A solid composition comprising a salt of chlorhexidine selected from chlorhexidine digluconate and chlorhexidine diacetate or mixtures thereof and cetylpyridinium chloride

Abstract

This invention relates to solid compositions in powder or granular form, comprising chlorhexidine salts selected from chlorhexidine digluconate and chlorhexidine diacetate or mixtures thereof, and cetylpyridinium chloride, for the prevention and / or treatment of oral infectious lesions.

Description

Technical Field

[0001] This invention relates to the field of oral lesions. In particular, this invention relates to solid compositions comprising chlorhexidine salts selected from chlorhexidine digluconate and chlorhexidine diacetate or mixtures thereof, and cetylpyridinium chloride, for the prevention and / or treatment of oral infectious lesions. Background Technology

[0002] Chlorhexidine (CHX) is well-known for its use in the treatment of oral infections and in postoperative procedures in the oral cavity. Similarly, cetylpyridinium chloride (CPC) (or other quaternary ammonium salts) is well-known for its use in the daily control of oral microorganisms and viral loads to prevent potential infections. Many oral hygiene products, primarily mouthwashes, are available on the market formulated with these active ingredients.

[0003] The efficacy of these products is directly proportional to the "availability" of the antimicrobial agents they contain. The term "availability" for an antimicrobial agent refers to its ability to reach its preferred target. In the oral cavity, this target refers to pathogenic microorganisms that grow in saliva and on various oral surfaces in the form of biofilms. In this respect, different elements of the formulation have a significant impact on the availability of the antimicrobial agent.

[0004] Properly designed and formulated liquid formulations containing CHX or CHX and CPC are effective in treating oral infectious diseases, while daily use of CPC products supports the maintenance of optimal periodontal health.

[0005] While mouthwashes, when used in the prescribed dosage, are clearly useful as a way to prevent / treat oral diseases, they have many drawbacks, as listed below.

[0006] First, environmental concerns arise. In the composition of these formulations, depending on the product type, the main component is typically 80-85% water, while about 10% consists of a humectant / solvent system based on polyols (glycerol, sorbitol, etc.) and short-chain diols (propylene glycol, pentylene glycol, etc.). Only about 5% comprises sweeteners, colorants, preservatives, flavoring agents, emulsifiers, and active ingredients.

[0007] The water used to manufacture mouthwash includes not only the water that directly enters the composition of these products, but also the water required for the cleaning and disinfection of all the machinery used in manufacturing these products (reactors / mixers, pumps, filtration equipment, intermediate storage tanks, packaging machinery, and all necessary piping networks).

[0008] The amount of water involved in the entire manufacturing process of mouthwash is typically high, estimated at 3.0 kg per 1.0 kg of product. This water must possess certain distinct characteristics for use in the manufacture of these products, specifically: the absence of salt, chemical contaminants, chlorine, dissolved organic matter, and high microbial purity. The raw material for obtaining water with these characteristics is usually tap water used for human consumption.

[0009] The water treatment plant typically includes high-tech and expensive equipment such as reverse osmosis, microfiltration, and sterilization devices using ultraviolet light, usually generated by high-power UV lamps. Once water with the desired characteristics is obtained, it must be stored in appropriate tanks at a temperature below 20°C and continuously circulated through a pump system under constant turbulent flow while being continuously irradiated with high-power UV rays. If not used within 72 hours, it must be treated by controlled discharge into the wastewater system.

[0010] The entire water production / recycling system used to manufacture mouthwash is continuously monitored to detect potential microbial contamination or other types of events. All water loops used for manufacturing are regularly cleaned and maintained.

[0011] For all the reasons mentioned above, the production, maintenance, and control of water used to manufacture mouthwash are expensive, complex, and have a significant environmental impact.

[0012] In current mouthwash manufacturing technology, due to their high water content, another aspect to consider is the need to add a suitable preservative system to the formula to prevent / remove potential microbial contamination during use. In this regard, parabens, a group of chemical compounds commonly found in personal care products, come to mind. Despite considerable discussion, these products have been considered potential carcinogens by some authors.

[0013] The resulting products after palletizing are typically large and heavy, generating significant logistical work and resulting in high energy consumption (fossil fuels and electricity). Mouthwash packaging requires the use of packaging materials of consistent volume (mass), primarily composed of plastics, which are not always fully recyclable or necessarily recycled.

[0014] In short, the environmental problems arising from the manufacture, distribution, and use of water-based mouthwash can be summarized as follows: - Mouthwash manufacturing has a high demand for treated water (3.0 kg of water is consumed for every 1.0 kg of product manufactured), so the large volume of tap water suitable for human consumption is already a very limited resource when deducted from the population.

[0015] - A significant amount of energy is used to obtain water suitable for making mouthwash and to preserve it until it is used.

[0016] - Chemical reagents are used in the process of conditioning water for manufacturing and in the maintenance of its production facilities.

[0017] - The large amount of energy used to produce and regulate large volumes of mouthwash.

[0018] - Preservatives need to be added to mouthwash, and their long-term effects on microorganisms in the environment have not been fully assessed.

[0019] Transporting and distributing large and heavy mouthwashes is a huge logistical task that is costly and consumes a lot of fossil fuels.

[0020] - Packaging is required, including bottles (150-500 ml), caps, and dispensing cups; these materials are not always fully recyclable or necessarily recycled.

[0021] On the other hand, in most cases, the pathogens that cause oral diseases are essentially bacteria. These pathogens are usually present in low loads in healthy oral conditions, resulting in oral biofilms being primarily dominated by symbiotic bacteria in a homeostatic state with the host. Whether oral bacteria grow in biofilms attached to surfaces or are localized in saliva, they are always aggregated.

[0022] Oral biofilms form and adhere to the tooth surface according to a defined sequence of events, leading to a number of diseases, from tooth decay to periodontal disease (gingivitis and periodontitis) and peri-implant disease (mucositis and peri-implantitis).

[0023] Within this oral biofilm, pathogens are less susceptible to antibacterial agents because they are typically located in the deepest layer of the biofilm and are additionally protected by an extracellular matrix composed of polysaccharides, proteins, and DNA. The metabolism of different bacterial species constituting the supragingival and subgingival biofilms can induce lesions such as dental caries, triggered by the secretion of organic acids or by the degradation of the gingival epithelium and subsequent inflammatory response caused by the release of proteases and toxins.

[0024] Oral biofilms evolve, and their bioactivity can change. Once it "matures," it can become mineralized and form tartar. Its accumulation at the gingival margin can induce inflammation and aesthetic problems. It can only be removed mechanically.

