Oral care composition

Abstract

The present invention relates to oral care products such as mouthwash, periodontal gel, or toothpaste containing chlorhexidine and sodium DNA. These oral care products exhibit healing and anti-inflammatory activities in addition to antibacterial effects against gingivitis, bacterial plaque, and periodontitis, and by neutralizing oxidative stress, they can limit the occurrence and spread of irritation to the oral mucosa and promote affinity for the mucosa.

Description

Technology Field

[0001] The present invention relates to an oral care composition based on chlorhexidine and sodium DNA, e.g., an oral rinse, a dental gel, or a toothpaste, which prevents plaque formation on teeth and promotes trophism (or affinity: trophism) of the mucous membrane by limiting the occurrence and spread of irritation to the oral mucous membrane. Background Technology

[0002] In chlorhexidine-based oral care compositions, such as mouthwashes, the active ingredient is known as a potent antimicrobial substance due to its ability to penetrate the outer membrane of bacteria and aggregate internal proteins. Chlorhexidine also exhibits potent anti-plaque activity. Furthermore, solutions containing chlorhexidine are used at various concentrations to prevent postoperative complications.

[0003] However, prolonged use of chlorhexidine-based oral care compositions may cause irritation to the oral mucosa, for example, and prolonged use may reduce affinity.

[0004] In fact, the applicant confirmed that although the beneficial effects of chlorhexidine in the treatment of gingivitis, bacterial plaque, and periodontitis are known, the use of it is withheld during treatment, particularly long-term treatment, due to concerns about the side effects caused by the active ingredient on the oral mucosa. The problem to be solved

[0005] Accordingly, the objective of the present invention is to provide a novel oral care composition comprising chlorhexidine that is effective against gingivitis, bacterial plaque, and gingivitis and has healing and anti-inflammatory activity, which also neutralizes oxidative stress, thereby limiting the deformation of the cellular structure of the oral mucosa caused by the use of chlorhexidine and the occurrence and spread of irritation thereto, and thus can promote the affinity of the oral mucosa itself.

[0006] According to the present invention, the applicant discovered the surprising fact that these desirable properties can be achieved by using chlorhexidine in combination with sodium DNA.

[0007] Therefore, the present invention relates to an oral care composition comprising chlorhexidine and sodium DNA. means of solving the problem

[0008] Unexpectedly, the combination of sodium DNA and chlorhexidine not only provides a protective effect against chlorhexidine and a healing effect on wounds that may occur in the oral cavity in response to the latter’s irritating effect on the oral mucosa, but can also limit side effects that may occur when using chlorhexidine-based oral care compositions for a long period of time, specifically, side effects such as vacuolization, nuclear degeneration, and changes in cell structure including the expansion of intercellular spaces.

[0009] Due to the specific combination of sodium DNA and chlorhexidine, the oral care composition of the present invention has a series of features, such as overcoming the application and functional limitations of oral care compositions based on chlorhexidine alone, expanding the possibilities of use, and treating some side effects caused by long-term use.

[0010] The oral care composition according to the present invention actually enables effective protection at the cellular level against the side effects of chlorhexidine, thereby limiting the occurrence and progression of cellular structural deformation of the oral mucosa. In addition, it achieves a combination of antibacterial effects against gingivitis, bacterial plaque, and periodontitis, as well as healing and anti-inflammatory activities capable of neutralizing oxidative stress, and can also improve mucosal affinity by limiting the occurrence and progression of irritation of the oral mucosa. Due to these features, advantageous effects can be achieved without causing cellular-level irritation or side effects of chlorhexidine on the oral mucosa even with long-term use.

[0011] The applicant noted that one of the application and functional limitations, particularly regarding the use of chlorhexidine-based oral care compositions, is the occurrence of side effects—specifically, with long-term use—which cause structural deformation of mucosal cells, including vacuolation, nuclear degeneration, and expansion of intercellular spaces, in addition to irritation of the oral mucosa.

[0012] Therefore, the applicant has confirmed the unexpected fact that the combination of sodium DNA and chlorhexidine not only provides a protective effect against chlorhexidine and a healing effect for wounds that may occur in the oral cavity against the irritating effect on the oral mucosa, but can also limit side effects that may occur when the active ingredient is used for a long period of time, specifically, changes in cell structure including vacuolation, degeneration of the cell nucleus, and expansion of the intercellular space.

[0013] Based on this, the applicant has defined and developed a novel oral care composition containing chlorhexidine, which is effective against gingivitis, bacterial plaque, and periodontitis, and which can block or significantly limit the occurrence of side effects resulting from the long-term use of the active ingredient, including changes in the cellular structure of the oral mucosa such as mucosal irritation and vacuolation, nuclear degeneration, and expansion of intercellular spaces.

[0014] In a preferred embodiment thereof, the oral care composition is selected from the group consisting of mouthwash, dental gel, and toothpaste.

[0015] In a preferred embodiment thereof, the oral care composition according to the present invention is an oral cleanser, specifically comprising chlorhexidine in a weight percentage (weight%) of 0.01 to 0.30 with respect to the total volume of the oral cleanser, at least one metabisulfite salt of an alkali metal or alkaline earth metal in a weight percentage of 0.01 to 0.2 to 0.1 to 0.5 to 0.1%, ascorbic acid in a weight percentage of 0.1 to 1.0%, and at least one polyvinylpyrrolidone-vinyl acetate copolymer in a weight percentage of 0.05 to 1%.

[0016] In another aspect, the present invention relates to sodium DNA for use in a method for treating a disease of the oral mucosa, wherein the disease involves a deformation of the cellular structure of the oral mucosa, and such deformation of the cellular structure is selected from the group consisting of vacuolation, nuclear degeneration, and expansion of the intercellular space.

[0017] In fact, it was discovered that sodium DNA has a protective effect on the cellular structure of the oral mucosa and can counteract the occurrence and development of cellular structural changes, including vacuolation, nuclear degeneration, and expansion of the intercellular space.

[0018] Accordingly, by limiting the side effects of treatment using an active ingredient aggressive to the cellular structure of the oral mucosa, such as chlorhexidine, therapeutic intervention can be made in relation to cellular deformation of the oral mucosa in terms of causality.

[0019] The applicant has confirmed that treating the side effects of chlorhexidine constitutes an innovative aspect of particular value, considering the aforementioned application and functional limitations regarding the use of chlorhexidine in oral care compositions.

