Compositions comprising chlorhexidine and active oxygen for the oral cavity

Abstract

The present invention relates to compositions for administration to the oral cavity, suitable for prophylaxis or treatment of diseases of the teeth and / or gums and / or the oral cavity, which comprises chlorhexidine and one or more peroxides that are decomposed into active oxygen, preferably hydrogen peroxide and / or carbamide peroxide and / or calcium peroxide.

Description

[0001] Compositions Comprising Chiorhexidine and Active Oxygen for the Orai Cavity

[0002] Description of the Invention

[0003] The present invention relates to compositions for administration to the oral cavity, suitable for prophylaxis or treatment of diseases of the teeth and / or gums and / or the oral cavity, which comprises chlorhexidine and one or more peroxides that are decomposed into active oxygen, preferably hydrogen peroxide and / or carbamide peroxide and / or calcium peroxide.

[0004] The document EP1998738B1 discloses oral care compositions comprising peroxide and a flavoring system that effectively masks the unpleasant taste attributed to peroxide. However, it does not necessarily comprise chlorhexidine, nor does it define its concentration.

[0005] The document WO2022221377A2 discloses topical disinfectant compositions intended for disinfecting skin or other surfaces, or for increasing their resistance to microbial transmission. These compositions include ethyl alcohol, chlorhexidine, an ester- containing moisturizing cream, and water, and optionally also include one or more surfactants, preservatives, colloidal silver, and hydrogen peroxide. However, these compositions are not Intended for dental or oral use.

[0006] Moreover, the documents US20150374772A1, CN107582737A and US20080175801A1 refer to oral compositions of hydrogen peroxide and chlorhexidine among other antimicrobials. However, there is no mention of the proper concentration of chlorhexidine that should be used.

[0007] Furthermore, the document DE3415147 refers on compositions of hydrogen peroxide and chlorhexidine, in the form of mouthwash or toothpaste. However, nowhere appears simultaneously the exact amounts of each of said two compounds, as well as the weight ratio of said two compounds as in the present application, as defined by some points below. However, prior art lacks any known compositions for administration to the oral cavity, suitable for prophylaxis or treatment of diseases of the teeth and / or gums and / or the oral cavity, which comprises chlorhexidine and one or more peroxides that are decomposed into active oxygen, preferably hydrogen peroxide and / or carbamide peroxide and / or calcium peroxide.

[0008] Given the significant challenge of addressing dental diseases, the identification of effective compositions capable of simultaneously preventing and treating various oral conditions that co-exist within the oral cavity is currently a critical clinical need.

[0009] Despite the known benefits of each individual component mentioned above, there still remains a continuous need for compositions that exhibit synergistic activity and prolonged protective efficacy.

[0010] Taking the aforementioned into consideration, the present invention addresses all the above limitations of the prior art and solves all the above problems of the state of the art, and indeed with unexpectedly advantages and unexpectedly improved outcomes in the management of symptoms, such as dental caries, halitosis, localized gingivitis and periodontitis, as well as promoting healing of ulcers, aphthous lesions, irritations, and wounds of the oral mucosa and gums. Moreover, the invention demonstrates enhanced oral antisepsis, effective removal of dental plaque, and prevention of plaque formation, enhanced bacteriostatic action, without any adverse effects and especially without causing any risk of burns to the mucous membranes of the oral cavity due to the specific amounts of peroxides, as well as enhanced hydration and healing of the mucosa due to hydration ingredients like hyaluronic acid.

[0011] Specifically, the present invention is defined by the following definitions:

[0012] Definition 1. Composition for administration to the oral cavity, suitable for prophylaxis or treatment of diseases of the teeth and / or gums and / or the oral cavity, which comprises chlorhexidine and one or more peroxides that are decomposed into active oxygen, preferably hydrogen peroxide and / or carbamide peroxide and / or calcium peroxide. Definition 2. Composition according to definition 1, which is in the form of mouthwash or toothpaste or gel or mouth drops or mouth foam or spray, preferably mouthwash or gel and wherein the amount of chlorhexidine ranges from 0,12 to 0,2 % w / w per formulation, preferably is 0,12 % w / w or 0,2 % w / w per formulation and the amount of hydrogen peroxide ranges from 0,8 to 1 % w / w per formulation, preferably is 0,8 % w / w or 1 % w / w per formulation.