[0025] Therefore, the key to oral biofilm control lies in reaching and destroying pathogenic species present in the structure through means that are easy for everyone to use and available to all.

[0026] Despite this demand, most mouthwashes on the market contain antibacterial molecules that are unable to degrade the extracellular matrix and break down pathogenic oral biofilms. At best, the antibacterial agents limit their action to the outermost layer of the oral biofilm, as demonstrated by confocal optical microscopy. Many formulations cannot penetrate more than one-third of the biofilm's thickness.

[0027] The consequence of this is insufficient control of oral biofilms, and mouthwash manufacturers tend to increase the concentration of antibacterial agents, which in turn increases the side effects (staining, loss of taste, etc.) when used in the mouth.

[0028] To address all the aforementioned problems, the inventors have developed a solid composition comprising a chlorhexidine salt selected from chlorhexidine digluconate and chlorhexidine diacetate or mixtures thereof, and cetylpyridinium chloride. This solid composition can be easily and instantly dissolved in a suitable volume of tap water or bottled water to become a mouthwash or a liquid for application via an oral irrigator, or even applied directly to the oral cavity.

[0029] Furthermore, the manufacturing technology for these solid dosage forms involves the use of very small amounts of deionized water obtained by treating tap water (primarily through mechanical cleaning and disinfection processes), estimated to be at most 10% by weight of the solid dosage form produced, rather than the 300% used in the case of classic mouthwash. This significantly reduces tap water consumption, energy consumption, and the use of chemical reagents associated with water production processes and reactor disinfection.

[0030] As mentioned above, the presence of preservatives in water-based mouthwashes is necessary due to the large amount of water present, which promotes the development of contaminating microbial species (bacteria, fungi, or yeasts) that jeopardize product integrity and patient health. On the other hand, while the solid formulation of the present invention is manufactured to avoid accidental microbial contamination, the use of preservatives is permitted by considering two fundamental facts: - The water content in these products is extremely low. Therefore, the potential for microbial contamination and proliferation is highly unlikely, as the conditions for bacterial growth are absent.

[0031] These compositions are typically administered as a single dose and are consumed very quickly after dissolving in tap or bottled water.

[0032] Another significant advantage is in transportation and distribution, thanks to the significantly reduced environmental impact of these solid dosage forms, as the volume and weight handled are much lower, a reduction of 90% compared to conventional mouthwash. The packaging can also be made using more environmentally friendly materials, and each dose is individual.

[0033] The article “Oradox: The future of dentistry DenPro” (December 12, 2023) (https: / / prevestdenprousa.com / wp-content / uploads / 2023 / 12 / Oradox-Oral-Care-Catalog.pdf) discloses effervescent tablets for oral care comprising a blend of chlorhexidine and cetylpyridinium chloride. In contrast, this invention does not include effervescent tablets as a solid composition because the components typically used to obtain effervescent tablets may inhibit antibacterial activity, particularly resulting in very low bioavailability values ​​for chlorhexidine.

[0034] EP0920857 discloses an oral composition for treating halitosis. The composition comprises: b) chlorhexidine disglucuronide, or other soluble and pharmaceutically acceptable chlorhexidine salts of equivalent concentration, at a concentration of 0.025 to 0.20% by weight; c) cetylpyridinium chloride or other pharmaceutically acceptable quaternary ammonium salts at a concentration of 0.025 to 0.10% by weight; and c) pharmaceutically acceptable salts or compounds of Zn(+2) and / or Cu(+2). In contrast, the present invention requires 10 times the concentration of chlorhexidine salts and cetylpyridinium chloride to achieve the effects disclosed herein, which do not include the treatment of halitosis. Summary of the Invention

[0035] This invention relates to solid compositions in powder or granular form, comprising: a) Selected from the following chlorhexidine salts: chlorhexidine digluconate and chlorhexidine diacetate, or mixtures thereof. and b) Cetylpyridinium chloride Used for the prevention and / or treatment of oral infectious lesions. Attached Figure Description

[0036] Figure 1 illustrates the use of various solid compositions containing CHX and CPC. gold Total bacterial count and biofilm viability in CFU / mL after treatment with a standard liquid formulation (reference liquid formulation, which is a commercially available mouthwash with 12% w / w CHX and 0.05% w / w CPC). Detailed Implementation

[0037] This invention relates to solid compositions in powder or granular form, comprising: a) Selected from the following chlorhexidine salts: chlorhexidine digluconate and chlorhexidine diacetate, or mixtures thereof. and b) Cetylpyridinium chloride Used for the prevention and / or treatment of oral infectious lesions. Wherein, the chlorhexidine digluconate, when present as the sole chlorhexidine salt, has a concentration of 0.220-2.200% w / w; or wherein, the chlorhexidine diacetate, when present as the sole chlorhexidine salt, has a concentration of 0.154-1.540% w / w; or wherein, when a mixture of chlorhexidine diacetate and chlorhexidine digluconate is present, the total amount of chlorhexidine, expressed as chlorhexidine digluconate, has a concentration of 0.220-2.200% w / w.

[0038] In one embodiment, the solid composition comprises chlorhexidine digluconate as the sole chlorhexidine salt and cetylpyridinium chloride as the sole chlorhexidine salt. In another embodiment, the solid composition comprises chlorhexidine diacetate as the sole chlorhexidine salt and cetylpyridinium chloride as the sole chlorhexidine salt. In yet another embodiment, the solid composition comprises chlorhexidine digluconate, chlorhexidine diacetate, and cetylpyridinium chloride.

[0039] In this disclosure and claims, terms such as “comprise,” “comprising,” “including,” and “having” are open-ended terms that may mean “include,” “including,” etc.; while terms such as “consisting of” or “consists of” refer to the elements mentioned after these terms and exclude other elements not mentioned.

[0040] Unless otherwise stated, all technical and scientific terms used in this document have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains. The singular terms “a,” “an,” and “the” include plural indicators unless the context clearly indicates otherwise. For example, if indicating “a seasoning,” it is understood that it can be one or more seasonings. Similarly, the word “or” is intended to include “and” unless the context clearly indicates otherwise.

[0041] It should be noted that the term “about” applies to values ​​used before and after this document that include an error range of ±5%, such as ±4%, ±3%, ±2%, ±1%.

