0178] H2O2 alone was not able to decompose the MB molecule; surprisingly, ACP had to be present to achieve this goal. [Example]

[0179] Decomposition of methylene blue when mixed with 7% H2O2 and various concentrations of ACP The objective was to determine whether methylene blue could be degraded by ACP nanoparticles alone (chemicals from Sigma Aldrich, synthesized by a mixture of monobasic and dibasic ammonium phosphates at pH 5.5) without HO in a composite hydrogel formulation containing pluronic acid (Sigma Aldrich AS, Oslo, Norway) at a concentration of 5% w / v. Increasing concentrations of HO (PERDROGEN® 30% HO (v / v), Sigma Aldrich AS, Oslo, Norway) were then added to the suspension, up to a maximum concentration of 7% v / v. The experimental procedure was the same as that described in Example 1.

[0180] Results are not shown. When 0.5 g / L of ACP alone was mixed with MB, little degradation was found. Addition of 5% v / v concentrated H2O2 increased MB degradation. Increasing the concentration of H2O2 in the suspension linearly increased MB degradation. With increasing H2O2 concentration, the pH decreased from 4.9 without H2O2 to 3.3 with 15% v / v H2O2.

[0181] ACP alone was unable to decompose MB molecules; H2O2 had to be present to achieve this goal. [Example]

[0182] Degradation of methylene blue when mixed with a 5% H2O2 suspension in composite hydrogel formulations containing pluronic acid (Sigma Aldrich AS, Oslo, Norway) at a concentration of 5% w / v and synthetic octacalcium phosphate (OCP) and fluoride-substituted calcium phosphate (F-CaP) From Examples 1 and 2, we selected HO (PERDROGEN® 30% HO (v / v), Sigma Aldrich AS, Oslo, Norway) in a composite hydrogel formulation containing pluronic acid (Sigma Aldrich AS, Oslo, Norway) at a concentration of 5% w / v, and synthetic octacalcium phosphate (OCP) and fluoride-substituted OCP concentrate to exploit this synergistic effect while creating a suspension that can be used in physiological environments ([HO] < 6% v / v and pH > 3).

[0183] Synthetic OCP and two types of fluoride-containing apatite-type calcium phosphate (hereinafter referred to as F-CaP) were prepared according to a previously reported method. Briefly, fluoride-containing apatite-type calcium phosphate (hereinafter referred to as HF-CaP) was synthesized by hydrolysis using F- by incubating OCP powder in 150 mM Tris buffer containing 50 ppm F- (as sodium fluoride: NaF) at 37 °C. The initial concentration of the buffer was 1.5 ppm. The pH was varied from 7.1 to 9.9. The incubation of HF-CaP lasted for 10 or 60 min. On the other hand, fluoride-containing apatite-type calcium phosphate from coprecipitation with F (hereafter referred to as CF-CaP) was prepared by applying the coprecipitation of OCP in the presence of F. Following a previously described synthesis method, calcium acetate solution was added to a sodium hydrogen phosphate solution containing F (as NaF) at 70 °C for 30 min. The F concentration initially used ranged from 12 to 230 ppm. All collected samples were washed several times with distilled water and dried overnight at 105 °C.

[0184] The aim was to discover whether NaCl and NaF salts could further increase the decomposition of MB when introduced into the selected suspensions. Results are not shown.

[0185] Interestingly, doping the suspension with NaCl reduced MB degradation by half compared to suspensions containing only OCP and H2O2. Substitution with F (Sigma Aldrich AS, Oslo, Norway) reduced MB degradation even more strongly, nearly preventing this degradation from occurring compared to suspensions containing only OCP and H2O2.

[0186] Doping the H2O2 / OCP suspension with NaF (Sigma Aldrich AS, Oslo, Norway) and NaCl (Sigma Aldrich AS, Oslo, Norway) salts did not increase MB degradation.

[0187] Changes in Ca2+ and inorganic phosphate ion concentrations on F-CaP coatings The concentrations of Ca2+ and inorganic phosphate ions (Pi) in the culture medium were determined using Calcium E and Phosphor C tests (Wako Pure Chemical Industries, Osaka, Japan), respectively. One hundred microliters of α-MEM containing 10% FBS was added to each well of a 96-well tissue culture plate coated with F-CaP or OCP. After incubating the plate at 37°C in a 5% carbon dioxide atmosphere for 3 days, the supernatant was collected and quantitatively analyzed for Ca2+ and Pi.