[0013] Definition 3. Composition according to definition 1, which is in the form of mouthwash or toothpaste or gel or mouth drops or mouth foam or spray, preferably mouthwash or gel and wherein the amount of chlorhexidine ranges from 0,12 to 0,2 % w / w per formulation, preferably is 0,12 % w / w or 0,2 % w / w per formulation and wherein the amount of carbamide peroxide ranges from 0,01 to 40,0 % w / w per formulation, preferably from 11 to 35 % w / w per formulation, more preferably is 11 % w / w or 16 % w / w or 22 % w / w or 35 % w / w per formulation.

[0014] Definition 4. Composition according to definition 1, which is in the form of mouthwash or toothpaste or gel or mouth drops or mouth foam or spray, preferably mouthwash or gel and wherein the amount of chlorhexidine ranges from 0,12 to 0,2 % w / w per formulation, preferably is 0,12 % w / w or 0,2 % w / w per formulation and wherein the amount of calcium peroxide ranges from 0,01 to 5,0 % w / w per formulation, preferably from 0,05 to 0,1 % w / w per formulation.

[0015] Definition 5. Composition according to any of the definitions 1 to 4, which may further comprise per formulation one or more additional active substances, preferably cetylpyridinium chloride and / or hydroxyapatite and / or plant extracts with antimicrobial activity for example mint and / or fluoride derivatives and / or bisabolol and / or phosphates and / or activated carbon and / or cymenol and / or sucralfate and / or ectoin and / or glycyrrhetinic acid. Definition 6. Composition according to definition 5, wherein the amount of sucralfate ranges from 1 to 30 % w / w, preferably from 1 to 6 % w / w, more preferably is 3 % w / w.

[0016] Definition 7. Composition according to definition 5, wherein the amount of ectoin ranges from 0,1 to 10 % w / w, preferably from 0,5 to 5 % w / w, more preferably is 1 % w / w.

[0017] Definition 8. Composition according to definition 5, wherein the amount of glycyrrhetinic acid ranges from 0,1 to 10 % w / w, preferably from 0,5 to 5 % w / w, more preferably is 1 % w / w.

[0018] Definition 9. Composition according to any of the definitions 1 to 8, which additionally comprises per formulation one or more excipients, selected from one or more diluents and / or one or more humectants, and / or one or more flavor enhancers and / or one or more sweeteners and / or one or more preservatives and / or one or more pH adjusting agents and / or one or more fragrances and / or one or more surfactants and / or one or more oxidizing agents and / or more chelating agents and / or one or more soothing agents and / or one or more stabilizing agents.

[0019] Definition 10. Composition according to definition 9, wherein the solvent is preferably water and / or glycerin, the humectant is preferably glycerin, the sweetener is preferably xylitol and / or sodium acetosulfamate, the surfactant is preferably Poloxamer and / or PEG derivatives, the pH adjusting agent is preferably phosphoric acid and / or tetrasodium pyrophosphate, the chelating agent is preferably EDTA, the soothing agent is preferably bisaboloi and / or allantoin.

[0020] Definition 11, Composition according to any of definitions 1 to 10, which comprises chlorhexidine in an amount of 0,2 % w / w and hydrogen peroxide in an amount of 1.

[0021] % w / w, said composition is formulated into a mouthwash. Definition 12. Composition according to any of definitions 1 to 10, which comprises chlorhexidine in an amount of 0,2 % w / w and hydrogen peroxide in an amount of 0,8 % w / w, said composition is formulated into a mouthwash. Definition 13. Composition according to any of definitions 1 to 10, which comprises chlorhexidine in an amount of 0,2 % w / w and hydrogen peroxide in an amount of 1 % w / w, said composition is formulated into a gel.