[0042] As used herein, the terms “treat,” “treatment,” or “treating,” etc., refer to the improvement of at least one identifiable symptom of an oral infectious lesion listed herein. In another embodiment, “treat,” “treatment,” or “treating,” etc., refer to the improvement of at least one measurable physical parameter, which may not necessarily be identifiable by the patient. In another embodiment, “treat,” “treatment,” or “treating,” etc., refer to suppressing the progression of at least one identifiable symptom of an oral infectious lesion listed herein. In another embodiment, “treat,” “treatment,” or “treating,” etc., refer to slowing the progression of at least one identifiable symptom of an oral infectious lesion listed herein or reversing such progression. As used herein, “prevent,” “prevention,” or “preventing,” and their cognates, refer to delaying the onset or reducing the risk of acquiring or recurring at least one identifiable symptom of an oral infectious lesion listed herein. The general terms “prevent”, “prevention”, or “preventing” also include the prevention of recurrence in subjects who have previously experienced oral infectious lesions listed in this article.

[0043] As used herein, the term “prevention and / or treatment” includes both “prevention and treatment” and “prevention or treatment”.

[0044] As described above, when the solid composition of the present invention comprises chlorhexidine disglucuronide and CPC as the sole chlorhexidine salt, the chlorhexidine disglucuronide is present at a concentration of 0.220-2.200% w / w relative to the total solid composition.

[0045] As described above, when the solid composition of the present invention comprises chlorhexidine diacetate and CPC as the sole chlorhexidine salt, the chlorhexidine diacetate is present at a concentration of 0.154-1.540% w / w relative to the total solid composition.

[0046] As described above, when a mixture of chlorhexidine diacetate and chlorhexidine disglucuronate is used as a chlorhexidine salt in addition to CPC in the solid composition of the present invention, the total amount of each salt shall in any case not exceed the concentration of CHX, expressed as CHX disglucuronate, at 0.220-2.200% w / w relative to the total solid composition.

[0047] In another preferred embodiment, cetylpyridinium chloride is present at a concentration of 0.133-1.100% w / w relative to the total solids composition.

[0048] In another preferred embodiment, the solid composition of the present invention does not contain any salts or compounds of Zn(+2) and / or Cu(+2).

[0049] For the solid compositions constituting the present invention, common art components found in formulations of solid compositions may be added, such as one or more solid compressible polyols, one or more solid or semi-solid emulsifiers, and one or more calcium ion chelating agents. More optionally, the solid compositions of the present invention further comprise flavoring agents, sweeteners, flow aids, and mixtures thereof. Preferably, and independently, the solid or semi-solid emulsifiers are present at a concentration of 0.5-5.0% w / w, the flavoring agents at a concentration of 0.55-2.20% w / w, the sweeteners at a concentration up to 0.110% w / w, the coloring agents at a concentration up to 0.165% w / w, the calcium ion chelating agents at a concentration of 1.50-30.00% w / w, and the flow aids at a concentration up to 10% w / w. The solid compressible polyols are added in sufficient amounts to 100% w / w.

[0050] In another preferred embodiment, the solid composition of the invention is dissolved in water to reconstitute into a liquid or mouthwash for immediate use, or alternatively, a liquid for application via an oral irrigator is prepared by simple immediate dissolution in a suitable volume of tap water or bottled water. In other words, the invention also relates to oral irrigators or mouthwashes comprising the solid composition according to the invention, said solid composition being in powder or granule form, comprising: a) Selected from the following chlorhexidine salts: chlorhexidine digluconate and chlorhexidine diacetate, or mixtures thereof. and b) Cetylpyridinium chloride The solid composition is dissolved in water for immediate use, and Wherein, the chlorhexidine digluconate, when present as the sole chlorhexidine salt, has a concentration of 0.220-2.200% w / w; or wherein, the chlorhexidine diacetate, when present as the sole chlorhexidine salt, has a concentration of 0.154-1.540% w / w; or wherein, when a mixture of chlorhexidine diacetate and chlorhexidine digluconate is present, the total amount of chlorhexidine, expressed as chlorhexidine digluconate, has a concentration of 0.220-2.200% w / w. Used for the prevention and / or treatment of oral infectious lesions.

[0051] In another preferred embodiment of the oral rinse or mouthwash, cetylpyridinium chloride is present at a concentration of 0.133-1.100% w / w relative to the total solids composition.

[0052] Alternatively, in another preferred embodiment, the solid composition of the present invention is applied directly to the oral cavity. By way of example only, for the preferred concentration of the indicated antibacterial agent, the amount of solid to obtain a sufficient concentration of CHX and CPC is 1.5 grams, used as follows: Powders and granules: a. 1.5 g dissolved in 15 ml of untreated tap or bottled water: Use the resulting liquid immediately, similar to the dosage of a corresponding “standard” mouthwash with the same usage.

[0053] b. 1.5g directly into the mouth: Allow it to dissolve in the mouth, then the patient brings water into the mouth and rinses and removes the residue as with a classic mouthwash.

[0054] c. Dissolve 30 grams in 300 ml of untreated tap or bottled water: Use the resulting liquid immediately with an oral irrigator of appropriate capacity. The amount of solid to be used should always be numerically equal to 10% of the volume of water in the irrigator device.

[0055] In another preferred embodiment, oral infectious lesions include, but are not limited to: caries in deciduous and / or permanent teeth, postoperative infections in the oral cavity, gingivitis, periodontitis, oral mucositis, peri-implant mucositis, peri-implantitis, aphthous stomatitis, fungi, sexually transmitted infections in the oral cavity, oral infectious lesions inducing aspiration pneumonia in intubated and / or ICU (Intensive Care Unit) patients, oral infectious lesions inducing aspiration pneumonia in patients with gastroesophageal reflux, infected oral ulcers, and herpetic gingivostomatitis. In a more preferred embodiment, oral infectious lesions are selected from: caries in deciduous and / or permanent teeth, postoperative infections in the oral cavity, gingivitis, periodontitis, oral mucositis, peri-implant mucositis, peri-implantitis, aphthous stomatitis, fungi, sexually transmitted infections in the oral cavity, oral infectious lesions inducing aspiration pneumonia in intubated and / or ICU (Intensive Care Unit) patients, oral infectious lesions inducing aspiration pneumonia in patients with gastroesophageal reflux, infected oral ulcers, and herpetic gingivostomatitis.