[0020] In another aspect, the present invention therefore relates to sodium DNA used in a method for treating side effects of chlorhexidine in patients receiving chlorhexidine treatment, which involve changes in the cell structure of the patient's oral mucosa, wherein said changes in cell structure are selected from the group consisting of vacuolation, nuclear degeneration and expansion of intercellular space. Brief explanation of the drawing

[0021] Figure 1 is a schematic cross-sectional view of a part of the device used in the experiment according to Example 1. Figure 2 shows the results of an MTT viability test on ROE cells at different treatment times using solutions (A, B, C, and D) according to Example 1. Figure 3 shows the results of an MTT viability test on ROE cells at different treatment times using solutions (A, B, C, and D) according to Example 1, after treatment with a 3 volume% H2O2 solution for 1 minute. Figure 4 shows the 3D reconstruction of the ROE samples at CLSM observation and maximum intensity projection after each of the solutions (A, B, C, and D) according to Example 1 were treated for 30 minutes. Figure 5 shows the CLSM observation and 3D reconstruction of the ROE sample at maximum intensity projection after treatment with a 3 volume% H2O2 solution for 1 minute, followed by treatment with the solutions according to Example 1 (A, B, C, and D) for 30 minutes each. Figure 6 shows each region of the ROE sample after treatment for 30 minutes each using the solution (A, B, C, and D) according to Example 1. Figure 7 shows the regions of the ROE sample after treatment with a 3 volume% H2O2 solution for 1 minute, followed by treatment with the solution according to Example 1 (A, B, C, and D) for 30 minutes each. Specific details for implementing the invention

[0022] The present invention may be illustrated in one or more aspects regarding the following preferred features, which may be combined with one another if desired depending on the application requirements.

[0023] Within the scope of the contents of this specification and the claims below, all numerical sizes, variables, percentages, etc., representing quantities are deemed to be expressed by the term "approximately" in all situations unless otherwise noted. Additionally, ranges of all numerical sizes include all possible combinations of maximum and minimum values ​​and all possible combinations of intermediate ranges, as well as the following ranges.

[0024] Within the scope of the present invention, a combination of two substances has been identified as chlorhexidine and sodium DNA, and due to their combined antibacterial, healing, anti-inflammatory, and oxidative stress neutralizing properties, they can be used as active ingredients in an oral care composition that is particularly effective against gingivitis, bacterial plaque, and periodontitis, and at the same time, can promote the affinity of the oral mucosa itself by limiting the occurrence and development of cellular structural deformation of the oral mucosa caused by the use of chlorhexidine.

[0025] More specifically, the present invention relates to an oral care composition comprising chlorhexidine and sodium DNA.

[0026] The following expressions are used in the present invention:

[0027] - "Weight % relative to the total volume of the mouthwash" is the amount of the corresponding ingredient in grams present in 100 milliliters (mL) of the mouthwash;

[0028] - "Chlorhexidine" means compound 1,1'-hexamethylenebis[5-(p-chlorophenyl)biguanide] and its salts or complexes, unless otherwise specified;

[0029] - "Sodium DNA" means the sodium salt of deoxyribonucleic acid that can be obtained, for example, by extracting natural deoxyribonucleic acid from the tissue of a male sturgeon's gonad and subsequently purifying, depolymerizing, and neutralizing with sodium ions.

[0030] Even without being based on a specific theory, it is believed that the combination of sodium DNA and chlorhexidine can not only provide a protective effect against the latter’s irritating effect on the oral mucosa and a healing effect for wounds that may occur in the oral cavity, but also limit side effects resulting from the long-term use of chlorhexidine-based oral care compositions, including changes in cell structure such as vacuolation, nuclear degeneration, and expansion of intercellular space.

[0031] The applicant has noted, in particular, that one of the application and functional limitations of using chlorhexidine-based oral care compositions—in the case of long-term use—is that, in addition to oral mucosal irritation, it entails changes at the cellular structural level of the mucosa, including vacuolation, nuclear degeneration, and expansion of intercellular spaces.

[0032] The applicant has therefore discovered the unexpected fact that the combination of sodium DNA and chlorhexidine can not only provide a protective effect against its irritating effect on the oral mucosa and a healing effect for wounds that may occur in the oral cavity, but also limit side effects of long-term use of the active ingredient, such as deformation of cell structure including vacuolation, nuclear degeneration, and expansion of intercellular space.

[0033] Accordingly, the applicant was able to define and develop a novel oral care composition containing chlorhexidine that is effective against gingivitis, bacterial plaque, and periodontitis, while simultaneously not causing or significantly limiting side effects resulting from long-term use of the active ingredient, such as irritation of the oral mucosa including vacuolation, nuclear degeneration, and expansion of intercellular spaces, and even deformation of cell structure.

[0034] Due to a specific combination of sodium DNA and chlorhexidine, the oral care composition according to the present invention has a series of characteristics that can overcome the application and functional limitations of oral care compositions based on chlorhexidine alone, expand the possibilities for application, and cure some of the side effects associated with long-term use.

[0035] The oral care composition according to the present invention can effectively combine an effective protective action at the cellular level with the side effects of chlorhexidine, thereby limiting the occurrence and progression of cellular structural deformation of the oral mucosa, while achieving a combination of effective antibacterial effects against gingivitis, bacterial plaque, and periodontitis, as well as healing and anti-inflammatory activities capable of neutralizing oxidative stress, and can also promote mucosal affinity by limiting the occurrence and progression of irritation of the oral mucosa. Due to these features, it can be used particularly effectively even for a long period without the irritating effects and side effects of chlorhexidine at the cellular level on the oral mucosa.

[0036] In a preferred embodiment, the oral care composition is selected from the group consisting of oral rinses, periodontal gels, and toothpaste.

[0037] In a first preferred embodiment thereof, the oral care composition according to the present invention is an oral rinse comprising chlorhexidine sodium DNA.

[0038] The mouthwash according to the present invention comprises chlorhexidine. Preferably, the amount of chlorhexidine contained in the mouthwash is in the range of 0.01 to 0.30 weight%, more preferably 0.05 to 0.30 weight%, and even more preferably 0.09 to 0.20 weight% with respect to the total volume of the mouthwash.

[0039] In the mouthwash according to the present invention, chlorhexidine may advantageously exist in the form of salts and complex salts. Preferably, the mouthwash according to the present invention comprises chlorhexidine in the form of salts and complex salts. As a chlorhexidine salt, for example, chlorhexidine digluconic acid or chlorhexidine diacetate may be used in the mouthwash according to the present invention. Preferably, the mouthwash according to the present invention comprises chlorhexidine in the form of chlorhexidine gluconic acid.

[0040] The oral rinse according to the present invention contains sodium DNA.

[0041] Preferably, the amount of sodium DNA in the mouthwash is in the range of 0.01 to 0.2 weight%, preferably 0.05 to 0.1 weight%, relative to the total volume of the mouthwash.

[0042] Sodium DNA suitable for the purpose of the present invention is a commercially available material, for example, a product marketed under the trade name Kalinat aw powder (Kalichem). The above amount of sodium DNA has been proven to be optimal for neutralizing the irritating effect of chlorhexidine on the oral mucosa, thereby providing a protective effect against irritation and a healing effect for wounds that may occur in the oral cavity, and thus promoting a suitable affinity for the oral mucosa itself.