[0022] Definition 14. Composition according to definition 1, which further comprises one or more forms of hyaluronic acid, preferably sodium hyaluronate.

[0023] Definition 15. Composition according to definition 14, which is in the form of mouthwash or toothpaste or gel or mouth drops or mouth foam or spray, preferably mouthwash or gel.

[0024] Definition 16. Composition according to definitions 14 and 15, wherein the amount of chlorhexidine ranges from above 0,05 to 10,0 % w / w per formulation, preferably from 0,1 to 2,0 % w / w per formulation, more preferably from 0,12 to 0,2 % w / w per formulation, particularly more preferably is 0,12 % w / w or 0,2 % w / w or 2,0 % w / w per formulation.

[0025] Definition 17. Composition according to any of the definitions 14 to 16, wherein the amount of hydrogen peroxide ranges from above 0,8 to 40,0 % w / w per formulation, preferably from 0,8 to 13 % w / w per formulation, more preferably from 0,8 to 1 % w / w per formulation, particularly more preferably is 0,8 % w / w or 1 % w / w per formulation.

[0026] Definition 18. Composition according to any of the definitions 14 to 17, wherein the amount of carbamide peroxide ranges from 0,01 to 40,0 % w / w per formulation. preferably from 11 to 35 % w / w per formulation, more preferably is 11 % w / w or 16 % w / w or 22 % w / w or 35 % w / w per formulation.

[0027] Definition 19. Composition according to any of the definitions 14 to 18, wherein the amount of calcium peroxide ranges from 0,01 to 5,0 % w / w per formulation, preferably from 0,05 to 0,1 % w / w per formulation.

[0028] Definition 20. Composition according to any of the definitions 14 to 19, wherein the amount of sodium hyaluronate ranges from 0,01 to 4 % w / w per formulation, preferably from 0,05 to 1,5 % w / w per formulation, more preferably is 0,05 % or 0,41 % w / w per formulation.

[0029] Definition 21. Composition according to any of the definitions 14 to 20, which may further comprise per formulation one or more additional active substances, preferably cetyl pyridinium chloride and / or hydroxyapatite and / or plant extracts with antimicrobial activity for example mint and / or fluoride derivatives and / or bisabolol and / or phosphates and / or activated carbon and / or cymenol and / or sucralfate and / or ectoIn and / or glycyrrhetinlc acid.

[0030] Definition 22. Composition according to definition 21, wherein the amount of sucralfate ranges from 1 to 30 % w / w, preferably from 1 to 6 % w / w, more preferably is 3 % w / w.

[0031] Definition 23. Composition according to definition 2.1, wherein the amount of ectoin ranges from 0,1 to 10 % w / w, preferably from 0,5 to 5 % w / w, more preferably is 1 % w / w.

[0032] Definition 24. Composition according to definition 21, wherein the amount of glycyrrhetinic acid ranges from 0,1 to 10 % w / w, preferably from 0,5 to 5 % w / w, more preferably is 1 % w / w. Definition 25. Composition according to any of the definitions 14 to 24, which additionally comprises per formulation one or more excipients, selected from one or more diluents and / or one or more humectants, and / or one or more flavor enhancers and / or one or more sweeteners and / or one or more preservatives and / or one or more pH adjusting agents and / or one or more fragrances and / or one or more surfactants and / or one or more oxidizing agents and / or more chelating agents and / or one or more soothing agents and / or one or more stabilizing agents. Definition 26. Composition according to definition 25, wherein the solvent is preferably water and / or glycerin, the humectant is preferably glycerin, the sweetener Is preferably xylitol and / or sodium acetosulfamate, the surfactant is preferably Poloxamer and / or PEG derivatives, the pH adjusting agent is preferably phosphoric acid and / or tetrasodium pyrophosphate, the chelating agent is preferably EDTA, the soothing agent is preferably bisabolol and / or allantoin.