[0056] According to the embodiments included herein, this disclosure also relates to a method for preventing and / or treating oral infectious lesions, comprising the steps of: administering a therapeutically effective amount or dose of a solid composition as defined above, i.e., in powder or granule form, comprising: a) Selected from the following chlorhexidine salts: chlorhexidine digluconate and chlorhexidine diacetate, or mixtures thereof. and b) Cetylpyridinium chloride Wherein, the chlorhexidine digluconate, when present as the sole chlorhexidine salt, has a concentration of 0.220-2.200% w / w; or wherein, the chlorhexidine diacetate, when present as the sole chlorhexidine salt, has a concentration of 0.154-1.540% w / w; or wherein, when a mixture of chlorhexidine diacetate and chlorhexidine digluconate is present, the total amount of chlorhexidine, expressed as chlorhexidine digluconate, has a concentration of 0.220-2.200% w / w. Including all possible preferred embodiments, Or administer a therapeutically effective amount or dose of mouthwash or oral rinse as defined above in this application.

[0057] In the context of this invention, the terms "therapeutic effective dose" and "therapeutic effective amount" are used to refer to the amount of the target composition that results in prevention, delay of symptom onset, or improvement of symptoms. Therapeutic effective amount and the frequency of therapeutic effective administration can be determined by methods known in the art.

[0058] It should be noted that, unless the context otherwise requires, any implementation described herein can be considered either alone or in combination with any other implementation described herein. In other words, for example, a preferred option of a defining feature may be combined with a more preferred or less preferred option of another feature.

[0059] The present invention will now be illustrated by means of embodiments, which should in no way be regarded as limiting the invention.

[0060] Example Materials for manufacturing the compositions of the present invention indicated in A1-A3 - Stainless steel sieves are suitable for homogenizing the particle size of raw materials before, during, and at the final screening of particles.

[0061] - Mixer / pulverizer to ensure effective mixing of solids and homogenization of particle size that makes up the mixture.

[0062] - Kneading system for incorporating CHX compound solutions - A volumetric metering system of suitable size and accuracy for incorporating calculated amounts of CHX solution with known density (g / ml) and concentration (w / w).

[0063] - An oven set at 40°C and under vacuum is used for the drying stage of the product.

[0064] - Suitable packaging materials for storing the obtained granules prior to packaging.

[0065] A1. A process for obtaining a composition comprising CHX disaccharide and CPC. 1. Load the selected, pre-sieved compressible polyol (main component) into the mixer / grinder.

[0066] 2. Load the selected, pre-sieved calcium ion complexing agent into a mixer / grinder. Mix it at room temperature for 5–20 minutes.

[0067] 3. Load the selected, pre-sieved solid emulsifier into a mixer / grinder. Mix it at room temperature for 5–20 minutes.

[0068] 4. Optionally, load the selected, pre-sieved sweetener compatible with CHX and CPC into a mixer / grinder. Mix at room temperature for 5–20 minutes.

[0069] 5. Load the pre-sieved active ingredient CPC (cetylpyridinium chloride) into a mixer / grinder. Mix it at room temperature for 5-45 minutes.

[0070] 6. Optionally, load one or more pre-sieved additional components into a mixer / grinder. Mix at room temperature for 5–45 minutes.

[0071] 7. Extract the obtained solid mixture from the mixer / grinder and sieve it.

[0072] 8. Introduce the sieved solids into the kneading system and fill the four separate portions with the desired volume of CHX disglucopyrate solution, mixing for 5-15 minutes after each addition.

[0073] 9. The wet solid was dried under vacuum at 40°C for 3 to 16 hours until all the water added to the CHX disaccharide solution was completely removed.

[0074] 10. Crush and sieve the obtained dry solids. Optionally, place the crushed and sieved solids from step 10 into a mixer / grinder. Add the desired amount of flavoring and mix at room temperature for 5-20 minutes.

[0075] 11. Extract the obtained solid mixture from the mixer / grinder and sieve it.

[0076] 12. Store the obtained granular powder in suitable packaging materials.

[0077] A2. Procedure for obtaining a composition comprising CHX diacetate and CPC 1. Load the selected, pre-sieved compressible polyol (main component) into the mixer / grinder.

[0078] 2. Load the selected, pre-sieved calcium ion complexing agent into a mixer / grinder. Mix it at room temperature for 5–20 minutes.

[0079] 3. Load the selected, pre-sieved solid emulsifier into a mixer / grinder. Mix it at room temperature for 5–20 minutes.

[0080] 4. Optionally, load the desired amount of flavoring into a mixer / grinder and mix at room temperature for 5–20 minutes.

[0081] 5. Optionally, load the selected, pre-sieved sweetener compatible with CHX and CPC into a mixer / grinder. Mix at room temperature for 5–20 minutes.

[0082] 6. Load the pre-sieved active ingredient CPC (cetylpyridinium chloride) into a mixer / grinder. Mix it at room temperature for 5-45 minutes.

[0083] 7. Load the pre-sieved active ingredient CHX (chlorhexidine diacetate) into a mixer / grinder. Mix at room temperature for 5-45 minutes.

[0084] 8. Optionally, load one or more pre-sieved additional components into a mixer / grinder. Mix at room temperature for 5–45 minutes.

[0085] 9. Extract the obtained solid mixture from the mixer / grinder and sieve it.

[0086] 10. Return the sieved solids from step 9 to the mixer / grinder. Adjust the internal temperature of the machine to between 50 and 70°C and mix for 5-45 minutes.

[0087] 11. Adjust the machine temperature to 25°C. When this temperature is reached, mix for 5 to 30 minutes.

[0088] 12. Extract the obtained solid mixture from the mixer / grinder and sieve it.

[0089] 13. Store the obtained granular powder in suitable packaging materials.

[0090] A3: Procedure for obtaining a composition comprising a mixture of CHX diacetate and CHX disaccharide, and CPC. 1. Load the selected, pre-sieved compressible polyol (main component) into the mixer / grinder.

[0091] 2. Load the selected, pre-sieved calcium ion complexing agent into a mixer / grinder. Mix it at room temperature for 5–20 minutes.

[0092] 3. Load the selected, pre-sieved solid emulsifier into a mixer / grinder. Mix it at room temperature for 5–20 minutes.

[0093] 4. Optionally, load the selected, pre-sieved sweetener compatible with CHX and CPC into a mixer / grinder. Mix at room temperature for 5–20 minutes.

[0094] 5. Load the pre-sieved active ingredient CPC (cetylpyridinium chloride) into a mixer / grinder. Mix it at room temperature for 5-20 minutes.

[0095] 6. Load the pre-sieved active ingredient CHX (chlorhexidine diacetate) into a mixer / grinder. Mix it at room temperature for 5-45 minutes.

[0096] 7. Optionally, load one or more pre-sieved additional components into a mixer / grinder. Mix at room temperature for 5–45 minutes.

[0097] 8. Extract the obtained solid mixture from the mixer / grinder and sieve it.

