Multifunctional cleansing and / or debridement composition

Abstract

The present invention relates to multifunctional cleansing and / or debridement compositions. The present invention discloses a kit for providing an antimicrobial and / or anti-inflammatory composition for in situ cleaning and / or debridement of biological surfaces and / or biological material surfaces, the kit comprising at least three components: a) H2O2 at a concentration of at most 10% v / v, b) a composite hydrogel formulation comprising poloxamer at a concentration of from 10% w / v to 40% w / v, c) a debridement tool comprising a plurality of bristles and consisting of titanium and / or a titanium alloy, where component a) and component b) remain separate from each other until they are simultaneously mixed and applied in situ to a biological surface and / or a biological material surface, and where component a) and component b) remain separate from each other until they are simultaneously mixed and applied in situ to the biological surface and / or the biological material surface. The composition is a liquid at a temperature of at most 30 DEG C.

Description

[0001] This application is a divisional application of the Chinese patent application with the application date of March 18, 2021, application number 202180034972.0, and invention name “Multifunctional cleaning and / or debridement composition”. Technical Field

[0002] The present invention relates to a novel multifunctional debridement and / or antifouling composition comprising a final concentration of 0.1% v / v to 5% v / v H2O2 and a composite hydrogel formulation containing pluronic acid at a concentration of 10% w / v to 40% w / v, wherein the composition is in liquid form at room temperature, for example at a temperature of up to 30° C. The composition disclosed herein is antimicrobial and / or anti-inflammatory and is particularly useful for peri-implantitis treatment and implant health maintenance, periodontitis and periodontal health, as well as wound care and chronic ulcer care.

[0003] The present invention also relates to the use of the composition according to the invention for cleaning and / or debridement of biological surfaces and / or biological material surfaces, such as, in particular, in situ implants and / or surfaces in the oral cavity. The composition according to the invention can be used together with an implant cleaning and / or debridement tool (e.g., a brush, a dental drill or a curette).

[0004] In one embodiment, the composition according to the invention is provided as a kit, wherein at least two components (H2O2 and pluronic acid) are optionally kept separate and mixed immediately upon concomitant and / or simultaneous administration. Background Art

[0005] Biological surfaces and / or biological material surfaces are prone to in situ contamination, i.e., accumulation of biofilm and necrotic tissue, since they are in constant contact with and often multiplied by a large number of microorganisms. Therefore, they require regular cleaning and debridement using antibacterial and anti-inflammatory compositions without causing damage to the surrounding biological tissues of the patient and without inducing microbial resistance.

[0006] Biofilm

[0007] Biofilms are structured communities of microorganisms that are firmly attached to surfaces and surrounded by a self-produced three-dimensional (3D) extracellular matrix. Biofilms can form on or inside biological or non-biological surfaces and can be found in both natural and industrial environments.

[0008] Biofilm can be formed on the surface or in implanted medical tubes and medical devices, and can also be formed on the surface and inside the human body, such as on mucosal surfaces, or on other body orifice surfaces, or in open wounds, which can cause infection in patients. The inflammatory response to this then leads to the accumulation of necrotic tissue, which in turn leads to the subsequent inflammatory response of the body. In particular, biofilm can be formed in the oral cavity and often leads to oral diseases, such as caries or periodontitis, gingivitis or peri-implantitis. The extracellular matrix of such biofilm contains polymer substances, such as exopolysaccharides (EPS). The matrix produced by microorganisms can provide necessary support for biofilm assembly. In addition, it can promote the adhesion and coagulation of microorganisms, while hindering diffusion, thereby making biofilm extremely difficult to handle or remove from the surface.

[0009] The extracellular matrix makes it difficult to eliminate microbial biofilms in the oral cavity and human body, as well as on biomaterials such as implants and medical devices, by antibodies, antibiotics, and immune cells, which are largely unable to penetrate the dense extracellular matrix to kill the embedded microorganisms.

[0010] Biofilm on biological surfaces and implants can be removed by chemical and / or mechanical cleaning and / or debridement.

[0011] Debridement

[0012] Debridement is the medical removal of dead, damaged and / or infected tissue from a patient to enhance the healing potential of the remaining healthy tissue. Debridement removal can be surgical, mechanical, chemical, autolytic (self-digesting), and by maggot therapy, in which certain species of live maggots selectively feed only on dead tissue.

[0013] Nevertheless, mechanical cleaning and / or debridement of the surface is not sufficient, as it does not provide any secondary chemical and / or biological cleaning / decontamination effect, thus, for example, leaving the surface open to immediate re-colonization with microorganisms, or even leaving behind small amounts of previous microbial populations, for example on inaccessible areas of rough surfaces.

[0014] Therefore, several antimicrobial and / or anti-inflammatory agents are currently used in antifouling treatments.

[0015] Hydrogen Peroxide

[0016] Hydrogen peroxide (H2O2) is a very pale blue liquid that is colorless in dilute solution and slightly more viscous than water. It is a weak acid. It has strong oxidizing properties and is therefore a strong bleaching agent, used primarily for bleaching paper, but can also be used as a disinfectant and oxidizing agent. Hydrogen peroxide in the form of carbamide peroxide is widely used for teeth whitening (bleaching), both in professionally applied products and in self-applied products.

[0017] Hydrogen peroxide is unstable and decomposes slowly in the presence of light. Due to its instability, hydrogen peroxide is usually stored in a weakly acidic solution in a dark bottle along with a stabilizer.

[0018] Hydrogen peroxide can be used to sterilize a variety of surfaces, including surgical tools, and as a vapor (VHP) for room sterilization. H2O2 exhibits broad-spectrum efficacy against viruses, microorganisms, including but not limited to bacteria, yeasts, and bacterial spores. In general, activity against Gram-positive bacteria is higher than against Gram-negative bacteria; however, the presence of catalase or other peroxidases in these organisms can increase tolerance at lower concentrations. Sporicidal activity requires higher concentrations of H2O2 (10% v / v to 30% v / v) and longer contact times.

[0019] Hydrogen peroxide is viewed as an environmentally safe alternative to chlorine-based bleaches because it degrades to form oxygen and water and is generally recognized as a safe antimicrobial agent by the US Food and Drug Administration (FDA).

[0020] Historically, hydrogen peroxide was used to sterilize wounds. Today, it is thought to inhibit healing and cause scarring because it destroys newly formed skin cells at high concentrations. One study found that only very low concentrations (0.03% v / v solution, which is a 100-fold dilution of typical 3% v / v peroxide) induced healing, and only if it was not applied repeatedly. A 0.5% v / v solution was found to hinder healing.

[0021] Pluronic acid

[0022] Poloxamer or Poloxamers are triblock copolymers of poly(ethylene oxide)poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO). Synthetic polymers of this group are thermoreversible in aqueous solution. The sol-gel transition is controlled by the composition, molecular weight and concentration of the constituent block polymers. The hydrophilic ethylene oxide and the hydrophobic propylene oxide give Pluronic an amphiphilic structure - meaning that it has polar water-soluble groups attached to non-polar water-insoluble hydrocarbon chains. The amphiphilic block copolymer molecules self-assemble into micelles (stacked chains of molecules) in aqueous solution. Micelle formation is temperature-dependent and affects the degradation properties of the biomaterial: below a certain characteristic temperature (called the critical micelle temperature), both the ethylene oxide and propylene oxide blocks are hydrated, and the PPO block becomes soluble.

[0023] Pluronic can exist as liquid, paste or solid.Due to their amphiphilic properties (there are hydrophobic and hydrophilic components), Pluronic has surfactant properties that allow them to interact with hydrophobic surfaces and biofilms.Amphiphilicity also causes the ability of each block copolymer (called monomer) to combine and form micelles in aqueous solution.When the concentration of block copolymer is lower than the critical micelle concentration (CMC), the monomer is still present in water as a molecular solution.However, as the concentration of block copolymer increases to higher than CMC, the monomer will self-assemble and form micelles, and micelles can present spherical, rod-like or lamellar geometries.Their shape depends on the length and concentration of block copolymers (i.e. EO and PO) and temperature.Micelles usually have a hydrophobic core (in this case, PO chain) and a hydrophilic shell (i.e. EO chain).

[0024]

[0025] Pluronic F-127, also known as Poloxamer 407, is commonly used in tissue engineering because a consistent product is commercially available that will undergo a sol-gel transition near physiological temperature and pH. A disadvantage of Pluronic F-127 is its rapid rate of degradation in vivo. To overcome this problem, Pluronic F-127 is often cross-linked with another α-hydroxyl or amino acid to change the chemical structure of its depsipeptide unit.

[0026] Pluronic acid forms thermosensitive hydrogels that are often stabilized by the addition of high molecular weight acids such as hyaluronic acid.

[0027] Studies have demonstrated the positive effects of pluronic acid formulations in reducing inflammation, protecting tissues from damage and hindering microbial adhesion. In addition, it is EMA and FDA approved, fully biocompatible and safe for clinical use, with no known harmful effects on human cells.

[0028] Nevertheless, it is difficult to apply as a cleanser and debridement agent because it automatically forms a stable gel at temperatures above 18°C ​​or even between 12°C and 20°C (depending on its concentration) (see Figure 1A and Figure 1B ), which makes it unsuitable for use in small channels and / or on rough surfaces, and for administration with a syringe.

[0029] Therefore, a means for in situ cleaning and / or debridement of contaminated biological surfaces and / or biological material surfaces, or for preventing in situ contamination of biological surfaces and / or biological material surfaces by cleaning and / or sterilizing, for example, biological surfaces in the oral cavity, is still sought. The present invention proposes for the first time such means for effectively cleaning and / or debridement even of inaccessible areas and / or rough hard surfaces, such as surfaces in the oral cavity. Summary of the invention

[0030] The present invention relates to a novel antimicrobial and / or anti-inflammatory composition for in situ cleaning and / or debridement of biological surfaces and / or biological material surfaces, comprising at least two components:

[0031] a. H2O2 at a final concentration of 0.1% v / v to 5% v / v, and

[0032] b. A composite hydrogel formulation comprising pluronic acid at a concentration of 10% w / v to 40% w / v,

[0033] Therein, the composition is liquid at room temperature, such as at a temperature up to 30°C, such as at a temperature of 20°C to 30°C, such as at 25°C.

[0034] The composition disclosed herein is characterized in that it comprises components a. and b. in a ratio such that the composition is in a liquid state rather than a gel state at room temperature.

[0035] In one embodiment of the antimicrobial 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% w / v to 40% w / v, for example a concentration of at least 10% w / v, for example 10% w / v, 15% w / v, 20% w / v, 25% w / v, 30% w / v, 35% w / v or 40% w / v.

[0036] In another embodiment of the antimicrobial 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, for example up to 15% w / v, 20% w / v, 25% w / v, 30% w / v or 35% w / v.

[0037] The antimicrobial and / or anti-inflammatory composition according to the present invention may be a composition wherein the H2O2 of component a. has a final concentration of 0.1% v / v to 5% v / v, for example 0.5% v / v to 3.0% v / v.

[0038] The antimicrobial and / or anti-inflammatory composition according to the invention may also comprise water and / or saline.

[0039] The two components of the antimicrobial and / or anti-inflammatory composition according to the invention may be in one solution, or at least the two components may be kept separate from each other until they are simultaneously mixed and applied in situ to a biological surface and / or biomaterial surface.

[0040] In the antimicrobial and / or anti-inflammatory composition according to the invention, wherein the components are kept separate from each other prior to administration, the separate component a. may be a composition comprising H2O2 in a concentration of at least 10-50% v / v.

[0041] The composition according to the present invention may also contain microparticles having an average particle size (D50) of 20-200 μm. The concentration of the microparticles is generally about 0.5-1000 g / L, such as about 0.5-300 g / L.

[0042] The microparticles may be organic or inorganic.

[0043] The inorganic microparticles contained in the composition according to the present invention may be selected from metal compounds.

[0044] In another aspect, the microparticles are polymer particles, mineral particles and / or metal particles.

[0045] In one aspect, the microparticles comprised in the composition according to the invention are biodegradable, for example selected from the group consisting of bare zinc, iron, silicon, magnesium, manganese, silver and palladium.

[0046] In one aspect, the composition according to the invention further comprises a composition that releases the following ions Ca 2+ 、F - , Sr 2+ Mg 2+ The particles are particles of one of the above or particles containing calcium salt compound powder, calcium oxide compound powder, calcium ion source and / or calcium phosphate compound powder.