[0033] Definition 27. Composition according to any of definitions 14 to 26, which comprises chlorhexidlne in an amount of 0,2 % w / w, hydrogen peroxide in an amount of 1 % w / w and sodium hyaluronate in an amount of 0,05 % w / w, said composition is formulated in mouthwash or gel or toothpaste or spray.

[0034] Definition 28. Composition according to any of definitions 14 to 26, which comprises chlorhexidlne in an amount of 0,2 % w / w, hydrogen peroxide in an amount of 1 % w / w and sodium hyaluronate in an amount of 0,41 % w / w, said composition is formulated in mouthwash or gel or toothpaste or spray,

[0035] It was surprisingly found that the specific composition of the present invention presented more intense results compared to compositions comprising each ingredient individually or some of the ingredients without the exact combination or without the exact quantities or without the appropriate pharmaceutical form / formulation. Furthermore, it was surprisingly found that the composition of the invention exhibited synergistic activity in contrast to compositions comprising only some of the components or in different concentrations.

[0036] It was also surprisingly found that the specific combination of the invention showed effectiveness even after dental implant procedures.

[0037] Though the composition is advantageous without hyaluronic acid, when it comprises also hyaluronic acid, there is synergy and surprisingly much better results, mostly in term of moisturizing.

[0038] Moreover, when the amounts of the various compounds are within the ranges disclosed in the above definitions, the advantages are surprisingly much better.

[0039] Finally, it was surprisingly found that the more is restricted the scope of the claims, the more intense are the effects and the advantages of the present invention.

[0040] The compositions of the present invention can be prepared by methods already known in the state of art.

[0041] The present invention is further described by the following indicative, but non-limiting examples.

[0042] Example 1: In a preferred embodiment the composition of the present invention comprises the following:

[0043] The composition of the Example 1 is formulated into mouthwash. The composition of the present Example 1 exhibits all the advantages of the present invention mentioned above. Exampte 2: In a preferred embodiment the composition of the present invention comprises the following:

[0044] The composition of the Example 2 is formulated into mouthwash, The composition of the present Example 2 exhibits all the advantages of the present invention mentioned above. Example 3: In a preferred embodiment the composition of the present invention comprises the following:

[0045] The composition of the Exampie 3 is formulated into gel.

[0046] The composition of the present Example 3 exhibits all the advantages of the present invention mentioned above. Example 4: in a preferred embodiment the composition of the present invention comprises the following:

[0047] The composition of the Example 4 is formulated into mouthwash.

[0048] The composition of the present Example 4 exhibits all the advantages of the present invention mentioned above. Example 5: In a preferred embodiment the composition of the present invention comprises the foilowing:

[0049] The composition of the Example 5 is formulated Into mouthwash, The composition of the present Example 5 exhibits all the advantages of the present invention mentioned above. Example 6: In a preferred embodiment the composition of the present invention comprises the following:

[0050] The composition of the Example 6 is formulated into gel. The composition of the present Example 6 exhibits all the advantages of the present invention mentioned above. Example 7: In a preferred embodiment the composition of the present invention comprises the following:

[0051] The composition of the Exampie 7 is formulated into mouthwash. The composition of the present Example 7 exhibits all the advantages of the present invention mentioned above.

Claims

Claims1. Composition for administration to the oral cavity, suitable for prophylaxis or treatment of diseases of the teeth and / or gums and / or the oral cavity, which comprises chlorhexidine and one or more peroxides that are decomposed into active oxygen, preferably hydrogen peroxide and / or carbamide peroxide and / or calcium peroxide.2, Composition according to claim 1, which is in the form of mouthwash or toothpaste or gel or mouth drops or mouth foam or spray, preferably mouthwash or gel and wherein the amount of chlorhexidine ranges from 0,12 to 0,2 % w / w per formulation, preferably is 0,12 % w / w or 0,2 % w / w per formulation and the amount of hydrogen peroxide ranges from 0,8 to 1 % w / w per formulation, preferably is 0,8 % w / w or 1 % w / w per formulation.