[0098] 9. Introduce the sieved solids into the kneading system and fill the four separate portions with the desired volume of CHX disglucopyrate solution, mixing for 5-15 minutes after each addition.

[0099] 10. The wet solid was dried under vacuum at 40°C for 3 to 16 hours until all water added to the CHX disaccharide solution was completely removed.

[0100] 11. Crush the obtained dry solids and sieve them.

[0101] 12. Place the pulverized and sieved solids from step 11 into a mixer / grinder. Optionally add the desired amount of flavoring and mix at room temperature for 5–20 minutes.

[0102] 13. Extract the obtained solid mixture from the mixer / grinder and sieve it.

[0103] 14. Store the obtained granular powder in suitable packaging materials.

[0104] B. Analysis of the products obtained from items A1 to A3 Physical parameter analysis 1. Visual inspection of the uniformity of solids / particles. Acceptable: The solids must be uniform.

[0105] 2. Product solubility in different types of water (1.5 g solid dissolved in 15 g water). Specifically, the product solubility was tested in tap water, bottled / treated non-carbonated mineral water, and analytical grade deionized water. Acceptable: A clear or slightly turbid solution must be obtained in all types of water used, without suspended solids and / or residual precipitates.

[0106] 3. Density of the solid (g / ml): This parameter is measured by accurately weighing 50 ml of the solid into volumetric flasks of equal volume. Density is indicated by the following ratio: d(g / ml) = Solid weight (g) / 50 (volume of volumetric flask, in ml). Acceptable: The obtained value is between 0.500 and 0.800 g / ml.

[0107] 4. Determine the pH of the solution obtained by dissolving 1.5 g of solid in 15 g of analytical grade deionized water. Measure using an electronic pH meter with the appropriate calibration electrode. Acceptable: The obtained value is between 5.5 and 7.

[0108] Analysis of antimicrobial agents (CHX and CPC) CHX and CPC should be analyzed using a high-resolution and sensitive automated chromatographic system, particularly HPLC (High Performance Liquid Chromatography) and / or UPLC (Ultra-High Performance Liquid Chromatography) systems. Titration of these active ingredients should be performed on a solution obtained by dissolving 1.5 g of the solid in 15 g of deionized water (HPLC / UPLC mass). Results obtained should be extrapolated to the solid.

[0109] 1. Chlorhexidine digluconate (CHX-dg): a. In solution: ±10% of the expected theoretical value (0.0200-0.200% w / w) b. In solids: ±15% of the expected theoretical value (0.2200-2.200% w / w) 2. Chlorhexidine diacetate (CHX-da): a. In solution: ±10% of the expected theoretical value (0.0140-0.140% w / w) b. In solids: ±15% of the expected theoretical value (0.1540-1.540% w / w) 3. cetylpyridinium chloride a. In solution: ±10% of the expected theoretical value (0.0125-0.100% w / w) b. In solids: ±15% of the expected theoretical value (0.1375-1.100% w / w) Analysis of major impurities from CHX It is well known in the art that the active ingredient can form p-chloroaniline (PCA) via CHX (CHX-da or CHX-dg) when subjected to heat stress (temperature > 40°C) or unsuitable pH (< 5.0). The toxicity of this impurity is also well known. Therefore, a maximum allowable concentration of 3 ppm is permitted in mouthwashes containing CHX.

[0110] The impurity was measured using a high-resolution and sensitive automated chromatographic system, particularly HPLC and / or UPLC. The titration of these active ingredients should be performed on a solution obtained by dissolving 1.5 g of the solid in 15 g of deionized water (HPLC / UPLC mass).

[0111] As stated above, the maximum amount of PCA present in a solution obtained by dissolving 1.5 g of solid in 15 g of deionized water (HPLC / UPLC mass) should be 3.0 ppm.

[0112] Stability Study To verify that physical parameters, antimicrobial agent concentration, and PCA impurity levels remained within defined limits, stability studies were conducted at 40°C (75% RH) and then extrapolated to 25°C.

[0113] The expected analytical procedures and limits are those already described for the analysis of the above products. Conditions of 40°C and 75% RH were obtained using a calibrated climate chamber with continuous temperature and humidity control. To calculate the stability time at 40°C equivalent to 3 years at 25°C, the value of the kinetic parameter AAF (accelerated aging factor) was used. For a stability temperature of 40°C and an extrapolated temperature T of 25°C, the AAF value is 2.828. Therefore, the time at 40°C equivalent to 3 years (365 × 3 days) at 25°C is: (365 × 3) / 2.828 = 387 days, equivalent to 12.9 months.

[0114] In practice, 15 grams of the product to be analyzed are placed in each of 13 100 ml borosilicate glass vials, each fitted with an airtight cap made of inert material and placed upright. The analysis cycle for each vial is once a month, as defined in the appropriate calendar.

[0115] Assuming zero-order kinetics, the results were plotted linearly over time (days) with the antimicrobial agent recovery percentage and PCA ppm. Based on the obtained data, a linear equation was derived, from which the time (years) for 90% antimicrobial agent recovery at 40°C was calculated. To extrapolate this time to 25°C, this time was multiplied by the AAF value, which in this case is 2.828.

[0116] In the case of PCA impurities, the time required for a maximum of 3 ppm to form in a solution obtained by dissolving 1.5 g of solid product in 15 g of water at 25°C was calculated using a similar procedure.

[0117] This allows us to extrapolate the shelf life of solid products contained in the CHX-CPC combination at 25°C.

[0118] Measurement of antimicrobial activity Overgrowth of periodontal pathogens in the gingival sulcus is a contributing factor to periodontal disease. Following the accumulation and active metabolism of pathogenic biofilms, clinical signs of inflammation, gingival bleeding, periodontal pockets, and bone degradation confirm the development of periodontitis. Therefore, controlling bacterial loads in different oral niches appears to be key to preventing the establishment of such biofilms in the subgingival space. Daily mouthwashes should be formulated with antimicrobial molecules capable of controlling the bacterial load of oral pathogens. To achieve this, chlorhexidine (CHX) and cetylpyridinium chloride (CPC) are primarily used in Europe and the United States.

[0119] The in vitro effectiveness of these mouthwashes is typically assessed using cultures of planktonic bacteria; however, microbial growth in the oral environment primarily occurs in the form of biofilms. Therefore, the evaluation of the actual effectiveness of the product must be conducted using a research model that simulates the lifestyle of the microorganisms present in the oral environment. For this purpose, an oral biofilm model composed of symbiotic bacteria and periodontal pathogens was used, which simulates the growth conditions of pathogenic subgingival biofilms.