[0047] In a further aspect, the composition according to the invention comprises a fluoride ion source.

[0048] The composition according to the invention may also comprise at least one reticulating and / or scaffolding component which, after administration, increases the physical strength and / or chemical durability of the composition.

[0049] Alternatively or additionally, the composition according to the invention may comprise biologically active substances.

[0050] Furthermore, the composition according to the invention may also comprise further antimicrobial substances and / or debridement components.

[0051] The composition according to the invention has in one aspect a shelf life of at least 1 year at RT.

[0052] The present invention also relates to a kit comprising a composition according to the invention, comprising at least two containers, a syringe and a vial, comprising said separate components a. and b., respectively, a connector device, an applicator tip and an instruction booklet and optionally a mixing device and a debridement tool, 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 also comprise an instruction booklet, a mixing device, an applicator tip and a debridement tool, such as a brush.

[0053] The antimicrobial and / or anti-inflammatory composition according to the invention is intended for in situ debridement and / or cleaning of biological surfaces and / or biomaterial surfaces, for example for in situ removal of biofouling, biofilm and / or necrotic tissue from such biological surfaces and / or biomaterial surfaces.

[0054] The antimicrobial and / or anti-inflammatory composition according to the invention can generally be used for the treatment and / or prevention of peri-implantitis, gingivitis and / or mucositis, peri-implant mucositis and / or periodontitis.

[0055] Therefore, the present invention relates to a method for treating and / or preventing peri-implantitis, gingivitis and / or mucositis, peri-implant mucositis and / or periodontitis, comprising cleaning and / or debridement of biological surfaces and / or biomaterial surfaces in situ by applying a composition according to the invention to said contaminated, biofilm-bearing and / or necrotic surfaces.

[0056] Definitions and Abbreviations

[0057] The term "microparticles" is intended herein to describe particles having an average particle size (D50) of about 1 μm to 1000 μm. Typically, in the present invention, microparticles having an average particle size (D50) of 20-200 μm are used.

[0058] The present invention provides means for cleaning and / or debridement of medical and / or dental implants.In the present context, the term "implant" generally refers to a medical and / or dental implant.

[0059] In the present context, the term "dental implant" includes within its scope any device intended to be implanted in the oral cavity of a vertebrate, in particular a mammal, such as a human, for example in a dental restoration procedure. The dental implant herein is selected from the group consisting of implants, rods, bridges, abutments, crowns, caps and prosthetic parts in the oral cavity. A dental implant may also be referred to as a dental prosthetic device. Typically, a dental implant consists of one or more implant parts. For example, a dental implant typically comprises a dental fixture connected to secondary implant parts, such as an abutment and / or a dental restoration, such as a crown, bridge or denture. However, any device intended for implantation, such as a dental fixture, may be referred to as an implant alone, even if other parts are to be connected to it.

[0060] In the present context, the term "orthopedic implant" includes within its scope any device intended to be implanted in the body of a vertebrate, in particular a mammal, such as a human, to maintain and restore the function of the musculoskeletal system, in particular the joints and bones, including the relief of pain in these structures. Non-limiting examples of orthopedic implants are hip prostheses, knee prostheses, elbow prostheses, finger prostheses, cochlear prostheses and fixation screws.

[0061] In the present context, the term "vascular stent" refers to a tubular implant arranged for insertion into a blood vessel of a vertebrate, in particular a mammal, such as a human, to prevent or counteract local flow constriction, ie to counteract a significant reduction in the diameter of the vessel.

[0062] Hard tissues are, for example, bones, cementum, dentin, enamel, teeth, tooth roots, cartilage, and ligaments. Soft tissues are tissues that connect, support, or surround other structures and organs of the body, other than hard tissues such as bones. Soft tissues include tendons, ligaments, fascia, skin, fibrous tissue, fat, and synovium, muscles, nerves, and blood vessels.

[0063] In the present context, the term "debridement" means cleaning tissue surfaces, such as surgically exposed hard and / or soft tissue surfaces, to remove, for example, biofilm, calculus, microorganisms, unwanted tissue, cells and cell residues, scar tissue and / or necrotic tissue. For example, debridement can be performed to control and / or treat local infection, inflammation, foreign body reaction, pathological conditions and / or regenerative processes (e.g., periodontitis, peri-implantitis).

[0064] As used herein, "biofilm" includes 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 may include teeth, mucosa, apatite, bone, and non-biological (e.g., implants, dentures, tubes, etc.) surfaces.

[0065] In the present context, the term "peroxide" is used interchangeably with hydrogen peroxide (H2O2).

[0066] A microorganism or microbe is a microscopic organism that can exist as a single cell or as a colony of cells. Microorganisms include all single-celled organisms and are therefore very diverse. All archaea and bacteria are microorganisms (prokaryotes). Some protists are related to animals, and some to green plants. Many multicellular organisms are microscopic, i.e. microscopic animals, some fungi, and some algae.

[0067] An antimicrobial is an agent that kills microorganisms or stops their growth. Antimicrobials 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 can also be classified according to their function. Agents that kill microorganisms are microbicides, while those that only inhibit their growth are called biostatics, both of which are included in the term "antimicrobial". Using antimicrobials to treat infections is called antimicrobial chemotherapy, while using antimicrobials to prevent infections is called antimicrobial prophylaxis.

[0068] A virus is a small infectious agent that replicates only inside the living cells of an organism. Viruses can infect all types of life forms, from animals and plants to microorganisms, including bacteria and archaea.

[0069] Antiviral drugs are a class of drugs that are specifically designed to treat viral infections 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, antiviral drugs do not kill their target pathogens; instead, they inhibit their development.

[0070] Antivirals are a class of antimicrobials, which is a larger group that also includes antibiotics (also called antibacterial), antifungal and antiparasitic drugs or antivirals based on monoclonal antibodies. Most antivirals are considered relatively harmless to the host and can therefore be used to treat infections. They should be distinguished from virucides, which are not drugs but inactivate or destroy viral particles inside or outside the body. Some plants (such as eucalyptus and Australian tea tree) produce natural antivirals.

[0071] As used in this context, the term "antimicrobial" means that the composition is effective against microorganisms and viruses. In its broadest sense, the composition of the present invention is antimicrobial, i.e. it is an antibacterial, antiviral, bactericide and / or viricide.

[0072] As used herein, the terms "about" or "approximately" mean within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, ie, the limitations of the measurement system. BRIEF DESCRIPTION OF THE DRAWINGS

[0073] Figure 1A : The sol-gel transition temperature of Pluronic f-127 in H2O2 at a concentration of 3.5% v / v (lower figure) is compared with the sol-gel transition temperature of Pluronic f-127 in pure water (upper figure).

[0074] Figure 1B : Sol-gel transition of Pluronic f-127 (30% w / v) in different concentrations (v / v) of hydrogen peroxide relative to % H2O2. DETAILED DESCRIPTION

[0075] The compositions described herein are a long sought after means for effectively cleaning and / or debridement of biological surfaces and / or biological material surfaces in situ, such as but not limited to surfaces in the oral cavity, for rapid and effective treatment without damaging the surface structure to be cleaned, and leaving substantially no residue of contaminating material, while exhibiting antimicrobial and / or anti-inflammatory effects.

[0076] The composition described herein is a water-soluble and easily rinsed-off, tissue-friendly nonionic surfactant. It contains a non-toxic formulation of active ingredients well-studied in clinical use, particularly suitable for injection, oral administration and dermal administration. The composition described herein for the first time has been shown to be non-sensitizing and non-irritating in clinical trials. The composition of the present invention is compatible with other therapeutic agents against biofouling and inflammation.

[0077] The composition described herein has a liquid state at room temperature, making it easy to mix and apply. At a temperature not exceeding 30° C. (e.g., at RT), it exhibits an easy-flowing liquid consistency and a surfactant effect, which enables the composition to reach difficult places when applied to narrow defects. When applied, the patient's natural body temperature triggers micelle connection and quickly forms a stable gel at body temperature, thereby making long-term and close contact with the implant surface and tissue at the application site.

[0078] The compositions described herein can also be formulated to contain bioresorbable microparticles to aid in mechanical debridement of micro-rough implant surfaces. This will promote the cleaned surface with intact original structure. The gel-particle suspension can be applied with a debridement tool such as a brush (e.g. ) or other cleaning devices.

[0079] The composition of the present invention simulates the natural release of peroxides produced by human cells from reactive oxygen (ROS). The charge from the reactive oxygen destroys the microbial membrane, and oxygen itself is also toxic to anaerobic bacteria. Human cells themselves are protected from ROS by enzymes in their cell membranes, and local tissues can benefit from the increase in oxygen. Microorganisms do not have this protection, and they cannot develop resistance because there are fundamental differences in their cell membrane designs. Therefore, the composition can effectively dissolve biofilms, debris and mineral deposits, as well as dissolve extracellular organic matter at the application site.

[0080] Additionally, the acidic nature of peroxide aids in the cellular dissolution of mineral deposits, as well as the breakdown and removal of extracellular organic matter and calcifications from contaminated implants.

[0081] Cells use peroxides as a second messenger system that activates the cell's defense against microorganisms. The compositions disclosed herein mimic this signal to stimulate and strengthen the local cellular defense network.

[0082] The use of the composition proposed herein also removes carbon contamination from the titanium-containing implant surface and reactivates the titanium dioxide layer of the implant, through the active oxygen released from the hydrogel. This process reestablishes the original charge and hydrophilicity of the implant, thereby restoring the optimal biological surface properties. This is a major factor for the further survival or even successful reintegration of the treated implant. This effect can be seen in the experimental part by improved cell spreading and superhydrophilicity.

[0083] The composition of the present invention is an advanced micelle-forming gel formulation that works synergistically with naturally occurring oxygen to break down and remove biofouling, eliminate microorganisms, maintain tissue and implant moisturization, and reactivate titanium implant surfaces.

[0084] The hydrogel component and active oxygen of the composition work synergistically to avoid blistering and keep oxygen in the proper position on the surface to prolong biological and chemical action. Use of the composition provides moisture and allows charged oxygen to act without the risk of tissue and / or implant drying out, during which time the active oxygen eradicates microorganisms that are subsequently suspended and trapped inside the gel formed at body temperature. Organic pollutants are then denatured by the action of strong detergents, decomposed and dissolved by active oxygen and trapped in the gel. Both the gel and oxygen reduce inflammation and support tissue health. The gel formed at body temperature allows prolonged local action of active oxygen, which in turn strengthens the cellular defense network. In synergy, both the gel and active oxygen remove pollutants and reactivate the implant surface. The inverse thermodynamics of the gel works together with the destructive action of active oxygen to form a balance between the micelle-sol-state and the gel-state, thereby significantly increasing the decontamination effect.

[0085] The composition described herein is a novel formulation of a biocompatible hydrogel having strong, non-ionic detergent properties and improved sol-gel kinetics for dissolving and entrapping debris and microorganisms, thereby effectively cleaning and / or debridement of biological surfaces and / or biomaterial surfaces in situ. It is easily rinsed off with water and completely decomposes into water, oxygen, and carbon oxides.

[0086] The compositions disclosed herein provide a new and improved means for: treating and eliminating biofilms; preventing biofilm formation; biofilm extracellular matrix degradation; and inhibiting bacterial viability and growth within biofilms. In particular, the subject matter disclosed herein provides a composition for preventing and / or treating oral diseases (e.g., caries, periodontitis, gingivitis, mucositis, and / or peri-implantitis).

[0087] The present invention itself is based on a combination of hydrogen peroxide (H2O2) and pluronic acid in a concentration such that the composition is in liquid form at room temperature, i.e., at a temperature not exceeding 30°C, but is converted into a gel state in situ at the site of application due to the temperature rise to body temperature. The H2O2 component of the composition can be in the form of a concentrate in a separate vial used for mixing immediately before use (at a concentration of at least 10-50% v / v.) for application with a mixing connector (usually with a Luer lock design) in one embodiment, or provided as a hydrogel directly dissolved into a composition of pluronic acid and water (or saline), with a typical final concentration of 0.5% to 5%. The pluronic component itself can be any one of the pluronic acids, such as type F-127. The concentration of pluronic acid is typically 0.1-10% w / v, such as 0.1-2.5% w / v.