[0043] Preferably, the oral rinse according to the present invention comprises at least one metabisulfite salt of an alkali metal or an alkaline earth metal.

[0044] The presence of at least one metabisulfite of the above alkali metal or alkaline earth metal prevents the defect of blackening of teeth, which is a side effect of chlorhexidine.

[0045] Preferably, at least one metabisulfite of an alkali metal or alkaline earth metal is selected from the group consisting of sodium metabisulfite, potassium metabisulfite, and calcium metabisulfite. More preferably, the mouthwash according to the present invention comprises sodium metabisulfite.

[0046] Preferably, the amount of at least one metabisulfite salt of an alkali metal or alkaline earth metal in the oral rinse according to the present invention is in the range of 0.1 to 0.5 weight%, more preferably 0.15 to 0.3 weight% with respect to the total volume of the oral rinse.

[0047] Preferably, the mouthwash according to the present invention comprises ascorbic acid.

[0048] Preferably, the amount of ascorbic acid in the oral rinse according to the present invention is in the range of 0.1 to 1.0 weight% with respect to the total volume of the oral rinse.

[0049] The presence of ascorbic acid prevents the drawback of tooth blackening, a side effect of chlorhexidine.

[0050] Preferably, the mouthwash according to the present invention comprises ascorbic acid and at least one metabisulfite salt of an alkali metal or alkaline earth metal, and more preferably comprises 0.1 to 0.5 weight% of at least one metabisulfite salt of an alkali metal or alkaline earth metal and 0.1 to 1.0 weight% of ascorbic acid based on the total volume of the mouthwash.

[0051] The combination of the aforementioned amounts of ingredients has been proven to be optimal for neutralizing the side effects of chlorhexidine, such as tooth blackening.

[0052] Preferably, the mouthwash according to the present invention comprises sodium tribasic citrate.

[0053] Preferably, the amount of sodium tribasic citrate in the oral rinse according to the present invention is in the range of 0.8 to 2.0 weight%, more preferably 0.8 to 1.2 weight%, with respect to the total volume of the oral rinse.

[0054] If sodium tribasic citrate is present in the above amount, the pH of the mouthwash can be advantageously adjusted to an optimal value for use.

[0055] In a preferred embodiment, the mouthwash according to the present invention comprises ascorbic acid and sodium tribasic citrate. More preferably, the mouthwash according to the present invention comprises 0.1 to 1 weight% of ascorbic acid and 0.8 to 2.0 weight% of sodium tribasic citrate based on the total volume of the mouthwash.

[0056] In fact, it was discovered that the combination of ascorbic acid and sodium tribasic citrate can stabilize the formulation of the oral rinse according to the present invention.

[0057] Preferably, the mouthwash according to the present invention comprises at least one polyvinylpyrrolidone-vinyl acetate copolymer. Polyvinylpyrrolidone-vinyl acetate copolymer suitable for the purposes of the present invention is a commercially available material, such as a product available on the market under the trade name Luviskol® (BASF SE).

[0058] The above-mentioned at least one polyvinylpyrrolidone-vinyl acetate copolymer advantageously provides film-forming and anti-plaque action in an oral rinse according to the present invention.

[0059] Preferably, the amount of at least one polyvinylpyrrolidone-vinyl acetate copolymer in the oral rinse according to the present invention is in the range of 0.05 to 1 weight%, more preferably 0.3 to 1 weight%, with respect to the total volume of the oral rinse.

[0060] In a preferred embodiment thereof, the oral care composition according to the present invention is an oral rinse, specifically comprising, with respect to the total volume of the oral rinse, 0.01 to 0.30 weight% of chlorhydrin, 0.01 to 0.2 weight%, preferably 0.01 to 0.1 weight% of sodium DNA, 0.1 to 0.5 weight% of at least one metabisulfite salt of an alkali metal or alkaline earth metal, 0.1 to 1.0 weight% of ascorbic acid, and 0.05 to 1 weight%, more preferably 0.3 to 1 weight% of at least one polyvinylpyrrolidone-vinyl acetate copolymer.

[0061] The oral rinse according to the present invention may contain one or more other known possible ingredients for a solution for an oral care composition.

[0062] In particular, the oral rinse according to the present invention may further include one or more additives selected from the group consisting of sweeteners, flavorings, humectants, preservatives, emulsifiers, pH adjusters, food colorings, etc.

[0063] As a sweetener, the mouthwash according to the present invention may include, for example, xylitol, sodium saccharinate, acesulfame potassium, sucralose, stevia extract, etc.

[0064] As a flavoring agent, the mouthwash according to the present invention may include, for example, peppermint, menthol, anitol, mentaviridis, cinnamon, clove, eucalyptol, etc.

[0065] As a humectant, the oral rinse according to the present invention may include, for example, propylene glycol, sorbitol, glycerin, etc.

[0066] As a preservative, the oral rinse according to the present invention may include, for example, benzoate, methylisothiazolinone, etc.

[0067] As a solubilizing surfactant, the oral rinse according to the present invention may include, for example, hydrogenated castor oil Peg40, poloxamer 407, etc.

[0068] As a pH adjuster, the oral rinse according to the present invention may include, for example, sodium citrate, citric acid, etc.

[0069] As a coloring agent, the oral rinse according to the present invention may include, for example, CI 19140, CIU 42090, CI 17200, etc.

[0070] The oral rinse according to the present invention is conveniently prepared in a known manner in the form of a solution or suspension dissolved in a suitable solvent medium, such as water.

[0071] According to a preferred embodiment, the mouthwash according to the present invention comprises the following components:

[0072] 1. Water

[0073] 2. Xylitol

[0074] 3. Propylene Glycol

[0075] 4. Hydrogenated castor oil PEG 40

[0076] 5. Ascorbic acid

[0077] 6. Chlorhexidine digluconate

[0078] 7. Polyvinylpyrrolidone-vinyl acetate copolymer

[0079] 8. Sodium DNA

[0080] 9. Flavoring

[0081] 10. Poloxamer 407

[0082] 11. Sodium metabisulfite

[0083] 12. Sodium citrate

[0084] 13. Citric acid

[0085] 14. CI 42090

[0086] 15. CI 17200

[0087] In another embodiment, the oral care composition according to the present invention is a periodontal gel comprising chlorhexidine and sodium DNA.

[0088] According to a preferred embodiment, the periodontal gel according to the present invention comprises the following components:

[0089] 1. Water

[0090] 2. Propylene Glycol

[0091] 3. Hydroxyethyl cellulose

[0092] 4. Polyvinylpyrrolidone-vinyl acetate copolymer

[0093] 5. Hydrogenated castor oil PEG 40

[0094] 6. Chlorhexidine digluconate

[0095] 7. Sodium acetate

[0096] 8. Sodium DNA

[0097] 9. Menthol

[0098] 10. Peppermint oil

[0099] 11. Acetic acid

[0100] 12. Sodium metabisulfite

[0101] 13. Ascorbic acid

[0102] Preferably, the periodontal gel according to the present invention comprises 0.5 to 1.0 weight percent of chlorhexidine with respect to the total volume of the dental gel.