[0188] The dissolution behavior of F-CaP or OCP particles was investigated after incubation with α-MEM for 3 days at 37°C. The Ca2+ concentrations in the supernatants of HF1.80-CaP and HF3.33-CaP were significantly reduced compared with the uncoated controls. Conversely, the Ca2+ concentrations in the medium from CF-CaP coatings were equal to or slightly greater than those of OCP. [Example]

[0189] pH measurements of different suspensions of composite hydrogel formulations containing pluronic acid (Sigma Aldrich AS, Oslo, Norway) at a concentration of 10% w / v. pH is an important factor in wound healing and the pH of the suspension can be altered by different calcium phosphate (from Example 3) concentrations and other added ingredients.

[0190] Laboratory pH meter (Blueline 14 pH with pH Electrode) The pH in the different solutions was measured using a Meter Lab 850 Set (Scott Glass Ltd, Stafford, UK). Below is a list of the pH values ​​obtained after the given concentrations: 1. A mixture of 5% v / v H2O2 and 1.6 g / L 1.6 g / L ACP gave a pH of 4.4 ± 0.1. 2. A mixture of 5% v / v H2O2 + 1.6 g / L HA gave a pH of 5.2 ± 0.1. 3. A mixture of 5% v / v H2O22 + 1.6 g / L CaPF2 gave a pH of 6.1 ± 0.0. 4. A mixture of 5% v / v H2O2 + 1.6 g / L OCP-F + 1.6 g / L ACP gave a pH of 4.2 ± 0.1. 5. A mixture of 5% H2O2 + 1.6 g / L HA-F + 1.6 g / L ACP gave a pH of 5.9 ± 0.0.

[0191] The range for the various test suspensions was from 4.2 to 6.1. [Example]

[0192] Various calcium phosphate suspensions Solutions of various calcium phosphates at 2 g / L were purchased from Sigma Aldrich (hydroxylapatite, calcium hydroxide phosphate, HapCa). 10 (PO4)6(OH)2, tribasic calcium phosphate [Ca5(OH)(PO4)3] x , β-TCP, β-tricalcium phosphate Ca3O8P2, α-tricalcium phosphate Ca3O8P2), and CaP in Examples 1-4, and were mixed with 3 vol.% H2O2 in Examples 1 and 2 (PERDROGEN® 30% H2O2 (v / v), Sigma Aldrich AS, Oslo, Norway).

[0193] The amount of calcium in the different compositions was determined using atomic absorption spectroscopy (AAS; AANALYST400, Perkin Elmer, USA). AAS samples were acidified with HCl to dissolve precipitated minerals, and then lanthanum chloride was added at a concentration of 10 mg / mL to precipitate the phosphates. Acetylene was used as the carrier gas. Three independent samples were measured per data point. [Example]

[0194] Antibacterial effect of Ca-P particles against Staphylococcus aureus This example describes the antibacterial potential of activated CA-P particles.

[0195] Bacteria: Staphylococcus aureus (S. aureus) is an important human commensal and opportunistic pathogen that causes a wide range of infections. It is one of the most well-known bacterial causes of postoperative infections. Therefore, S. aureus was chosen for this experiment.

[0196] procedure: Three gels were treated with 1, 2, and 5% v / v HO (PERDROGEN® 30% HO (v / v), Sigma Aldritch AS, Oslo, Norway) suspensions mixed with 0.5, 1.6, and 20 g / L of CaP from Example 5. The control was a Pluronic gel without particles.

[0197] These gels were loaded with 500 μl of Staphylococcus aureus culture medium (stock solution) diluted in 4 ml of PBS (Dulbecco's PBS, Sigma-Aldrich, St. Louis, MO, USA) before mixing with the suspension. A 10 μl droplet of this stock solution was placed on top of the gel. After UV light exposure for the test group was completed, small squares of gel were individually placed into 1.5 ml Eppendorf tubes containing 500 μl of cell culture medium (without antibiotics) from Invitrogen (GIBSCO MEM, Invitrogen, Carlsbad, CA, USA). All Eppendorf tubes containing gels and bacteria were placed in an incubator at 37°C in the dark for 20 hours. After 20 hours, all samples were removed from the incubator. A baseline calibration of the spectrometer (Perkin Elmer UV-Vis 200, Oslo, Norway) was performed with only 700 μl of cell culture medium. Next, three Eppendorf tubes containing only 500 μl of cell culture medium + 10 μl of stock solution were analyzed. The tubes were then shaken one by one and a volume of 400 μl from each tube was transferred to a microcentrifuge. The 1.5 ml cuvette contained 700 μl of the liquid to be analyzed.