[0088] Pluronic acid is used as solubilizing agent and cleaning agent, as well as wetting agent and dynamic viscosity modifier in compositions disclosed herein. When heated to body temperature, hydrogel preparation forms viscous gel by self-organizing the micelle of pluronic acid into stacking structure. This makes gel stay at application site and exert its activity in needed place. This hydrogel activity is further improved by adding charged oxygen that dissolves stacking micelle (packed micelle) structure, thereby establishing dynamic equilibrium between sol state and gel state. This dynamic state helps to effectively dissolve and trap particles, microorganisms and pollutants in debridement procedure.

[0089] The present invention is based on the synergistic effect between pluronic acid and peroxide. Pluronic acid has the inverse thermodynamic ability to form a "stacked" micellar structure, in which several micelles combine to form a hydrogel. This ability increases with the rise in temperature and transitions to a gel state under physiological conditions (e.g., >20 degrees Celsius). This sol-gel transition forms a stable gel on, for example, living skin, mucous membranes, wounds to serve as a moisture and / or wound dressing that can absorb organic pollutants to a certain extent to prolong the effect.

[0090] However, when mixed with hydrogen peroxide, the present invention discloses for the first time that the sol-gel transition is more dynamic and less stable, so that the transition between the sol state (single solubilized micelle) and the gel state (stacking micellar structure) is in "dynamic" equilibrium with the peroxide radical activity even under physiological conditions (=high temperature). In fact, this means that in the presence of peroxide, the stacking micellar structure is dissolved and constantly reformed (not only by reducing or increasing temperature) when the gel is applied to human tissue / skin / mucous membrane. This effect significantly increases the detergent and the trapping effect of pluronic acid.

[0091] Combined with the action of hydrogen peroxide in releasing oxygen free radicals on viral particles, microorganisms, and necrotic tissue, the sol-gel transition dissolves and entraps organic contaminants, which are then removed when the gel is washed off.

[0092] Another advantage of the present composition is that adding hydrogen peroxide to pluronic acid improves the temperature when forming stacked micelle structure.That is, the pluronic acid gel containing low concentration peroxide is liquid at room temperature, and therefore can be applied by syringe needle or distribution bottle without blocking nozzle.It is impossible to use pluronic acid alone, because it has begun to form stable " stacked micelle " gel at room temperature, and therefore is difficult to squeeze out in the narrow tip of syringe or the pump applicator of distribution bottle.Therefore, the pluronic gel for wound care is sold in the form of boxed or tubed gel.

[0093] The increasing effect of the combination of weak peroxide and pluronic acid was unexpected and surprising.

[0094] The reduced viscosity of the pluronic hydrogel in combination with the peroxide also helps during application. It enables the cleaning and / or debridement composition to reach narrow spaces and undercuts that the pluronic gel alone cannot enter due to its gel-state properties at physiological temperatures. Thus, it is more effective in cleaning rough (implant) surfaces, narrow spaces, such as between bones and implants / teeth, and in wrinkles on the skin.

[0095] Composition

[0096] The present invention relates to a novel antimicrobial and / or anti-inflammatory composition for in situ cleaning and / or debridement of biological surfaces and / or biological material surfaces, comprising at least two components:

[0097] a. H2O2 at a final concentration of 0.1-5 v / v, and

[0098] b. A composite hydrogel formulation comprising pluronic acid at a concentration of 10-40% w / v, and

[0099] Therein, the composition is liquid at room temperature, such as at a temperature up to 30°C, such as at a temperature of 20-30°C, such as at 25°C.

[0100] The composition disclosed herein is characterized in that it comprises components a. and b. in a ratio such that the composition is liquid rather than gel at room temperature. The typical concentration ratio of component a. and component b. is about 1:10 (H2O2 concentration: pluronic acid concentration). In general, the higher the concentration of pluronic acid, the higher the concentration of H2O2 required to keep the composition in a liquid state (sol state) at a temperature of 20-30°C. Exemplary concentration ratios can be, for example, >2.0% v / v H2O2:15% w / v pluronic acid, >2.5% v / v H2O2:20% w / v pluronic acid, >3% v / v H2O2:25% w / v pluronic acid, >3.5% v / v H2O2:30% w / v pluronic acid, >5% v / v H2O2:40% w / v pluronic acid.

[0101] In one embodiment of the antimicrobial 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 a concentration of at least 10% w / v, for example 10% w / v, 15% w / v, 20% w / v, 25% w / v, 30% w / v, 35% w / v or 40% w / v.

[0102] In another embodiment of the antimicrobial 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, for example up to 15% w / v, 20% w / v, 25% w / v, 30% w / v or 35% w / v.

[0103] The antimicrobial and / or anti-inflammatory composition according to the present invention may be a composition wherein the H2O2 of component a. has a final concentration of 0.1-5% v / v, such as 0.5-3% v / v, such as 0.1-5% v / v. In one embodiment, the H2O2 of component a. has a final concentration of no more than 5% v / v, such as 0.1-5% v / v, such as 1% v / v, 2% v / v, 3% v / v, 4% v / v or 5% v / v.

[0104] The antimicrobial and / or anti-inflammatory composition according to the invention may also comprise water and / or saline.

[0105] The two components of the antimicrobial and / or anti-inflammatory composition according to the invention may be in one solution, or at least the two components may be kept separate from each other until they are simultaneously mixed and applied in situ to a biological surface and / or biomaterial surface.

[0106] In the antimicrobial and / or anti-inflammatory composition according to the invention, wherein the components are kept separate from each other prior to administration, the separated component a. may be a composition comprising H2O2 at a concentration of at least 10-50% v / v, for example at most 10% v / v, 20% v / v, 30% v / v, 40% v / v or 50% v / v. In one embodiment, the composition of the invention comprises H2O2 at a concentration of 30% v / v.

[0107] Emulsifiers and / or viscosity modifiers

[0108] In one embodiment, the antimicrobial and / or anti-inflammatory composition according to the present invention further comprises one or more emulsifiers and / or viscosity modifiers. The emulsifiers and / or viscosity modifiers may be selected from the group consisting of glycerol, glycols, polyethylene glycol (PEG), polyoxyethylene polyoxypropylene block copolymers (Pluronic polyols), glycol alginate (PGA), CMC (carboxymethyl cellulose), glycerol, aloe gel, alginate, hyaluronic acid (HA) and chitosan.

[0109] The antimicrobial and / or anti-inflammatory composition according to the present invention may further comprise one or more cleaning agents selected from the group consisting of SDS (sodium dodecyl sulfate), sodium stannate, sodium pyrophosphate, 8-hydroxyquinoline (oxine) and SLS (sodium lauryl sulfate).

[0110] The antimicrobial and / or anti-inflammatory compositions according to the present invention may also comprise one or more flavoring oils, such as, but not limited to, oils of spearmint, peppermint, wintergreen, sassafras, clove, sage, eucalyptus, marjoram, cinnamon, as well as methyl salicylate and menthol.

[0111] The antimicrobial and / or anti-inflammatory composition according to the invention may further comprise one or more weakly acidic buffers.

[0112] particle

[0113] The composition according to the present invention may also contain microparticles having an average particle size (D50) of 20-200 μm. The concentration of the microparticles is generally about 0.5-1000 g / L, such as about 0.5-300 g / L.

[0114] The composition according to the present invention may comprise a composition that releases one or more selected from the group consisting of Ca 2+ 、F - , Sr 2+ and Mg 2+ Particles composed of groups of ions.

[0115] In one aspect, the composition according to the present invention comprises microparticles consisting 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 sucrose, calcium oxalate, calcium gluconate, calcium propionate, calcium caseinate, calcium glycerophosphate, and combinations thereof.

[0116] In another aspect, the composition according to the present invention comprises microparticles consisting of a calcium oxide compound powder selected from the group consisting of calcium oxide, calcium peroxide, calcium hydroxide and combinations thereof.

[0117] In another aspect, the composition according to the 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 wherein the phosphate ion source is sodium phosphate, diphosphate.

[0118] In yet another aspect, the composition according to the present invention comprises microparticles consisting of 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 phosphite, amorphous calcium phosphate, calcium hydroxide phosphate, and combinations thereof.

[0119] In yet another aspect, the composition according to the invention comprises additional microparticles consisting of a compound selected from the group consisting of silicon dioxide, silicate glass, quartz, zinc oxide, barium sulfate, barium silicate, strontium silicate, barium borosilicate, strontium borosilicate, borosilicates, lithium silicates, amorphous silicon dioxide, bismuth compounds, aminated or deaminated calcium phosphates, aluminum oxide, zirconium oxide, tin oxide, titanium dioxide, apatite, silica glass fillers, calcium silicate-based fillers, hydroxyapatite, barium sulfate, bismuth subcarbonate, iron, silicon, magnesium, zinc, silver, manganese, palladium, radium or mixtures thereof.

[0120] In another aspect, the microparticles comprised in the composition according to the present invention 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.

[0121] In addition, the composition according to the present invention may further comprise a fluoride ion source, wherein the fluoride ion source may be selected from the group consisting of Na2SiF6, CaF2, SrF2, NaF, NaPO3F, NaKF6PO3, K2SiF6, F6.NaP, NaSbF6, KSbF6, F6KP and mixtures thereof.

[0122] When the composition according to the invention is intended for cleaning and / or debridement of dental implants having metal surfaces, the microparticles are preferably biocompatible and solid (hard) and may also be biodegradable.

[0123] The solid particles can be selected from the group of materials consisting of: TiO2i zirconium oxide, diamond dust (carbon), polymers, polylactic acid (bean), minerals, ceramics, aluminum oxide, calcium carbonate, calcium phosphate, apatite crystals, bone ceramic particles (hydroxyapatite / calcium phosphate), titanium, zirconium, alumina, corundum, pumice and silica.

[0124] The choice of material for the solid particles preferably depends on which material (eg a metal implant or a hard tissue surface) is to be cleaned / debrided by the composition of the invention, to accommodate the roughness of the material to allow effective cleaning / debriding of the material while still not damaging it.

[0125] One advantage of selecting microparticles of the above specified sizes is that surface treatment of dental implants typically results in the formation of indentations with a diameter size of 80-180 μm. Thus, the presence of solid microparticles in the composition of the present invention makes the composition particularly suitable for in situ cleaning and / or debridement of intraoral implants, as the microparticles are of a size that allows them to enter the indentations to clean these, while still being large enough not to cause an inflammatory response and / or be encased in a fibrous capsule by the body.

[0126] The microparticles may be organic or inorganic.

[0127] The organic microparticles comprised in the composition according to the invention may be selected from the non-limiting group consisting of amino acid crystals, biopolymers, chitosan, alginate, pluronic acid, collagen, hyaluronic acid, PEG and organic acids (including insoluble salts thereof, such as but not limited to tartar).

[0128] The inorganic microparticles contained in the composition according to the invention may be chosen from metal compounds, for example from the group consisting of iron, titanium, silicon magnesium, zinc, zirconium, silver, manganese, palladium, radium, calcium and barium.

[0129] In one aspect, the microparticles comprised in the composition according to the invention are biodegradable, for example selected from the group consisting of bare zinc, iron, silicon, magnesium, manganese, silver and palladium.

[0130] The antimicrobial and / or anti-inflammatory compositions according to the invention comprising microparticles are typically formulated as a suspension of solid particles in a liquid.

[0131] Netting and / or scaffolding components

[0132] The composition according to the invention may also comprise at least one net-forming and / or scaffolding component. Typically, at least one net-forming and / or scaffolding component is selected from the group consisting of silk fibers, carbon fibers, silicates, borosilicates, collagen and spider web silk, which improves the physical strength and / or chemical longevity of the composition after application.

[0133] Bioactive substances

[0134] Alternatively or additionally, the composition according to the invention may comprise a biologically active substance, typically selected from the group consisting of: an EMD, a peptide, a drug, a biologically active ion, a small molecule, a radioactive molecule, an antimicrobial molecule and a radiopaque molecule.

[0135] Debridement components and antimicrobial substances

[0136] Furthermore, the composition according to the invention may also comprise further antimicrobial substances and / or debridement components.

[0137] In this context, the additional antimicrobial substance comprised in the composition according to the invention may be chosen from the non-exclusive list consisting of amoxicillin, doxycycline, cephalexin, ciprofloxacin, clindamycin, metronidazole, azithromycin, sulfamethoxazole and trimethoprim.

[0138] In one aspect, the additional antimicrobial substances comprised in the composition according to the invention are tetracycline, doxycycline, macrolides, penicillins (stabilized), chlorhexidine, chloramines and mixtures thereof.