[0120] Furthermore, the anti-biofilm ability of the compositions of the present invention is compared with that of commercial liquid formulations containing CHX and CPC. gold A comparison of the effects of standard mouthwashes.

[0121] Biofilms used to evaluate the antimicrobial activity of solid compositions containing CHX and CPC as described herein Formation and growth Stage 1: Biofilm formation and growth.

[0122] Oral flora: Oral streptococci ( Streptoccus oralis (ATCC35037), Actinomyces nipponense ( Actinomyces naeslundii (ATCC19039), Veillonella microphylla ( Veillonella parvula (ATCC10790), Fusobacterium nucleatum ( Fusobacterium nucleatum (ATCC10953), Porphyromonas gingivalis ( Porphyromonas gingivalis (ATCC33277) and Aggregates actinomycetes ( Aggregatibacter actinomycetemcomitansSingle-species liquid cultures of (ATCC 33384) were grown at 36.5°C in BHI (brain and heart infusion) liquid medium (referred to as BHI-II) supplemented with heme chloride, menadione, and glutamate. Each species should be used when its growth is at the end of its exponential phase. Subsequently, a mixture of cultures of six species was prepared, with the following final concentrations for each species: *Streptococcus oralis* 10E3 cfu / mL, *Actinomyces negrius* and *Veillonella spp.* 10E4 cfu / mL, *Fusobacterium nucleatum* 10E5 cfu / mL, *Actinomyces acicularis* and *Porphyromonas gingivalis* 10E6 cfu / mL. 1 mL of the mixture was inoculated into the wells of a microtiter plate containing a sterile hydroxyapatite disc simulating a tooth surface. The inoculum was incubated anaerobicly at 36.5°C for 96 hours. After 48 hours, the medium was replaced; 700 μL was removed and 700 μL of BHI-II medium was added.

[0123] Phase 2: Treat the obtained biofilm with the composition of the present invention to evaluate its antibacterial activity.

[0124] After the incubation period, the biofilms grown on the hydroxyapatite discs were treated with a freshly prepared solution obtained by dissolving 1.5 g of the solid composition to be analyzed in 15 g of water. To remove unattached cells, the biofilms were rinsed by immersion in sterile phosphate-buffered saline, followed by rinsing with the dissolved composition in mouthwash for 2 minutes. Excess composition was then removed by immersing the biofilms again in PBS. The treated biofilms were depolymerized by shaking for 5 minutes. The resulting bacterial suspension was serially diluted 1 / 10 in PBS, and 0.1 mL of this suspension was inoculated onto blood agar plates supplemented with heme chloride-menaquinone. These were incubated anaerobically for 5 days. For the counting of *Actinomyces actinomycetes* species, 0.1 mL of the serially diluted solution was plated on a solid medium containing a bacitracin selective for that species and incubated under microaerophilic conditions. Each formulation to be evaluated was tested on 25 biofilms grown on hydroxyapatite discs. The counts of the six species are expressed as log 10 CFU / mL. The results were statistically analyzed using the Jamovi software application and the Mann-Whitney U test was used for significance comparison. The significance level was set at 0.05.

[0125] Examples of the Compositions, Compositions of the Invention and Comparative Examples Comparative Example 01: Internal Reference Number: S / EML-03-00-A / 01 (Products containing CHX-dichlorohydrochloride + CPC) Composition: 1. Add xylitol to a sufficient amount (100% xylitol). 2. Sodium gluconate 11.0g 3. Polosham 407 1.98 4. Seasoning 1.10% 5. Sodium saccharin 0.11% 6. Theoretical value of chlorhexidine dihydrochloride 0.85% in reconstituted solution: 0.077%.

[0126] 7. Theoretical value of CPC 0.55% in recombinant solution: 0.050%.

[0127] Analysis results Appearance: Uniform white powder (qualified) pH: (Not measured due to the presence of undissolved solids) Solid density (g / ml): 0.650 (qualified) Solubility (*): Undissolved crystalline solids are present (unacceptable) CHX-dichlorohydrochloride (in reconstituted solution): (not measured) The composition has a solubility problem due to the use of chlorhexidine hydrochloride, which has low solubility in aqueous media.

[0128] Example 02: Internal Reference Number: S / EML-07-00-A / 01 (for products with CHX-dg + CPC) Composition: 1. Add xylitol to a final volume of 100ml. 2. Sodium gluconate 11.0% 3. Polosham 4071.98% 4. Seasoning 1.10% 5. Theoretical value of chlorhexidine digluconate 1.32% in reconstituted solution: 0.120% 6. Theoretical value of CPC 0.55% in recombinant solution: 0.050% Analysis results Appearance: Uniform white powder (qualified) pH: 6.61 (*) (Pass) Solid density (g / ml): 0.686 (qualified) Solubility: A clear solution in any type of water (qualified) CHX-dg (in recombinant solution): 0.117% (Recovery%: 97.5%) (Acceptable) CHX-dg (in solids): 1.266% (Recovery%: 95.9%) (Acceptable) CPC (in reconstituted solution): 0.047% (Recovery%: 94.0%) (Acceptable) CPC (in solids): 0.511% (Recovery%: 92.9%) (Qualified) Comparative Example 03: Internal Reference Number: S / EML-10-00-A / 01 (Only for products with CHX-dg) Composition: 1. Add xylitol to a final volume of 100ml. 2. Sodium gluconate 11.0% 3. Polosham 4071.98% 4. Seasoning 1.10% 5. Theoretical value of chlorhexidine digluconate 1.32% in reconstituted solution: 0.120% Analysis results Appearance: Uniform white powder (qualified) pH: 6.61 (*) (Pass) Solid density (g / ml): 0.680 (qualified) Solubility: (*) A clear solution in any type of water (qualified) CHX-dg (in recombinant solution): 0.117% (Recovery%: 97.5%) (Acceptable) CHX-dg (in solids): 1.179% (Recovery%: 90.0%) (Acceptable) Comparative Example 04: Internal Reference Number: S / EML-11-00-A / 01 (Only for products with CHX-da) Composition: 1. Add xylitol to a final volume of 100%. 2. Sodium gluconate 11.0% 3. Polosham 4071.98% 4. Seasoning 1.10% 5. The theoretical value of chlorhexidine diacetate 0.92% in the reconstituted solution is 0.084%. Analysis results Appearance: Uniform white powder (qualified) pH: 6.64 (*) (Pass) Solid density (g / ml): 0.710 (qualified) Solubility: (*) A clear solution in any type of water (qualified) CHX-da (in recombinant solution): 0.075% (Recovery%: 90.0%) (Acceptable) CHX-da (in solids): 0.831% (Recovery%: 90.3%) (Compliant) Comparative Example 05: Internal Reference Number: S / EML-12-00-A / 01 (Products without CHX and CPC) Its manufacturing and use are the same.