[0198] The results showed that the presence of CaP particles did not alter the antibacterial properties. [Example]

[0199] Antibacterial effect of Ca-P particles against Pseudomonas aeruginosa This example describes the antibacterial activity of the Ca-P particles described in Example 4.

[0200] Bacteria: Pseudomonas aeruginosa is an opportunistic pathogen that causes a wide range of infections and is frequently found in chronic wounds.

[0201] procedure: Different gels were treated with 3%, 5%, and 7% HO (PERDROGEN® 30% HO (v / v), Sigma-Aldrich AS, Oslo, Norway) suspensions in Pluronic gels at concentrations (0.1, 1, and 5% v / v) mixed with 0.5, 2, and 5 g / L of Ca-P (Example 4). Controls were gels without suspension. These gels were loaded with 500 μl of a Staphylococcus aureus culture medium (stock solution) diluted in 4 ml of PBS (Dulbecco's PBS, Sigma-Aldrich, St. Louis, MO, USA) before mixing with the suspension. A 10 μl drop of this stock solution was placed on top of the gel. After UV light exposure for the test group was completed, small squares of gel were individually placed into 1.5 ml Eppendorf tubes containing 500 μl of Invitrogen (GIBSCO MEM, Invitrogen, Carlsbad, CA, USA) cell culture medium (without antibiotics). All Eppendorf tubes containing gel and bacteria were placed in an incubator at 37°C in the dark for 20 hours. After 20 hours, all samples were removed from the incubator. A baseline calibration of the spectrometer (Perkin Elmer UV-Vis 200, Oslo, Norway) was performed using only 700 μl of cell culture medium. Next, three Eppendorf tubes containing only 500 μl of cell culture medium plus 10 μl of stock solution were analyzed. The test tubes were then shaken one by one, and a volume of 400 μl from each tube was mixed with 300 μl of cell culture medium. A 1.5 ml cuvette contained 700 μl of the liquid to be analyzed. [Example]

[0202] Antibacterial effect of bioceramic particles against Escherichia coli This example describes the antibacterial potential of various bioceramics.

[0203] Bacteria: E. coli can be present in chronic wounds.

[0204] procedure: The antibacterial efficacy of the three gels was tested using 3.5 and 7.5 g / L HO (PERDROGEN® 30% HO (v / v), Sigma Aldritch AS, Oslo, Norway) suspensions mixed with 0.5, 1.6, and 20 g / L ZrO and TiO (Aeroxide P25, Evonik AG, Essen, Germany). Controls included gels without suspension and gels treated only with 5% v / v HO (PERDROGEN® 30% HO (v / v), Sigma Aldritch AS, Oslo, Norway) in Pluronic gel at concentrations of 0.1, 1, and 5% v / v.

[0205] These gels were loaded with 500 μl of Staphylococcus aureus culture medium (stock solution) diluted in 4 ml of PBS (Dulbecco's PBS, Sigma-Aldrich, St. Louis, MO, USA) before mixing with the suspension. A 10 μl droplet of this stock solution was placed on top of the gel. After UV light exposure for the test group was completed, small squares of gel were individually placed into 1.5 ml Eppendorf tubes containing 500 μl of cell culture medium (without antibiotics) from Invitrogen (GIBSCO MEM, Invitrogen, Carlsbad, CA, USA). All Eppendorf tubes containing gels and bacteria were placed in an incubator at 37°C in the dark for 20 hours. After 20 hours, all samples were removed from the incubator. A baseline calibration of the spectrometer (Perkin Elmer UV-Vis 200, Oslo, Norway) was performed with only 700 μl of cell culture medium. Next, three Eppendorf tubes containing only 500 μl of cell culture medium plus 10 μl of stock solution were analyzed. The tubes were then shaken one by one, and a volume of 400 μl from each tube was mixed with 300 μl of cell culture medium. A 1.5 ml cuvette contained 700 μl of the liquid to be analyzed.