3. Composition according to claim 1, which is in the form of mouthwash or toothpaste or gel or mouth drops or mouth foam or spray, preferably mouthwash or gel and wherein the amount of chlorhexidine ranges from 0,12 to 0,2 % w / w per formulation, preferably is 0,12 % w / w or 0,2 % w / w per formulation and wherein the amount of carbamide peroxide ranges from 0,01 to 40,0 % w / w per formulation, preferably from 11 to 35 % w / w per formulation, more preferably is 11 % w / w or 16 % w / w or 22 % w / w or 35 % w / w per formulation.

4. Composition according to claim 1, which is in the form of mouthwash or toothpaste or gel or mouth drops or mouth foam or spray, preferably mouthwash or gel and wherein the amount of chlorhexidine ranges from 0,12 to 0,2 % w / w per formulation, preferably is 0,12 % w / w or 0,2 % w / w per formulation and wherein the amount of calcium peroxide ranges from 0,01 to 5,0 % w / w per formulation, preferably from 0,05 to 0,1 % w / w per formulation.

5. Composition according to any of the claims 1 to 4, which may further comprise per formulation one or more additional active substances, preferably cetyipyrldiniumchloride and / or hydroxyapatite and / or plant extracts with antimicrobial activity for example mint and / or fluoride derivatives and / or bisabolol and / or phosphates and / or activated carbon and / or cymenol and / or sucralfate and / or ectoin and / or glycyrrhetinic acid.

6. Composition according to claim 5, wherein the amount of sucralfate ranges from 1 to 30 % w / w, preferably from 1 to 6 % w / w, more preferably is 3 % w / w.

7. Composition according to claim 5, wherein the amount of ectoin ranges from 0,1 to 10 % w / w, preferably from 0,5 to 5 % w / w, more preferably is 1 % w / w.

8. Composition according to claim 5, wherein the amount of glycyrrhetinic acid ranges from 0,1 to 10 % w / w, preferably from 0,5 to 5 % w / w, more preferably is 1 % w / w.

9. Composition according to any of the claims 1 to 8, which additionally comprises per formulation one or more excipients, selected from one or more diluents and / or one or more humectants, and / or one or more flavor enhancers and / or one or more sweeteners and / or one or more preservatives and / or one or more pH adjusting agents and / or one or more fragrances and / or one or more surfactants and / or one or more oxidizing agents and / or more chelating agents and / or one or more soothing agents and / or one or more stabilizing agents.

10. Composition according to claim 9, wherein the solvent is preferably water and / or glycerin, the humectant is preferably glycerin, the sweetener is preferably xylitol and / or sodium acetosulfamate, the surfactant is preferably Poloxamer and / or PEG derivatives, the pH adjusting agent is preferably phosphoric acid and / or tetrasodium pyrophosphate, the chelating agent is preferably EDTA, the soothing agent is preferably bisabolol and / or allantoin.

11. Composition according to any of claims 1 to 10, which comprises chlorhexidine in an amount of 0,2 % w / w and hydrogen peroxide in an amount of 1 % w / w, said composition is formulated into a mouthwash.

12. Composition according to any of claims 1 to 10, which comprises chlorhexidine in an amount of 0,2 % w / w and hydrogen peroxide in an amount of 0,8 % w / w, said composition is formulated into a mouthwash,13. Composition according to any of claims 1 to 10, which comprises chlorhexidine in an amount of 0,2 % w / w and hydrogen peroxide in an amount of 1 % w / w, said composition is formulated into a gel.

14. Composition according to claim 1, which further comprises one or more forms of hyaluronic acid, preferably sodium hyaluronate,15. Composition according to claim 14, which is in the form of mouthwash or toothpaste or gei or mouth drops or mouth foam or spray, preferably mouthwash or gel.