[0139] In one aspect, the composition according to the invention further comprises an additional anti-inflammatory substance.

[0140] Minimum 1 year shelf life at room temperature (RT)

[0141] The composition according to the invention has in one aspect a shelf life of at least 1 year at RT.

[0142] Reagent test kit

[0143] The present invention also relates to a kit comprising a composition according to the invention, comprising at least two containers, respectively comprising said separate components a. and b., a syringe and a vial, a connector device, an applicator tip and an instruction booklet and optionally a mixing device and a debridement tool, 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 also comprise an instruction booklet, a mixing device, an applicator tip and a debridement tool, such as but not limited to a brush.

[0144] The antimicrobial and / or anti-inflammatory compositions according to the invention may be mixed before application and final storage, or stored separately and mixed directly or shortly before and / or at the time of application. Therefore, 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 or more (third or fourth, etc.) containers comprising components c), d), e), etc., which may, for example, comprise microparticles and / or reticulating materials and / or bioactive substances and / or debridement components and / or additional antimicrobial and / or anti-inflammatory substances.

[0145] Optionally, such a kit may also include instructions for preparing the composition of the present invention. The kit may also include one or more devices for applying the composition to a subject. Such devices may, for example, be a syringe or an implant cleaning and / or debridement tool for cleaning and / or debridement of an implant, such as an implant in the oral cavity.

[0146] Preferably, the implant cleaning and / or debridement tool comprises an elongated base member formed by at least two mutually twisted wires, and a plurality of bristles fixed between and extending away from the twisted wires, whereby the bristles are positioned in a cleaning portion at a first end of the base member; and the bristles are composed of titanium and / or a titanium alloy. The kit of the present invention may also comprise the composition of the present invention in one or more containers and an implant cleaning and / or debridement tool for cleaning and / or debridement of an implant in the oral cavity.

[0147] One example of such an implant cleaning / debridement tool for cleaning dental implants and / or debriding hard tissue surfaces is disclosed in US 6,345,406 and another example is given in WO 2009 / 083281.

[0148] The implant cleaning / debridement tool disclosed in WO 2009 / 083281 has bristles with a diameter of 0.2 mm. In one aspect of the invention, the composition of the invention is particularly suitable for use with the tool, which comprises solid particles of a certain size in the composition, the size of which will allow effective cleaning of implants and / or hard surfaces in the oral cavity. For this aspect, the particles are optimally of a size of about 150 pm, such as 100 pm to 150 pm, because when the particles are 10-100 pm, the body tends to integrate the particles into the fibrous capsule.

[0149] Thus, the present invention relates in one aspect to a kit comprising a composition according to any one of the preceding claims, comprising:

[0150] a. at least two containers, each containing the components a. and b.,

[0151] b. Syringes and vials,

[0152] c. Connector device,

[0153] d. an applicator tip, and

[0154] e.Instruction booklet.

[0155] In another aspect, the invention relates to a kit, further comprising:

[0156] f. Mixing device and

[0157] g. Debridement tools.

[0158] In a preferred aspect herein, the kit comprising the composition according to the invention generally provides the two components a. and b. in a two-chamber syringe, which also comprises an instruction booklet, a mixing device, an applicator tip and optionally a debridement tool.

[0159] In one aspect of the invention, the kit further comprises a bone graft material, such as any commercially available bone graft material (Titanoxyd scaffold, BioOss, Emdogain, Bioceramics, SmartBone, etc.).

[0160] use

[0161] The compositions disclosed herein are intended for in situ cleaning and / or debridement of biological surfaces and / or biological material surfaces.

[0162] The compositions disclosed herein are particularly useful in peri-implant defect applications, but the formulations can be tailored to suit a variety of clinical procedures.

[0163] For example, formulations used to treat and / or prevent peri-implantitis often contain higher levels of reactive oxygen species and micromechanical debridement particles.

[0164] Typical formulations for the treatment and / or prevention of peri-implant mucositis will contain increased reactive oxygen species and increased sol-gel activity.

[0165] Typical preparations used for peri-implant maintenance, peri-implant prevention, and postoperative follow-up contain high ROS concentrations.

[0166] However, the compositions disclosed herein may also be used in other oral procedures, such as during surgical debridement of periodontal defects, in preparation for regenerative procedures, periodontal maintenance therapy, periodontitis prevention (dental care), and endodontic treatment, both in endodontics and periapical surgery.

[0167] Additionally, the compositions disclosed herein may also be used for cleaning and / or debridement outside the oral cavity, such as, but not limited to, during orthopedic remedial surgery, debridement of transdermal devices, skin wound care for cleaning acute wounds, and / or debridement of chronic ulcers and burns.

[0168] The antimicrobial and / or anti-inflammatory composition according to the invention can generally be used for the treatment and / or prevention of peri-implantitis, gingivitis and / or mucositis, peri-implant mucositis and / or periodontitis.

[0169] Peri-implantitis is a typical complication associated with dental restorations performed with the use of implants, i.e. peri-implant disease, which is well known to those skilled in the art as an inflammatory reaction in which the bone support of the implant is lost and accompanied by inflammation. The etiology of the disease depends on the state of the peri-implant tissue, implant design, roughness, poor alignment of the implant components, external morphology and excessive mechanical loads.

[0170] The antimicrobial and / or anti-inflammatory compositions described herein provide for the first time a means for effectively and rapidly cleaning implants and / or for debridement of hard surfaces in the oral cavity without damaging the anatomy or the implants and / or hard surfaces themselves, and leaving substantially no residue of contaminating material on the treated surfaces.

[0171] Thus, the present invention relates in one aspect to an antimicrobial and / or anti-inflammatory composition as defined herein and / or a kit for the preparation of a composition of the invention as defined herein for use as a medicament.

[0172] Therefore, the present invention relates to the use of an antimicrobial and / or anti-inflammatory composition according to the present invention for cleaning and / or debridement of implants in the oral cavity (e.g. in situ implants), hard surfaces in the oral cavity (e.g. the outer surfaces of hard tissue in the oral cavity), surgically exposed hard surfaces in the oral cavity, wounds in the oral cavity (e.g. wounds caused by peri-implantitis or surgical wounds, periodontal defects and / or periodontal wounds), and / or oral hard tissue defects.

[0173] The present invention also relates to the use of an antimicrobial and / or anti-inflammatory composition as defined herein and / or a kit for preparing a composition of the present invention as defined herein for the preparation of a medicament and / or a pharmaceutical composition and / or a cosmetic composition for cleaning and / or debridement of implants in the oral cavity (e.g. in situ implants), hard surfaces in the oral cavity (e.g. the outer surfaces of hard tissue in the oral cavity), surgically exposed hard surfaces in the oral cavity, wounds in the oral cavity (e.g. wounds caused by peri-implantitis or surgical wounds, periodontal defects and / or periodontal wounds), and / or oral hard tissue defects.

[0174] The present invention also relates to the use of an antimicrobial and / or anti-inflammatory composition as defined herein or a kit for preparing a composition of the present invention as defined herein for cleaning and / or debridement of implants in the oral cavity (e.g. in situ implants), hard surfaces in the oral cavity (e.g. the outer surfaces of hard tissue in the oral cavity), surgically exposed hard surfaces in the oral cavity, wounds in the oral cavity (e.g. wounds caused by peri-implantitis or surgical wounds, periodontal defects and / or periodontal wounds) and / or oral hard tissue defects.

[0175] Another preferred embodiment herein relates to the use of an antimicrobial and / or anti-inflammatory composition according to the present invention together with an implant cleaning and / or debridement tool for cleaning an implant in the oral cavity and / or debridement of a hard surface in the oral cavity. The implant cleaning and / or debridement tool is characterized in that, for example, it comprises an elongated base member formed by at least two mutually twisted wires, and a plurality of bristles fixed between the twisted wires and extending away from the twisted wires, whereby the bristles are positioned in a cleaning portion at a first end of the base member; and the bristles comprise or consist of titanium and / or a titanium alloy.

[0176] Many medical implants (e.g. dental implants, orthopedic implants and vascular stents) are metallic, i.e. they are made of metallic materials. The present invention therefore relates to antimicrobial and / or anti-inflammatory compositions according to the present invention, alternatively for use with implant cleaning and / or debridement tools for cleaning and / or debridement of implants made of metallic materials. Examples of metallic materials commonly used to construct metallic medical implants are steel, titanium, zirconium, tantalum, niobium, hafnium and alloys thereof. In particular, titanium and titanium alloys have been shown to be suitable for constructing medical implants.

[0177] On the other hand, both medical and dental implants can be at least partially and completely (all-ceramic implants) composed of porcelain and / or ceramics, such as zirconium oxide and / or hydroxyapatite, or any other ceramic or porcelain material suitable for implantation known to those skilled in the art. Therefore, the present invention also relates to the use of the antimicrobial and / or anti-inflammatory composition according to the present invention alternatively with implant cleaning and / or debridement tools for cleaning and / or debridement of implants made of or comprising porcelain and / or ceramics. Therefore, the present invention also relates to the use of the composition of the present invention for preparing a medicament and / or pharmaceutical composition and / or cosmetic composition for cleaning and / or debridement of implants made of or comprising porcelain and / or ceramics. In addition, the present invention relates to the use of the composition of the present invention alternatively for cleaning and / or debridement of implants made of or comprising porcelain and / or ceramics.

[0178] Dental implants are often used in tooth restoration procedures for patients who have lost one or more teeth. Dental implants include dental fixtures that serve as artificial tooth root replacements. Thus, the dental fixtures serve as the roots of new teeth. Dental fixtures are typically screws, i.e., they have the shape of a screw and are typically made of titanium, titanium alloys, zirconium, or zirconium alloys. The screw is surgically implanted into the jawbone, where the bone is in close contact with the implant surface after bone tissue grows around the screw and the screw is fixed in the bone. Once the implant screw is firmly anchored in the jawbone, it can be elongated by connecting an abutment to the screw. Like the screw, the abutment can be made of titanium, titanium alloys, zirconium, or zirconium alloys. The shape and size of the abutment used are adjusted so that it passes precisely upward through the mucosa after being connected to the screw. A dental restoration such as a crown, bridge, or denture can then be attached to the abutment. Alternatively, the implant screw has such a shape and size that it passes upward through the mucosa after implantation, so that no abutment is required and a dental restoration such as a crown, bridge, or denture can be directly attached to the screw.

[0179] Therefore, the present invention relates to the use of an antimicrobial and / or anti-inflammatory composition according to the present invention, alternatively together with an implant cleaning and / or debridement tool, for cleaning and / or debridement of any part of a dental implant selected from the group consisting of: a dental fixture (e.g., a screw, abutment) and a dental restoration (e.g., a crown, a bridge or a denture). Therefore, the present invention also relates to the use of a composition according to the present invention for the preparation of a medicament and / or pharmaceutical composition and / or cosmetic composition for cleaning and / or debridement of any part of a dental implant selected from the group consisting of a dental fixture (e.g., a screw, abutment) and a dental restoration (e.g., a crown, a bridge or a denture). In addition, the present invention relates to the use of a composition according to the present invention for cleaning and / or debridement of any part of a dental implant selected from the group consisting of a dental fixture (e.g., a screw, abutment) and a dental restoration (e.g., a crown, a bridge or a denture).

[0180] The present invention also relates to the use of an antimicrobial and / or anti-inflammatory composition according to the invention, alternatively together with an implant cleaning and / or debridement tool, for cleaning and / or debridement of orthopedic implants, for example for preserving and restoring the function of the musculoskeletal system, in particular joints and bones, including relieving pain in these structures, and / or for cleaning and / or debridement of vascular stents (i.e. tubular implants arranged to be inserted into blood vessels to prevent or counteract local flow constriction). Therefore, the present invention also relates to the use of a composition according to the invention for the preparation of a medicament for cleaning and / or debridement of orthopedic implants, for example for preserving and restoring the function in the musculoskeletal system, in particular joints and bones, including relieving pain in these structures, and / or for cleaning and / or debridement of vascular stents. In addition, the present invention relates to the use of a composition according to the invention for cleaning and / or debridement of orthopedic implants, for example for preserving and restoring the function in the musculoskeletal system, in particular joints and bones, including relieving pain in these structures, and / or for cleaning and / or debridement of vascular stents.