[0206] The presence of ZrO2 did not alter the antibacterial activity, but surprisingly, the presence of TiO2 did, and the effect was linear with concentration. [Example]

[0207] Antibacterial effect of fluorine-doped activated Bioglas against Staphylococcus aureus This example describes the antibacterial potential of Bioglass™ 45S5 (MOSCI Corp. Rolla, Missouri MO 65401) mixed in suspensions of 3, 5, and 7.5 HO (PERDROGEN® 30% HO (v / v), Sigma Aldritch AS, Oslo, Norway) mixed with 0.5, 1.6, and 20 g / L of Bioglass™ 45S5.

[0208] Bacteria: Staphylococcus aureus (S. aureus) is an important human resident and opportunistic pathogen that causes a wide range of infections. It is one of the most well-known bacteria responsible for postoperative infections. Therefore, S. aureus was chosen for this experiment.

[0209] procedure: Gels were treated with a suspension of 5% v / v HO (PERDROGEN® 30% HO (v / v), Sigma Aldrich AS, Oslo, Norway) mixed with various concentrations of bioglass. The suspensions were then doped with 0.01, 0.5, 1, and 3 atomic weight percent fluorine. Doping was achieved by adding an equivalent amount of NaF to the suspension. The amount of fluorine on the surface was detected and quantified by X-ray photoelectron spectroscopy (XPS). Controls included gels without suspension and gels treated with only 5% v / v HO (PERDROGEN® 30% HO (v / v), Sigma Aldrich AS, Oslo, Norway).

[0210] These gels were loaded with 500 μl of Staphylococcus aureus culture (stock solution) diluted in 4 ml of PBS (Dulbecco's PBS, Sigma-Aldrich, St. Louis, MO, USA) before mixing with the suspension. A 10 μl droplet of this stock solution was placed on top of the gel. After UV light exposure of the test group was completed, small squares of gel were individually placed in 1.5 ml Eppendorf tubes containing 500 μl of cell culture medium (without antibiotics) from Invitrogen (GIBSCO MEM, Invitrogen, Carlsbad, CA, USA). All Eppendorf tubes containing gels and bacteria were placed in an incubator at 37°C in the dark for 20 hours. After 20 hours, all samples were incubate. The tubes were then shaken one by one, and a volume of 400 μl from each tube was mixed with 300 μl of cell culture medium. A 1.5 ml cuvette contained 700 μl of the liquid to be analyzed.

[0211] The results show that the number of particles has little effect on the antibacterial properties, while the most dominant factors were the amounts of Pluronic gel and H2O2. [Example]

[0212] Biofilm removal This example describes the antibacterial potential of Pluronic gel at concentrations (0.1, 1 and 5% v / v). In vitro test: Biomass evaluation after washing.

[0213] Sample preparation Chemically pure (cp) titanium discs with a diameter of 6.2 mm and a height of 2 mm were used. They had similar machined surface geometries (wavy and lathed). After production, the discs were rinsed in an ultrasonic bath with 40% v / v NaOH and 50% v / v HNO3 to remove contaminants, then rinsed with deionized water to reach a neutral pH and stored in 70% v / v ethanol at room temperature. The coins were then placed in Eppendorf tubes and sterilized by steam autoclaving.

[0214] Four chemical decontamination agents were selected for in vitro testing: sterile saline H2O (VWR, Oslo, Norway), chlorhexidine, 3% v / v H2O2 (VWR, Oslo, Norway), and a mixture of 3% v / v H2O2 and 2 g / L TiO2 (2 g nanoparticles: P25 Aeroxide, Degussa Evonik, Evonik Industries AG, Essen, Germany).

[0215] Inoculation, washing and analysis Fifteen sterile titanium disks were inoculated into each group. The control group was inoculated with brain heart infusion medium (BHI) alone, while the test groups (four) were inoculated with bacterial culture (10 μl S. epidermidis + 5 ml BHI). The incubation time was set at 35°C for 24 h in an aerobic atmosphere. The disks were then transferred to new wells, rinsed with sterile saline, exposed to four selected chemical agents for 2 min, and rinsed again with sterile saline. The amount of biofilm present on the titanium sample surface was assessed using the safranin staining method: after 10 min of exposure to a 0.1% safranin solution, the disks were rinsed with distilled water, air-dried, and exposed to a 30% acetic acid solution to release the colored biomass from the titanium surface. The staining intensity was analyzed at a wavelength of 530 nm using a Synergy HT Multi-Detection Microplate Reader (Biotek, VT, USA).