[0129] Composition: 1. Add xylitol to a final volume of 100%. 2. Sodium gluconate 11.0% 3. Polosham 4071.98% 4. Seasoning 1.10% Analysis results Appearance: Uniform white powder (qualified) pH: 6.69 (*) (Pass) Solid density (g / ml): 0.720 (qualified) Solubility: (*) A clear solution in any type of water (qualified) CPC (in reconstituted solution): 0.047% (Recovery%: 94.0%) (Acceptable) CPC (in solids): 0.511% (Recovery%: 92.9%) (Qualified) Example 06: Internal Reference Number: S / EML-08-00-A / 01 (for products with CHX-da + CPC) Composition: 1. Add xylitol to a final volume of 100%. 2. Sodium gluconate 11.0% 3. Polosham 4071.98% 4. Seasoning 1.10% 5. The theoretical value of chlorhexidine diacetate 0.92% in the reconstituted solution: 0.084% 6. Theoretical value of CPC 0.55% in recombinant solution: 0.050% Analysis results Appearance: Uniform white powder (qualified) pH: 6.71 (*) (Pass) Solid density (g / ml): 0.720 (qualified) Solubility (*): Clear solution in any type of water (qualified) CHX-da (in recombinant solution): 0.088% (Recovery%: 105.4%) (Acceptable) CHX-da (in solids): 0.863% (Recovery%: 106.6%) (Acceptable) CPC (in reconstituted solution): 0.052% (Recovery%: 104.0%) (Acceptable) CPC (in solids): 0.560% (Recovery%: 101.8%) (Qualified) Example 07: Internal Reference Number: S / EML-13-00-A / 01 (Product containing CHX-da + CPC + L-leucine) Composition: 1. Add xylitol to a final volume of 100%. 2. Sodium gluconate 11.0% 3. L-Leucine 5.00% (as fluidizer) 4. Polosham 4071.98% 5. Seasoning 1.10% 6. The theoretical value of chlorhexidine diacetate 0.92% in reconstituted solution: 0.084% 7. Theoretical value of CPC 0.55% in recombinant solution: 0.050% Analysis results Appearance: Uniform white powder (qualified) pH: 6.71 (*) (Pass) Solid density (g / ml): 0.730 (qualified) Solubility (*): Clear solution in any type of water (qualified) CHX-da (in recombinant solution): 0.086% (Recovery%: 102.4%) (Acceptable) CHX-da (in solids): 1.006% (Recovery%: 109.3%) (Compliant) CPC (in reconstituted solution): 0.052% (Recovery%: 104.0%) (Acceptable) CPC (in solids): 0.611% (Recovery%: 111.1%) (Qualified) Example 08: Internal Reference Number: S / EML-15-00-A / 01 (Product containing CHX-dg + CPC + L-leucine) Composition: 1. Add xylitol to a final volume of 100%. 2. Sodium gluconate 11.0% 3. L-Leucine 5.00% (as fluidizer) 4. Polosham 4071.98% 5. Seasoning 1.10% 6. Theoretical value of chlorhexidine digluconate 1.32% in reconstituted solution: 0.120% 7. Theoretical value of CPC 0.55% in recombinant solution: 0.050% Analysis results Appearance: Uniform white powder (qualified) pH: 6.61 (*) (Pass) Solid density (g / ml): 0.690 (qualified) Solubility (*): Clear solution in any type of water (qualified) CHX-dg (in recombinant solution): 0.117% (Recovery%: 97.5%) (Acceptable) CHX-dg (in solids): 1.402% (Recovery%: 106.2%) (Acceptable) CPC (in reconstituted solution): 0.053% (Recovery%: 96.4%) (Acceptable) CPC (in solids): 0.628% (Recovery%: 114.2%) (Qualified) Comparative Example 09: Internal Reference Number: S / EML-09-00-A / 01 (Products with CPC but without CHX) Its manufacturing and use of the CHX-da composition are the same: 1. Add xylitol to a final volume of 100%. 2. Sodium gluconate 11.0% 3. Polosham 4071.98% 4. Seasoning 1.10% 5. Theoretical value of CPC 0.55% in reconstituted solution: 0.050% Analysis results Appearance: Uniform white powder (qualified) pH: 6.63 (*) (Pass) Solid density (g / ml): 0.670 (qualified) Solubility: A clear solution in any type of water (qualified) CPC (in reconstituted solution): 0.051% (Recovery %: 102) (Acceptable) CPC (in solids): 0.504% (Recovery%: 91.6%) (Qualified) Example 10: Internal Reference Number: S / EML-17-00-A / 01 (Product with CHX-dg + CHX da + CPC) Composition: 1. Add xylitol to a final volume of 100%. 2. Sodium gluconate 11.0% 3. Poloxamer 407 1.98% 4. Seasoning 1.10% 5. Chlorhexidine digluconate 0.66% has a theoretical value of 0.060% in reconstituted solution. 6. The theoretical value of chlorhexidine diacetate 0.46% in the reconstituted solution: 0.042% 7. Theoretical value of CPC 0.55% in reconstituted solution: 0.050% Analysis results Appearance: Uniform white powder (qualified) pH: 6.61 (*) (Pass) Solid density (g / ml): 0.686 (qualified) Solubility: A clear solution in any type of water (qualified) Total CHX (as CHX disaccharide) in recombinant solution: 0.121% (recovery%: 100.8%) (acceptable) Total CHX (as CHX disgluconate) in solids: 1.240% (Recovery%: 93.9%) (Acceptable) CPC (in reconstituted solution): 0.049% (Recovery%: 98.0%) (Acceptable) CPC (in solids): 0.536% (Recovery%: 97.4%) (Qualified) Note: (*): Parameters measured by dissolving 1.5 g of solid product in 15.0 g of analytical grade deionized water or a solution obtained by multiples thereof.

[0130] C. Analysis of the antimicrobial efficacy of the compositions in the examples The table below shows the bacterial counts of the different formulations evaluated and the multi-species oral biofilms grown under in vitro conditions, in log 10 cfu / mL.

[0131] Table 1.

[0132] Figure 1 plots the results presented in Table 1. This is in addition to showing the results obtained with various solid compositions containing CHX and CPC, as well as... goldIn addition to the total bacterial count (log10 cfu / mL) of the bacteria grown after treatment of the biofilm with the standard liquid formulation, the survival rate was also shown.