[0103] Preferably, the periodontal gel according to the present invention comprises a maximum amount of 0.3 weight%, more preferably 0.01 to 0.3 weight% of sodium DNA with respect to the total volume of the periodontal gel.

[0104] In another preferred embodiment, the oral care composition according to the present invention is a toothpaste comprising chlorhexidine and sodium DNA.

[0105] According to a preferred embodiment, the toothpaste according to the present invention comprises the following ingredients:

[0106] 1. Sorbitol

[0107] 2. Water

[0108] 3. Silica (hydrated silica)

[0109] 4. Glycerol

[0110] 5. Xylitol

[0111] 6. Cocamidopropyl Betaine

[0112] 7. Polyvinylpyrrolidone-vinyl acetate copolymer

[0113] 8. Hydrogenated castor oil PEG 40

[0114] 9. Flavoring

[0115] 10. Chlorhexidine digluconate

[0116] 11. Carboxymethyl cellulose

[0117] 12. Ascorbic acid

[0118] 13. Sodium metabisulfite

[0119] 14. Sodium DNA

[0120] 15. Sodium Saccharin

[0121] 16. Sodium Benzoate

[0122] 17. Sodium citrate

[0123] Preferably, the toothpaste according to the present invention contains 0.05 to 0.2 weight percent of chlorhexidine with respect to the total volume of the toothpaste.

[0124] Preferably, at least one inorganic fluoride may optionally be present in the toothpaste according to the present invention.

[0125] Preferably, the amount of sodium DNA in the toothpaste according to the present invention is in the range of 0.01 to 0.05 weight percent with respect to the total volume of the toothpaste.

[0126] In another aspect, the present invention also relates to the use of the oral care composition according to the present invention as an anti-irritant for the oral mucosa.

[0127] In another aspect, the present invention relates to the use of the oral care composition according to the present invention as a healing agent for the oral mucosa.

[0128] Preferably, the oral mucosa includes periodontal tissue.

[0129] In fact, it was discovered that thanks to the combination of sodium DNA and chlorhexidine, the oral care composition according to the present invention can neutralize the irritating effect of the latter on the oral mucosa, thereby providing a protective effect on the mucosa and a healing effect on wounds that may occur in the oral cavity.

[0130] In addition, it was confirmed that the combination of sodium DNA and chlorhexidine can limit side effects of long-term use of chlorhexidine-based oral care compositions, including changes in cell structure such as vacuolation, nuclear degeneration, and expansion of intercellular space, and thus can resolve one of the application and functional limitations of the product.

[0131] Preferably, the present invention relates to the use of an oral care composition according to the present invention in a method for treating at least one disease selected from the group consisting of gingivitis, bacterial plaque, and periodontitis.

[0132] Furthermore, it was discovered that the oral care composition according to the present invention is also effective in treating oral implant mucositis. Accordingly, in another aspect, the present invention also relates to the use of the oral care composition according to the present invention in a method for treating oral implant mucositis.

[0133] In another aspect thereof, the present invention relates to the use of sodium DNA for use in a method for treating diseases of the oral mucosa, wherein the disease involves changes in the cellular structure of the oral mucosa, and such changes in cellular structure are selected from the group consisting of vacuolation, nuclear degeneration, and expansion of the intercellular space.

[0134] In fact, it was confirmed that sodium DNA can impart a protective effect to the cellular structure of the oral mucosa, thereby preventing the occurrence and progression of cellular structural changes, including vacuolation, nuclear degeneration, and expansion of the intercellular space.

[0135] Preferably, this oral mucosa includes periodontal tissue.

[0136] The applicant has also discovered the unexpected fact that, through the protective action of the sodium DNA, therapeutic intervention in cell deformation of any cause is possible by limiting the side effects of treatment, for example, by using active ingredients such as chlorhexidine that proceed specifically to the cellular structure of the oral mucosa.

[0137] The applicant has confirmed that resolving the chlorhexidine side effects caused by the use of a chlorhexidine-based oral care composition constitutes an innovative aspect of particular value in light of the aforementioned application and functional limitations.

[0138] In another aspect thereof, the present invention also relates to sodium DNA used in a method for alleviating side effects of chlorhexidine in a patient receiving treatment with chlorhexidine, the side effects of which involve changes in the cell structure of the patient's oral mucosa, and such changes in cell structure are selected from the group consisting of vacuolation, nuclear degeneration and expansion of intercellular space.

[0139] Preferably, the oral mucosa includes periodontal tissue.

[0140] Experimental section

[0141] Accordingly, the present invention is described through several embodiments considered for the purpose of non-limiting examples.

[0142] Example 1

[0143] Materials and Methods

[0144] All reagents, culture media, and disposable materials were obtained from Merck (E. Merck AG, Darmstadt, Germany). 0.5 cm² of reconstituted human oral epithelial cell samples (hereinafter "ROE") (SkinEthic HOE TM Human oral epithelium was obtained from EPISKIN (EPISKIN, Lyon Cedex 7, France). Sodium DNA (hereinafter "NaDNA", Kalinat® AW) was obtained from ALICHEM (Kalichem, Brescia, Italy).

[0145] The following preservative-free mouthwash solutions were tested:

[0146] A. A mouthwash containing 0.2 wt% chlorhexidine relative to the total volume of the mouthwash (positive control);

[0147] B. Mouthwash containing 0.2 wt% chlorhexidine and 0.01 wt% NaDNA based on the total volume of the mouthwash (test group);

[0148] C. A mouthwash containing 0.01 wt% of NaDNA relative to the total volume of the mouthwash;

[0149] D. Phosphate buffered saline (PBS, negative control).

[0150] Reconstructed human oral epithelial cells (ROE)

[0151] 32 ROE samples were used. The ROE samples were opened under a fume hood in the presence of sterile airflow. The samples were arranged in a 24-well transport plate containing a medium with agarose nutrients.

[0152] Samples were extracted from transport plates and agarose was removed. Next, samples were placed in 6-well plates containing nutrient medium (RPMI 1640 medium supplemented with 20% fetal bovine serum, 1% L-glutamine, and 1% penicillin / streptomycin). Before the test, the culture plates were incubated overnight at 37°C under a 5% CO2 atmosphere with 100% relative humidity.

[0153] bioreactor

[0154] Tests were performed on two commercially available drip flow bioreactors (DFR 110; BioSurface Technologies, Bozeman, MT, USA) modified to allow a tray containing the sample to be installed on the bottom of the flow cell and to immerse the ROE sample in the surrounding circulation medium. This allows the nutrient medium to be used at a continuous flow rate.