[0216] result Optical density analysis on a Synergy HT Multi Detection microplate reader showed that samples exposed to mixtures of 3% v / v H2O2 and various gel concentrations were significantly different from the control. Furthermore, higher pluronic acid concentrations and higher hydrogen peroxide concentrations improved biofilm removal. [Example]

[0217] Biofilm regrowth after exposure to activated TiO2 microparticles This example describes the antibacterial potential of activated TiO2 microparticles in preventing biofilm regrowth after disinfection.

[0218] In vitro test: Bacterial regrowth Another test was conducted to determine biofilm viability after disinfection. The method, from inoculation to disinfection, was similar to the safranin staining analysis performed in Example 10 above, using the same four products. However, this time, after the disinfection step, the samples were rinsed with NaCl and reincubated in pure BHI medium at 35°C for 4 hours. The medium was collected and analyzed using the same spectrophotometer as for safranin staining, but this time at a wavelength of 600 nm. The absorbance intensity was compared between the control and test groups.

[0219] The results of this experiment should show significantly lower levels of bacterial regrowth in samples exposed to a mixture of 3% v / v H2O2 and 2 g / L TiO2 compared to the control group and samples exposed to H2O2 alone. [Example]

[0220] Application to periodontitis treatment The two-component Pluronic-hydrogen peroxide gel described herein is intended for topical application to clean teeth. Cleansing is the medical removal of dead, damaged, or infected tissue and improves the healing ability of remaining healthy tissue. In oral surgery and dentistry, cleansing also refers to the removal of biofilm / plaque (considering that plaque may also be considered a mineralized biofilm) that has accumulated on the roots of teeth. The gel assists in cleaning teeth; it effectively increases the effectiveness of mechanical removal of biofilm / plaque from the tooth surface; because biofilm / plaque causes an inflammatory state, removal provides benefits in the following aspects: - Inhibition of the breakdown of dental tissue - Inflammation suppression - Reduce the development of periodontitis, bone damage and tooth loss The intended use of the device is for systematic professional use in the treatment of periodontitis and in patients at risk of the problems listed above.

[0221] The gel device can be used as part of any debridement technique, alone or as an adjunct to mechanical removal remedies (e.g., certain toothbrushes, hand instruments, or power devices). There are no product incompatibilities with the materials that make up most common brushes or with materials used in reconstructive or cosmetic dentistry.

[0222] Mix the gel: 1) The contents of the syringe must be injected completely into the vial containing hydrogen peroxide: 2) Shake the vial to aid mixing without removing the syringe; 3) Draw the mixture into the syringe, remove the vial, screw the tip tightly on the luer lock connection, and use it as is to apply the gel to the area of ​​interest.

[0223] The mixed gel should be used within 20 minutes, as the active hydrogen peroxide loses potency after this time. The peroxide and gel decompose into water, carbon dioxide, and oxygen, so the loss of activity does not harm the patient or the environment.

[0224] Use of Pluronic-Peroxide Gel in Periodontal Surgery: 1. After the mucoperiosteal flap in the area selected for periodontal surgery is removed, the exposed root surface is mechanically debrided to remove excess plaque and / or calculus. 2. The gel is then applied topically to the exposed and cleaned root / implant surface for 2 minutes. Gel is applied to the areas of the surface that will be covered by soft tissue after the flap is replaced and sutured. 3. Aggressive rubbing ("burnishing") can be applied by hand instruments, brushes such as brushes, ultrasonic devices or any other suitable powered device, laser or compressed air, as these will reduce the efficacy of the gel. 4. After debridement, the root surface and adjacent tissues should be thoroughly rinsed with sterile saline. 5. Apply regenerative treatment devices, if planned. 6. The valve is repositioned and secured with sutures. If gel is used, no special postoperative precautions are required. 7. After the final rinse, care must be taken to avoid recontamination of the conditioned root / implant surface before treatment with the regenerative product. [Example]

[0225] Application to peri-implantitis treatment The two-component Pluronic-hydrogen peroxide gel described herein is intended for topical application to debride implants. Debridement is the medical removal of dead, damaged, or infected tissue, improving the healing ability of remaining healthy tissue. In oral surgery and dentistry, debridement also refers to the removal of biofilm / plaque (considering that plaque may also be considered a mineralized biofilm) that has accumulated on the implant surface. The gel assists in debridement of the implant; it effectively increases the effectiveness of mechanical removal of biofilm / plaque from the implant surface; because biofilm / plaque causes an inflammatory state, removal provides benefits in the following aspects: - Suppression of peri-implant tissue degradation - Suppression of local inflammation - Reduce the risk of peri-implantitis, bone damage and tooth loss The intended use of the device is for systematic professional use in the surgical treatment of peri-implantitis in patients at risk for the problems listed above.