[0133] Statistical analysis showed that all compositions were significantly more effective than the negative control.

[0134] The commercial liquid formulation was significantly more effective than the formulations of Examples 3, 4, and 5. Furthermore, it showed no significant difference from the formulations of Examples 2 and 6.

[0135] The composition of Example 2 was significantly more effective than the compositions of Examples 3, 4, and 5. Furthermore, it was not significantly different from the composition of Example 6.

[0136] The composition of Example 6 was significantly more effective than the compositions of Examples 3, 4, and 5. Furthermore, it did not differ significantly from the formulation of Example 2.

[0137] There were no statistically significant differences between the formulations of Examples 2 and 6. There were also no statistically significant differences between these formulations and commercial liquid formulations. All three formulations were statistically equivalent in their antimicrobial efficacy against multi-species oral biofilms grown and treated under in vitro conditions.

[0138] The composition of Example 3 is significantly more effective than the formulation of Example 5.

[0139] There was no significant difference in the antimicrobial effectiveness between the compositions of Examples 3 and 4.

[0140] Summary of antibacterial activities of different compositions A. Examples with combined CPC + CHX dg S / EML-07-00-A / 01 (Example 2): Significantly more effective than S / EML-10-00-A / 01 (Example 3 - Blank without CPC and with CHX dg). S / EML-07-00-A / 01 (Example 2): Significantly more effective than S / EML-11-00-A / 01 (Example 4 - Blank without CPC and with CHX da). S / EML-07-00-A / 01 (Example 2): Significantly more effective than S / EML-12-00-A / 01 (Example 5 - Complete blank without CPC and without CHX). S / EML-07-00-A / 01 (Example 2): No significant difference from S / EML-08-00-A / 01 (Example 6-CPC + CHX da). The activity of S / EML-07-00-A / 01 (Example 2-CPC + CHX dg) = S / EML-08-00-A / 01 = liquid commercial formulation.

[0141] B. An embodiment with combined CPC + CHX da S / EML-08-00-A / 01 (Example 6): Significantly more effective than S / EML-10-00-A / 01 (Example 3 - blank without CPC and with CHX dg). S / EML-08-00-A / 01 (Example 6): Significantly more effective than S / EML-11-00-A / 01 (Example 4 - Blank without CPC and with CHX da). S / EML-08-00-A / 01 (Example 6): Significantly more effective than S / EML-12-00-A / 01 (Example 5 - Complete blank without CPC and without CHX). S / EML-07-00-A / 01 (Example 6): No significant difference from S / EML-07-00-A / 01 (Example 2-CPC + CHX da). The activity of S / EML-08-00-A / 01 (Example 6 - CPC + CHX dg) = S / EML-07-00-A / 01 (Example 2 - CPC + CHX dg) = Commercial liquid formulation.

Claims

1. A solid composition in powder or granule form, comprising: a) Selected from the following chlorhexidine salts: chlorhexidine digluconate and chlorhexidine diacetate, or mixtures thereof. and b) Cetylpyridinium chloride Used for the prevention and / or treatment of oral infectious lesions. Wherein, the chlorhexidine digluconate, when present as the sole chlorhexidine salt, has a concentration of 0.220-2.200% w / w; or wherein, the chlorhexidine diacetate, when present as the sole chlorhexidine salt, has a concentration of 0.154-1.540% w / w; or wherein, when a mixture of chlorhexidine diacetate and chlorhexidine digluconate is present, the total amount of chlorhexidine, expressed as chlorhexidine digluconate, has a concentration of 0.220-2.200% w / w.

2. The solid composition for use according to claim 1, wherein, Cetylpyridinium chloride exists at concentrations of 0.133–1.100% w / w.

3. The solid composition for use according to any one of claims 1 to 2, wherein, The prevention and / or treatment of oral infectious lesions is carried out by directly applying the solid composition to the oral cavity.

4. An oral rinse comprising a solid composition in powder or granule form, said solid composition comprising: a) Selected from the following chlorhexidine salts: chlorhexidine digluconate and chlorhexidine diacetate, or mixtures thereof. and b) Cetylpyridinium chloride The solid composition is dissolved in water for immediate use, and Wherein, the chlorhexidine digluconate, when present as the sole chlorhexidine salt, has a concentration of 0.220-2.200% w / w; or wherein, the chlorhexidine diacetate, when present as the sole chlorhexidine salt, has a concentration of 0.154-1.540% w / w; or wherein, when a mixture of chlorhexidine diacetate and chlorhexidine digluconate is present, the total amount of chlorhexidine, expressed as chlorhexidine digluconate, has a concentration of 0.220-2.200% w / w. Used for the prevention and / or treatment of oral infectious lesions.

5. A mouthwash comprising a solid composition in powder or granule form, said solid composition comprising: a) Selected from the following chlorhexidine salts: chlorhexidine digluconate and chlorhexidine diacetate, or mixtures thereof. and b) Cetylpyridinium chloride The solid composition is dissolved in water for immediate use, and Wherein, the chlorhexidine digluconate, when present as the sole chlorhexidine salt, has a concentration of 0.220-2.200% w / w; or wherein, the chlorhexidine diacetate, when present as the sole chlorhexidine salt, has a concentration of 0.154-1.540% w / w; or wherein, when a mixture of chlorhexidine diacetate and chlorhexidine digluconate is present, the total amount of chlorhexidine, expressed as chlorhexidine digluconate, has a concentration of 0.220-2.200% w / w. Used for the prevention and / or treatment of oral infectious lesions.

6. The oral rinsing agent for the purpose according to claim 4 or the mouthwash for the purpose according to claim 5, wherein, The cetylpyridinium chloride is present in the solid composition at a concentration of 0.133-1.100% w / w.

7. The solid composition for use according to any one of claims 1 to 3, or the oral rinse for use according to any one of claims 4 or 6, or the mouthwash for use according to any one of claims 5 or 6, wherein, The oral infectious lesions were selected from: - Caries in primary and / or permanent teeth; - Postoperative infection in the oral cavity; - Gingivitis - Periodontitis; - Oral mucositis; - Peri-implant mucositis; - Peri-implantitis; - Mouth ulcers; - Fungi; - Sexually transmitted infections in the oral cavity; - Oral infectious lesions that can induce aspiration pneumonia in intubated and / or intensive care unit patients; - Oral infectious lesions that can induce aspiration pneumonia in patients with gastroesophageal reflux disease; - Infected oral ulcers; and - Herpetic gingivostomatitis.

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