[0155] All trays and samples in the bioreactor containing the test tubes were sterilized using a chemical reactor utilizing hydrogen peroxide gas plasma technology before starting the experiment (Sterrad, ASP, Irvine, CA, USA). The maximum temperature was limited to 45°C to avoid thermal damage to the entire system. After sterilization, the bioreactor was assembled inside a sterile hood.

[0156] Test Procedure

[0157] Figure 1 is a schematic cross-sectional view of a portion of the apparatus used in the experiment, exemplarily showing one of the two bioreactors.

[0158] The system (1) includes a peristaltic pump (11), a drop flow reactor (10), and flow cells (14, 15 and 16) containing a sample. The drop flow reactor (10) is equipped with a flow chamber (21), an inlet (12), and a drain (13). The flow chamber (21) is configured to contain a flow medium (20).

[0159] The ROE samples were cut and separated from the support using a sterile scalpel and tweezers and placed inside a bioreactor made of polytetrafluoroethylene (PTFE) with eight flow cells (14, 15, and 16) each having three holes, and fixed and exposed to a flow medium (20) containing a nutrient medium (medium RPMI 1640, 20% fetal bovine serum, 1% L-glutamine, and 1% penicillin / streptomycin supplement). All trays were fixed to the bottom of each flow chamber (21) of two bioreactors (10) operating in parallel, and fresh nutrient medium was inoculated immediately. Next, the bioreactors were transferred to an incubator operating at 37°C, 5% CO2, and 100% relative humidity. Next, a computer-controlled multi-channel peristaltic pump (11) (RP-1, Rainin, Emeryville, CA, USA) was turned on and set to a flow rate of 9.6 ml / h to supply a continuous flow of fluid medium (20) containing nutrient medium through the flow cell. In FIG. 1, arrows (17, 18 and 19) schematically indicate the flow direction of the fluid medium (20). The peristaltic pump (11) supplies the fluid medium (20) through the inlet (12) of the reactor (10) to the flow chamber (21) of two bioreactors (10), and then discharges it through the drain (13).

[0160] After 24 hours, the pump (11) was stopped, and four flow cells (14, 15, and 16) were each treated with one (10 ml) of oral rinse (A, B, C, and D) per flow cell. In each flow cell, the bioreactor (10) was tilted for 25 minutes to treat two samples for 5 minutes and the other two samples for 30 minutes, resulting in the solution completely covering two lower samples. Next, the solution was returned to a horizontal position for the remaining 5 minutes to cover all four samples. The remaining four flow cells (14, 15, and 16) were first treated with a 3% H2O2 solution for 1 minute to induce hyperoxidative stress and cell damage, then the samples were thoroughly washed with sterile PBS for 1 minute, and the flow cells (14, 15, and 16) were treated with the oral rinse solution tested as described above. Again, in each flow cell, two samples were treated with an oral rinse solution for 5 minutes, while the other two samples were treated for 30 minutes.

[0161] After that, the pump (11) was operated to wash the mouthwash for 60 minutes, and the ROE sample was extracted again from the flow cell (14, 15 and 16), and then immediately cut into four equal parts using a sterile scalpel and tweezers, and then the following was performed.

[0162] Evaluation of samples

[0163] For each treatment, ROE samples underwent an MTT viability test (n = 4), followed by confocal laser scanning microscopy imaging (CLSM) (n = 2) and histological evaluation using optical and electron microscopy in TEM (n = 2).

[0164] MTT survival rate test

[0165] Cell viability was evaluated using the MTT viability test. The administration method was performed as follows: Two initiation stock solutions were prepared by dissolving 5 mg / ml of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) in sterile PBS and 0.3 mg / ml of N-methylphenazinium methyl sulfate (PMS) in sterile PBS. These solutions were stored in light-resistant glass vials at 2°C until the day of the experiment, when a new measurement solution was prepared by mixing the MTT stock solution, sterile PMS, and PBS stock solution in a ratio of 1:1:8, respectively. An eluent (LS) was prepared by dissolving 10% (v / v) sodium dodecyl sulfate and 50% (v / v) dimethylformamide in distilled water. ROEs, the target of the MTT test, were placed in each well of a 24-well sterile flat-bottom plate. Subsequently, 1 ml of FMS was pipetteed into each well, and the plate was incubated under light conditions at 37 °C for 1 hour. During incubation, electrons moved across the cell membrane, and although in small quantities, a cellular oxide-reduction mechanism converted this MTT yellow salt into insoluble purple formazan. The conversion reaction was facilitated by an intermediate electron acceptor (PMS). Next, the unreacted FMS was carefully removed from the wells using an aspirator, 1 ml of LS was added to each well to dissolve the formazan crystals, and the plate was incubated for an additional 1 hour under light conditions. Then, a total of 100 microliters of suspension was removed from each well, and the optical density (550 nm) was measured using a spectrophotometer (Genesys 10-S, Thermo Spectronic, Rochester, NY, USA).

[0166] CLSM observation

[0167] CLSM imaging was performed using the live / dead staining method as described in the previously disclosed literature (Brambilla E, Ionescu A, Mazzoni A, Cadenaro M, Gagliani M, Ferraroni M, Tay F, Pashley D, Breschi L. (2014)). The hydrophilicity of the dentin binding system influences the formation of Streptococcus mutant biofilms in vitro (Dent Mater. 30(8): 926-35). In summary, ROE samples subjected to CLSM observation were stained using the live / dead® viability kit for microscopic analysis (Invitrogen Ltd., Paisley, UK). The cellular fluorescently stained biomaterials were observed using CLSM (Eclipse Ti2 inverted CLSM, Nikon, Tokyo, Japan). Four randomly selected image stack regions were recorded for each ROE sample. Confocal images were acquired using a dry plan apochromat 20 x (NA 0.75) lens and digitized using Nikon software with an image resolution of 1024 x 1024 pixels and a zoom factor of 1.0. In each image stack area, 3D rendering reconstructions were obtained using Drissity 3D software as described in known literature (Lindhe J, Heyden G, Svanberg G, Loe H, Rindom Schiott C (1970); Effects of topical application of chlorhexidine on the oral mucosa of hamsters. J. Periodont. Res. 5(3): 177-182).

[0168] Histological evaluation

[0169] ROE samples for histological analysis were fixed overnight in a freshly prepared Karnovsky solution (a solution of 2.0% paraformaldehyde and 2.0% glutaraldehyde dissolved in 0.1M sodium cacodilate buffer).

[0170] After washing with a buffer solution, the samples were stained with 2% OsO4 and 2% uranyl acetate. Next, the samples were dehydrated with an acetone solution and inoculated into ipon-araldite resin (Fluka, Italy). For all samples in different experimental groups, 0.5 micron cross-sections for toluidine blue staining were prepared and observed using an optical microscope (Pro Plus Imaging software) and TEM (Zeiss microscope EM10) at a final magnification of 1500 x.