[0226] The gel can be used as part of any debridement technique, alone or as an adjunct to mechanical removal remedies (e.g., certain toothbrushes, hand instruments, or power devices). There are no incompatibilities with the materials that make up most common brushes or with materials used in reconstructive or cosmetic dentistry.

[0227] Mix the gel: 1) The contents of the syringe must be completely injected into the vial containing hydrogen peroxide. 2) Without removing the syringe, shake the vial to aid mixing. 3) Draw the mixture into the syringe, remove the vial, screw the tip tightly onto the luer lock connection, and use it to apply the gel to the desired area.

[0228] The mixed gel must be used within 20 minutes, as the active hydrogen peroxide loses potency after this time. The peroxide and gel decompose into water, carbon dioxide, and oxygen, so the loss of activity does not harm the patient or the environment.

[0229] Use of Pluronic-Peroxide Gel in Peri-Implantitis Surgery: 1. After the mucoperiosteal flap in the area selected for peri-implant surgery is removed, the exposed implant surface is mechanically debrided to remove excess plaque and / or calculus. 2. The mixed gel is then applied topically to the exposed and cleaned implant surface for 2 minutes. Apply the gel to the portion of the surface that will be covered by soft tissue after the flap is replaced and sutured. 3. Aggressive rubbing ("burnishing") is applied by hand instruments, brushes such as TiBrush, ultrasonic devices or any other suitable powered device. Avoid using plastics, lasers or compressed air as these will reduce the effectiveness of the gel. 4. After debridement, the root / implant surface and adjacent tissues should be thoroughly rinsed with sterile saline. 5. Apply regenerative treatment devices, if planned. 6. The valve is repositioned and secured with sutures. If gel is used, no special postoperative precautions are required. 7. After the final rinse, care should be taken to avoid recontamination of the conditioned implant surface before treatment with the regenerative product. [Example]

[0230] Application to peri-implant mucositis and gingivitis The two-component Pluronic-peroxide gel described herein is intended for topical application to clean teeth and implants. Cleansing is the medical removal of dead, damaged, or infected tissue, improving the healing ability of remaining healthy tissue. In oral surgery and dentistry, cleansing also refers to the removal of biofilm / plaque (considering that plaque may also be considered a mineralized biofilm) that has accumulated on tooth roots and implants. The gel assists in cleaning teeth; it effectively increases the effectiveness of mechanical removal of biofilm / plaque from the surface of teeth / implants; because biofilm / plaque causes an inflammatory state, removal provides benefits in the following aspects: - Inhibition of periodontal and peri-implant tissue degradation - Suppression of local inflammation - Suppression of the onset and progression of periodontitis and peri-implantitis, which cause bone, tooth and implant loss The intended use of the device is for systematic professional use in the routine oral hygiene of patients at risk for the problems listed above.

[0231] Nu Bone® Clean can be used as part of any cleaning technique, alone or as an adjunct to mechanical removal remedies (e.g., certain toothbrushes, hand instruments, or power devices). There are no product incompatibilities with the materials that make up most common brushes or those used in reconstructive or cosmetic dentistry.

[0232] Mix the gel: 1) The contents of the syringe must be completely injected into the vial containing the hydrogen peroxide. 2) Without removing the syringe, shake the vial to aid mixing. 3) Draw the mixture into the syringe, remove the vial, screw the tip tightly on the luer lock connection, and use it as is to apply the gel to the area of ​​interest.

[0233] The mixed gel must be used within 20 minutes, as the active hydrogen peroxide loses potency after this time. The peroxide and gel decompose into water, carbon dioxide, and oxygen, so the loss of activity does not harm the patient or the environment.