[0181] The surfaces of medical implants (e.g., dental implants, orthopedic implants, and vascular stents) or their vicinity must sometimes be cleaned after placement. This is particularly important when infection or contamination occurs, a progressive degenerative process that leads to the bone near the implant, known as peri-implantitis. In these cases, microorganisms and contaminants must be removed from the diseased implant surface to halt the progression of the disease and ensure the reintegration of the implant. Failure to clean the implant surface ultimately leads to loss of bone and implant, and makes further replacement therapy difficult and sometimes even impossible. In addition, the surface of the vascular stent may have to be cleaned during implantation to remove coagulation, and the interior of the vascular stent, i.e., the cavity within the vascular stent, may have to be cleaned in an endoscopic procedure during later treatment due to restenosis, i.e., vascular occlusion.

[0182] Therefore, the present invention relates to the use of the antimicrobial and / or anti-inflammatory composition according to the present invention, alternatively together with an implant cleaning and / or debridement tool, for cleaning and / or debridement of an implant or its vicinity after placement. Therefore, 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 debridement of an implant or its vicinity after placement. In addition, the present invention relates to the use of the composition of the present invention for cleaning and / or debridement of an implant or its vicinity after placement.

[0183] In addition, due to different reasons, it may be advantageous or necessary to debride the hard tissue surface exposed by surgery. For example, it may be advantageous or necessary to debride the hard tissue surface exposed by surgery before regenerative treatment, i.e., to prepare the hard tissue surface for regenerative treatment. Examples of diseases associated with the treatment of the hard tissue surface exposed by surgery, in which debridement is advantageous or necessary to prepare the surface for regenerative treatment, are: peri-implantitis, periodontitis lesions, marginal periodontitis, apical periodontitis, furcation defects, apical granulomas and cysts, bone cysts, bone tumors, bone granulomas, bone cancer, (infected) extraction sockets, alveolitis sicca ("dry socket"), cleaning of apical excision defects, local osteomyelitis, defects caused by trauma, excision or revision of implants, excision or repair of fractures, and removal of temporary bone implants (e.g., orthopedic bone plates, retainers, and screws). Additionally, it may be beneficial or necessary to debride articular surfaces in joints affected by arthritis and prior to initiating regenerative treatments of cartilage and ligaments.

[0184] Therefore, the present invention relates to the use of the antimicrobial and / or anti-inflammatory composition according to the present invention alternatively with an implant cleaning and / or debridement tool for cleaning and / or debridement of surgically exposed hard tissue surfaces prior to regenerative therapy. Therefore, the present invention also relates to the use of the composition according to the present invention for preparing a medicament and / or pharmaceutical composition and / or cosmetic composition for cleaning and / or debridement of surgically exposed hard tissue surfaces prior to regenerative therapy. In addition, the present invention relates to the use of the composition according to the present invention for cleaning and / or debridement of surgically exposed hard tissue surfaces prior to regenerative therapy.

[0185] The antimicrobial and / or anti-inflammatory composition according to the present invention can be used to clean the surface of the metal medical implant after infection and / or bone resorption during surgery, alternatively together with implant cleaning and / or debridement tools. Therefore, it can be used to clean the surface of metal dental implants and / or metal orthopedic implants. Therefore, it can be used to, for example, remove bacterial biofilm, debris, calculus or fibrous tissue from the surface of dental implants (e.g., titanium screws). Alternatively, it can be used together with other cleaning agents (i.e., antibacterial agents) to remove bacterial biofilm near dental fixtures during implantation. It can also be used to clean the surface or vicinity of abutments. Therefore, the present invention also relates to the use of the composition of the present invention for preparing a medicament for cleaning, for example, removing bacterial biofilm, debris, calculus or fibrous tissue from the surface of metal dental implants (e.g., titanium screws or abutments) or metal orthopedic implants. In addition, the present invention relates to the use of the composition of the present invention for cleaning, for example, removing bacterial biofilm, debris, calculus or fibrous tissue on the surface of metal dental implants (e.g., titanium screws or abutments) or metal orthopedic implants.

[0186] In addition, the antimicrobial and / or anti-inflammatory composition according to the present invention can be used to remove cement residues, bacterial biofilms, debris, stones or fibrous tissue from the surface of orthopedic implants, or to remove plaque from the surface of vascular stents, alternatively, it can be used to clean the interior of vascular stents, i.e., the cavity within the vascular stent, during endoscopic examinations during subsequent treatment due to restenosis (i.e., vascular occlusion).

[0187] A procedure involving the use of an antimicrobial and / or anti-inflammatory composition according to the present invention, optionally in combination with an implant cleaning and / or debridement tool, may, for example, involve the following steps: surgically exposing the hard tissue surface to be treated; removing the inflamed soft tissue; debride the surface by means of applying an antimicrobial and / or anti-inflammatory composition according to the present invention, optionally in combination with an implant cleaning and / or debridement tool; applying (regenerative) treatment as needed; replacing the soft tissue; suturing to obtain good primary closure and wound stability; and allowing the wound to heal.

[0188] In particular, the antimicrobial and / or anti-inflammatory composition according to the invention is used, alternatively together with an implant cleaning and / or debridement tool, in regenerative therapy (i.e., by e.g. The antimicrobial and / or anti-inflammatory composition according to the present invention is an effective tool for debridement of surgically exposed root surfaces, furcation defects and bone defects before implantation (such as by means of implant cleaning and / or debridement, Emdogain, bone graft material, autologous bone, membranes, etc.), and is particularly effective for removing granulation tissue and removing calcified biofilm clots (plaque) and subgingival calculus together with implant cleaning and / or debridement tools.

[0189] The antimicrobial and / or anti-inflammatory composition according to the present invention is advantageously used, alternatively in conjunction with an implant cleaning and / or debridement tool, for cleaning and / or debridement of both "hard" metal medical and / or dental implants having relatively hard surfaces (e.g., steel medical implants) and "soft" metal medical implants having delicate surfaces (e.g., medical and / or dental implants of titanium, titanium alloys, zirconium or zirconium alloys).

[0190] Furthermore, the antimicrobial and / or anti-inflammatory composition according to the invention does not leave behind contaminants, ie material residues, which are incompatible with the reintegration of the implanted structure. Thus, the risk of inflammation is minimal.

[0191] In particular, relatively rapid debridement procedures can be performed on surfaces that are otherwise difficult to clean and / or difficult to reach with hand instruments, alternatively with implant cleaning and / or debridement tools, by the antimicrobial and / or anti-inflammatory composition according to the present invention. Rapid treatment ensures better treatment results. As mentioned above, it is a well-known fact that the incidence and frequency of adverse reactions, such as postoperative effects, are directly related to, and are generally proportional to, the time used for debridement of surgically exposed hard tissue surfaces. Therefore, rapid debridement treatment ensures better overall treatment results.

[0192] In cases where the treatment plan for the defect includes the placement of a titanium implant or any other device made of titanium, the use of the antimicrobial and / or anti-inflammatory composition according to the present invention alternatively together with an implant cleaning and / or debridement tool is particularly advantageous because only titanium and no other metal ions or polymers that could cause undesirable and / or adverse clinical and / or biological effects could contaminate the treatment area, thereby hampering the outcome of the planned and / or future implantation procedure.

[0193] Oral Hygiene

[0194] In oral hygiene and dentistry, debridement refers to the removal of plaque and tartar that has accumulated on the teeth, which can be routinely performed by the skilled person for medical, hygienic and purely cosmetic reasons. Therefore, in one embodiment, the antimicrobial and / or anti-inflammatory composition according to the invention is used again alternatively with an implant cleaning and / or debridement tool to remove plaque and tartar that has accumulated on the patient's natural teeth or dental implants. The antimicrobial and / or anti-inflammatory composition according to the invention contains free radicalized oxygen and is therefore particularly suitable for bleaching natural and / or artificial teeth.

[0195] Microorganisms

[0196] The antimicrobial and / or anti-inflammatory composition according to the invention is generally intended for in situ debridement and / or cleaning of biological surfaces and / or biomaterial surfaces, for example for in situ removal of biofouling, biofilm and / or necrotic tissue from such biological surfaces and / or biomaterial surfaces.

[0197] Biofilms that can be prevented, eliminated and / or treated by the compositions of the present invention include, but are not limited to, biofilms present in the oral cavity (e.g., on tooth surfaces), on mucosal / soft tissue surfaces (e.g., gingival / periodontal membranes), and in dental canals (e.g., pulp canals).

[0198] In certain embodiments, biofilms that can be prevented, eliminated and / or treated by the compositions of the present invention include biofilms on and / or within the urinary tract, lungs, gastrointestinal tract, chronic wounds, and biofilms present on surfaces (e.g., implants) and within medical devices and medical lines (e.g., catheters, medical devices, and medical tubes).

[0199] The compositions of the invention can be used to reduce the growth and / or inhibit the viability of one or more microorganisms (eg, bacteria in a biofilm). For example, but not limited to, the bacteria may include Streptococcus mutctns (S. mutctns), Streptococcus sobrinus, Streptococcus sctnguis, Streptococcus gordonii, Streptococcus omlis, Streptococcus mitis, Actinomyces odontolyticus, Actinomyces viscosus, Actinomyces actinomycetemcomitctns, Ictctobctcillus spp., Porphyromoncts gingivctlis, Prevotellct intermedia, Bacteroides forsythus, Treponema denticola, denticola), Fusobacterium nucleatum, Campylobacter rectus, Eikenella corrodens, Veillonella spp., Micromonas micros, Porphyromonas cangingivalis, Haemophilus actinomycetemcomitans, Actinomyces spp., Bacillus spp., Mycobacterium spp., Fusobacterium spp., Streptococcus spp.), Staphylococcus aureus, Streptococcus pyogenes, Streptococcus agalectiae, Proteus mirabilis, Elebsiella pneumoniae, Acinetobacter spp., Enterococcus spp., Prevotella spp., Porphyromonas spp., Clostridium spp., Stenotrophomonas maltophilia, Porphyromonas cangingivalis, Candida albicans, Escherichia coli, and / or Pseudomonas aeruginosa. In certain embodiments, the bacterium is Streptococcus mutans, which is present in biofilms found in the oral cavity, such as on tooth surfaces.

[0200] The microorganisms most associated with implant failure are spirochetes and mobile forms of gram-negative anaerobes. The diagnosis can be based on changes in gingival color, bleeding and probing depth of peri-implant pockets, suppuration, x-rays and progressive loss of bone height around the teeth. To date, the most effective antibiotic therapy proven in the antimicrobial spectrum is a combination of amoxicillin and clavulanic acid. In addition to bacterial infections, microbial infections in the oral cavity can of course also include fungal and / or viral infections.

[0201] The antimicrobial and / or anti-inflammatory composition according to the present invention can effectively kill bacteria, fungi and / or viruses.

[0202] More importantly, the compositions described herein are antimicrobial without inducing microbial resistance, and are anti-inflammatory.

[0203] The present invention therefore relates to a method for treating and / or preventing peri-implantitis, gingivitis and / or mucositis, peri-implant mucositis and / or periodontitis, comprising cleaning and / or debridement of biological and / or biomaterial surfaces in situ by applying a composition according to the invention to said soiled, film-forming and / or necrotic surfaces.

[0204] Example

[0205] The following examples are included to provide guidance to those skilled in the art to practice representative embodiments of the subject matter disclosed herein. In view of the present invention and the general level of those skilled in the art, the skilled artisan will appreciate that the following examples are intended to be exemplary only, and that many variations, modifications and alterations may be employed without departing from the scope of the subject matter disclosed herein.

[0206] Example 1

[0207] Degradation of methylene blue when mixed with 3% v / vv / v H2O2 and fluoride ions released at various concentrations

[0208] Methylene blue (MB) is a heterocyclic aromatic compound with the following molecular formula: 16 H 18 N3SCl (AldrichSigmaAldrich, Oslo, Norway). It has many uses in many different fields, such as biology and chemistry. MB exemplifies organic materials and can therefore be used as a reagent to simulate bacteria, as seen in some publications, and is often used to study the degradation characteristics of H2O2. Therefore, the degradation of MB can be used as an in vivo degradation model for organic materials (e.g., bacteria) or dead, damaged and / or infected tissues. At room temperature, it is a solid, odorless, dark green powder that produces a blue solution when dissolved in water. When degraded in solution, methylene blue becomes colorless.

[0209] When methylene blue was analyzed by UV-visible spectrophotometry (Lambda 25, Perkin Elmer, USA), it absorbed light at 690 cm. This machine was used to quantify the degradation of MB.