[0171] result

[0172] MTT test

[0173] The data setup of the MTT survival rate study was preliminarily checked for distribution standardization (Shapiro-Wilk test) and equivariance (Levene test). Since the data did not have a normal distribution even after log transformation, nonvariance analysis was performed using the Wilcoxone test (p < 0.05).

[0174] The results obtained for ROE cells at different treatment times using solutions (A, B, C, and D) are shown in Fig. 2. Fig. 3 shows the results of the MTT viability test on ROE cells after treatment with a 3 volume% H2O2 solution for 1 minute and subsequent various treatments using solutions (A, B, C, and D).

[0175] As shown in Fig. 2, the survival rate after treatment with the mouthwash solution for 5 minutes was observed to be significantly lower in the sample treated with solution (C) compared to solution (B). No change in the survival rate of the solution was observed for the negative control (solution (D)). As a result of treating ROE samples with the mouthwash solution for 30 minutes, a significant decrease in the survival rate was confirmed by solution (C) in the chlorhexidine-containing solution. Treatment with 3 volume% H2O2 (Fig. 3) generally induced a decrease in the survival rate. For samples treated for 5 minutes, the survival rate after treatment with solution (A) was significantly higher than that of solution (B); however, after treatment for 30 minutes, the difference between the two solutions decreased significantly, and the survival rate was even more significantly higher for solutions (C and D). In addition, solution (C) showed a significantly higher survival rate than solution (D), which suggests significant and positive activity of NaDNA in cell survival.

[0176] CLSM observation

[0177] The confocal microscope reconstruction results obtained after treatment with the mouthwash solution for 5 minutes showed no difference between these groups. The reconstruction of the samples after 30 minutes of treatment is as shown in Fig. 4 (samples after 30 minutes of treatment using solutions (A, B, C, and D)) and Fig. 5 (samples after treatment with H2O2 for 1 minute and subsequent treatment with solutions (A, B, C, and D) for 30 minutes).

[0178] Samples treated with solution (A) and samples treated with a smaller amount of solution (B) showed good preservation of cell structure even when exposed to hydrogen peroxide. In the case of the negative control sample (D), dead cells were present on the surface, and after treatment with hydrogen peroxide, a layer consisting almost entirely of dead cells was observed on the surface. Samples treated with NaDHA (solution C) alone showed a much smaller amount of dead cells than the negative control, regardless of whether hydrogen peroxide was applied.

[0179] Histological evaluation

[0180] It was found that there was no difference between groups in the region (0.5 μm) of the ROE tissue obtained after 5 minutes of treatment with the mouthwash solution. The region of the sample after 30 minutes of treatment is as shown in Figure 6 (sample after 30 minutes of treatment with solutions (A, B, C, and D)) and Figure 7 (sample after 1 minute of treatment with H2O2 and subsequent 30 minutes of treatment with solutions (A, B, C, and D)).

[0181] Considering the samples in Fig. 6, the negative control (D) showed complete preservation of the tissue structure. The samples treated with solution (A) and the samples treated with a smaller amount of solution (B) exhibited changes in cell structure, such as vacuolation, nuclear denaturation, and initial expansion of the intercellular space in both the outer and basal layers. These changes in cell structure may be due to the activity of chlorhexidine. Indeed, when NaDNA was added to the chlorhexidine mouthwash (solution B), the changes in cell structure were found to be less than those of the chlorhexidine mouthwash alone (solution A). The samples treated with solution (C) exhibited the same changes, but were confined to the first cell layer. Upon treatment with hydrogen peroxide (see Fig. 7), as expected, extensive damage to ROE cells was observed, including pronounced vacuolation, nuclear denaturation, and expansion of the intercellular space. These changes were more pronounced in the negative control (D) and the samples treated with solution (A) (chlorhexidine alone). In the case of samples treated with solution (B), some cells without signs of denaturation could be identified in the innermost layer, and these cells received greater protection from reactive oxygen species generated by hydrogen peroxide, and NaDNA also acted to minimize cell damage. Samples treated with oral antiseptic (C) (NaDNA alone) showed minimal signs of cell denaturation.

[0182] In conclusion, NaDNA demonstrated a clear protective effect against oxidative stress-induced cell degeneration and exposure to mouthwashes containing chlorhexidine alone.

[0183] Example 2

[0184] The purpose of this experiment is to test the effect of the oral care composition according to the present invention in gel form under conditions of dental-implant mucositis, that is, under conditions of bleeding and diseased pockets (< 3 mm) upon probing around an implant without supporting bone.

[0185] Patient Selection

[0186] This study was conducted in accordance with the principles of clinical trials, in compliance with the standards of the Declaration of Helsinki and with the approval of the Ethics Committee for Biomedical Research in Chieti and Pescara. Accordingly, patients with dental-implant mucositis were recruited from the departments of Medicine, Oral Medicine, and Biotechnology for the purpose of evaluating bacterial plaque and inflammation control properties.

[0187] Patients selected for this study were enrolled in accordance with the principles specified in the Declaration of Helsinki regarding the conduct of scientific research and also the following internal criteria:

[0188] - Healthy patients, i.e., patients without: related systemic diseases such as primary diabetes, immune diseases, or hematological disorders; neoplasms; severe infectious diseases such as HIV or viral hepatitis accompanied by signs and / or symptoms of liver failure; intellectual difficulties; or lack of exercise;

[0189] - 18 years of age or older; and

[0190] - Experiment participants who agreed to specific notifications.

[0191] Selection candidates with implants affected by mucositis are defined as follows:

[0192] - Bleeding upon probing in the absence of supporting bone loss around the implant;

[0193] - No plant mobility;

[0194] - Presence of at least 2 mm of keratinized gingivitis around the implant;

[0195] - No implant restorations other than a single crown or bridge on up to 3 teeth; and

[0196] - No clear signs of overload or occlusal trauma.

[0197] The other principles are as follows:

[0198] - Not a complete extraction after implant surgery (If natural teeth are not present after surgery, it is impossible to measure variables such as plaque and bleeding).

[0199] - Non-smokers or light smokers (less than 10 cigarettes per day);

[0200] - Good oral hygiene with low plaque and bleeding indices and no periodontal lesions on other teeth (FMPS and FMBS ≤ 25%); and

[0201] - Patients with allergies to chlorhexidine gluconate, the formulation of the device, or other components of the placebo.

[0202] Selection of the primary evaluation index:

[0203] Primary Objective: Plaque Index Score: Recorded the presence (presence / absence) of plaque on the surface being evaluated.

[0204] Selection of Secondary Evaluation Index:

[0205] Recording of the following clinical variables:

[0206] - Bleeding on probing ("BOP"): Recorded whether bleeding occurred on probing.