[0234] The recommended use for non-invasive applications in peri-implant mucositis and gingivitis is as follows: 1. After removing supragingival plaque and calculus, mix the gel and apply it carefully into the periodontal pocket using a fine tip. Be careful not to apply too much pressure to avoid damaging the soft tissue. The applied pressure should cause slight ischemia of the gingiva at the application site, but should not cause pain or bleeding. 2. After application, allow the gel to sit for 1 minute and then cleanse the exposed surface of the tooth / implant using a cleaning implement of choice, typically a hand implement, ultrasonic device or brush. 3. After mechanical cleaning, wash away any remaining gel with water spray and suction. 4. Patients are rinsed with water as usual after the procedure. No special postoperative precautions are required. [Example]

[0235] Preventive and maintenance treatment for peri-implant and periodontal disease, and applications in maintaining peri-implant and periodontal health The two-component Pluronic-peroxide gel described herein is intended for topical application as a prophylactic tooth cleaning to maintain healthy peri-implant tissues and gums. The gel aids in tooth and implant cleaning and enhances the effectiveness of mechanical removal of biofilm / plaque from tooth / implant surfaces; since biofilm / plaque causes an inflammatory state, removal provides benefits in the following aspects: - Suppression of inflammation around implants and in periodontal tissues - Prevention of periodontal and peri-implant disease The intended use of the device is for systematic professional use in the routine oral hygiene of patients at risk of the problems listed above or as a maintenance treatment to avoid recurrence after surgical intervention.

[0236] The gel is used as part of any cleaning technique, alone or as an adjunct to mechanical removal remedies (e.g., certain toothbrushes, hand instruments, or power devices). There are no incompatibilities with the materials that make up most common brushes or with materials used in reconstructive or cosmetic dentistry.

[0237] Mix the gel: 1) The contents of the syringe must be completely injected into the vial containing the hydrogen peroxide. 2) Without removing the syringe, shake the vial to aid mixing. 3) Draw the mixture into the syringe, remove the vial, screw the tip tightly on the luer lock connection, and use it as is to apply the gel to the area of ​​interest.

[0238] The mixed gel must be used within 20 minutes, as the active hydrogen peroxide loses potency after this time. The peroxide and gel decompose into water, carbon dioxide, and oxygen, so the loss of activity does not harm the patient or the environment.

[0239] The recommended use of non-invasive preventative and maintenance treatments is as follows: 1. After removing supragingival plaque and calculus, mix the gel and use a fine applicator tip to carefully apply it around the sulcus and into the gingival pocket around the tooth / implant to be treated. When applying the gel into deep pockets, be careful not to use too much pressure to avoid damaging the soft tissue. 2. After application, leave the gel to work for 1-3 minutes without using any implements. The gel will chemically cleanse the targeted area. 3. After the cleaning time is over, the gel should be removed by water spray and suction. 4. If necessary, repeat the procedure until the surface is visibly clean. 5. Patients are rinsed with water as usual after the procedure. No special postoperative precautions are required. [Example]

[0240] Application to debridement of chronic skin ulcers The two-component Pluronic-peroxide gel described herein is intended for topical application to debride chronic cutaneous ulcers. Debridement is the medical removal of dead, damaged, or infected tissue to improve the healing ability of remaining healthy tissue. In wound care, debridement also refers to the removal of pathogenic biofilms that have accumulated on the wound surface. The gel assists in wound debridement; the gel prevents the wound from becoming damaged. This effectively increases the effectiveness of mechanical removal of biofilm from the wound surface while simultaneously increasing local oxygen levels. Because pathogenic biofilms can cause inflammatory conditions, removal provides benefits in the following aspects: - Inhibition of the degradation of epithelial and connective tissue - Suppression of local inflammation - Suppression of infection, necrosis and wound progression The intended use of the device is for systematic professional use in the repeated treatment of chronic skin wounds in patients at risk for the problems listed above.

[0241] The gel device can be used as part of any debridement technique, either alone or as an adjunct to mechanical removal remedies (e.g., certain brushes, hand instruments, or any type of wound dressing). Although there are no known product incompatibilities, the use of vacuum devices should be avoided as they may remove the active gel from the wound surface.

[0242] Mix the gel: The contents of the syringe should be injected completely into the vial containing the hydrogen peroxide. Without removing the syringe, shake the vial to aid mixing. The mixture is drawn into the syringe, the vial is removed, the tip is screwed tightly onto the luer lock connection, and used to apply the gel to the area of ​​interest.

[0243] The mixed gel must be used within 20 minutes, as the active hydrogen peroxide loses efficacy after this time. The peroxide and gel decompose into water, carbon dioxide, and oxygen, so the loss of activity does not harm the patient or the environment.