[0210] The aim was to measure whether methylene blue could be quenched by only 5% H2O2 ( 30% H2O2 (v / v), Sigma Aldrich AS, Oslo, Norway). Then, increasing concentrations of amorphous calcium phosphate ACP (by mixing two precursor components. Component A contained 40MB in a mixture of ammonium dihydrogen phosphate and diammonium hydrogen phosphate at pH 5.5) were added to the solution until a maximum concentration of 8 g / L.

[0211] 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.

[0212] When only 15% v / vv / v H2O2 ( When 30% H2O2 (v / v), Sigma Aldrich AS, Oslo, Norway) was mixed with MB, almost no degradation was found. Surprisingly, the presence of 0.25 g / L ACP in the suspension made MB degradation possible. 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.

[0213] H2O2 alone cannot decompose MB molecules; surprisingly, ACP must be present for this purpose.

[0214] Example 2

[0215] Degradation of methylene blue when mixed with 7% H2O2 and different concentrations of ACP

[0216] The aim was to measure whether methylene blue could be degraded by ACP nanoparticles alone (synthesized by chemicals from Sigma Aldritch, a mixture of ammonium dihydrogen phosphate and diammonium hydrogen phosphate, pH 5.5) in the absence of H2O2 in a composite hydrogel formulation containing pluronic acid (Sigma Aldrich AS, Oslo, Norway) at a concentration of 5% w / v. 30% H2O2 (v / v), Sigma Aldrich AS, Oslo, Norway) was added to the suspension to a maximum concentration of 7% v / v. The experimental procedure was the same as described in Example 1.

[0217] Results not shown. When only 0.5 g / L of ACP was mixed with MB, almost no degradation was found. Addition of 5% v / vv / v concentrated H2O2 increased MB degradation. Increasing the concentration of H2O2 in the suspension increased MB degradation in a linear manner. Increasing the concentration of H2O2 decreased the pH from 4.9 without H2O2 to 3.3 with 15% v / v H2O2.

[0218] ACP alone cannot decompose MB molecules; H2O2 must be present for this purpose.

[0219] Example 3

[0220] Degradation of methylene blue when mixed with a suspension of 5% H2O2 in a composite hydrogel formulation containing synthetic octacalcium phosphate (OCP) and fluoride-substituted calcium phosphate (F-CaP) at a concentration of 5% w / v of pluronic acid (Sigma Aldrich AS, Oslo, Norway)

[0221] From Examples 1 and 2, a composite hydrogel formulation containing pluronic acid (Sigma Aldrich AS, Oslo, Norway) at a concentration of 5% w / v was selected. 30% H2O2 (v / v), SigmaAldrich AS, Oslo, Norway) and synthetic octacalcium phosphate (OCP) as well as fluoride-substituted OCP concentrates were used to produce a suspension that exploits this synergistic effect but can also be used in a physiological environment ([H2O2] < 6% v / v and pH > 3).

[0222] Synthetic OCP and two types of fluoride-containing apatite calcium phosphate (hereinafter referred to as F-CaP) were prepared according to the previously reported method. In brief, apatite calcium phosphate containing fluoride ions (hereinafter referred to as HF-CaP) was synthesized by incubating OCP powder in 150mM Tris buffer containing 50ppm F- (as sodium fluoride: NaF) at 37°C (by F-hydrolysis). The initial pH of the buffer varied from 7.1 to 9.9. The incubation of HF-CaP lasted for 10 minutes or 60 minutes. In contrast, apatite calcium phosphate containing fluoride ions produced by co-precipitation with F- (hereinafter referred to as CF-CaP) was prepared by applying co-precipitation of OCP in the presence of F-. Calcium acetate solution was added to a sodium hydrogen phosphate solution containing F- (as NaF) at 70°C for 30 minutes according to the previously described synthesis method. The F- concentration initially used was in the range of 12-230ppm. All recovered samples were washed several times with distilled water and dried at 105°C overnight.

[0223] The aim was to find out whether NaCl and NaF salts further increase MB degradation when introduced into the selected suspensions. Results not shown.

[0224] Interestingly, doping the suspension with NaCl reduced MB degradation by half compared to the suspension containing only OCP and H2O2. Substitution with F (Sigma Aldrich AS, Oslo, Norway) was even more potent in reducing MB degradation compared to the suspension containing only OCP and H2O2, almost preventing it from occurring.

[0225] 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.

[0226] Ca on F-CaP coating 2+ and changes in inorganic phosphate ion concentration

[0227] The Ca content in the culture medium was determined using the Calcium E and Phosphorus C assays (Wako Pure Chemical Industries, Osaka, Japan), respectively. 2+ and inorganic phosphate ion (Pi) concentrations. 100 μl 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 the plates were incubated at 37°C in a 5% carbon dioxide environment for 3 days, the supernatant was collected for Ca 2+ and Pi quantitative analysis.

[0228] The dissolution behavior of F-CaP or OCP particles was investigated after incubation with α-MEM for 3 days at 37 °C. The Ca content of the supernatants of HF1.80-CaP and HF3.33-CaP was 2.34 wt.% and 1.3 wt.% respectively, relative to the uncoated control. 2+ In contrast, the Ca concentration in the culture medium from the CF-CaP coating 2+ Ca concentrations equal to or slightly above OCP 2+ concentration.

[0229] Example 4

[0230] pH measurements of various suspensions of composite hydrogel formulations containing pluronic acid (Sigma Aldrich AS, Oslo, Norway) at a concentration of 10% w / v

[0231] pH is an important factor in wound healing, and the pH of the suspension can be altered by varying the concentration of calcium phosphate (from Example 3) and other added components.

[0232] The pH in the different solutions was measured using a laboratory pH meter (pH Meter Lab 850 Set with Blueline 14 pH Electrode, Scott Glass Ltd, Staffordshire, UK). The following is a list of the pHs produced at the given concentrations:

[0233] A mixture of 1.5% v / v H2O2 and 1.6 g / L 1.6 g / L ACP resulted in pH = 4.4 ± 0.1.

[0234] A mixture of 2.5% v / v H2O2 + 1.6 g / L HA resulted in pH = 5.2 ± 0.1

[0235] A mixture of 3.5% v / v H2O2 + 1.6 g / L CaPF resulted in pH = 6.1 ± 0.0

[0236] A mixture of 4.5% v / v H2O2 + 1.6 g / L OCP-F + 1.6 g / L ACP resulted in pH = A 4.2 ± 0.1

[0237] A mixture of 5.5% H2O2 + 1.6 g / L HA-F + 1.6 g / L ACP resulted in pH = 5.9 ± 0.0

[0238] The various test suspensions ranged from 4.2 to 6.1.

[0239] Example 5

[0240] Suspensions containing different calcium phosphates

[0241] 2 g / L solutions of different calcium phosphates were purchased from Sigma Aldrich (hydroxyapatite, hydroxy calcium phosphate, Hap Ca 10 (PO4)6(OH)2, tricalcium phosphate [Ca5(OH)(PO4)3] x， β-TCP, β-tricalcium phosphate Ca3O8P2, α-tricalcium phosphate Ca3O8P2 and compared with CaP from Examples 1-4, and 3 vol.% H2O2 ( 30% H2O2 (v / v), Sigma Aldrich AS, Oslo, Norway).

[0242] The amount of calcium in the different compositions was determined using atomic absorption spectroscopy (AAS; AANALYST 400, Perkin Elmer, USA). The AAS samples were acidified with HCl to dissolve the precipitated minerals, and then lanthanum chloride was added at a concentration of 10 mg / mL to precipitate phosphates. Acetylene was used as a carrier gas. Three independent samples were measured for each data point.

[0243] Example 6

[0244] Antibacterial Effect of Ca-P Particles on Staphylococcus aureus

[0245] This example describes the antibacterial potential of activated CA-P particles.

[0246] bacteria:

[0247] Staphylococcus aureus (S. aureus) is an important human commensal and opportunistic pathogen that can cause a wide range of infections. They are one of the most well-known bacteria causing post-surgical infections. Therefore, S. aureus was chosen for this experiment.

[0248] program:

[0249] The antibacterial effects of the three gels were analyzed by mixing H2O2 (1% v / v, 2% v / v and 5% v / v) with 0.5 g / L, 1.6 g / L and 20 g / L of CaP of Example 5. The suspension was treated with 30% H2O2 (v / v), Sigma Aldritch AS, Oslo, Norway). The control was Pluronic gel without any particles.

[0250] These gels will be diluted in 4ml PBS (Dulbecco's PBS, Sigma-Aldrich, St. Louis, MO, USA) (stock solution) before mixing a suspension loaded with 500μl of Staphylococcus aureus broth. A drop of 10μl of this stock solution is placed on top of the gel. Once the UV exposure of the test group is reached, the small square gel is placed separately in a 1.5ml Eppendorf tube containing 500μl cell culture medium (without antibiotics) from Invitrogen (GIBSCO MEM, Invitrogen, Carlsbad, CA, USA). All Eppendorf tubes containing gels and bacteria are placed in an incubator at 37°C for 20 hours in the dark. After 20 hours, all samples are taken out of the incubator. The spectrometer (Perkin Elmer UV-Vis200, Oslo, Norway) is calibrated with only 700μl cell culture medium as a baseline. Then, three Eppendorf tubes containing only 500μl cell culture medium + 10μl stock solution are analyzed. Then, shake the tubes one by one and mix the 400 μl volume of each tube with 300 μl of cell culture medium. A 1.5 ml cuvette contains 700 μl of the liquid to be analyzed.

[0251] The results showed that the presence of CaP particles did not alter the changes in antibacterial properties.

[0252] Example 7

[0253] Antibacterial effect of CA-P particles on Pseudomonas aeruginosa

[0254] This example describes the antibacterial potential of the Ca-P particles as described in Example 4.

[0255] bacteria:

[0256] Pseudomonas aeroginosa bacteria are opportunistic pathogens that cause a wide range of infections and are often found in chronic wounds.

[0257] program:

[0258] The antibacterial effect of different gels was evaluated by 3%, 5% and 7% H2O2 ( 30% H2O2 (v / v), Sigma Aldritch AS, Oslo, Norway) in a suspension of pluronic gel at concentrations (0.1, 1 and 5% v / v) mixed with 0.5 g / L, 2 g / L and 5 g / L of Ca-P (Example 4). The control was a gel without any suspension.

[0259] These gels will be diluted in 4ml PBS (Dulbecco's PBS, Sigma-Aldrich, St. Louis, MO, USA) (stock solution) before mixing a suspension loaded with 500μl of Staphylococcus aureus broth. A drop of 10μl of this stock solution is placed on top of the gel. Once the UV exposure of the test group is reached, the small square gel is placed separately in a 1.5ml Eppendorf tube containing 500μl cell culture medium (without antibiotics) from Invitrogen (GIBSCO MEM, Invitrogen, Carlsbad, CA, USA). All Eppendorf tubes containing gels and bacteria are placed in an incubator at 37°C for 20 hours in the dark. After 20 hours, all samples are taken out of the incubator. The spectrometer (Perkin Elmer UV-Vis200, Oslo, Norway) is calibrated with only 700μl cell culture medium as a baseline. Then, three Eppendorf tubes containing only 500μl cell culture medium + 10μl stock solution are analyzed. Then, shake the tubes one by one and mix the 400 μl volume of each tube with 300 μl of cell culture medium. A 1.5 ml cuvette contains 700 μl of the liquid to be analyzed.

[0260] Example 8

[0261] Antibacterial effect of bioceramic particles on Escherichia coli bacteria

[0262] This example describes the antibacterial potential of various bioceramics.

[0263] bacteria:

[0264] Escherichia coli bacteria are sometimes present in chronic wounds.

[0265] program:

[0266] The antibacterial effects of the three gels were investigated by mixing 3, 5 and 7.5 g / L of H2O2 ( 30% H2O2 (v / v), SigmaAldritch AS, Oslo, Norway). The controls were gel without any suspension and gel with H2O2 ( 30% H2O2 (v / v), Sigma Aldritch AS, Oslo, Norway), 5% v / v) (at concentrations of (0.1% v / v, 1% v / v and 5% v / v) in Pluronic gel).