16. Composition according to claims 14 and 15, wherein the amount of chlorhexidine ranges from above 0,05 to 10,0 % w / w per formulation, preferably from 0,1 to 2,0 % w / w per formulation, more preferably from 0,12 to 0,2 % w / w per formulation, particularly more preferably is 0,12 % w / w or 0,2 % w / w or 2,0 % w / w per formulation.

17. Composition according to any of the claims 14 to 16, wherein the amount of hydrogen peroxide ranges from above 0,8 to 40,0 % w / w per formulation, preferably from 0,8 to 13 % w / w per formulation, more preferably from 0,8 to 1 % w / w per formulation, particularly more preferably is 0,8 % w / w or 1 % w / w per formulation.

18. Composition according to any of the claims 14 to 17, wherein the amount of carbamide peroxide ranges from 0,01 to 40,0 % w / w per formulation, preferably from 11 to 35 % w / w per formulation, more preferably is 11 % w / w or 16 % w / w or 22 % w / w or 35 % w / w per formulation.

19. Composition according to any of the claims 14 to 18, wherein the amount of calcium peroxide ranges from 0,01 to 5,0 % w / w per formulation, preferably from 0,05 to 0,1 % w / w per formulation.

20. Composition according to any of the claims 14 to 19, wherein the amount of sodium hyaluronate ranges from 0,01 to 4 % w / w per formulation, preferably from 0,05 to 1,5 % w / w per formulation, more preferably is 0,05 % or 0,41 % w / w per formulation.

21. Composition according to any of the claims 14 to 20, which may further comprise per formulation one or more additional active substances, preferably cetylpyridinium chloride and / or hydroxyapatite and / or plant extracts with antimicrobial activity for example mint and / or fluoride derivatives and / or bisabolol and / or phosphates and / or activated carbon and / or cymenol and / or sucralfate and / or ectoin and / or glycyrrhetinic acid.

22. Composition according to claim 21, wherein the amount of sucralfate ranges from 1 to 30 % w / w, preferably from 1 to 6 % w / w, more preferably is 3 % w / w.

23. Composition according to claim 21, wherein the amount of ectoin ranges from 0,1 to 10 % w / w, preferably from 0,5 to 5 % w / w, more preferably is 1 % w / w.

24. Composition according to claim 21, wherein the amount of glycyrrhetinic acid ranges from 0,1 to 10 % w / w, preferably from 0,5 to 5 % w / w, more preferably is 1 % w / w.

25. Composition according to any of the claims 14 to 24, which additionally comprises per formulation one or more excipients, selected from one or more diluents and / or one or more humectants, and / or one or more flavor enhancers and / or one or more sweeteners and / or one or more preservatives and / or one or more pH adjusting agents and / or one or more fragrances and / or one or more surfactants and / or one or more oxidizing agents and / or more chelating agents and / or one or more soothing agents and / or one or more stabilizing agents.

26. Composition according to claim 25, wherein the solvent Is preferably water and / or glycerin, the humectant is preferably glycerin, the sweetener is preferably xylitol and / or sodium acetosulfamate, the surfactant is preferably Poloxamer and / or PEG derivatives, the pH adjusting agent is preferably phosphoric acid and / or tetrasodium pyrophosphate, the chelating agent is preferably EDTA, the soothing agent is preferably bisabolol and / or allantoin.

27. Composition according to any of claims 14 to 26, which comprises chlorhexidine in an amount of 0,2 % w / w, hydrogen peroxide in an amount of 1 % w / w and sodium hyaluronate in an amount of 0,05 % w / w, said composition is formulated in mouthwash or gel or toothpaste or spray.

28. Composition according to any of claims 14 to 26, which comprises chlorhexidine in an amount of 0,2 % w / w, hydrogen peroxide in an amount of 1 % w / w and sodium hyaluronate in an amount of 0,41 % w / w, said composition is formulated in mouthwash or gel or toothpaste or spray.