[0244] The recommended use for non-invasive treatment of chronic wounds is as follows: 1. After removing purulent and excess wound fluid, mix the gel and apply it carefully to the wound surface using the provided applicator tip. 2. After application, leave the gel to work for 3-10 minutes, depending on the severity of the wound. During this time, do not use dressings or wipes. The gel will chemically cleanse the area. 3. Once the cleaning time is over, the gel should be removed with a damp wipe, removing as much of it as possible from the surface. Discard the wipe. 4. If necessary, repeat the procedure until the wound is visibly clean. 5. When the wound is cleansed satisfactorily, apply the gel to cover the wound. Distribute evenly and allow the gel to set. 6. Cover the gelled wound with a suitable wound dressing. 7. The gel and wound dressing should be left in place until the next scheduled wound debridement and / or wound dressing change. 8. Patients can continue their normal activities after the procedure. There are no special precautions to take when using the gel after surgery. [Example]

[0245] In vivo compatibility of CaP microparticles in pluronic gel and H2O2 Test System Species: Rabbit Lineage: New Zealand White

[0246] Experimental design Animals were identified by numbers 1 to 6 and assigned to dose groups.

[0247] Administration of test and control items The day before test item administration, hair was removed from an area of ​​at least 8 cm x 10 cm on the dorsal trunk region. The following day, four gauze patches (2.5 cm x 2.5 cm) were applied topically as shown in Table 1:

[0248] [Table 1]

[0249] Each patch was covered with microporous semi-occlusive tape and an elastic bandage was placed around the animal's torso.

[0250] After 1, 24, 48, 72, and 96 hours, the patches were removed and the test sites were delineated. The test sites were wiped with gauze and room temperature distilled water. Cold water (<15°C) was used to remove the last remnants of the Pluronic-peroxide gel. Route and dose level justification

[0251] The dermal route of administration was chosen for this study because this route has been defined as a potential route of human exposure, i.e., in wound care. A dose of 0.5 mL of each test article was chosen for this study because it is routinely used in studies of this type.

[0252] Skin scoring Frequency: 1, 24, 48, 72 and 96 hours after patch removal. Procedure: The skin was evaluated for erythema and eschar formation, edema formation, skin thickening, scaling and other reactions to treatment.

[0253] conclusion There were no necropsy or histological findings resulting from application of any of the test gels to intact rabbit skin 1 or 6 days after removal. The devices were deemed safe for testing on human skin.

Claims

1. An antibacterial and / or anti-inflammatory composition for in situ cleaning and / or wiping of biological and / or biomaterial surfaces, comprising at least two components a. H2O at a final concentration of 0.1-5% v / v ２ O ２ , and b. Composite hydrogel formulations containing pluronic acid at concentrations of 10-40% w / v and which is liquid at a temperature of up to 30°C.

2. At least two ingredients a.H ２ O ２ , and b. Composite hydrogel formulations containing pluronic acid 10. The antimicrobial and / or anti-inflammatory composition of claim 1, wherein the antimicrobial and / or anti-inflammatory compositions are mixed simultaneously and kept separate from each other until applied in situ to a biological and / or biomaterial surface.

3. The separate components a. are H ２ O ２ 3. The antibacterial and / or anti-inflammatory composition according to claim 1, wherein the composition comprises:

4. The composition according to any one of claims 1 to 3, further comprising fine particles having an average particle size (D50) of 20 to 200 µm, the fine particles being organic or inorganic.

5. The composition of claim 4 , wherein the microparticles are biodegradable.

6. The composition of any one of claims 1 to 5, further comprising at least one mesh-forming and / or scaffold-forming component.

7. The composition of any one of claims 1 to 6, further comprising a biologically active substance.

8. A kit comprising the composition of any one of claims 1 to 7, h. at least two containers each containing components a. and b.; i. syringes and vials; j. a connector device; k. an applicator tip, and l. Instructions The kit comprises:

9. m. Mixing devices, and n. Wiping tools 9. The kit of claim 8, further comprising:

10. A kit comprising the composition according to any one of claims 1 to 9, wherein the two components a. and b. are provided in a dual-chamber syringe.

11. 12. An antibacterial and / or anti-inflammatory composition according to any one of claims 1 to 11 for use in the in situ removal of biofouling, biofilms and / or necrotic tissue from biological and / or biomaterial surfaces.

12. 12. The antibacterial and / or anti-inflammatory composition according to any one of claims 1 to 11 for use in the treatment and / or prevention of peri-implantitis, gingivitis, mucositis, peri-implant mucositis, periodontitis and / or chronic and / or infected skin ulcers.

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