[0207] - Gum Index (Loe & Silness 1963): Recorded the health of periodontal tissues according to the following criteria:

[0208] 0 = normal gums;

[0209] 1 = Mild inflammation - Slight swelling and color change without bleeding upon probing

[0210] 2 = Moderate inflammation - Red and swollen tissue and bleeding upon probing

[0211] 3 = Severe inflammation - pronounced redness, swelling, ulceration, and bleeding tendency.

[0212] Statistical analysis

[0213] Descriptive data analysis was performed, and quantitative variables are expressed as mean and standard deviation. Student's T-test was used to compare the two experimental groups for the quantitative variables. The significance level was set at 5%. The normal distribution was determined by evaluating graphs using the Kilmogorov-Smirnov test (p-value > 0.05) and the 14-day response variable.

[0214] Experimental stage

[0215] The following gel was tested:

[0216] E. Gel containing 0.2 wt% chlorhexidine and 0.01 wt% NaDNA;

[0217] F. A "placebo" having the same composition as gel (E) but not containing chlorhexidine or NaDNA;

[0218] The sample size consisted of 24 patients with a 1:1 registration ratio between the two groups (12 patients per experimental group).

[0219] After recording clinical variables and oral care status, each patient was supplied with an anonymous gel tube, syringe, and application nozzle (three times a day for a total of 14 days). Patients supplied with gel (E) (containing 0.2 wt% chlorhexidine and 0.01 wt% NaDNA) were defined as Group A, while patients supplied with gel (F) ("placebo" gel) were defined as Group B.

[0220] The record targets to be checked during the follow-up were set as follows:

[0221] - Base value (time 0, "TO")

[0222] - 14 days post-surgery (Time 1, "T1")

[0223] In the T0 phase, periodontal records were generated by collecting plaque index, bleeding upon probing, and gingival index for each clinical protocol.

[0224] All patients completed the T0 and T1 clinical study phases. Accordingly, subjects were explained proper home oral care guidelines and re-evaluated after 14 days. In the T1 phase, periodontal records were created by collecting plaque index, probing bleeding, and gingival index for each clinical protocol. No adverse effects were recorded during the study period. Additionally, there were no inappropriate effects or side effects associated with the administration of gel (E) and (F).

[0225] result

[0226] 1st evaluation index

[0227] At time T0, baseline plaque index values ​​were detected as 2.4 ± 0.4 for Group A (Gel E) and 2.2 ± 0.5 for Group B (Gel F) (p > 0.05). After 2 weeks of treatment (T1), the measured plaque index was 0.5 ± 0.4 for Group A (Gel E) and 1.7 ± 1.9 for Group B (Gel F) (p < 0.05).

[0228] Second evaluation index

[0229] At time T0, baseline BOP values ​​were detected as 57.1% ± 15.2% for Group A (Gel E) and 55.3% ± 11.7% for Group B (Gel F) (p > 0.05). After 2 weeks of treatment (T1), the measured BOP was 14.3% ± 6.6% for Group A (Gel E) and 45.4% ± 9.8% for Group B (Gel F) (p < 0.05).

[0230] Data on gum index measured at different experimental times are as follows: baseline values ​​and data at T1, after 2 weeks of treatment, are shown in Table 1.

[0231] Group A (Gel E) Group B (Gel F) P-value Gum index at T0 2.21 ± 0.51 2.35 ± 0.67 p> 0.05 Gum index at T1 0.82 ± 0.53 1.62 ± 0.74 p<0.05

[0232] conclusion

[0233] At experimental time (T1), a statistically significant difference in primary plaque value variables is confirmed between Group A (Gel E) and Group B (Gel F). The advantages of this treatment were also demonstrated in relation to secondary indices regarding post-probing bleeding and gingival indices, and statistically significant differences in the evaluated variables were observed in Group A, thus confirming the efficacy of the oral care composition according to the present invention in the treatment of dental-implant mucositis.

[0234] Example 3

[0235] The purpose of this experiment is to clinically evaluate the antibacterial and inhibitory properties against dental plaque of the oral care composition according to the present invention, in the form of an oral rinse, used on the soft tissues of the oral cavity after 2 weeks in patients with periodontal disease.

[0236] Patient Selection

[0237] This study was conducted in accordance with the principles of clinical trials, in compliance with the standards of the Declaration of Helsinki and with the approval of the Ethics Committee for Biomedical Research in Chieti and Pescara. Accordingly, patients with periodontal disease were recruited from the departments of medicine, oral medicine, and biotechnology for the purpose of evaluating bacterial plaque and inflammation control properties.

[0238] Patients were recruited according to the following internal criteria:

[0239] - Patients with chronic periodontitis with probe examination (> 3 mm) on 20 or more teeth;

[0240] - Non-smokers or light smokers (less than 10 cigarettes per day);

[0241] Other criteria are as follows:

[0242] - Patients undergoing orthodontic treatment;

[0243] - Patients with no tolerance to or allergies to mouthwash;

[0244] - Smokers and drinkers;

[0245] - Patients who have received radiation therapy / chemotherapy within the last 5 years;

[0246] - Immunocompromised patients;

[0247] - Patients with systemic, renal, or cardiovascular disease; and

[0248] - Pregnant or breastfeeding women, or patients undergoing antibiotic and anti-inflammatory treatment.

[0249] Selection of the primary evaluation index:

[0250] Total Oral Plaque Score (FMPS): Record the presence of plaque at 4 locations per tooth and calculate the percentage for the surface.

[0251] Selection of Secondary Evaluation Index:

[0252] Total Oral Bleeding Score (FMBS): Record the presence or absence of bleeding at 4 locations per tooth upon probing and calculate the percentage for the surface.

[0253] Gum index

[0254] Gum Index (Loe & Silness 1963): Recorded the health of periodontal tissues according to the following criteria:

[0255] 0 = normal gums;

[0256] 1 = Mild inflammation - Slight swelling and color change without bleeding upon probing

[0257] 2 = Moderate inflammation - Red and swollen tissue and bleeding upon probing

[0258] 3 = Severe inflammation - pronounced redness, swelling, ulceration, and bleeding tendency.

[0259] Record complications, adverse effects, and the presence of secretions.

[0260] Statistical analysis

[0261] The distributions of FMPS, FMBS, and GI data at baseline, 1 week, and 2 weeks at different experimental times with respect to the experimental group were evaluated using the Kilmogorov-Smirnov test. The significance of the study data was evaluated using the Student T-test (p < 0.05).

[0262] experimental treatment

[0263] The following mouthwashes were tested:

[0264] G: Oral rinse containing 0.2 wt% chlorhexidine and 0.01 wt% NaDNA;

[0265] H. A "placebo" having the same composition as gel (E) but not containing chlorhexidine or NaDNA;

[0266] The sample size consisted of 54 patients with a 1:1 registration ratio between the two groups (27 patients per experimental group).

[0267] Patients who received the mouthwash (G) (containing 0.2 wt% chlorhexidine and 0.01 wt% NaDNA) were defined as Group A, while patients who received the mouthwash (H) ("placebo" gel) were defined as Group B.