[0267] These gels will be diluted in 4ml PBS (Dulbecco's PBS, Sigma-Aldrich, St. Louis, MO, USA) (stock solution) before mixing a suspension loaded with 500μl of Staphylococcus aureus broth. A drop of 10μl of this stock solution is placed on top of the gel. Once the UV exposure of the test group is reached, the small square gel is placed separately in a 1.5ml Eppendorf tube containing 500μl cell culture medium (without antibiotics) from Invitrogen (GIBSCO MEM, Invitrogen, Carlsbad, CA, USA). All Eppendorf tubes containing gels and bacteria are placed in an incubator at 37°C for 20 hours in the dark. After 20 hours, all samples are taken out of the incubator. The spectrometer (Perkin Elmer UV-Vis200, Oslo, Norway) is calibrated with only 700μl cell culture medium as a baseline. Then, three Eppendorf tubes containing only 500μl cell culture medium + 10μl stock solution are analyzed. Then, shake the tubes one by one and mix the 400 μl volume of each tube with 300 μl of cell culture medium. A 1.5 ml cuvette contains 700 μl of the liquid to be analyzed.

[0268] The presence of ZrO2 did not change the antibacterial activity, whereas surprisingly, the presence of TiO2 did. The effect on concentration was linear.

[0269] Example 9

[0270] Antibacterial effect of fluorine-doped activated Bioglas against Staphylococcus aureus

[0271] This example describes the Bioglass TM The antibacterial potential of 45S5 (MOSCI Corp. Rolla Missouri MO 65401) and compared with 0.5g / L, 1.6g / L and 20g / L Bioglass TM 45S5 mixed with 3, 5 and 7.5 H2O2 ( The samples were mixed in a suspension of 30% H2O2 (v / v), Sigma Aldritch AS, Oslo, Norway).

[0272] bacteria:

[0273] Staphylococcus aureus (S. aureus) is an important human commensal and opportunistic pathogen that can cause a wide range of infections. They are one of the most well-known bacteria causing post-surgical infections. Therefore, S. aureus was chosen for this experiment.

[0274] program:

[0275] The antibacterial effect of the gel was investigated by mixing 5% v / v H2O2 ( 30% H2O2 (v / v), Sigma Aldrich AS, Oslo, Norway) suspension. In addition, the suspension was doped with 0.01, 0.5, 1 and 3 atomic weight percent of fluorine. Doping was done by adding an equal amount of NaF to the suspension. X-ray spectroscopy (XPS) was used to detect and quantify the amount of fluorine on the surface. Controls were gels without any suspension and gels treated with only 5% v / v H2O2 ( 30% H2O2 (v / v, Sigma Aldritch AS, Oslo, Norway) treated gel.

[0276] These gels will be diluted in 4ml PBS (Dulbecco's PBS, Sigma-Aldrich, St. Louis, MO, USA) (stock solution) before mixing a suspension loaded with 500μl of Staphylococcus aureus broth. A drop of 10μl of this stock solution is placed on top of the gel. Once the UV exposure of the test group is reached, the small square gel is placed separately in a 1.5ml Eppendorf tube containing 500μl cell culture medium (without antibiotics) from Invitrogen (GIBSCO MEM, Invitrogen, Carlsbad, CA, USA). All Eppendorf tubes containing gels and bacteria are placed in an incubator at 37°C for 20 hours in the dark. After 20 hours, all samples are taken out of the incubator. The spectrometer (Perkin Elmer UV-Vis200, Oslo, Norway) is calibrated with only 700μl cell culture medium as a baseline. Then, three Eppendorf tubes containing only 500μl cell culture medium + 10μl stock solution are analyzed. Then, shake the tubes one by one and mix the 400 μl volume of each tube with 300 μl of cell culture medium. A 1.5 ml cuvette contains 700 μl of the liquid to be analyzed.

[0277] The results showed that the number of particles had little effect on the antibacterial properties, while the most important factors were the amount of Pluronic gel and H2O2.

[0278] Example 10

[0279] Biofilm Removal

[0280] This example describes the antibacterial potential of Pluronic gel at concentrations (0.1% v / v, 1% v / v and 5% v / v). In vitro testing: Biomass evaluation after cleaning.

[0281] Sample preparation

[0282] Chemically pure (cp) titanium disks with a diameter of 6.2 mm and a height of 2 mm were used. They had similar machined surface topography (waviness at the curled edge).

[0283] After production, the discs were cleaned with 40% v / v NaOH and 50% v / v HNO3 in an ultrasonic bath to remove contaminants, then rinsed with deionized water to achieve neutral pH and stored in 70% v / v ethanol at room temperature. Thereafter, the coins were placed in Eppendorf tubes and steam autoclaved.

[0284] Four cleaning chemicals 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).

[0285] Inoculation, cleaning and analysis

[0286] 15 sterile titanium discs were inoculated in each group. The control group was inoculated with brain heart infusion broth (BHI) only, while the test group (four) was inoculated with bacterial culture (10μl Staphylococcus epidermidis + 5ml BHI). The incubation time was set to 24 hours in an aerobic atmosphere at 35°C. The discs were then transferred to new wells, rinsed with sterile saline, then exposed to four selected chemical agents for two minutes, and then rinsed with sterile saline again. The amount of biofilm present on the surface of the titanium samples was assessed by using safranin staining: exposed to 0.1% safranin solution for 10 minutes, then rinsed with distilled water, air dried, and exposed to 30% acetic acid solution to release colored biomass from the titanium surface. The staining intensity was analyzed using a Synergy HT Multi-Detection Microplate Reader (Biotek, VT, USA) with a wavelength of 530nm.

[0287] result

[0288] Densitometric analysis in a Synergy HT multi-detection microplate reader showed that samples exposed to a mixture of 3% v / v H2O2 and different gel concentrations were significantly different from the control. In addition, higher pluronic acid concentrations and higher hydrogen peroxide concentrations increased biofilm removal.

[0289] Embodiment 11

[0290] Regrowth of biofilms after exposure to activated TiO2 microparticles

[0291] This example describes the antibacterial potential of activated TiO2 microparticles in preventing biofilm regrowth after disinfection.

[0292] In vitro test: bacterial regrowth

[0293] To determine the viability of the biofilm after disinfection, another test was performed. The method was similar to the safranin staining analysis performed in Example 10 above, from inoculation to disinfection using the same four products. However, this time, after the disinfection step, the samples were rinsed in NaCl and re-incubated in pure BHI medium at 35°C for 4 hours. The culture medium was collected and analyzed using the same spectrophotometer as used for safranin staining, but this time at a wavelength of 600nm. The absorbance intensity of the control and test groups was compared.

[0294] Results from this experiment should show a significant reduction in the level of bacterial regrowth on samples exposed to the 3% v / v H2O2 and 2 g / L TiO2 mixture compared to the control group and samples exposed to H2O2 alone.

[0295] Example 12

[0296] Applications for the treatment of periodontitis

[0297] The two-component Pluronic-Peroxide gel described herein is intended for debridement of teeth by topical application. Debridement is the medical removal of dead, damaged or infected tissue to enhance the healing potential of the remaining healthy tissue. In oral surgery and dentistry, debridement also refers to the removal of biofilm / plaque that accumulates on the roots of teeth (considering that plaque can also be considered a mineralized biofilm). The gel aids in tooth debridement; it effectively increases the efficiency of mechanical removal of biofilm / plaque from tooth surfaces; biofilm / plaque causes inflammatory conditions, so removal brings advantages in terms of:

[0298] - Reduce tooth tissue degeneration,

[0299] - Reduce inflammation,

[0300] -Reduces the occurrence of periodontitis, bone damage and tooth loss.

[0301] The intended use of the device is for the systematic professional treatment of periodontitis and patients at risk of such problems.

[0302] The gel device may be used as part of any debridement procedure, alone or as an adjunct to mechanical removal remedies (e.g., specific toothbrushes, handheld instruments, or powered devices). The product has no incompatibility with materials that constitute most common brushes or materials used in restorative or cosmetic dentistry.

[0303] Mixing gel:

[0304] 1) The contents of the syringe must be completely injected into the vial containing hydrogen peroxide;

[0305] 2) Shake the vial to aid mixing without removing the syringe;

[0306] 3) Draw the mixture into the syringe, remove the vial and tighten the tip into the Luer lock connection and use it to apply the gel directly to the area of ​​interest;

[0307] The mixed gel must be used within 20 minutes. This is because the active hydrogen peroxide loses its effectiveness after this time. Since the peroxide and the gel decompose into water, carbon dioxide and oxygen, the inactivity does not pose any harm to the patient or the environment.

[0308] Uses of Pluronic-Peroxide Gel in Periodontal Surgery:

[0309] 1. Following reflection of the mucoperiosteal flap in the area selected for periodontal surgery, mechanical debridement of the exposed root surface is performed to remove any excess plaque and / or calculus.

[0310] 2. The gel is then applied topically to the exposed and debrided root / implant surface for 2 minutes. The gel is applied to those portions of the surface that will be covered by soft tissue once the flap is replaced and sutured.

[0311] 3. Active friction («polishing») may be applied by means of hand-held instruments, brushes (such as a brush), ultrasonic devices or any other selected electrical device, laser or compressed air, as these reduce the effectiveness of the gel.

[0312] 4. After debridement, the root surface and adjacent tissues must be thoroughly rinsed with sterile saline solution.

[0313] 5. If planned, apply one or more regenerative therapy devices.

[0314] 6. Reposition the flap and secure with sutures. There are no special postoperative precautions when using the gel.

[0315] 7. Care should be taken to avoid recontamination of the treated root / implant surface after final irrigation and before treatment with regenerative products.

[0316] Embodiment 13

[0317] Application for peri-implantitis treatment

[0318] The two-component Pluronic-Peroxide gel described herein is intended for debridement of implanted implants by topical application. Debridement is the medical removal of dead, damaged or infected tissue to improve the healing potential of the remaining healthy tissue. In oral surgery and dentistry, debridement also refers to the removal of biofilm / plaque that has accumulated on the implant surface (considering that plaque can also be considered a mineralized biofilm). The gel facilitates implant debridement; it effectively increases the efficiency of mechanical removal of biofilm / plaque from the implant surface; biofilm / plaque causes inflammatory conditions, so removal offers advantages in terms of:

[0319] - Reduce the degeneration of peri-implant tissue,

[0320] - Reduce local inflammation,

[0321] -Reduce the occurrence of peri-implantitis, bone damage and implant loss.

[0322] The intended use of the device is for the systematic professional surgical treatment of peri-implantitis in patients at risk for the above mentioned problems.

[0323] The gel may be used as part of any debridement procedure, alone or as an adjunct to mechanical removal remedies (e.g., specific toothbrushes, hand-held instruments, or powered devices). The product has no incompatibilities with the materials that make up most common brushes or with materials used in restorative or cosmetic dentistry.

[0324] Mixing gel:

[0325] 1) The contents of the syringe must be completely injected into the vial containing hydrogen peroxide;

[0326] 2) Shake the vial to aid mixing without removing the syringe;

[0327] 3) Draw the mixture into the syringe, remove the vial and tighten the tip into the Luer lock connection and use it to apply the gel directly to the area of ​​interest.

[0328] The mixed gel must be used within 20 minutes. This is because the active hydrogen peroxide loses its effectiveness after this time. Since the peroxide and the gel decompose into water, carbon dioxide and oxygen, the inactivity does not pose any harm to the patient or the environment.

[0329] Use of Pluronic-Peroxide Gel in Peri-implantitis Surgery:

[0330] 1. After reflection of the mucoperiosteal flap in the area selected for peri-implant surgery, the exposed implant surface is mechanically debrided to remove any excess plaque and / or calculus.

[0331] 2. The mixed gel is then applied topically onto the exposed and debrided implant surface for 2 minutes. The gel is applied to those portions of the surface that will be covered by soft tissue once the flap is replaced and sutured.

[0332] 3. Active friction («polishing») can be applied by hand instruments, brushes such as (TiBrush), ultrasonic devices or any other electric device of choice. Avoid the use of implantoplasty, lasers or compressed air, as these reduce the efficacy of the gel.

[0333] 4. After debridement, the root / implant surface and adjacent tissues must be thoroughly rinsed with sterile saline solution.

[0334] 5. If planned, apply one or more regenerative therapy devices.

[0335] 6. Reposition the flap and secure with sutures. There are no special postoperative precautions when using the gel.

[0336] 7. Care should be taken to avoid recontamination of the treated implant surface after final flushing and before treatment with regenerative products.