[0268] Research stage

[0269] Experimental Phase (V1) - Screening to assess patient eligibility and acceptance of the study. Informed consent and approval of oral care guidelines.

[0270] Experimental Phase (V2) (Baseline) - Create a periodontal record by recording Total Oral Plaque Values ​​(FMPS), Total Oral Bleeding Values ​​(FMBS), and Gingival Index (GI). Provide each patient with a mouthwash package associated with their assigned study group (A or B) and perform a 10 ml rinse procedure. The protocol includes performing a total of three rinse procedures daily (after breakfast and dinner) at home during a two-week treatment period.

[0271] Experimental Phase (V3) (Week 1) - Compare with the results recorded for FMPS, FMB, and GI indices as follows.

[0272] Experimental Phase (V4) (Week 2) - Compare with the results of the final treatment to remove FMPS, MFBS, GI and any potential spots.

[0273] result

[0274] 1st evaluation index

[0275] At time V2, the detected baseline FMPS values ​​were 52.7 ± 9.2 for Group A (mouthwash G) and 58.2 ± 6.1 for Group B (mouthwash H) (p > 0.05). At the first week of treatment (V3), the measured FMPS was confirmed to be 13.3 ± 5.6 for Group A and 18.7 ± 4.3 for Group B (p < 0.05). At the second week of treatment (V4), the measured FMBS was confirmed to be 14.2 ± 4.1 for Group A and 20.3 ± 5.2 for Group B (p < 0.05).

[0276] Second evaluation index

[0277] At time V2, the baseline detected FMBS was 46.7 ± 8.7 for group A and 49.2 ± 6.2 for group B (p > 0.05). At the first week of treatment (V3), the measured FMBS was found to be 12.7 ± 4.2 for group A and 18.5 ± 5.9 for group B (p < 0.05). Finally, at the second week of treatment (V4), the FMBS was found to be 13.1 ± 3.2 for group A and 19.8 ± 4.9 for group B (p < 0.05).

[0278] The data on the gum index measured at different experimental times are as follows: baseline values, data at the first and second week of treatment are shown in Table 2.

[0279] Group A (mouthwash G) Group B (mouthwash H) P-value Gum index in V2 (base value) 2.85 ± 0.47 2.71 ± 0.51 p> 0.05 Gum Index in V3 (Week 1) 1.14 ± 0.55 1.75 ± 0.49 p<0.05 Gum Index in V4 (Week 2) 1.09 ± 0.44 1.96 ± 0.39 p<0.05

[0280] conclusion

[0281] At experimental time (V3), a statistically significant difference in primary FMPS variables is identified between Group A and Group B. After 2 weeks of treatment, the average FMPS level was proven to remain below 20% in Group A. In this regard, the benefits of the above treatment were also demonstrated in relation to secondary indices regarding FMBS and gingival indices, and statistically significant differences in clinical variables are observed in Group A. This is evidence showing a correlation with the beneficial effects induced by the oral care composition according to the present invention on the gum tissues of the treated subjects.

Claims

Claim 1 An oral care composition comprising sodium DNA used in a method for treating side effects of chlorhexidine in a patient receiving chlorhexidine treatment, wherein the side effects involve deformation of the cellular structure of the oral mucosa of the patient, and the deformation of the cellular structure is selected from the group consisting of vacuolation, degeneration of the cell nucleus, and expansion of the intercellular space. Claim 2 An oral care composition comprising sodium DNA, characterized in that, in claim 1, the chlorhexidine treatment comprises chlorhexidine and sodium DNA and is performed using sodium DNA. Claim 3 In paragraph 2, the oral care composition comprising sodium DNA is characterized in that the oral care composition comprising chlorhexidine and sodium DNA is selected from the group consisting of oral rinses, periodontal gels, and toothpaste. Claim 4 An oral care composition comprising sodium DNA, characterized in that, in paragraph 3, the oral care composition is an oral rinse, and the amount of chlorhexidine is in the range of 0.01 to 0.30 weight% relative to the total volume of the oral rinse. Claim 5 An oral care composition comprising sodium DNA, characterized in that, in claim 3 or 4, the oral care composition is an oral rinse and chlorhexidine is in the form of a salt or complex salt. Claim 6 An oral care composition containing sodium DNA, characterized in that, in paragraph 3, the oral care composition is an oral rinse, and the amount of sodium DNA is in the range of 0.01 to 0.2 weight% with respect to the total volume of the oral rinse. Claim 7 An oral care composition comprising sodium DNA, characterized in that, in paragraph 3, the oral care composition is an oral rinse comprising at least one metabisulfite salt of an alkali metal or an alkylto metal. Claim 8 In paragraph 3, the oral care composition is characterized as being an oral rinse containing ascorbic acid, and the oral care composition containing sodium DNA. Claim 9 In paragraph 3, the oral care composition is characterized as being an oral rinse comprising at least one polyvinylpyrrolidone-vinyl acetate copolymer, and is an oral care composition comprising sodium DNA. Claim 10 In paragraph 3, the oral care composition is characterized as being an oral rinse containing sodium DNA, wherein the oral care composition is an oral rinse containing sodium tribasic citric acid. Claim 11 In claim 3, the oral care composition is characterized as being an oral cleanser comprising 0.01 to 0.30 weight% of chlorhexidine, 0.01 to 0.2 weight% of sodium DNA, 0.1 to 0.5 weight% of at least one metabisulfite salt of an alkali metal or alkaline earth metal, 0.1 to 1.0 weight% of ascorbic acid, and 0.05 to 1 weight% of at least one polyvinylpyrrolidone-vinyl acetate copolymer, based on the total volume of the oral cleanser. Claim 12 An oral care composition containing sodium DNA, characterized in that, in paragraph 3, the oral care composition is a periodontal gel containing 0.5 to 1.0 weight% of chlorhexidine based on the total weight of the periodontal gel. Claim 13 An oral care composition according to claim 3 or 12, characterized in that the oral care composition is a periodontal gel containing sodium DNA in an amount of up to 0.3 weight% with respect to the total weight of the periodontal gel. Claim 14 An oral care composition containing sodium DNA, characterized in that, in paragraph 3, the oral care composition is a toothpaste containing 0.05 to 0.2 weight percent of chlorhexidine based on the total volume of the toothpaste. Claim 15 An oral care composition according to claim 3 or 14, characterized in that the oral care composition is a toothpaste containing sodium DNA in an amount of 0.01 to 0.05 weight% with respect to the total volume of the toothpaste. Claim 16 An oral care composition comprising sodium DNA, characterized in that, in claim 1, the chlorhexidine treatment is for treating at least one disease selected from the group consisting of gingivitis, bacterial plaque, and periodontitis. Claim 17 delete Claim 18 delete Claim 19 delete Claim 20 delete

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