[0337] Embodiment 14

[0338] Application for peri-implant mucositis and gingivitis

[0339] The two-component Pluronic-Peroxide gel described herein is intended for the debridement of teeth and placed implants by topical application. Debridement is the medical removal of dead, damaged or infected tissue to enhance the healing potential of the remaining healthy tissue. In oral surgery and dentistry, debridement also refers to the removal of biofilm / plaque that accumulates on tooth roots and implants (considering that plaque can also be considered a mineralized biofilm). The gel facilitates tooth debridement; it effectively increases the efficiency of mechanical removal of biofilm / plaque from tooth / implant surfaces; biofilm / plaque causes inflammatory conditions, so removal offers advantages in terms of:

[0340] - Reduce the degeneration of periodontal and peri-implant tissues,

[0341] - Reduce local inflammation,

[0342] - Reduce the onset and progression of periodontitis and peri-implantitis that lead to bone, tooth and implant loss.

[0343] The intended use of the device is systematic professional use in the regular oral hygiene of patients at risk of the above-mentioned problems.

[0344] Nu Clean can be used as part of any debridement procedure, alone or as an adjunct to mechanical removal remedies (e.g., specific toothbrushes, handheld instruments, or powered devices). The product has no incompatibilities with materials that make up most common brushes or materials used in restorative or cosmetic dentistry.

[0345] Mixing gel:

[0346] 1. The contents of the syringe must be completely injected into the vial containing hydrogen peroxide.

[0347] 2. Shake the vial to aid mixing without removing the syringe.

[0348] 3. Draw the mixture into the syringe, remove the vial and tighten the tip in the Luer lock connection and use it to apply the gel directly to the area of ​​interest.

[0349] The mixed gel must be used within 20 minutes. This is because the active hydrogen peroxide loses its effectiveness after this time. Since the peroxide and the gel decompose into water, carbon dioxide and oxygen, the inactivity does not pose any harm to the patient or the environment.

[0350] The recommended method of use for non-invasive administration for peri-implant mucositis and gingivitis is:

[0351] 1. After removing supragingival plaque and tartar, mix the gel and carefully apply it into the periodontal pocket using the narrow tip. Be careful not to apply too much pressure to avoid soft tissue damage. Due to the pressure applied, there should be slight ischemia of the gums at the application site, but there should not be any pain or bleeding.

[0352] 2. After application, allow the gel to sit for one minute and then use the debridement tool of choice, usually a hand instrument, ultrasonic device, or brush, to clean the exposed surface of the tooth / implant.

[0353] 3. After mechanical cleaning is completed, rinse off any remaining gel using a water spray and suction.

[0354] 4. Patients can wash off with water normally after the procedure. There are no special post-operative precautions.

[0355] Embodiment 15

[0356] Applications for the prevention and maintenance of peri-implant disease and periodontal disease and for protecting peri-implant health and periodontal health

[0357] The two-component pluronic-peroxide gel described herein is intended for preventive cleaning of teeth by topical application to maintain healthy peri-implant tissue and gums. The gel aids in cleaning teeth and implants and improves the efficiency of mechanical removal of biofilm / plaque from tooth / implant surfaces; biofilm / plaque causes inflammatory conditions, so removal provides advantages in terms of:

[0358] - Reduce inflammation around implants and periodontal tissues,

[0359] -Prevent the onset of periodontal disease and peri-implant disease.

[0360] The intended use of the device is to be used systematically professionally for regular oral hygiene in patients at risk for the above mentioned problems or as a maintenance treatment after surgical intervention to avoid recurrence.

[0361] The gel may be used as part of any cleaning routine, alone or as an adjunct to mechanical removal remedies (e.g., specific toothbrushes, handheld instruments, or powered devices). The product has no incompatibilities with the materials that make up most common brushes or with materials used in restorative or cosmetic dentistry.

[0362] Mixing gel:

[0363] 1. The contents of the syringe must be completely injected into the vial containing hydrogen peroxide.

[0364] 2. Shake the vial to aid mixing without removing the syringe.

[0365] 3. Draw the mixture into the syringe, remove the vial and tighten the tip in the Luer lock connection and use it to apply the gel directly to the area of ​​interest.

[0366] The mixed gel must be used within 20 minutes. This is because the active hydrogen peroxide loses its effectiveness after this time. Since the peroxide and the gel decompose into water, carbon dioxide and oxygen, the loss of activity does not pose any harm to the patient or the environment.

[0367] The recommended approach for non-invasive prevention and maintenance therapy is as follows:

[0368] 1. After removing supragingival plaque and tartar, mix the gel and carefully apply it around the crevicular sulcus and into any gum pockets surrounding the tooth / implant to be treated using the narrow applicator tip. When applying the gel into deep pockets, be careful not to apply too much pressure to avoid damaging the soft tissue.

[0369] 2. After application, allow the gel to sit for one to three minutes to work. Do not use any instruments during this time. The gel will chemically clean the area of ​​interest.

[0370] 3. After the cleaning time is over, the gel should be removed by water spray and suction.

[0371] 4. Repeat the procedure if necessary until the surface looks clean.

[0372] 5. Patients can wash with water normally after the procedure. There are no special post-operative precautions.

[0373] Example 16

[0374] Application for debridement of chronic skin ulcers

[0375] The two-component Pluronic-Peroxide gel described herein is intended for the debridement of chronic skin ulcers by topical application. Debridement is the medical removal of dead, damaged or infected tissue to enhance the healing potential of the remaining healthy tissue. In wound care, debridement also refers to the removal of microbial biofilms that accumulate on the wound surface. The gel aids in the debridement of wounds; it effectively increases the efficiency of mechanical removal of biofilm from the wound surface while increasing local oxygen levels. Microbial biofilms can cause inflammatory conditions, so removal has advantages in:

[0376] - Reduces degeneration of epithelial and connective tissue,

[0377] - Reduce local inflammation,

[0378] -Reduces the occurrence of infection, necrosis and wound progression.

[0379] The intended use of the device is for systematic professional use for repeated treatment of chronic skin wounds in patients at risk for the above-mentioned problems.

[0380] The gel device can be used as part of any debridement procedure, alone or as an adjunct to mechanical removal of remedies (specific brushes, handheld instruments or any type of wound dressing). There are no incompatibilities with known products, but simultaneous use of a vacuum device should be avoided as it can remove active gel from the wound surface.

[0381] Mixing gel:

[0382] The contents of the syringe must be completely poured into the vial containing hydrogen peroxide.

[0383] Shake the vial to aid mixing without removing the syringe.

[0384] Draw the mixture into the syringe, remove the vial and tighten the tip in the Luer lock connection and use it to apply the gel directly to the area of ​​interest.

[0385] The mixed gel must be used within 20 minutes. This is because the active hydrogen peroxide loses its effectiveness after this time. Since the peroxide and the gel decompose into water, carbon dioxide and oxygen, the loss of activity does not pose any harm to the patient or the environment.

[0386] The recommended approach for non-invasive treatment of chronic wounds is as follows:

[0387] 1. After removing pus and excess wound fluid, mix the gel and apply carefully on the wound surface using the included applicator tip.

[0388] 2. After application, allow the gel to sit for three to ten minutes to work, depending on the severity of the wound. Do not use any dressings or wipes during this time. The gel will chemically clean the area of ​​interest.

[0389] 3. When cleaning time is complete, the gel should be removed using a damp wipe to remove as much of the surface as possible. Discard the wipe.

[0390] 4. Repeat the procedure if necessary until the wound looks clean.

[0391] 5. When the wound is satisfactorily debrided, apply the gel a final time to cover the wound. Spread evenly and allow the gel to set.

[0392] 6. Cover the wound with gel with a suitable wound dressing.

[0393] 7. The gel and wound dressing should remain in place until the next scheduled wound debridement and / or wound dressing change.

[0394] 8. Patients can lead a normal life after the procedure. There are no special post-operative precautions when using the gel.

[0395] Embodiment 17

[0396] Compatibility of CaP Microparticles in Pluronic Gel and H2O2 in Vivo

[0397] Test system

[0398] Species: Rabbit

[0399] Variety: New Zealand White

[0400] Experimental design

[0401] Animals were identified as numbers 1 to 6 and assigned to dose groups.

[0402] Administration of test and control items

[0403] One day prior to test item application, hair was removed from an area of ​​at least 8 cm x 10 cm across the dorsal region of the trunk. The next day, 4 gauze patches (2.5 cm x 2.5 cm) were topically applied as shown in Table 1:

[0404]

[0405] Table 1

[0406] Each patch was covered with microporous semi-occlusive tape, and an elastic bandage was wrapped around the animal's trunk.

[0407] The patches were removed and the test sites were demarcated at 1 hour, 24 hours, 48 ​​hours, 72 hours, and 96 hours. The test sites were wiped with gauze and room temperature distilled water. To remove the last remnants of the Pluronic-Peroxide gel, cold water (less than 15 degrees Celsius) was used.

[0408] Justification of route and dose level

[0409] The dermal route of administration was chosen for this study because this route has been defined as a possible route of human exposure, namely in wound care.

[0410] A dose of 0.5 mL per test item was chosen for this study because it is commonly used in this type of study.

[0411] Skin score

[0412] Frequency: 1 hour, 24 hours, 48 ​​hours, 72 hours, and 96 hours after patch removal.

[0413] Procedure: The skin is assessed for erythema and eschar formation, edema formation, skin thickening, desquamation, and any other response to treatment.

[0414] in conclusion

[0415] Application of any of the test gels to intact rabbit skin resulted in no necropsy or histological findings after 1 day or 6 days post removal. The device was considered safe for testing in human skin applications.

Claims

1. A kit for providing an antimicrobial and / or anti-inflammatory composition for in situ cleaning and / or debridement of biological surfaces and / or biological material surfaces, the kit comprising at least three components: a) H2O2 in a concentration of up to 10% v / v, b) a composite hydrogel formulation comprising poloxamer at a concentration of 10% w / v to 40% w / v, c) a debridement tool, the debridement tool comprising a plurality of bristles, and the bristles are composed of titanium and / or a titanium alloy, in, Component a) and component b) are kept separate from each other until they are mixed simultaneously and applied in situ to the biological surface and / or biological material surface, and wherein the composition is liquid at a temperature of at most 30°C.

2. The kit for providing an antimicrobial and / or anti-inflammatory composition according to claim 1, wherein: The composition comprises H2O2 at a final concentration of 0.1% v / v to 4% v / v.

3. The kit for providing an antimicrobial and / or anti-inflammatory composition according to claim 1 or 2, wherein: The composite hydrogel formulation comprises poloxamer 407.

4. The kit for providing an antimicrobial and / or anti-inflammatory composition according to claim 1, wherein: The debridement tool c) includes an elongated base member formed by at least two mutually twisted wires, and a plurality of bristles fixed between the twisted wires and extending away from the twisted wires, whereby the bristles are positioned in a cleaning portion at a first end of the base member; and the bristles are composed of titanium and / or titanium alloy.

5. The kit for providing an antimicrobial and / or anti-inflammatory composition according to claim 1, further comprising microparticles having an average particle size (D50) of 20 μm to 200 μm, wherein: The microparticles are organic or inorganic.

6. The kit for providing an antimicrobial and / or anti-inflammatory composition according to claim 5, wherein: The microparticles are biodegradable.

7. The kit for providing an antimicrobial and / or anti-inflammatory composition according to claim 1, further comprising at least one reticulating and / or scaffolding component.

8. The kit for providing an antimicrobial and / or anti-inflammatory composition according to claim 1, further comprising a biologically active substance.

9. The kit for providing an antimicrobial and / or anti-inflammatory composition according to claim 1, comprising: i) at least two containers, which respectively contain the component a), the component b) and the component c), ii) Syringes and vials, iii) connector device, iv) an applicator tip, and v) Instruction booklet.

10. A kit for providing an antimicrobial and / or anti-inflammatory composition according to claim 9, further comprising a mixing device.

11. The kit for providing an antimicrobial and / or anti-inflammatory composition according to claim 1, wherein: Component a) and component b) are provided in a two-chamber syringe.

12. Use of the antimicrobial and / or anti-inflammatory composition provided by the kit according to any one of claims 1 to 11 in the preparation of a preparation for in situ removal of biofouling, biofilm and / or necrotic tissue from biological surfaces and / or biological material surfaces.

13. Use of an antimicrobial and / or anti-inflammatory composition provided by a kit according to any one of claims 1 to 11 in the preparation of a formulation for the treatment and / or prevention of peri-implantitis, gingivitis, mucositis, peri-implant mucositis, periodontitis, and / or chronic and / or infectious skin ulcers.

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